FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Levy, BR Pilver, CE Pietrzak, RH AF Levy, Becca R. Pilver, Corey E. Pietrzak, Robert H. TI Lower prevalence of psychiatric conditions when negative age stereotypes are resisted SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Aging; Age stereotypes; Mental health; Stress; Suicide; Anxiety; Posttraumatic stress disorder; Veterans ID SELF-PERCEPTIONS; MALE VETERANS; WAR VETERANS; PRIMARY-CARE; SUICIDE; HEALTH; DEPRESSION; ANXIETY; EXPECTATIONS; RESILIENCE AB Older military veterans are at greater risk for psychiatric disorders than same-aged non-veterans. However, little is known about factors that may protect older veterans from developing these disorders. We considered whether an association exists between the potentially stress-reducing factor of resistance to negative age stereotypes and lower prevalence of the following outcomes among older veterans: suicidal ideation, anxiety, and posttraumatic stress disorder (PTSD). Participants consisted of 2031 veterans, aged 55 or older, who were drawn from the National Health and Resilience in Veterans Study, a nationally representative survey of American veterans. The prevalence of all three outcomes was found to be significantly lower among participants who fully resisted negative age stereotypes, compared to those who fully accepted them: suicidal ideation, 5.0% vs. 30.1%; anxiety, 3.6% vs. 34.9%; and PTSD, 2.0% vs. 18.5%, respectively. The associations followed a graded linear pattern and persisted after adjustment for relevant covariates, including age, combat experience, personality, and physical health. These findings suggest that developing resistance to negative age stereotypes could provide older individuals with a path to greater mental health. (C) 2014 Published by Elsevier Ltd. C1 [Levy, Becca R.] Yale Univ, Sch Publ Hlth, Social & Behav Sci Div, New Haven, CT 06520 USA. [Pilver, Corey E.] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT 06520 USA. [Pietrzak, Robert H.] Yale Univ, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, VA Connecticut Healthcare Syst,Sch Med, West Haven, CT 06516 USA. [Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. RP Levy, BR (reprint author), Yale Univ, Sch Publ Hlth, Social & Behav Sci Div, 60 Coll St, New Haven, CT 06520 USA. EM becca.levy@yale.edu FU Becca Levy from the National Institute on Aging [R01AG023993]; National Heart, Lung and Blood Institute [R01HL089314]; National Institute of Mental Health [5-T32-MH01423537] FX This research was supported by grants to Becca Levy from the National Institute on Aging (R01AG023993), and the National Heart, Lung and Blood Institute (R01HL089314). Corey Pilver was supported by a National Institute of Mental Health postdoctoral fellowship (5-T32-MH01423537). The National Health and Resilience in Veterans Study and Robert Pietrzak were supported by the United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder. NR 30 TC 6 Z9 6 U1 1 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD OCT PY 2014 VL 119 BP 170 EP 174 DI 10.1016/j.socscimed.2014.06.046 PG 5 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AU2YI UT WOS:000345480000020 PM 25189737 ER PT J AU Yoo, S Pettersson, A Jordahl, KM Lis, RT Lindstrom, S Meisner, A Nuttall, EJ Stack, EC Stampfer, MJ Kraft, P Brown, M Loda, M Giovannucci, EL Kantoff, PW Mucci, LA AF Yoo, Sun Pettersson, Andreas Jordahl, Kristina M. Lis, Rosina T. Lindstrom, Sara Meisner, Allison Nuttall, Elizabeth J. Stack, Edward C. Stampfer, Meir J. Kraft, Peter Brown, Myles Loda, Massimo Giovannucci, Edward L. Kantoff, Philip W. Mucci, Lorelei A. TI Androgen Receptor CAG Repeat Polymorphism and Risk of TMPRSS2: ERG-Positive Prostate Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID N-TERMINAL DOMAIN; GENE; REARRANGEMENT; FUSION; COHORT AB Background: The androgen receptor (AR) is an essential gene in prostate cancer pathogenesis and progression. Genetic variation in AR exists, including a polymorphic CAG repeat sequence that is inversely associated with transcriptional activity. Experimental data suggest that heightened AR activity facilitates formation of TMPRSS2:ERG, a gene fusion present in approximately 50% of tumors of patients with prostate cancer. Methods: We undertook a nested case-control study to investigate the hypothesis that shorter CAG repeat length would be associated with prostate cancer risk defined by TMPRSS2: ERG status. The study included 291 men with prostate cancer (147 ERG-positive) and 1,221 cancer-free controls. ORs and 95% confidence intervals (CI) were calculated using logistic regression. Results: Median CAG repeat length (interquartile range) among controls was 22 (20-24). Men with shorter CAG repeats had an increased risk of ERG-positive (OR, 1.07 per 1 repeat decrease; 95% CI, 1.00-1.14), but not ERG-negative prostate cancer (OR, 0.99 per 1 repeat decrease; 95% CI, 0.93-1.05). Conclusions: These data suggest that shorter CAG repeats are specifically associated with development of TMPRSS2: ERG-positive prostate cancer. Impact: Our results provide supportive evidence that androgen signaling underlies the development of prostate tumors that harbor TMPRSS2: ERG. Moreover, these results suggest that TMPRSS2: ERG may represent a unique molecular subtype of prostate cancer with an etiology distinct from TMPRSS2: ERG-negative disease. (C) 2014 AACR. C1 [Yoo, Sun; Pettersson, Andreas; Jordahl, Kristina M.; Lindstrom, Sara; Meisner, Allison; Nuttall, Elizabeth J.; Stampfer, Meir J.; Kraft, Peter; Giovannucci, Edward L.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Lis, Rosina T.; Stack, Edward C.; Loda, Massimo] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Lis, Rosina T.; Stack, Edward C.; Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Stampfer, Meir J.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Stampfer, Meir J.; Giovannucci, Edward L.; Mucci, Lorelei A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Brown, Myles; Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Mucci, LA (reprint author), Harvard Univ, Sch Publ Hlth, 677 Huntington Ave,9th Floor, Boston, MA 02115 USA. EM apetters@hsph.harvard.edu; lmucci@hsph.harvard.edu OI Brown, Myles/0000-0002-8213-1658 FU Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence (SPORE) in Prostate Cancer [P50CA090381-08]; Prostate Cancer Foundation; Swedish Research Council [2009-7309]; Royal Physiographic Society in Lund, Sweden; [NCICA136578]; [CA141298]; [CA097193]; [PO1 CA055075]; [UM1CA167552]; [U01CA098233] FX This work was financially supported by the Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence (SPORE) in Prostate Cancer P50CA090381-08 (to P.W. Kantoff and E.L. Giovannucci), and the NCICA136578 (to L.A. Mucci and E.L. Giovannucci), CA141298 (to M.J Stampfer), CA097193 (to J.M. Gaziano), PO1 CA055075 (to W. Willett and E.L. Giovannucci), UM1CA167552 (to W. Willett), and U01CA098233 to D.J. Hunter, P. Kraft, and S. Lindstrom). L.A. Mucci is supported by the Prostate Cancer Foundation. A. Pettersson is supported by the Swedish Research Council 2009-7309 and the Royal Physiographic Society in Lund, Sweden. NR 18 TC 9 Z9 9 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2014 VL 23 IS 10 BP 2027 EP 2031 DI 10.1158/1055-9965.EPI-14-0020 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AT9XP UT WOS:000345277400008 PM 24925673 ER PT J AU Song, MY Wu, KN Chan, AT Fuchs, CS Giovannucci, EL AF Song, Mingyang Wu, Kana Chan, Andrew T. Fuchs, Charles S. Giovannucci, Edward L. TI Plasma 25-Hydroxyvitamin D and Risk of Colorectal Cancer after Adjusting for Inflammatory Markers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID C-REACTIVE PROTEIN; VITAMIN-D STATUS; CALCIUM; MEN; HEALTH; WOMEN; SUPPLEMENTATION AB Despite the substantial epidemiologic evidence on the inverse association between circulating 25-hydroxyvitamin D [25(OH)D] and colorectal cancer, it remains controversial whether this relationship is causal or due to confounding by inflammation. We reevaluated the association between plasma 25(OH)D and colorectal cancer risk by additionally accounting for inflammatory markers in a prospective case-control study nested within the Nurses' Health Study and Health Professionals Follow-up Study (615 cases and 1,209 matched controls). Conditional logistic regression was used to estimate relative risk (RR) and 95% confidence interval (CI) of colorectal cancer in relation to quartiles of plasma 25(OH)D. Results were compared before and after adjusting for inflammatory markers in the multivariable model. Plasma 25(OH)D was associated with reduced risk of colorectal cancer (multivariable RR comparing extreme quartiles = 0.71; 95% CI, 0.52-0.97; P-trend = 0.01). Additional adjustment for C-reactive protein, IL6, soluble tumor necrosis factor receptor 2, or a composite inflammatory score did not change the results [multivariable (including inflammatory score) RR = 0.72; 95% CI, 0.53-0.98; P-trend = 0.02). Our findings suggest that confounding by inflammation, as reflected by circulating inflammatory markers, does not appear to account for the inverse association between plasma 25(OH)D and colorectal cancer. (C)2014 AACR. C1 [Song, Mingyang; Wu, Kana; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Song, Mingyang; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Div Network Med, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Giovannucci, EL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA. EM egiovann@hsph.harvard.edu RI Song, Mingyang/M-6701-2013 OI Song, Mingyang/0000-0002-1324-0316 FU NIH [P01 CA87969, R01 CA49449, UM1 CA167552, P01 CA 55075, 1U54CA155626] FX This work was supported by the NIH (P01 CA87969 to S.E. Hankinson, M. Song, A.T. Chan, E.L. Giovannucci; R01 CA49449 to S.E. Hankinson; UM1 CA167552 to W.C. Willett; P01 CA 55075 to W.C. Willett, M. Song, A.T. Chan, E.L. Giovannucci; and 1U54CA155626 to F.B. Hu). NR 24 TC 5 Z9 6 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2014 VL 23 IS 10 BP 2175 EP 2180 DI 10.1158/1055-9965.EPI-14-0712 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AT9XP UT WOS:000345277400024 PM 25106774 ER PT J AU Aggarwal, S Jakobiec, FA Hamrah, P AF Aggarwal, Shruti Jakobiec, Frederick A. Hamrah, Pedram TI Bilateral Adult Epibulbar Xanthogranulomas Suspicious for Erdheim-Chester Disease SO CORNEA LA English DT Article DE xanthogranuloma; conjunctiva; histiocytosis; Langerhans cells; CD68; Erdheim-Chester disease; Touton giant cells ID JUVENILE XANTHOGRANULOMA; ORBITAL XANTHOGRANULOMA; LIMBAL XANTHOGRANULOMA AB Purpose: The aim of this study was to report the clinical, imaging, and histopathological findings of bilateral, conjunctival adult-onset xanthogranulomas that raised the prospect of a mild form of Erdheim-Chester disease. Methods: This is a case report. Results: A 35-year-old white male complaining of ocular irritation, presented with bilateral, nasal and temporal, yellow, elevated conjunctival lumps first noticed 1.5 years back, which were not associated with other ocular findings. The lesions were firm, attached to the underlying episclera, and measured 1.1 x 0.9, 1.1 x 0.8, 1.2 x 0.5, and 0.5 x 0.5 cm in the temporal and nasal right and left eyes, respectively. Each mass was fleshy with vascularity at the peripheral margin. Histopathologic evaluation after excisional biopsy revealed lipidized xanthoma cells, multiple Touton giant cells, and lymphocytes. Immunohistochemical staining was positive for adipophilin (lipid), CD68(+), CD163(+) histiocytes, CD3(+) T cells (with CD8(+) cytotoxic T cells > CD4(+) T-helper cells), and virtually no CD20(+) B cells or IgG4(+) plasma cells. The patient later acquired similar xanthogranulomatous subcutaneous lesions on the extremities. Positron emission tomography scans showed sclerosis in the medullary cavities of the tibia and the radius of both legs and arms, and an absence of retroperitoneal lesions. A normal serum immunoelectrophoresis and the absence of a BRAF gene mutation were demonstrated. Conclusions: Adult-onset xanthogranuloma can present as a solitary conjunctival mass without periocular or orbital involvement. The clinical, histopathologic, and radiologic findings in this case are suggestive of Erdheim-Chester disease without displaying any life-threatening lesions to date. Histopathologic and imaging studies can help in obtaining a diagnosis. Ophthalmologists should be aware that xanthogranulomatous conditions may have potential systemic implications, and a thorough systemic evaluation is recommended for lesions that initially seemed to be isolated in nature. C1 [Aggarwal, Shruti; Hamrah, Pedram] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Ocular Surface Ima, Boston, MA USA. [Aggarwal, Shruti; Hamrah, Pedram] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Cornea & Refract S, Boston, MA USA. [Aggarwal, Shruti; Jakobiec, Frederick A.; Hamrah, Pedram] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jakobiec, Frederick A.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Hamrah, P (reprint author), Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM pedram_hamrah@meei.harvard.edu FU NIH [K08-EY020575]; Research to Prevent Blindness; Falk Medical Research Foundation FX Supported by NIH K08-EY020575 (P.H.), Research to Prevent Blindness Career Development Award (P.H.), and Falk Medical Research Foundation (P.H.). NR 24 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD OCT PY 2014 VL 33 IS 10 BP 1113 EP 1117 PG 5 WC Ophthalmology SC Ophthalmology GA AP1WR UT WOS:000341863300021 PM 25014153 ER PT J AU Razmara, A Bakhadirov, K Batra, A Feske, SK AF Razmara, Ali Bakhadirov, Khamid Batra, Ayush Feske, Steven K. TI Cerebrovascular Complications of Pregnancy and the Postpartum Period SO CURRENT CARDIOLOGY REPORTS LA English DT Article DE Cerebrovascular complications.; Pregnancy; Postpartum period; Ischemic stroke; Hemorrhagic stroke; Cerebral venous thrombosis; Pre-eclampsia-eclampsia ID REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY; TISSUE-PLASMINOGEN ACTIVATOR; HEALTH-CARE PROFESSIONALS; ARTERIOVENOUS-MALFORMATIONS; VENOUS THROMBOSIS; RISK-FACTORS; ENCEPHALOPATHY SYNDROME; THROMBOLYTIC THERAPY; STROKE-ASSOCIATION; CONTRAST-MEDIA AB Cerebrovascular complications of pregnancy, though uncommon, threaten women with severe morbidity or death, and they are the main causes of major long-term disability associated with pregnancy. In this review, we discuss the epidemiology, pathophysiology, presentation and diagnosis, and management and outcomes of ischemic and hemorrhagic stroke and cerebral venous thrombosis. We also discuss the posterior reversible encephalopathy syndrome, the reversible cerebral vasoconstriction syndrome including postpartum cerebral angiopathy, and their relationship as overlapping manifestations of pre-eclampsia-eclampsia. C1 [Razmara, Ali; Bakhadirov, Khamid] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Razmara, Ali; Bakhadirov, Khamid] Brigham & Womens Hosp, Boston, MA 02115 USA. [Batra, Ayush] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Batra, Ayush] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Feske, Steven K.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Feske, SK (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM arazmara@partners.org; bakhadirov.khamidulla@mgh.harvard.edu; abatra@partners.org; sfeske@partners.org NR 53 TC 5 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3782 EI 1534-3170 J9 CURR CARDIOL REP JI Curr. Cardiol. Rep. PD OCT PY 2014 VL 16 IS 10 AR 532 DI 10.1007/s11886-014-0532-1 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AT6ZX UT WOS:000345086700004 PM 25239155 ER PT J AU Sarkis, RA Nehme, R Chemali, ZN AF Sarkis, Rani A. Nehme, Romy Chemali, Zeina N. TI Neuropsychiatric and seizure outcomes in nonparaneoplastic autoimmune limbic encephalitis SO EPILEPSY & BEHAVIOR LA English DT Article DE Autoimmune; Limbic encephalitis; Seizures; Behavior; Outcomes; NMDA; VGKC; Employment; Relapses; Refractory epilepsy ID TEMPORAL-LOBE EPILEPSY; RECEPTOR ANTIBODIES; DIAGNOSIS; ONSET AB Introduction: Autoimmune limbic encephalitis is an inflammatory condition often associated with an underlying neoplasm. However, a subset of patients does not have an underlying tumor and have a nonparaneoplastic form of this condition. The focus in the literature has been on the acute phase of this illness, but long-term follow-up is lacking. Methods: A retrospective chart review, over a period of 15 years, of patients carrying a diagnosis of encephalitis was performed. Inclusion criteria included a clinical presentation consistent with limbic encephalitis (subacute behavioral change, seizures, or anterograde memory decline) and an identifiable autoantibody, inflammatory CSF (>5 white blood cells/mm(3)), or limbic hyperintensities on MRI. Readmission rates and long-term psychiatric, psychosocial, and seizure outcomes were evaluated. Results: A total of 16 patients were identified. Clinical presentation included new-onset seizures in 14 (88%), behavioral changes in 7 (44%), and memory decline in 5 (31%). Four (25%) patients presented with status epilepticus. Five patients had antibodies against NMDAR (N-methyl-D-aspartate receptor) and four against VGKC (voltage gated potassium channel) complex. An inflammatory CSF was noted in 7 (44%) and MRI changes in 9 (56%). Four were readmitted during the follow-up period. Around half the patients continued to have medically drug/treatment-refractory seizures, while 7 (44%) had a new psychiatric diagnosis (mood disorder, anxiety disorder, or impulse control disorder). The majority of the patients continued to reside at home, while 43% of previously employed patients lost employment. Conclusion: Nonparaneoplastic autoimmune limbic encephalitis is a neuropsychiatric condition presenting with a combination of seizures (sometimes status epilepticus), behavioral changes, and memory decline. After the acute phase, patients are at risk of readmissions, medically refractory seizures, chronic mood and anxiety disorders, and loss of employment. (C) 2014 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Neuropsychiat Clin, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuropsychiat Clin, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sarkis, RA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM rsarkis@partners.org; rnehme2@partners.org; zelchemali@mgh.harvard.edu OI Sarkis, Rani/0000-0001-8291-7864 NR 24 TC 7 Z9 8 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD OCT PY 2014 VL 39 BP 21 EP 25 DI 10.1016/j.yebeh.2014.07.018 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA AT9FM UT WOS:000345233400005 PM 25171259 ER PT J AU Plana, JC Galderisi, M Barac, A Ewer, MS Ky, B Scherrer-Crosbie, M Ganame, J Sebag, IA Agler, DA Badano, LP Banchs, J Cardinale, D Carver, J Cerqueira, M DeCara, JM Edvardsen, T Flamm, SD Force, T Griffin, BP Jerusalem, G Liu, JE Magalhaes, A Marwick, T Sanchez, LY Sicari, R Villarraga, HR Lancellotti, P AF Plana, Juan Carlos Galderisi, Maurizio Barac, Ana Ewer, Michael S. Ky, Bonnie Scherrer-Crosbie, Marielle Ganame, Javier Sebag, Igal A. Agler, Deborah A. Badano, Luigi P. Banchs, Jose Cardinale, Daniela Carver, Joseph Cerqueira, Manuel DeCara, Jeanne M. Edvardsen, Thor Flamm, Scott D. Force, Thomas Griffin, Brian P. Jerusalem, Guy Liu, Jennifer E. Magalhaes, Andreia Marwick, Thomas Sanchez, Liza Y. Sicari, Rosa Villarraga, Hector R. Lancellotti, Patrizio TI Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING LA English DT Article DE Chemotherapy; Doxorubicin; Trastuzumab; Left ventricular dysfunction; Three-dimensional echocardiography; Early detection; Strain; Biomarkers ID VENTRICULAR EJECTION FRACTION; CARDIAC MAGNETIC-RESONANCE; CONGESTIVE-HEART-FAILURE; ANTHRACYCLINE-INDUCED CARDIOTOXICITY; DOBUTAMINE-STRESS ECHOCARDIOGRAPHY; TRASTUZUMAB-INDUCED CARDIOTOXICITY; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; HIGH-DOSE CHEMOTHERAPY; NATIVE VALVULAR REGURGITATION C1 [Plana, Juan Carlos; Agler, Deborah A.; Cerqueira, Manuel; Flamm, Scott D.; Griffin, Brian P.] Cleveland Clin, Cleveland, OH 44106 USA. [Galderisi, Maurizio] Federico II Univ Hosp, Naples, Italy. [Barac, Ana] Medstar Washington Hosp Ctr, Washington, DC USA. [Ewer, Michael S.; Banchs, Jose; Sanchez, Liza Y.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ky, Bonnie] Univ Penn, Philadelphia, PA 19104 USA. [Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ganame, Javier] McMaster Univ, Hamilton, ON, Canada. [Sebag, Igal A.] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Sebag, Igal A.] McGill Univ, Montreal, PQ, Canada. [Badano, Luigi P.] Univ Padua, Padua, Italy. [Cardinale, Daniela] European Inst Oncol, Milan, Italy. [Carver, Joseph] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [DeCara, Jeanne M.] Univ Chicago Med, Chicago, IL USA. [Edvardsen, Thor] Oslo Univ Hosp, Oslo, Norway. [Edvardsen, Thor] Univ Oslo, Oslo, Norway. [Force, Thomas] Temple Univ, Philadelphia, PA 19122 USA. [Jerusalem, Guy; Lancellotti, Patrizio] Univ Liege, Liege, Belgium. [Liu, Jennifer E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Magalhaes, Andreia] Santa Marie Univ Hosp, Lisbon, Portugal. [Marwick, Thomas] Menzies Res Inst Tasmania, Hobart, Tas, Australia. [Sicari, Rosa] CNR, Inst Clin Physiol, I-56100 Pisa, Italy. [Villarraga, Hector R.] Mayo Clin, Rochester, MN USA. RP Plana, JC (reprint author), Cleveland Clin, Cleveland, OH 44106 USA. RI Edvardsen, Thor/F-4079-2012; OI Edvardsen, Thor/0000-0002-3800-765X; Force, Thomas/0000-0002-0450-8659; Galderisi, Maurizio/0000-0003-0311-9069; Badano, Luigi/0000-0002-0379-3283 FU Genentech; Cell Therapeutics; Perceptive Informatics, Inc; Siemens Healthcare; Pfizer, Inc; National Health and Medical Research Council in Australia; Royal Hobart Hospital Foundation; Philips Medical Systems; Siemens; GE Medical Systems FX The following authors reported no actual or potential conflicts of interest in relation to this document: J.C.P., M. G., M. S-C., J.G., D. A. A., L. P. B., J.B., D. C., J.C., T. E., B. G., G.J., J.E.L., A. M., L.Y.S., R. S., H. R. V., and P. L. The following authors reported relationships with one or more commercial interests: A. B. received research funding and lectures honoraria from Genentech and consultancy fees from Cell Therapeutics. M. C. received a grant from Perceptive Informatics, Inc; consults for GE Healthcare, FluoroPharma and Astellas; and serves on the speakers bureau for Astellas. J.M.D. served as a consultant for Epsilon Imaging and Methylgene. M. S. E. consults or serves as advisory board member for Roche Laboratories, Cell Therapeutics, GlaxoSmithKline, and Boehringer Ingelheim. S. D. F. serves on advisory boards for Philips Healthcare, Bayer Healthcare, and TeraRecon and received institutional research support from Siemens Healthcare. T. F. consults for GlaxoSmithKline. B. K. received an investigator-initiated award from Pfizer, Inc. T. M. received research funding from the National Health and Medical Research Council in Australia and the Royal Hobart Hospital Foundation, an equipment grant from Philips Medical Systems and Siemens, and a project grant from GE Medical Systems. I. A. S. serves on the speakers bureau for Lantheus. NR 239 TC 77 Z9 79 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2047-2404 EI 2047-2412 J9 EUR HEART J-CARD IMG JI Eur. Heart J.-Cardiovasc. Imaging PD OCT PY 2014 VL 15 IS 10 BP 1063 EP 1093 DI 10.1093/ehjci/jeu192 PG 31 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AT8NB UT WOS:000345188700001 PM 25239940 ER PT J AU Heng, M Kwon, JY AF Heng, Marilyn Kwon, John Y. TI Response to Li et al, "Limitations of Percutaneous Osteotomy for Malunited Tongue-Type Calcaneal Fractures" SO FOOT & ANKLE INTERNATIONAL LA English DT Letter C1 [Heng, Marilyn] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kwon, John Y.] Mercy Med Ctr, Baltimore, MD USA. RP Heng, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mheng@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD OCT PY 2014 VL 35 IS 10 BP 1096 EP 1096 DI 10.1177/1071100714547345 PG 1 WC Orthopedics SC Orthopedics GA AT8NJ UT WOS:000345189500021 PM 25293647 ER PT J AU Shahbabaie, A Golesorkhi, M Zamanian, B Ebrahimpoor, M Keshvari, F Nejati, V Fregni, F Ekhtiari, H AF Shahbabaie, Alireza Golesorkhi, Mehrshad Zamanian, Behnam Ebrahimpoor, Mitra Keshvari, Fatemeh Nejati, Vahid Fregni, Felipe Ekhtiari, Hamed TI State dependent effect of transcranial direct current stimulation (tDCS) on methamphetamine craving SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Addiction; cue-induced craving; methamphetamine; non-invasive brain stimulation; transcranial direct current stimulation ID NONINVASIVE BRAIN-STIMULATION; PREFRONTAL CORTEX; MAGNETIC STIMULATION; NEUROIMAGING EVIDENCE; CORTICAL STIMULATION; ALZHEIMERS-DISEASE; SMOKING CUES; USERS; SCHIZOPHRENIA; MODULATION AB Transcranial direct current stimulation (tDCS) has been shown to modulate subjective craving ratings in drug dependents by modification of cortical excitability in dorsolateral prefrontal cortex (DLPFC). Given the mechanism of craving in methamphetamine (meth) users, we aimed to test whether tDCS of DLPFC could also alter self-reported craving in abstinent meth users while being exposed to meth cues. In this double-blinded, crossover, sham-controlled study, thirty two right-handed abstinent male meth users were recruited. We applied 20 min 'anodal' tDCS (2 mA) or 'sham' tDCS over right DLPFC in a random sequence while subjects performed a computerized cue-induced craving task (CICT) starting after 10 min of stimulation. Immediate craving was assessed before the stimulation, after 10 min of tDCS, and after tDCS termination by visual analog scale (VAS) of 0 to 100. Anodal tDCS of rDLPFC altered craving ratings significantly. We found a significant reduction of craving at rest in real tDCS relative to the sham condition (p=0.016) after 10 min of stimulation. On the other hand, cue-induced VAS craving was rated significantly higher in the real condition in comparison with sham stimulation (p=0.012). Our findings showed a state dependent effect of tDCS: while active prefrontal tDCS acutely reduced craving at rest in the abstinent meth users, it increased craving during meth-related cue exposure. These findings reflect the important role of the prefrontal cortex in both cue saliency evaluation and urge to meth consumption. Research highlights: DLPFC plays an important role in the modulation of meth craving; anodal tDCS on the right DLPFC decreases immediate craving at rest after 10 min; cue-induced meth craving rating increases under the active online stimulation of the right DLPFC; TDCS has a state dependent effect on craving in meth users. C1 [Shahbabaie, Alireza; Golesorkhi, Mehrshad; Ekhtiari, Hamed] Inst Cognit Sci Studies, Translat Neurosci Program, Tehran 1594834111, Iran. [Shahbabaie, Alireza; Zamanian, Behnam; Ekhtiari, Hamed] Univ Tehran Med Sci, Iranian Natl Ctr Addict Studies, Tehran, Iran. [Shahbabaie, Alireza; Golesorkhi, Mehrshad; Ebrahimpoor, Mitra; Ekhtiari, Hamed] Univ Tehran Med Sci, Neuroimaging & Anal Grp, Res Ctr Mol & Cellular Imaging, Tehran, Iran. [Keshvari, Fatemeh; Nejati, Vahid] Shahid Beheshti Univ, Fac Educ & Psychol, Tehran, Iran. [Fregni, Felipe] Spaulding Rehabil Hosp, Spaulding Neuromodulat Ctr, Dept Phys Med & Rehabil, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Ekhtiari, H (reprint author), Inst Cognit Sci Studies, Translat Neurosci Program, 18 Vali E Asr Ave, Tehran 1594834111, Iran. EM h.ekhtiari@iricss.org OI Ebrahimpoor, Mitra/0000-0002-2299-876X FU Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Sciences; Institute for Cognitive Science Studies (ICSS) FX This study was done with non-financial support from RSO at Vardij center, and was supported by grants from the Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Sciences and the Institute for Cognitive Science Studies (ICSS). Authors would like to thank Mr Abbas Deilamizadeh CEO of RSO for his personal commitments and support during the project and Miss Ensiyeh Ghasemian Shirvan for her valuable efforts during all steps of the project. The authors are grateful to the participants for committing the time to this study. NR 45 TC 14 Z9 15 U1 2 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD OCT PY 2014 VL 17 IS 10 BP 1591 EP 1598 DI 10.1017/S1461145714000686 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AT5TL UT WOS:000345004900007 PM 24825251 ER PT J AU Arakaki, RY Strazzula, L Woo, E Kroshinsky, D AF Arakaki, Ryan Y. Strazzula, Lauren Woo, Elaine Kroshinsky, Daniela TI The Impact of Dermatology Consultation on Diagnostic Accuracy and Antibiotic Use Among Patients With Suspected Cellulitis Seen at Outpatient Internal Medicine Offices A Randomized Clinical Trial SO JAMA DERMATOLOGY LA English DT Article ID SOFT-TISSUE INFECTIONS; SKIN AB IMPORTANCE Cellulitis is a common and costly problem, often diagnosed in the outpatient setting. Many cutaneous conditions may clinically mimic cellulitis, but little research has been done to assess the magnitude of the problem. OBJECTIVE To determine if obtaining dermatology consultations in the outpatient primary care setting could assist in the diagnosis of pseudocellulitic conditions and reduce the rate of unnecessary antibiotic use. DESIGN, SETTING, AND PARTICIPANTS Nonblinded randomized clinical trial of competent adults who were diagnosed as having cellulitis by their primary care physicians (PCPs), conducted at outpatient internal medical primary care offices affiliated with a large academic medical center. INTERVENTIONS Outpatient dermatology consultation. MAIN OUTCOMES AND MEASURES Primary outcomes were final diagnosis, antibiotic use, and need for hospitalization. RESULTS A total of 29 patients (12 male and 17 female) were enrolled for participation in this trial. Nine patients were randomized to continue with PCP management (control group), and 20 patients were randomized to receive a dermatology consultation (treatment group). Of the 20 patients in the dermatology consultation group, 2 (10%) were diagnosed as having cellulitis. In the control group, all 9 patients were diagnosed as having cellulitis by PCPs, but dermatologist evaluation determined that 6 (67%) of these patients had a psuedocellulitis rather than true infection. All 9 patients (100%) in the control group were treated for cellulitis with antibiotics vs 2 patients (10%) in the treatment group (P < .001). One patient in the control group was hospitalized. All patients in the treatment group reported improvement of their cutaneous condition at the 1-week follow-up examination. CONCLUSIONS AND RELEVANCE Dermatology consultation in the primary care setting improves the diagnostic accuracy of suspected cellulitis and decreases unnecessary antibiotic use in patients with pseudocellulitic conditions. Obtaining an outpatient dermatology consultation may be a cost-effective strategy that improves quality of care. C1 [Arakaki, Ryan Y.; Strazzula, Lauren; Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Woo, Elaine] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Kroshinsky, D (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,200, Boston, MA 02114 USA. EM dkroshinsky@partners.org FU Dermatology Foundation FX This study was supported in part by The Dermatology Foundation. NR 8 TC 16 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD OCT PY 2014 VL 150 IS 10 BP 1056 EP 1061 DI 10.1001/jamadermatol.2014.1085 PG 6 WC Dermatology SC Dermatology GA AT9WH UT WOS:000345274000004 PM 25143179 ER PT J AU Reddy, S Dick, AM Gerber, MR Mitchell, K AF Reddy, Shivani Dick, Alexandra M. Gerber, Megan R. Mitchell, Karen TI The Effect of a Yoga Intervention on Alcohol and Drug Abuse Risk in Veteran and Civilian Women with Posttraumatic Stress Disorder SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID NATIONAL COMORBIDITY SURVEY; SUBSTANCE USE DISORDERS; RANDOMIZED CONTROLLED-TRIAL; ALTERNATIVE MEDICINE USERS; LARGE MILITARY COHORT; MENTAL-HEALTH; AFGHANISTAN VETERANS; SURVEY-REPLICATION; PTSD TREATMENT; CARE AB Background: Individuals with posttraumatic stress disorder (PTSD) often exhibit high-risk substance use behaviors. Complementary and alternative therapies are increasingly used for mental health disorders, although evidence is sparse. Objectives: Investigate the effect of a yoga intervention on alcohol and drug abuse behaviors in women with PTSD. Secondary outcomes include changes in PTSD symptom perception and management and initiation of evidence-based therapies. Materials and Methods: The current investigation analyzed data from a pilot randomized controlled trial comparing a 12-session yoga intervention with an assessment control for women age 18 to 65 years with PTSD. The Alcohol Use Disorder Identification Test (AUDIT) and Drug Use Disorder Identification Test (DUDIT) were administered at baseline, after the intervention, and a 1-month follow-up. Linear mixed models were used to test the significance of the change in AUDIT and DUDIT scores over time. Treatment-seeking questions were compared by using Fisher exact tests. Results: The mean AUDIT and DUDIT scores decreased in the yoga group; in the control group, mean AUDIT score increased while mean DUDIT score remained stable. In the linear mixed models, the change in AUDIT and DUDIT scores over time did not differ significantly by group. Most yoga group participants reported a reduction in symptoms and improved symptom management. All participants expressed interest in psychotherapy for PTSD, although only two participants, both in the yoga group, initiated therapy. Conclusions: Results from this pilot study suggest that a specialized yoga therapy may play a role in attenuating the symptoms of PTSD, reducing risk of alcohol and drug use, and promoting interest in evidence-based psychotherapy. Further research is needed to confirm and evaluate the strength of these effects. C1 [Reddy, Shivani; Gerber, Megan R.] Boston Univ, Sch Med, Dept Gen Internal Med, Boston, MA 02130 USA. [Mitchell, Karen] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02130 USA. [Reddy, Shivani; Gerber, Megan R.] VA Boston Healthcare Syst, Dept Med, Womens Hlth, Boston, MA USA. [Dick, Alexandra M.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Mitchell, Karen] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. RP Reddy, S (reprint author), Boston Univ, Sch Med, Dept Gen Internal Med, 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM shivani.reddy@bmc.org OI Gerber, Megan/0000-0002-8444-5554 NR 54 TC 4 Z9 4 U1 8 U2 27 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 EI 1557-7708 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD OCT 1 PY 2014 VL 20 IS 10 BP 750 EP 756 DI 10.1089/acm.2014.0014 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA AU6AO UT WOS:000345684700003 PM 25211372 ER PT J AU Li, YC Chen, YZ Liu, WC Thadhani, R AF Li, Yan Chun Chen, Yunzi Liu, Weicheng Thadhani, Ravi TI MicroRNA-mediated mechanism of vitamin D regulation of innate immune response SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE Vitamin D; Inflammation; Macrophage; miR-155; SOCS1; NF-kappaB; IKK beta; Negative feedback loop ID INFLAMMATORY-BOWEL-DISEASE; KAPPA-B ACTIVATION; D-RECEPTOR; NONCODING RNA; 1,25-DIHYDROXYVITAMIN D-3; TRANSGENIC MICE; CELL LYMPHOMAS; MIR-155; GENE; MACROPHAGES AB Macrophages play a critical role in innate immune response to protect the host from pathogenic microorganisms. Inflammatory response is regulated by negative feedback mechanisms to prevent detrimental effects. The SOCS family of proteins is key component of the negative feedback loop that regulates the intensity, duration and quality of cytokine signaling, whereas miR-155 is a key regulator of Toll-like receptor (TLR) signaling that targets SOCS1 in activated macrophages to block the negative feedback loop. Recently we showed that 1,25-dihydroxyvitamin D (1,25(OH)(2) D-3) modulates innate immune response by targeting the miR-155-SOCS1 axis. We found that Vdr deletion leads to hyper inflammatory response in mice and macrophage cultures when challenged with lipopolysaccharide (LPS), due to miR-155 overproduction to excessively suppress SOCS1. Using mice with bic/miR-155 deletion we confirmed that 1,25(OH)(2)D-3 suppresses inflammation and stimulates SOCS1 by down-regulating miR-155. Mechanistically 1,25(OH)2 D3 down-regulates bic transcription by blocking NF-kappa B activation, which is mediated by a kappa B cis-DNA element identified within the first intron of the bic gene. At the molecular level, we demonstrated that VDR inhibits NF-kappa B activation by directly interacting with IKK beta protein. Our studies identified a novel mechanism whereby VDR signaling attenuates TLR-mediated inflammation by enhancing the negative feedback regulation. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Li, Yan Chun; Chen, Yunzi; Liu, Weicheng] Univ Chicago, Dept Med, Div Biol Sci, Chicago, IL 60637 USA. [Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA 02114 USA. RP Li, YC (reprint author), Univ Chicago, Dept Med, 900 E 57th St,KCBD 9110, Chicago, IL 60637 USA. EM cyan@medicine.bsd.uchicago.edu FU NIH [R01HL085793, R01DK092143] FX NIH R01HL085793, R01DK092143. NR 52 TC 13 Z9 14 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD OCT PY 2014 VL 144 SI SI BP 81 EP 86 DI 10.1016/j.jsbmb.2013.09.014 PN A PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AT8KS UT WOS:000345182900013 PM 24103701 ER PT J AU Manchikanti, L Singh, V Falco, FJE Benyamin, RM Hirsch, JA AF Manchikanti, Laxmaiah Singh, Vijay Falco, Frank J. E. Benyamin, Ramsin M. Hirsch, Joshua A. TI Epidemiology of Low Back Pain in Adults SO NEUROMODULATION LA English DT Article DE Chronic low back pain; comorbid factors; health-care utilization; loss of productivity; socioeconomic effects ID PELVIC GIRDLE PAIN; INTERVENTION CENTER-NORRTALJE; HEALTH-CARE EXPENDITURES; ANTECEDENT RISK-FACTOR; CHRONIC NONCANCER PAIN; OF-THE-LITERATURE; 5-YEAR FOLLOW-UP; FUTURE LOW-BACK; UNITED-STATES; GENERAL-POPULATION AB Objective: Low back pain affects many individuals. It has profound effects on well-being and is often the cause of significant physical and psychological health impairments. Low back pain also affects work performance and social responsibilities, such as family life, and is increasingly a major factor in escalating health-care costs. A global review of the prevalence of low back pain in the adult general population has shown its point prevalence to be approximately 12%, with a one-month prevalence of 23%, a one-year prevalence of 38%, and a lifetime prevalence of approximately 40%. Furthermore, as the population ages over the coming decades, the number of individuals with low back pain is likely to increase substantially. This comprehensive review is undertaken to assess the increasing prevalence of lowback pain and the influence of comorbid factors, along with escalating costs. Materials and Methods: A narrative review with literature assessment. Results: In the USA, lowback pain and related costs are escalating. Based on the available literature, it appears that the prevalence of low back pain continues to increase, along with numerous modalities and their application in managing low back pain. Comorbid factors with psychological disorders and multiple medical problems, including obesity, smoking, lack of exercise, increasing age, and lifestyle factors, are considered as risk factors for low back pain. Conclusion: Although it has been alleged that lowback pain resolves in approximately 80% to 90% of patients in about six weeks, irrespective of the administration or type of treatment, with only 5% to 10% of patients developing persistent back pain, this concept has been frequently questioned as the condition tends to relapse and most patients experience multiple episodes years after the initial attack. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Singh, Vijay] Spine Pain Diagnost Associates, Niagara, WI USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys Newark, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Urbana, IL 61801 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 130 TC 38 Z9 39 U1 9 U2 37 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1094-7159 EI 1525-1403 J9 NEUROMODULATION JI Neuromodulation PD OCT PY 2014 VL 17 SU 2 SI SI BP 3 EP 10 DI 10.1111/ner.12018 PG 8 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA AT9FP UT WOS:000345233700002 PM 25395111 ER PT J AU Soriano, LC Bateman, BT Rodriguez, LAG Hernandez-Diaz, S AF Cea Soriano, Lucia Bateman, Brian T. Garcia Rodriguez, Luis A. Hernandez-Diaz, Sonia TI Prescription of antihypertensive medications during pregnancy in the UK SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE pregnancy; hypertension; treatment patterns; antihypertensive medications; THIN; pharmacoepidemiology ID CONVERTING ENZYME-INHIBITORS; HYPERTENSIVE DISORDERS; RECEPTOR ANTAGONISTS; 1ST TRIMESTER; POPULATION; MANAGEMENT; EXPOSURE AB Purpose This study aimed to describe the management of antihypertensive medications in pregnancy by general practitioners in the UK and compare it with current guidelines. Methods We used electronic medical records from The Health Improvement Network database from 1996 to 2010 to identify completed pregnancies. The study cohort included the first pregnancy identified during the study period in women aged 13-49 years. Information on both hypertension diagnoses and prescription of specific antihypertensive medications within the 90 days before the last menstrual period (LMP) and during pregnancy was ascertained from electronic medical records. Results Among 148 544 eligible pregnancies, we identified 1995 (1.3%) during which the women had pre-existing hypertension diagnosed by the LMP date. Overall, the prevalence of antihypertensive medications during the first trimester was 1.5%; beta-blockers were the most commonly prescribed antihypertensive. Among women with pre-existing hypertension, 36% were prescribed an antihypertensive medication during the 90 days before the LMP. Among those, 9.6% and 22.2% had discontinued their medication by the first and second trimesters, respectively. For contraindicated drugs such as angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, the corresponding discontinuation rates were around 25% and 70%. Women who switched therapy received preferably either methyldopa or an alpha/beta-blocker. Conclusions In this population of UK pregnant women, prescription patterns of antihypertensive medications were dominated by recommended treatments, although some patients continued on contraindicated drugs throughout pregnancy or switched to preferred agents in a delayed fashion. Copyright (C) 2014 John Wiley & Sons, Ltd. C1 [Cea Soriano, Lucia; Garcia Rodriguez, Luis A.] Spanish Ctr Pharmacoepidemiol Res CEIFE, Madrid, Spain. [Cea Soriano, Lucia; Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bateman, Brian T.] Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Sch Med,Massachusetts Gen Hosp,Dept Anesthesia Cr, Boston, MA 02115 USA. RP Soriano, LC (reprint author), Spanish Ctr Pharmacoepidemiol Res CEIFE, Madrid, Spain. EM luciaceife@gmail.com NR 25 TC 2 Z9 2 U1 1 U2 4 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 OCT PY 2014 VL 23 IS 10 BP 1051 EP 1058 DI 10.1002/pds.3641 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AT6WF UT WOS:000345076800008 ER PT J AU El-Sherief, AH Lau, CT Wu, CC Drake, RL Abbott, GF Rice, TW AF El-Sherief, Ahmed H. Lau, Charles T. Wu, Carol C. Drake, Richard L. Abbott, Gerald F. Rice, Thomas W. TI International Association for the Study of Lung Cancer (IASLC) Lymph Node Map: Radiologic Review with CT Illustration SO RADIOGRAPHICS LA English DT Article ID FORTHCOMING 7TH EDITION; STAGING PROJECT; TNM CLASSIFICATION; PROPOSALS; REVISION; DESCRIPTORS AB Accurate clinical or pretreatment stage classification of lung cancer leads to optimal treatment outcomes and improved prognostication. Such classification requires an accurate assessment of the clinical extent of regional lymph node metastasis. Consistent and reproducible regional lymph node designations facilitate reliable assessment of the clinical extent of regional lymph node metastasis. Regional lymph node maps, such as the Naruke lymph node map and the Mountain-Dresler modification of the American Thoracic Society lymph node map, were proposed for this purpose in the past. The most recent regional lymph node map to be published is the International Association for the Study of Lung Cancer (IASLC) lymph node map. The IASLC lymph node map supersedes all previous maps and should be used in tandem with the current seventh edition of the tumor, node, metastasis stage classification for lung cancer. (C) RSNA, 2014 . radiographics.rsna.org C1 [El-Sherief, Ahmed H.; Lau, Charles T.] Cleveland Clin, Div Thorac Imaging, Cleveland, OH 44195 USA. [Rice, Thomas W.] Cleveland Clin, Div Thorac & Cardiovasc Surg, Cleveland, OH 44195 USA. [Wu, Carol C.; Abbott, Gerald F.] Massachusetts Gen Hosp, Div Thorac Imaging & Intervent, Boston, MA 02114 USA. [Drake, Richard L.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. RP El-Sherief, AH (reprint author), Cleveland Clin, Div Thorac Imaging, 9500 Euclid Ave,Desk Hb6, Cleveland, OH 44195 USA. EM ahelsherief@gmail.com FU Cum Laude award FX Recipient of a Cum Laude award for an education exhibit at the 2011 RSNA Annual Meeting. Received March 25, 2013; revision requested July 21 and received May 20, 2014; final version accepted May 21. For this journal-based SA-CME activity, the authors, editor, and reviewers have disclosed no relevant relationships. Address correspondence to A. H. E. (e-mail: ahelsherief@gmail.com). NR 14 TC 9 Z9 9 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD OCT PY 2014 VL 34 IS 6 BP 1680 EP 1691 DI 10.1148/rg.346130097 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AT5SC UT WOS:000345001100014 PM 25310423 ER PT J AU Nickell, LT Lichtenberger, JP Khorashadi, L Abbott, GF Carter, BW AF Nickell, Larry T., Jr. Lichtenberger, John P., III Khorashadi, Leila Abbott, Gerald F. Carter, Brett W. TI Multimodality Imaging for Characterization, Classification, and Staging of Malignant Pleural Mesothelioma SO RADIOGRAPHICS LA English DT Article ID EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY; EPITHELIOID HEMANGIOENDOTHELIOMA; CERVICAL MEDIASTINOSCOPY; EXTRAPLEURAL PNEUMONECTOMY; COMPUTED-TOMOGRAPHY; DIAGNOSIS; CT; TUMORS; MANIFESTATIONS; ASSOCIATION AB Malignant pleural mesothelioma (MPM) is the most common primary malignancy of the pleura and is associated with asbestos exposure in approximately 80% of patients. The patient prognosis is poor, with a median survival of 9-17 months after diagnosis. However, improved survival and decreased morbidity and mortality have been demonstrated when the diagnosis is made in the early stages of disease and specific treatment strategies are implemented. A staging system that focuses on the extent of primary tumor (T), lymph node involvement (N), and metastatic disease (M) has been devised by the International Mesothelioma Interest Group and emphasizes factors related to overall survival. Radiologists should recognize the manifestations of MPM across multiple imaging modalities, translate these findings into the updated staging system, and understand the effects of appropriate staging on treatment and survival. Computed tomography (CT) remains the primary imaging modality used to evaluate MPM and efficiently demonstrates the extent of primary tumor, intrathoracic lymphadenopathy, and extrathoracic spread. However, additional imaging modalities, such as magnetic resonance (MR) imaging of the thorax and positron emission tomography (PET)/CT with fluorodeoxyglucose, have emerged in recent years and are complementary to CT for disease staging and evaluation of patients with MPM. Thoracic MR imaging is particularly useful for identifying invasion of the chest wall, mediastinum, and diaphragm, and PET/CT can accurately demonstrate intrathoracic and extrathoracic lymphadenopathy and metastatic disease. (C) RSNA, 2014 . radiographics.rsna.org C1 [Nickell, Larry T., Jr.] Baylor Univ, Med Ctr, Dept Radiol, Dallas, TX USA. [Lichtenberger, John P., III] David Grant Med Ctr, Dept Radiol, Fairfield, CA USA. [Khorashadi, Leila] Mt Auburn Hosp, Dept Radiol, Cambridge, MA 02238 USA. [Abbott, Gerald F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Carter, Brett W.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. RP Carter, BW (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, 1515 Holcombe Blvd,Unit 1478, Houston, TX 77030 USA. EM bcarter2@mdanderson.org FU Certificate of Merit award FX Recipient of a Certificate of Merit award for an education exhibit at the 2012 RSNA Annual Meeting. Received March 1, 2013; revision requested June 7 and received November 9; accepted November 22. For this journal-based SA-CME activity, the authors J.P.L., G. F. A., and B. W. C. have provided disclosures (see p 1705); all other authors, the editor, and the reviewers have disclosed no relevant relationships. Address correspondence to B. W. C. (e-mail: bcarter2@mdanderson.org). NR 47 TC 10 Z9 10 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD OCT PY 2014 VL 34 IS 6 BP 1692 EP 1706 DI 10.1148/rg.346130089 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AT5SC UT WOS:000345001100015 PM 25310424 ER PT J AU Makar, RS Padmanabhan, A Kim, HC Anderson, C Sugrue, MW Linenberger, M AF Makar, Robert S. Padmanabhan, Anand Kim, Haewon C. Anderson, Christina Sugrue, Michele W. Linenberger, Michael TI Use of Laboratory Tests to Guide Initiation of Autologous Hematopoietic Progenitor Cell Collection by Apheresis: Results From the Multicenter Hematopoietic Progenitor Cell Collection by Apheresis Laboratory Trigger Survey SO TRANSFUSION MEDICINE REVIEWS LA English DT Review DE HPC(A) collection; PB CD34+cell count; Trigger; Mobilization ID COLONY-STIMULATING FACTOR; BLOOD STEM-CELLS; PERIPHERAL-BLOOD; G-CSF; PREDICTIVE-VALUE; BREAST-CANCER; CD34(+) CELLS; MOBILIZATION; TRANSPLANTATION; HARVEST AB Limited literature describes the value of laboratory "triggers" to guide collection of peripheral blood (PB) hematopoietic progenitor cells (HPCs) by apheresis [HPC(A)]. We used a web-based survey to determine which parameters are used to initiate autologous HPC(A) collection in adult and pediatric patients and to identify common practice patterns. Members of the AABB Cellular Therapy Product Collection and Clinical Practices Subsection and the American Society for Apheresis HPC Donor Subcommittee drafted and developed relevant survey questions. A web link to the survey was distributed by electronic newsletter or email. Responses from 67 programs that perform autologous HPC(A) collections, including academic medical centers (n = 46), blood centers (n = 10), community hospitals (n = 5), and a variety of other medical institutions (n = 6), were analyzed. Ninety-three percent (62/67) of programs used a laboratory parameter to initiate HPC(A) collection. In both adult (40/54, 74%) and pediatric (29/38, 76%) patients, the PB CD34+ cell count was the most common parameter used to initiate HPC(A) collection. The median PB CD34+ trigger value was 10/mu L for both patient populations. Among centers routinely using the PB CD34+ cell count to initiate apheresis, 51% (22/43) first sent the test before the patient presented for collection. Although more than 90% of centers used a laboratory test to trigger apheresis in cytokine-mobilized (44/48) or chemomobilized patients (50/53), only 57% (30/53) used a laboratory trigger if the patient was mobilized with granulocyte colony-stimulating factor plus plerixafor. Forty-two percent (21/50) of programs that routinely measured the PB CD34+ count before collection and discontinued further HPC(A) collection based on product CD34+ cell yield also stopped if the PB CD34+ value before apheresis was considered too low to proceed. Most programs use the PB CD34+ cell count to trigger autologous HPC(A) collection. Some centers also use this parameter to stop further collections. Laboratory tests are used less frequently to initiate apheresis when patients are mobilized with plerixafor. These data reveal ongoing diversity in clinical practices and suggest that consensus guidelines on use of laboratory parameters may further optimize HPC(A) collection. (C) 2014 Elsevier Inc. All rights reserved. C1 [Makar, Robert S.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Padmanabhan, Anand] Blood Ctr Wisconsin, Inst Med Sci, Milwaukee, WI USA. [Kim, Haewon C.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Apheresis Serv,Dept Pediat, Philadelphia, PA 19104 USA. [Anderson, Christina] Carter BloodCare, Clin Apheresis Serv, Dallas, TX USA. [Sugrue, Michele W.] Univ Florida Coll Med, Dept Med, Gainesville, FL USA. [Linenberger, Michael] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. RP Makar, RS (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, 55 Fruit St,GRJ-2-206C, Boston, MA 02114 USA. EM rmakar@partners.org NR 34 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0887-7963 EI 1532-9496 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD OCT PY 2014 VL 28 IS 4 BP 198 EP 204 DI 10.1016/j.tmrv.2014.08.002 PG 7 WC Hematology SC Hematology GA AT6OS UT WOS:000345059300003 PM 25311468 ER PT J AU Jensen, JD Delcambre, MR Nguyen, G Sami, N AF Jensen, J. Daniel Delcambre, Macey Renault Nguyen, Gloria Sami, Naveed TI Biologic Therapy with or Without Topical Treatment in Psoriasis: What Does the Current Evidence Say? SO AMERICAN JOURNAL OF CLINICAL DERMATOLOGY LA English DT Article ID SEVERE PLAQUE PSORIASIS; PROPIONATE SPRAY 0.05-PERCENT; ADD-ON THERAPY; CALCIPOTRIOL OINTMENT; COMBINATION THERAPY; OPEN-LABEL; MODERATE; MULTICENTER; EFFICACY; ETANERCEPT AB Biologic therapy represents a relatively new class of drugs which have revolutionized the treatment of psoriasis and are used with increasing frequency in order to control this chronic, systemic inflammatory disease. However, it is unclear what role there is for combination therapy of biologics with traditional topical agents. The purpose of this article is to assess the literature on the role of topical agents as adjuvants to biological treatments in the treatment of psoriasis and identify areas for further research. A MEDLINE search was performed in order to identify English-language publications from 1996 to 2014 examining combination biologic therapy with topical medications in the treatment of psoriasis. Data from these clinical studies are summarized and the outcomes are discussed. In general, the addition of adjuvant topical therapy to systemic biologic therapy allowed for a reduction in dosage and side effects of both agents, maintenance of initial response to biologics, treatment of recalcitrant lesions in partial responders, and potential acceleration of response to biologic therapies. The current data, though limited, suggest that using topical therapies as adjunct treatment to biologics is a well tolerated and effective means of controlling psoriasis and improving quality of life for patients. However, the treating physician should remain attentive to signs of adverse events and seek opportunities to reduce the dose or treatment frequency during chronic use. C1 [Jensen, J. Daniel] Univ Alabama, Dept Dermatol, South Birmingham, AL 35294 USA. [Delcambre, Macey Renault] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. [Nguyen, Gloria] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. [Sami, Naveed] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Sami, N (reprint author), Univ Alabama, Dept Dermatol, EFH 414,1530 3rd Ave, South Birmingham, AL 35294 USA. EM nsami@uab.edu NR 33 TC 0 Z9 0 U1 1 U2 4 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1175-0561 EI 1179-1888 J9 AM J CLIN DERMATOL JI Am. J. Clin. Dermatol. PD OCT PY 2014 VL 15 IS 5 BP 379 EP 385 DI 10.1007/s40257-014-0089-1 PG 7 WC Dermatology SC Dermatology GA AT0BN UT WOS:000344602100001 PM 25027461 ER PT J AU Yang, CS Kroshinksy, D Cummings, BM AF Yang, Catherine S. Kroshinksy, Daniela Cummings, Brian M. TI Neonatal Junctional Epidermolysis Bullosa: Treatment Conundrums and Ethical Decision Making SO AMERICAN JOURNAL OF CLINICAL DERMATOLOGY LA English DT Review ID SQUAMOUS-CELL CARCINOMA; GRONINGEN PROTOCOL; MUTATIONAL PROFILE; CARRIER FREQUENCY; MEDICAL FUTILITY; CHILDREN; TRANSPLANTATION; COMPLICATIONS; EXPERIENCE; NEWBORN AB Junctional epidermolysis bullosa (JEB), generalized severe (previously called JEB, Herlitz-type) has an extremely poor prognosis, with a mean age of death at 5 months old and most dead before age 3 years. We describe a typical case of a neonate with JEB who developed failure to thrive before his death from fungal septicemia at 4 months of age. This case highlights the ethical considerations of invasive treatments such as gastrostomy tube placements, intubations, and central line placements in neonates with JEB. We review the literature as well as discuss the ethical conundrums in the care of patients with JEB and other severe forms of epidermolysis bullosa. C1 [Yang, Catherine S.] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02903 USA. [Kroshinksy, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Cummings, Brian M.] Massachusetts Gen Hosp Children, Dept Pediat, Boston, MA USA. RP Yang, CS (reprint author), Brown Univ, Warren Alpert Med Sch, Dept Dermatol, 593 Eddy St,APC 1018, Providence, RI 02903 USA. EM catherine_yang@brown.edu NR 43 TC 1 Z9 1 U1 0 U2 4 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1175-0561 EI 1179-1888 J9 AM J CLIN DERMATOL JI Am. J. Clin. Dermatol. PD OCT PY 2014 VL 15 IS 5 BP 445 EP 450 DI 10.1007/s40257-014-0091-7 PG 6 WC Dermatology SC Dermatology GA AT0BN UT WOS:000344602100006 PM 25117154 ER PT J AU Johnson, DA Barkun, AN Cohen, LB Dominitz, JA Kaltenbach, T Martel, M Robertson, DJ Boland, CR Giardello, FM Lieberman, DA Levin, TR Rex, DK AF Johnson, David A. Barkun, Alan N. Cohen, Larry B. Dominitz, Jason A. Kaltenbach, Tonya Martel, Myriam Robertson, Douglas J. Boland, C. Richard Giardello, Frances M. Lieberman, David A. Levin, Theodore R. Rex, Douglas K. TI Optimizing Adequacy of Bowel Cleansing for Colonoscopy: Recommendations From the US Multi-Society Task Force on Colorectal Cancer SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID ORAL SODIUM-PHOSPHATE; RANDOMIZED CONTROLLED-TRIAL; POLYETHYLENE-GLYCOL SOLUTION; ELECTROLYTE LAVAGE SOLUTION; PLUS ASCORBIC-ACID; INVESTIGATOR-BLINDED TRIAL; HIGH-DOSE SENNA; INCREASE SCREENING COLONOSCOPY; ADENOMA DETECTION RATE; CLEAR LIQUID DIET AB Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States (1). Colonoscopy can prevent CRC by the detection and removal of precancerous lesions. In addition to CRC screening and surveillance, colonoscopy is used widely for the diagnostic evaluation of symptoms and other positive CRC screening tests. Regardless of indication, the success of colonoscopy is linked closely to the adequacy of preprocedure bowel cleansing. Unfortunately, up to 20-25% of all colonoscopies are reported to have an inadequate bowel preparation (2,3). The reasons for this range from patient-related variables such as compliance with preparation instructions and a variety of medical conditions that make bowel cleansing more difficult to unit-specific factors (eg, extended wait times aft er scheduling of colonoscopy) (4). Adverse consequences of ineffective bowel preparation include lower adenoma detection rates, longer procedural time, lower cecal intubation rates, increased electrocautery risk, and shorter intervals between examinations (3,5-7). Bowel preparation formulations intended for precolonoscopy cleansing are assessed based on their efficacy, safety, and tolerability. Lack of specific organ toxicity is considered to be a prerequisite for bowel preparations. Between cleansing efficacy and tolerability, however, the consequences of inadequate cleansing suggest that efficacy should be a higher priority than tolerability. Consequently, the choice of a bowel cleansing regimen should be based on cleansing efficacy first and patient tolerability second. However, efficacy and tolerability are closely interrelated. For example, a cleansing agent that is poorly tolerated and thus not fully ingested may not achieve an adequate cleansing. The goals of this consensus document are to provide expert, evidence-based recommendations for clinicians to optimize colonoscopy preparation quality and patient safety. Recommendations are provided using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) scoring system, which weighs the strength of the recommendation and the quality of the evidence (8). C1 [Johnson, David A.] Eastern VA Med Sch, Norfolk, VA 23507 USA. [Barkun, Alan N.; Martel, Myriam] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Cohen, Larry B.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Dominitz, Jason A.] Univ Washington, Seattle, WA 98195 USA. [Kaltenbach, Tonya] Stanford Univ, Sch Med, Vet Affairs Palo Alto, Palo Alto, CA 94304 USA. [Robertson, Douglas J.] VA Med Ctr, Portland, OR USA. [Robertson, Douglas J.] Geisel Sch Med Dartmouth, White River Jct, VT USA. [Boland, C. Richard] Baylor Univ, Med Ctr, Dallas, TX USA. [Giardello, Frances M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Lieberman, David A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Levin, Theodore R.] Kaiser Permanente Med Ctr, Walnut Creek, CA USA. [Rex, Douglas K.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. RP Johnson, DA (reprint author), Eastern VA Med Sch, Norfolk, VA 23507 USA. EM dajevms@aol.com OI Dominitz, Jason/0000-0002-8070-7086 FU Boston Scientific and Cook; Salix; Olympus America, Inc; Braintree Laboratories and Ferring Pharmaceuticals; Given Imaging; Olympus America Corp FX These authors disclose the following: David Johnson has served as a consultant and clinical investigator for Epigenomics, as a consultant for Given Imaging, and as a clinical investigator for Exact Sciences; A. Barkun has served as a consultant for Olympus, Inc, and Pendopharm, Inc, and has received clinical research support from Boston Scientific and Cook; L. B. Cohen has served as a consultant and on the speaker's bureau and received research support from Salix, and as a consultant for Braintree; T. Kaltenbach has been a research grant recipient and consultant for Olympus America, Inc, D.J. Robertson has served as a consultant for Given Imaging; D. A. Lieberman has served on the scientific advisory boards for Exact Sciences, Given Imaging, and Roche, and as a consultant for MOTUS; and D. K. Rex has received research support and served as a consultant for Braintree Laboratories and Ferring Pharmaceuticals, Given Imaging, and Olympus America Corp, has served as a consultant for Epigenomics and Exact Sciences, and has served on the speaker's bureau for Boston Scientific, Inc. The remaining authors disclose no conflicts. NR 252 TC 31 Z9 31 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2014 VL 109 IS 10 BP 1528 EP 1545 DI 10.1038/ajg.2014.272 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS7UM UT WOS:000344460100005 PM 25223578 ER PT J AU Ford, AC Quigley, EMM Lacy, BE Lembo, AJ Saito, YA Schiller, LR Soffer, EE Spiegel, BMR Moayyedi, P AF Ford, Alexander C. Quigley, Eamonn M. M. Lacy, Brian E. Lembo, Anthony J. Saito, Yuri A. Schiller, Lawrence R. Soffer, Edy E. Spiegel, Brennan M. R. Moayyedi, Paul TI Efficacy of Prebiotics, Probiotics, and Synbiotics in Irritable Bowel Syndrome and Chronic Idiopathic Constipation: Systematic Review and Meta-analysis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; LACTOBACILLUS-PLANTARUM 299V; QUALITY-OF-LIFE; SIGNIFICANTLY REDUCES SYMPTOMS; PLACEBO-CONTROLLED-TRIAL; DOUBLE-BLIND; CLINICAL-TRIAL; FERMENTED MILK; FECAL MICROBIOTA; PRIMARY-CARE AB OBJECTIVES: Irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC) are functional bowel disorders. Evidence suggests that disturbance in the gastrointestinal microbiota may be implicated in both conditions. We performed a systematic review and meta-analysis to examine the efficacy of prebiotics, probiotics, and synbiotics in IBS and CIC. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Randomized controlled trials (RCTs) recruiting adults with IBS or CIC, which compared prebiotics, probiotics, or synbiotics with placebo or no therapy, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardized or weighted mean difference with a 95% CI. RESULTS: The search strategy identified 3,216 citations. Forty-three RCTs were eligible for inclusion. The RR of IBS symptoms persisting with probiotics vs. placebo was 0.79 (95% CI 0.70-0.89). Probiotics had beneficial effects on global IBS, abdominal pain, bloating, and flatulence scores. Data for prebiotics and synbiotics in IBS were sparse. Probiotics appeared to have beneficial effects in CIC (mean increase in number of stools per week = 1.49; 95% CI = 1.02-1.96), but there were only two RCTs. Synbiotics also appeared beneficial (RR of failure to respond to therapy = 0.78; 95% CI 0.67-0.92). Again, trials for prebiotics were few in number, and no definite conclusions could be drawn. CONCLUSIONS: Probiotics are effective treatments for IBS, although which individual species and strains are the most beneficial remains unclear. Further evidence is required before the role of prebiotics or synbiotics in IBS is known. The efficacy of all three therapies in CIC is also uncertain. C1 [Ford, Alexander C.] St James Univ Hosp, Leeds Gastroenterol Inst, Leeds LS9 7TF, W Yorkshire, England. [Ford, Alexander C.] Univ Leeds, Leeds Inst Biomed & Clin Sci, Leeds, W Yorkshire, England. [Quigley, Eamonn M. M.] Houston Methodist Hosp, Dept Med, Div Gastroenterol & Hepatol, Houston, TX USA. [Lacy, Brian E.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Lembo, Anthony J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Saito, Yuri A.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Schiller, Lawrence R.] Baylor Univ, Med Ctr, Digest Hlth Associates Texas, Dallas, TX USA. [Soffer, Edy E.] Univ So Calif, Div Gastroenterol Cedars Sinai, Los Angeles, CA USA. [Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. [Moayyedi, Paul] McMaster Univ, Hlth Sci Ctr, Div Gastroenterol, Hamilton, ON, Canada. RP Ford, AC (reprint author), St James Univ Hosp, Leeds Gastroenterol Inst, Room 125,4th Floor,Bexley Wing,Beckett St, Leeds LS9 7TF, W Yorkshire, England. EM alexf12399@yahoo.com RI Ford, Alexander/K-5491-2012; Moayyedi, Paul/M-6178-2014 OI Ford, Alexander/0000-0001-6371-4359; Moayyedi, Paul/0000-0002-3616-9292 FU American College of Gastroenterology FX This work was supported by American College of Gastroenterology. NR 72 TC 85 Z9 91 U1 14 U2 66 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2014 VL 109 IS 10 BP 1547 EP 1561 DI 10.1038/ajg.2014.202 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS7UM UT WOS:000344460100007 PM 25070051 ER PT J AU Baryawno, N Scadden, DT AF Baryawno, Ninib Scadden, David T. TI Blood loses it when nerves go bad SO CELL RESEARCH LA English DT Editorial Material ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW NICHE; MUTATION; JAK2 AB Myeloproliferative neoplasms are diseases that arise in the stem cells of the blood. In a recent paper published in Nature, Arranz et al. demonstrated that abrogation of sympathetic nerve fibers reduced bone marrow Nestin(+) mesenchymal cells, which in turn led to an expansion of hematopoietic stem cells and progression of myeloproliferative neoplasms. C1 [Baryawno, Ninib; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Baryawno, Ninib; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Baryawno, Ninib; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM david_scadden@harvard.edu OI Baryawno, Ninib/0000-0001-8211-8368 NR 12 TC 1 Z9 1 U1 0 U2 5 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD OCT PY 2014 VL 24 IS 10 BP 1151 EP 1152 DI 10.1038/cr.2014.98 PG 2 WC Cell Biology SC Cell Biology GA AT5OZ UT WOS:000344993300001 PM 25070156 ER PT J AU Choi, YS Fisher, DE AF Choi, Yeon Sook Fisher, David E. TI UV and melanoma: the TP53 link SO CELL RESEARCH LA English DT Editorial Material ID ULTRAVIOLET-RADIATION; MICE; MUTATIONS AB Ultraviolet radiation (UVR) is a major risk factor for melanoma development, but it has been unclear exactly how UVR leads to melanomagenesis. In a recent publication in Nature, Viros et al. identify TP53/Trp53 as a UVR-target gene in melanoma and show that UVR-induced TP53/Trp53 mutations accelerate BRAF(V600E)-driven melanomagenesis. C1 [Choi, Yeon Sook; Fisher, David E.] Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr,Med Sch, Boston, MA 02114 USA. RP Fisher, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr,Med Sch, 55 Fruit St, Boston, MA 02114 USA. EM dfisher3@partners.org FU NIAMS NIH HHS [R01 AR043369] NR 11 TC 0 Z9 0 U1 1 U2 12 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD OCT PY 2014 VL 24 IS 10 BP 1157 EP 1158 DI 10.1038/cr.2014.95 PG 2 WC Cell Biology SC Cell Biology GA AT5OZ UT WOS:000344993300004 PM 25033756 ER PT J AU Trebicka, E Shanmugam, NKN Mikhailova, A Alter, G Cherayil, BJ AF Trebicka, Estela Shanmugam, Nanda Kumar N. Mikhailova, Anastassia Alter, Galit Cherayil, Bobby J. TI Effect of Human Immunodeficiency Virus Infection on Plasma Bactericidal Activity against Salmonella enterica Serovar Typhimurium SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID NONTYPHOIDAL SALMONELLA; CRYPTOCOCCUS-NEOFORMANS; NEISSERIA-MENINGITIDIS; DISEASE; HIV-1; BACTEREMIA; ANTIBODIES; ADULTS; BLOCKING; IGG AB Individuals with human immunodeficiency virus (HIV) infection have increased susceptibility to invasive disease caused by Salmonella enterica serovar Typhimurium. Studies from Africa have suggested that this susceptibility is related in part to the development of a high level of lipopolysaccharide (LPS)-specific IgG that is able to inhibit the killing of S. Typhimurium by bactericidal antibodies in healthy individuals. To explore this issue further, we examined the bactericidal activity against S. Typhimurium using serum and plasma samples from healthy controls and various clinical subgroups of HIV-infected adults in the United States. We found that the bactericidal activity in the samples from HIV-positive elite controllers was comparable to that from healthy individuals, whereas it was significantly reduced in HIV-positive viremic controllers and untreated chronic progressors. As demonstrated previously for healthy controls, the bactericidal activity of the plasma from the elite controllers was inhibited by preincubation with S. Typhimurium LPS, suggesting that it was mediated by anti-LPS antibodies. S. Typhimurium LPS-specific IgG was significantly reduced in all subgroups of HIV-infected individuals. Interestingly, and in contrast to the healthy controls, plasma from all HIV-positive subgroups inhibited in vitro killing of S. Typhimurium by plasma from a healthy individual. Our results, together with the findings from Africa, suggest that multiple mechanisms may be involved in the HIV-induced dysregulation of humoral immunity to S. Typhimurium. C1 [Trebicka, Estela; Shanmugam, Nanda Kumar N.; Cherayil, Bobby J.] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. [Mikhailova, Anastassia; Alter, Galit] MIT, Ragon Inst, Massachusetts Gen Hosp, Cambridge, MA 02139 USA. [Mikhailova, Anastassia; Alter, Galit] Harvard Univ, Cambridge, MA 02138 USA. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. EM cherayil@helix.mgh.harvard.edu FU Public Health Service from the National Institute of Allergy and Infectious Diseases [R01 AI089700]; Nutrition and Obesity Research Center at Harvard [P30DK040561] FX This work was supported by Public Health Service grant R01 AI089700 to B.J.C. from the National Institute of Allergy and Infectious Diseases, and by the Nutrition and Obesity Research Center at Harvard (P30DK040561 to W. Allan Walker). NR 37 TC 6 Z9 6 U1 2 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD OCT PY 2014 VL 21 IS 10 BP 1437 EP 1442 DI 10.1128/CVI.00501-14 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AT0TN UT WOS:000344647800008 PM 25121777 ER PT J AU Kulke, MH O'Dorisio, T Phan, A Bergsland, E Law, L Banks, P Freiman, J Frazier, K Jackson, J Yao, JC Kvols, L Lapuerta, P Zambrowicz, B Fleming, D Sands, A AF Kulke, Matthew H. O'Dorisio, Thomas Phan, Alexandria Bergsland, Emily Law, Linda Banks, Phillip Freiman, Joel Frazier, Kenny Jackson, Jessica Yao, James C. Kvols, Larry Lapuerta, Pablo Zambrowicz, Brian Fleming, Douglas Sands, Arthur TI Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide SO ENDOCRINE-RELATED CANCER LA English DT Article DE adult; carcinoid syndrome; diarrhea; neuroendocrine tumor; serotonin; tryptophan hydroxylase ID NEUROENDOCRINE TUMORS; HEART-DISEASE AB Serotonin produced by neuroendocrine tumors is believed to be a principal cause of the diarrhea in carcinoid syndrome. We assessed the safety and efficacy of telotristat etiprate, an oral serotonin synthesis inhibitor, in patients with diarrhea associated with carcinoid syndrome. In this prospective, randomized study, patients with evidence of carcinoid tumor and >= 4 bowel movements (BMs)/day despite stable-dose octreotide LAR depot therapy were enrolled in sequential, escalating, cohorts of four patients per cohort. In each cohort, one patient was randomly assigned to placebo and three patients to telotristat etiprate, at 150, 250, 350, or 500 mg three times a day (tid). In a subsequent cohort, one patient was assigned to placebo and six patients to telotristat etiprate 500 mg tid. Patients were assessed for safety, BM frequency (daily diary), 24 h urinary 5-hydroxyindoleacetic acid (u5-HIAA), and adequate relief of carcinoid gastrointestinal symptoms (using a weekly questionnaire). Twenty-three patients were treated: 18 received telotristat etiprate and five received placebo. Adverse events were generally mild. Among evaluable telotristat etiprate-treated patients, 5/18 (28%) experienced a >= 30% reduction in BM frequency for >= 2 weeks, 9/16 (56%) experienced biochemical response (>= 50% reduction or normalization in 24-h u5-HIAA) at week 2 or 4, and 10/18 (56%) reported adequate relief during at least 1 of the first 4 weeks of treatment. Similar activity was not observed in placebo-treated patients. Telotristat etiprate was well tolerated. Our observations suggest that telotristat etiprate has activity in controlling diarrhea associated with carcinoid syndrome. Further studies confirming these findings are warranted. C1 [Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [O'Dorisio, Thomas] Univ Iowa, Hosp & Clin, Iowa City, IA USA. [Phan, Alexandria; Yao, James C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bergsland, Emily] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Law, Linda; Banks, Phillip; Freiman, Joel; Frazier, Kenny; Jackson, Jessica; Lapuerta, Pablo; Zambrowicz, Brian; Fleming, Douglas; Sands, Arthur] Lexicon Pharmaceut Inc, The Woodlands, TX USA. [Kvols, Larry] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM Matthew_Kulke@dfci.harvard.edu FU Lexicon Pharmaceuticals, Inc. FX This study was funded in whole by Lexicon Pharmaceuticals, Inc. ClinicalTrials.gov registry: # NCT00853047. NR 14 TC 35 Z9 35 U1 1 U2 7 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD OCT PY 2014 VL 21 IS 5 BP 705 EP 714 DI 10.1530/ERC-14-0173 PG 10 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA AT2TG UT WOS:000344788400016 PM 25012985 ER PT J AU Omoto, M Katikireddy, KR Rezazadeh, A Dohlman, TH Chauhan, SK AF Omoto, Masahiro Katikireddy, Kishore R. Rezazadeh, Alexandra Dohlman, Thomas H. Chauhan, Sunil K. TI Mesenchymal Stem Cells Home to Inflamed Ocular Surface and Suppress Allosensitization in Corneal Transplantation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE mesenchymal stem cells; homing; cornea transplantation; allosensitization; antigen-presenting cells ID ANTIGEN-PRESENTING CELLS; REGULATORY T-CELLS; BONE-MARROW; PENETRATING KERATOPLASTY; ALLOGRAFT-REJECTION; SURVIVAL; MODEL; RECONSTRUCTION; INFUSION; PROLONG AB PURPOSE. To investigate whether systemically injected syngeneic mesenchymal stem cells (MSCs) can home to the transplanted cornea, suppress induction of alloimmunity, and promote allograft survival. METHODS. Mesenchymal stem cells were generated from bone marrow of wild-type BALB/c or GFP (green fluorescent protein)(+) C57BL/6 mice, and 1 x 10(6) cells were intravenously injected to allografted recipients 3 hours after surgery. Mesenchymal stem cells homing to the cornea were examined at day 3 post transplantation by immunohistochemistry. MHC (major histocompatibility complex) II(+)CD11c(+) cells were detected in the cornea and lymph nodes (LNs) 14 days post transplantation using flow cytometry. Cytokine expression of bone marrow-derived dendritic cells (BMDCs) was determined using real-time PCR. ELISPOT assay was used to assess indirect and direct host T cell allosensitization, and graft survival was evaluated by slit-lamp biomicroscopy weekly up to 8 weeks. RESULTS. Intravenously injected GFP(+) MSCs were found in abundance in the transplanted cornea, conjunctiva, and LNs, but not in the ungrafted (contralateral) tissue. The frequencies of mature MHC II(+)CD11c(+) antigen-presenting cells (APCs) were substantially decreased in the corneas and draining LNs of MSC-injected allograft recipients compared to control recipients. Maturation and function of in vitro cultured BMDCs were decreased when cocultured with MSCs. Draining LNs of MSC-injected allograft recipients showed lower frequencies of IFN gamma-secreting Th1 cells compared to the control group. Allograft survival rate was significantly higher in MSC-injected recipients compared to non-MSC-injected recipients. CONCLUSIONS. Our data demonstrate that systemically administered MSCs specifically home to the inflamed ocular surface and promote allograft survival by inhibiting APC maturation and induction of alloreactive T cells. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. RP Chauhan, SK (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM Sunil_Chauhan@meei.harvard.edu FU U.S. Department of Defense, Massachusetts Lions Eye Research Award; Eleanor and Miles Shore Fellowship for Scholars in Medicine, Harvard Medical School FX Supported in part by grants from the U.S. Department of Defense, Massachusetts Lions Eye Research Award, and the Eleanor and Miles Shore Fellowship for Scholars in Medicine, Harvard Medical School. NR 35 TC 8 Z9 8 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2014 VL 55 IS 10 DI 10.1167/iovs.14-15413 PG 8 WC Ophthalmology SC Ophthalmology GA AT1ZS UT WOS:000344730500010 PM 25228546 ER PT J AU van der Ent, W Burrello, C Teunisse, AFAS Ksander, BR van der Velden, PA Jager, MJ Jochemsen, AG Snaar-Jagalska, BE AF van der Ent, Wietske Burrello, Claudia Teunisse, Amina F. A. S. Ksander, Bruce R. van der Velden, Pieter A. Jager, Martine J. Jochemsen, Aart G. Snaar-Jagalska, B. Ewa TI Modeling of Human Uveal Melanoma in Zebrafish Xenograft Embryos SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE uveal melanoma; xenotransplantation; zebrafish; drug treatment ID IN-VIVO; CELL-LINES; CANCER MODEL; ESTABLISHMENT; ACTIVATION; MUTATIONS; BAP1; METASTASIS; INHIBITION; EXPRESSION AB PURPOSE. Uveal melanoma (UM) is fatal in up to 50% of patients because of liver metastases that are refractory to therapies currently available. While murine xenograft models for human uveal melanoma are available, they have limited utility for screening large compound libraries in drug discovery studies. Therefore, new robust preclinical models are needed that can efficiently evaluate drug efficacy for treatment of this malignancy. METHODS. Uveal melanoma cell lines generated from primary tumors (92.1, Mel270) and metastases (OMM2.3, OMM2.5, OMM1) were injected into the yolk of 2-day-old zebrafish embryos. After 6 days, proliferation and active migration was quantified via automated confocal image analysis. To determine the suitability of this xenotransplantation model for drug testing, drugs with three different activities (dasatinib, quisinostat, and MLN-4924) were added to the water of uveal melanoma-engrafted embryos. RESULTS. All tested UM cell lines proliferated and migrated in the embryos; significant differences could be discerned between cell lines: Cells derived from metastases showed more migration and proliferation than cells derived from the primary tumors, and provided preclinical models for drug testing. Addition of the Src-inhibitor dasatinib in the water of engrafted embryos reduced proliferation and migration of high Src-expressing 92.1 cells, but did not affect low Src-expressing metastatic OMM2.3 cells. Two experimental anticancer drugs, quisinostat (a histone deacetylase inhibitor) and MLN-4924 (neddylation pathway inhibitor), blocked migration and proliferation of 92.1 and OMM2.3. CONCLUSIONS. We established a zebrafish xenograft model of human uveal melanoma with demonstrated applicability for screening large libraries of compounds in drug discovery studies. C1 [van der Ent, Wietske; Burrello, Claudia; Snaar-Jagalska, B. Ewa] Leiden Univ, Inst Biol, NL-2300 RC Leiden, Netherlands. [van der Ent, Wietske] Leiden Univ, Med Ctr, Dept Pathol, NL-2300 RC Leiden, Netherlands. [Teunisse, Amina F. A. S.; Jochemsen, Aart G.] Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2300 RC Leiden, Netherlands. [Ksander, Bruce R.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Schepens Eye Res I, Boston, MA USA. [van der Velden, Pieter A.; Jager, Martine J.] Leiden Univ, Med Ctr, Dept Ophthalmol, NL-2300 RC Leiden, Netherlands. RP Jochemsen, AG (reprint author), Leiden Univ, Med Ctr, POB 9600, NL-2300 RC Leiden, Netherlands. EM a.g.jochemsen@lumc.nl; b.e.snaar-jagalska@biology.leidenuniv.nl FU Stichting Kinderen Kankervrij [30677] FX Supported by Stichting Kinderen Kankervrij, Project 30677. NR 44 TC 11 Z9 12 U1 1 U2 9 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2014 VL 55 IS 10 DI 10.1167/iovs.14-15202 PG 11 WC Ophthalmology SC Ophthalmology GA AT1ZS UT WOS:000344730500008 PM 25249605 ER PT J AU Vaidya, SA Korner, C Sirignano, MN Amero, M Bazner, S Rychert, J Allen, TM Rosenberg, ES Bosch, RJ Altfeld, M AF Vaidya, Sagar A. Korner, Christian Sirignano, Michael N. Amero, Molly Bazner, Sue Rychert, Jenna Allen, Todd M. Rosenberg, Eric S. Bosch, Ronald J. Altfeld, Marcus TI Tumor Necrosis Factor alpha Is Associated With Viral Control and Early Disease Progression in Patients With HIV Type 1 Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE TNF-alpha; HIV/AIDS; inflammation; disease progression; viral load set point ID PLASMA-LEVELS; INFLAMMATION; ACTIVATION AB Inflammation in early human immunodeficiency virus type 1 (HIV-1) disease progression is not well characterized. Ninety patients with untreated primary HIV-1 infection were studied to determine associations of inflammatory proteins with early disease progression. High plasma tumor necrosis factor alpha (TNF-alpha) levels (>= 8.5 pg/mL) were significantly associated with an increased viral load set point and shorter times to reaching a CD4(+) T-cell count of <500 cells/mm(3) and initiating antiretroviral therapy. The increased risk of reaching a CD4(+) T-cell count of <500 cells/mm(3) in the group with high TNF-alpha levels was driven by viral load but was independent of concurrent CD4(+) T-cell count. Thus, TNF-alpha appears to be an important mediator of inflammation in patients with poor viral control and early HIV-1 disease progression. C1 [Vaidya, Sagar A.; Korner, Christian; Sirignano, Michael N.; Amero, Molly; Allen, Todd M.; Altfeld, Marcus] Ragon Inst MGH MIT & Harvard, Cambridge, England. [Vaidya, Sagar A.; Bazner, Sue; Rychert, Jenna; Rosenberg, Eric S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bosch, Ronald J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Altfeld, Marcus] Heinrich Pette Inst, Dept Viral Immunol, Hamburg, Germany. RP Altfeld, M (reprint author), Heinrich Pette Inst, Martinistr 52, D-20251 Hamburg, Germany. EM marcus.altfeld@hpi.uni-hamburg.de RI Allen, Todd/F-5473-2011 FU National Institutes of Health [P01 AI074415, T32 AI07387-23, P30 AI060354-10]; Bill and Melinda Gates Foundation; Doris Duke Charitable Foundation [208682]; Philip T. and Susan Ragon Foundation FX This work was supported by the National Institutes of Health (grants P01 AI074415 [to M. Altfeld and R. J. B.] and T32 AI07387-23 and P30 AI060354-10 [to S. A. V.]), the Bill and Melinda Gates Foundation, the Doris Duke Charitable Foundation (grant 208682), and the Philip T. and Susan Ragon Foundation. NR 15 TC 13 Z9 13 U1 3 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 1 PY 2014 VL 210 IS 7 BP 1042 EP 1046 DI 10.1093/infdis/jiu206 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AT0ED UT WOS:000344609100006 PM 24688071 ER PT J AU Minen, MT Camprodon, J Nehme, R Chemali, Z AF Minen, Mia T. Camprodon, Joan Nehme, Romy Chemali, Zeina TI The neuropsychiatry of tinnitus: a circuit-based approach to the causes and treatments available SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Review ID TRANSCRANIAL MAGNETIC STIMULATION; DORSAL COCHLEAR NUCLEUS; POSITRON-EMISSION-TOMOGRAPHY; RANDOMIZED CLINICAL-TRIAL; AWAKE GUINEA-PIGS; AUDITORY-CORTEX; BRAIN-STEM; SUBJECTIVE TINNITUS; EVOKED-RESPONSES; FUNCTIONAL CONNECTIVITY AB Patients presenting with tinnitus commonly have neuropsychiatric symptoms with which physicians need to be familiar. We provide an overview of tinnitus, including its types and pathophysiology. We discuss how recent methods such as transcranial magnetic stimulation, positron emission tomography, MRI, magnetoencephalography and quantitative EEG improve our understanding of the pathophysiology of tinnitus and connect tinnitus to the neuropsychiatric symptoms. We then explain why treatment of the tinnitus patient falls within the purview of neuropsychiatry. Psychiatric problems such as depression, anxiety and personality disorders are discussed. We also discuss how stress, headache, cognitive processing speed and sleep disturbance are associated with tinnitus. Finally, we provide a brief overview of treatment options and discuss the efficacy of various medications, including benzodiazepines, antidepressants, antipsychotics and mood-stabilising agents, and various non-pharmacological treatment options, such as cognitive behavioural therapy, habituation therapy and acupuncture. We also discuss how brain stimulation therapies are being developed for the treatment of tinnitus. In conclusion, a review of the literature demonstrates the varied neuropsychiatric manifestations of tinnitus. Imaging studies help to explain the mechanism of the association. However, more research is needed to elucidate the neurocircuitry underlying the association. C1 [Minen, Mia T.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Minen, Mia T.; Camprodon, Joan; Chemali, Zeina] Harvard Univ, Sch Med, Boston, MA USA. [Camprodon, Joan; Chemali, Zeina] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Camprodon, Joan; Nehme, Romy; Chemali, Zeina] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Chemali, Zeina] Massachusetts Eye Ear Infirm, Boston, MA USA. RP Minen, MT (reprint author), Brigham & Womens Faulkner Hosp, Dept Neurol, 1153 Ctr St,Suite 4970, Boston, MA 02130 USA. EM mia.t.minen@gmail.com NR 128 TC 4 Z9 4 U1 0 U2 25 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 EI 1468-330X J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD OCT PY 2014 VL 85 IS 10 BP 1138 EP 1144 DI 10.1136/jnnp-2013-307339 PG 7 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA AS7SW UT WOS:000344456000231 PM 24744443 ER PT J AU Kaup, AR Drummond, SPA Eyler, LT AF Kaup, Allison R. Drummond, Sean P. A. Eyler, Lisa T. TI Brain Functional Correlates of Working Memory: Reduced Load-Modulated Activation and Deactivation in Aging without Hyperactivation or Functional Reorganization SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Aging; Working memory; Cognition; Functional neuroimaging; fMRI; Individual differences ID AGE-RELATED DIFFERENCES; ADULT LIFE-SPAN; PERFORMANCE; FMRI; RECRUITMENT; MODEL; PET AB We aimed to identify brain functional correlates of working memory performance in aging, in hopes of facilitating understanding of mechanisms that promote better versus worse working memory in late-life. Among 64 healthy adults, aged 23 to 78, we examined the relationship between age, working memory performance, and brain functional response during task performance. We focused on the association between working memory load-modulated functional response and individual differences in performance and whether these function-performance relationships differed with age. As expected, older age was associated with poorer working memory performance. Older age was also associated with reduced load-modulated activation including in bilateral prefrontal and parietal regions and left caudate as well as reduced deactivation including in the medial prefrontal cortex. Contrary to findings of hyperactivation in aging, we found no evidence of increased activation with older age. Positive associations identified between brain response and performance did not differ with age. Our findings suggest that the neural mechanisms underlying better versus worse working memory performance are age-invariant across adulthood, and argue against a pattern of functional reorganization in aging. Results are discussed within the broader literature, in which significant heterogeneity in findings between studies has been common. C1 [Kaup, Allison R.] Univ Calif San Francisco, San Francisco VA Med Ctr, Sierra Pacific Mental Illness Res Educ & Clin Ctr, San Francisco, CA 94143 USA. [Kaup, Allison R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Kaup, Allison R.] Univ Calif San Francisco, San Diego State Univ, Joint Doctoral Program Clin Psychol, San Francisco, CA 94143 USA. [Drummond, Sean P. A.] VA San Diego Hlth Care Syst, Psychol Serv, San Diego, CA USA. [Drummond, Sean P. A.; Eyler, Lisa T.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Eyler, Lisa T.] Univ Calif San Diego, Sam & Rose Stein Inst Res Aging, La Jolla, CA 92093 USA. [Eyler, Lisa T.] VA San Diego Healthcare Syst, Mental Illness Res Educ & Clin Ctr, San Diego, CA USA. RP Kaup, AR (reprint author), San Francisco VA Med Ctr, 4150 Clement St,116H, San Francisco, CA 94121 USA. EM allison.kaup@ucsf.edu FU NIMH T-32 Fellowship in Geriatric Mental Health [T32 MH019934]; [R01 MH083968]; [R01 AG024506] FX This study was funded by R01 MH083968 awarded to Dr. Eyler, R01 AG024506 awarded to Dr. Drummond, and the NIMH T-32 Fellowship in Geriatric Mental Health (T32 MH019934) awarded to Dilip V. Jeste, M.D. Infrastructure support was provided to one of the studies by the VA San Diego Center for Excellence in Stress and Mental Health. Writing of this manuscript was supported by Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Medical Research Service of the San Francisco Veterans Affairs Medical Center, and the Department of Veterans Affairs Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC). The authors have no conflicts of interest to disclose. NR 20 TC 3 Z9 3 U1 2 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 EI 1469-7661 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD OCT PY 2014 VL 20 IS 9 BP 945 EP 950 DI 10.1017/S1355617714000824 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA AT4YD UT WOS:000344947600008 PM 25263349 ER PT J AU Paunescu, TG Shum, WWC Huynh, C Lechner, L Goetze, B Brown, D Breton, S AF Paunescu, Teodor G. Shum, Winnie W. C. Huynh, Chuong Lechner, Lorenz Goetze, Bernhard Brown, Dennis Breton, Sylvie TI High-resolution helium ion microscopy of epididymal epithelial cells and their interaction with spermatozoa SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE epididymis; spermatozoa; helium ion microscopy; principal and clear cells; epididymosomes ID SCANNING-ELECTRON-MICROSCOPY; MALE REPRODUCTIVE-TRACT; VACUOLAR H+-ATPASE; V-ATPASE; INTERCALATED CELLS; RAT EPIDIDYMIS; CLEAR CELLS; BASAL-CELLS; LUMINAL ACIDIFICATION; SEMINIFEROUS TUBULES AB We examined the rat and mouse epididymis using helium ion microscopy (HIM), a novel imaging technology that uses a scanning beam of He+ ions to produce nanometer resolution images of uncoated biological samples. Various tissue fixation, sectioning and dehydration methods were evaluated for their ability to preserve tissue architecture. The cauda epididymidis was luminally perfused in vivo to remove most spermatozoa and the apical surface of the epithelial lining was exposed, Fixed epididymis samples were then subjected to critical point drying (CPD) and HIM. Apical stereocilia in principal cells and smaller apical membrane extensions in clear cells were clearly distinguishable in both rat and mouse epididymis using this technology. After perfusion with an activating solution containing CPT-cAMP, a permeant analog of cAMP, clear cells exhibited an increase in the number and size of membrane ruffles or microplicae. In contrast, principal cells did not exhibit detectable structural modifications. High-resolution HIM imaging clearly showed the ultrastructure of residual sperm cells including the presence of concentric rings on the midpiece and of cytoplasmic droplets in some spermatozoa. Close epithelium sperm interactions were also detected. We found a number of sperm cells whose heads were anchored within the epididymal epithelium. In certain cases the surface of the sperm cytoplasmic droplet was covered with vesicle-like structures whose size is consistent with that of epididymosomes. In conclusion we describe here the first application of HIM technology to the study of the structure and morphology of the rodent epididymis. HIM technology represents a major imaging breakthrough that can be successfully applied to study the epididymis and spermatozoa, with the goal of advancing our understanding of their structure and function. C1 [Paunescu, Teodor G.; Shum, Winnie W. C.; Brown, Dennis; Breton, Sylvie] Massachusetts Gen Hosp, Dept Med, Program Membrane Biol, Boston, MA 02114 USA. [Paunescu, Teodor G.; Shum, Winnie W. C.; Brown, Dennis; Breton, Sylvie] Massachusetts Gen Hosp, Ctr Syst Biol, Div Nephrol, Boston, MA 02114 USA. [Paunescu, Teodor G.; Shum, Winnie W. C.; Brown, Dennis; Breton, Sylvie] Harvard Univ, Sch Med, Simches Res Ctr, Boston, MA 02114 USA. [Huynh, Chuong; Lechner, Lorenz; Goetze, Bernhard] Carl Zeiss Microscopy, Peabody, MA 01960 USA. RP Breton, S (reprint author), Massachusetts Gen Hosp, Dept Med, Program Membrane Biol, CPZN 8204,185 Cambridge St, Boston, MA 02114 USA. EM breton.sylvie@mgh.harvard.edu FU NIH [DK073266, DK042956, HD040793, DK097124, DK085715]; Zeiss Corporation FX This work was supported by NIH grants DK073266 to T.G.P., DK042956 to D.B., HD040793, DK097124 and DK085715 to S.B. Additional funding was provided by a sponsored research agreement to D.B. from the Zeiss Corporation. NR 83 TC 8 Z9 8 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 EI 1460-2407 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD OCT PY 2014 VL 20 IS 10 BP 929 EP 937 DI 10.1093/molehr/gau052 PG 9 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA AT0HT UT WOS:000344618300001 PM 25015675 ER PT J AU Maire, CL Ligon, KL AF Maire, Cecile L. Ligon, Keith L. TI Molecular pathologic diagnosis of epidermal growth factor receptor SO NEURO-ONCOLOGY LA English DT Review DE diagnostics; EGFR; GBM; pathology; sequencing ID EGFR KINASE INHIBITORS; PRIMARY GLIOBLASTOMAS; HUMAN GLIOMAS; STEM-CELLS; MUTATIONS; LANDSCAPE; GENES; AMPLIFICATION; ASTROCYTOMAS; EXPRESSION AB Epidermal growth factor receptor (EGFR) was one of the first oncogenes identified in glioblastoma (GBM) and remains one of the most attractive therapeutic targets. Genomic alterations in EGFR are present in 57% of patients and are strikingly diverse, including gene amplification, rearrangements, and point mutations. Each aberration class has important clinical implications for diagnosis, prognosis, or therapeutic investigation of EGFR in clinical trials. Somatic copy number alterations (SCNAs) are the most common abnormalities in EGFR, with gene amplification present in > 43% of patients. The presence of EGFR amplification is often used now to support the diagnosis of GBM and discriminate GBM from other gliomas. It is currently detected in clinical labs using fluorescence in situ hybridization, colorimetric in situ hybridization or, more recently multiplex genomic technologies such as array CGH or targeted next-generation sequencing approaches. Rearrangements of EGFR are most commonly internal deletions leading to activation of the receptor including EGFRvIII and, less commonly, EGFRvII and other variants, which are collectively seen in 25% of GBM patients. EGFRvIII is readily detected via mutation-specific antibodies, but heterogeneity of this and other deletion variants has hindered reliable detection of these aberrations using genomic DNA-based methods. RNA expression profiling (Nanostring and anchored multiplex PCR) has additional potential as a rapid and reliable strategy for detecting EGFR rearrangements with high sensitivity. Single nucleotide variants in EGFR are relatively rare and diverse but are efficiently detected using the targeted or exome-sequencing assays that are now entering clinical pathology practice. The advent of multiplex technologies has revealed the fact that multiple aberrations of EGFR are present in at least 30% of patients with EGFR disruption, a fact recently highlighted by more quantitative sequencing techniques and single cell analysis of GBM. Diagnostic assays used to evaluate EGFR and other receptor tyrosine kinases will therefore be increasingly used to measure and resolve this heterogeneity in order to better understand their mechanisms of resistance. In summary, the diagnostic approaches for identifying clinically relevant EGFR aberrations have rapidly advanced and are providing insights into more effective inhibition of this familiar oncogene in GBM and other cancers. C1 [Maire, Cecile L.; Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02215 USA. [Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Ligon, Keith L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ligon, KL (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. EM keith_ligon@dfci.harvard.edu FU NCI NIH HHS [P50 CA165962, P01CA14256, P50CA165962, R01CA170592, R01 CA170592, P01 CA095616, P01 CA142536] NR 38 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 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2014 VL 16 SU 8 BP viii1 EP viii6 DI 10.1093/neuonc/nou294 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AT0KZ UT WOS:000344626300001 PM 25342599 ER PT J AU Reardon, DA Wen, PY Mellinghoff, IK AF Reardon, David A. Wen, Patrick Y. Mellinghoff, Ingo K. TI Targeted molecular therapies against epidermal growth factor receptor: Past experiences and challenges SO NEURO-ONCOLOGY LA English DT Review DE EGFRvIII; epidermal growth factor receptor; glioblastoma; tyrosine kinase inhibitor ID PHASE-II TRIAL; NEWLY-DIAGNOSED GLIOBLASTOMA; RECURRENT MALIGNANT GLIOMA; CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; BRAIN-TUMOR CONSORTIUM; METASTATIC COLORECTAL-CANCER; PROGRESSION-FREE SURVIVAL; DOSE WEEKLY ERLOTINIB; RADIATION-THERAPY AB Epidermal growth factor receptor (EGFR) has emerged as a highly attractive therapeutic target in glioblastoma (GBM) based on its high frequency of gene amplification and mutation and its identification as an upstream trigger of dysregulated cell signaling cascades that drive GBM pathophysiology. Extensive investment has been committed in an attempt to exploit EGFR therapeutically to improve outcome for GBM patients, including the development of a variety of EGFR-targeting therapeutics as well as the participation of hundreds of participants in multiple, carefully constructed clinical trials. In this review, we summarize the design and results of clinical trials evaluating EGFR tyrosine kinase inhibitors in recurrent and newly diagnosed GBM patients. While overall results thus far have been disappointing, it is premature to discount EGFR as a therapeutic target in GBM on the basis of these studies given the limitations in study design and the pharmacology of first-generation EGFR kinase inhibitors. Although important lessons have been learned, critical questions remain unanswered and warrant further study. C1 [Reardon, David A.; Wen, Patrick Y.; Mellinghoff, Ingo K.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA. RP Reardon, DA (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave,Dana 2134, Boston, MA 02215 USA. EM david_reardon@dfci.harvard.edu FU NINDS NIH HHS [R01 NS080944] NR 81 TC 11 Z9 11 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2014 VL 16 SU 8 BP viii7 EP viii13 DI 10.1093/neuonc/nou232 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AT0KZ UT WOS:000344626300002 PM 25342602 ER PT J AU Lipshultz, SE Diamond, MB Franco, VI Aggarwal, S Leger, K Santos, MV Sallan, SE Chow, EJ AF Lipshultz, Steven E. Diamond, Melissa B. Franco, Vivian I. Aggarwal, Sanjeev Leger, Kasey Santos, Maria Veronica Sallan, Stephen E. Chow, Eric J. TI Managing Chemotherapy-Related Cardiotoxicity in Survivors of Childhood Cancers SO PEDIATRIC DRUGS LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDRENS ONCOLOGY GROUP; ANTHRACYCLINE-INDUCED CARDIOTOXICITY; LONG-TERM SURVIVORS; CONGESTIVE-HEART-FAILURE; CARDIAC RISK-FACTORS; TISSUE DOPPLER-ECHOCARDIOGRAPHY; VENTRICULAR EJECTION FRACTION; DOXORUBICIN-TREATED SURVIVORS; MYOCARDIAL PERFORMANCE INDEX AB In the US, children diagnosed with cancer are living longer, but not without consequences from the same drugs that cured their cancer. In these patients, cardiovascular disease is the leading cause of non-cancer-related morbidity and mortality. Although this review focuses on anthracycline-related cardiomyopathy in childhood cancer survivors, the global lifetime risk of other cardiovascular diseases such as atherosclerosis, arrhythmias and intracardiac conduction abnormalities, hypertension, and stroke also are increased. Besides anthracyclines, newer molecularly targeted agents, such as vascular endothelial growth factor receptor and tyrosine kinase inhibitors, also have been associated with acute hypertension, cardiomyopathy, and increased risk of ischemic cardiac events and arrhythmias, and are summarized here. This review also covers other risk factors for chemotherapy-related cardiotoxicity (including both modifiable and non-modifiable factors), monitoring strategies (including both blood and imaging-based biomarkers) during and following cancer treatment, and discusses the management of cardiotoxicity (including prevention strategies such as cardioprotection by use of dexrazoxane). C1 [Lipshultz, Steven E.; Franco, Vivian I.] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Lipshultz, Steven E.; Franco, Vivian I.] Childrens Hosp Michigan, Childrens Res Ctr Michigan, Detroit, MI 48201 USA. [Diamond, Melissa B.] Univ Miami, Miller Sch Med, Dept Pediat, Div Pediat Cardiol, Miami, FL 33136 USA. [Aggarwal, Sanjeev] Wayne State Univ, Sch Med, Dept Pediat, Div Pediat Cardiol, Detroit, MI 48201 USA. [Aggarwal, Sanjeev] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Leger, Kasey] Univ Texas SW Med Ctr Dallas, Dept Pediat Hematol Oncol, Dallas, TX 75390 USA. [Santos, Maria Veronica] Univ Fed Sao Paulo, Inst Oncol Pediat GRAACC, Dept Cardiol & Pediat Oncol, BR-04023062 Sao Paulo, Brazil. [Sallan, Stephen E.] Harvard Univ, Sch Med, Dept Pediat, Div Pediat Oncol, Boston, MA 02115 USA. [Sallan, Stephen E.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chow, Eric J.] Univ Washington, Seattle Childrens Hosp, Fred Hutchinson Canc Res Ctr, Dept Pediat, Seattle, WA 98109 USA. RP Lipshultz, SE (reprint author), Wayne State Univ, Sch Med, Dept Pediat, 3901 Beaubien Blvd,Suite 1K40, Detroit, MI 48201 USA. EM slipshultz@med.miami.edu FU National Cancer Institute [K07 CA151775]; Leukemia and Lymphoma Society; St. Baldricks' Foundation FX The authors have no conflicts of interest that are directly relevant to the content of this review. Eric Chow is supported by grants from the National Cancer Institute (K07 CA151775), the Leukemia and Lymphoma Society, and the St. Baldricks' Foundation. NR 165 TC 6 Z9 6 U1 1 U2 11 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1174-5878 EI 1179-2019 J9 PEDIATR DRUGS JI Pediatr. Drugs PD OCT PY 2014 VL 16 IS 5 BP 373 EP 389 DI 10.1007/s40272-014-0085-1 PG 17 WC Pediatrics; Pharmacology & Pharmacy SC Pediatrics; Pharmacology & Pharmacy GA AT0KJ UT WOS:000344624800004 PM 25134924 ER PT J AU Larsen, CE Alford, DR Trautwein, MR Jalloh, YK Tarnacki, JL Kunnenkeri, SK Fici, DA Yunis, EJ Awdeh, ZL Alper, CA AF Larsen, Charles E. Alford, Dennis R. Trautwein, Michael R. Jalloh, Yanoh K. Tarnacki, Jennifer L. Kunnenkeri, Sushruta K. Fici, Dolores A. Yunis, Edmond J. Awdeh, Zuheir L. Alper, Chester A. TI Dominant Sequences of Human Major Histocompatibility Complex Conserved Extended Haplotypes from HLA-DQA2 to DAXX SO PLOS GENETICS LA English DT Article ID MHC HAPLOTYPES; MEIOTIC RECOMBINATION; ANCESTRAL HAPLOTYPES; DIABETES-MELLITUS; HLA HAPLOTYPES; DISEASE; REGION; ASSOCIATION; GENOMICS; PROJECT AB We resequenced and phased 27 kb of DNA within 580 kb of the MHC class II region in 158 population chromosomes, most of which were conserved extended haplotypes (CEHs) of European descent or contained their centromeric fragments. We determined the single nucleotide polymorphism and deletion-insertion polymorphism alleles of the dominant sequences from HLA-DQA2 to DAXX for these CEHs. Nine of 13 CEHs remained sufficiently intact to possess a dominant sequence extending at least to DAXX, 230 kb centromeric to HLA-DPB1. We identified the regions centromeric to HLA-DQB1 within which single instances of eight "common" European MHC haplotypes previously sequenced by the MHC Haplotype Project (MHP) were representative of those dominant CEH sequences. Only two MHP haplotypes had a dominant CEH sequence throughout the centromeric and extended class II region and one MHP haplotype did not represent a known European CEH anywhere in the region. We identified the centromeric recombination transition points of other MHP sequences from CEH representation to non-representation. Several CEH pairs or groups shared sequence identity in small blocks but had significantly different (although still conserved for each separate CEH) sequences in surrounding regions. These patterns partly explain strong calculated linkage disequilibrium over only short (tens to hundreds of kilobases) distances in the context of a finite number of observed megabase-length CEHs comprising half a population's haplotypes. Our results provide a clearer picture of European CEH class II allelic structure and population haplotype architecture, improved regional CEH markers, and raise questions concerning regional recombination hotspots. C1 [Larsen, Charles E.; Alford, Dennis R.; Trautwein, Michael R.; Jalloh, Yanoh K.; Tarnacki, Jennifer L.; Kunnenkeri, Sushruta K.; Fici, Dolores A.; Awdeh, Zuheir L.; Alper, Chester A.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Larsen, Charles E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Fici, Dolores A.; Awdeh, Zuheir L.] Pulsar Clin Technol, Cambridge, MA USA. [Yunis, Edmond J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Yunis, Edmond J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Alper, Chester A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Larsen, CE (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. EM chester.alper@childrens.harvard.edu FU Juvenile Diabetes Research Foundation [5-2007-788, 1-2008-472]; National Heart, Lung, and Blood Institute of the National Institutes of Health [HL-29583]; Immune Disease Institute/Program in Cellular and Molecular Medicine FX This work was supported by grants 5-2007-788 and 1-2008-472 from the Juvenile Diabetes Research Foundation (http://jdrf.org), HL-29583 from the National Heart, Lung, and Blood Institute (www.nhlbi.nih.gov) of the National Institutes of Health and institutional funds from the Immune Disease Institute/Program in Cellular and Molecular Medicine (www.idi.harvard.edu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 4 Z9 4 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2014 VL 10 IS 10 AR e1004637 DI 10.1371/journal.pgen.1004637 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA AT0UR UT WOS:000344650700019 PM 25299700 ER PT J AU Slaats, GG Ghosh, AK Falke, LL Le Corre, S Shaltiel, IA van de Hoek, G Klasson, TD Stokman, MF Logister, I Verhaar, MC Goldschmeding, R Nguyen, TQ Drummond, IA Hildebrandt, F Giles, RH AF Slaats, Gisela G. Ghosh, Amiya K. Falke, Lucas L. Le Corre, Stephanie Shaltiel, Indra A. van de Hoek, Glenn Klasson, Timothy D. Stokman, Marijn F. Logister, Ive Verhaar, Marianne C. Goldschmeding, Roel Nguyen, Tri Q. Drummond, Iain A. Hildebrandt, Friedhelm Giles, Rachel H. TI Nephronophthisis-Associated CEP164 Regulates Cell Cycle Progression, Apoptosis and Epithelial-to-Mesenchymal Transition SO PLOS GENETICS LA English DT Article ID DNA-DAMAGE; RENAL CILIOPATHIES; KIDNEY; FIBROSIS; SNAIL; DISEASE; MUTATIONS; STABILITY; CENTRIOLE; ORIGIN AB We recently reported that centrosomal protein 164 (CEP164) regulates both cilia and the DNA damage response in the autosomal recessive polycystic kidney disease nephronophthisis. Here we examine the functional role of CEP164 in nephronophthisis-related ciliopathies and concomitant fibrosis. Live cell imaging of RPE-FUCCI (fluorescent, ubiquitination-based cell cycle indicator) cells after siRNA knockdown of CEP164 revealed an overall quicker cell cycle than control cells, although early S-phase was significantly longer. Follow-up FACS experiments with renal IMCD3 cells confirm that Cep164 siRNA knockdown promotes cells to accumulate in S-phase. We demonstrate that this effect can be rescued by human wildtype CEP164, but not disease-associated mutants. siRNA of CEP164 revealed a proliferation defect over time, as measured by CyQuant assays. The discrepancy between accelerated cell cycle and inhibited overall proliferation could be explained by induction of apoptosis and epithelial-to-mesenchymal transition. Reduction of CEP164 levels induces apoptosis in immunofluorescence, FACS and RT-QPCR experiments. Furthermore, knockdown of Cep164 or overexpression of dominant negative mutant allele CEP164 Q525X induces epithelial-to-mesenchymal transition, and concomitant upregulation of genes associated with fibrosis. Zebrafish injected with cep164 morpholinos likewise manifest developmental abnormalities, impaired DNA damage signaling, apoptosis and a pro-fibrotic response in vivo. This study reveals a novel role for CEP164 in the pathogenesis of nephronophthisis, in which mutations cause ciliary defects coupled with DNA damage induced replicative stress, cell death, and epithelial-to-mesenchymal transition, and suggests that these events drive the characteristic fibrosis observed in nephronophthisis kidneys. C1 [Slaats, Gisela G.; Klasson, Timothy D.; Logister, Ive; Verhaar, Marianne C.; Giles, Rachel H.] Univ Med Ctr Utrecht, Dept Hypertens & Nephrol, Utrecht, Netherlands. [Ghosh, Amiya K.] Univ Michigan, Dept Internal Med, Div Geriatr & Palliat Med, Ann Arbor, MI 48109 USA. [Falke, Lucas L.; Goldschmeding, Roel; Nguyen, Tri Q.] Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands. [Le Corre, Stephanie; Drummond, Iain A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. [Le Corre, Stephanie; Drummond, Iain A.] Harvard Univ, Sch Med, Dept Genet, Charlestown, MA USA. [Shaltiel, Indra A.] Univ Med Ctr Utrecht, Dept Med Oncol, Utrecht, Netherlands. [van de Hoek, Glenn; Stokman, Marijn F.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Hildebrandt, Friedhelm] Boston Childrens Hosp, Div Nephrol, Boston, MA USA. [Hildebrandt, Friedhelm] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Slaats, GG (reprint author), Univ Med Ctr Utrecht, Dept Hypertens & Nephrol, Utrecht, Netherlands. EM r.giles@umcutrecht.nl RI Nguyen, Tri/A-9508-2009; Falke, Lucas/D-5288-2017; OI Nguyen, Tri/0000-0001-6475-0706; Falke, Lucas/0000-0003-0020-433X; Verhaar, Marianne/0000-0002-3276-6428 FU European Community [241955]; Dutch Kidney Foundation Consortium [CP11.18, 13A3D103]; National Institutes of Health [DK068306, DK088767]; Netherlands Institute for Regenerative Medicine (NIRM) [FES0908]; Netherlands Organisation for Scientific Research (NWO/ZonMw) Vidi-grant [016.096.359]; NIH [DK070263]; Foundation 'De Drie Lichten' in the Netherlands; Dutch Kidney Foundation; EMBO fellowship program FX This research was supported by grants from the European Community's Seventh Framework Programme FP7/2009 under grant agreement no: 241955, SYSCILIA, the Dutch Kidney Foundation Consortium CP11.18 "KOUNCIL" and 13A3D103 (to RHG) and by grants from the National Institutes of Health (to FH) (DK068306 and DK088767). FH is an Investigator of the Howard Hughes Medical Institute, a Doris Duke Distinguished Clinical Scientist, and a Warren E. Grupe Professor. RG, TQN, and LLF are supported by the Netherlands Institute for Regenerative Medicine (NIRM, Grant No. FES0908). MCV is supported by the Netherlands Organisation for Scientific Research (NWO/ZonMw) Vidi-grant 016.096.359. IAD and SLC were supported by NIH grant DK070263. GGS further acknowledges support from Foundation 'De Drie Lichten' in the Netherlands, the Dutch Kidney Foundation, and the EMBO fellowship program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 13 Z9 14 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2014 VL 10 IS 10 AR e1004594 DI 10.1371/journal.pgen.1004594 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA AT0UR UT WOS:000344650700008 PM 25340510 ER PT J AU Yeh, JS Austad, KE Franklin, JM Chimonas, S Campbell, EG Avorn, J Kesselheim, AS AF Yeh, James S. Austad, Kirsten E. Franklin, Jessica M. Chimonas, Susan Campbell, Eric G. Avorn, Jerry Kesselheim, Aaron S. TI Association of Medical Students' Reports of Interactions with the Pharmaceutical and Medical Device Industries and Medical School Policies and Characteristics: A Cross-Sectional Study SO PLOS MEDICINE LA English DT Article ID CONFLICTS-OF-INTEREST; NATIONAL-SURVEY; RESPONSE RATES; EDUCATION; PHYSICIANS; SUPPORT; REPRESENTATIVES; PROMOTION; ATTITUDES; EXPOSURE AB Background: Professional societies use metrics to evaluate medical schools' policies regarding interactions of students and faculty with the pharmaceutical and medical device industries. We compared these metrics and determined which US medical schools' industry interaction policies were associated with student behaviors. Methods and Findings: Using survey responses from a national sample of 1,610 US medical students, we compared their reported industry interactions with their schools' American Medical Student Association (AMSA) PharmFree Scorecard and average Institute on Medicine as a Profession (IMAP) Conflicts of Interest Policy Database score. We used hierarchical logistic regression models to determine the association between policies and students' gift acceptance, interactions with marketing representatives, and perceived adequacy of faculty-industry separation. We adjusted for year in training, medical school size, and level of US National Institutes of Health (NIH) funding. We used LASSO regression models to identify specific policies associated with the outcomes. We found that IMAP and AMSA scores had similar median values (1.75 [interquartile range 1.50-2.00] versus 1.77 [1.50-2.18], adjusted to compare scores on the same scale). Scores on AMSA and IMAP shared policy dimensions were not closely correlated (gift policies, r = 0.28, 95% CI 0.11-0.44; marketing representative access policies, r = 0.51, 95% CI 0.36-0.63). Students from schools with the most stringent industry interaction policies were less likely to report receiving gifts (AMSA score, odds ratio [OR]: 0.37, 95% CI 0.19-0.72; IMAP score, OR 0.45, 95% CI 0.19-1.04) and less likely to interact with marketing representatives (AMSA score, OR 0.33, 95% CI 0.15-0.69; IMAP score, OR 0.37, 95% CI 0.14-0.95) than students from schools with the lowest ranked policy scores. The association became nonsignificant when fully adjusted for NIH funding level, whereas adjusting for year of education, size of school, and publicly versus privately funded school did not alter the association. Policies limiting gifts, meals, and speaking bureaus were associated with students reporting having not received gifts and having not interacted with marketing representatives. Policy dimensions reflecting the regulation of industry involvement in educational activities (e. g., continuing medical education, travel compensation, and scholarships) were associated with perceived separation between faculty and industry. The study is limited by potential for recall bias and the cross-sectional nature of the survey, as school curricula and industry interaction policies may have changed since the time of the survey administration and study analysis. Conclusions: As medical schools review policies regulating medical students' industry interactions, limitations on receipt of gifts and meals and participation of faculty in speaking bureaus should be emphasized, and policy makers should pay greater attention to less research-intensive institutions. C1 [Yeh, James S.; Austad, Kirsten E.; Franklin, Jessica M.; Avorn, Jerry; Kesselheim, Aaron S.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, PORTAL, Boston, MA 02115 USA. [Yeh, James S.; Austad, Kirsten E.; Franklin, Jessica M.; Campbell, Eric G.; Avorn, Jerry; Kesselheim, Aaron S.] Harvard Univ, Sch Med, Boston, MA USA. [Chimonas, Susan] Columbia Univ, Ctr Med Profess, New York, NY USA. [Campbell, Eric G.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Yeh, JS (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, PORTAL, 75 Francis St, Boston, MA 02115 USA. EM akesselheim@partners.org FU Attorney General Consumer; Prescriber Education Grant Program; Greenwall Faculty Scholarship in Bioethics; Robert Wood Johnson Foundation; Agency for Healthcare Research Quality [K08HS18465] FX Survey funded by a grant from the Edmond J. Safra Center for Ethics at Harvard University. Institute of Medicine as Profession's data were made possible by a grant from the state Attorney General Consumer and Prescriber Education Grant Program, which is funded by the multi-state settlement of consumer fraud claims regarding the marketing of the prescription drug Neurontin. ASK is supported by a Greenwall Faculty Scholarship in Bioethics, a Robert Wood Johnson Foundation Investigator Award in Health Policy Research, and a career development award from the Agency for Healthcare Research & Quality (K08HS18465). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 2 Z9 2 U1 4 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD OCT PY 2014 VL 11 IS 10 AR e1001743 DI 10.1371/journal.pmed.1001743 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AS7UU UT WOS:000344460900005 PM 25314155 ER PT J AU Evangelista, KV Hahn, B Wunder, EA Ko, AI Haake, DA Coburn, J AF Evangelista, Karen V. Hahn, Beth Wunder, Elsio A., Jr. Ko, Albert I. Haake, David A. Coburn, Jenifer TI Identification of Cell-Binding Adhesins of Leptospira interrogans SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID OUTER-MEMBRANE PROTEINS; PATHOGENIC LEPTOSPIRA; EXTRACELLULAR-MATRIX; BORRELIA-BURGDORFERI; PHAGE DISPLAY; TREPONEMA-PALLIDUM; YERSINIA-PSEUDOTUBERCULOSIS; ENDOTHELIAL-CELLS; INVASIN PROTEIN; CULTURED-CELLS AB Leptospirosis is a globally distributed bacterial infectious disease caused by pathogenic members of the genus Leptospira. Infection can lead to illness ranging from mild and non-specific to severe, with jaundice, kidney and liver dysfunction, and widespread endothelial damage. The adhesion of pathogenic Leptospira species (spp.), the causative agent of leptospirosis, to host tissue components is necessary for infection and pathogenesis. While it is well-established that extracellular matrix (ECM) components play a role in the interaction of the pathogen with host molecules, we have shown that pathogenic Leptospira interrogans binds to host cells more efficiently than to ECM components. Using in vitro phage display to select for phage clones that bind to EA. hy926 endothelial cells, we identified the putative lipoproteins LIC10508 and LIC13411, and the conserved hypothetical proteins LIC12341 and LIC11574, as candidate L. interrogans sv. Copenhageni st. Fiocruz L1-130 adhesins. Recombinant LIC11574, but not its L. biflexa homologue LBF1629, exhibited dose-dependent binding to both endothelial and epithelial cells. In addition, LIC11574 and LIC13411 bind to VE-cadherin, an endothelial cell receptor for L. interrogans. Extraction of bacteria with the non-ionic detergent Triton X-114 resulted in partitioning of the candidate adhesins to the detergent fraction, a likely indication that these proteins are outer membrane localized. All candidate adhesins were recognized by sera obtained from leptospirosis patients but not by sera from healthy individuals as assessed by western blot. This work has identified bacterial adhesins that are potentially involved in L. interrogans infection of the mammalian host, and through cadherin binding, may contribute to dissemination and vascular damage. Our findings may be of value in leptospirosis control and prevention, with the bacterial adhesins potentially serving as targets for development of diagnostics, therapeutics, and vaccines. C1 [Evangelista, Karen V.; Coburn, Jenifer] Med Coll Wisconsin, Grad Program Microbiol Immunol & Mol Genet, Milwaukee, WI 53226 USA. [Hahn, Beth; Coburn, Jenifer] Med Coll Wisconsin, Dept Med, Div Infect Dis, Milwaukee, WI 53226 USA. [Wunder, Elsio A., Jr.; Ko, Albert I.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA. [Haake, David A.] VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. RP Evangelista, KV (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM jcoburn@mcw.edu RI Ko, Albert/P-2343-2015; Wunder, Elsio/C-2733-2013 FU National Institutes of Health [R21 AI077560, R56 AI087835,, R21 AI093509, R01 AI 034431, R01 AI 052473, R01 TW009504, U01 AI088752]; Veterans Affairs Merit Review award FX This work was supported by National Institutes of Health grants R21 AI077560, R56 AI087835, and R21 AI093509 to JC, R01 AI 034431 to DAH, R01 AI 052473, R01 TW009504, and U01 AI088752 to AIK, and by a Veterans Affairs Merit Review award to DAH. None of the funders had any role in the design or analysis of experiments, the preparation of the manuscript, or the decision to publish. NR 75 TC 7 Z9 7 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD OCT PY 2014 VL 8 IS 10 AR e3215 DI 10.1371/journal.pntd.0003215 PG 14 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AS9WJ UT WOS:000344589000033 PM 25275630 ER PT J AU Witchell, TD Eshghi, A Nally, JE Hof, R Boulanger, MJ Wunder, EA Ko, AI Haake, DA Cameron, CE AF Witchell, Timothy D. Eshghi, Azad Nally, Jarlath E. Hof, Rebecca Boulanger, Martin J. Wunder, Elsio A., Jr. Ko, Albert I. Haake, David A. Cameron, Caroline E. TI Post-translational Modification of LipL32 during Leptospira interrogans Infection SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID OUTER-MEMBRANE; PATHOGENIC LEPTOSPIRA; RICKETTSIA-PROWAZEKII; PROTEOMIC ANALYSIS; CALCIUM-BINDING; PLASMA FIBRONECTIN; MASS-SPECTROMETRY; SURFACE PROTEIN; ANTIGEN; LIPOPROTEIN AB Background: Leptospirosis, a re-emerging disease of global importance caused by pathogenic Leptospira spp., is considered the world's most widespread zoonotic disease. Rats serve as asymptomatic carriers of pathogenic Leptospira and are critical for disease spread. In such reservoir hosts, leptospires colonize the kidney, are shed in the urine, persist in fresh water and gain access to a new mammalian host through breaches in the skin. Methodology/Principal Findings: Previous studies have provided evidence for post-translational modification (PTM) of leptospiral proteins. In the current study, we used proteomic analyses to determine the presence of PTMs on the highly abundant leptospiral protein, LipL32, from rat urine-isolated L. interrogans serovar Copenhageni compared to in vitro-grown organisms. We observed either acetylation or tri-methylation of lysine residues within multiple LipL32 peptides, including peptides corresponding to regions of LipL32 previously identified as epitopes. Intriguingly, the PTMs were unique to the LipL32 peptides originating from in vivo relative to in vitro grown leptospires. The identity of each modified lysine residue was confirmed by fragmentation pattern analysis of the peptide mass spectra. A synthetic peptide containing an identified tri-methylated lysine, which corresponds to a previously identified LipL32 epitope, demonstrated significantly reduced immunoreactivity with serum collected from leptospirosis patients compared to the peptide version lacking the tri-methylation. Further, a subset of the identified PTMs are in close proximity to the established calcium-binding and putative collagen-binding sites that have been identified within LipL32. Conclusions/Significance: The exclusive detection of PTMs on lysine residues within LipL32 from in vivo-isolated L. interrogans implies that infection-generated modification of leptospiral proteins may have a biologically relevant function during the course of infection. Although definitive determination of the role of these PTMs must await further investigations, the reduced immune recognition of a modified LipL32 epitope suggests the intriguing possibility that LipL32 modification represents a novel mechanism of immune evasion within Leptospira. C1 [Witchell, Timothy D.; Eshghi, Azad; Hof, Rebecca; Boulanger, Martin J.; Cameron, Caroline E.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada. [Nally, Jarlath E.] Univ Coll Dublin, Sch Vet Med, Dublin 2, Ireland. [Wunder, Elsio A., Jr.; Ko, Albert I.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA. [Wunder, Elsio A., Jr.; Ko, Albert I.] Brazilian Minist Hlth, Oswaldo Cruz Fdn, Goncalo Moniz Res Ctr, Salvador, BA, Brazil. [Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Witchell, TD (reprint author), Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada. EM caroc@uvic.ca RI Ko, Albert/P-2343-2015; Wunder, Elsio/C-2733-2013 FU Natural Sciences and Engineering Research Council of Canada [327186]; Canada Research Chair Program; Michael Smith Foundation for Health Research Scholar Program; Science Foundation Ireland [05/YI/B696]; Research Stimulus Fund (Department of Agriculture, Food & Marine, Ireland) [06/363]; Veterans Affairs Merit Review award; Public Health Service from the National Institute of Allergy and Infectious Diseases [AI-034431]; Natural History of Leptospirosis [R01AI052473]; Ecoepidemiology of Leptospirosis [R01TW009504]; Disease Determinants of Urban Leptospirosis [U01AI088752]; Natural Sciences and Engineering Research Council (NSERC) FX This research was supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (327186; CEC), the Canada Research Chair Program (CEC) and the Michael Smith Foundation for Health Research Scholar Program (CEC). This research was also funded in part by Science Foundation Ireland award 05/YI/B696 (JEN), The Research Stimulus Fund (06/363 Department of Agriculture, Food & Marine, Ireland; JEN), Veterans Affairs Merit Review award (DAH), Public Health Service grant AI-034431 from the National Institute of Allergy and Infectious Diseases (DAH), and grants R01AI052473 (Natural History of Leptospirosis; AIK and EAW), R01TW009504 (Ecoepidemiology of Leptospirosis; AIK and EAW) and U01AI088752 (Disease Determinants of Urban Leptospirosis; AIK and EAW). MJB is supported by an operating grant from the Natural Sciences and Engineering Research Council (NSERC) and by the Canada Research Chair program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 6 Z9 6 U1 2 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD OCT PY 2014 VL 8 IS 10 AR e3280 DI 10.1371/journal.pntd.0003280 PG 9 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AS9WJ UT WOS:000344589000078 PM 25356675 ER PT J AU Buffen, K Oosting, M Quintin, J Ng, A Kleinnijenhuis, J Kumar, V van de Vosse, E Wijmenga, C van Crevel, R Oosterwijk, E Grotenhuis, AJ Vermeulen, SH Kiemeney, LA van de Veerdonk, FL Chamilos, G Xavier, RJ van der Meer, JWM Netea, MG Joosten, LAB AF Buffen, Kathrin Oosting, Marije Quintin, Jessica Ng, Aylwin Kleinnijenhuis, Johanneke Kumar, Vinod van de Vosse, Esther Wijmenga, Cisca van Crevel, Reinout Oosterwijk, Egbert Grotenhuis, Anne J. Vermeulen, Sita H. Kiemeney, Lambertus A. van de Veerdonk, Frank L. Chamilos, Georgios Xavier, Ramnik J. van der Meer, Jos W. M. Netea, Mihai G. Joosten, Leo A. B. TI Autophagy Controls BCG-Induced Trained Immunity and the Response to Intravesical BCG Therapy for Bladder Cancer SO PLOS PATHOGENS LA English DT Article ID NATURAL-KILLER-CELLS; CANDIDA-ALBICANS; RANDOMIZED-TRIAL; DENDRITIC CELLS; CHILD SURVIVAL; HOST-DEFENSE; WEST-AFRICA; VACCINATION; MONOCYTES; IMMUNOTHERAPY AB The anti-tuberculosis-vaccine Bacillus Calmette-Guerin (BCG) is the most widely used vaccine in the world. In addition to its effects against tuberculosis, BCG vaccination also induces non-specific beneficial effects against certain forms of malignancy and against infections with unrelated pathogens. It has been recently proposed that the non-specific effects of BCG are mediated through epigenetic reprogramming of monocytes, a process called trained immunity. In the present study we demonstrate that autophagy contributes to trained immunity induced by BCG. Pharmacologic inhibition of autophagy blocked trained immunity induced in vitro by stimuli such as beta-glucans or BCG. Single nucleotide polymorphisms (SNPs) in the autophagy genes ATG2B (rs3759601) and ATG5 (rs2245214) influenced both the in vitro and in vivo training effect of BCG upon restimulation with unrelated bacterial or fungal stimuli. Furthermore, pharmacologic or genetic inhibition of autophagy blocked epigenetic reprogramming of monocytes at the level of H3K4 trimethylation. Finally, we demonstrate that rs3759601 in ATG2B correlates with progression and recurrence of bladder cancer after BCG intravesical instillation therapy. These findings identify a key role of autophagy for the nonspecific protective effects of BCG. C1 [Buffen, Kathrin; Oosting, Marije; Quintin, Jessica; Kleinnijenhuis, Johanneke; van Crevel, Reinout; van de Veerdonk, Frank L.; van der Meer, Jos W. M.; Netea, Mihai G.; Joosten, Leo A. B.] Radboud Univ Nijmegen, Dept Internal Med, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Buffen, Kathrin; Oosting, Marije; Quintin, Jessica; Kleinnijenhuis, Johanneke; van Crevel, Reinout; van de Veerdonk, Frank L.; van der Meer, Jos W. M.; Netea, Mihai G.; Joosten, Leo A. B.] Radboud Univ Nijmegen, RIMLS, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Ng, Aylwin; Xavier, Ramnik J.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. [Ng, Aylwin; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Ng, Aylwin; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Kumar, Vinod; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [van de Vosse, Esther] Leiden Univ, Dept Infect Dis, Med Ctr, Leiden, Netherlands. [Oosterwijk, Egbert; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Dept Urol, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Grotenhuis, Anne J.; Vermeulen, Sita H.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Dept Hlth Evidence, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Grotenhuis, Anne J.; Vermeulen, Sita H.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, RIHS, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Vermeulen, Sita H.] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Chamilos, Georgios] Univ Crete, Dept Med, Iraklion, Crete, Greece. RP Buffen, K (reprint author), Radboud Univ Nijmegen, Dept Internal Med, Med Ctr, NL-6525 ED Nijmegen, Netherlands. EM leo.joosten@radboudumc.nl RI Kiemeney, Lambertus/D-3357-2009; Oosting, Marije/H-7437-2015; van Crevel, reinout/A-6636-2010; Joosten, Leo/H-3138-2015; Oosterwijk, Egbert/P-5466-2014; Netea, Mihai/N-5155-2014; Kleinnijenhuis, Johanneke/P-6309-2015; Grotenhuis, Anne/Q-1596-2015; van de Veerdonk, Frank/C-7256-2008; Vermeulen, H.H.M./L-4716-2015; kleinnijenhuis, johanneke/G-7978-2016; van der Meer, Jos/C-8521-2013; Wijmenga, Cisca/D-2173-2009; van de Vosse, Esther/B-7285-2009; OI Kiemeney, Lambertus/0000-0002-2368-1326; van de Veerdonk, Frank/0000-0002-1121-4894; van der Meer, Jos/0000-0001-5120-3690; van de Vosse, Esther/0000-0001-5199-3426; Wijmenga, Cisca/0000-0002-5635-1614 FU Dutch Arthritis Foundation [NR 10-1-303]; Vici grant of the Netherlands Organization for Scientific Research; European Research Council under the European Union [2012- 322698]; Vidi grant of the Netherlands Organization for Scientific Research [017.106.310]; Radboud University Medical Centre (RUMC) FX KB is supported by a grant of the Dutch Arthritis Foundation (NR 10-1-303). MGN is supported by a Vici grant of the Netherlands Organization for Scientific Research. CW is supported by an grant from the European Research Council under the European Union's Seventh Framework Program (FP/2007-2013)/ ERC Grant Agreement no. 2012- 322698. RvC is supported by a Vidi grant of the Netherlands Organization for Scientific Research (017.106.310). AG is supported by a research investment grant of the Radboud University Medical Centre (RUMC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 21 Z9 21 U1 2 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD OCT PY 2014 VL 10 IS 10 AR e1004485 DI 10.1371/journal.ppat.1004485 PG 10 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AS9FO UT WOS:000344548800059 PM 25356988 ER PT J AU Patel, MS Lypson, ML Miller, DD Davis, MM AF Patel, Mitesh S. Lypson, Monica L. Miller, D. Douglas Davis, Matthew M. TI A Framework for Evaluating Student Perceptions of Health Policy Training in Medical School SO ACADEMIC MEDICINE LA English DT Editorial Material ID EDUCATION; CARE AB Problem Nearly half of graduating medical students in the United States report that medical school provides inadequate instruction in topics related to health policy. Although most medical schools report some form of policy education, there lacks a standard for teaching core concepts and evaluating student satisfaction. Approach Responses to the Association of American Medical College's Medical School Graduation Questionnaire were obtained for the years 2007-2008 and 2011-2012 and mapped to domains of training in health policy curricula for four domains: systems and principles; value and equity; quality and safety; and politics and law. Chi-square tests were used to test differences among unadjusted temporal trends. Multiple logistic regression models were fit to the outcome variables and adjusted for student characteristics, student preferences, and medical school characteristics. Outcomes Compared with 2007-2008, students' perceptions of training in 2011-2012 increased on a relative basis by 11.7% for components within systems and principles, 2.8% for quality and safety, and 6.8% for value and equity. Components within politics and law had a composite decline of 4.8%. Multiple logistic regression models found higher odds of reporting satisfaction with training over time for all components within the domains of systems and principles, quality and safety, and value and equity (P < .01), with the exception of medical economics. Next Steps Medical student perceptions of training in health policy improved over time. Causal factors for these trends require further study. Despite improvement, nearly 40% of graduating medical students still report inadequate instruction in health policy. C1 [Patel, Mitesh S.] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Patel, Mitesh S.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Lypson, Monica L.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Lypson, Monica L.] Vet Affairs Healthcare Syst, Ann Arbor, MI USA. [Miller, D. Douglas] Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada. [Davis, Matthew M.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Davis, Matthew M.] Univ Michigan, Gerald R Ford Sch Publ Policy, Ann Arbor, MI 48109 USA. RP Patel, MS (reprint author), 423 Guardian Dr,1303B Blockley Hall, Philadelphia, PA 19104 USA. EM mpatel@upenn.edu FU Department of Veterans Affairs; Robert Wood Johnson Foundation FX Dr. Patel was supported by the Department of Veterans Affairs and the Robert Wood Johnson Foundation. NR 5 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD OCT PY 2014 VL 89 IS 10 BP 1375 EP 1379 DI 10.1097/ACM.0000000000000408 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA AR9LQ UT WOS:000343896100023 PM 25006706 ER PT J AU Yock, TI Constine, LS Mahajan, A AF Yock, Torunn I. Constine, Louis S. Mahajan, Anita TI Protons, the brainstem, and toxicity: Ingredients for an emerging dialectic SO ACTA ONCOLOGICA LA English DT Editorial Material ID CEREBRAL RADIATION NECROSIS; HYPERFRACTIONATED RADIOTHERAPY; TUMORS; CHILDHOOD; CHILDREN; EPENDYMOMA; THERAPY; CHEMOTHERAPY; IRRADIATION; STRATEGIES C1 [Yock, Torunn I.] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Constine, Louis S.] Univ Rochester, Med Ctr, Rochester, NY 14627 USA. [Mahajan, Anita] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Yock, TI (reprint author), Massachusetts Gen Hosp, Proton Ctr, 55 Fruit St, Boston, MA 02114 USA. EM tyock@partners.org NR 25 TC 3 Z9 3 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0284-186X EI 1651-226X J9 ACTA ONCOL JI Acta Oncol. PD OCT PY 2014 VL 53 IS 10 BP 1279 EP 1282 DI 10.3109/0284186X.2014.957415 PG 4 WC Oncology SC Oncology GA AS0ZP UT WOS:000344005600001 PM 25327262 ER PT J AU McLaurin, EB Marsico, NP Ackerman, SL Ciolino, JB Williams, JM Villanueva, L Hollander, DA AF McLaurin, Eugene B. Marsico, Nicholas P. Ackerman, Stacey L. Ciolino, Joseph B. Williams, Julia M. Villanueva, Linda Hollander, David A. TI Ocular Itch Relief with Alcaftadine 0.25% Versus Olopatadine 0.2% in Allergic Conjunctivitis: Pooled Analysis of Two Multicenter Randomized Clinical Trials SO ADVANCES IN THERAPY LA English DT Article DE Alcaftadine; Allergic conjunctivitis; Antiallergic; Conjunctival allergen challenge model; Ocular itch; Olopatadine; Ophthalmology ID HISTAMINE H-4 RECEPTOR; CHALLENGE MODEL; PHASE-III; ANTIHISTAMINE; EPIDEMIOLOGY; EFFICACY; SURFACE; TIME AB The efficacy and safety of the once-daily topical ophthalmic solutions, alcaftadine 0.25% and olopatadine 0.2%, in preventing ocular itching associated with allergic conjunctivitis were evaluated. Pooled analysis was conducted of two double-masked, multicenter, active- and placebo-controlled studies using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis. Subjects were randomized 1:1:1 to receive alcaftadine 0.25%, olopatadine 0.2%, or placebo. The primary efficacy measure was subject-evaluated mean ocular itching at 3 min post-CAC and 16 h after treatment instillation. Secondary measures included ocular itching at 5 and 7 min post-CAC. Ocular itch was determined over all time points measured (3, 5, and 7 min) post-CAC and the proportion of subjects with minimal itch (itch score < 1) and zero itch (itch score = 0) was also assessed. A total of 284 subjects were enrolled in the two studies. At 3 min post-CAC and 16 h after treatment instillation, alcaftadine 0.25% achieved a significantly lower mean itch score compared with olopatadine 0.2% (0.50 vs. 0.87, respectively; P = 0.0006). Alcaftadine demonstrated a significantly lower mean itch score over all time points compared with olopatadine (0.68 vs. 0.92, respectively; P = 0.0390); both alcaftadine- and olopatadine-treated subjects achieved significantly lower overall mean ocular itching scores compared with placebo (2.10; P < 0.0001 for both actives). Minimal itch over all time points was reported by 76.1% of alcaftadine-treated subjects compared with 58.1% of olopatadine-treated subjects (P = 0.0121). Treatment with alcaftadine 0.25% and olopatadine 0.2% was safe and well tolerated; no serious adverse events were reported. Once-daily alcaftadine 0.25% ophthalmic solution demonstrated greater efficacy in prevention of ocular itching compared with olopatadine 0.2% at 3 min post-CAC (primary endpoint), and over all time points, 16 h post-treatment instillation. Alcaftadine and olopatadine both provided effective relief compared with placebo and were generally well tolerated. C1 [McLaurin, Eugene B.] Total Eye Care PA, Memphis, TN 38119 USA. [Marsico, Nicholas P.] East West Eye Inst, Los Angeles, CA USA. [Ackerman, Stacey L.] Philadelphia Eye Associates, Philadelphia, PA USA. [Ciolino, Joseph B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Williams, Julia M.; Villanueva, Linda; Hollander, David A.] Allergan Pharmaceut Inc, Irvine, CA 92715 USA. RP McLaurin, EB (reprint author), Total Eye Care PA, 6060 Primacy Pkwy,Suite 200, Memphis, TN 38119 USA. EM totaleyeresearch@mac.com FU Allergan, Inc., Irvine, CA FX This research was supported by Allergan, Inc., Irvine, CA. Writing and editorial assistance was provided by Kakuri M. Omari, PhD, of Evidence Scientific Solutions, Philadelphia, PA, and funded by Allergan, Inc., Irvine, CA. All named authors meet the International Committee of Medical Journal Editors criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. All authors had full access to all of the data in this study when requested and take complete responsibility for the integrity of the data and accuracy of the data analysis. The authors received no compensation related to the development of the manuscript. Article processing charges were funded by Allergan, Inc., Irvine, CA. The data were presented in part at the 2014 American Academy of Allergy, Asthma and Immunology Annual Meeting, February 28-March 4, San Diego, CA, 2014, and the 2014 American Society of Cataract and Refractive Surgery Annual Symposium, April 24-29, 2014, Boston, MA. NR 32 TC 6 Z9 6 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0741-238X EI 1865-8652 J9 ADV THER JI Adv. Ther. PD OCT PY 2014 VL 31 IS 10 BP 1059 EP 1071 DI 10.1007/s12325-014-0155-3 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA AS5PI UT WOS:000344322000003 PM 25260889 ER PT J AU Nasri, HZ Westgate, MN Macklin, EA Holmes, LB AF Nasri, Hanah Z. Westgate, Marie-Noel Macklin, Eric A. Holmes, Lewis B. TI Vascular Limb Defects and Maternal Age SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE vascular disruption limb defects; maternal age ID VILLUS; MALFORMATIONS; DEFICIENCIES; DISRUPTIONS; MISOPROSTOL; TRIMESTER; EXPOSURE AB Background: The prenatal diagnosis procedure chorionic villus sampling is associated with increased risk of vascular disruption limb defects. Some studies have suggested that these defects are more common among infants born to women 35 years and older while other studies have shown a correlation with younger mothers. Methods: All infants with vascular disruption defects were identified in the Active Malformations Surveillance Program at Brigham and Women's Hospital in the years 1972-1974, 1979-2011. We compared the rate of occurrence of infants with vascular limb defects among women in theses age groups: <19, 20 to 34, and >= 35 years to the rate of occurrence of infants with preaxial polydactyly, adjusting for race. Infants with an identifiable cause of their defects were excluded. Results: 106 infants with vascular disruption defects and 67 with preaxial polydactyly were identified. Seventeen percent of the infants with vascular disruption defects and 25% of the infants with preaxial polydactyly were born to women 35 and older (p = 0.23). In contrast, 16% of the infants with vascular disruption defects were born to young mothers (<19 years) compared with 6.0% of the mothers of infants with preaxial polydactyly (adjusted odds ratio vs. 35+ years = 5.3, 95% confidence interval 1.4-21, p = 0.017). Conclusion: Women 35 years old or older did not have increased risk for having a child with vascular disruption defects, but these defects were more common among infants of young (<= 19) mothers, compared with the preaxial polydactyly group. (C) 2014 Wiley Periodicals, Inc. C1 [Nasri, Hanah Z.; Westgate, Marie-Noel; Holmes, Lewis B.] MassGen Hosp Children, Med Genet Unit, Boston, MA 02114 USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Macklin, Eric A.] Harvard Univ, Sch Med, Boston, MA USA. RP Nasri, HZ (reprint author), MassGen Hosp Children, Med Genet Unit, 175 Cambridge St,Room 502, Boston, MA 02114 USA. EM hnasri@partners.org OI Macklin, Eric/0000-0003-1618-3502 FU Center for Birth Defects Research and Prevention in the Massachusetts Department of Public Health FX Salary support was provided through a sub-grant from the Center for Birth Defects Research and Prevention in the Massachusetts Department of Public Health. The funding agency had no role in the conduction of the study nor was it involved in the analysis of the findings. NR 24 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD OCT PY 2014 VL 100 IS 10 BP 760 EP 763 DI 10.1002/bdra.23294 PG 4 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA AS5YT UT WOS:000344343100004 PM 25181518 ER PT J AU Fukumoto, M Amanuma, T Kuwahara, Y Shimura, T Suzuki, M Mori, S Kumamoto, H Saito, Y Ohkubo, Y Duan, Z Sano, K Oguchi, T Kainuma, K Usami, S Kinoshita, K Lee, I Fukumoto, M AF Fukumoto, Motoi Amanuma, Tatsuya Kuwahara, Yoshikazu Shimura, Tsutomu Suzuki, Masatoshi Mori, Shiro Kumamoto, Hiroyuki Saito, Yohei Ohkubo, Yasuhito Duan, Zhenfeng Sano, Kenji Oguchi, Tomohiro Kainuma, Kazuyuki Usami, Shinichi Kinoshita, Kengo Lee, Inchul Fukumoto, Manabu TI Guanine nucleotide-binding protein 1 is one of the key molecules contributing to cancer cell radioresistance SO CANCER SCIENCE LA English DT Article DE GTP-binding proteins; head and neck neoplasms; neoplasms; radiation; radiation oncology ID DOUBLE-STRAND BREAKS; ENDOTHELIAL-CELLS; INFLAMMATORY DISEASES; INTERFERON-GAMMA; GTP-BINDING; GUANYLATE; EXPRESSION; SURVIVAL; REPAIR; OVEREXPRESSION AB Standard fractionated radiotherapy for the treatment of cancer consists of daily irradiation of 2-Gy X-rays, 5days a week for 5-8weeks. To understand the characteristics of radioresistant cancer cells and to develop more effective radiotherapy, we established a series of novel, clinically relevant radioresistant (CRR) cells that continue to proliferate with 2-Gy X-ray exposure every 24h for more than 30days in vitro. We studied three human and one murine cell line, and their CRR derivatives. Guanine nucleotide-binding protein 1 (GBP1) gene expression was higher in all CRR cells than their corresponding parental cells. GBP1 knockdown by siRNA cancelled radioresistance of CRR cells in vitro and in xenotransplanted tumor tissues in nude mice. The clinical relevance of GBP1 was immunohistochemically assessed in 45 cases of head and neck cancer tissues. Patients with GBP1-positive cancer tended to show poorer response to radiotherapy. We recently reported that low dose long-term fractionated radiation concentrates cancer stem cells (CSCs). Immunofluorescence staining of GBP1 was stronger in CRR cells than in corresponding parental cells. The frequency of Oct4-positive CSCs was higher in CRR cells than in parental cells, however, was not as common as GBP1-positive cells. GBP1-positive cells were radioresistant, but radioresistant cells were not necessarily CSCs. We concluded that GBP1 overexpression is necessary for the radioresistant phenotype in CRR cells, and that targeting GBP1-positive cancer cells is a more efficient method in conquering cancer than targeting CSCs. C1 [Fukumoto, Motoi; Amanuma, Tatsuya; Kuwahara, Yoshikazu; Shimura, Tsutomu; Suzuki, Masatoshi; Fukumoto, Manabu] Tohoku Univ, Inst Dev Aging & Canc, Dept Pathol, Sendai, Miyagi 980, Japan. [Mori, Shiro] Tohoku Univ, Dept Oral & Maxillofacial Surg, Sendai, Miyagi 980, Japan. [Kumamoto, Hiroyuki] Tohoku Univ, Grad Sch Dent, Dept Oral Med & Surg, Div Oral Pathol, Sendai, Miyagi 980, Japan. [Saito, Yohei; Ohkubo, Yasuhito] Tohoku Pharmaceut Univ, Dept Radiopharm, Sendai, Miyagi, Japan. [Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Sano, Kenji] Shinshu Univ, Sch Med, Dept Pathol, Matsumoto, Nagano 390, Japan. [Oguchi, Tomohiro; Kainuma, Kazuyuki; Usami, Shinichi] Shinshu Univ, Sch Med, Dept Otorhinolaryngol, Matsumoto, Nagano 390, Japan. [Kinoshita, Kengo] Tohoku Univ, Grad Sch Informat Sci, Sendai, Miyagi 980, Japan. [Lee, Inchul] Asan Med Ctr, Dept Pathol, Seoul, South Korea. RP Fukumoto, M (reprint author), Tohoku Univ, Dept Pathol, IDAC, Aoba Ku, 4-1 Seiryou Machi, Sendai, Miyagi 980, Japan. EM fukumoto@idac.tohoku.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan; Ministry of Health, Labor and Welfare of Japan; Japan Science and Technology Agency FX Ministry of Education, Culture, Sports, Science and Technology of Japan; Ministry of Health, Labor and Welfare of Japan; Japan Science and Technology Agency. NR 30 TC 5 Z9 5 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1347-9032 EI 1349-7006 J9 CANCER SCI JI Cancer Sci. PD OCT PY 2014 VL 105 IS 10 BP 1351 EP 1359 DI 10.1111/cas.12489 PG 9 WC Oncology SC Oncology GA AS4KT UT WOS:000344245400016 PM 25098609 ER PT J AU Mittal, N Domian, IJ AF Mittal, Nikhil Domian, Ibrahim J. TI Persistent Integration of Reprogramming Factors Impairs the In Vitro Cardiogenic Potential of Induced Pluripotent Stem Cells SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Editorial Material DE Editorials; induced pluripotent stem cells; nuclear reprogramming; regeneration; regenerative medicine; stem cells ID HUMAN FIBROBLASTS; GENERATION; INDUCTION; CARDIOMYOCYTES; TRANSPOSITION; PIGGYBAC C1 [Mittal, Nikhil] Inst Bioengn & Nanotechnol, Cell & Tissue Engn Grp, Singapore, Singapore. [Domian, Ibrahim J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA. [Domian, Ibrahim J.] Harvard Univ, Sch Med, Boston, MA USA. [Domian, Ibrahim J.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Domian, IJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charles River Plaza CPZN 3200,185 Cambridge St, Boston, MA 02114 USA. EM domian@mgh.harvard.edu OI Mittal, Nikhil/0000-0002-2360-7134 NR 18 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2014 VL 7 IS 5 BP 571 EP 572 DI 10.1161/CIRCGENETICS.114.000825 PG 2 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AS6IU UT WOS:000344368200001 PM 25518041 ER PT J AU Tada, H Won, HH Melander, O Yang, J Peloso, GM Kathiresan, S AF Tada, Hayato Won, Hong-Hee Melander, Olle Yang, Jian Peloso, Gina M. Kathiresan, Sekar TI Multiple Associated Variants Increase the Heritability Explained for Plasma Lipids and Coronary Artery Disease SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE coronary artery disease; genetics; genome-wide association study; lipids ID GENOME-WIDE ASSOCIATION; MISSING HERITABILITY; RISK; MYSTERY; TRAITS; LOCI AB Background Plasma lipid levels as well as coronary artery disease (CAD) have been shown to be highly heritable with estimates ranging from 40% to 60%. However, top variants detected by large-scale genome-wide association studies explain only a fraction of the total variance in plasma lipid phenotypes and CAD. Methods and Results We performed a conditional and joint association analysis using summary-level statistics from 2 large genome-wide association meta-analyses: the Global Lipids Genetics Consortium (GLGC) study, and the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) study. There were 100 184 individuals from 46 GLGC studies for plasma lipids, and 22 233 cases and 64 762 controls from 14 studies for CAD. We detected several loci where multiple independent single-nucleotide polymorphisms were associated with lipid traits within a locus (12 out of 33 loci for high-density lipoprotein cholesterol, 10 of 35 loci for low-density lipoprotein cholesterol, 13 of 44 loci for total cholesterol, and 8 of 28 loci for triglycerides), reaching genome-wide significance (P<5x10(-8)), nearly doubling the heritability explained by genome-wide association studies (from 3.6 to 7.6% for high-density lipoprotein cholesterol, from 5.0 to 8.8% for low-density lipoprotein cholesterol, from 5.5 to 8.8% for total cholesterol, and from 5.7 to 8.5% for triglycerides). Multiple single-nucleotide polymorphisms were also associated with CAD (3 of 15 loci; an increase from 9.6% to 11.4% of heritability explained). Conclusions These results demonstrate that a portion of the missing heritability for lipid traits and CAD can be explained by multiple variants at each locus. C1 [Tada, Hayato; Won, Hong-Hee; Peloso, Gina M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Tada, Hayato; Won, Hong-Hee; Peloso, Gina M.; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Melander, Olle] Lund Univ, Dept Clin Sci, Lund, Sweden. [Melander, Olle] Skane Univ Hosp, Dept Internal Med, Malmo, Sweden. [Yang, Jian] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-252, Boston, MA 02114 USA. EM sekar@broadinstitute.org RI Yang, Jian/A-5852-2010 OI Yang, Jian/0000-0003-2001-2474 FU Japanese Circulation Society; Swedish Cancer Society; Swedish Medical Research Council; Swedish Dairy Association; Albert Pahlsson Foundation; Gunnar Nilsson Foundation; Malmo city council; European Research Council [StG-282255]; Swedish Heart and Lung Foundation; Swedish Research Council; Novo Nordisk Foundation; Skane University Hospital; Medical Faculty, Lund University; governmental funding of clinical research within the national health services; Albert Pahlsson Research Foundation; Region Skane; King Gustav V and Queen Victoria Foundation; Marianne and Marcus Wallenberg Foundation; National Heart, Lung, and Blood Institute [T32HL007208]; Massachusetts General Hospital (MGH); Howard Goodman Fellowship from MGH; Donovan Family Foundation [R01HL107816]; Fondation Leducq FX H. Tada is supported by a grant for studying overseas from Japanese Circulation Society. The Malmo Diet and Cancer study was made possible by grants from the Swedish Cancer Society, the Swedish Medical Research Council, the Swedish Dairy Association, the Albert Pahlsson and Gunnar Nilsson Foundations, and the Malmo city council. O. Melander is supported by the European Research Council (StG-282255); the Swedish Heart and Lung Foundation; Swedish Research Council; the Novo Nordisk Foundation; the Skane University Hospital donation funds; the Medical Faculty, Lund University; the governmental funding of clinical research within the national health services; the Albert Pahlsson Research Foundation; Region Skane; the King Gustav V and Queen Victoria Foundation; and the Marianne and Marcus Wallenberg Foundation. G. M. Peloso is supported by award number T32HL007208 from the National Heart, Lung, and Blood Institute. S. Kathiresan is supported by a Research Scholar award from the Massachusetts General Hospital (MGH), the Howard Goodman Fellowship from MGH, the Donovan Family Foundation, R01HL107816, and a grant from Fondation Leducq. NR 18 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2014 VL 7 IS 5 BP 583 EP 587 DI 10.1161/CIRCGENETICS.113.000420 PG 5 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AS6IU UT WOS:000344368200004 PM 25170055 ER PT J AU Wu, C Arora, P AF Wu, Connie Arora, Pankaj TI Long Noncoding RNA-MicroRNA-mRNA A Novel Tripartite Axis in the Regulation of Cardiac Hypertrophy SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Editorial Material DE cardiac hypertrophy; gene expression; regulation; microRNA C1 [Wu, Connie] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr,Cardiol Div,Med Sch, Boston, MA USA. [Arora, Pankaj] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. RP Arora, P (reprint author), Univ Alabama Birmingham, Div Cardiol, 1808 7th Ave South,BDB 201, Birmingham, AL 35294 USA. EM parora@uabmc.edu OI Arora, Pankaj/0000-0003-2420-3550 NR 6 TC 2 Z9 3 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2014 VL 7 IS 5 BP 729 EP 731 DI 10.1161/CIRCGENETICS.114.000866 PG 3 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AS6IU UT WOS:000344368200021 PM 25336446 ER PT J AU Owens, BD Tokish, JM Provencher, MT AF Owens, Brett D. Tokish, John M. Provencher, Matthew T. TI Dedication SO CLINICS IN SPORTS MEDICINE LA English DT Editorial Material C1 [Owens, Brett D.] Uniformed Serv Univ Hlth Sci, US Mil Acad, Keller Army Hosp, West Point, NY 10996 USA. [Tokish, John M.] Steadman Hawkins Clin Carolinas, Greenville, SC 29615 USA. [Provencher, Matthew T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Sports Med Serv, Boston, MA 02114 USA. RP Owens, BD (reprint author), Uniformed Serv Univ Hlth Sci, US Mil Acad, Keller Army Hosp, West Point, NY 10996 USA. EM owensbrett@gmail.com NR 0 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 0278-5919 EI 1556-228X J9 CLIN SPORT MED JI Clin. Sports Med. PD OCT PY 2014 VL 33 IS 4 BP XVII EP XVIII DI 10.1016/j.csm.2014.07.002 PG 2 WC Sport Sciences SC Sport Sciences GA AS7KJ UT WOS:000344434800003 PM 25280624 ER PT J AU Dumont, GD Golijanin, P Provencher, MT AF Dumont, Guillaume D. Golijanin, Petar Provencher, Matthew T. TI Shoulder Instability in the Military SO CLINICS IN SPORTS MEDICINE LA English DT Article DE Shoulder dislocation; Glenohumeral instability; Bankart lesion; Glenoid bone loss; ALPSA; HAGL; Labrum; Military ID GLENOID BONE LOSS; TRAUMATIC ANTERIOR DISLOCATION; ARTHROSCOPIC CAPSULOLABRAL REPAIR; SLEEVE AVULSION LESION; HILL-SACHS LESION; EXTERNAL ROTATION; BANKART REPAIR; GLENOHUMERAL INSTABILITY; HUMERAL AVULSION; BARE SPOT AB Shoulder instability is common in the military population. Such factors as young age, male gender, activity level, and unique job characteristics and duties predispose the military population to increased rates of shoulder instability. The initial treatment of shoulder instability has historically been nonoperative; however, in military personnel who have several characteristics predisposing them to recurrent instability, early surgical intervention may be favorable. Appropriate preoperative imaging and understanding of pathologic lesions are necessary to ensure selection of the appropriate surgical technique. Bony reconstruction procedures, such as the Bristow-Latarjet procedure, iliac crest bone graft, or osteochondral allograft transfer to the anterior glenoid, may be necessary. C1 [Dumont, Guillaume D.] Univ S Carolina, Sch Med, Dept Orthopaed Surg & Sports Med, Columbia, SC 29203 USA. [Golijanin, Petar] Massachusetts Gen Hosp, Sports Med Serv, Boston, MA 02114 USA. [Provencher, Matthew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sports Med Serv, Boston, MA 02114 USA. RP Dumont, GD (reprint author), Univ S Carolina, Sch Med, Dept Orthopaed Surg & Sports Med, 2 Med Pk,Suite 404, Columbia, SC 29203 USA. EM gddumont@gmail.com NR 72 TC 1 Z9 1 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-5919 EI 1556-228X J9 CLIN SPORT MED JI Clin. Sports Med. PD OCT PY 2014 VL 33 IS 4 BP 707 EP + DI 10.1016/j.csm.2014.06.006 PG 15 WC Sport Sciences SC Sport Sciences GA AS7KJ UT WOS:000344434800012 PM 25280618 ER PT J AU Spielberg, JM Miller, GA Warren, SL Sutton, BP Banich, M Heller, W AF Spielberg, Jeffrey M. Miller, Gregory A. Warren, Stacie L. Sutton, Bradley P. Banich, Marie Heller, Wendy TI TRANSDIAGNOSTIC DIMENSIONS OF ANXIETY AND DEPRESSION MODERATE MOTIVATION-RELATED BRAIN NETWORKS DURING GOAL MAINTENANCE SO DEPRESSION AND ANXIETY LA English DT Article DE amygdale; anxiety; depression; dorsolateral prefrontal cortex; orbitofrontal cortex; network; transdiagnostic ID POSTTRAUMATIC-STRESS-DISORDER; GENERALIZED SOCIAL PHOBIA; INCREASED AMYGDALA ACTIVATION; DOWN ATTENTIONAL CONTROL; PREFRONTAL CORTEX; FUNCTIONAL CONNECTIVITY; AVOIDANCE MOTIVATION; UNIPOLAR DEPRESSION; EXECUTIVE FUNCTION; MAJOR DEPRESSION AB BackgroundAdvancing research on the etiology, prevention, and treatment of psychopathology requires the field to move beyond modular conceptualizations of neural dysfunction toward understanding disturbance in key brain networks. Although some studies of anxiety and depression have begun doing so, they typically suffer from several drawbacks, including: (1) a categorical approach ignoring transdiagnostic processes, (2) failure to account for substantial anxiety and depression comorbidity, (3) examination of networks at rest, which overlooks disruption manifesting only when networks are challenged. Accordingly, the present study examined relationships between transdiagnostic dimensions of anxiety/depression and patterns of functional connectivity while goal maintenance was challenged. MethodsParticipants (n = 179, unselected community members and undergraduates selected to be high/low on anxiety/depression) performed a task in which goal maintenance was challenged (color-word Stroop) while fMRI data were collected. Analyses examined moderation by anxiety/depression of condition-dependent coupling between regions of dorsolateral prefrontal cortex (dlPFC) previously associated with approach and avoidance motivation and amygdala/orbitofrontal cortex (OFC). ResultsAnxious arousal was positively associated with amygdalaright dlPFC coupling. Depression was positively associated with OFCright dlPFC coupling and negatively associated with OFCleft dlPFC coupling. ConclusionsFindings advance the field toward an integrative model of the neural instantiation of anxiety/depression by identifying specific, distinct dysfunctions associated with anxiety and depression in networks important for maintaining approach and avoidance goals. Specifically, findings shed light on potential neural mechanisms involved in attentional biases in anxiety and valuation biases in depression and underscore the importance of examining transdiagnostic dimensions of anxiety/depression while networks are challenged. C1 [Spielberg, Jeffrey M.; Miller, Gregory A.; Warren, Stacie L.; Sutton, Bradley P.; Heller, Wendy] Univ Illinois, Dept Psychol, Champaign, IL USA. [Miller, Gregory A.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Warren, Stacie L.] St Louis VA Med Ctr, St Louis, MO USA. [Banich, Marie] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. RP Spielberg, JM (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave 182 JP, Boston, MA 02130 USA. EM spielbergjm@gmail.com RI Sutton, Bradley/A-4801-2008; OI Sutton, Bradley/0000-0002-8443-0408; Warren, Stacie/0000-0002-6096-5950; Spielberg, Jeffrey/0000-0001-8348-7157 FU NIMH NIH HHS [R01 MH061358] NR 71 TC 6 Z9 6 U1 4 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD OCT PY 2014 VL 31 IS 10 BP 805 EP 813 DI 10.1002/da.22271 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA AS3KL UT WOS:000344176200001 PM 24753242 ER PT J AU Cadogan, M Thoma, B Chan, TM Lin, M AF Cadogan, Mike Thoma, Brent Chan, Teresa M. Lin, Michelle TI Free Open Access Meducation (FOAM): the rise of emergency medicine and critical care blogs and podcasts (2002-2013) SO EMERGENCY MEDICINE JOURNAL LA English DT Article ID EDUCATION AB Disruptive technologies are revolutionising continuing professional development in emergency medicine and critical care (EMCC). Data on EMCC blogs and podcasts were gathered prospectively from 2002 through November 2013. During this time there was a rapid expansion of EMCC websites, from two blogs and one podcast in 2002 to 141 blogs and 42 podcasts in 2013. This paper illustrates the explosive growth of EMCC websites and provides a foundation that will anchor future research in this burgeoning field. C1 [Cadogan, Mike] Sir Charles Gairdner Hosp, Dept Emergency Med, Perth, WA, Australia. [Thoma, Brent] Massachusetts Gen Hosp, Learning Lab, Boston, MA 02114 USA. [Thoma, Brent] Massachusetts Gen Hosp, Dept Emergency Med, Div Med Simulat, Boston, MA 02114 USA. [Thoma, Brent] Univ Saskatchewan, Dept Emergency Med, Saskatoon, SK, Canada. [Thoma, Brent; Chan, Teresa M.; Lin, Michelle] MedEdLIFE Org Res Collaborat, San Francisco, CA USA. [Chan, Teresa M.] McMaster Univ, Dept Med, Div Emergency Med, Hamilton, ON, Canada. [Lin, Michelle] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. RP Thoma, B (reprint author), Univ Saskatchewan, Royal Univ Hosp, EM Residency Training Program, Dept Emergency Med, Room 2686 103 Hosp Dr, Saskatoon, SK S7N 0W8, Canada. EM brent.thoma@usask.ca RI Cadogan, Mike/J-6479-2014; OI Cadogan, Mike/0000-0002-1281-9828; Chan, Teresa/0000-0001-6104-462X; Thoma, Brent/0000-0003-1124-5786 NR 7 TC 34 Z9 34 U1 1 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1472-0205 EI 1472-0213 J9 EMERG MED J JI Emerg. Med. J. PD OCT PY 2014 VL 31 IS E1 BP E76 EP E77 DI 10.1136/emermed-2013-203502 PG 2 WC Emergency Medicine SC Emergency Medicine GA AS2BG UT WOS:000344083400014 PM 24554447 ER PT J AU Rosen, R Amirault, J Liu, HY Mitchell, P Hu, L Khatwa, U Onderdonk, A AF Rosen, Rachel Amirault, Janine Liu, Hongye Mitchell, Paul Hu, Lan Khatwa, Umakanth Onderdonk, Andrew TI Changes in Gastric and Lung Microflora With Acid Suppression Acid Suppression and Bacterial Growth SO JAMA PEDIATRICS LA English DT Article ID VENTILATOR-ASSOCIATED PNEUMONIA; RESPIRATORY-TRACT; HEALTHY-CHILDREN; RISK; COLONIZATION; MICROBIOTA; REFLUX; OVERGROWTH; POSITIVITY; INHIBITORS AB IMPORTANCE The use of acid suppression has been associated with an increased risk of upper and lower respiratory tract infections in the outpatient setting but the mechanism behind this increased risk is unknown. We hypothesize that this infection risk results from gastric bacterial overgrowth with subsequent seeding of the lungs. OBJECTIVES To determine if acid-suppression use results in gastric bacterial overgrowth, if there are changes in lung microflora associated with the use of acid suppression, and if changes in lung microflora are related to full-column nonacid gastroesophageal reflux. DESIGN, SETTING, AND PARTICIPANTS A 5-year prospective cohort study at a tertiary care center where children ages 1 to 18 years were undergoing bronchoscopy and endoscopy for the evaluation of chronic cough. Acid-suppression use was assessed through questionnaires with confirmation using an electronic medical record review. MAIN OUTCOMES AND MEASURES Our primary outcome was to compare differences in concentration and prevalence of gastric and lung bacteria between patients who were and were not receiving acid-suppression therapy. We compared medians using the Wilcoxon signed rank test and determined prevalence ratios using asymptotic standard errors and 95% confidence intervals. We determined correlations between continuous variables using Pearson correlation coefficients and compared categorical variables using the Fisher exact test. RESULTS Forty-six percent of patients taking acid-suppression medication had gastric bacterial growth compared with 18% of untreated patients (P=.003). Staphylococcus (prevalence ratio, 12.75 [95% CI, 1.72-94.36]), Streptococcus (prevalence ratio, 6.91 [95% CI, 1.64-29.02]), Veillonella (prevalence ratio, 9.56 [95% CI, 1.26-72.67]), Dermabacter (prevalence ratio, 4.78 [95% CI, 1.09-21.02]), and Rothia (prevalence ratio, 6.38 [95% CI, 1.50-27.02]) were found more commonly in the gastric fluid of treated patients. The median bacterial concentration was higher in treated patients than in untreated patients (P=.001). There was no difference in the prevalence (P>.23) of different bacterial genera or the median concentration of total bacteria (P=.85) in the lungs between treated and untreated patients. There were significant positive correlations between proximal nonacid reflux burden and lung concentrations of Bacillus (r = 0.47, P=.005), Dermabacter (r = 0.37, P=.008), Lactobacillus (r = 0.45, P=.001), Peptostreptococcus (r = 0.37, P=.008), and Capnocytophagia (r = 0.37, P=.008). CONCLUSIONS AND RELEVANCE Acid-suppression use results in gastric bacterial overgrowth of genera including Staphylococcus and Streptococcus. Full-column nonacid reflux is associated with greater concentrations of bacteria in the lung. Additional studies are needed to determine if acid suppression-related microflora changes predict clinical infection risk; these results suggest that acid suppression use may need to be limited in patients at risk for infections. C1 [Rosen, Rachel; Amirault, Janine] Boston Childrens Hosp, Dept Gastroenterol, Aerodigest Ctr, Boston, MA 02115 USA. [Liu, Hongye; Mitchell, Paul] Boston Childrens Hosp, Clin Res Ctr, Boston, MA 02115 USA. [Hu, Lan] Dana Farber Canc Inst, Ctr Computat Canc Biol, Boston, MA 02115 USA. [Khatwa, Umakanth] Boston Childrens Hosp, Dept Pulm Med, Aerodigest Ctr, Boston, MA 02115 USA. [Onderdonk, Andrew] Brigham & Womens Hosp, Dept Microbiol, Boston, MA 02115 USA. RP Rosen, R (reprint author), Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM rachel.rosen@childrens.harvard.edu FU National Institutes of Health [K23 DK073713, 1R03DK089146, K24DK082792A]; Translational Research Program at Boston Children's Hospital FX This work was supported by grants K23 DK073713, 1R03DK089146, and K24DK082792A from the National Institutes of Health and a junior investigator award from the Translational Research Program at Boston Children's Hospital. NR 27 TC 13 Z9 13 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD OCT PY 2014 VL 168 IS 10 BP 932 EP 937 DI 10.1001/jamapediatrics.2014.696 PG 6 WC Pediatrics SC Pediatrics GA AT1NC UT WOS:000344699800019 PM 25133779 ER PT J AU Schultz, CL Mitra, N Schapira, MM Lambert, MP AF Schultz, Corinna L. Mitra, Nandita Schapira, Marilyn M. Lambert, Michele P. TI Influence of the American Society of Hematology Guidelines on the Management of Newly Diagnosed Childhood Immune Thrombocytopenia SO JAMA PEDIATRICS LA English DT Article ID PEDIATRIC-HEMATOLOGY/ONCOLOGY; INTRAVENOUS IMMUNOGLOBULIN; NATURAL-HISTORY; PURPURA; CHILDREN; HEMORRHAGE; ADULTS; TRENDS; CARE; ITP AB IMPORTANCE In 2011, the American Society of Hematology (ASH) published updated guidelines for the management of childhood immune thrombocytopenia (ITP) recommending management with observation alone when there are mild or no bleeding symptoms, regardless of platelet count. Little is known about practice patterns of newly diagnosed ITP in the United States. OBJECTIVE To understand the impact of management recommendations on practice patterns. DESIGN, SETTING, AND PARTICIPANTS Retrospective medical record review in the Children's Hospital of Philadelphia, a large, urban, pediatric tertiary care hospital in Philadelphia, Pennsylvania. The study involved 311 pediatric patients with newly diagnosed ITP managed between January 1, 2007, and December 31, 2012. MAIN OUTCOMES AND MEASURES Management type (observation alone vs pharmacotherapy) was determined via medical record review and electronic pharmacy data at diagnosis and within 6 months after diagnosis. RESULTS Overall, 44.7% of patients were managed with observation alone at diagnosis, with a significant increase from 34.9% in 2007-2010 to 49.2% in 2011 (P<.02) and 71.1% in 2012 (P<.001). Of those treated, 99% were treated with intravenous immunoglobulin. In multivariable logistic regression, younger age (odds ratio, 0.92; 95% CI, 0.87-0.99), lower platelet count (odds ratio, 0.86; 95% CI, 0.83-0.89), and earlier period (2007-2010) of diagnosis (odds ratio, 0.17; 95% CI, 0.09-0.34) were significantly associated with increased odds of pharmacologic management. During 2010-2012, 20.8% of patients were also treated within 6 months after diagnosis. There was no significant difference by year or initial management type in those who received this later pharmacotherapy. Additionally, 19.6% of patients had documented bleeding symptoms beyond cutaneous bruising or petechiae at diagnosis. Intracranial hemorrhage at diagnosis was rare (0.6%). CONCLUSIONS AND RELEVANCE We demonstrated a significant practice change in the management of newly diagnosed ITP at a pediatric care tertiary care hospital in the United States surrounding revision of the ASH management guidelines for childhood ITP. Our experience supports adoption of observation alone for a proportion of patients with newly diagnosed childhood ITP. This form of management did not lead to an increase in later treatment or an increase in delayed bleeding symptoms. C1 [Schultz, Corinna L.; Lambert, Michele P.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Mitra, Nandita] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Mitra, Nandita; Schapira, Marilyn M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Schapira, Marilyn M.; Lambert, Michele P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Schapira, Marilyn M.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Schultz, CL (reprint author), Dept Hematol, 34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM schultzc1@email.chop.edu FU Division of Hematology, The Children's Hospital of Philadelphia FX This study was supported by the Division of Hematology, The Children's Hospital of Philadelphia. NR 24 TC 5 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 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD OCT PY 2014 VL 168 IS 10 AR e142214 DI 10.1001/jamapediatrics.2014.2214 PG 7 WC Pediatrics SC Pediatrics GA AT1NC UT WOS:000344699800002 PM 25288142 ER PT J AU Richman, JS Itani, KMF Deierhoi, RJ Henderson, WG Hawn, MT AF Richman, Joshua S. Itani, Kamal M. F. Deierhoi, Rhiannon J. Henderson, William G. Hawn, Mary T. TI Improved Outcomes Associated With a Revised Quality Measure for Continuing Perioperative beta-Blockade SO JAMA SURGERY LA English DT Article ID MAJOR NONCARDIAC SURGERY; SURGICAL CARE; POSTOPERATIVE MORTALITY; RISK ADJUSTMENT; CARDIAC RISK; PROGRAM; WITHDRAWAL AB IMPORTANCE The Surgical Care Improvement Project perioperative beta-blocker (BB) (SCIP-BB) continuation measure was revised in 2012 to incorporate inpatient BB continuation after discharge from the postanesthesia care unit. OBJECTIVE To determine whether adherence to the original or revised SCIP-BB measure is associated with decreased adverse events. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using national Veterans Affairs patient-level data on adherence to the original SCIP-BB measure and inpatient BB continuation for operations between July 2006 and August 2009. METHODS Data for SCIP-BB measure adherence, inpatient BB continuation, and patient and procedure risk variables were used to estimate the associations between adherence to the original and revised SCIP-BB measures and outcomes of major adverse cardiovascular or cerebrovascular events (MACCEs) and their components of cardiovascular events, cerebrovascular events, and 30-day mortality. In addition to unadjusted estimates, propensity score matching and bootstrapping were used to estimate the associations and generate 95% CIs. MAIN OUTCOMES AND MEASURES Major adverse cardiovascular or cerebrovascular events. RESULTS Of 14 420 nonemergent operations with at least 2 postoperative inpatient days, 13 170 (91.3%) adhered to the original SCIP-BB measure, and 480 (3.3%) experienced a MACCE. Propensity score-matched analyses showed that adherence to the original SCIP-BB measure was not associated with MACCEs (odds ratio [OR], 1.00; 95% CI, 0.66-1.54) but was associated with increased cerebrovascular events (OR, 3.01; 95% CI, 1.00-10.07). Adherence to the revised SCIP-BB measure occurred in 11 597 (80.4%), and in matched analysis adherence was associated with decreased MACCEs (OR, 0.75; 95% CI, 0.57-0.95), cardiovascular events (OR, 0.66; 95% CI, 0.46-0.93), and 30-day mortality (OR, 0.74; 95% CI, 0.53-0.98). Adherence to the revised SCIP-BB measure was not associated with increased cerebrovascular events (OR, 1.22; 95% CI, 0.62-2.38). CONCLUSIONS AND RELEVANCE Adherence to the original SCIP-BB measure was associated with increased cerebrovascular events but not improved cardiovascular event outcomes. beta-Blocker continuation consistent with the revised SCIP-BB measure is associated with reduced MACCEs, cardiovascular events, and 30-day mortality. These data provide a cautionary tale of implementing performance measures before they have been rigorously tested. Although the observed associations between adherence to the revised SCIP-BB measure and outcomes are promising, they should be evaluated in the postimplementation period. C1 [Richman, Joshua S.; Deierhoi, Rhiannon J.; Hawn, Mary T.] Birmingham Vet Affairs Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL 35294 USA. [Richman, Joshua S.; Deierhoi, Rhiannon J.; Hawn, Mary T.] Univ Alabama Birmingham, Dept Surg, Sect Gastrointestinal Surg, Birmingham, AL USA. [Itani, Kamal M. F.] Boston Univ, Dept Surg, Vet Affairs Boston Hlth Care Syst, Boston, MA 02215 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. [Henderson, William G.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Henderson, William G.] Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. [Henderson, William G.] Univ Colorado, Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. RP Richman, JS (reprint author), Birmingham Vet Affairs Med Ctr, Ctr Surg Med Acute Care Res & Transit, 1922 Seventh Ave S,Kracke Bldg 428, Birmingham, AL 35294 USA. EM jrichman@uab.edu FU VA Health Services Research and Development Career Development Award [CDA2 09-014-3]; VA Health Services Research and Development program [PPO 10-296] FX Dr Richman was supported by VA Health Services Research and Development Career Development Award CDA2 09-014-3. This study was funded by grant PPO 10-296 from the VA Health Services Research and Development program. NR 18 TC 4 Z9 4 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD OCT PY 2014 VL 149 IS 10 BP 1031 EP 1037 DI 10.1001/jamasurg.2014.351 PG 7 WC Surgery SC Surgery GA AS0SC UT WOS:000343987300009 PM 25141795 ER PT J AU Gandaglia, G Ghani, KR Sood, A Meyers, JR Sammon, JD Schmid, M Varda, B Briganti, A Montorsi, F Sun, M Menon, M Kibel, AS Trinh, QD AF Gandaglia, Giorgio Ghani, Khurshid R. Sood, Akshay Meyers, Jessica R. Sammon, Jesse D. Schmid, Marianne Varda, Briony Briganti, Alberto Montorsi, Francesco Sun, Maxine Menon, Mani Kibel, Adam S. Quoc-Dien Trinh TI Effect of Minimally Invasive Surgery on the Risk for Surgical Site Infections Results From the National Surgical Quality Improvement Program (NSQIP) Database SO JAMA SURGERY LA English DT Article ID OPEN GASTRIC BYPASS; LAPAROSCOPIC SURGERY; COLORECTAL SURGERY; WOUND INFECTIONS; MORBIDITY; HEALTH; CARE; SURVEILLANCE; APPENDECTOMY; DECREASES AB IMPORTANCE Surgical site infection (SSI) represents the second most common cause of hospital-acquired infection and the most common type of infection in patients undergoing surgery. However, evidence is scarce regarding the effect of the surgical approach (open surgery vs minimally invasive surgery [MIS]) on the risk for SSIs. OBJECTIVE To evaluate the role of the surgical approach on the risk for SSIs in a large contemporary cohort of patients undergoing surgery across different specialties. DESIGN, SETTING, AND PARTICIPANTS The American College of Surgeons National Surgical Quality Improvement Program database is a national, prospective perioperative database specifically developed to assess quality of surgical care. We queried the database from January 1, 2005, through December 31, 2011, for patients undergoing appendectomy (n = 97 780), colectomy (n = 118 407), hysterectomy (n = 26 639), or radical prostatectomy (n = 11 183). EXPOSURES Thirty-day SSIs. MAIN OUTCOMES AND MEASURES We abstracted the data on 30-day SSIs and compared patients undergoing open procedures and MIS using propensity score matching. Logistic regression analyses of the matched cohorts tested the association between the surgical approach and risk for SSIs. RESULTS The overall 30-day rates of SSIs were 5.4% for appendectomy, 12.1% for colectomy, 2.8% for hysterectomy, and 1.7% for prostatectomy. After propensity score matching, MIS was associated with lower rates of postoperative SSIs in patients undergoing MIS vs open procedures for appendectomy (3.8% vs 7.0%; P < .001), colectomy (9.3% vs 15.0%; P < .001), hysterectomy (1.8% vs 3.9%; P < .001), and radical prostatectomy (1.0% vs 2.4%; P < .001). In logistic regression analyses, MIS was associated with lower odds of SSIs in patients treated with appendectomy (odds ratio [OR], 0.52 [95% CI, 0.48-0.58]; P < .001), colectomy (OR, 0.58 [95% CI, 0.55-0.61]; P < .001), hysterectomy (OR, 0.44 [95% CI, 0.37-0.53]; P < .001), and radical prostatectomy (OR, 0.39 [95% CI, 0.25-0.61]; P < .001). CONCLUSIONS AND RELEVANCE The proportion of patients developing SSIs within 30 days after surgery can be substantial and depends on the type of surgery. Minimally invasive surgery is significantly associated with reduced odds of SSIs. This advantage should be considered when assessing the overall benefits of minimally invasive techniques. C1 [Gandaglia, Giorgio; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ H2X 1P1, Canada. [Gandaglia, Giorgio; Briganti, Alberto; Montorsi, Francesco] Univ Vita Salute San Raffaele, Urol Res Inst, San Raffaele Sci Inst, Milan, Italy. [Ghani, Khurshid R.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Sood, Akshay; Meyers, Jessica R.; Sammon, Jesse D.; Menon, Mani] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. [Schmid, Marianne; Varda, Briony; Kibel, Adam S.; Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Surg & Publ Hlth,Div Urol Surg,Med Sch, Boston, MA 02115 USA. RP Gandaglia, G (reprint author), Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, 264 Blvd Rene Levesque E,Room 228, Montreal, PQ H2X 1P1, Canada. EM giorgio.gandaglia@gmail.com NR 28 TC 18 Z9 18 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD OCT PY 2014 VL 149 IS 10 BP 1039 EP 1044 DI 10.1001/jamasurg.2014.292 PG 6 WC Surgery SC Surgery GA AS0SC UT WOS:000343987300011 PM 25143176 ER PT J AU Hwabejire, JO Kaafarani, HMA Lee, J Yeh, DD Fagenholz, P King, DR de Moya, MA Velmahos, GC AF Hwabejire, John O. Kaafarani, Haytham M. A. Lee, Jarone Yeh, Daniel D. Fagenholz, Peter King, David R. de Moya, Marc A. Velmahos, George C. TI Patterns of Injury, Outcomes, and Predictors of In-Hospital and 1-Year Mortality in Nonagenarian and Centenarian Trauma Patients SO JAMA SURGERY LA English DT Article ID LONG-TERM SURVIVAL; GERIATRIC TRAUMA; MANAGEMENT AB IMPORTANCE With the dramatic growth in the very old population and their concomitant heightened exposure to traumatic injury, the trauma burden among this patient population is estimated to be exponentially increasing. OBJECTIVE To determine the clinical outcomes and predictors of in-hospital and 1-year mortality in nonagenarian and centenarian trauma patients (NCTPs). DESIGN, SETTING, AND PARTICIPANTS All patients 90 years or older admitted to a level 1 academic trauma center between January 1, 2006, and December 31, 2010, with a primary diagnosis of trauma were included. Standard trauma registry data variables were supplemented by systematic medical record review. Cumulative mortality rates at 1, 3, 6, and 12 months after discharge were investigated using the Social Security Death Index. Univariate and multivariable analyses were performed to identify the predictors of in-hospital and 1-year postdischarge cumulative mortalities. MAIN OUTCOMES AND MEASURES Length of hospital stay, in-hospital mortality, and cumulative mortalities at 1, 3, 6, and 12 months after discharge. RESULTS Four hundred seventy-four NCTPs were included; 71.7% were female, and a fall was the predominant mechanism of injury (96.4%). The mean patient age was 93 years, the mean Injury Severity Score was 12, and the mean number of comorbidities per patient was 4.4. The in-hospital mortality was 9.5% but cumulatively escalated at 1, 3, 6, and 12 months after discharge to 18.5%, 26.4%, 31.3%, and 40.5%, respectively. Independent predictors of in-hospital mortality were the Injury Severity Score (odds ratio [OR], 1.09; 95% CI, 1.02-1.16; P = .01), mechanical ventilation (OR, 6.23; 95% CI, 1.42-27.27; P = .02), and cervical spine injury (OR, 4.37; 95% CI, 1.41-13.50; P =.01). Independent predictors of cumulative 1-year mortality were head injury (OR, 2.65; 95% CI, 1.24-5.67; P = .03) and length of hospital stay (OR, 1.06; 95% CI, 1.02-1.11; P = .005). Cumulative 1-year mortality in NCTPs with a head injury was 51.1% and increased to 73.2% if the Injury Severity Score was 25 or higher and to 78.7% if mechanical ventilation was required. Most NCTPs required rehabilitation; only 8.9% were discharged to home. CONCLUSIONS AND RELEVANCE Despite lowin-hospital mortality, the cumulative mortality rate among NCTPs at 1 year after discharge is significant, particularly in the presence of head injury, spine injury, mechanical ventilation, high injury severity, or prolonged length of hospital stay. These considerations can help guide clinical decisions and family discussions. C1 [Hwabejire, John O.; Kaafarani, Haytham M. A.; Lee, Jarone; Yeh, Daniel D.; Fagenholz, Peter; King, David R.; de Moya, Marc A.; Velmahos, George C.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Hwabejire, John O.; Kaafarani, Haytham M. A.; Lee, Jarone; Yeh, Daniel D.; Fagenholz, Peter; King, David R.; de Moya, Marc A.; Velmahos, George C.] Harvard Univ, Sch Med, Boston, MA USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM gvelmahos@partners.org OI King, David/0000-0003-1028-1478 NR 15 TC 7 Z9 7 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD OCT PY 2014 VL 149 IS 10 BP 1054 EP 1059 DI 10.1001/jamasurg.2014.473 PG 6 WC Surgery SC Surgery GA AS0SC UT WOS:000343987300015 PM 25133434 ER PT J AU Greenstein, RJ Cameron, DW Brown, ST AF Greenstein, Robert John Cameron, D. W. Brown, Sheldon T. TI "Add-on" is scientifically more accurate than "Placebo control" in multiple Inflammatory Bowel Disease (IBD) trials SO JOURNAL OF CROHNS & COLITIS LA English DT Letter DE Crohn's disease; Ulcerative colitis; Clinical trials; Placebo; Anti-inflammatory; Immunemodulators ID AVIUM SUBSPECIES PARATUBERCULOSIS C1 [Greenstein, Robert John; Brown, Sheldon T.] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. [Cameron, D. W.] Ottawa Hosp Res Inst, Ottawa, ON, Canada. RP Greenstein, RJ (reprint author), James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. OI Cameron, Bill/0000-0002-0090-3539 NR 5 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-9946 EI 1876-4479 J9 J CROHNS COLITIS JI J. Crohns Colitis PD OCT 1 PY 2014 VL 8 IS 10 BP 1334 EP 1335 DI 10.1016/j.crohns.2014.03.015 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS2RU UT WOS:000344128100025 PM 24768214 ER PT J AU Bekkers, S Becker, SJE Bossen, JKJ Mudgal, CS Ring, D Vranceanu, AM AF Bekkers, Stijn Becker, Stephanie J. E. Bossen, Jeroen K. J. Mudgal, Chaitanya S. Ring, David Vranceanu, Ana-Maria TI Relationships between pain misconceptions, disability, patients' goals and interpretation of information from hand therapists SO JOURNAL OF HAND THERAPY LA English DT Article DE Disability; Hand therapy; Negative pain thoughts; Misconceptions ID MEDICAL INFORMATION; PERCEPTION; QUICKDASH; MEMORY; MODEL; FEAR AB Introduction: Patient interpretation of advice from hand therapists may be related to nonadaptive pain thoughts (automatic, overprotective, unduly pessimistic statements triggered by nociception and exacerbated by psychological distress). Purpose of the study: This study aimed to determine whether there were correlations between participants' hand therapy goals, interpretation of advice from hand therapists, nonadaptive pain thoughts, and upper extremity-specific disability. Methods: One hundred and five participants completed questionnaires assessing nonadaptive pain thoughts, upper extremity-specific disability, lessons from hand therapists, and hand therapy goals. Results: Nonadaptive pain thoughts correlated with disability and were bi-directionally related to participant goals and interpretation of advice from hand therapists. Discussion: Patients' nonadapative pain thoughts and the words/concepts used by hand therapists are both important in recovery from upper extremity illness. Conclusions: Hand therapists should be mindful that nonadaptive pain thoughts are an important determinant of disability and that such thoughts can affect and be affected by their recommendations. Level of evidence: n/a (C) 2014 Hanley & Belfus, an imprint of Elsevier Inc. All rights reserved. C1 [Bekkers, Stijn; Becker, Stephanie J. E.; Bossen, Jeroen K. J.; Mudgal, Chaitanya S.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Vranceanu, Ana-Maria] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Behav Med Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Hand & Upper Extrem Serv, Boston, MA 02114 USA. EM dring@mgh.harvard.edu OI Ring, David/0000-0002-6506-4879; Bekkers, Stijn/0000-0002-8330-9243 FU Fondsendesk - Vrije Universiteit Amsterdam; Netherlands; Anna Foundation|NOREF; Genootschap Noorthey; Stichting Vreedefonds FX SB and JKJB were supported by a faculty grant for medical students from Fondsendesk - Vrije Universiteit Amsterdam, the Netherlands, for Scientific Research. SJEB was supported by Dutch research grants from Anna Foundation|NOREF, Genootschap Noorthey, and Stichting Vreedefonds, The Netherlands, for Scientific Research. NR 25 TC 0 Z9 0 U1 1 U2 2 PU HANLEY & BELFUS-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0894-1130 EI 1545-004X J9 J HAND THER JI J. Hand Ther. PD OCT-DEC PY 2014 VL 27 IS 4 BP 287 EP 295 DI 10.1016/j.jht.2014.06.003 PG 9 WC Orthopedics; Rehabilitation; Surgery SC Orthopedics; Rehabilitation; Surgery GA AS0LD UT WOS:000343967700003 PM 25064147 ER PT J AU Bekkers, S Vranceanu, AM Ring, D AF Bekkers, Stijn Vranceanu, Ana-Maria Ring, David TI Response letter regarding the Clinical Commentary SO JOURNAL OF HAND THERAPY LA English DT Letter C1 [Bekkers, Stijn; Vranceanu, Ana-Maria; Ring, David] Massachusetts Gen Hosp, Yawkee Ctr, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkee Ctr, Dept Orthopaed Surg, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Ring, David/0000-0002-6506-4879; Bekkers, Stijn/0000-0002-8330-9243 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0894-1130 EI 1545-004X J9 J HAND THER JI J. Hand Ther. PD OCT-DEC PY 2014 VL 27 IS 4 BP 298 EP 298 DI 10.1016/j.jht.2014.07.005 PG 1 WC Orthopedics; Rehabilitation; Surgery SC Orthopedics; Rehabilitation; Surgery GA AS0LD UT WOS:000343967700005 PM 25220714 ER PT J AU Marcum, ZA Hanlon, JT Strotmeyer, ES Newman, AB Shorr, RI Simonsick, EM Bauer, DC Boudreau, R Donohue, JM Perera, S AF Marcum, Zachary A. Hanlon, Joseph T. Strotmeyer, Elsa S. Newman, Anne B. Shorr, Ronald I. Simonsick, Eleanor M. Bauer, Douglas C. Boudreau, Robert Donohue, Julie M. Perera, Subashan CA Hlth Aging & Body Composition Stud TI Gastroprotective Agent Underuse in High-Risk Older Daily Nonsteroidal Anti-Inflammatory Drug Users over Time SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE nonsteroidal anti-inflammatory drug; older adults; gastroprotection ID COX-2 INHIBITORS; NSAIDS; CARE; OSTEOARTHRITIS; PREVENTION; ELDERS AB ObjectivesTo examine whether older adults taking nonsteroidal anti-inflammatory drugs (NSAIDs) decreased the underuse of gastroprotective agents over time. DesignBefore-and-after study. SettingHealth, Aging and Body Composition Study. ParticipantsDaily users of a NSAID (prescription and over the counter (OTC)) at visits in 2002-03 (preperiod; n=404) and 2006-07 (postperiod; n=172). The sample had a meanstandard deviation age of 78.22.7 at the preperiod visit and 81.92.7 at the postperiod visit. The majority were white and female and had 12 or more years of education. MeasurementsUnderusers were defined as persons taking nonselective NSAIDs who were at risk of peptic ulcer disease (PUD; because of current warfarin or glucocorticoid use or history of PUD) and not using a proton pump inhibitor (PPI) or persons taking cyclooxygenase 2 (COX-2) selective NSAIDs and aspirin who were at risk of PUD (having at least one risk factor) and not using a PPI. ResultsDaily NSAID use decreased from 17.6% to 11.3% (P<.001), and gastroprotective agent underuse decreased from 23.5% to 15.1% (P=.008). Controlling for important covariates, having prescription insurance was somewhat protective against underuse in the preperiod (adjusted odds ratio (AOR)=0.78, 95% confidence interval (CI)=0.46-1.34; P=.37), but more so and significantly in the postperiod (AOR=0.41, 95% CI=0.18-0.93; P=.03). Having prescription insurance was more protective in the post- than in the preperiod (less gastroprotective agent underuse; adjusted ratio of OR=0.53, 95% CI=0.22-1.29; P=.16), but this increased protection was not statistically significant. ConclusionIn older daily NSAID users at high risk of PUD, having prescription insurance and adequate gastroprotective use was more common in the post- than in the preperiod. C1 [Marcum, Zachary A.; Hanlon, Joseph T.; Newman, Anne B.; Perera, Subashan] Univ Pittsburgh, Div Geriatr Med, Sch Med, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Strotmeyer, Elsa S.; Newman, Anne B.; Boudreau, Robert] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Shorr, Ronald I.] Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Gainesville, FL 32608 USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Sch Med, Dept Med, Div Gen Internal Med, San Francisco, CA USA. [Boudreau, Robert; Perera, Subashan] Univ Pittsburgh, Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. [Donohue, Julie M.] Univ Pittsburgh, Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15213 USA. RP Marcum, ZA (reprint author), Univ Pittsburgh, Div Geriatr Med, Sch Med, 3471 Fifth Ave,Suite 500, Pittsburgh, PA 15213 USA. EM zam12@pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036; Boudreau, Robert/0000-0003-0162-5187; Donohue, Julie/0000-0003-2418-6017 FU Intramural NIH HHS; NIA NIH HHS [R01 AG027017, K07 AG033174, K07AG033174, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, P30 AG024827, P30AG024827, R01 AG028050, R01AG027017, R01AG028050, T32 AG021885]; NINR NIH HHS [R01 NR012459] NR 19 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2014 VL 62 IS 10 BP 1923 EP 1927 DI 10.1111/jgs.13066 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AS6QA UT WOS:000344386400015 PM 25284702 ER PT J AU Hanlon, JT Semla, TP Schmader, KE AF Hanlon, Joseph T. Semla, Todd P. Schmader, Kenneth E. TI Medication Misadventures in Older Adults: Literature from 2013 SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE medication errors; adverse drug events; age; pharmacoepidemiology ID SERUM ANTICHOLINERGIC ACTIVITY; RANDOMIZED-CONTROLLED-TRIAL; DRUG; POPULATION; HYDROCHLOROTHIAZIDE; CHLORTHALIDONE; ASSOCIATIONS; PEOPLE; BURDEN; RISK AB The objective of this paper is to review articles published in 2013 examining drug-related problems in the elderly and comment on their potential impact on clinical practice. To identify articles, we did a systematic search of the English-language literature restricted to those aged 65+from January 2013 to December 2013 using Medline and Google Scholar and a combination of the following search terms: drug-related problems, medication-related problems, medication errors, suboptimal prescribing, inappropriate prescribing, underutilization, polypharmacy, medication monitoring, medication dispensing, medication administration, medication adherence, adverse drug events, and adverse drug withdrawal events. A manual search of major general medicine and clinical pharmacology journals was also conducted to identify additional articles. A total of 51 articles were identified of which 20 were chosen to highlight. Three were annotated and critiqued and the additional 17 articles were summarized in an appendix. One article reported the results of a randomized controlled trial that showed that a pharmacist intervention successfully reduced suboptimal prescribing in older hospital patients. Another paper from this group previously reported data from the same study showing that the intervention also reduced medication related readmissions to the hospital. An observational study compared the use of two thiazide diuretics in older outpatients. They found that chlorthalidone was more likely to cause hypokalemia than hydrochlorothiazide. Finally, in a randomized controlled trial a pharmacist intervention resulted in the reduction of anticholinergic burden but did result in an improvement in cognition. These studies highlight that medication errors and adverse drug events continue to be important issues for health care professionals caring for older adults. C1 [Hanlon, Joseph T.] Univ Pittsburgh, Div Geriatr, Dept Med, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Biomed Informat, Sch Med, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Geriatr Pharmaceut Outcomes & Gero Informat Res &, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Semla, Todd P.] Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA. [Semla, Todd P.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. [Semla, Todd P.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Schmader, Kenneth E.] Duke Univ, Med Ctr, Sch Med, Div Geriatr,Dept Med, Durham, NC 27710 USA. [Schmader, Kenneth E.] Durham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. RP Hanlon, JT (reprint author), Univ Pittsburgh, Dept Geriatr Med, Kaufman Med Bldg,Suite 514,3471 5th Ave, Pittsburgh, PA 15213 USA. EM jth14@pitt.edu FU NIA NIH HHS [R01 AG037451, P30AG028716, R01AG037451, P30AG024827, R01AG027017, P30 AG024827, K07 AG033174, K07AG033174, P30 AG028716, T32 AG021885, R01 AG027017] NR 18 TC 2 Z9 3 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2014 VL 62 IS 10 BP 1950 EP 1953 DI 10.1111/jgs.13026 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AS6QA UT WOS:000344386400020 PM 25333528 ER PT J AU Edes, T Kinosian, B Vuckovic, NH Nichols, LO Becker, MM Hossain, M AF Edes, Thomas Kinosian, Bruce Vuckovic, Nancy H. Nichols, Linda Olivia Becker, Margaret Mary Hossain, Monir TI Better Access, Quality, and Cost for Clinically Complex Veterans with Home-Based Primary Care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE frail elders; policy; home care services; chronic disease; patient-centered care ID RISK ADJUSTMENT; MEDICARE; FRAIL; MODEL AB In successfully reducing healthcare expenditures, patient goals must be met and savings differentiated from cost shifting. Although the Department of Veterans Affairs (VA) Home Based Primary Care (HBPC) program for chronically ill individuals has resulted in cost reduction for the VA, it is unknown whether cost reduction results from restricting services or shifting costs to Medicare and whether HBPC meets patient goals. Cost projection using a hierarchical condition category (HCC) model adapted to the VA was used to determine VA plus Medicare projected costs for 9,425 newly enrolled HBPC recipients. Projected annual costs were compared with observed annualized costs before and during HBPC. To assess patient perspectives of care, 31 veterans and caregivers were interviewed from three representative programs. During HBPC, Medicare costs were 10.8% lower than projected, VA plus Medicare costs were 11.7% lower than projected, and combined hospitalizations were 25.5% lower than during the period without HBPC. Patients reported high satisfaction with HBPC team access, education, and continuity of care, which they felt contributed to fewer exacerbations, emergency visits, and hospitalizations. HBPC improves access while reducing hospitalizations and total cost. Medicare is currently testing the HBPC approach through the Independence at Home demonstration. C1 [Edes, Thomas] US Dept Vet Affairs, Off Clin Operat & Management, Washington, DC USA. [Kinosian, Bruce] Univ Penn, Sch Med, Div Geriatr, Philadelphia, PA 19104 USA. [Kinosian, Bruce] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Kinosian, Bruce] Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. [Kinosian, Bruce] Philadelphia Vet Affairs Med Ctr, Geriatr & Extended Care Data Anal Ctr, Philadelphia, PA USA. [Vuckovic, Nancy H.] Intel Corp, Hlth Strategies & Solut, Portland, OR USA. [Nichols, Linda Olivia] Vet Affairs Med Ctr, Caregiver Ctr, Memphis, TN USA. [Nichols, Linda Olivia] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Becker, Margaret Mary] US Dept Vet Affairs, Vet Affairs New England Healthcare Syst, Vet Integrated Serv Network 1, Bedford, MA USA. [Hossain, Monir] US Dept Vet Affairs, Off Assistant Deputy Secretary Hlth Policy & Plan, Field Off, Medicare & Medicaid Anal Ctr, Braintree, MA USA. RP Edes, T (reprint author), Dept Vet Affairs, 810 Vermont Ave NW, Washington, DC 20420 USA. EM thomas.edes@va.gov NR 25 TC 25 Z9 25 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2014 VL 62 IS 10 BP 1954 EP 1961 DI 10.1111/jgs.13030 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AS6QA UT WOS:000344386400021 PM 25333529 ER PT J AU Liang, SH Yokell, DL Normandin, MD Rice, PA Jackson, RN Shoup, TM Brady, TJ El Fakhri, G Collier, TL Vasdev, N AF Liang, Steven H. Yokell, Daniel L. Normandin, Marc D. Rice, Peter A. Jackson, Raul N. Shoup, Timothy M. Brady, Thomas J. El Fakhri, Georges Collier, Thomas L. Vasdev, Neil TI First Human Use of a Radiopharmaceutical Prepared by Continuous-Flow Microfluidic Radiofluorination: Proof of Concept with the Tau Imaging Agent [F-18]T807 SO MOLECULAR IMAGING LA English DT Article ID DOSE-ON-DEMAND; RADIOSYNTHESIS; TECHNOLOGY; REACTOR AB Despite extensive preclinical imaging with radiotracers developed by continuous-flow microfluidics, a positron emission tomographic (PET) radiopharmaceutical has not been reported for human imaging studies by this technology. The goal of this study was to validate the synthesis of the tau radiopharmaceutical 7-(6-fluoropyridin-3-yl)-5H-pyrido[4,3-b] indole ([F-18]T807) and perform first-in-human PET scanning enabled by microfluidic flow chemistry. [F-18]T807 was synthesized by our modified one-step method and adapted to suit a commercial microfluidic flow chemistry module. For this proof of concept, the flow system was integrated to a GE Tracerlab FXFN unit for high-performance liquid chromatography purification and formulation. Three consecutive productions of [F-18]T807 were conducted to validate this radiopharmaceutical. Uncorrected radiochemical yields of 17 +/- 1% of crude [F-18]T807 (approximate to 500 mCi, radiochemical purity 95%) were obtained from the microfluidic device. The crude material was then purified, and. 100 mCi of the final product was obtained in an overall uncorrected radiochemical yield of 5 +/- 1% (n = 3), relative to starting [F-18]fluoride (end of bombardment), with high radiochemical purity (>= 99%) and high specific activities (6 Ci/mu mol) in 100 minutes. A clinical research study was carried out with [F-18]T807, representing the first reported human imaging study with a radiopharmaceutical prepared by this technology. C1 Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Advion Inc, Ithaca, NY USA. RP Vasdev, N (reprint author), Massachusetts Gen Hosp, NMMI 55 Fruit St,White 427, Boston, MA 02114 USA. EM vasdev.neil@mgh.harvard.edu RI Normandin, Marc/C-6728-2015 OI Normandin, Marc/0000-0003-1645-523X FU Alzheimer's Drug Discovery Foundation; Advion, Inc FX Financial disclosure of authors: We thank the Alzheimer's Drug Discovery Foundation and Advion, Inc for generously providing funding and/or equipment for this research. NR 16 TC 3 Z9 3 U1 3 U2 18 PU B C DECKER INC PI HAMILTON PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1535-3508 EI 1536-0121 J9 MOL IMAGING JI Mol. Imaging PD OCT PY 2014 VL 13 DI 10.2310/7290.2014.00025 PG 5 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA AS4AL UT WOS:000344215900004 ER PT J AU Bove, R Musallam, A Healy, BC Raghavan, K Glanz, BI Bakshi, R Weiner, H De Jager, PL Miller, KK Chitnis, T AF Bove, R. Musallam, A. Healy, B. C. Raghavan, K. Glanz, B. I. Bakshi, R. Weiner, H. De Jager, P. L. Miller, K. K. Chitnis, T. TI Low testosterone is associated with disability in men with multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE Body mass index; cognition; cognitive impairment; disability; hormones; hypogonadism; leptin; multiple sclerosis; testosterone ID TANDEM MASS-SPECTROMETRY; VITAMIN-D; REFERENCE RANGES; COGNITIVE DETERIORATION; FOLLOW-UP; MS; AXIS; HYPOGONADISM; DETERMINANTS; IMPAIRMENT AB Background: Gonadal steroids may modulate disease course in multiple sclerosis (MS). Objective: To assess the prevalence and clinical associations of hypogonadism in men with MS. Methods: Male patients, aged 18-65 years, with relapsing remitting MS (RRMS) or clinically-isolated syndrome (CIS) and their first symptom < 10 years prior were selected from a longitudinal clinical study. We measured their hormones in stored morning blood samples, and collected their Expanded Disability Status Scale (EDSS) scores every 6 months and their Symbol Digit Modalities Test (SDMT) results annually. Results: Our analysis included 96 men with a mean age of 40 years, EDSS of 1.1 and disease duration of 4.6 years. Of these men, 39% were hypogonadal (total testosterone < 288 ng/dL); none showed compensatory elevations in luteinizing hormone. Their low testosterone levels and testosterone:estradiol ratios were negatively correlated with body mass index (BMI) and leptin, and showed no correlation with 25-hydroxy-vitamin D levels. In our primary cross-sectional analyses, there was a negative age-adjusted correlation between total testosterone and EDSS (p = 0.044). In the age-adjusted longitudinal analyses, higher baseline testosterone levels were associated with less decline in SDMT (p = 0.012). Conclusions: Men with MS may experience hypogonadotropic hypogonadism. Low testosterone levels may be associated with worse clinical outcomes. A potential neuroprotective role for testosterone warrants further investigation. C1 [Chitnis, T.] Partners Multiple Sclerosis Ctr, Brookline, MA 02445 USA. [Bove, R.; Musallam, A.; Healy, B. C.; Glanz, B. I.; Bakshi, R.; Weiner, H.; De Jager, P. L.; Chitnis, T.] Brigham & Womens Hosp, Dept Neurol, Partners Multiple Sclerosis Ctr, Brookline, MA USA. [Bove, R.; Healy, B. C.; Raghavan, K.; Glanz, B. I.; Bakshi, R.; Weiner, H.; De Jager, P. L.; Miller, K. K.; Chitnis, T.] Harvard Univ, Sch Med, Boston, MA USA. [Bove, R.; Weiner, H.; De Jager, P. L.; Chitnis, T.] Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA USA. [Healy, B. C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Miller, K. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Chitnis, T (reprint author), Partners Multiple Sclerosis Ctr, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA. EM tchitnis@rics.bwh.harvard.edu FU National Multiple Sclerosis Society [RG-4256A4/2]; National Multiple Sclerosis Society/American Brain Foundation [FAN 1761-A-1]; Harvard Catalyst/The Harvard Clinical and Translational Science Center; National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health (NIH) [8UL1TR000170-05] FX This work was supported by the National Multiple Sclerosis Society (grant number RG-4256A4/2 to TC and the National Multiple Sclerosis Society/American Brain Foundation Clinician Scientist Award number FAN 1761-A-1 to RB); the Harvard Catalyst/The Harvard Clinical and Translational Science Center; and the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health (NIH) (Award 8UL1TR000170-05); Harvard University and its affiliated academic health care centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of any funder. NR 39 TC 11 Z9 11 U1 0 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD OCT PY 2014 VL 20 IS 12 BP 1584 EP 1592 DI 10.1177/1352458514527864 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AS2WD UT WOS:000344136400007 PM 24710799 ER PT J AU Chen, O Riedemann, L Etoc, F Herrmann, H Coppey, M Barch, M Farrar, CT Zhao, J Bruns, OT Wei, H Guo, P Cui, J Jensen, R Chen, Y Harris, DK Cordero, JM Wang, ZW Jasanoff, A Fukumura, D Reimer, R Dahan, M Jain, RK Bawendi, MG AF Chen, Ou Riedemann, Lars Etoc, Fred Herrmann, Hendrik Coppey, Mathieu Barch, Mariya Farrar, Christian T. Zhao, Jing Bruns, Oliver T. Wei, He Guo, Peng Cui, Jian Jensen, Russ Chen, Yue Harris, Daniel K. Cordero, Jose M. Wang, Zhongwu Jasanoff, Alan Fukumura, Dai Reimer, Rudolph Dahan, Maxime Jain, Rakesh K. Bawendi, Moungi G. TI Magneto-fluorescent core-shell supernanoparticles SO NATURE COMMUNICATIONS LA English DT Article ID ONE-POT SYNTHESIS; QUANTUM DOTS; DRUG-DELIVERY; THERANOSTIC APPLICATIONS; HYBRID NANOPARTICLES; NANOCRYSTALS; RESONANCE; NANOCOMPOSITES; SUPERLATTICES; NANOMEDICINE AB Magneto-fluorescent particles have been recognized as an emerging class of materials that exhibit great potential in advanced applications. However, synthesizing such magnetofluorescent nanomaterials that simultaneously exhibit uniform and tunable sizes, high magnetic content loading, maximized fluorophore coverage at the surface and a versatile surface functionality has proven challenging. Here we report a simple approach for co-assembling magnetic nanoparticles with fluorescent quantum dots to form colloidal magneto-fluorescent supernanoparticles. Importantly, these supernanoparticles exhibit a superstructure consisting of a close-packed magnetic nanoparticle 'core', which is fully surrounded by a 'shell' of fluorescent quantum dots. A thin layer of silica coating provides high colloidal stability and biocompatibility, and a versatile surface functionality. We demonstrate that after surface pegylation, these silica-coated magneto-fluorescent supernanoparticles can be magnetically manipulated inside living cells while being optically tracked. Moreover, our silica-coated magneto-fluorescent supernanoparticles can also serve as an in vivo multi-photon and magnetic resonance dual-modal imaging probe. C1 [Chen, Ou; Zhao, Jing; Bruns, Oliver T.; Wei, He; Cui, Jian; Jensen, Russ; Chen, Yue; Harris, Daniel K.; Cordero, Jose M.; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Riedemann, Lars; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Riedemann, Lars; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Etoc, Fred; Coppey, Mathieu; Dahan, Maxime] Inst Curie, CNRS, Lab Phys Chim Curie, UMR168, F-75248 Paris, France. [Herrmann, Hendrik; Reimer, Rudolph] Heinrich Pette Inst, D-20251 Hamburg, Germany. [Herrmann, Hendrik] Bernhard Nocht Inst Trop Med, D-20359 Hamburg, Germany. [Barch, Mariya; Jasanoff, Alan] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Farrar, Christian T.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Guo, Peng] Harvard Univ, Sch Med, Childrens Hosp Boston, Vasc Biol Program, Boston, MA 02115 USA. [Wang, Zhongwu] Cornell Univ, Wilson Lab, CHESS, Ithaca, NY 14853 USA. [Jasanoff, Alan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Jasanoff, Alan] MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA. RP Bawendi, MG (reprint author), MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mgb@mit.edu RI Bruns, Oliver/D-6735-2015; Riedemann, Lars/J-5725-2014 OI Bruns, Oliver/0000-0002-5738-0126; Riedemann, Lars/0000-0002-9510-1845 FU NIH [5-U54-CA151884, P01-CA080124, R01-CA126642, R01-CA163815, R01-CA096915, R01-DA028299, R01-NS076462]; ARO through the Institute for Soldier Nanotechnologies [W911NF-13-D-0001]; Department of Energy [DE-FG02-07ER46454]; NIH funded Laser Biomedical Resource Center (LBRC) [9-P41-EB015871-26A1]; MIT Center for Excitonics, an Energy Frontier Research Center - U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE SC0001088]; Federal Share/National Cancer Institute Proton Beam Program Income Grants; Mildred-Scheel-Fellowship (Deutsche Krebshilfe) by the German Cancer Aid; DoD Breast Cancer Research Innovator award [W81XWH-10-1-0016]; Human Frontier Science Program [RGP0005/2007]; Federal Ministry of Education and Research (BMBF) [01EZ0829]; EMBO long-term fellowship; NSF & NIH/NIGMS via NSF award [DMR-0936384]; National Science Foundation [DMR-08-19762]; [ANR 10 IDEX 0001 02 PSL] FX This work received support from the NIH through 5-U54-CA151884 (M. G. B.), P01-CA080124 (R.K.J.), R01-CA126642 (M. G. B., D. F., R.K.J.), R01-CA163815 (R.K.J.), R01-CA096915 (D. F.), the ARO through the Institute for Soldier Nanotechnologies (W911NF-13-D-0001, M. G. B.), J. C. was supported by the Department of Energy through DE-FG02-07ER46454 (FCS measurements), the NIH funded Laser Biomedical Resource Center (LBRC) 9-P41-EB015871-26A1 (M. G. B.), R. J. was supported as part of the MIT Center for Excitonics, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Award Number DE SC0001088 (Single particle fluorescence measurements). We also acknowledge funding from the Federal Share/National Cancer Institute Proton Beam Program Income Grants (R. K. J.), Mildred-Scheel-Fellowship (Deutsche Krebshilfe) by the German Cancer Aid (L. R.), a DoD Breast Cancer Research Innovator award (W81XWH-10-1-0016) (R. K. J.), the Human Frontier Science Program (grant no. RGP0005/2007) (M. D. and M. G. B) and the program ANR 10 IDEX 0001 02 PSL (M. D.). M. B. and A. J. are supported by the NIH through R01-DA028299 and R01-NS076462 to A.J.. H. H. was supported by the Federal Ministry of Education and Research (BMBF, 01EZ0829). O.T.B. is supported by EMBO long-term fellowship. CHESS is supported by the NSF & NIH/NIGMS via NSF award DMR-0936384 (Z.W.). This work made use of the MRSEC Shared Experimental Facilities at MIT, supported by the National Science Foundation under award number DMR-08-19762. NR 51 TC 44 Z9 44 U1 17 U2 191 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2014 VL 5 AR 5093 DI 10.1038/ncomms6093 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AS0OS UT WOS:000343978000010 PM 25298155 ER PT J AU Lee, SK Mortensen, LJ Lin, CP Tung, CH AF Lee, Seung Koo Mortensen, Luke J. Lin, Charles P. Tung, Ching-Hsuan TI An authentic imaging probe to track cell fate from beginning to end SO NATURE COMMUNICATIONS LA English DT Article ID STAUROSPORINE-INDUCED APOPTOSIS; IN-VIVO; OXIDATIVE STRESS; NECROSIS; AGENT; DEATH; PHOSPHATIDYLSERINE; NANOPARTICLES; DOXORUBICIN; DYNAMICS AB Accurate tracing of cell viability is critical for optimizing delivery methods and evaluating the efficacy and safety of cell therapeutics. A nanoparticle-based cell tracker is developed to image cell fate from live to dead. The particle is fabricated from two types of optically quenched polyelectrolytes, a life indicator and a death indicator, through electrostatic interactions. On incubation with cells, the fabricated bifunctional nanoprobes are taken up efficiently and the first colour is produced by normal intracellular proteolysis, reflecting the healthy status of the cells. Depending on the number of coated layers, the signal can persist for several replication cycles. However, as the cells begin dying, the second colour appears quickly to reflect the new cell status. Using this chameleon-like cell tracker, live cells can be distinguished from apoptotic and necrotic cells instantly and definitively. C1 [Lee, Seung Koo; Tung, Ching-Hsuan] Weill Cornell Med Coll, Dept Radiol, Mol Imaging Innovat Inst, New York, NY 10021 USA. [Mortensen, Luke J.; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Tung, CH (reprint author), Weill Cornell Med Coll, Dept Radiol, Mol Imaging Innovat Inst, 413 East 69th St,Box 290, New York, NY 10021 USA. EM cht2018@med.cornell.edu OI Mortensen, Luke/0000-0002-4331-4099; Tung, Ching-Hsuan/0000-0001-6648-6195 FU NIH [CA135312]; DOD [W81XWH-11-1-0442] FX We thank Dr Benedict Law for the helpful discussion and Myung Shin Han for preparing the drawing. This study was supported in part by NIH CA135312 and DOD W81XWH-11-1-0442. NR 52 TC 5 Z9 5 U1 4 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2014 VL 5 AR 5216 DI 10.1038/ncomms6216 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AS0QO UT WOS:000343982800005 PM 25323442 ER PT J AU Leung, CS Yeung, TL Yip, KP Pradeep, S Balasubramanian, L Liu, JS Wong, KK Mangala, LS Armaiz-Pena, GN Lopez-Berestein, G Sood, AK Birrer, MJ Mok, SC AF Leung, Cecilia S. Yeung, Tsz-Lun Yip, Kay-Pong Pradeep, Sunila Balasubramanian, Lavanya Liu, Jinsong Wong, Kwong-Kwok Mangala, Lingegowda S. Armaiz-Pena, Guillermo N. Lopez-Berestein, Gabriel Sood, Anil K. Birrer, Michael J. Mok, Samuel C. TI Calcium-dependent FAK/CREB/TNNC1 signalling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential SO NATURE COMMUNICATIONS LA English DT Article ID TUMOR MICROENVIRONMENT; GENE-EXPRESSION; PKC-THETA; T-CELLS; FIBROBLASTS; ACTIVATION; ANGIOGENESIS; CHEMOTAXIS; SIGNATURE; PATTERNS AB Ovarian cancer is the most lethal gynaecologic malignancy in the United States, and advanced serous ovarian adenocarcinoma is responsible for most ovarian cancer deaths. However, the stroma-derived molecular determinants that modulate patient survival are yet to be characterized. Here we identify a stromal gene signature for advanced high-grade serous ovarian cancer using microdissected stromal ovarian tumour samples and find that stromal microfibrillar-associated protein 5 (MFAP5) is a prognostic marker for poor survival. Further functional studies reveal that FAK/CREB/TNNC1 signalling pathways mediate the effect of MFAP5 on ovarian cancer cell motility and invasion potential. Targeting stromal MFAP5 using MFAP5-specific siRNA encapsulated in chitosan nanoparticles significantly decreases ovarian tumour growth and metastasis in vivo, suggesting that it may be a new modality of ovarian cancer treatment. C1 [Leung, Cecilia S.; Yeung, Tsz-Lun; Pradeep, Sunila; Wong, Kwong-Kwok; Mangala, Lingegowda S.; Armaiz-Pena, Guillermo N.; Sood, Anil K.; Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. [Leung, Cecilia S.; Wong, Kwong-Kwok; Sood, Anil K.; Mok, Samuel C.] Univ Texas Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA. [Yip, Kay-Pong; Balasubramanian, Lavanya] Univ S Florida, Dept Mol Pharmacol & Physiol, Tampa, FL 33612 USA. [Liu, Jinsong] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Mangala, Lingegowda S.; Lopez-Berestein, Gabriel; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNAs, Houston, TX 77030 USA. [Lopez-Berestein, Gabriel; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Lopez-Berestein, Gabriel] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Birrer, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Birrer, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. EM mbirrer@partners.org; scmok@mdanderson.org RI Yip, Kay-Pong/H-4639-2012; OI Yip, Kay-Pong/0000-0003-4364-6701; Armaiz-Pena, Guillermo N/0000-0002-9081-5339; Wong, Kwong-Kwok/0000-0002-0375-6669 FU MD Anderson Ovarian Cancer SPORE grant from the National Institutes of Health [P50CA083639]; MD Anderson Cancer Center Support Grant from the National Institutes of Health [CA016672]; US Department of Health and Human Services; Gilder Foundation; Cancer Prevention Research Institute of Texas [RP100094]; Mary L. Chapman Foundation; [RO1CA133057]; [RO1CA142832]; [RC4CA156551]; [U54CA151668]; [UH2 TR000943] FX This study was supported in part by grants RO1CA133057, RO1CA142832, RC4CA156551, U54CA151668, UH2 TR000943, MD Anderson Ovarian Cancer SPORE grant P50CA083639 and MD Anderson Cancer Center Support Grant CA016672 from the National Institutes of Health; the US Department of Health and Human Services; the Gilder Foundation; grant RP100094 from the Cancer Prevention Research Institute of Texas; and funding from the Mary L. Chapman Foundation. NR 35 TC 15 Z9 16 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2014 VL 5 AR 5092 DI 10.1038/ncomms6092 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AS0OS UT WOS:000343978000009 PM 25277212 ER PT J AU Postmus, I Trompet, S Deshmukh, HA Barnes, MR Li, XH Warren, HR Chasman, DI Zhou, KX Arsenault, BJ Donnelly, LA Wiggins, KL Avery, CL Griffin, P Feng, QP Taylor, KD Li, G Evans, DS Smith, AV de Keyser, CE Johnson, AD de Craen, AJM Stott, DJ Buckley, BM Ford, I Westendorp, RGJ Slagboom, PE Sattar, N Munroe, PB Sever, P Poulter, N Stanton, A Shields, DC O'Brien, E Shaw-Hawkins, S Chen, YDI Nickerson, DA Smith, JD Dube, MP Boekholdt, SM Hovingh, GK Kastelein, JJP McKeigue, PM Betteridge, J Neil, A Durrington, PN Doney, A Carr, F Morris, A McCarthy, MI Groop, L Ahlqvist, E Bis, JC Rice, K Smith, NL Lumley, T Whitsel, EA Sturmer, T Boerwinkle, E Ngwa, JS O'Donnell, CJ Vasan, RS Wei, WQ Wilke, RA Liu, CT Sun, FG Guo, XQ Heckbert, SR Post, W Sotoodehnia, N Arnold, AM Stafford, JM Ding, JZ Herrington, DM Kritchevsky, SB Eiriksdottir, G Launer, LJ Harris, TB Chu, AY Giulianini, F MacFadyen, JG Barratt, BJ Nyberg, F Stricker, BH Uitterlinden, AG Hofman, A Rivadeneira, F Emilsson, V Franco, OH Ridker, PM Gudnason, V Liu, YM Denny, JC Ballantyne, CM Rotter, JI Cupples, LA Psaty, BM Palmer, CNA Tardif, JC Colhoun, HM Hitman, G Krauss, RM Jukema, JW Caulfield, MJ AF Postmus, Iris Trompet, Stella Deshmukh, Harshal A. Barnes, Michael R. Li, Xiaohui Warren, Helen R. Chasman, Daniel I. Zhou, Kaixin Arsenault, Benoit J. Donnelly, Louise A. Wiggins, Kerri L. Avery, Christy L. Griffin, Paula Feng, QiPing Taylor, Kent D. Li, Guo Evans, Daniel S. Smith, Albert V. de Keyser, Catherine E. Johnson, Andrew D. de Craen, Anton J. M. Stott, David J. Buckley, Brendan M. Ford, Ian Westendorp, Rudi G. J. Slagboom, P. Eline Sattar, Naveed Munroe, Patricia B. Sever, Peter Poulter, Neil Stanton, Alice Shields, Denis C. O'Brien, Eoin Shaw-Hawkins, Sue Chen, Y. -D. Ida Nickerson, Deborah A. Smith, Joshua D. Dube, Marie Pierre Boekholdt, S. Matthijs Hovingh, G. Kees Kastelein, John J. P. McKeigue, Paul M. Betteridge, John Neil, Andrew Durrington, Paul N. Doney, Alex Carr, Fiona Morris, Andrew McCarthy, Mark I. Groop, Leif Ahlqvist, Emma Bis, Joshua C. Rice, Kenneth Smith, Nicholas L. Lumley, Thomas Whitsel, Eric A. Stuermer, Til Boerwinkle, Eric Ngwa, Julius S. O'Donnell, Christopher J. Vasan, Ramachandran S. Wei, Wei-Qi Wilke, Russell A. Liu, Ching-Ti Sun, Fangui Guo, Xiuqing Heckbert, Susan R. Post, Wendy Sotoodehnia, Nona Arnold, Alice M. Stafford, Jeanette M. Ding, Jingzhong Herrington, David M. Kritchevsky, Stephen B. Eiriksdottir, Gudny Launer, Leonore J. Harris, Tamara B. Chu, Audrey Y. Giulianini, Franco MacFadyen, Jean G. Barratt, Bryan J. Nyberg, Fredrik Stricker, Bruno H. Uitterlinden, Andre G. Hofman, Albert Rivadeneira, Fernando Emilsson, Valur Franco, Oscar H. Ridker, Paul M. Gudnason, Vilmundur Liu, Yongmei Denny, Joshua C. Ballantyne, Christie M. Rotter, Jerome I. Cupples, L. Adrienne Psaty, Bruce M. Palmer, Colin N. A. Tardif, Jean-Claude Colhoun, Helen M. Hitman, Graham Krauss, Ronald M. Jukema, J. Wouter Caulfield, Mark J. CA Welcome Trust Case Control Consort TI Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins SO NATURE COMMUNICATIONS LA English DT Article ID PLASMA LIPOPROTEIN(A) LEVELS; HUMAN PREFRONTAL CORTEX; GENE-EXPRESSION; WHOLE-GENOME; INDUCED MYOPATHY; DISEASE; LOCI; VARIANTS; THERAPY; BLOOD AB Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response. C1 [Postmus, Iris; Trompet, Stella; Westendorp, Rudi G. J.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands. [Postmus, Iris; Westendorp, Rudi G. J.; Slagboom, P. Eline; Uitterlinden, Andre G.; Hofman, Albert] Netherlands Consortium Healthy Ageing, NL-2300 RC Leiden, Netherlands. [Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands. [Deshmukh, Harshal A.; Zhou, Kaixin; Donnelly, Louise A.; Doney, Alex; Carr, Fiona; Morris, Andrew; Palmer, Colin N. A.; Colhoun, Helen M.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 9SY, Scotland. [Barnes, Michael R.; Shaw-Hawkins, Sue] Queen Mary Univ London, Genome Ctr, Barts & London Sch Med, William Harvey Res Inst, London EC1M 6BQ, England. [Barnes, Michael R.; Warren, Helen R.; Munroe, Patricia B.; Shaw-Hawkins, Sue; Caulfield, Mark J.] Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, London EC1M 6BQ, England. [Li, Xiaohui; Taylor, Kent D.; Chen, Y. -D. Ida; Guo, Xiuqing; Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA. [Warren, Helen R.; Munroe, Patricia B.; Caulfield, Mark J.] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Dept Clin Pharmacol, London EC1M 6BQ, England. [Chasman, Daniel I.; Chu, Audrey Y.; Giulianini, Franco; MacFadyen, Jean G.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. [Chasman, Daniel I.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Arsenault, Benoit J.; Dube, Marie Pierre; Tardif, Jean-Claude] Univ Montreal, Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Wiggins, Kerri L.; Li, Guo; de Craen, Anton J. M.; Bis, Joshua C.; Lumley, Thomas; Sotoodehnia, Nona; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. [Avery, Christy L.; Whitsel, Eric A.; Stuermer, Til] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Griffin, Paula; Ngwa, Julius S.; Liu, Ching-Ti; Sun, Fangui; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Feng, QiPing] Vanderbilt Univ, Dept Clin Pharmacol, Nashville, TN 37240 USA. [Evans, Daniel S.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA. [Smith, Albert V.; Eiriksdottir, Gudny; Emilsson, Valur; Gudnason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland. [Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, IS-101 Reykjavik, Iceland. [de Keyser, Catherine E.; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [de Keyser, Catherine E.] Hlth Care Inspectorate, NL-2595 AN The Hague, Netherlands. [Johnson, Andrew D.] NHLBI, FHS, Framingham, MA 01702 USA. [Stott, David J.] Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow G31 2ER, Lanark, Scotland. [Buckley, Brendan M.] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork 30, Ireland. [Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow G12 8QQ, Lanark, Scotland. [Westendorp, Rudi G. J.] Leyden Acad Vital & Ageing, NL-2333 AA Leiden, Netherlands. [Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2300 RC Leiden, Netherlands. [Sattar, Naveed] BHF Glasgow Cardiovasc Res Ctr, Fac Med, Glasgow G12 8QQ, Lanark, Scotland. [Sever, Peter; Poulter, Neil] Univ London Imperial Coll Sci Technol & Med, Int Ctr Circulatory Hlth, London SW7 2AZ, England. [Stanton, Alice] Royal Coll Surgeons Ireland, Dublin 2, Ireland. [Stanton, Alice] Beaumont Hosp, Dublin 9, Ireland. [Shields, Denis C.; O'Brien, Eoin] Univ Coll Dublin, Conway Inst, Dublin 4, Ireland. [Shields, Denis C.] Univ Coll Dublin, Sch Med & Med Sci, Dublin 4, Ireland. [Nickerson, Deborah A.; Smith, Joshua D.] Univ Washington, Dept Genome Sci, Seattle, WA 98101 USA. [Boekholdt, S. Matthijs] Acad Med Ctr, Dept Cardiol, NL-1100 DD Amsterdam, Netherlands. [Hovingh, G. Kees; Kastelein, John J. P.] Acad Med Ctr, Dept Vasc Med, NL-1100 DD Amsterdam, Netherlands. [McKeigue, Paul M.] Univ Edinburgh, Edinburgh EH9 3JR, Midlothian, Scotland. [Betteridge, John] UCL, London WC1E 6BT, England. [Neil, Andrew] Univ Oxford, Oxford OX1 2JD, England. [Durrington, Paul N.] Univ Manchester, Sch Biosci, Cardiovasc Res Grp, Manchester M13 9NT, Lancs, England. [McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. [McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Groop, Leif; Ahlqvist, Emma] Lund Univ, Dept Clin Sci Diabet & Endocrinol, S-20502 Malmo, Sweden. [Rice, Kenneth; Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98115 USA. [Smith, Nicholas L.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Smith, Nicholas L.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA. [Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs Off Res & Dev, Seattle, WA 98101 USA. [Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1142, New Zealand. [Whitsel, Eric A.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA. [O'Donnell, Christopher J.; Cupples, L. Adrienne] NHLBI Framingham Heart Study, Framingham, MA 01701 USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA 02115 USA. [O'Donnell, Christopher J.] NHLBI, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Epidemiol, Framingham, MA 01701 USA. [Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01701 USA. [Wei, Wei-Qi; Denny, Joshua C.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37240 USA. [Wilke, Russell A.] Sanford Healthcare, Ctr IMAGENETICS, Dept Internal Med, Fargo, ND 58104 USA. [Heckbert, Susan R.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. [Post, Wendy] Johns Hopkins Univ, Dept Cardiol, Baltimore, MD 21218 USA. [Sotoodehnia, Nona] Univ Washington, Harborview Med Ctr, Div Cardiol, Seattle, WA 98101 USA. [Stafford, Jeanette M.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Ding, Jingzhong; Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Herrington, David M.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Cardiol Sect, Winston Salem, NC 27157 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA. [Launer, Leonore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog Biometry, NIH, Bethesda, MD 20892 USA. [Barratt, Bryan J.] AstraZeneca, Personalised Healthcare & Biomarkers, Macclesfield SK10 4TG, Cheshire, England. [Nyberg, Fredrik] AstraZeneca Res & Dev, S-48183 Molndal, Sweden. [Nyberg, Fredrik] Univ Gothenburg, Unit Occupat & Environm Med, S-40530 Gothenburg, Sweden. [Stricker, Bruno H.; Uitterlinden, Andre G.; Rivadeneira, Fernando] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Denny, Joshua C.] Vanderbilt Univ, Dept Med, Vanderbilt, TN 37240 USA. [Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA. [Colhoun, Helen M.] Univ Dundee, Dept Publ Hlth, Dundee DD1 9SY, Scotland. [Hitman, Graham] Queen Mary Univ, Barts & London Sch Med & Dent, London E1 2A1, England. [Krauss, Ronald M.] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. [Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, NL-1105 AZ Amsterdam, Netherlands. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, NL-3511 GC Utrecht, Netherlands. RP Jukema, JW (reprint author), Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands. EM j.w.jukema@lumc.nl; m.j.caulfield@qmul.ac.uk RI Palmer, Colin/C-7053-2008; Slagboom, P. Eline/R-4790-2016; Dube, Marie-Pierre/B-9364-2008; Blackwell, Jenefer/H-3015-2015; Jankowski, Janusz/H-2706-2012; Gudnason, Vilmundur/K-6885-2015; Deloukas, Panos/B-2922-2013; Rivadeneira, Fernando/O-5385-2015; Smith, Albert/K-5150-2015; Study, GoDARTS/K-9448-2016; Johnson, Andrew/G-6520-2013; Boekholdt, Matthijs/G-7562-2014 OI Pirinen, Matti/0000-0002-1664-1350; Corvin, Aiden/0000-0001-6717-4089; Stanton, Alice/0000-0002-4961-165X; Ramachandran, Vasan/0000-0001-7357-5970; Gillman, Matthew/0000-0002-2340-6930; Plomin, Robert/0000-0002-0756-3629; Colhoun, Helen/0000-0002-8345-3288; Wood, Nicholas/0000-0002-9500-3348; Palmer, Colin/0000-0002-6415-6560; Slagboom, P. Eline/0000-0002-2875-4723; Dube, Marie-Pierre/0000-0001-8442-4393; Jankowski, Janusz/0000-0003-2130-9181; Gudnason, Vilmundur/0000-0001-5696-0084; Deloukas, Panos/0000-0001-9251-070X; Rivadeneira, Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845; FU Bristol-Myers Squibb, USA; European Union [HEALTH-F2-2009-223004]; Netherlands Consortium for Healthy Ageing (NGI) [05060810]; Pfizer, USA; National Institutes for Health Research (NIHR) as part of the portfolio of translational research of the NIHR Biomedical Research Unit at Barts; NIHR Biomedical Research Centre at Imperial College; International Centre for Circulatory Health Charity; Medical Research Council [G952010]; Pfizer, Diabetes UK; Department of Health; National Institutes of Health from the National Heart, Lung, and Blood Institute [U19 HL069757]; National Center for Advancing Translational Sciences [UL1TR000124, 2 UL1 TR000445]; Pfizer; NIH [N01-AG-1-2100]; NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); National Heart, Lung, and Blood Institute contracts [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute contract [U01HG004402]; National Institutes of Health contract [HHSN268200625226C]; National Institutes of Health and NIH Roadmap for Medical Research [UL1RR025005]; National Center for Research Resources [UL1 RR024975]; National Human Genome Research Institute [U01-HG04603]; National Insitute of General Medical Sciences [RC2-GM092318]; NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, HL080295, N01HC85086, HL087652, HL105756, HL103612, HL085251, HL073410, HL068986]; National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA) [AG023629]; National Center for Advancing Translational Sciences; CTSI grant [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant [DK063491]; National Heart Lung and Blood Institute of the National Institutes of Health; Boston University School of Medicine [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center [R01HL103612]; Wellcome Trust United Kingdom Type 2 Diabetes Case Control Collection (GoDARTS); Scottish Health Informatics Programme; Wellcome Trust Case Control Consortium; Diabetes UK [07/0003525]; Wellcome Trust [084727/Z/08/Z, 085475/Z/08/Z, 085475/B/08/Z]; EU IMI-SUMMIT programme; NIA [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]; National Institutes of Health [HHSN268200782096C]; Intramural Research Program of the NIH, National Institute on Aging; National Heart, Lung, and Blood Institute (NHLBI); MESA investigators; Clinical Translational Science Institute grant [UL1RR033176]; AstraZeneca; Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly; Ministry of Education, Culture and Science; Ministry of Health Welfare and Sports; European Commission; Municipality of Rotterdam; Netherlands Genomics Initiative (NGI) Netherlands Organization for Scietific Research (NOW) [050-060-810]; [N01 HC-95159]; [N01-HC-95169]; [RR024156] FX PROSPER/PHASE: The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial was supported by an investigator-initiated grant from Bristol-Myers Squibb, USA. The study was conducted, analysed and reported independently of the company. The GWAS project PHASE has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement HEALTH-F2-2009- 223004. A part of the genotyping was funded by The Netherlands Consortium for Healthy Ageing (NGI: 05060810). Professor Dr J.W.J. is an established clinical investigator of The Netherlands Heart Foundation (2001 D 032).; ASCOT: The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) trial was funded by an investigator-initiated grant from Pfizer, USA. The study was investigator led and was conducted, analysed and reported independently of the company. The Genomewide Association Scan was funded by the National Institutes for Health Research (NIHR) as part of the portfolio of translational research of the NIHR Biomedical Research Unit at Barts and the NIHR Biomedical Research Centre at Imperial College, the International Centre for Circulatory Health Charity and the Medical Research Council through G952010. On behalf of the ASCOT investigators, we thank all ASCOT trial participants, physicians, nurses, and practices in the participating countries for their important contribution to the study.; CARDS: We thank the other investigators, the staff and the participants of the CARDS study. A full list of CARDS investigators can be found in original CARDS paper71. CARDS was funded by grants to the Universities of London and Manchester by Pfizer, Diabetes UK and the Department of Health.; PARC: This research was supported by the National Institutes of Health: grant U19 HL069757 from the National Heart, Lung, and Blood Institute, and grant UL1TR000124 from the National Center for Advancing Translational Sciences.; TNT: The TNT study was funded by Pfizer, who also provided support for genotyping.; AGES: This study has been funded by NIH contract N01-AG-1-2100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063. The researchers are indebted to the participants for their willingness to participate in the study.; ARIC: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. We thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research.; BioVU: BioVU receives support through the National Center for Research Resources UL1 RR024975, which is now the National Center for Advancing Translational Sciences, 2 UL1 TR000445. Genotyping was supported via grant U01-HG04603 from the National Human Genome Research Institute and RC2-GM092318 from the National Insitute of General Medical Sciences.; CHS: This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083 and N01HC85086; and NHLBI grants HL080295, HL087652, HL105756 and HL103612 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG023629 from the National Institute on Aging (NIA). A full list of CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center.; Framingham HS: The Framingham Heart Study work was supported by the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine (Contract No. N01-HC-25195), its contract with Affymetrix, Inc. for genotyping services (Contract No. N02-HL-6-4278) and based on analyses by Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center, also supported by R01HL103612 (PI psaty, subcontract PI, Vasan).; GoDARTS: We are grateful to all the participants who took part in this study, to the general practitioners, to the Scottish School of Primary Care for their help in recruiting the participants and to the whole team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The Wellcome Trust provides support for Wellcome Trust United Kingdom Type 2 Diabetes Case Control Collection (GoDARTS) and informatics support is provided by the Chief Scientist Office. The Wellcome Trust funds the Scottish Health Informatics Programme, provides core support for the Wellcome Trust Centre for Human Genetics in Oxford and funds the Wellcome Trust Case Control Consortium. This research was specifically funded by Diabetes UK (07/0003525) and the Wellcome Trust (084727/Z/08/Z, 085475/Z/08/Z and 085475/B/08/Z). Genotyping of the GoDARTS samples (sample 2) was also funded as part of the EU IMI-SUMMIT programme. K.Z. holds a Henry Wellcome Post-Doctoral Fellowship.; Health ABC: The Health ABC study was supported by NIA contracts N01AG62101, N01AG62103 and N01AG62106. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging.; HVH: This Heart and Vascular Health Study research was supported by NHLBI grants HL085251, HL073410, HL085251 and HL068986.; MESA: The Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SNP Health Association Resource (SHARe) are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support is provided by grants and contracts N01 HC-95159 through N01-HC-95169 and RR024156. Additional funding was supported in part by the Clinical Translational Science Institute grant UL1RR033176 and is now at the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124. We thank the other investigators in the Pharmarcogenetics Working Group, the staff and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.; JUPITER: Genetic analysis in JUPITER was supported by a research grant from AstraZeneca to D. C. and P. M.; Rotterdam study: The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; and the European Commission and Municipality of Rotterdam. This work was supported by the Netherlands Genomics Initiative (NGI) Netherlands Organization for Scietific Research (NOW; 050-060-810). NR 71 TC 51 Z9 52 U1 1 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2014 VL 5 AR 5068 DI 10.1038/ncomms6068 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AS0OK UT WOS:000343977100003 PM 25350695 ER PT J AU Ellingson, BM Wen, PY van den Bent, MJ Cloughesy, TF AF Ellingson, Benjamin M. Wen, Patrick Y. van den Bent, Martin J. Cloughesy, Timothy F. TI Pros and cons of current brain tumor imaging SO NEURO-ONCOLOGY LA English DT Article DE clinical trials; endpoints; MRI; RANO; response assessment ID HIGH-GRADE GLIOMAS; RECURRENT MALIGNANT GLIOMA; RESPONSE ASSESSMENT CRITERIA; BEVACIZUMAB PLUS IRINOTECAN; RADIATION-THERAPY; GLIOBLASTOMA-MULTIFORME; ANTIANGIOGENIC THERAPY; PHASE-II; NEUROONCOLOGY CRITERIA; ADJUVANT TEMOZOLOMIDE AB Over the past 20 years, very few agents have been approved for the treatment of brain tumors. Recent studies have highlighted some of the challenges in assessing activity in novel agents for the treatment of brain tumors. This paper reviews some of the key challenges related to assessment of tumor response to therapy in adult high-grade gliomas and discusses the strengths and limitations of imaging-based endpoints. Although overall survival is considered the "gold standard" endpoint in the field of oncology, progression-free survival and response rate are endpoints that hold great value in neuro-oncology. Particular focus is given to advancements made since the January 2006 Brain Tumor Endpoints Workshop, including the development of Response Assessment in Neuro-Oncology criteria, the value of T2/fluid-attenuated inversion recovery, use of objective response rates and progression-free survival in clinical trials, and the evaluation of pseudoprogression, pseudoresponse, and inflammatory response in radiographic images. C1 [Ellingson, Benjamin M.] Univ Calif Los Angeles, Dept Radiol Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Ellingson, Benjamin M.] Univ Calif Los Angeles, Dept Biomed Phys, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Ellingson, Benjamin M.] Univ Calif Los Angeles, Dept Bioengn, Henry Samueli Sch Engn & Appl Sci, Los Angeles, CA 90024 USA. [Ellingson, Benjamin M.; Cloughesy, Timothy F.] Univ Calif Los Angeles, Brain Res Inst, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Ellingson, Benjamin M.; Cloughesy, Timothy F.] Univ Calif Los Angeles, UCLA Neurooncol Program, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Wen, Patrick Y.] Harvard Univ, Sch Med, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [van den Bent, Martin J.] Erasmus MC Canc Inst, Dept Neurooncol, Rotterdam, Netherlands. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Ellingson, BM (reprint author), Univ Calif Los Angeles, Dept Radiol Sci, David Geffen Sch Med, 924 Westwood Blvd,Suite 615, Los Angeles, CA 90024 USA. EM bellingson@mednet.ucla.edu NR 92 TC 11 Z9 11 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2014 VL 16 SU 7 BP 2 EP 11 DI 10.1093/neuonc/nou224 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AS4IO UT WOS:000344238200002 PM 25313235 ER PT J AU Reardon, DA Ballman, KV Buckner, JC Chang, SM Ellingson, BM AF Reardon, David A. Ballman, Karla V. Buckner, Jan C. Chang, Susan M. Ellingson, Benjamin M. TI Impact of imaging measurements on response assessment in glioblastoma clinical trials SO NEURO-ONCOLOGY LA English DT Article DE clinical trials; glioblastoma; imaging; MRI; response assessment ID PHASE-II TRIAL; BRAIN-TUMOR CONSORTIUM; RECURRENT MALIGNANT GLIOMA; PROGRESSION-FREE SURVIVAL; LOW-GRADE GLIOMAS; DOSE-INTENSE TEMOZOLOMIDE; LONG-TERM OUTCOMES; RADIATION-THERAPY; PSEUDO-PROGRESSION; IMATINIB MESYLATE AB We provide historical and scientific guidance on imaging response assessment for incorporation into clinical trials to stimulate effective and expedited drug development for recurrent glioblastoma by addressing 3 fundamental questions: (i) What is the current validation status of imaging response assessment, and when are we confident assessing response using today's technology? (ii) What imaging technology and/or response assessment paradigms can be validated and implemented soon, and how will these technologies provide benefit? (iii) Which imaging technologies need extensive testing, and how can they be prospectively validated? Assessment of T1 +/- contrast, T2/FLAIR, diffusion, and perfusion-imaging sequences are routine and provide important insight into underlying tumor activity. Nonetheless, utility of these data within and across patients, as well as across institutions, are limited by challenges in quantifying measurements accurately and lack of consistent and standardized image acquisition parameters. Currently, there exists a critical need to generate guidelines optimizing and standardizing MRI sequences for neuro-oncology patients. Additionally, more accurate differentiation of confounding factors (pseudoprogression or pseudoresponse) may be valuable. Although promising, diffusion MRI, perfusion MRI, MR spectroscopy, and amino acid PET require extensive standardization and validation. Finally, additional techniques to enhance response assessment, such as digital T1 subtraction maps, warrant further investigation. C1 [Reardon, David A.] Harvard Univ, Sch Med, Ctr Neurooncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Ballman, Karla V.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA. [Buckner, Jan C.] Mayo Clin, Dept Oncol, Rochester, MN USA. [Chang, Susan M.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Ellingson, Benjamin M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA. [Ellingson, Benjamin M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomed Phys, Los Angeles, CA 90095 USA. [Ellingson, Benjamin M.] Univ Calif Los Angeles, Dept Bioengn, Henry Samueli Sch Engn & Appl Sci, Los Angeles, CA USA. [Ellingson, Benjamin M.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. [Ellingson, Benjamin M.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Neurooncol Program, Los Angeles, CA 90095 USA. RP Reardon, DA (reprint author), Harvard Univ, Sch Med, Ctr Neurooncol, Dana Farber Canc Inst, 450 Brookline Ave,Dana 2134, Boston, MA 02215 USA. EM david_reardon@dfci.harvard.edu NR 72 TC 6 Z9 6 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2014 VL 16 SU 7 BP 24 EP 35 DI 10.1093/neuonc/nou286 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AS4IO UT WOS:000344238200004 PM 25313236 ER PT J AU Wen, PY Cloughesy, TF Ellingson, BM Reardon, DA Fine, HA Abrey, L Ballman, K Bendszuz, M Buckner, J Chang, SM Prados, MD Pope, WB Sorensen, AG van den Bent, M Yung, WKA AF Wen, Patrick Y. Cloughesy, Timothy F. Ellingson, Benjamin M. Reardon, David A. Fine, Howard A. Abrey, Lauren Ballman, Karla Bendszuz, Martin Buckner, Jan Chang, Susan M. Prados, Michael D. Pope, Whitney B. Sorensen, Alma Gregory van den Bent, Martin Yung, Wai-Kwan Alfred TI Report of the Jumpstarting Brain Tumor Drug Development Coalition and FDA clinical trials neuroimaging endpoint workshop (January 30, 2014, Bethesda MD) SO NEURO-ONCOLOGY LA English DT Article DE brain tumor; endpoints; neuroimaging; RANO; workshop ID RECURRENT MALIGNANT GLIOMA; HIGH-GRADE GLIOMAS; PROGRESSION-FREE SURVIVAL; III RANDOMIZED-TRIAL; PHASE-II; RESPONSE ASSESSMENT; INTEROBSERVER VARIABILITY; GLIOBLASTOMA-MULTIFORME; WORKING GROUP; SOLID TUMORS AB On January 30, 2014, a workshop was held on neuroimaging endpoints in high-grade glioma. This workshop was sponsored by the Jumpstarting Brain Tumor Drug Development Coalition, consisting of the National Brain Tumor Society, the Society for Neuro-Oncology, Accelerate Brain Cancer Cure, and the Musella Foundation for Research and Information, and conducted in collaboration with the Food and Drug Administration. The workshop included neuro-oncologists, neuroradiologists, radiation oncologists, neurosurgeons, biostatisticians, patient advocates, and representatives from industry, clinical research organizations, and the National Cancer Institute. This report summarizes the presentations and discussions of that workshop and the proposals that emerged to improve the Response Assessment in Neuro-Oncology (RANO) criteria and standardize neuroimaging parameters. C1 [Wen, Patrick Y.; Reardon, David A.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02215 USA. [Cloughesy, Timothy F.; Ellingson, Benjamin M.; Pope, Whitney B.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Fine, Howard A.] NYU, Langone Med Ctr, New York, NY USA. [Abrey, Lauren] Hoffmann La Roche AG, Basel, Switzerland. [Ballman, Karla] Mayo Clin Rochester, Dept Biostat, Rochester, MN USA. [Bendszuz, Martin] Heidelberg Univ, Dept Neuroradiol, Heidelberg, Germany. [Buckner, Jan] Mayo Clin Rochester, Dept Med Oncol, Rochester, MN USA. [Chang, Susan M.; Prados, Michael D.] Univ Calif San Francisco, Brain Tumor Ctr, San Francisco, CA 94143 USA. [Sorensen, Alma Gregory] Siemens Healthcare North Amer, Malvern, PA USA. [van den Bent, Martin] Erasmus MC Daniel den Hoed Canc Ctr, Dept Neurooncol, Rotterdam, Netherlands. [Yung, Wai-Kwan Alfred] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA. EM pwen@partners.org NR 63 TC 15 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2014 VL 16 SU 7 BP 36 EP 47 DI 10.1093/neuonc/nou226 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AS4IO UT WOS:000344238200005 PM 25313237 ER PT J AU Maguire, C Ramirez, S Merkel, S Sena-Esteves, M Breakefield, X AF Maguire, Casey A. Ramirez, Servio H. Merkel, Steven F. Sena-Esteves, Miguel Breakefield, Xandra O. TI Gene Therapy for the Nervous System: Challenges and New Strategies SO NEUROTHERAPEUTICS LA English DT Review DE Gene delivery; Central nervous system; Virus vector; Nonviral gene delivery; Gene therapy ID BLOOD-BRAIN-BARRIER; AMYOTROPHIC-LATERAL-SCLEROSIS; NEURAL STEM-CELLS; NEURONAL CEROID-LIPOFUSCINOSIS; CONVECTION-ENHANCED DELIVERY; ADENOASSOCIATED VIRUS TYPE-2; SPINAL MUSCULAR-ATROPHY; HERPES-SIMPLEX-VIRUS; X-LINKED ADRENOLEUKODYSTROPHY; ASTROCYTE-SPECIFIC EXPRESSION AB Current clinical treatments for central nervous system (CNS) diseases, such as Parkinson's disease and glioblastoma do not halt disease progression and have significant treatment morbidities. Gene therapy has the potential to "permanently" correct disease by bringing in a normal gene to correct a mutant gene deficiency, knocking down mRNA of mutant alleles, and inducing cell-death in cancer cells using transgenes encoding apoptosis-inducing proteins. Promising results in clinical trials of eye disease (Leber's congenital aumorosis) and Parkinson's disease have shown that gene-based neurotherapeutics have great potential. The recent development of genome editing technology, such as zinc finger nucleases, TALENS, and CRISPR, has made the ultimate goal of gene correction a step closer. This review summarizes the challenges faced by gene-based neurotherapeutics and the current and recent strategies designed to overcome these barriers. We have chosen the following challenges to focus on in this review: (1) delivery vehicles (both virus and nonviral), (2) use of promoters for vector-mediated gene expression in CNS, and (3) delivery across the blood-brain barrier. The final section (4) focuses on promising pre-clinical/clinical studies of neurotherapeutics. C1 [Maguire, Casey A.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Breakefield, Xandra O.] Harvard Univ, Sch Med, Neurosci Program, Mol Neurogenet Unit, Charlestown, MA 02129 USA. [Sena-Esteves, Miguel] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. [Ramirez, Servio H.; Merkel, Steven F.] Temple Univ, Sch Med, Pathol & Lab Med, Philadelphia, PA 19122 USA. RP Maguire, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM cmaguire@mgh.harvard.edu FU National Institutes of Health/National Cancer Institute (NIH/NCI) by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH [U19 CA179563]; Voices Against Brain Cancer; National Institute on Drug Abuse (NIDA) training grant [T32 DA007237]; NIH/National Institute of Neurological Disorders and Stroke (NINDS) [R01 NS086570-01]; Shriners Hospitals for Children [85110-PHI-14]; NIH/NINDS [R21 NS081374-01]; [CA069246] FX We thank Ms. Suzanne McDavitt for skilled editorial assistance, Ms. Emily Mills at Millstone Design for preparation of figures and Dr. Thurman Wheeler for scientific insights. This work was supported by National Institutes of Health/National Cancer Institute (NIH/NCI) U19 CA179563, which is supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director and CA069246 and Voices Against Brain Cancer (XOB). The work performed in the authors' laboratory is supported by grants from a National Institute on Drug Abuse (NIDA) training grant: T32 DA007237 (S.M.), NIH/National Institute of Neurological Disorders and Stroke (NINDS) R01 NS086570-01 (S. H. R.) and The Shriners Hospitals for Children 85110-PHI-14 (S. H. R.). C. M. is supported by an NIH/NINDS R21 NS081374-01. C. M. has a financial interest in Exosome Diagnostics, Inc. C.M.'s interests were reviewed and are managed by the Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. C. M. has filed patent applications related to the vexosome technology. NR 256 TC 20 Z9 21 U1 4 U2 67 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD OCT PY 2014 VL 11 IS 4 BP 817 EP 839 DI 10.1007/s13311-014-0299-5 PG 23 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AS3AI UT WOS:000344147100013 PM 25159276 ER PT J AU Huybrechts, KF Palmsten, K Avorn, J Cohen, LS Holmes, LB Franklin, JM Mogun, H Levin, R Kowal, M Setoguchi, S Hernandez-Diaz, S AF Huybrechts, Krista F. Palmsten, Kristin Avorn, Jerry Cohen, Lee S. Holmes, Lewis B. Franklin, Jessica M. Mogun, Helen Levin, Raisa Kowal, Mary Setoguchi, Soko Hernandez-Diaz, Sonia TI Antidepressant Use in Pregnancy and the Risk for Cardiac Defects EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB The use of antidepressants during pregnancy has increased, with prevalences of 8% to 13% in the United States. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants during pregnancy. Because varied associations between drug use and fetal congenital cardiac malformations have been reported, this cohort study was performed to assess the risk for congenital cardiac defects after parturient use of antidepressants. The study cohort was drawn from the Medicaid Analytic eXtract for 2000 to 2007. This data set contains individual-level demographic and Medicaid enrollment information as well as data on all filled outpatient medication prescriptions. The exposure period extended from the date of the last menstrual period through day 90 of pregnancy (first trimester). Exposure categories were any SSRI, paroxetine, sertraline, fluoxetine, tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), bupropion, and other antidepressants. The reference group comprised parturients without antidepressant use during the first trimester. Congenital cardiac malformations included any cardiac malformation, right ventricular outflow tract obstruction, ventricular septal defect, and other cardiac malformations. Covariates included sociodemographic information; known or suspected risk factors of congenital cardiac malformations; use of teratogenic, other psychotropic, antidiabetic, and antihypertensive medications; and number of distinct prescription drugs used. Logistic regression analysis was used to estimate odds ratios for cardiac malformations. Because the odds ratio is an excellent approximation of the risk ratio in the case of rare outcomes, results are reported as relative risks (RRs). Of 949,504 eligible pregnancies, during the first trimester, 64,389 women (6.8%) used an antidepressant, 46,144 women (4.9%) were exposed to an SSRI, 5954 (0.6%) were exposed to a TCA, 6904 (0.7%) were exposed to an SNRI, 8856 (0.9%) were exposed to bupropion, and 7055 (0.7%) were exposed to other antidepressants. Sertraline was used by 14,040 women; paroxetine, by 11,126; and fluoxetine, by 11,048. Cardiac malformations were diagnosed in 6403 infants who were not exposed to an antidepressant during the first trimester (72.3 cardiac malformations per 10,000 infants) compared with 580 infants who were exposed (90.1 cardiac malformations per 10,000 infants). This higher unadjusted risk among exposed infants was observed for each specific type of malformation examined. In unadjusted analyses, the RR of any cardiac malformation was 1.25 with SSRIs (95% CI, 1.13-1.38), 0.98 with TCAs (95% CI, 0.72-1.32), 1.51 with SNRIs (95% CI, 1.20-1.90), 1.19 with bupropion (95% CI, 0.95-1.49), and 1.46 with other antidepressants (95% CI, 1.16-1.83). The propensity-score-adjusted RR of any cardiac malformation was 1.06 among women exposed to SSRIs (95% CI, 0.93-1.22), 0.77 for exposure to TCAs (95% CI, 0.52-1.14), 1.20 for exposure to SNRIs (95% CI, 0.91-1.57), 0.92 for exposure to bupropion (95% CI, 0.69-1.22), and 1.21 for exposure to other antidepressants (95% CI, 0.91-1.60). No significant associations were found between paroxetine and right ventricular outflow obstruction (1.07; 95% CI, 0.59-1.93) or between sertraline and ventricular septal defect (1.04; 95% CI, 0.76-1.41). The RR of cardiac malformations associated with SSRI use was 1.04 for those on antidepressant monotherapy (95% CI, 0.90-1.21) and 1.17 for polytherapy (95% CI, 0.90-1.53). Relative risks for associations between cardiac malformations and maternal diabetes, use of an anticonvulsant agent, and multifetal pregnancy were 3.7, 1.6, and 2.9, respectively (95% CI, 3.4-4.0; 95% CI, 1.3-1.8; and 95% CI, 2.8-3.1, respectively). After adjustment for depression and other confounding factors, these results fail to support previous findings of an association between antidepressant use and cardiac anomalies. Evidence implies low absolute risks and argues against important cardiac teratogenic effects associated with the most commonly used antidepressants. C1 [Huybrechts, Krista F.; Avorn, Jerry; Franklin, Jessica M.; Mogun, Helen; Levin, Raisa; Kowal, Mary; Setoguchi, Soko] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, Boston, MA 02115 USA. [Huybrechts, Krista F.; Avorn, Jerry; Franklin, Jessica M.; Mogun, Helen; Levin, Raisa; Kowal, Mary; Setoguchi, Soko] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Palmsten, Kristin; Hernandez-Diaz, Sonia] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Cambridge, MA 02138 USA. [Cohen, Lee S.] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Holmes, Lewis B.] MassGeneral Hosp Children, Med Genet Unit, Boston, MA USA. [Setoguchi, Soko] Duke Univ, Sch Med, Durham, NC USA. RP Huybrechts, KF (reprint author), Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD OCT PY 2014 VL 69 IS 10 BP 579 EP 581 DI 10.1097/01.ogx.0000456348.32099.6d PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AS7RS UT WOS:000344453200006 ER PT J AU Ledermann, J Harter, P Gourley, C Friedlander, M Vergote, I Rustin, G Scott, CL Meier, W Shapira-Frommer, R Safra, T Matei, D Fielding, A Spencer, S Dougherty, B Orr, M Hodgson, D Barrett, JC Matulonis, U AF Ledermann, Jonathan Harter, Philipp Gourley, Charlie Friedlander, Michael Vergote, Ignace Rustin, Gordon Scott, Clare L. Meier, Werner Shapira-Frommer, Ronnie Safra, Tamar Matei, Daniela Fielding, Anitra Spencer, Stuart Dougherty, Brian Orr, Maria Hodgson, Darren Barrett, J. Carl Matulonis, Ursula TI Olaparib Maintenance Therapy in Patients With Platinum-Sensitive Relapsed Serous Ovarian Cancer: A Preplanned Retrospective Analysis of Outcomes by BRCA Status in a Randomised Phase 2 Trial EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Greater than 20% of cases of high-grade serous ovarian cancer are due to germline or somatically acquired BRCA mutations. Poly(ADP-ribose) polymerase inhibitors have been investigated as treatment for a number of tumors, including those due to BRCA mutations. One potent oral poly(ADP-ribose) polymerase inhibitor, olaparib, has shown antitumor activity in patients with both BRCA and sporadic high-grade serous ovarian cancer. A previous randomized, double-blind, placebo-controlled phase 2 study showed that twice-daily maintenance treatment with oral olaparib in patients with platinum-sensitive recurrent serous ovarian cancer significantly improved progression-free survival (PFS). Subgroup analysis suggested that olaparib may increase PFS longer in patients with known BRCA status than in those with unknown mutation status. Data from the second interim analysis of overall survival and a retrospective, preplanned analysis of data from the above trial were used to determine whether patients with BRCA mutations would most likely benefit from daily maintenance treatment with oral olaparib. Enrolled patients had received 2 or more courses of platinum-based regimens and were required to have shown a partial or complete objective response to their most recent platinum-based regimen. Patients were randomly assigned using an interactive voice response system to receive oral olaparib 400 mg twice daily or matching placebo. Randomization was stratified by time to progression on penultimate platinum-based regimen, objective response to the most recent platinum-based regimen prior to randomization, and ethnic descent. The primary study outcome was PFS in the overall population, stratified by BRCA status. Between 2008 and 2010, 265 patients were enrolled. Among these, 136 were randomly assigned to receive olaparib and 129 to placebo. BRCA mutation status was known for 254 (96%) of the patients (131 [96%] in the olaparib group vs 123 [95%] in the placebo group); of these, 74 (56%) versus 62 (50%), respectively, had a known deleterious or suspected deleterious BRCA mutation. Patients with a BRCA mutation who received olaparib had a significantly longer median PFS than did those in the placebo group (11.2 months [95% confidence interval {CI}, 83 months-not calculable] vs 4.3 months [95% CI, 3.0-5.4 months]; the hazard ratio (HR) was 0.18, with a 95% CI of 0.10 to 0.31; P < 0.0001. Olaparib had a similar benefit in patients with wild-type BRCA, but the difference between groups was lower (7.4 months [95% CI, 5.5-10.3 months] vs 5.5 months [95% CI, 3.7-5.6 months]; HR, 0.54; 95% CI, 0.34-0.85; P = 0.007). Interim analysis of median overall survival (58% maturity) found no significant difference between the 2 groups in overall survival; the HR was 0.88, with a 95% CI of 0.64 to 1.21; P = 0.44. Results were similar for patients with mutated BRCA (HR, 0.73; 95% CI, 0.45-1.17; P = 0.19) and wild-type BRCA (HR, 0.99; 95% CI, 0.63-1.55; P = 0.96). The most common grade 3 or worse adverse events reported were fatigue (7% in the olaparib group vs 3% in the placebo group) and anemia (5% vs <1%). Serious adverse events occurred in 18% of patients in the olaparib group and 9% in the placebo group. Few patients discontinued therapy because of adverse events. The tolerability profile was similar among patients with mutated BRCA and those in the overall population. These findings show that patients with platinum-sensitive relapsed serous ovarian cancer with a BRCA mutation have the greatest likelihood of benefiting from olaparib maintenance therapy. The data suggest that a therapeutic approach based on BRCA mutation status could maximize clinical benefit in this population. C1 [Ledermann, Jonathan] UCL, UCL Canc Inst, London, England. [Harter, Philipp] Kliniken Essen Mitte, Essen, Germany. [Gourley, Charlie] Univ Edinburgh, Canc Res UK Ctr, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Friedlander, Michael] Univ New S Wales, Prince Wales Clin Sch, Randwick, NSW, Australia. [Vergote, Ignace] Univ Leuven, Leuven, Belgium. [Rustin, Gordon] Mt Vernon Hosp, Northwood HA6 2RN, Middx, England. [Scott, Clare L.] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Meier, Werner] Evangel Krankenhaus, Dusseldorf, Germany. [Shapira-Frommer, Ronnie] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Safra, Tamar] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. [Matei, Daniela] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Fielding, Anitra; Spencer, Stuart; Orr, Maria; Hodgson, Darren] AstraZeneca, Macclesfield, Cheshire, England. [Dougherty, Brian; Barrett, J. Carl] AstraZeneca, Waltham, MA USA. [Matulonis, Ursula] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ledermann, J (reprint author), UCL, UCL Canc Inst, London, England. NR 0 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD OCT PY 2014 VL 69 IS 10 BP 594 EP 596 DI 10.1097/OGX.0000000000000107 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AS7RS UT WOS:000344453200014 ER PT J AU Goodman, KA Milgrom, SA Herman, JM Abdel-Wahab, M Azad, N Blackstock, AW Das, P Hong, TS Jabbour, SK Jones, WE Konski, AA Koong, AC Kumar, R Rodriguez-Bigas, M Small, W Thomas, CR Suh, WW AF Goodman, Karyn A. Milgrom, Sarah A. Herman, Joseph M. Abdel-Wahab, May Azad, Nlofer Blackstock, A. William Das, Prajnan Hong, Theodore S. Jabbour, Salma K. Jones, William E., III Konski, Andre A. Koong, Albert C. Kumar, Rachit Rodriguez-Bigas, Miguel Small, William, Jr. Thomas, Charles R., Jr. Suh, W. Warren TI ACR Appropriateness Criteria (R) Rectal Cancer: Metastatic Disease at Presentation SO ONCOLOGY-NEW YORK LA English DT Article ID COLORECTAL LIVER METASTASES; LONG-TERM SURVIVAL; PHASE-III TRIAL; 1ST-LINE TREATMENT; RADIOFREQUENCY ABLATION; INFUSIONAL FLUOROURACIL; SYSTEMIC CHEMOTHERAPY; 10-YEAR EXPERIENCE; RADIATION-THERAPY; HEPATIC RESECTION AB The management of rectal cancer in patients with metastatic disease at presentation is highly variable. There are no phase III trials addressing therapeutic approaches, and the optimal sequencing of chemotherapy, radiation therapy, and surgery remains unresolved. Although chemoradiation is standard for patients with stage II/III rectal cancer, its role in the metastatic setting is controversial. Omitting chemoradiation may not be appropriate in all stage IV patients, particularly those with symptomatic primary tumors. Moreover, out-comes in this setting are vastly different, as some treatments carry the potential for cure in selected patients, while others are purely palliative. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application, by the panel, of a well-established consensus methodology (Modified Delphi) to rate the appropriateness of imaging and treatment procedures. In instances in which evidence is lacking or not definitive, expert opinion may be used as the basis for recommending imaging or treatment. C1 [Goodman, Karyn A.; Milgrom, Sarah A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Herman, Joseph M.; Azad, Nlofer] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Abdel-Wahab, May] Cleveland Clin, Cleveland, OH 44106 USA. [Azad, Nlofer] Amer Soc Clin Oncol, Chicago, IL USA. [Blackstock, A. William] Wake Forest Univ, Winston Salem, NC 27109 USA. [Das, Prajnan; Rodriguez-Bigas, Miguel] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hong, Theodore S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jabbour, Salma K.] Rutgers State Univ, Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA. [Jones, William E., III] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Konski, Andre A.] Chester Cty Hosp, W Chester, PA USA. [Koong, Albert C.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Kumar, Rachit] Johns Hopkins Univ, Baltimore, MD USA. [Rodriguez-Bigas, Miguel] Amer Coll Surg, Chicago, IL USA. [Small, William, Jr.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. [Thomas, Charles R., Jr.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Suh, W. Warren] Canc Ctr Santa Barbara, Santa Barbara, CA USA. RP Goodman, KA (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. FU Genentech FX Joseph M. Herman, MD, reports a conflict of interest related to relationships with Nucletron and Genentech. Prajnan Das, MD, reports research support from Genentech. NR 59 TC 1 Z9 1 U1 0 U2 3 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD OCT PY 2014 VL 28 IS 10 BP 867 EP + PG 7 WC Oncology SC Oncology GA AS2TW UT WOS:000344133200008 PM 25323613 ER PT J AU Merlin, JS Turan, JM Herbey, I Westfall, AO Starrels, JL Kertesz, SG Saag, MS Ritchie, CS AF Merlin, Jessica S. Turan, Janet M. Herbey, Ivan Westfall, Andrew O. Starrels, Joanna L. Kertesz, Stefan G. Saag, Michael S. Ritchie, Christine S. TI Aberrant Drug-Related Behaviors: A Qualitative Analysis of Medical Record Documentation in Patients Referred to an HIV/Chronic Pain Clinic SO PAIN MEDICINE LA English DT Article DE HIV; Aberrant Behavior; Opioid; Misuse ID CHRONIC NONCANCER PAIN; OPIOID-PRESCRIBING PRACTICES; CHRONIC NONMALIGNANT PAIN; HIV-INFECTED PATIENTS; PRIMARY-CARE; REPORTED OUTCOMES; THERAPY; MANAGEMENT; ABUSE; COHORT AB BackgroundDue to rising rates of opioid addiction and overdose among individuals on chronic opioid therapy, aberrant drug-related behaviors (ADRBs) are an important and challenging issue. Our objective was to qualitatively investigate the documentation of ADRBs in the medical record. MethodsManually abstracted provider notes from an HIV primary care clinic were analyzed using content analysis methods. ResultsCategories of ADRBs identified included patients requesting opioids, obtaining nonprescribed opioids, and becoming emotional about opioids. We also identified several types of provider language used when documenting ADRBs, including purely descriptive language and emotional language such as labeling, frustration, and concern, and responses such as setting conditions for opioid prescription and action-oriented language. ConclusionsThe impact of including emotional language in the medical record is unknown. Development of instruments that can be used to facilitate ADRB documentation, as well as evidence-based approaches to addressing ADRBs, is needed. C1 [Merlin, Jessica S.; Herbey, Ivan; Westfall, Andrew O.; Saag, Michael S.] Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Turan, Janet M.] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA. [Kertesz, Stefan G.] Univ Alabama Birmingham, Div Prevent Med, Dept Med, Birmingham, AL 35294 USA. [Starrels, Joanna L.] Albert Einstein Coll Med, Div Gen Internal Med, Bronx, NY 10467 USA. [Starrels, Joanna L.] Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. [Kertesz, Stefan G.] Birmingham VA Med Ctr, Birmingham, AL USA. [Ritchie, Christine S.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ritchie, Christine S.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Ritchie, Christine S.] Jewish Home San Francisco Ctr Res Aging, San Francisco, CA USA. RP Merlin, JS (reprint author), Univ Alabama Birmingham, Dept Med, Div Infect Dis, BBRB 222,1530 3rd Ave S, Birmingham, AL 35294 USA. EM jmerlin@uab.edu FU University of Alabama at Birmingham (UAB) Center for AIDS Research CFAR; NIH [P30 A1027767]; NIAID; NCI; NICHD; NHLBI; NIDA; NIMH; NIA; FIC; OAR FX This research was supported by the University of Alabama at Birmingham (UAB) Center for AIDS Research CFAR, an NIH-funded program (P30 A1027767) that was made possible by the following institutes: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, FIC, and OAR. NR 40 TC 2 Z9 2 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD OCT PY 2014 VL 15 IS 10 BP 1724 EP 1733 DI 10.1111/pme.12533 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AS4KO UT WOS:000344244800008 PM 25138608 ER PT J AU Hasegawa, K Espinola, JA Brown, DFM Camargo, CA AF Hasegawa, Kohei Espinola, Janice A. Brown, David F. M. Camargo, Carlos A., Jr. TI Trends in U.S. Emergency Department Visits for Opioid Overdose, 1993-2010 SO PAIN MEDICINE LA English DT Article DE Opioids; Overdose; Emergency Department; Epidemiology; Time Trend ID VITAL SIGNS OVERDOSES; UNITED-STATES; CHRONIC PAIN; SUICIDAL THOUGHTS; DRUG OVERDOSE; DEATHS; RELIEVERS; IDEATION; PLANS; RATES AB ObjectiveEmergency department (ED) visits for opioid overdose provide an important marker of acute morbidity. We sought to evaluate national trends of ED visits for opioid overdose. Design, Setting, and ParticipantsThe National Hospital Ambulatory Medical Care Survey, 1993-2010, was used to identify ED visits for opioid overdose. Outcome MeasuresOutcome measures were national ED visit rates for opioid overdose per 100,000 U.S. population and per 100,000 ED visits. ResultsFrom 1993 to 2010, there were approximately 731,000 ED visits (95% CI, 586,000-877,000 visits) for opioid overdose, representing an overall rate of 14 ED visits (95% CI, 12-17 visits) per 100,000 population and 37 ED visits (95% CI, 31-45 visits) per 100,000 ED visits. Of these, 41% (95% CI, 33-50%) were for prescription opioid overdose. Between 1993 and 2010, the national visit rate increased from 7 to 27 per 100,000 population (+307%; P-trend=0.03), and from 19 to 63 per 100,000 ED visits (+235%; P-trend<0.001). Stratified analyses of the visit rate per population showed upward, but nonsignificant, trends across multiple demographic groups and U.S. regions. In stratified analyses of the visit rate per 100,000 ED visits, the rate increased significantly in several groups: age <20 years (+1188%; P-trend=0.002), age 20-29 years (+155%; P-trend=0.04), age 50 years (+231%; P-trend=0.04), female (+234%; P-trend=0.001), male (+80%; P-trend=0.04), whites (+187%; P-trend<0.001), and patients in the South (+371%; P-trend<0.001). ConclusionIn a nationally representative database of U.S. ED visits, we found that the ED visit rate for opioid overdose quadrupled from 1993 to 2010. Our findings suggest that previous prevention measures may not be adequate. C1 [Hasegawa, Kohei; Espinola, Janice A.; Brown, David F. M.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM khasegawa1@partners.org FU Eleanor and Miles Shore Fellowship Program (Boston, MA) FX Dr. Hasegawa was supported, in part, by Eleanor and Miles Shore Fellowship Program (Boston, MA). The funding organization had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. NR 29 TC 9 Z9 9 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD OCT PY 2014 VL 15 IS 10 BP 1765 EP 1770 DI 10.1111/pme.12461 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA AS4KO UT WOS:000344244800013 PM 25139712 ER PT J AU Malka, R Delgado, FF Manalis, SR Higgins, JM AF Malka, Roy Delgado, Francisco Feijo Manalis, Scott R. Higgins, John M. TI In Vivo Volume and Hemoglobin Dynamics of Human Red Blood Cells SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID HUMAN-ERYTHROCYTES; VESICLES; RETICULOCYTE; AREA; MICROVESICLES; TRANSFUSION; MEMBRANE; DYE AB Human red blood cells (RBCs) lose similar to 30% of their volume and similar to 20% of their hemoglobin (Hb) content during their,similar to 100-day lifespan in the bloodstream. These observations are well-documented, but the mechanisms for these volume and hemoglobin loss events are not clear. RBCs shed hemoglobin-containing vesicles during their life in the circulation, and this process is thought to dominate the changes in the RBC physical characteristics occurring during maturation. We combine theory with single-cell measurements to investigate the impact of vesiculation on the reduction in volume, Hb mass, and membrane. We show that vesicle shedding alone is sufficient to explain membrane losses but not volume or Hb losses. We use dry mass measurements of human RBCs to validate the models and to propose that additional unknown mechanisms control volume and Hb reduction and are responsible for similar to 90% of the observed reduction. RBC population characteristics are used in the clinic to monitor and diagnose a wide range of conditions including malnutrition, inflammation, and cancer. Quantitative characterization of cellular maturation processes may help in the early detection of clinical conditions where maturation patterns are altered. C1 [Malka, Roy; Higgins, John M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Malka, Roy; Higgins, John M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Malka, Roy; Higgins, John M.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Delgado, Francisco Feijo; Manalis, Scott R.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Manalis, Scott R.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. RP Malka, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM Roy_Malka@hms.harvard.edu; John_Higgins@hms.harvard.edu FU Institute for Collaborative Biotechnologies from the US Army Research Office [W911NF-09-D-0001]; NIH; NIH [1DP2DK098087] FX This work was funded by the Institute for Collaborative Biotechnologies Contract W911NF-09-D-0001 from the US Army Research Office (SRM). NIH Director's New Innovator Award and NIH grant 1DP2DK098087 (JMH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 2 Z9 3 U1 1 U2 8 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 OCT PY 2014 VL 10 IS 10 AR e1003839 DI 10.1371/journal.pcbi.1003839 PG 12 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA AS9FG UT WOS:000344547900005 PM 25299941 ER PT J AU Prerau, MJ Hartnack, KE Obregon-Henao, G Sampson, A Merlino, M Gannon, K Bianchi, MT Ellenbogen, JM Purdon, PL AF Prerau, Michael J. Hartnack, Katie E. Obregon-Henao, Gabriel Sampson, Aaron Merlino, Margaret Gannon, Karen Bianchi, Matt T. Ellenbogen, Jeffrey M. Purdon, Patrick L. TI Tracking the Sleep Onset Process: An Empirical Model of Behavioral and Physiological Dynamics SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID WRIST ACTIGRAPHY; BINARY MEASURES; HYPNAGOGIC EEG; WAKEFULNESS; INSOMNIA; CONVERGENCE; RESPIRATION; PERFORMANCE; POPULATION; TRANSITION AB The sleep onset process (SOP) is a dynamic process correlated with a multitude of behavioral and physiological markers. A principled analysis of the SOP can serve as a foundation for answering questions of fundamental importance in basic neuroscience and sleep medicine. Unfortunately, current methods for analyzing the SOP fail to account for the overwhelming evidence that the wake/sleep transition is governed by continuous, dynamic physiological processes. Instead, current practices coarsely discretize sleep both in terms of state, where it is viewed as a binary (wake or sleep) process, and in time, where it is viewed as a single time point derived from subjectively scored stages in 30-second epochs, effectively eliminating SOP dynamics from the analysis. These methods also fail to integrate information from both behavioral and physiological data. It is thus imperative to resolve the mismatch between the physiological evidence and analysis methodologies. In this paper, we develop a statistically and physiologically principled dynamic framework and empirical SOP model, combining simultaneously-recorded physiological measurements with behavioral data from a novel breathing task requiring no arousing external sensory stimuli. We fit the model using data from healthy subjects, and estimate the instantaneous probability that a subject is awake during the SOP. The model successfully tracked physiological and behavioral dynamics for individual nights, and significantly outperformed the instantaneous transition models implicit in clinical definitions of sleep onset. Our framework also provides a principled means for cross-subject data alignment as a function of wake probability, allowing us to characterize and compare SOP dynamics across different populations. This analysis enabled us to quantitatively compare the EEG of subjects showing reduced alpha power with the remaining subjects at identical response probabilities. Thus, by incorporating both physiological and behavioral dynamics into our model framework, the dynamics of our analyses can finally match those observed during the SOP. C1 [Prerau, Michael J.; Hartnack, Katie E.; Obregon-Henao, Gabriel; Sampson, Aaron; Purdon, Patrick L.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. [Merlino, Margaret; Gannon, Karen; Bianchi, Matt T.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Ellenbogen, Jeffrey M.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. RP Prerau, MJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. EM prerau@nmr.mgh.harvard.edu OI Obregon-Henao, Gabriel/0000-0003-1622-6090 FU NIH [DP2-OD006454] FX Research supported by an NIH New Innovator Award DP2-OD006454, (PLP) http://commonfund.nih.gov/newinnovator/index. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 5 Z9 5 U1 2 U2 18 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 OCT PY 2014 VL 10 IS 10 AR e1003866 DI 10.1371/journal.pcbi.1003866 PG 19 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA AS9FG UT WOS:000344547900021 PM 25275376 ER PT J AU Ahmed, M Solbiati, L Brace, CL Breen, DJ Callstrom, MR Charboneau, JW Chen, MH Choi, BI de Baere, T Dodd, GD Dupuy, DE Gervais, DA Gianfelice, D Gillams, AR Lee, FT Leen, E Lencioni, R Littrup, PJ Livraghi, T Lu, DS McGahan, JP Meloni, MF Nikolic, B Pereira, PL Liang, P Rhim, H Rose, SC Salem, R Sofocleous, CT Solomon, SB Soulen, MC Tanaka, M Vogl, TJ Wood, BJ Goldberg, SN AF Ahmed, Muneeb Solbiati, Luigi Brace, Christopher L. Breen, David J. Callstrom, Matthew R. Charboneau, J. William Chen, Min-Hua Choi, Byung Ihn de Baere, Thierry Dodd, Gerald D., III Dupuy, Damian E. Gervais, Debra A. Gianfelice, David Gillams, Alice R. Lee, Fred T., Jr. Leen, Edward Lencioni, Riccardo Littrup, Peter J. Livraghi, Tito Lu, David S. McGahan, John P. Meloni, Maria Franca Nikolic, Boris Pereira, Philippe L. Liang, Ping Rhim, Hyunchul Rose, Steven C. Salem, Riad Sofocleous, Constantinos T. Solomon, Stephen B. Soulen, Michael C. Tanaka, Masatoshi Vogl, Thomas J. Wood, Bradford J. Goldberg, S. Nahum CA Int Working Grp Image-Guided Tumor Interventional Oncology Sans Front Soc Interventional Radiology Cardiovasc Interventional Radiolog TI Image-guided Tumor Ablation: Standardization of Terminology and Reporting Criteria-A 10-Year Update SO RADIOLOGY LA English DT Article ID PERCUTANEOUS RADIOFREQUENCY ABLATION; RENAL-CELL CARCINOMA; VIVO PORCINE LIVER; TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; IRREVERSIBLE ELECTROPORATION ABLATION; CONTRAST-ENHANCED ULTRASOUND; INTERNALLY COOLED ELECTRODES; LONG-TERM SURVIVAL; QUALITY-OF-LIFE; HEPATOCELLULAR-CARCINOMA AB Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes. (C) RSNA, 2014 C1 [Ahmed, Muneeb] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Solbiati, Luigi] Osped Gen, Dept Radiol, Busto Arsizio, Italy. [Brace, Christopher L.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Brace, Christopher L.] Univ Wisconsin, Dept Biomed Engn, Sch Med & Publ Hlth, Madison, WI USA. [Brace, Christopher L.] Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Breen, David J.] Southampton Univ Hosp, Dept Radiol, Southampton, Hants, England. [Callstrom, Matthew R.; Charboneau, J. William] Mayo Clin, Dept Radiol, Rochester, MN USA. [Chen, Min-Hua] Peking Univ, Dept Ultrasound, Sch Oncol, Beijing 100871, Peoples R China. [Choi, Byung Ihn] Seoul Natl Univ Hosp, Dept Radiol, Seoul 110744, South Korea. [de Baere, Thierry] Inst Cancerol Gustave Roussy, Dept Imaging, Villejuif, France. [Dodd, Gerald D., III] Univ Colorado, Dept Radiol, Sch Med, Aurora, CO USA. [Dupuy, Damian E.] Rhode Isl Hosp, Dept Diagnost Radiol, Providence, RI USA. [Gervais, Debra A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Gianfelice, David] Univ Hlth Network, Laval, PQ, Canada. [Gillams, Alice R.] London Clin, Dept Imaging, London, England. [Lee, Fred T., Jr.] Univ Wisconsin Hosp & Clin, Dept Radiol, Madison, WI 53792 USA. [Leen, Edward] Royal Infirm, Dept Radiol, Glasgow G31 2ER, Lanark, Scotland. [Lencioni, Riccardo] Univ Pisa, Dept Diagnost Imaging & Intervent, Cisanello Hosp, Pisa Univ Hosp, Pisa, Italy. [Lencioni, Riccardo] Univ Pisa, Sch Med, I-56100 Pisa, Italy. [Littrup, Peter J.] Wayne State Univ, Dept Radiol, Karmonos Canc Inst, Detroit, MI USA. [Lu, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. [McGahan, John P.] UC Davis Med Ctr, Dept Radiol, Ctr Ambulatory Care, Sacramento, CA USA. [Meloni, Maria Franca] Osped Valduce, Dept Radiol, Como, Italy. [Nikolic, Boris] Albert Einstein Med Ctr, Dept Radiol, Philadelphia, PA 19141 USA. [Pereira, Philippe L.] Heidelberg Univ, Clin Radio ,Minimally Invas Therapies & Nucl Med, Acad Hosp, Heilbronn, Germany. [Liang, Ping] Chinese Peoples Liberat Army Gen Hosp, Dept Intervent Ultrasound, Beijing, Peoples R China. [Rhim, Hyunchul] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Diagnost Radiol, Seoul, South Korea. [Rose, Steven C.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. [Salem, Riad] Northwestern Univ, Dept Radiol, Chicago, IL USA. [Sofocleous, Constantinos T.; Solomon, Stephen B.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Soulen, Michael C.] Univ Penn, Dept Radiol, Hosp Univ Penn, Philadelphia, PA 19104 USA. [Tanaka, Masatoshi] Yokokura Hosp, Dept Hepatol, Miyama, Japan. [Vogl, Thomas J.] Goethe Univ Frankfurt, Inst Diagnost & Intervent Radiol, Univ Hosp Frankfurt, D-60054 Frankfurt, Germany. [Wood, Bradford J.] NIH, Bethesda, MD 20892 USA. [Goldberg, S. Nahum] Hadassah Hebrew Univ, Med Ctr, Dept, Image Guided Therapy & Intervent Oncol Unit, Jerusalem, Israel. RP Ahmed, M (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 1 Deaconess Rd,WCC-308B, Boston, MA 02215 USA. EM mahmed@bidmc.harvard.edu FU NeuWave Medical; University of Wisconsin; Galil Medical; Siemens Medical; GE Medical; Thermedical; Samsung Electronics; Terumo; HS-Medical; Boston-Scientific; BSD Medical; Covidien; Springer Verlag; UpToDate; Covidien/Valleylab; Endocare; Ethicon Endo-Surgery; Philips; Celon Olympus; Siemens Medical Solutions; GE Healthcare; AngioDyamics; Guerbet LLC; BTG; Merit Medical; Cooperative Research and Development Agreement (CRADA) Philips Healthcare; CRADA Biocompatibles BTG; CRADA Perfint; CRADA Celsion; CRADA Invivo; AngioDynamics; Cosman Medical FX M.A. No relevant conflicts of interest to disclose. L.S. No relevant conflicts of interest to disclose. C.L.B. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received consultancy fees from NeuWave Medical, author and institution received payment for patents (planned, pending, or issued) from University of Wisconsin and NeuWave Medical, received payment for stock/stock options from NeuWave Medical. Other relationships: none to disclose. D.J.B. Financial activities related to the present article: paid for occasional proctoring by Galil Medical. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. M.R.C. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received grants from Galil Medical, Siemens Medical, GE Medical, Thermedical. Other relationships: none to disclose. J.W.C. No relevant conflicts of interest to disclose. M.H.C. No relevant conflicts of interest to disclose. B.I.C. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: institution received a research grant from Samsung Electronics. Other relationships: none to disclose. T.d.B. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received personal fees from Terumo, a grant from HS-Medical, and payment for travel to a meeting from Boston-Scientific. Other relationships: none to disclose. G. D. D. No relevant conflicts of interest to disclose. D. E. D. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: paid for board membership by BSD Medical, received consultancy fees from BSD Medical and Covidien, received grants or has grants pending from NeuWave Medical, received payment for lectures including service on speakers bureaus from BSD Medical, was paid royalties by Springer Verlag and UpToDate, received stock or stock options from BSD Medical,. Other relationships: none to disclose. D. A. G. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received a research grant from Covidien/Valleylab. Other relationships: none to disclose. D. G. No relevant conflicts of interest to disclose. A. R. G. Financial activities related to the present article: received consulting fee or honorarium from Covidien, received fees for participatient in review activities such as data monitoring boards, statistical analysis, end point committees, and the like from Covidien. Financial activities not related to the present article: was paid for board membership, consultancy, and lectures including service on speakers bureaus by Covidien. Other relationships: none to disclose. F. T. L. Financial activities related to the present article: received payment from NeuWave Medical. Financial activities not related to the present article: received royalties from Covidien, is a stockholder and on the Board of Directors for NeuWave Medical, has a patent on the Switching Controller with royalties paid from Covidien, has multiple patents on heat-based thermal therapies for microwave ablation systems licensed to NeuWave Medical. Other relationships: none to disclose. E. L. No relevant conflicts of interest to disclose. R. L. No relevant conflicts of interest to disclose. P.J.L.; No relevant conflicts of interest to disclose. T. L. No relevant conflicts of interest to disclose. D. S. L. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: institution received grants or has grants pending from Endocare and Ethicon Endo-Surgery, received payment for lectures including service on speakers bureaus from Philips. Other relationships: none to disclose. J.P.M. No relevant conflicts of interest to disclose. M. F. M. No relevant conflicts of interest to disclose. B.N. No relevant conflicts of interest to disclose. P. L. P. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received a grant from Celon Olympus; fees for conferences from Siemens Medical Solutions; consultant's honoraries from Terumo Europe, Terumo Germany, and Microsulis; materials from AngioDynamics. Other relationships: none to disclose. P. L. No relevant conflicts of interest to disclose. H. R. No relevant conflicts of interest to disclose. S. C. R. No relevant conflicts of interest to disclose. R. S. No relevant conflicts of interest to disclose. C. T. S. No relevant conflicts of interest to disclose. S. B. S. Financial activities related to the present article: institution received a grant from GE Healthcare; author received consulting fee or honorarium from AngioDyamics, Covidien, and GE Healthcare. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. M. C. S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: author received consultancy fees from Guerbet LLC, BTG, Merit Medical; institution received grants or has grants pending from Guerbet LLC and BTG; author received payment for lectures including service on speakers bureaus from Sirtex; author received royalties from Cambridge University Press. Other relationships: none to disclose. M. T. No relevant conflicts of interest to disclose. T.J.V. No relevant conflicts of interest to disclose. B.J.W. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: institution received grants or has grants pending from Cooperative Research and Development Agreement (CRADA) Philips Healthcare, CRADA Biocompatibles BTG, CRADA Perfint, CRADA Celsion, CRADA Invivo; the National Institutes of Health has intellectual property in the field. Other relationships: none to disclose. S.N.G. Financial activities related to the present article: institution received a grant for sponsored research from AngioDynamics; author received consulting fee or honorarium from AngioDynamics. Financial activities not related to the present article: author received consultancy fees from Cosman Medical and institution received grants or has grants pending from Cosman Medical. Other relationships: none to disclose. NR 100 TC 96 Z9 100 U1 4 U2 23 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2014 VL 273 IS 1 BP 241 EP 260 DI 10.1148/radiol.14132958 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AS4GO UT WOS:000344232100027 PM 24927329 ER PT J AU Sanchez-Martinez, M Lopez-Cuenca, A Marin, F Flores-Blanco, PJ Narbon, AG de las Heras-Gomez, I Sanchez-Galian, CJ Valdes-Chavarri, M Januzzi, JL Manzano-Fernandez, S AF Sanchez-Martinez, Marianela Lopez-Cuenca, Angel Marin, Francisco Flores-Blanco, Pedro J. Narbon, Andrea Garcia de las Heras-Gomez, Ignacio Sanchez-Galian, Maria J. Valdes-Chavarri, Mariano Januzzi, James L. Manzano-Fernandez, Sergio TI Red Cell Distribution Width and Additive Risk Prediction for Major Bleeding in Non-ST-segment Elevation Acute Coronary Syndrome SO REVISTA ESPANOLA DE CARDIOLOGIA LA English DT Article DE Red cell distribution width; Bleeding; Acute coronary syndrome ID HOSPITAL-ACQUIRED ANEMIA; LONG-TERM MORTALITY; MYOCARDIAL-INFARCTION; HEART-FAILURE; OLDER-ADULTS; INTERVENTION; IMPACT; OUTPATIENTS; PROGNOSIS; OUTCOMES AB Introduction and objectives: Red cell distribution width has been linked to an increased risk for in-hospital bleeding in patients with non-ST-segment elevation acute coronary syndrome. However, its usefulness for predicting bleeding complications beyond the hospitalization period remains unknown. Our aim was to evaluate the complementary value of red cell distribution width and the CRUSADE scale to predict long-term bleeding risk in these patients. Methods: Red cell distribution width was measured at admission in 293 patients with non-ST-segment elevation acute coronary syndrome. All patients were clinically followed up and major bleeding events were recorded (defined according to Bleeding Academic Research Consortium Definition criteria). Results: During a follow-up of 782 days [interquartile range, 510-1112 days], events occurred in 30 (10.2%) patients. Quartile analyses showed an abrupt increase in major bleedings at the fourth red cell distribution width quartile (> 14.9%; P = .001). After multivariate adjustment, red cell distribution width > 14.9% was associated with higher risk of events (hazard ratio = 2.67; 95% confidence interval, 1.17-6.10; P = .02). Patients with values <= 14.9% and a CRUSADE score <= 40 had the lowest events rate, while patients with values > 14.9% and a CRUSADE score > 40 points (high and very high risk) had the highest rate of bleeding (log rank test, P < .001). Further, the addition of red cell distribution width to the CRUSADE score for the prediction of major bleeding had a significant integrated discrimination improvement of 5.2% (P < .001) and a net reclassification improvement of 10% (P = .001). Conclusions: In non-ST-segment elevation acute coronary syndrome patients, elevated red cell distribution width is predictive of increased major bleeding risk and provides additional information to the CRUSADE scale. (C) 2013 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved. C1 [Sanchez-Martinez, Marianela; Marin, Francisco; Flores-Blanco, Pedro J.; Sanchez-Galian, Maria J.; Valdes-Chavarri, Mariano; Manzano-Fernandez, Sergio] Hosp Clin Univ Virgen Arrixaca, Dept Cardiol, Murcia 30120, Spain. [Lopez-Cuenca, Angel] Hosp Vega Lorenzo Guirao, Dept Med Interna, Murcia, Spain. [Narbon, Andrea Garcia; de las Heras-Gomez, Ignacio] Hosp Clin Univ Virgen Arrixaca, Dept Bioquim, Murcia, Spain. [Valdes-Chavarri, Mariano; Manzano-Fernandez, Sergio] Univ Murcia, Fac Med, Dept Med Interna, Murcia, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Manzano-Fernandez, S (reprint author), Univ Murcia, Hosp Clin Univ Virgen Arrixaca, Dept Cardiol, Ctra Madrid Cartagena S-N, Murcia 30120, Spain. EM sergiosmf13@hotmail.com FU Abbott; Boston Scientifics; Bayer; AstraZeneca; Daiichi-Sankyo; BMS/Pfizer; Boehringer Ingelheim; Roche Diagnostics; Critical Diagnostics; Siemens; Singulex FX Dr. Marin has received funding for research, consultancy and lecturing from Abbott, Boston Scientifics, Bayer, AstraZeneca, Daiichi-Sankyo, BMS/Pfizer and Boehringer Ingelheim. Dr. Januzzi reports grant support from Roche Diagnostics, Critical Diagnostics, Siemens and Singulex. NR 30 TC 4 Z9 4 U1 0 U2 1 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0300-8932 EI 1579-2242 J9 REV ESP CARDIOL JI Rev. Esp. Cardiol. PD OCT PY 2014 VL 67 IS 10 BP 830 EP 836 DI 10.1016/j.rec.2013.12.018 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AS3JK UT WOS:000344173500008 PM 25262129 ER PT J AU Ferrone, S AF Ferrone, Soldano TI Therapeutic Monoclonal Antibodies: Introduction SO SEMINARS IN ONCOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ferrone, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sferrone@mgh.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2014 VL 41 IS 5 BP 556 EP 558 DI 10.1053/j.seminoncol.2014.09.011 PG 3 WC Oncology SC Oncology GA AS5KL UT WOS:000344309800002 PM 25440602 ER PT J AU Sabbatino, F Wang, YY Wang, XH Schwab, JH Ferrone, S Ferrone, CR AF Sabbatino, Francesco Wang, Yangyang Wang, Xinhui Schwab, Joseph H. Ferrone, Soldano Ferrone, Cristina R. TI Novel Tumor Antigen-Specific Monoclonal Antibody-Based Immunotherapy to Eradicate Both Differentiated Cancer Cells and Cancer-Initiating Cells in Solid Tumors SO SEMINARS IN ONCOLOGY LA English DT Review ID ALDEHYDE DEHYDROGENASE-ACTIVITY; STEM-CELLS; BREAST-CANCER; PROSPECTIVE IDENTIFICATION; PANCREATIC-CANCER; SIGNALING PATHWAYS; EPITHELIAL-CELLS; PROSTATE-CANCER; DRUG-RESISTANCE; POOR-PROGNOSIS AB A growing body of experimental and clinical evidence strongly suggests that the resistance of cancer-initiating cells (CICs) to conventional therapies represents a major obstacle to the successful treatment of a malignant disease. To overcome this limitation a novel combinatorial tumor antigen (TA)-specific monoclonal antibody (mAb) strategy has been developed. In this strategy TA-specific mAbs are combined with chemotherapeutic agents and/or small molecules that inhibit aberrantly activated signaling pathways in cancer cells and especially in CICs. The in vitro results we have obtained indicate that this strategy is very effective in eradicating both differentiated cancer cells and CICs in several types of malignant disease. If the in vitro results have in vivo relevance, the strategy we have designed may have an impact on the treatment of malignant diseases. (C) 2014 Published by Elsevier Inc. C1 [Sabbatino, Francesco; Wang, Yangyang; Wang, Xinhui; Ferrone, Soldano; Ferrone, Cristina R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Schwab, Joseph H.; Ferrone, Soldano] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Wang, YY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM cferrone@mgh.harvard.edu RI Sabbatino, Francesco/F-4992-2014 OI Sabbatino, Francesco/0000-0001-6431-8278 FU PHS [RO1CA138188, RO1CA110249, R21 CA164756, R21CA173120, R03CA175957]; National Cancer Institute; Fondazione Umberto Veronesi Post Doctoral Fellowship; Fondazione Umberto Veronesi; Susan Komen Post Doctoral Fellowship [KG111486]; Susan G. Komen for the Cure Foundation FX This work was supported by PHS grants no. RO1CA138188, RO1CA110249, R21 CA164756, R21CA173120, R03CA175957 awarded by the National Cancer Institute, by Fondazione Umberto Veronesi Post Doctoral Fellowship awarded by the Fondazione Umberto Veronesi, and by Susan Komen Post Doctoral Fellowship KG111486 awarded by the Susan G. Komen for the Cure Foundation. Conflicts of interest: none. NR 107 TC 2 Z9 2 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 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2014 VL 41 IS 5 BP 685 EP 699 DI 10.1053/j.seminoncol.2014.08.007 PG 15 WC Oncology SC Oncology GA AS5KL UT WOS:000344309800013 PM 25440613 ER PT J AU Rodriguez, D Preston, MA Barrisford, GW Olumi, AF Feldman, AS AF Rodriguez, Dayron Preston, Mark A. Barrisford, Glen W. Olumi, Aria F. Feldman, Adam S. TI Clinical features of leiomyosarcoma of the urinary bladder: Analysis of 183 cases SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Cancer; Urinary bladder; Leiomyosarcoma; SEER; Outcomes; Prognostic factors ID SMOOTH-MUSCLE NEOPLASMS; SARCOMA; EXPERIENCE; THERAPY; ADULTS AB Introduction: Experience with management of urinary bladder leiomyosarcoma (LMS) is rare. Therefore, to better elucidate the disease characteristics of urinary bladder LMS, we utilized a large population-based cancer registry to examine the epidemiology, natural history, pathological characteristics, prognostic factors, and treatment outcomes. Material and methods: The Surveillance, Epidemiology, and End Results database (1973-2010) was used to identify cases by tumor site and histology codes. The association between clinical and demographic characteristics and long-term survival was examined. Results: A total of 183 histologically confirmed cases were identified between 1973 and 2010. The annual age-adjusted incidence rate was 0.23 cases per 1,000,000 and did not significantly change over time. Median age of the patients was 65 years (interquartile range: 47-78 y). Of the patients with a known pathologic tumor stage (n = 164), 50% had a regional or distant disease. Overall, 63.2% of patients with known histologic grade (n = 106), had poorly differentiated or undifferentiated histology. Most patients (92.9%) received cancer-directed surgery (CDS), with 34.4% having radical or partial cystectomy. Only 7.7% of patients received radiation therapy in combination with surgery. The median disease-specific survival was 46 months. Five- and 10-year cancer-specific survival rates were 47%, and 35%, respectively. On multivariate analysis, a worse outcome was associated with an undifferentiated tumor grade, distant disease, and failure to undergo CDS. Conclusion: This series represents the largest cohort of LMS of the urinary bladder studied to date. LMS commonly presented as high grade and advanced stage with a poor prognosis. Reduced disease-specific survival was associated with increasing age, undifferentiated tumor grade, distant disease, and failure to undergo CDS. (C) 2014 Elsevier Inc. All rights reserved. C1 [Rodriguez, Dayron; Preston, Mark A.; Barrisford, Glen W.; Olumi, Aria F.; Feldman, Adam S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02163 USA. RP Feldman, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02163 USA. EM afeldman@partners.org NR 23 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 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD OCT PY 2014 VL 32 IS 7 BP 958 EP 965 DI 10.1016/j.urolonc.2014.01.025 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AS0LP UT WOS:000343968900004 PM 25027684 ER PT J AU Ardestani, G Rogelio, DRO Reyes, RC Laude, RP AF Ardestani, Goli Rogelio, Diana Rose O. Reyes, Roberto C. Laude, Rita P. TI Genetic diversity of two Philippine native freshwater goby species (Perciformes: Gobiidae): implications for conservation SO AQUATIC CONSERVATION-MARINE AND FRESHWATER ECOSYSTEMS LA English DT Article DE genetic diversity; Gobiidae; conservation; isozyme; Philippines ID ALLELE FREQUENCY DATA; FRESH-WATER; GENETIC DIVERSITY; ANADROMOUS FISHES; POPULATIONS; MARINE; CHARACIFORMES; BIODIVERSITY; BIOGEOGRAPHY; STRATEGIES AB Appropriate decision-making in conservation programmes requires an understanding of the population genetic structure of various indigenous species. However, in lake and river ecosystems rated as biodiversity conservation priority areas in the Philippines, the diversity of many species remains uncharacterized.To address the existing gap, genetic diversity of two native freshwater fishes, Glossogobius celebius (Valenciennes, 1837) and Glossogobius giuris (Hamilton, 1822) was measured. Genetic structure and estimates of genetic variation for each species was determined using isozyme analysis.A higher level of genetic variation was observed within G. celebius populations compared with G. giuris. Genetic structure indicated that the observed genetic variation in G. giuris is due to the variation among the populations. The results suggest the presence of geographical barriers even in adjacent aquatic ecosystems that could restrict gene flow among G. giuris populations.This study supports the need for immediate conservation interventions for both species as they show a low level of genetic diversity in addition to being threatened in their own environment. Possible measures include translocation and establishment of a refuge population of the species studied to be complemented with location-specific strategies that would enhance their habitat conditions. In addition, education and enhancing the awareness of the local community regarding habitat protection are strongly recommended. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Ardestani, Goli; Rogelio, Diana Rose O.; Reyes, Roberto C.; Laude, Rita P.] Univ Philippines, Coll Arts & Sci, Inst Biol Sci, Los Banos Uplb, Philippines. [Ardestani, Goli] MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Ardestani, G (reprint author), MassGen Hosp Children, Pediat Endocrine Unit, 55 Fruit St,BHX410, Boston, MA 02114 USA. EM gardestani@mgh.harvard.edu FU Department of Science and Technology (DOST) in the Philippines FX The authors thank the Department of Science and Technology (DOST) in the Philippines for financial assistance through the Fish Ark project. The guidance and help of the personnel of the Molecular and Biology and Biotechnology (MBB) Laboratory of the University of the Philippines Los Banos are greatly appreciated. The authors would like to thank Dr David Rhoads of MassGeneral Hospital for Children (MGH) for his comments on the manuscript and inputs from Dr Finbarr Horgan of the International Rice Research Institute (IRRI). NR 42 TC 1 Z9 1 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1052-7613 EI 1099-0755 J9 AQUAT CONSERV JI Aquat. Conserv.-Mar. Freshw. Ecosyst. PD OCT PY 2014 VL 24 IS 5 BP 592 EP 600 DI 10.1002/aqc.2462 PG 9 WC Environmental Sciences; Marine & Freshwater Biology; Water Resources SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Water Resources GA AR7KH UT WOS:000343757800003 ER PT J AU Albiges, L De Velasco, G Fay, AP Caella, M Carvo, I Song, JX Genega, EM Gupta, M Bhatt, RS McDermott, DF Atkins, MB Vande Woude, GF Choueiri, TK Signoretti, S AF Albiges, Laurence De Velasco, Guillermo Fay, Andre P. Caella, Marcella Carvo, Ingrid Song, Jiaxi Genega, Elizabeth M. Gupta, Mamta Bhatt, Rupal S. McDermott, David F. Atkins, Michael B. Vande Woude, George F. Choueiri, Toni K. Signoretti, Sabina TI Differential expression of MET between primary and metastatic sites in clear cell Renal Cell Carcinomas (ccRCCs) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 13th International Kidney Cancer Symposium CY OCT 24-25, 2014 CL Chicago, IL C1 [Albiges, Laurence; De Velasco, Guillermo; Fay, Andre P.; Caella, Marcella; Carvo, Ingrid; Song, Jiaxi; Genega, Elizabeth M.; Gupta, Mamta; Bhatt, Rupal S.; McDermott, David F.; Choueiri, Toni K.; Signoretti, Sabina] Dana Farber Harvard Canc Ctr, Kidney Canc Program, Boston, MA USA. [Atkins, Michael B.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. [Vande Woude, George F.] Van Andel Res Inst, Grand Rapids, MI 49503 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 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD OCT PY 2014 VL 114 SU 4 SI SI BP 1 EP 1 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AS6TA UT WOS:000344393900002 ER PT J AU Choueiri, TK Plimack, ER Gupta, S Cho, D Hutson, TE Puzanov, I George, S Olencki, T Vaishampayan, U Chakrabarti, D Pithavala, YK Williams, JA Rosbrook, B Tarazi, JC Atkins, MB AF Choueiri, T. K. Plimack, E. R. Gupta, S. Cho, D. Hutson, T. E. Puzanov, I. George, S. Olencki, T. Vaishampayan, U. Chakrabarti, D. Pithavala, Y. K. Williams, J. A. Rosbrook, B. Tarazi, J. C. Atkins, M. B. TI Trial in progress: phase 1b dose-finding study of axitinib plus pembrolizumab for first-line treatment of advanced renal cell carcinoma (RCC) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 13th International Kidney Cancer Symposium CY OCT 24-25, 2014 CL Chicago, IL C1 [Choueiri, T. K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Plimack, E. R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Gupta, S.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Cho, D.] NYU, Med Ctr, New York, NY 10016 USA. [Hutson, T. E.] Baylor Sammons Canc Ctr Texas Oncol, Dallas, TX USA. [Puzanov, I.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [George, S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Olencki, T.] Ohio State Univ, Sch Med, Columbus, OH 43210 USA. [Vaishampayan, U.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Chakrabarti, D.] Pfizer Oncol, Collegeville, PA USA. [Pithavala, Y. K.; Williams, J. A.; Rosbrook, B.; Tarazi, J. C.] Pfizer Oncol, San Diego, CA USA. [Atkins, M. B.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. NR 1 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD OCT PY 2014 VL 114 SU 4 SI SI BP 4 EP 5 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA AS6TA UT WOS:000344393900008 ER PT J AU Fay, AP Van Allen, EM Murray, B Albiges, L Signoretti, S Ho, TH Hakimi, AA Mickey, S McDermott, DF Atkins, MB Garraway, LA Choueiri, TK AF Fay, Andre P. Van Allen, Eliezer M. Murray, Bradley Albiges, Laurence Signoretti, Sabina Ho, Thai H. Hakimi, A. Ari Mickey, Suzanne McDermott, David F. Atkins, Michael B. Garraway, Levi A. Choueiri, Toni K. TI Whole-exome sequencing predicting two extreme phenotypes of response to VEGF-targeted therapies in metastatic clear cell renal cell carcinoma (mRCC) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 13th International Kidney Cancer Symposium CY OCT 24-25, 2014 CL Chicago, IL C1 [Fay, Andre P.; Van Allen, Eliezer M.; Albiges, Laurence; Signoretti, Sabina; Mickey, Suzanne; McDermott, David F.; Garraway, Levi A.; Choueiri, Toni K.] Dana Farber Harvard Canc Ctr, Kidney Canc Program, Boston, MA USA. [Van Allen, Eliezer M.; Murray, Bradley; Garraway, Levi A.] Broad Inst & Harvard, Cambridge, MA USA. [Ho, Thai H.] Mayo Clin, Scottsdale, AZ USA. [Hakimi, A. Ari] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Atkins, Michael B.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD OCT PY 2014 VL 114 SU 4 SI SI BP 6 EP 7 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA AS6TA UT WOS:000344393900011 ER PT J AU Hammers, H Plimack, ER Infante, JR Ernstoff, MS Rini, B Mcdermott, DF Razak, A Pal, SK Voss, MH Sharma, P Kollmannsberger, C Heng, DYC Spratlin, J Shen, Y Kurland, JF Gagnier, P Amin, A AF Hammers, H. Plimack, E. R. Infante, J. R. Ernstoff, M. S. Rini, B. Mcdermott, D. F. Razak, A. Pal, S. K. Voss, M. H. Sharma, P. Kollmannsberger, C. Heng, D. Y. C. Spratlin, J. Shen, Y. Kurland, J. F. Gagnier, P. Amin, A. TI Phase I study of nivolumab in combination with ipilimumab (IPI) in metastatic renal cell carcinoma (mRCC) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 13th International Kidney Cancer Symposium CY OCT 24-25, 2014 CL Chicago, IL C1 [Hammers, H.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Plimack, E. R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Infante, J. R.] Sarah Cannon Res Inst Tennessee Oncol PLLC, Nashville, TN USA. [Ernstoff, M. S.] Norris Cotton Canc Ctr, Dartmouth Hitchcock Med Ctr, Geisel Sch Med, Lebanon, NH USA. [Rini, B.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Mcdermott, D. F.] Dana Farber Harvard Canc Ctr, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Razak, A.] Univ Toronto, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Pal, S. K.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Voss, M. H.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Sharma, P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kollmannsberger, C.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Heng, D. Y. C.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. [Spratlin, J.] Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada. [Shen, Y.; Kurland, J. F.; Gagnier, P.] Bristol Myers Squibb Co, Princeton, NJ USA. [Amin, A.] Levine Canc Inst, Charlotte, NC USA. NR 0 TC 0 Z9 1 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD OCT PY 2014 VL 114 SU 4 SI SI BP 8 EP 8 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AS6TA UT WOS:000344393900014 ER PT J AU Hammers, H Sternberg, C Mcdermott, DF Larkin, J Ravaud, A Rini, B Sharma, P Bhagavatheeswaran, P Gagnier, P Motzer, R AF Hammers, H. Sternberg, C. Mcdermott, D. F. Larkin, J. Ravaud, A. Rini, B. Sharma, P. Bhagavatheeswaran, P. Gagnier, P. Motzer, R. TI A phase 3, randomized, open-label study of nivolumab combined with ipilimumab versus sunitinib monotherapy in subjects with previously untreated metastatic renal cell carcinoma SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 13th International Kidney Cancer Symposium CY OCT 24-25, 2014 CL Chicago, IL C1 [Hammers, H.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Sternberg, C.] San Camillo Hosp, Rome, Italy. [Sternberg, C.] Forlanini Hosp, Rome, Italy. [Mcdermott, D. F.] Dana Farber Harvard Canc Ctr, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Larkin, J.] Royal Marsden NHS Fdn Trust, London, England. [Ravaud, A.] Hop St Andre, Bordeaux, France. [Rini, B.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Sharma, P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bhagavatheeswaran, P.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Gagnier, P.] Bristol Myers Squibb Co, Princeton, NJ USA. [Motzer, R.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD OCT PY 2014 VL 114 SU 4 SI SI BP 9 EP 9 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AS6TA UT WOS:000344393900015 ER PT J AU Kaymakcalan, MD Xie, WL Albiges, L North, S Kollmannsberger, C Smoragiewicz, M Kroeger, N Wells, JC Rha, SY Lee, JL Fay, AP Heng, DYC Choueiri, TK AF Kaymakcalan, Marina D. Xie, Wanling Albiges, Laurence North, Scott Kollmannsberger, Christian Smoragiewicz, Martin Kroeger, Nils Wells, J. Connor Rha, Sun-Young Lee, Jae Lyun Fay, Andre P. Heng, Daniel Y. C. Choueiri, Toni K. TI Risk factors and a model to predict toxicity-related treatment discontinuation in patients with metastatic renal cell carcinoma (mRCC) treated with vascular endothelial growth factor (VEGF)-targeted therapy: results from the international metastatic RCC database consortium (IMDC) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 13th International Kidney Cancer Symposium CY OCT 24-25, 2014 CL Chicago, IL C1 [Kaymakcalan, Marina D.; Xie, Wanling; Albiges, Laurence; Fay, Andre P.; Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [North, Scott; Heng, Daniel Y. C.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Kollmannsberger, Christian; Smoragiewicz, Martin] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Kroeger, Nils; Wells, J. Connor] Tom Baker Canc Clin, Calgary, AB, Canada. [Rha, Sun-Young] Yonsei Univ, Coll Med, Seoul, South Korea. [Lee, Jae Lyun] Asan Med Ctr, Seoul, South Korea. 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 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD OCT PY 2014 VL 114 SU 4 SI SI BP 11 EP 11 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AS6TA UT WOS:000344393900018 ER PT J AU Motzer, R Rini, B Mcdermott, D Redman, B Kuzel, T Harrison, M Vaishampayan, U Drabkin, H George, S Logan, T Margolin, K Plimack, ER Waxman, I Lambert, A Hammers, H AF Motzer, R. Rini, B. Mcdermott, D. Redman, B. Kuzel, T. Harrison, M. Vaishampayan, U. Drabkin, H. George, S. Logan, T. Margolin, K. Plimack, E. R. Waxman, I. Lambert, A. Hammers, H. TI Patients with PD-L1 expression by IHC 1/2/3 demonstrated evidence of increased activity. Durable responses were observed in mRCC patients, warranting further study Randomized, dose-ranging phase II trial of nivolumab for metastatic renal cell carcinoma (mRCC) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 13th International Kidney Cancer Symposium CY OCT 24-25, 2014 CL Chicago, IL C1 [Motzer, R.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Rini, B.] Dana Farber Harvard Canc Ctr, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Mcdermott, D.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Kuzel, T.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Harrison, M.] Duke Univ, Med Ctr, Durham, NC USA. [Vaishampayan, U.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Drabkin, H.] Med Univ S Carolina, Charleston, SC 29425 USA. [George, S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Logan, T.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Margolin, K.] Seattle Canc Care Alliance, Seattle, WA USA. [Plimack, E. R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Waxman, I.] Bristol Myers Squibb Co, Princeton, NJ USA. [Lambert, A.] Bristol Myers Squibb, Braine Lalleud, Belgium. [Hammers, H.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD OCT PY 2014 VL 114 SU 4 SI SI BP 12 EP 12 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AS6TA UT WOS:000344393900021 ER PT J AU Zinn, E Vandenberghe, LH AF Zinn, Eric Vandenberghe, Luk H. TI Adeno-associated virus: fit to serve SO CURRENT OPINION IN VIROLOGY LA English DT Article ID ASSEMBLY-ACTIVATING PROTEIN; ENHANCED GENE DELIVERY; DIRECTED EVOLUTION; CANINE PARVOVIRUS; RECEPTOR; HOST; SEROTYPES; THERAPY; PROTECTION; ANTIBODIES AB Adeno-associated virus (AAV) is a helper-dependent parvovirus which has not been linked with human disease. This aspect, in combination with its broad cell and tissue tropism, and limited viral host response has made it an attractive vector system for gene therapy. The viral protein capsid, the primary interface with the host, is the main determinant for these phenotypes, is highly variable, and is most subject to pressures during replication. Here, we explore the evolutionary path of AAV and other parvoviruses in respect to these phenotypes, as well as directed evolution and engineering strategies that have exploited the lessons learned from natural selection in order to address remaining limitations of AAV as a therapeutic gene transfer platform. C1 [Zinn, Eric; Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Vandenberghe, LH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. EM luk_vandenberghe@meei.harvard.edu OI Zinn, Eric/0000-0001-6993-5443 FU NIH [1DP1OD008267-01]; Curing Kids Fund; Foundation for Retinal Research; Foundation Fighting Blindness (Individual Investigator Award and Center Grant); Research to Prevent Blindness FX Research was supported by NIH 1DP1OD008267-01, The Curing Kids Fund, Foundation for Retinal Research, Foundation Fighting Blindness (Individual Investigator Award and Center Grant), Research to Prevent Blindness and Institutional Funds. EZ and LHV are inventors on patents related to AAV gene therapy. LHV has served as a consultant and is inventor on technologies licensed to biotechnology and pharmaceutical industries. LHV is co-founder and consultant to GenSight Biologics. NR 53 TC 14 Z9 15 U1 0 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1879-6257 J9 CURR OPIN VIROL JI Curr. Opin. Virol. PD OCT PY 2014 VL 8 BP 90 EP 97 DI 10.1016/j.coviro.2014.07.008 PG 8 WC Virology SC Virology GA AR8TE UT WOS:000343846400017 PM 25128609 ER PT J AU Loeken, MR AF Loeken, Mary R. TI Opportunities and challenges for repair of macrovascular disease using circulating blood-derived progenitor cells SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Editorial Material ID STEM/PROGENITOR CELLS; VASCULAR-DISEASE; BONE-MARROW; THERAPY AB There are currently few solutions for diabetic vascular disease that involve repair of damaged tissues. The manuscript by Porat et al. in this issue, suggests a possible method to use a patient's own circulating blood cells to provide progenitors to repair damaged vascular tissues. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 Joslin Diabet Ctr, Sect Islet & Regenerat Cell Biol, Boston, MA 02215 USA. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Sect Islet & Regenerat Cell Biol, One Joslin Pl, Boston, MA 02215 USA. EM mary.loeken@joslin.harvard.edu OI Loeken, Mary/0000-0002-8056-9816 FU NIDDK NIH HHS [R01 DK058300] NR 15 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1520-7560 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD OCT PY 2014 VL 30 IS 7 BP 554 EP 555 DI 10.1002/dmrr.2564 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AS0NX UT WOS:000343975300003 PM 25315433 ER PT J AU Dugast, AS Stamatatos, L Tonelli, A Suscovich, TJ Licht, AF Mikell, I Ackerman, ME Streeck, H Klasse, PJ Moore, JP Alter, G AF Dugast, Anne-Sophie Stamatatos, Leonidas Tonelli, Andrew Suscovich, Todd J. Licht, Anna F. Mikell, Iliyana Ackerman, Margaret E. Streeck, Hendrik Klasse, P. J. Moore, John P. Alter, Galit TI Independent evolution of Fc- and Fab-mediated HIV-1-specific antiviral antibody activity following acute infection SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE ADCC; Antibodies; HIV; IgG3 ID HUMAN-IMMUNODEFICIENCY-VIRUS; DEPENDENT CELLULAR CYTOTOXICITY; HIV-INFECTION; NEUTRALIZING ANTIBODY; TYPE-1 INFECTION; GLYCOFORM SELECTION; DISEASE PROGRESSION; GAMMA RECEPTORS; HIGH-THROUGHPUT; IGG SUBCLASSES AB Fc-related antibody activities, such as antibody-dependent cellular cytotoxicity (ADCC), or more broadly, antibody-mediated cellular viral inhibition (ADCVI), play a role in curbing early SIV viral replication, are enriched in human long-term infected nonprogressors, and could potentially contribute to protection from infection. However, little is known about the mechanism by which such humoral immune responses are naturally induced following infection. Here, we focused on the early evolution of the functional antibody response, largely driven by the Fc portion of the antibody, in the context of the evolving binding and neutralizing antibody response, which is driven mainly by the antibody-binding fragment (Fab). We show that ADCVI/ ADCC-inducing responses in humans are rapidly generated following acute HIV-1 infection, peak at approximately 6 months postinfection, but decay rapidly in the setting of persistent immune activation, as Fab-related activities persistently increase. Moreover, the loss of Fc activity occurred in synchrony with a loss of HIV-specific IgG3 responses. Our data strongly suggest that Fc- and Fab-related antibody functions are modulated in a distinct manner following acute HIV infection. Vaccination strategies intended to optimally induce both sets of antiviral antibody activities may, therefore, require a fine tuning of the inflammatory response. C1 [Dugast, Anne-Sophie; Tonelli, Andrew; Suscovich, Todd J.; Licht, Anna F.; Alter, Galit] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. [Stamatatos, Leonidas; Mikell, Iliyana] Seattle Biomed Res Inst, Seattle, WA 98109 USA. [Stamatatos, Leonidas; Mikell, Iliyana] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Ackerman, Margaret E.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Streeck, Hendrik] US Mil HIV Res Program, Silver Spring, MD USA. [Klasse, P. J.; Moore, John P.] Weill Cornell Med Coll, New York, NY USA. RP Alter, G (reprint author), MIT, Massachusetts Gen Hosp, Ragon Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM galter@partners.org RI Dugast, AnneSophie/L-9541-2015 FU [R01 AI080289]; [R01AI081625]; [R37 AI36082]; [OPP 1032817] FX We are grateful for technical assistance provided by Elizabeth Michael. This work was supported by R01 AI080289, R01AI081625, and R37 AI36082, Gates and OPP 1032817. NR 57 TC 19 Z9 19 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2014 VL 44 IS 10 BP 2925 EP 2937 DI 10.1002/eji.201344305 PG 13 WC Immunology SC Immunology GA AR8LW UT WOS:000343827600011 PM 25043633 ER PT J AU Korner, C Granoff, ME Amero, MA Sirignano, MN Vaidya, SA Jost, S Allen, TM Rosenberg, ES Altfeld, M AF Koerner, Christian Granoff, Mitchell E. Amero, Molly A. Sirignano, Michael N. Vaidya, Sagar A. Jost, Stephanie Allen, Todd M. Rosenberg, Eric S. Altfeld, Marcus TI Increased frequency and function of KIR2DL1-3(+) NK cells in primary HIV-1 infection are determined by HLA-C group haplotypes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE HIV-1; HLA-C; Inhibitory killer-cell immunoglobulin-like receptors (KIRs); Natural killer (NK) cells ID NATURAL-KILLER-CELL; VIRUS TYPE-1 INFECTION; IMMUNOGLOBULIN-LIKE RECEPTORS; CLASS-I; SURFACE EXPRESSION; SLOW PROGRESSORS; ACTIVATING KIRS; CYTOMEGALOVIRUS; EXPANSION; LIGAND AB The acquisition and maintenance of NK-cell function is mediated by inhibitory killer-cell immunoglobulin-like receptors (KIRs) through their interaction with HLA class I molecules. Recently, HLA-C expression levels were shown to be correlated with protection against multiple outcomes of HIV-1 infection; however, the underlying mechanisms are poorly understood. As HLA-C is the natural ligand for the inhibitory receptors KIR2DL1 and KIR2DL2/3, we sought to determine whether HLA-C group haplotypes affect NK-cell responses during primary HIV-1 infection. The phenotypes and functional capacity of NK cells derived from HIV-1-positive and HIV-1-negative individuals were assessed (N = 42 and N = 40, respectively). HIV-1 infection was associated with an increased frequency of KIR2DL1-3(+) NK cells. Further analysis showed that KIR2DL1(+) NK cells were selectively increased in individuals homozygous for HLA-C2, while HLA-C1-homozygous individuals displayed increased proportions of KIR2DL2/3(+) NK cells. KIR2DL1-3(+) NK cells were furthermore more polyfunctional during primary HIV-1 infection in individuals also encoding for their cognate HLA-C group haplotypes, as measured by degranulation and IFN-gamma and TNF-alpha production. These results identify a novel relationship between HLA-C and KIR2DL(+) NK-cell subsets and demonstrate that HLA-C-mediated licensing modulates NK-cell responses to primary HIV-1 infection. C1 [Koerner, Christian; Granoff, Mitchell E.; Amero, Molly A.; Sirignano, Michael N.; Vaidya, Sagar A.; Jost, Stephanie; Allen, Todd M.; Altfeld, Marcus] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Vaidya, Sagar A.; Rosenberg, Eric S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Altfeld, Marcus] Heinrich Pette Inst, Leibniz Inst Expt Virol, D-20251 Hamburg, Germany. RP Altfeld, M (reprint author), Heinrich Pette Inst, Leibniz Inst Expt Virol Head, Res Unit Viral Immunol, Martinistr 52, D-20251 Hamburg, Germany. EM marcus.altfeld@hpi.uni-hamburg.de RI Allen, Todd/F-5473-2011 FU National Institutes of Health (NIH) [R01-AI067031-08, P01-AI104715]; Doris Duke Charitable Foundation [208682]; Ragon Institute of MGH; MIT; Harvard; NIH [T32-AI07387-23, P30-AI060354-10] FX The authors gratefully acknowledge the support and assistance of the Ragon Institute Imaging Core for the flow cytometry experiments. The authors gratefully acknowledge the scientific advice by Mary Carrington, Maureen Martin and Ying Qi. The authors thank Angelique Holzemer and Wilfredo Garcia Beltran for helpful discussions. This study was supported by the National Institutes of Health (NIH) (R01-AI067031-08, P01-AI104715), the Doris Duke Charitable Foundation (#208682), and the Ragon Institute of MGH, MIT and Harvard. Sagar A. Vaidya was supported by the NIH (T32-AI07387-23, P30-AI060354-10). NR 48 TC 10 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2014 VL 44 IS 10 BP 2938 EP 2948 DI 10.1002/eji.201444751 PG 11 WC Immunology SC Immunology GA AR8LW UT WOS:000343827600012 PM 25043727 ER PT J AU Pensa, S Lloyd-Lewis, B Sargeant, TJ Resemann, HK Kahn, CR Watson, CJ AF Pensa, Sara Lloyd-Lewis, Bethan Sargeant, Timothy J. Resemann, Henrike K. Kahn, C. Ronald Watson, Christine J. TI Signal transducer and activator of transcription 3 and the phosphatidylinositol 3-kinase regulatory subunits p55 alpha and p50 alpha regulate autophagy in vivo SO FEBS JOURNAL LA English DT Article DE autophagy; mammary gland; p55; p50; PI3K; Stat3 ID MAMMARY-GLAND INVOLUTION; CELL-DEATH; STAT3; PATHWAY; APOPTOSIS; MICE; SUPPRESSION; PROTEINS; KNOCKOUT; CANCER AB Mammary gland involution involves a process that includes one of the most dramatic examples of cell death in an adult mammalian organism. We have previously shown that signal transducer and activator of transcription 3 (Stat3) regulates a lysosomal pathway of cell death in the first 48h of involution and induces lysosome leakiness in mammary epithelial cells. Interestingly, Stat3 is associated also with the striking induction of autophagy that occurs concomitantly with cell death, presumably as a transient survival mechanism. The phosphatidylinositol3-kinase regulatory subunits p55 and p50 are dramatically and specifically upregulated at the transcriptional level by Stat3 at the onset of involution. We show here that ablation of either Stat3 or p55/p50 invivo affects autophagy during involution. We used two different cell culture models (normal mammary epithelial cells and mouse embryonic fibroblasts) to further investigate the role of p55/p50 in autophagy regulation. Our results demonstrate a direct role for p55/p50 as inhibitors of autophagy mediated by p85. Thus, Stat3 and its downstream targets p55/p50 are key regulators of the balance between autophagy and cell death invivo. C1 [Pensa, Sara; Lloyd-Lewis, Bethan; Sargeant, Timothy J.; Resemann, Henrike K.; Watson, Christine J.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Watson, CJ (reprint author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England. EM cjw53@cam.ac.uk FU BBSRC; MRC [BB/D012937/1, MR/J001023/1]; Marie Curie IEF fellowship (EU Marie Curie grant) [273365]; Cambridge Cancer Centre FX We thank Beth Levine for critically reading the manuscript and for her helpful suggestions; Jeremy Skepper for assistance with the transmission electron microscopy; Helen Skelton for tissue histology; and members of C.J. Watson's laboratory for helpful discussions. This work was funded by BBSRC and MRC grants (BB/D012937/1 and MR/J001023/1) awarded to CJW. SP is the recipient of a Marie Curie IEF fellowship (EU Marie Curie grant number 273365). HKR is the recipient of a PhD studentship of the Cambridge Cancer Centre. NR 28 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1742-464X EI 1742-4658 J9 FEBS J JI FEBS J. PD OCT PY 2014 VL 281 IS 20 BP 4557 EP 4567 DI 10.1111/febs.13035 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AR9TG UT WOS:000343918500001 PM 25205393 ER PT J AU Zignego, AL Wojcik, GL Cacoub, P Visentini, M Casato, M Mangia, A Latanich, R Charles, ED Gragnani, L Terrier, B Piazzole, V Dustin, LB Khakoon, SI Busch, MP Lauer, GM Kim, AY Alric, L Thomas, DL Duggal, P AF Zignego, A. L. Wojcik, G. L. Cacoub, P. Visentini, M. Casato, M. Mangia, A. Latanich, R. Charles, E. D. Gragnani, L. Terrier, B. Piazzole, V. Dustin, L. B. Khakoon, S. I. Busch, M. P. Lauer, G. M. Kim, A. Y. Alric, L. Thomas, D. L. Duggal, P. TI Genome-wide association study of hepatitis C virus- and cryoglobulin-related vasculitis SO GENES AND IMMUNITY LA English DT Article ID MIXED CRYOGLOBULINEMIA; INFECTED PATIENTS; IMPUTATION; CELLS; RISK; SUSCEPTIBILITY; PREVALENCE; LYMPHOMAS; DISEASES; REGION AB The host genetic basis of mixed cryoglobulin vasculitis is not well understood and has not been studied in large cohorts. A genome-wide association study was conducted among 356 hepatitis C virus (HCV) RNA-positive individuals with cryoglobulin-related vasculitis and 447 ethnically matched, HCV RNA-positive controls. All cases had both serum cryoglobulins and a vasculitis syndrome. A total of 899 641 markers from the Illunnina HumanOmni1-Quad chip were analyzed using logistic regression adjusted for sex, as well as genetically determined ancestry. Replication of select single-nucleotide polymorphisms (SNPs) was conducted using 91 cases and 180 controls, adjusting for sex and country of origin. The most significant associations were identified on chromosome 6 near the NOTCH4 and MHC class II genes. A genome-wide significant association was detected on chromosome 6 at SNP rs9461776 (odds ratio = 2.16, P= 1.16E - 07) between HLA-DRB1 and DQA1: this association was further replicated in additional independent samples (meta-analysis P=7.1 x 10(-9)). A genome-wide significant association with cryoglobulin-related vasculitis was identified with SNPs near NOTCH4 and MHC Class II genes. The two regions are correlated and it is difficult to disentangle which gene is responsible for the association with mixed cryoglobulinemia vasculitis in this extended major histocompatibility complex region. C1 [Zignego, A. L.; Gragnani, L.] Univ Florence, Florence, Italy. [Wojcik, G. L.; Duggal, P.] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Cacoub, P.; Terrier, B.] Sorbonne Univ, Univ Paris 06, UMR 7211, Paris, France. [Cacoub, P.; Terrier, B.] Sorbonne Univ, Univ Paris 06, Inflammat Immunopathol Biotherapy Dept DHU i2B, Paris, France. [Cacoub, P.] INSERM, UMR S 959, Paris, France. [Cacoub, P.] CNRS, FRE3632, Paris, France. [Cacoub, P.] Grp Hosp Pitie Salpetriere, AP HP, Dept Internal Med & Clin Immunol, F-75634 Paris, France. [Visentini, M.; Casato, M.] Univ Rome, Rome, Italy. [Mangia, A.; Piazzole, V.] Casa Sollievo della Sofferenza Hosp, Liver Unit, San Giovanni Rotondo, Italy. [Latanich, R.; Thomas, D. L.] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. [Charles, E. D.] Rockefeller Univ, New York, NY 10021 USA. [Khakoon, S. I.] Univ Southampton, Southampton, Hants, England. [Busch, M. P.] Blood Syst Res Inst, San Francisco, CA USA. [Lauer, G. M.; Kim, A. Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Alric, L.] Univ Toulouse 3, CHU Purpan Hosp, F-31062 Toulouse, France. RP Duggal, P (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 North Wolfe St,E6539, Baltimore, MD 21205 USA. EM pduggal@jhu.edu RI GRAGNANI, LAURA/K-7751-2013; Dustin, Lynn/G-5690-2011; VISENTINI, MARCELLA/K-4161-2016; OI GRAGNANI, LAURA/0000-0001-6800-9149; Dustin, Lynn/0000-0002-2619-1867; VISENTINI, MARCELLA/0000-0002-4053-6091; Khakoo, Salim/0000-0002-4057-9091; CASATO, MILVIA/0000-0003-1841-6808 FU Merck through the National Institutes of Health [R01DA013324]; Office of AIDS Research; National Heart, Lung and Blood Institute [R01HL076902]; National Institutes of Health [R01 AI060561, K08AI075031, DA033541, AI066345, AI082630]; Center for Translational Science Award [CCL3001018]; Center for Translational Science Award from the National Center for Research Resources, a component of National Institutes of Health [UL1 RR024143]; Wellcome Trust [WT076991MA]; AIRC (Associazione Italiana per la Ricerca sul Cancro); ITT (Istituto Toscano Tumori); Fondazione Cassa di Risparmio di Firenze; Fondazione Umberto Veronesi FX This study was supported in part by research funding from Merck (to DLT and PD), through the National Institutes of Health, R01DA013324 (to DT) and the Office of AIDS Research. The REVELL study was funded by a grant from the National Heart, Lung and Blood Institute (R01HL076902). This work was supported in part by the National Institutes of Health (R01 AI060561 to LBD and K08AI075031 to EDC), Center for Translational Science Award (Pilot Grant CCL3001018; to EDC) and Center for Translational Science Award (Grant UL1 RR024143, to Rockefeller University), from the National Center for Research Resources, a component of National Institutes of Health. GML and AYK are supported by grants from the National Institutes of Health (DA033541, AI066345 and AI082630). The work was supported by a Wellcome Trust SCF Grant (WT076991MA) to SIK. The study was funded by AIRC (Associazione Italiana per la Ricerca sul Cancro), by ITT (Istituto Toscano Tumori) and by Fondazione Cassa di Risparmio di Firenze; Dr LG was supported by a fellowship from Fondazione Umberto Veronesi. NR 40 TC 15 Z9 15 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 EI 1476-5470 J9 GENES IMMUN JI Genes Immun. PD OCT-NOV PY 2014 VL 15 IS 7 BP 500 EP 505 DI 10.1038/gene.2014.41 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA AS0IG UT WOS:000343960500009 PM 25030430 ER PT J AU Ausubel, FM AF Ausubel, Frederick M. TI Twists and Turns: My Career Path and Concerns About the Future SO GENETICS LA English DT Editorial Material ID GENES; COMPLEMENTATION; MUTAGENESIS; MUTANTS; SITE AB THE Genetics Society of America's Thomas Hunt Morgan Medal is awarded to an individual GSA member for lifetime achievement in the field of genetics. The 2014 recipient is Frederick Ausubel, whose 40-year career has centered on host-microbe interactions and host innate immunity. He is widely recognized as a key scientist responsible for establishing the modern postrecombinant DNA field of host-microbe interactions using simple nonvertebrate hosts. He has used genetic approaches to conduct pioneering work that spawned six related areas of research: the evolution and regulation of Rhizobium genes involved in symbiotic nitrogen fixation; the regulation of Rhizobium genes by two-component regulatory systems involving histidine kinases; the establishment of Arabidopsis thaliana as a worldwide model system; the identification of a large family of plant disease resistance genes; the identification of so-called multi-host bacterial pathogens; and the demonstration that Caenorhabditis elegans has an evolutionarily conserved innate immune system that shares features of both plant and mammalian immunity. C1 [Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. FU NIDDK NIH HHS [P30 DK040561] NR 11 TC 0 Z9 0 U1 3 U2 6 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD OCT PY 2014 VL 198 IS 2 BP 431 EP 434 DI 10.1534/genetics.114.169102 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA AR9HX UT WOS:000343885300004 PM 25316778 ER PT J AU Duska, LR Blessing, JA Rotmensch, J Mannel, RS Hanjani, P Rose, PG Dizon, DS AF Duska, Linda R. Blessing, John A. Rotmensch, Jacob Mannel, Robert S. Hanjani, Parviz Rose, Peter G. Dizon, Don S. TI A Phase II evaluation of ixabepilone (IND #59699, NSC #710428) in the treatment of recurrent or persistent leiomyosarcoma of the uterus: An NRG Oncology/Gynecologic Oncology Group Study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ixabepilone; Uterine leiomyosarcoma ID GEMCITABINE PLUS DOCETAXEL; ADVANCED UTERINE SARCOMA; SOFT-TISSUE SARCOMA; SOLID TUMORS; 2ND-LINE CHEMOTHERAPY; PROGNOSTIC FACTORS; EPOTHILONE ANALOG; TRIAL; THERAPY; PACLITAXEL AB Objective. The combination of gemcitabine and docetaxel is the standard first-line therapy for recurrent or metastatic uterine leiomyosarcoma. There is no standard second-line therapy. Ixabepilone is a semi-synthetic analog of epothilone B that binds to the same site on beta tubulin as paclitaxel and may be a more potent polymerizer of tubulin. We sought to determine the activity of ixabepilone as a single agent as second-line treatment for patients with metastatic uterine leiomyosarcoma who had received taxane based therapy. Methods. Eligible-women with unresectable uterine leiomyosarcoma progressing after prior cytotoxic therapy containing a taxane were treated with ixabepilone 40 mg/m(2) on day one of a 21 day cycle. Patients with prior pelvic radiation were treated without dose reduction. Response Evaluation Criteria in Solid Tumors (RECIST) response was assessed by computed tomography (CT). Results. Twenty-three of 26 women were evaluable (two wrong histology, one never treated) with two of 23 receiving 1 cycle of therapy. There were no complete or partial responses. Stable disease (SD) was seen in four patients (17.4%, median 3.4 months). Seventeen patients (73.9%) had increasing disease (PD) and two patients were inevaluable per RECIST. One patient had SD over 6 cycles of treatment. Median PFS for all 23 patients was 1.4 months and overall survival was 7.0 months. The predominant grade 3 or 4 toxicity was uncomplicated myelosuppression: neutropenia grade 3 (13%), grade 4 (17%), and anemia grade 3 (22%). Conclusion. Ixabepilone as a single agent is not an active second-line therapy for uterine leiomyosarcoma previously treated with a taxane. (C) 2014 Elsevier Inc. All rights reserved. C1 [Duska, Linda R.] Univ Virginia Hlth Syst, Div Gynecol Oncol, Charlottesville, VA 22908 USA. [Blessing, John A.] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. [Rotmensch, Jacob] Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. [Mannel, Robert S.] Univ Oklahoma, Hlth Sci Ctr, Peggy & Charles Stephenson Canc Ctr, Oklahoma City, OK 73104 USA. [Hanjani, Parviz] Abington Mem Hosp, Hanjani Inst Gynecol Oncol, Abington, PA 19001 USA. [Rose, Peter G.] Cleveland Clin, Cleveland, OH 44195 USA. [Dizon, Don S.] Massachusetts Gen Hosp, GYN Oncol, Boston, MA 02114 USA. RP Duska, LR (reprint author), Univ Virginia Hlth Syst, Div Gynecol Oncol, POB 800712, Charlottesville, VA 22908 USA. EM lduska@virginia.edu; blessing@gogstats.org; jacob_rotmensch@rush.edu; Robert-mannel@ouhsc.edu; phanjani@amh.org; rosep@ccf.org; ddizon@partners.org FU National Cancer Institute [CA 27469]; Gynecologic Oncology Group Statistical Office [CA 37517]; NRG Oncology Grant [1 U10 CA180822] FX This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical Office (CA 37517) and the NRG Oncology Grant (1 U10 CA180822). The following Gynecologic Oncology Group member institutions participated in the primary treatment studies: Abington Memorial Hospital, Walter Reed National Military Medical Center, University of Mississippi Medical Center, University of North Carolina at Chapel Hill, Rush University Medical Center, Cleveland Clinic Foundation, Washington University School of Medicine, Women's Cancer Center of Nevada, University of Oklahoma Health Sciences Center, University of Virginia, University of Chicago, Case Western Reserve University, University of Wisconsin Hospital and Clinics, Women and Infants Hospital, and Carolinas Medical Center/Levine Cancer Institute. NR 47 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2014 VL 135 IS 1 BP 44 EP 48 DI 10.1016/j.ygyno.2014.07.101 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AS0GK UT WOS:000343955900009 PM 25091619 ER PT J AU Worley, MJ Davis, M Berhie, SH Muto, MG Feltmate, CM Berkowitz, RS Horowitz, NS Campos, SM AF Worley, Michael J., Jr. Davis, Michelle Berhie, Saba H. Muto, Michael G. Feltmate, Colleen M. Berkowitz, Ross S. Horowitz, Neil S. Campos, Susana M. TI Mucinous differentiation does not impact stage or risk of recurrence among patients with grade 1, endometrioid type, endometrial carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Mucinous differentiation; Endometrial cancer; Well differentiated ID GYNECOLOGIC-ONCOLOGY-GROUP; ADENOCARCINOMA; CANCER AB Objective. To evaluate whether the presence of mucinous differentiation influences histopathologic findings, stage distribution, or rate of recurrence among women with grade 1, endometrioid type, endometrial carcinoma. Methods. This was a retrospective cohort study of all patients with grade 1, endornetrioid type, endometrial carcinoma between January 2005 and December 2012. Patients were separated by the presence or absence of mucinous differentiation and then compared. Results. Of 655 patients, mucinous differentiation was present in 137 (20.9%) and absent in 518 (79.1%) patients. Compared to the group without mucinous differentiation, the group containing mucinous differentiation was older at diagnosis (mean: 61.1 vs. 58.5 years, OR, 95% CI; 1.03, 1.01-1.05) and more likely to have myometrial invasion (61.3% vs. 51.5%, OR, 95% CI; 1.49, 1.01-2.19). Additional histopathologic findings including: tumor size, cervical stromal invasion, adnexal involvement, LVI and/or the presence of positive lymph nodes were similar between groups. Mucinous differentiation did not affect stage distribution, as most patients were stage 1A (85.4% vs. 863%). The median PFS for the entire group has yet to be reached. The mean PFS for the entire study sample was 94.7 months. There was no difference in mean PFS when comparing the group with mucinous differentiation to the group without mucinous differentiation (98 vs. 93.4 months, p = 0.07). Conclusions. In the setting of grade 1, endometrioid type, endometrial carcinoma, mucinous differentiation is more common in older patients and is associated with an increased likelihood of myometrial invasion. However, stage distribution and risk of recurrence are not affected. (C) 2014 Elsevier Inc. All rights reserved. C1 [Worley, Michael J., Jr.; Muto, Michael G.; Feltmate, Colleen M.; Berkowitz, Ross S.; Horowitz, Neil S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. [Davis, Michelle] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Berhie, Saba H.] Harvard Univ, Sch Med, Boston, MA USA. [Campos, Susana M.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02215 USA. RP Campos, SM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Susana_campos@dfci.harvard.edu NR 12 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 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2014 VL 135 IS 1 BP 54 EP 57 DI 10.1016/j.ygyno.2014.07.098 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AS0GK UT WOS:000343955900011 PM 25088333 ER PT J AU Huckfeldt, RM Shah, AS AF Huckfeldt, Rachel M. Shah, Ankoor S. TI Sterile subperiosteal fluid collections accompanying orbital wall infarction in sickle-cell disease SO JOURNAL OF AAPOS LA English DT Article ID COMPRESSION SYNDROME; OSTEOMYELITIS; CELLULITIS; CHILDREN; ANEMIA AB Infarction of the orbital wall is an uncommon manifestation of sickle cell disease (SCD) that may mimic an infectious process. We report a patient with two separate orbital infarctions with different presenting symptoms involving different bones. Radiologic-guided sampling of a periosteal fluid collection in the first episode showed likely sterile inflammatory exudates. This case highlights the range of findings in orbital wall infarction in SCD as well as helpful clinical and imaging entities that may differentiate infarction from infection, allowing early diagnosis and appropriate management. C1 [Shah, Ankoor S.] Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Shah, AS (reprint author), Boston Childrens Hosp, Dept Ophthalmol, Fegan 4,300 Longwood Ave, Boston, MA 02115 USA. EM ankoor.shah@childrens.harvard.edu NR 12 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 EI 1528-3933 J9 J AAPOS JI J. AAPOS PD OCT PY 2014 VL 18 IS 5 BP 485 EP 487 DI 10.1016/j.jaapos.2014.04.004 PG 3 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA AR8XH UT WOS:000343854200017 PM 25439304 ER PT J AU Tiedemann, LM Lefebvre, DR Wan, MJ Dagi, LR AF Tiedemann, Laura M. Lefebvre, Daniel R. Wan, Michael J. Dagi, Linda R. TI Iatrogenic inferior oblique palsy: intentional disinsertion during transcaruncular approach to orbital fracture repair SO JOURNAL OF AAPOS LA English DT Article AB Hypotropia following orbital fracture repair is traditionally attributed to residual tissue entrapment, scarring, direct muscle injury, or damage to the branches of the oculomotor nerve serving the inferior oblique or inferior rectus muscles. We present a case of acquired hypotropia and incyclotropia that occurred following repair of an orbital fracture involving the floor and medial wall. In order to enable adequate visualization and treatment of the combined fractures, access via a transcaruncular approach and disinsertion of the inferior oblique muscle at its origin was necessary. Whereas the possibility of inferior oblique paresis due to repair of an orbital fracture via the transcaruncular approach has received some acknowledgment, there are no prior reports in the ophthalmic literature. Strabismus surgeons should be aware of this possibility when planning surgical correction of hypotropia and incyclotropia in similar cases. C1 [Tiedemann, Laura M.; Wan, Michael J.; Dagi, Linda R.] Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. [Lefebvre, Daniel R.] Massachusetts Eye & Ear Infirm, Div Ophthalm Plast Surg, Boston, MA 02114 USA. [Lefebvre, Daniel R.; Wan, Michael J.; Dagi, Linda R.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Dagi, LR (reprint author), Boston Childrens Hosp, Dept Ophthalmol, Fegan 4,300 Longwood Avenues, Boston, MA 02115 USA. EM Linda.Dagi@childrens.harvard.edu NR 4 TC 2 Z9 2 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 EI 1528-3933 J9 J AAPOS JI J. AAPOS PD OCT PY 2014 VL 18 IS 5 BP 511 EP 514 DI 10.1016/j.jaapos.2014.06.005 PG 4 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA AR8XH UT WOS:000343854200029 PM 25266842 ER PT J AU Arfianti, E Barn, V Haigh, WG Ioannou, GN Teoh, N Farrell, G AF Arfianti, E. Barn, V. Haigh, W. G. Ioannou, G. N. Teoh, N. Farrell, G. TI Exercise slows growth of dysplastic hepatocytes by improving insulin sensitivity and enhancing DNA damage surveillance pathways in mice genetically predisposed to obesity and diabetes SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 [Arfianti, E.; Barn, V.; Teoh, N.; Farrell, G.] Canberra Hosp, ANU Med Sch, Liver Res Grp, Garran, ACT, Australia. [Haigh, W. G.; Ioannou, G. N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA USA. [Haigh, W. G.; Ioannou, G. N.] Univ Washington, Seattle, WA 98195 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 EI 1440-1746 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD OCT PY 2014 VL 29 SU 2 SI SI BP 1 EP 1 DI 10.1111/jgh.12736_2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AR9AM UT WOS:000343863000002 ER PT J AU Jais, B Rebours, V Tang, Y Gill, R Leong, RWL Malleo, G Salvia, R Moran, R Lennon, AM Marchegiani, G Castillo, CF Ha, Y Kim, MH Hirai, I Kimura, W Jang, JY Kim, SW Kang, CM Lee, WJ Crippa, S Falconi, M Gomatos, IP Neoptolemos, J Milanetto, AC Sperti, C Ricci, C Casadei, R Bissolati, M Balzano, G Frigerio, I Girelli, R Delhaye, M Bernier, B Wang, H Jang, KT Song, DH Huggett, M Oppong, K Pererva, L Kopchak, K Chiaro, MD Segersvard, R Lee, LS Conwell, D Oswaldt, A Campos, V Garcete, GA Napoleon, B Levy, P AF Jais, B. Rebours, V. Tang, Y. Gill, R. Leong, R. W. L. Malleo, G. Salvia, R. Moran, R. Lennon, A. M. Marchegiani, G. Castillo, C. F. Ha, Y. Kim, M. H. Hirai, I. Kimura, W. Jang, J. Y. Kim, S. W. Kang, C. M. Lee, W. J. Crippa, S. Falconi, M. Gomatos, I. P. Neoptolemos, J. Milanetto, A. C. Sperti, C. Ricci, C. Casadei, R. Bissolati, M. Balzano, G. Frigerio, I. Girelli, R. Delhaye, M. Bernier, B. Wang, H. Jang, K. T. Song, D. H. Huggett, M. Oppong, K. Pererva, L. Kopchak, K. Chiaro, M. D. Segersvard, R. Lee, L. S. Conwell, D. Oswaldt, A. Campos, V. Garcete, G. A. Napoleon, B. Levy, P. TI Pancreatic serous cystadenoma-related mortality is almost nil - results of a multinational study under the auspices of the International Association of Pancreatology and the European Pancreatic Club SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 [Jais, B.; Rebours, V.; Levy, P.] Hop Beaujon, Clichy, France. [Tang, Y.; Leong, R. W. L.] Concord Gen Repatriat Hosp, Sydney, NSW, Australia. [Gill, R.; Leong, R. W. L.] Bankstown Lidcombe Hosp, Sydney, NSW, Australia. [Malleo, G.; Salvia, R.] Univ Verona Hosp Trust, Verona, Italy. [Moran, R.; Lennon, A. M.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Marchegiani, G.; Castillo, C. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ha, Y.; Kim, M. H.] Asan Med Ctr, Seoul, South Korea. [Hirai, I.; Kimura, W.] Yamagata Univ, Fac Med, Yamagata 990, Japan. [Jang, J. Y.; Kim, S. W.] Seoul Natl Univ, Seoul, South Korea. [Kang, C. M.; Lee, W. J.] Yonsei Univ, Severance Hosp, Seoul 120749, South Korea. [Crippa, S.; Falconi, M.] Osped Riuniti Acad Hosp, Ancona, Italy. [Gomatos, I. P.; Neoptolemos, J.] Royal Liverpool & Broadgreen Univ Hosp, Liverpool, Merseyside, England. [Milanetto, A. C.; Sperti, C.] Univ Padua, Padua, Italy. [Ricci, C.; Casadei, R.] St Orsola Marcello Malpighi Hosp, Bologna, Italy. [Bissolati, M.; Balzano, G.] Ist Sci San Raffaele, I-20132 Milan, Italy. [Frigerio, I.; Girelli, R.] Clin Pederzoli, Pancreat Unit, Verona, Italy. [Delhaye, M.; Bernier, B.] Free Univ Brussels, Erasme Hosp, B-1050 Brussels, Belgium. [Wang, H.] Southwest Hosp, Chongqing, Peoples R China. [Jang, K. T.; Song, D. H.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Huggett, M.; Oppong, K.] Freeman Rd Hosp, Newcastle Upon Tyne, Tyne & Wear, England. [Pererva, L.; Kopchak, K.] Natl Inst Surg & Transplantol, Kiev, Ukraine. [Chiaro, M. D.; Segersvard, R.] Karolinska Univ Hosp, Stockholm, Sweden. [Lee, L. S.; Conwell, D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Oswaldt, A.; Campos, V.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Garcete, G. A.; Napoleon, B.] Hop Prive Jean Mermoz, Lyon, France. NR 0 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 EI 1440-1746 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD OCT PY 2014 VL 29 SU 2 SI SI BP 48 EP 48 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AR9AM UT WOS:000343863000091 ER PT J AU Greer, JA Pirl, WF Jackson, VA Muzikansky, A Lennes, IT Gallagher, ER Prigerson, HG Temel, JS AF Greer, Joseph A. Pirl, William F. Jackson, Vicki A. Muzikansky, Alona Lennes, Inga T. Gallagher, Emily R. Prigerson, Holly G. Temel, Jennifer S. TI Perceptions of Health Status and Survival in Patients With Metastatic Lung Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Non-small cell lung cancer; metastatic; health status; survival ID EARLY PALLIATIVE CARE; COOPERATIVE-ONCOLOGY-GROUP; OF-LIFE CARE; TREATMENT PREFERENCES; OLDER PERSONS; STAGE CANCER; DEPRESSION; CHEMOTHERAPY; OUTCOMES; END AB Context. Cognitive awareness of having a terminal illness is associated with critical treatment decisions and outcomes. However, little is known about the course and correlates of such perceptions in patients with metastatic lung cancer. Objectives. We explored changes in perceptions of health status over time in patients with metastatic non-small cell lung cancer (NSCLC) and whether awareness of having a terminal illness was associated with survival. Methods. For this secondary analysis of clinical trial data, we assessed perceptions of health status at baseline, 12, 18, and 24 weeks. At each time point, patients with metastatic NSCLC completed a measure of quality of life (Functional Assessment of Cancer Therapy-Trial Outcome Index) and also reported whether they were "relatively healthy,'' "seriously but not terminally ill,'' or "seriously and terminally ill.'' We reviewed patients' medical records to gather data on clinical characteristics. Results. At baseline, 49.3% reported being relatively healthy, whereas the remainder self-identified as seriously but not terminally ill (38.2%) or seriously and terminally ill (12.5%). Over multiple assessments, 24.8% reported having a terminal illness. Adjusting for known prognostic factors, patients' time-varying perceptions of health status remained a significant predictor of survival (hazards ratio = 1.50, 95% CI = 1.07-2.09, P = 0.019). Conclusion. A minority of patients with metastatic NSCLC acknowledged being terminally ill. Those reporting that they were seriously and terminally ill had shorter survival compared with those who did not consider themselves terminally ill, even after adjusting for decline in physical and functional well-being. (C) 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Greer, Joseph A.; Pirl, William F.; Jackson, Vicki A.; Muzikansky, Alona; Lennes, Inga T.; Gallagher, Emily R.; Temel, Jennifer S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Prigerson, Holly G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Greer, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Yawkey Bldg,Suite 10B,55 Fruit St, Boston, MA 02114 USA. EM jgreer2@mgh.harvard.edu FU American Society of Clinical Oncology Career Development Award FX This work was supported by an American Society of Clinical Oncology Career Development Award (Principal Investigator: Dr. Temel), and gifts from the Joanne Hill Monahan Cancer Fund and Golf Fights Cancer. The authors declare no conflicts of interest. NR 31 TC 5 Z9 5 U1 0 U2 2 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 OCT PY 2014 VL 48 IS 4 BP 548 EP 557 DI 10.1016/j.jpainsymman.2013.10.016 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AR8YF UT WOS:000343856500008 PM 24680623 ER PT J AU Garrido, MM AF Garrido, Melissa M. TI Propensity Scores: A Practical Method for Assessing Treatment Effects in Pain and Symptom Management Research SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Propensity score; treatment effect; causality; randomized controlled trial; palliative care ID MENTAL-HEALTH-CARE; CAUSAL INFERENCE; MEDICAL-RESEARCH; OLDER-ADULTS; MODEL; PRINCIPLES; BALLOON; TRIALS; COSTS AB When conducting research on pain and symptom management interventions for seriously ill individuals, randomized controlled trials are not always feasible or ethical to conduct. Secondary analyses of observational data sets that include information on treatments experienced and outcomes for individuals who did and did not receive a given treatment can be conducted, but confounding because of selection bias can obscure the treatment effect in which one is interested. Propensity scores provide a way to adjust for observable characteristics that differ between treatment and comparison groups. This article provides conceptual guidance in addition to an empirical example to illustrate two areas of propensity score analysis that often lead to confusion in practice: covariate selection and interpretation of resultant treatment effects. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine. C1 [Garrido, Melissa M.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Garrido, Melissa M.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. RP Garrido, MM (reprint author), James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, 4A-17,130 W, Bronx, NY USA. OI Garrido, Melissa/0000-0002-8986-3536 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [11-201/CDP 12-255]; National Palliative Care Research Center FX Dr. Garrido is supported by a Career Development Award from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (CDA 11-201/CDP 12-255). The views expressed in this article are those of the author and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. government. Data collection for this study was supported by a Junior Faculty Career Development Award from the National Palliative Care Research Center. The author declares no conflicts of interest. NR 25 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD OCT PY 2014 VL 48 IS 4 BP 711 EP 718 DI 10.1016/j.jpainsymman.2014.05.014 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AR8YF UT WOS:000343856500022 PM 24937162 ER PT J AU Kinnier, CV Asare, EA Mohanty, S Paruch, JL Rajaram, R Bilimoria, KY AF Kinnier, Christine V. Asare, Elliot A. Mohanty, Sanjay Paruch, Jennifer L. Rajaram, Ravi Bilimoria, Karl Y. TI Risk Prediction Tools in Surgical Oncology SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE decision support techniques; patient-centered care; nomograms; health literacy ID TREATMENT DECISION-MAKING; PATIENT-CENTERED CARE; INFLAMMATORY-BOWEL-DISEASE; EARLY BREAST-CANCER; PROGNOSTIC MODEL; REPORTED OUTCOMES; INFORMED-CONSENT; RANDOMIZED-TRIAL; HEALTH LITERACY; AID AB Healthcare has increasingly focused on patient engagement and shared decision-making. Decision aids can promote engagement and shared decision making by providing patients and their providers with care options and outcomes. This article discusses decision aids for surgical oncology patients. Topics include: short-term risk prediction following surgery, long-term risk prediction of survival and recurrence, the combination of short-and long-term risk prediction to help guide treatment choice, and decision aid usability, transparency, and accessibility. (C) 2014 Wiley Periodicals, Inc. C1 [Kinnier, Christine V.; Bilimoria, Karl Y.] Northwestern Univ, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Kinnier, Christine V.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Asare, Elliot A.; Mohanty, Sanjay; Paruch, Jennifer L.; Rajaram, Ravi] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Asare, Elliot A.] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Mohanty, Sanjay] Henry Ford Hosp, Dept Surg, Detroit, MI 48202 USA. [Paruch, Jennifer L.] Univ Chicago, Pritzker Sch Med, Dept Surg, Chicago, IL 60637 USA. [Rajaram, Ravi] Northwestern Univ, Feinberg Sch Med, Ctr Healthcare Studies, Chicago, IL 60611 USA. [Rajaram, Ravi] NW Mem Hosp, Dept Surg, Chicago, IL 60611 USA. [Bilimoria, Karl Y.] Robert H Lurie Comprehens Canc Ctr, Northwestern Inst Comparat Effectiveness Res NICE, Chicago, IL USA. RP Bilimoria, KY (reprint author), Northwestern Univ, Dept Surg, Surg Outcomes & Qual Improvement Ctr, 676 N St Clair St,Suite 6-650, Chicago, IL 60611 USA. EM k-bilimoria@northwestern.edu NR 67 TC 3 Z9 3 U1 0 U2 2 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 OCT PY 2014 VL 110 IS 5 SI SI BP 500 EP 508 DI 10.1002/jso.23714 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA AR9FP UT WOS:000343878500004 PM 24975865 ER PT J AU Kneisl, JS Coleman, MM Raut, CP AF Kneisl, Jeffrey S. Coleman, Michelle M. Raut, Chandrajit P. TI Outcomes in the Management of Adult Soft Tissue Sarcomas SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE outcomes; management; soft tissue sarcoma; retroperitoneal sarcoma; gastrointestinal stromal tumor ID GASTROINTESTINAL STROMAL TUMORS; TERM-FOLLOW-UP; PHASE-II TRIAL; MICROSCOPICALLY POSITIVE MARGINS; POSITRON-EMISSION-TOMOGRAPHY; AMERICAN JOINT COMMITTEE; CANCER-CENTERS-SARCOMA; LYMPH-NODE METASTASIS; IMATINIB MESYLATE; RETROPERITONEAL SARCOMA AB Adult soft tissue sarcomas (STSs) are heterogeneous neoplasms that account for 11,410 new diagnoses and 4,390 deaths per year. This article summarizes recent NCCN guidelines for diagnosis and management of STSs of the extremities and retroperitoneum, as well as gastrointestinal stromal tumors (GIST). AJCC staging and recently reported NCDB data regarding outcomes are reviewed. Currently accepted STS prognostic variables are presented, as are future directions regarding the utility of molecular prognosticators and nomograms. (C) 2014 Wiley Periodicals, Inc. C1 [Kneisl, Jeffrey S.] Carolinas Healthcare Syst, Levine Canc Inst, Dept Orthopaed Surg, Charlotte, NC 28204 USA. [Coleman, Michelle M.] Univ N Carolina, Dept Biol, Charlotte, NC 28223 USA. [Raut, Chandrajit P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Dana Farber Canc Inst,Ctr Sarcoma & Bon, Boston, MA 02115 USA. RP Kneisl, JS (reprint author), Carolinas Healthcare Syst, Levine Canc Inst, Dept Orthopaed Surg, 1021 Morehead Med Dr, Charlotte, NC 28204 USA. EM jeffrey.kneisl@carolinashealthcare.org NR 103 TC 8 Z9 9 U1 1 U2 6 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 OCT PY 2014 VL 110 IS 5 SI SI BP 527 EP 538 DI 10.1002/jso.23685 PG 12 WC Oncology; Surgery SC Oncology; Surgery GA AR9FP UT WOS:000343878500007 PM 24965077 ER PT J AU Shnaider, P Vorstenbosch, V Macdonald, A Wells, SY Monson, CM Resick, PA AF Shnaider, Philippe Vorstenbosch, Valerie Macdonald, Alexandra Wells, Stephanie Y. Monson, Candice M. Resick, Patricia A. TI Associations Between Functioning and PTSD Symptom Clusters in a Dismantling Trial of Cognitive Processing Therapy in Female Interpersonal Violence Survivors SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CLINICAL-TRIAL; RESIDUAL INSOMNIA; CHILDHOOD ABUSE; VETERANS; EXPOSURE; SCALE; AVOIDANCE; VICTIMS AB This study conducted secondary analyses of a published trial and sought to determine if different domains of psychosocial functioning (e.g., daily living, work, nonfamily relationships) improved following trauma-focused treatment for posttraumatic stress disorder (PTSD). Cognitive processing therapy (CPT), an empirically supported treatment that involves evaluating trauma-related beliefs and written trauma accounts, was compared to its components: CPT without the written accounts or written accounts only in a sample of 78 women with PTSD secondary to interpersonal violence. Overall and individual domains of functioning significantly improved with treatment and results were similar across treatment groups, Fs (2, 150) 11.87, ps < .001. Additionally, we investigated whether changes in different PTSD symptom clusters were associated with outcomes in domains of psychosocial functioning, after collapsing across treatment condition. Multiple hierarchical linear regression analyses revealed that overall clinician-assessed PTSD symptom reduction was associated with outcomes in all domains of functioning, s = .44 to .68, ps < .001. Additionally, improvements in the emotional numbing symptom cluster were associated with outcomes in the nonfamily relationships domain, = .42, p < .001, and improvements in the hyperarousal symptom cluster were associated with outcomes in the overall, daily living, and household tasks domains, s = .34 to .39, ps < .01. Results suggest that it may be important to monitor improvements in emotional numbing and hyperarousal symptoms throughout treatment to increase the likelihood of changes in psychosocial functioning. Resumen Este estudio condujo un analisis secundario de un ensayo publicado y busco determinar si diferentes dominios de funcionamiento psicosocial (ej., vida diaria, trabajo, relaciones no familiares) mejoraron despues de un tratamiento enfocado en el trauma para trastorno por estres post-traumatico (TEPT). La terapia de procesamiento cognitivo (TPC), un tratamiento respaldado empiricamente que involucra la evaluacion de las creencias relacionadas al trauma y los relatos escritos del trauma, fue comparado con sus componentes: TPC sin los relatos escritos o solamente relatos escritos en una muestra de 78 mujeres con TEPT secundario a violencia interpersonal. Los dominios de funcionamiento generales e individuales aumentaron significativamente con el tratamiento y los resultados fueron similares a traves de los grupos de tratamiento, Fs (2, 150) 11.87, ps < .001. Adicionalmente, investigamos si los cambios en los diferentes grupos de sintomas de TEPT se asociaron con resultados en dominios de funcionamiento psicosocial, despues de colapsar a traves de las condiciones de tratamiento. Un analisis de regresion linear multiple jerarquica revelo que la reduccion general de sintomas de TEPT evaluada por clinicos se asocio con los resultados en todos los dominios de funcionamiento s = .44 to .68, ps < .001. Adicionalmente, mejorias en el grupo de sintomas de entumecimiento emocional se asociaron con los resultados del dominio de relaciones no familiares, = .42,p < .001, y mejorias en el grupo de sintomas de hiperexcitabilidad se asociaron con los resultados generales en los dominios, de vida diaria y tareas domesticas s = .34 to .39, ps < .01.Los resultados sugieren que puede ser importante monitorear las mejorias en los sintomas de entumecimiento emocional e hiperexcitabilidad a lo largo del tratamiento para aumentar la probabilidad de cambios en el funcionamiento psicosocial. C1 [Shnaider, Philippe; Monson, Candice M.] Ryerson Univ, Dept Psychol, Toronto, ON M5B 2K3, Canada. [Vorstenbosch, Valerie] Sunnybrook Hlth Sci Ctr, Frederick W Thompson Anxiety Disorders Ctr, Toronto, ON M4N 3M5, Canada. [Macdonald, Alexandra; Monson, Candice M.] US VA Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Macdonald, Alexandra] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Wells, Stephanie Y.] San Diego State Univ, San Diego, CA 92182 USA. [Wells, Stephanie Y.] Univ Calif San Diego, Dept Psychol, San Diego, CA 92103 USA. [Resick, Patricia A.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. RP Shnaider, P (reprint author), Ryerson Univ, Dept Psychol, 350 Victoria St, Toronto, ON M5B 2K3, Canada. EM philippe.shnaider@psych.ryerson.ca NR 29 TC 3 Z9 3 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2014 VL 27 IS 5 BP 526 EP 534 DI 10.1002/jts.21954 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AR9WS UT WOS:000343928000004 PM 25322882 ER PT J AU Resick, PA Suvak, MK Wells, SY AF Resick, Patricia A. Suvak, Michael K. Wells, Stephanie Y. TI The Impact of Childhood Abuse Among Women With Assault-Related PTSD Receiving Short-Term Cognitive-Behavioral Therapy SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL COMORBIDITY SURVEY; SEXUAL-ABUSE; PROCESSING THERAPY; PHYSICAL ABUSE; SURVIVORS; VICTIMS; TRIAL; ADOLESCENTS; EXPOSURE AB This study examined the effect of child sexual or physical abuse on brief cognitive-behavioral therapy treatments with adults with posttraumatic stress disorder (PTSD). We analyzed secondary data from two randomized controlled trials (Resick, Nishith, Weaver, Astin, & Feuer, 2002; Resick etal., 2008) that included women with PTSD who did or did not have child sexual abuse (CSA) or child physical abuse (CPA) histories to determine whether childhood abuse impacted dropout rate or reduction in PTSD symptoms. In Study 1, presence, duration, or severity of CSA was not associated with dropout; however, frequency of CSA significantly predicted dropout (OR=1.23). A significant CPA Severity x Treatment Group interaction emerged such that CPA severity was associated with greater dropout for prolonged exposure (PE; OR=1.45), but not cognitive processing therapy (CPT; OR=0.90). Study 2 found no differences in dropout. Study 1, comparing CPT and PE among women who experienced at least 1 rape found no differences in outcome based on childhood abuse history (r(p)(2)s=.000-.009). Study 2, a dismantling study of CPT with women seeking treatment for adult or child sexual or physical abuse found that for those with no childhood abuse, CPT-C, the cognitive-only version of CPT, had an advantage, whereas both forms of CPT worked best for those with higher frequency of childhood abuse; the effect size was small. Resumen Este estudio examino el efecto del abuso infantil, sexual o fisico a en el tratamiento con terapia cognitivo conductual breve (TCCB) en adultos con TEPT. Analizamos DATOS secundarios de dos estudios controlados randomizados (Resick y col. 2002, Resick y col. 2008) que incluyeron mujeres con TEPT quienes tenian o no antecedentes de abuso sexual infantil (ASI) o maltrato fisico infantil (MFI) para determinar si el abuso infantil impacto en las tasas de abandono o reduccion de sintomas de TEPT. En la muestra 1, la presencia, duracion o severidad del ASI no se asocio con el abandono, sin embargo, la frecuencia del AS significativamente predijo el abandono (OR=1.23). Una interaccion significativa entre la severidad de ASI x grupo de tratamiento surgio de manera que la severidad del ASI se asocio con mayor abandono para la terapia de exposicion prolongada (OR=1.45), pero no en la terapia de procesamiento cognitivo (OR=0.90). El Estudio 2 no encontro diferencias en el abandono. El Estudio 1, comparando la terapia de procesamiento cognitivo (TPC) con la terapia de exposicion prolongada (EP) entre mujeres que sufrieron al menos un violacion, no encontraron diferencias en los resultados basados en la historia de abuso infantil (rp 2S=.000-.009). En el Estudio 2, un estudio de descomposicion de TPC entre mujeres que buscaron tratamiento por abuso sexual o fisico, ya sea en la adultez o infancia, encontro que para aquellas sin abuso infantil, la TPC-C, que es la version solo cognitiva de la TPC, tenia una ventaja, mientras que ambas formas de TPC funcionaron mejor para aquellas mujeres con mayor frecuencia de abuso sexual, el tamano del efecto fue pequeno. C1 [Resick, Patricia A.; Suvak, Michael K.; Wells, Stephanie Y.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Resick, Patricia A.] Duke Univ, Med Ctr, Durham, NC 27701 USA. [Suvak, Michael K.] Suffolk Univ, Dept Psychol, Boston, MA USA. RP Resick, PA (reprint author), Duke Univ, Med Ctr, 411 West Chapel Hill St,Suite 200, Durham, NC 27701 USA. EM patricia.resick@duke.edu NR 33 TC 3 Z9 3 U1 10 U2 36 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2014 VL 27 IS 5 BP 558 EP 567 DI 10.1002/jts.21951 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AR9WS UT WOS:000343928000008 PM 25322885 ER PT J AU Guffanti, G Ashley-Koch, AE Roberts, AL Garrett, ME Solovieff, N Ratanatharathorn, A De Vivo, I Dennis, M Ranu, H Smoller, JW Liu, Y Purcell, SM Beckham, J Hauser, MA Koenen, KC AF Guffanti, G. Ashley-Koch, A. E. Roberts, A. L. Garrett, M. E. Solovieff, N. Ratanatharathorn, A. De Vivo, I. Dennis, M. Ranu, H. Smoller, J. W. Liu, Y. Purcell, S. M. Beckham, J. Hauser, M. A. Koenen, K. C. CA Vet Affairs Mid-Atlantic Mental Il TI No association between RORA polymorphisms and PTSD in two independent samples SO MOLECULAR PSYCHIATRY LA English DT Letter ID POSTTRAUMATIC-STRESS-DISORDER; SCALE C1 [Guffanti, G.] Columbia Univ, Dept Psychiat, New York, NY 10027 USA. [Ashley-Koch, A. E.; Garrett, M. E.; Liu, Y.; Hauser, M. A.] Duke Univ, Dept Med, Durham, NC USA. [Roberts, A. L.; De Vivo, I.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Solovieff, N.; Smoller, J. W.; Purcell, S. M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Solovieff, N.; Smoller, J. W.; Purcell, S. M.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Solovieff, N.; Smoller, J. W.; Purcell, S. M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Ratanatharathorn, A.; Koenen, K. C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Dennis, M.] Duke Univ, Dept Psychiat, Durham, NC USA. [Ranu, H.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Purcell, S. M.] Mt Sinai Sch Med, Div Psychiat Gen, New York, NY USA. [Beckham, J.] Durham Vet Affairs Med Ctr, Durham, NC USA. RP Guffanti, G (reprint author), Columbia Univ, Dept Psychiat, New York, NY 10027 USA. EM mike.hauser@duke.edu; kck5@cumc.columbia.edu RI Koenen, Karestan/K-5402-2014; OI Roberts, Andrea/0000-0001-5023-4399; Koenen, Karestan/0000-0003-3293-4281; Van Voorhees, Elizabeth/0000-0003-3475-1737; Ashley-Koch, Allison/0000-0001-5409-9155 NR 10 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT PY 2014 VL 19 IS 10 BP 1056 EP 1057 DI 10.1038/mp.2014.19 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AR5ZN UT WOS:000343661700003 PM 25048002 ER PT J AU Boraska, V Franklin, CS Floyd, JAB Thornton, LM Huckins, LM Southam, L Rayner, NW Tachmazidou, I Klump, KL Treasure, J Lewis, CM Schmidt, U Tozzi, F Kiezebrink, K Hebebrand, J Gorwood, P Adan, RAH Kas, MJH Favaro, A Santonastaso, P Fernandez-Aranda, F Gratacos, M Rybakowski, F Dmitrzak-Weglarz, M Kaprio, J Keski-Rahkonen, A Raevuori, A Van Furth, EF 't Landt, MCTSO Hudson, JI Reichborn-Kjennerud, T Knudsen, GPS Monteleone, P Kaplan, AS Karwautz, A Hakonarson, H Berrettini, WH Guo, Y Li, D Schork, NJ Komaki, G Ando, T Inoko, H Esko, T Fischer, K Mannik, K Metspalu, A Baker, JH Cone, RD Dackor, J DeSocio, JE Hilliard, CE O'Toole, JK Pantel, J Szatkiewicz, JP Taico, C Zerwas, S Trace, SE Davis, OSP Helder, S Buhren, K Burghardt, R de Zwaan, M Egberts, K Ehrlich, S Herpertz-Dahlmann, B Herzog, W Imgart, H Scherag, A Scherag, S Zipfel, S Boni, C Ramoz, N Versini, A Brandys, MK Danner, UN de Kovel, C Hendriks, J Koeleman, BPC Ophoff, RA Strengman, E van Elburg, AA Bruson, A Clementi, M Degortes, D Forzan, M Tenconi, E Docampo, E Escaramis, G Jimenez-Murcia, S Lissowska, J Rajewski, A Szeszenia-Dabrowska, N Slopien, A Hauser, J Karhunen, L Meulenbelt, I Slagboom, PE Tortorella, A Maj, M Dedoussis, G Dikeos, D Gonidakis, F Tziouvas, K Tsitsika, A Papezova, H Slachtova, L Martaskova, D Kennedy, JL Levitan, RD Yilmaz, Z Huemer, J Koubek, D Merl, E Wagner, G Lichtenstein, P Breen, G Cohen-Woods, S Farmer, A McGuffin, P Cichon, S Giegling, I Herms, S Rujescu, D Schreiber, S Wichmann, HE Dina, C Sladek, R Gambaro, G Soranzo, N Julia, A Marsal, S Rabionet, R Gaborieau, V Dick, DM Palotie, A Ripatti, S Widen, E Andreassen, OA Espeseth, T Lundervold, A Reinvang, I Steen, VM Le Hellard, S Mattingsdal, M Ntalla, I Bencko, V Foretova, L Janout, V Navratilova, M Gallinger, S Pinto, D Scherer, SW Aschauer, H Carlberg, L Schosser, A Alfredsson, L Ding, B Klareskog, L Padyukov, L Courtet, P Guillaume, S Jaussent, I Finan, C Kalsi, G Roberts, M Logan, DW Peltonen, L Ritchie, GRS Barrett, JC Estivill, X Hinney, A Sullivan, PF Collier, DA Zeggini, E Bulik, CM AF Boraska, V. Franklin, C. S. Floyd, J. A. B. Thornton, L. M. Huckins, L. M. Southam, L. Rayner, N. W. Tachmazidou, I. Klump, K. L. Treasure, J. Lewis, C. M. Schmidt, U. Tozzi, F. Kiezebrink, K. Hebebrand, J. Gorwood, P. Adan, R. A. H. Kas, M. J. H. Favaro, A. Santonastaso, P. Fernandez-Aranda, F. Gratacos, M. Rybakowski, F. Dmitrzak-Weglarz, M. Kaprio, J. Keski-Rahkonen, A. Raevuori, A. Van Furth, E. F. 't Landt, M. C. T. Slof-Op Hudson, J. I. Reichborn-Kjennerud, T. Knudsen, G. P. S. Monteleone, P. Kaplan, A. S. Karwautz, A. Hakonarson, H. Berrettini, W. H. Guo, Y. Li, D. Schork, N. J. Komaki, G. Ando, T. Inoko, H. Esko, T. Fischer, K. Maennik, K. Metspalu, A. Baker, J. H. Cone, R. D. Dackor, J. DeSocio, J. E. Hilliard, C. E. O'Toole, J. K. Pantel, J. Szatkiewicz, J. P. Taico, C. Zerwas, S. Trace, S. E. Davis, O. S. P. Helder, S. Buehren, K. Burghardt, R. de Zwaan, M. Egberts, K. Ehrlich, S. Herpertz-Dahlmann, B. Herzog, W. Imgart, H. Scherag, A. Scherag, S. Zipfel, S. Boni, C. Ramoz, N. Versini, A. Brandys, M. K. Danner, U. N. de Kovel, C. Hendriks, J. Koeleman, B. P. C. Ophoff, R. A. Strengman, E. van Elburg, A. A. Bruson, A. Clementi, M. Degortes, D. Forzan, M. Tenconi, E. Docampo, E. Escaramis, G. Jimenez-Murcia, S. Lissowska, J. Rajewski, A. Szeszenia-Dabrowska, N. Slopien, A. Hauser, J. Karhunen, L. Meulenbelt, I. Slagboom, P. E. Tortorella, A. Maj, M. Dedoussis, G. Dikeos, D. Gonidakis, F. Tziouvas, K. Tsitsika, A. Papezova, H. Slachtova, L. Martaskova, D. Kennedy, J. L. Levitan, R. D. Yilmaz, Z. Huemer, J. Koubek, D. Merl, E. Wagner, G. Lichtenstein, P. Breen, G. Cohen-Woods, S. Farmer, A. McGuffin, P. Cichon, S. Giegling, I. Herms, S. Rujescu, D. Schreiber, S. Wichmann, H-E Dina, C. Sladek, R. Gambaro, G. Soranzo, N. Julia, A. Marsal, S. Rabionet, R. Gaborieau, V. Dick, D. M. Palotie, A. Ripatti, S. Widen, E. Andreassen, O. A. Espeseth, T. Lundervold, A. Reinvang, I. Steen, V. M. Le Hellard, S. Mattingsdal, M. Ntalla, I. Bencko, V. Foretova, L. Janout, V. Navratilova, M. Gallinger, S. Pinto, D. Scherer, S. W. Aschauer, H. Carlberg, L. Schosser, A. Alfredsson, L. Ding, B. Klareskog, L. Padyukov, L. Courtet, P. Guillaume, S. Jaussent, I. Finan, C. Kalsi, G. Roberts, M. Logan, D. W. Peltonen, L. Ritchie, G. R. S. Barrett, J. C. Estivill, X. Hinney, A. Sullivan, P. F. Collier, D. A. Zeggini, E. Bulik, C. M. CA Wellcome Trust Case Control Conso TI A genome-wide association study of anorexia nervosa SO MOLECULAR PSYCHIATRY LA English DT Article DE anorexia nervosa; body mass index; eating disorders; genome-wide association study; GWAS; metabolic ID MAJOR DEPRESSIVE DISORDER; POPULATION-BASED TWIN; OF-THE-LITERATURE; BODY-MASS INDEX; EATING-DISORDERS; BULIMIA-NERVOSA; RISK-FACTORS; MEDICAL COMPLICATIONS; ANXIETY DISORDERS; CONTROLLED FAMILY AB Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P = 3.01 x 10(-7)) in SOX2OT and rs17030795 (P = 5.84 x 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P = 5.76 x 10(-6)) between CUL3 and FAM124B and rs1886797 (P = 8.05 x 10(-6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P= 4x10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field. C1 [Boraska, V.; Franklin, C. S.; Floyd, J. A. B.; Huckins, L. M.; Southam, L.; Rayner, N. W.; Tachmazidou, I.; Soranzo, N.; Palotie, A.; Finan, C.; Logan, D. W.; Peltonen, L.; Ritchie, G. R. S.; Barrett, J. C.; Zeggini, E.] Wellcome Trust Sanger Inst, Cambridge, England. [Boraska, V.] Univ Split, Sch Med, Split, Croatia. [Floyd, J. A. B.] Queen Mary Univ London, John Vane Sci Ctr, William Harvey Res Inst, London, England. [Floyd, J. A. B.] Queen Mary Univ London, John Vane Sci Ctr, London Sch Med & Dent, London, England. [Thornton, L. M.; Tozzi, F.; Baker, J. H.; Hilliard, C. E.; Taico, C.; Zerwas, S.; Trace, S. E.; Yilmaz, Z.; Sullivan, P. F.; Bulik, C. M.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Rayner, N. W.] WTCHG, Oxford, England. [Rayner, N. W.] OCDEM, Oxford, England. [Klump, K. L.] Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. [Treasure, J.; Schmidt, U.] Kings Coll London, Inst Psychiat, Sect Eating Disorders, London, England. [Lewis, C. M.; Davis, O. S. P.; Helder, S.; Breen, G.; Cohen-Woods, S.; Farmer, A.; McGuffin, P.; Kalsi, G.; Roberts, M.; Collier, D. A.] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London, England. [Kiezebrink, K.] Hlth Serv Res Unit, Aberdeen, Scotland. 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[Gonidakis, F.] Univ Athens, Sch Med, Dept Psychiat 1, Eating Disorders Unit, GR-11527 Athens, Greece. [Tsitsika, A.] Univ Athens, Sch Med, P&A Kyriakou Childrens Hosp, AHU,Dept Pediat 2, GR-11527 Athens, Greece. [Papezova, H.; Martaskova, D.] Charles Univ Prague, Fac Med 1, Dept Psychiat, Prague, Czech Republic. [Slachtova, L.] Charles Univ Prague, Fac Med 1, Dept Pediat, Prague, Czech Republic. [Lichtenstein, P.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Cichon, S.; Herms, S.] Univ Bonn, Inst Human Genet, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Cichon, S.] Res Ctr, Inst Neurosci & Med INM 1, Julich, Germany. [Cichon, S.; Herms, S.] Univ Basel, Dept Biomed, Div Med Genet, Basel, Switzerland. [Giegling, I.; Rujescu, D.] Univ Halle Wittenberg, Klinikum Med Fak, D-06108 Halle, Germany. [Schreiber, S.] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Wichmann, H-E] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany. [Wichmann, H-E] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Dina, C.] Inst Pasteur, Inst Biol, CNRS 8090, F-59019 Lille, France. [Sladek, R.] McGill Univ, Montreal, PQ, Canada. [Sladek, R.] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Gambaro, G.] Catholic Univ, Columbus Gemelly Hosp, Dept Internal Med & Med Specialties, Div Nephrol, Rome, Italy. [Julia, A.; Marsal, S.] Univ Vall Hebron, Inst Recerca Hosp, URR, Barcelona, Spain. [Gaborieau, V.] IARC, Genet Epidemiol Grp, Lyon, France. [Dick, D. M.] Virginia Commonwealth Univ, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Palotie, A.; Ripatti, S.; Widen, E.] Univ Helsinki, Finnish Inst Mol Med Finland FIMM, Helsinki, Finland. [Palotie, A.] Broad Inst MIT & Harvard, Program Human & Populat Genet, Cambridge, MA USA. [Ripatti, S.; Widen, E.] Finnish Inst Occupat Hlth, Helsinki, Finland. [Andreassen, O. A.; Espeseth, T.; Mattingsdal, M.] Univ Oslo, Oslo Univ Hosp, Div Mental Hlth & Addict, KG Jebsen Ctr Psychosis Res,NORMENT, Oslo, Norway. [Andreassen, O. A.; Espeseth, T.; Mattingsdal, M.] Univ Oslo, Inst Clin Med, Oslo, Norway. [Espeseth, T.; Reinvang, I.] Univ Oslo, Dept Psychol, Oslo, Norway. [Lundervold, A.] Univ Bergen, Dept Biol & Med Psychol, Bergen, Norway. [Lundervold, A.] Haraldsplass Deaconess Hosp, Kavli Res Ctr Aging & Dementia, Bergen, Norway. [Lundervold, A.] Univ Bergen, KG Jebsen Ctr Res Neuropsychiat Disorders, Bergen, Norway. [Steen, V. M.; Le Hellard, S.] Univ Bergen, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res, Dept Clin Sci, Bergen, Norway. [Steen, V. M.; Le Hellard, S.] Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, N-5021 Bergen, Norway. [Bencko, V.] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic. [Foretova, L.; Navratilova, M.] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Janout, V.] Palacky Univ, CR-77147 Olomouc, Czech Republic. [Gallinger, S.] Univ Hlth Network, Toronto Gen Hosp, Toronto, ON, Canada. [Gallinger, S.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Pinto, D.] Mt Sinai Sch Med, Seaver Autism Ctr, Dept Psychiat, New York, NY USA. [Pinto, D.] Mt Sinai Sch Med, Seaver Autism Ctr, Dept Genet, New York, NY USA. [Pinto, D.] Mt Sinai Sch Med, Seaver Autism Ctr, Dept Genom Sci, New York, NY USA. [Pinto, D.] Mt Sinai Sch Med, Mindich Child Hlth & Dev Inst, New York, NY USA. [Scherer, S. W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada. [Scherer, S. W.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Aschauer, H.; Carlberg, L.; Schosser, A.] Med Univ Vienna, Dept Psychiat & Psychotherapy, Vienna, Austria. [Alfredsson, L.; Ding, B.] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Klareskog, L.; Padyukov, L.] Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Solna, Sweden. [Courtet, P.; Guillaume, S.; Jaussent, I.] Univ Montpellier I, INSERM, U1061, Montpellier, France. [Courtet, P.; Guillaume, S.; Jaussent, I.] CHU Montpellier, Dept Emergency Psychiat, Montpellier, France. [Ritchie, G. R. S.] Wellcome Trust Genome Campus, European Bioinformat Inst, European Mol Biol Lab, Cambridge, England. [Collier, D. A.] Eli Lilly & Co, Erl Wood Manor, Windlesham, Surrey, England. [Bulik, C. M.] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. RP Bulik, CM (reprint author), Univ N Carolina, Dept Psychiat, CB 7160, Chapel Hill, NC 27599 USA. EM cbulik@med.unc.edu RI Gallinger, Steven/E-4575-2013; Scherer, Stephen /B-3785-2013; Pantel, Jacques/C-6563-2014; Cohen-Woods, Sarah/F-8674-2014; Dina, Christian/D-3535-2015; Lewis, Cathryn/A-5225-2010; Slachtova, Lenka/A-1770-2013; Guo, Yiran/H-4120-2011; Janout, Vladimir/M-5133-2014; Hinney, Anke/D-6953-2011; Escaramis, Georgia/B-2997-2015; rabionet, raquel/A-7407-2009; ramoz, nicolas/K-3316-2015; Ripatti, Samuli/H-9446-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; Breen, Gerome/A-5540-2010; Collier, David/D-1649-2011; van Furth, Eric/M-9849-2015; Huemer, Julia/N-7521-2015; Estivill, Xavier/A-3125-2013; rabionet, raquel/C-8379-2009; Slagboom, P. Eline/R-4790-2016; Boraska Perica, Vesna/D-8230-2017; OI lichtenstein, paul/0000-0003-3037-5287; Julia Cano, Antonio/0000-0001-6064-3620; Kaminska, Deborah/0000-0002-9256-1117; Logan, Darren /0000-0003-1545-5510; Gillman, Matthew/0000-0002-2340-6930; Soranzo, Nicole/0000-0003-1095-3852; guillaume, sebastien/0000-0002-6769-9982; Zeggini, Eleftheria/0000-0003-4238-659X; Barrett, Jeffrey/0000-0002-1152-370X; Slof-Op 't Landt, Rita/0000-0001-6135-2163; Cohen-Woods, Sarah/0000-0003-2199-6129; Tozzi, Federica/0000-0002-3536-2920; Tziouvas, Konstantinos M/0000-0002-6863-7708; Scherag, Andre/0000-0002-9406-4704; Klareskog, Lars/0000-0001-9601-6186; Andreassen, Ole A./0000-0002-4461-3568; Huckins, Laura/0000-0002-5369-6502; Santonastaso, Paolo/0000-0002-7408-0563; Alfredsson, Lars/0000-0003-1688-6697; FERNANDEZ-ARANDA, FERNANDO/0000-0002-2968-9898; Maxwell, Alexander P./0000-0002-6110-7253; Keski-Rahkonen, Anna/0000-0002-6713-7488; de Kovel, Carolien/0000-0002-7818-1396; GORWOOD, Philip/0000-0003-1845-3676; Roberts, Marion/0000-0001-6824-4413; Ouwehand, Willem/0000-0002-7744-1790; Treasure, Janet/0000-0003-0871-4596; Kaprio, Jaakko/0000-0002-3716-2455; JIMENEZ-MURCIA, SUSANA/0000-0002-3596-8033; Padyukov, Leonid/0000-0003-2950-5670; Scherer, Stephen /0000-0002-8326-1999; Pantel, Jacques/0000-0002-9015-6281; Dina, Christian/0000-0002-7722-7348; Lewis, Cathryn/0000-0002-8249-8476; Guo, Yiran/0000-0002-6549-8589; Hinney, Anke/0000-0001-5659-0706; Escaramis, Georgia/0000-0002-5416-3177; rabionet, raquel/0000-0001-5006-8140; Ripatti, Samuli/0000-0002-0504-1202; Breen, Gerome/0000-0003-2053-1792; Collier, David/0000-0003-4087-1559; van Furth, Eric/0000-0002-1131-0886; Huemer, Julia/0000-0003-1942-763X; Estivill, Xavier/0000-0002-0723-2256; rabionet, raquel/0000-0001-5006-8140; Slagboom, P. Eline/0000-0002-2875-4723; Yilmaz, Zeynep/0000-0002-8145-1596; Ehrlich, Stefan/0000-0003-2132-4445 FU genomewide association study of anorexia nervosa [WTCCC3 WT088827/Z/09] FX This work was funded by a grant from the WTCCC3 WT088827/Z/09 entitled 'A genomewide association study of anorexia nervosa'. NR 72 TC 54 Z9 55 U1 6 U2 56 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT PY 2014 VL 19 IS 10 BP 1085 EP 1094 DI 10.1038/mp.2013.187 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AR5ZN UT WOS:000343661700008 PM 24514567 ER PT J AU Ryan, CJ Saylor, PJ Everly, JJ Sartor, O AF Ryan, Charles J. Saylor, Philip J. Everly, Jason J. Sartor, Oliver TI Bone-Targeting Radiopharmaceuticals for the Treatment of Bone-Metastatic Castration-Resistant Prostate Cancer: Exploring the Implications of New Data SO ONCOLOGIST LA English DT Article DE Bone-metastatic castration-resistant prostate cancer; Pain; Skeletal-related events; Radium-223; Overall survival ID MITOXANTRONE PLUS PREDNISONE; SKELETAL-RELATED EVENTS; DOUBLE-BLIND; RANDOMIZED-TRIAL; ABIRATERONE ACETATE; INCREASED SURVIVAL; ZOLEDRONIC ACID; PHASE-III; PAIN; CHEMOTHERAPY AB Background. Clinical features of patients with castration-resistant prostate cancer (CRPC) are characterized by a high incidence of bone metastases, which are associated with impairment of quality of life, pain, skeletal-related events (SREs), and a negative impact on prognosis. Advances in the understanding of cancer cell-bone stroma interactions and molecular mechanisms have recently permitted the development of new agents. Purpose. We review the merits, applications, and limitations of emerging data sets on bone-metastatic CRPC with a focus on radium-223, an a-emitting radiopharmaceutical, and its use in therapy for this disease. Methods. References for this review were identified through searches of PubMed and Medline databases, and only papers published in English were considered. Related links in the databases were reviewed, along with relevant published guidelines, recently published abstracts from major medical meetings, and transcripts from a recent round table of clinical investigators. Results. Prior to radium-223, available bone-targeted therapies demonstrated the ability to delay SREs and palliate bone pain in patients with metastatic CRPC but without evidence of improvement in overall survival (OS). In a randomized controlled phase III trial, radium-223 demonstrated the ability to improve OS and delay SREs in docetaxel-pretreated or docetaxel-unfit men with symptomatic bone-metastatic CRPC and was not associated with significantly more grade 3 or 4 adverse events than placebo. Conclusion. Radium-223 has a targeted effect on bone metastases in CRPC and has an important role in docetaxel-pretreated or docetaxel-unfit men with symptomatic bone-metastatic CRPC. C1 [Ryan, Charles J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Med, Div Hematol Oncol, San Francisco, CA 94143 USA. [Saylor, Philip J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02115 USA. [Everly, Jason J.] Educ Concepts Grp LLC, Atlanta, GA USA. [Sartor, Oliver] Tulane Canc Ctr, Tulane Med Sch, Dept Med, New Orleans, LA USA. [Sartor, Oliver] Tulane Canc Ctr, Tulane Med Sch, Dept Urol, New Orleans, LA USA. RP Ryan, CJ (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Med, Div Hematol Oncol, 1600 Divisadero St,MZ Bldg A, San Francisco, CA 94143 USA. EM ryanc@medicine.ucsf.edu FU Algeta US/Bayer HealthCare Pharmaceuticals, Inc. FX We thank Drs. David Quinn, Howard Sandler, William K. Oh, Daniel P. Petrylak, Jeff M. Michalski, E. David Crawford, Leonard G. Gomella, and Joel B. Nelson for participating in a round table discussion. The round table discussion was supported by an educational grant from Algeta US/Bayer HealthCare Pharmaceuticals, Inc. NR 40 TC 6 Z9 7 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 OCT PY 2014 VL 19 IS 10 BP 1012 EP 1018 DI 10.1634/theoncologist.2013-0472 PG 7 WC Oncology SC Oncology GA AR9QS UT WOS:000343910500004 PM 25232039 ER PT J AU Dizon, DS AF Dizon, Don S. TI My Father's Final Lesson SO ONCOLOGIST LA English DT Editorial Material C1 [Dizon, Don S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dizon, DS (reprint author), 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM ddizon@partners.org NR 1 TC 0 Z9 0 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 OCT PY 2014 VL 19 IS 10 BP 1110 EP 1111 DI 10.1634/theoncologist.2014-0301 PG 2 WC Oncology SC Oncology GA AR9QS UT WOS:000343910500017 PM 25209377 ER PT J AU Kuten-Shorrer, M Hochberg, EP Woo, SB AF Kuten-Shorrer, Michal Hochberg, Ephraim P. Woo, Sook-Bin TI Lichenoid Mucosal Reaction to Rituximab SO ONCOLOGIST LA English DT Editorial Material C1 [Kuten-Shorrer, Michal] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Hochberg, Ephraim P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Ctr Lymphoma, Boston, MA 02115 USA. [Hochberg, Ephraim P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Woo, Sook-Bin] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kuten-Shorrer, M (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. NR 8 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 OCT PY 2014 VL 19 IS 10 BP E12 EP E13 DI 10.1634/theoncologist.2014-0169 PG 2 WC Oncology SC Oncology GA AR9QS UT WOS:000343910500002 PM 25170011 ER PT J AU Hellmuth, JC Szczepanowski, M Staiger, A Pastore, A Hartmann, S Tschuri, S Hansmann, ML Ott, G Rosenwald, A Louissaint, A Kridel, R van Hummelen, P Ducar, MD Hiddemann, W Sehn, LH Moccia, AA Gascoyne, RD Weinstock, DM Klapper, W Weigert, O AF Hellmuth, J. C. Szczepanowski, M. Staiger, A. Pastore, A. Hartmann, S. Tschuri, S. Hansmann, M. -L. Ott, G. Rosenwald, A. Louissaint, Jr. A. Kridel, R. van Hummelen, P. Ducar, M. D. Hiddemann, W. Sehn, L. H. Moccia, A. A. Gascoyne, R. D. Weinstock, D. M. Klapper, W. Weigert, O. TI Gastrointestinal follicular lymphoma (FL) differs from nodal FL by absence of EZH2 mutations SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Hellmuth, J. C.; Pastore, A.; Hiddemann, W.; Weigert, O.] LMU Munchen, Med Klin & Poliklin 3, Munich, Germany. [Hellmuth, J. C.; Pastore, A.; Tschuri, S.; Hiddemann, W.; Weigert, O.] Helmholtz Zentrum, Munich, Germany. [Szczepanowski, M.; Klapper, W.] Univ Klinikum Schleswig Holstein, Inst Pathol Kiel, Sekt Hamatopathol & Lymphknotenregister, Kiel, Germany. [Staiger, A.; Ott, G.] Robert Bosch Krankenhaus, Dr Margarete Fischer Bosch Inst Klin Pharmakol, Stuttgart, Germany. [Hartmann, S.; Hansmann, M. -L.] Univ Frankfurt Klinikum, Dr Senckenberg Inst Pathol, Frankfurt, Germany. [Rosenwald, A.] Univ Wurzburg, Inst Pathol, Wurzburg, Germany. [Louissaint, Jr. A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kridel, R.; Sehn, L. H.; Moccia, A. A.; Gascoyne, R. D.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada. [van Hummelen, P.; Ducar, M. D.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Weinstock, D. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2014 VL 37 SU 5 MA P246 BP 75 EP 75 PG 1 WC Oncology SC Oncology GA AR8HS UT WOS:000343816900175 ER PT J AU Hess, G Kirsch, A Wong, RS Casper, C Munshi, N Fossa, A Cavet, J Bandekar, R Rothman, M Puchalski, TA Chaturvedi, S van de Velde, H Vermeulen, J van Rhee, F AF Hess, G. Kirsch, A. Wong, R. S. Casper, C. Munshi, N. Fossa, A. Cavet, J. Bandekar, R. Rothman, M. Puchalski, T. A. Chaturvedi, S. van de Velde, H. Vermeulen, J. van Rhee, F. TI A multicenter, randomized, double-blind, placebo-controlled study of the efficacy and safety of Siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with Multicentric Castleman's disease SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Hess, G.] Johannes Gutenberg Univ Mainz, Med Klin & Poliklin 3, D-55122 Mainz, Germany. [Kirsch, A.] Med Versorgungszentrum Onkol Schwerpunkt Oskar He, Berlin, Germany. [Wong, R. S.] Chinese Univ Hong Kong, Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. [Casper, C.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Munshi, N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Fossa, A.] Norwegian Radium Hosp, Oslo, Norway. [Cavet, J.] Christie NHS Fdn Trust, Manchester, Lancs, England. Univ Manchester, Manchester, Lancs, England. [Bandekar, R.] Janssen Res & Dev, Spring House, PA USA. [Rothman, M.] Janssen Res & Dev, Washington, DC USA. [van de Velde, H.] Janssen Res & Dev, Beerse, Belgium. [Vermeulen, J.] Janssen Res & Dev, Leiden, Netherlands. [van Rhee, F.] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2014 VL 37 SU 5 MA P251 BP 77 EP 77 PG 1 WC Oncology SC Oncology GA AR8HS UT WOS:000343816900180 ER PT J AU Venkataramani, V Frosch, A Kuffer, S Pape, V Kiecke, C Koch, R Trumper, L Rogers, JT Strobel, P Wulf, GG AF Venkataramani, V. Frosch, A. Kueffer, S. Pape, V Kiecke, C. Koch, R. Truemper, L. Rogers, J. T. Stroebel, P. Wulf, G. G. TI Alzheimer Amyloid Precursor Protein protects cancer stem cells against ER stress SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Venkataramani, V.; Pape, V; Kiecke, C.; Koch, R.; Truemper, L.; Wulf, G. G.] UMG Goettingen, Gottingen, Germany. [Frosch, A.; Kueffer, S.; Stroebel, P.] UMG Goettingen, Abt Pathol, Gottingen, Germany. [Rogers, J. T.] Massachusetts Gen Hosp, Charlestown, MA USA. [Rogers, J. T.] Harvard Univ, Sch Med, Dept Psychiat, Neurochem Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2014 VL 37 SU 5 MA P284 BP 90 EP 90 PG 1 WC Oncology SC Oncology GA AR8HS UT WOS:000343816900213 ER PT J AU Schlumberger, M Tahara, M Wirth, L Robinson, B Brose, M Elisei, R Dutcus, C de las Heras, B Zhu, J Habra, M Newbold, K Shah, MH Hoff, AO Gianoukakis, AG Kiyota, N Taylor, M Kim, SB Krzyzanowska, M Sherman, SI AF Schlumberger, M. Tahara, M. Wirth, L. Robinson, B. Brose, M. Elisei, R. Dutcus, C. de las Heras, B. Zhu, J. Habra, M. Newbold, K. Shah, M. H. Hoff, A. O. Gianoukakis, A. G. Kiyota, N. Taylor, M. Kim, S-B Krzyzanowska, M. Sherman, S., I TI A phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with I-refractory differentiated thyroid cancer (SELECT) SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Schlumberger, M.] Inst Gustave Roussy, Villejuif, France. [Schlumberger, M.] Univ Paris Sud, Villejuif, France. [Tahara, M.] Natl Canc Ctr Hosp East, Div Head & Neck Med Oncol, Kashiwa, Chiba, Japan. [Wirth, L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Robinson, B.] Univ Sydney, Kolling Inst Med Res, Sydney, NSW 2006, Australia. [Brose, M.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Elisei, R.] Azienda Osped Univ, Pisa, Italy. [Dutcus, C.; Zhu, J.] Eisai Inc, Oncol, Woodcliff Lake, NJ USA. [de las Heras, B.] Eisai Inc, Oncol, Hatfield, Herts, England. [Habra, M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Newbold, K.] Royal Marsden Natl Hlth Serv Trust, London, England. [Shah, M. H.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Hoff, A. O.] Univ Sao Paulo, Inst Canc Sao Paulo, Sao Paulo, Brazil. [Gianoukakis, A. G.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Kiyota, N.] Kobe Univ Hosp, Kobe, Hyogo, Japan. [Taylor, M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Kim, S-B] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. [Krzyzanowska, M.] Princess Margaret Canc Ctr, Toronto, ON, Canada. RI Kiyota, Naomi/K-3226-2016 NR 0 TC 0 Z9 0 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2014 VL 37 SU 5 MA V398 BP 119 EP 119 PG 1 WC Oncology SC Oncology GA AR8HS UT WOS:000343816900289 ER PT J AU Fan, F Vallet, S Sattler, M Tonon, G Bashari, MH Bakiri, L Goldschmidt, H Wagner, EF Jaeger, D Podar, K AF Fan, F. Vallet, S. Sattler, M. Tonon, G. Bashari, M. H. Bakiri, L. Goldschmidt, H. Wagner, E. F. Jaeger, D. Podar, K. TI The AP-1 transcription factor JunB promotes multiple myeloma (MM) cell proliferation, survival and drug resistance in the bone marrow microenvironment SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Fan, F.; Vallet, S.; Bashari, M. H.; Jaeger, D.; Podar, K.] Heidelberg Univ, Heidelberg, Germany. [Fan, F.; Vallet, S.; Bashari, M. H.; Jaeger, D.; Podar, K.] Natl Ctr Tumorerkrankungen, Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany. [Sattler, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tonon, G.] Ist Sci San Raffaele, Div Mol Oncol, I-20132 Milan, Italy. [Bakiri, L.; Wagner, E. F.] BBVA Fdn, Natl Canc Res Ctr CNIO, Madrid, Spain. [Goldschmidt, H.] Uniklin Heidelberg, Heidelberg, Germany. RI Bashari, Muhammad Hasan/H-7079-2016; Wagner, Erwin/G-9637-2012 OI Bashari, Muhammad Hasan/0000-0001-7298-0317; Wagner, Erwin/0000-0001-7872-0196 NR 0 TC 0 Z9 0 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2014 VL 37 SU 5 MA V593 BP 192 EP 192 PG 1 WC Oncology SC Oncology GA AR8HS UT WOS:000343816900466 ER PT J AU Wedeh, G Cerny-Reiterer, S Hadzijusufovic, E Eisenwort, G Herrmann, H Blatt, K Muellauer, L Schwaab, J Bradner, JE Sperr, WR Reiter, A Horny, HP Willmann, M Zuber, J Arock, M Valent, P AF Wedeh, G. Cerny-Reiterer, S. Hadzijusufovic, E. Eisenwort, G. Herrmann, H. Blatt, K. Muellauer, L. Schwaab, J. Bradner, J. E. Sperr, W. R. Reiter, A. Horny, H. -P. Willmann, M. Zuber, J. Arock, M. Valent, P. TI Bromodomain- containing protein 4 (BRD4): a novel therapeutic target in advanced mast cell neoplasms SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Wedeh, G.; Arock, M.] Ecole Normale Super, LBPA CNRS UMR8113, Cachan, France. [Wedeh, G.; Cerny-Reiterer, S.; Hadzijusufovic, E.; Blatt, K.; Sperr, W. R.; Valent, P.] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, Vienna, Austria. [Cerny-Reiterer, S.; Hadzijusufovic, E.; Eisenwort, G.; Herrmann, H.; Sperr, W. R.; Valent, P.] Med Univ Vienna, Ludwig Boltzmann Cluster Oncol, Vienna, Austria. [Hadzijusufovic, E.; Willmann, M.] Univ Vet Med, Dept Clin Compan Anim & Horses, Clin Small Anim, Clin Unit Internal Med, Vienna, Austria. [Muellauer, L.] Med Univ Vienna, Dept Pathol, Vienna, Austria. [Schwaab, J.; Reiter, A.] Heidelberg Univ, Dept Med 3, Div Hematol, Mannheim, Germany. [Bradner, J. E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Horny, H. -P.] Univ Munich, Inst Pathol, D-80539 Munich, Germany. [Zuber, J.] Res Inst Mol Pathol, A-1030 Vienna, Austria. RI Hadzijusufovic, Emir/B-8109-2016 OI Hadzijusufovic, Emir/0000-0001-7409-4204 NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2014 VL 37 SU 5 MA V616 BP 198 EP 199 PG 2 WC Oncology SC Oncology GA AR8HS UT WOS:000343816900482 ER PT J AU Ulirsch, JC Weaver, MA Bortsov, AV Soward, AC Swor, RA Peak, DA Jones, JS Rathlev, NK Lee, DC Domeier, RM Hendry, PL McLean, SA AF Ulirsch, Jacob C. Weaver, Mark A. Bortsov, Andrey V. Soward, April C. Swor, Robert A. Peak, David A. Jones, Jeffrey S. Rathlev, Niels K. Lee, David C. Domeier, Robert M. Hendry, Phyllis L. McLean, Samuel A. TI No man is an island: Living in a disadvantaged neighborhood influences chronic pain development after motor vehicle collision SO PAIN LA English DT Article DE Musculoskeletal pain; Motor vehicle collision; Neighborhood effects; FKBP5; Gene-by-environment interaction ID DISPARITIES GEOCODING PROJECT; POSTTRAUMATIC-STRESS-DISORDER; WHIPLASH-ASSOCIATED DISORDERS; CHRONIC WIDESPREAD PAIN; INJECTION-DRUG USERS; SOCIOECONOMIC-STATUS; GLUCOCORTICOID-RECEPTOR; MUSCULOSKELETAL PAIN; INCOME INEQUALITY; DNA METHYLATION AB Living in a lower socioeconomic status neighborhood has been shown to alter stress system function and is associated with a number of adverse health outcomes, but its influence on musculoskeletal pain (MSP) outcomes after traumatic stress exposures such as motor vehicle collision (MVC) has not been assessed. We performed a multicenter, prospective study that enrolled 948 European-American individuals within 24 hours of MVC who were discharged home after emergency department evaluation. Follow-up evaluations were completed via telephone or Internet survey 6 weeks, 6 months, and 1 year after MVC on 91%, 89%, and 91% of participants, respectively. A robust aggregate measure of census tract neighborhood disadvantage was derived, and individual-level characteristics assessed included socioeconomic and demographic characteristics, pain prior to MVC, litigation status, and opioid use. MSP was assessed in the emergency department; MSP and pain interference with daily activity were assessed at 6 weeks, 6 months, and 1 year. After adjustment for individual-level factors, living in more disadvantaged neighborhoods was associated with increased MSP (P = 0.0009) and increased pain interference with daily function (P < 0.0001). The relationship between neighborhood disadvantage and MSP was moderated by a common single nucleotide polymorphism, rs2817038, 5' of the gene encoding FKBP5, a functional regulator of glucocorticoid receptor sensitivity (interaction P-value = 0.0015). These data support the hypothesis that low neighborhood socioeconomic status increases the likelihood of worse MSP outcomes after traumatic stress exposures such as MVC, and that this influence is mediated in part via its influence on stress system function. (C) 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Ulirsch, Jacob C.; Bortsov, Andrey V.; Soward, April C.; McLean, Samuel A.] Univ N Carolina, TRYUMPH Res Program, Chapel Hill, NC 27599 USA. [Ulirsch, Jacob C.; Bortsov, Andrey V.; Soward, April C.; McLean, Samuel A.] Univ N Carolina, Dept Anesthesiol, Chapel Hill, NC 27599 USA. [Weaver, Mark A.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. [Weaver, Mark A.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Swor, Robert A.] William Beaumont Hosp, Dept Emergency Med, Royal Oak, MI 48072 USA. [Peak, David A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Jones, Jeffrey S.] Spectrum Hlth Syst, Dept Emergency Med, Grand Rapids, MI USA. [Rathlev, Niels K.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. [Lee, David C.] N Shore Univ Hosp, Dept Emergency Med, Manhasset, NY USA. [Domeier, Robert M.] St Joseph Mercy Hlth Syst, Dept Emergency Med, Ypsilanti, MI USA. [Hendry, Phyllis L.] Univ Florida, Dept Emergency Med, Jacksonville, FL USA. [McLean, Samuel A.] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC 27599 USA. RP McLean, SA (reprint author), Univ N Carolina, Sch Med, Wing C,CB 7010, Chapel Hill, NC 27599 USA. EM smclean@aims.unc.edu OI McLean, Samuel/0000-0001-9482-3582 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [R01AR056328]; National Center for Advancing Translational Sciences [1UL1TR001111-01] FX We would like to thank our participants without whom this research would not be possible. We would also like to thank Dr Paul Voss at the Odum Institute for his advice during the initial phases of this project, and Ms June Hu for her valuable assistance. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R01AR056328. M. A. W. was supported by the National Center for Advancing Translational Sciences through Grant 1UL1TR001111-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 61 TC 7 Z9 7 U1 6 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD OCT PY 2014 VL 155 IS 10 BP 2116 EP 2123 DI 10.1016/j.pain.2014.07.025 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA AR8NI UT WOS:000343831300030 PM 25107859 ER PT J AU Goske, MJ Strauss, KJ Westra, SJ Frush, DP AF Goske, Marilyn J. Strauss, Keith J. Westra, Sjirk J. Frush, Donald P. TI The Image Gently ALARA CT summit on new CT technologies for children SO PEDIATRIC RADIOLOGY LA English DT Editorial Material C1 [Goske, Marilyn J.; Strauss, Keith J.] Cincinnati Childrens Hosp Med Ctr, Dept Radiol, Cincinnati, OH 45229 USA. [Westra, Sjirk J.] Massachusetts Gen Hosp, Sect Pediat Radiol, Boston, MA 02114 USA. [Frush, Donald P.] Duke Univ, Med Ctr, Div Pediat Radiol, Durham, NC USA. RP Goske, MJ (reprint author), Cincinnati Childrens Hosp Med Ctr, Dept Radiol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM Marilyn.Goske@cchmc.org RI Frush, Donald/M-6457-2015 OI Frush, Donald/0000-0002-6928-4465 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD OCT PY 2014 VL 44 SU 3 BP 403 EP 403 DI 10.1007/s00247-014-3076-z PG 1 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA AR6WL UT WOS:000343721300001 PM 25304694 ER PT J AU Brink, JA AF Brink, James A. TI Clinical decision-making tools for exam selection, reporting and dose tracking SO PEDIATRIC RADIOLOGY LA English DT Article DE Computed tomography; Utilization; Decision support; Radiation; Dose; Tracking; Registries; Children ID RADIATION-EXPOSURE; CANCER-RISKS; WHITE PAPER; CT; SUPPORT AB Although many efforts have been made to reduce the radiation dose associated with individual medical imaging examinations to "as low as reasonably achievable," efforts to ensure such examinations are performed only when medically indicated and appropriate are equally if not more important. Variations in the use of ionizing radiation for medical imaging are concerning, regardless of whether they occur on a local, regional or national basis. Such variations among practices can be reduced with the use of decision support tools at the time of order entry. These tools help reduce radiation exposure among practices through the appropriate use of medical imaging. Similarly, adoption of best practices among imaging facilities can be promoted through tracking the radiation exposure among imaging patients. Practices can benchmark their aggregate radiation exposures for medical imaging through the use of dose index registries. However several variables must be considered when contemplating individual patient dose tracking. The specific dose measures and the variation among them introduced by variations in body habitus must be understood. Moreover the uncertainties in risk estimation from dose metrics related to age, gender and life expectancy must also be taken into account. C1 Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brink, JA (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 55 Fruit St,FND-216, Boston, MA 02114 USA. EM jabrink@partners.org NR 19 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD OCT PY 2014 VL 44 SU 3 BP 418 EP 421 DI 10.1007/s00247-014-3015-z PG 4 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA AR6WL UT WOS:000343721300005 PM 25304698 ER PT J AU Singh, S Kalra, MK AF Singh, Sarabjeet Kalra, Mannudeep K. TI Standardized CT protocols and nomenclature: better, but not yet there SO PEDIATRIC RADIOLOGY LA English DT Article DE Radiation dose optimization; Standardization; Scan parameters; Computed tomography ID COMPUTED-TOMOGRAPHY; RECONSTRUCTION TECHNIQUES; DOSE REDUCTION; HOSPITALS AB Radiation dose associated with CT is an important safety concern in patient care, especially in children. Technical advancements in multidetector-row CT scanner technology offer several advantages for clinical applications; these advancements have considerably increased CT utilization and enhanced the complexity of CT scanning protocols. Furthermore there are several scan manufacturers spearheading these technical advancements, leading to different commercial names causing confusion among the users, especially at imaging sites with scanners from different vendors. Several scientific studies and the National Council on Radiation Protection and Measurements (NCRP) have shown variation in CT radiation doses for same body region and similar scanning protocols. Therefore there is a need for standardization of scanning protocols and nomenclature of scan parameters. The following material reviews the status and challenges in standardization of CT scanning and nomenclature. C1 [Singh, Sarabjeet; Kalra, Mannudeep K.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Singh, S (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM ssingh6@mgh.harvard.edu NR 20 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD OCT PY 2014 VL 44 SU 3 BP 440 EP 443 DI 10.1007/s00247-014-3096-8 PG 4 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA AR6WL UT WOS:000343721300009 PM 25304702 ER PT J AU Rehani, MM AF Rehani, Madan M. TI Multi-national findings on radiation protection of children SO PEDIATRIC RADIOLOGY LA English DT Article DE Computed tomography; Pediatric; Developing countries; Global; Radiation dose ID LATIN-AMERICA; 40 COUNTRIES; IAEA SURVEY; EUROPE; ASIA AB This article reviews issues of radiation protection in children in 52 low-resource countries. Extensive information was obtained through a survey by the International Atomic Energy Agency (IAEA); wide-ranging information was available from 40 countries and data from the other countries pertained to frequency of pediatric CT examinations. Of note is that multi-detector CT (MDCT) was available in 77% of responses to the survey, typically nodal centers in these countries. Nearly 75% of these scanners were reported to have dose displays. The pediatric CT usage was lower in European facilities as compared to Asian and African facilities, where usage was twice as high. The most frequently scanned body part was the head. Frequent use of 120 kVp was reported in children. The ratio of maximum to minimum CT dose index volume (CTDIvol) values varied between 15 for abdomen CT in the age group 5-10 years and 100 for chest CT in the age group < 1 year. In 8% of the CT systems, CTDI values for pediatric patients were higher than those for adults in at least one age group and for one type of examination. Use of adult protocols for children was associated with CTDIw or CTDIvol values in children that were double those of adults for head and chest examination and 50% higher for abdomen examination. Patient dose records were kept in nearly half of the facilities, with the highest frequency in Europe (55% of participating facilities), and in 49% of Asian, 36% of Latin American and 14% of African facilities. The analysis of the first-choice examinations in seven clinical conditions showed that practice was in accordance with guidelines for only three of seven specified clinical conditions. C1 [Rehani, Madan M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rehani, Madan M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rehani, MM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM madan.rehani@gmail.com NR 7 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD OCT PY 2014 VL 44 SU 3 BP 475 EP 478 DI 10.1007/s00247-014-3125-7 PG 4 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA AR6WL UT WOS:000343721300014 PM 25304707 ER PT J AU Rehani, MM AF Rehani, Madan M. TI CT imaging in a large part of the world: what we know and what we can learn SO PEDIATRIC RADIOLOGY LA English DT Article DE Computed tomography; Practice survey; Diagnostic reference levels; Radiation exposure; Radiation effects; International organizations; Regulation ID PEDIATRIC COMPUTED-TOMOGRAPHY; LATIN-AMERICA; 40 COUNTRIES; IAEA SURVEY; EUROPE; ASIA AB This paper describes how cooperation among international organizations, as modeled in Europe, can work to improve imaging safety and standards for children throughout the world. This is demonstrated in the mechanisms employed in a large-scale multi-national study on CT imaging safety practices described elsewhere in this issue of Pediatric Radiology. Here we learn approaches through which CT safety standards have been achieved and the international resources available to help in standardizing safety practices in medical imaging. There are unique strengths of the approach in Europe, which has mandatory requirements on member states to facilitate strengthening of radiation protection. Most countries have national regulatory mechanisms for radiation protection in medicine. International organizations play a significant role in supporting projects in lower-resource countries such that a large proportion of radiologic professionals in low-resource countries are trained through assistance by these organizations. Many of these international organizations make it possible for professionals worldwide to download free training material. Collaboration among international organizations and the Image Gently campaign toward consensus with regard to radiation protection can go further than individual opinions in promoting a higher standard of radiation protection around the world. C1 [Rehani, Madan M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rehani, Madan M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rehani, MM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM madan.rehani@gmail.com NR 17 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD OCT PY 2014 VL 44 SU 3 BP 511 EP 514 DI 10.1007/s00247-014-3045-6 PG 4 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA AR6WL UT WOS:000343721300021 PM 25304713 ER PT J AU Westra, SJ AF Westra, Sjirk J. TI The communication of the radiation risk from CT in relation to its clinical benefit in the era of personalized medicine SO PEDIATRIC RADIOLOGY LA English DT Article DE Computed tomography; Radiation dose; Stochastic risk; Carcinogenesis; Personalized medicine; Risk communication ID COMPUTED-TOMOGRAPHY SCANS; CANCER-RISKS; THYROID-CANCER; SUBSEQUENT RISK; EXPOSURE; CHILDHOOD; STRATEGIES; COHORT; HEAD AB The theory of radiation carcinogenesis has been debated for decades. Most estimates of the radiation risks from CT have been based on extrapolations from the lifespan follow-up study of atomic bomb survivors and on follow-up studies after therapeutic radiation, using the linear no-threshold theory. Based on this, many population-based projections of induction of future cancers by CT have been published that should not be used to estimate the risk to an individual because of their large margin of error. This has changed recently with the publication of three large international cohort follow-up studies, which link observed cancers to CT scans received in childhood. A fourth ongoing multi-country study in Europe is expected to have enough statistical power to address the limitations of the prior studies. The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) report released in 2013 specifically addresses variability in response of the pediatric population exposed to ionizing radiation. Most authorities now conclude that there is enough evidence to link future cancers to the radiation exposure from a single CT scan in childhood but that cancer risk estimates for individuals must be based on the specifics of exposure, age at exposure and absorbed dose to certain tissues. Generalizations are not appropriate, and the communication of the CT risk to individuals should be conducted within the framework of personalized medicine. C1 Massachusetts Gen Hosp, Div Pediat Radiol, Boston, MA 02114 USA. RP Westra, SJ (reprint author), Massachusetts Gen Hosp, Div Pediat Radiol, 34 Fruit St,White 246A, Boston, MA 02114 USA. EM swestra@partners.org NR 36 TC 3 Z9 3 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD OCT PY 2014 VL 44 SU 3 BP 515 EP 518 DI 10.1007/s00247-014-3139-1 PG 4 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA AR6WL UT WOS:000343721300022 PM 25304714 ER PT J AU Westra, SJ AF Westra, Sjirk J. TI The communication of the radiation risk from CT in relation to its clinical benefit in the era of personalized medicine SO PEDIATRIC RADIOLOGY LA English DT Article DE Computed tomography; Utilization; Radiation dose; Risk communication; Benefit-risk ratio; Pediatric ID COMPUTED-TOMOGRAPHY UTILIZATION; PEDIATRIC CHEST CT; EMERGENCY-DEPARTMENT; INFORMED-CONSENT; INDUCED CANCER; IONIZING-RADIATION; NUCLEAR-MEDICINE; CYSTIC-FIBROSIS; UNITED-STATES; HEALTH-RISKS AB In order to personalize the communication of the CT risk, we need to describe the risk in the context of the clinical benefit of CT, which will generally be much higher, provided a CT scan has a well-established clinical indication. However as pediatric radiologists we should be careful not to overstate the benefit of CT, being aware that medico-legal pressures and the realities of health care economics have led to overutilization of the technology. And even though we should not use previously accumulated radiation dose to a child as an argument against conducting a clinically indicated scan (the "sunk-cost" bias), we should consider patients' radiation history in the diagnostic decision process. As a contribution to future public health, it makes more sense to look for non-radiating alternatives to CT in the much larger group of basically healthy children who are receiving occasional scans for widely prevalent conditions such as appendicitis and trauma than to attempt lowering CT use in the smaller group of patients with chronic conditions with a limited life expectancy. When communicating the CT risk with individual patients and their parents, we should acknowledge and address their concerns within the framework of informed decision-making. When appropriate, we may express the individual radiation risk, based on estimates of summated absorbed organ dose, as an order of magnitude rather than as an absolute number, and compare this with the much larger natural cancer incidence over a child's lifetime, and with other risks in medicine and daily life. We should anticipate that many patients cannot make informed decisions on their own in this complex matter, and we should offer our guidance while maintaining respect for patient autonomy. Proper documentation of the informed decision process is important for future reference. In concert with our referring physicians, pediatric radiologists are well-equipped to tackle the complexities associated with the communication of CT risk, a task that often falls upon us, and by becoming more involved in the diagnostic decision process we can add value to the health care system. C1 Massachusetts Gen Hosp, Div Pediat Radiol, Boston, MA 02114 USA. RP Westra, SJ (reprint author), Massachusetts Gen Hosp, Div Pediat Radiol, 34 Fruit St,White 246A, Boston, MA 02114 USA. EM swestra@partners.org NR 81 TC 4 Z9 4 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD OCT PY 2014 VL 44 SU 3 BP 525 EP 533 DI 10.1007/s00247-014-3087-9 PG 9 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA AR6WL UT WOS:000343721300024 PM 25304716 ER PT J AU Pruitt, LD Luxton, DD Shore, P AF Pruitt, Larry D. Luxton, David D. Shore, Peter TI Additional Clinical Benefits of Home-Based Telemental Health Treatments SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article DE telemental health; home-based; telehealth; telemedicine; telecommunications ID SOCIAL SUPPORT; TELEPSYCHIATRIC CONSULTATION; MENTAL-ILLNESS; PRIMARY-CARE; FOLLOW-UP; TELEHEALTH; OUTCOMES; SATISFACTION; TELEMEDICINE; VETERANS AB Home-based telemental health (HBTMH) has several important benefits for both patients and clinical practitioners including improved access to services, convenience, flexibility, and potential cost savings. HBTMH also has the potential to offer additional clinical benefits that are not realized with traditional in-office alternatives. Through a review of the empirical literature, this article presents and evaluates evidence of the clinical benefits and limitations of HBTMH. Particular topics include treatment attendance and satisfaction, social support, access to contextual information, patient and practitioner safety, and concerns about privacy and stigma. By making use of commonly available communication technologies, HBTMH affords opportunities to bridge gaps in care to meet current and future mental health care needs. C1 [Pruitt, Larry D.; Luxton, David D.] Natl Ctr Telehealth & Technol, Tacoma, WA 98431 USA. [Luxton, David D.] Univ Washington, Sch Med, Seattle, WA USA. [Shore, Peter] Portland VA Med Ctr, Portland, OR USA. [Shore, Peter] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Pruitt, LD (reprint author), Natl Ctr Telehealth & Technol, 9933 W Hayes St, Tacoma, WA 98431 USA. EM Larry.d.pruitt21.ctr@mail.mil OI Pruitt, Larry/0000-0001-6925-7830 NR 59 TC 6 Z9 6 U1 3 U2 11 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 EI 1939-1323 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD OCT PY 2014 VL 45 IS 5 BP 340 EP 346 DI 10.1037/a0035461 PG 7 WC Psychology, Multidisciplinary SC Psychology GA AR9BU UT WOS:000343866900007 ER PT J AU Turnell, A Rasmussen, V Butow, P Juraskova, I Kirsten, L Wiener, L Patenaude, A Hoekstra-Weebers, J AF Turnell, Adrienne Rasmussen, Victoria Butow, Phyllis Juraskova, Ilona Kirsten, Laura Wiener, Lori Patenaude, Andrea Hoekstra-Weebers, Josette TI Stress and Burnout in Psychosocial Oncology Staff Prevalence and Predictors SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Turnell, Adrienne; Rasmussen, Victoria; Butow, Phyllis; Juraskova, Ilona] Univ Sydney, Sydney, NSW 2006, Australia. [Kirsten, Laura] Nepean Canc Care Ctr, Sydney, NSW, Australia. [Wiener, Lori] Ctr Canc Res NCI, Bethesda, MD USA. [Patenaude, Andrea] Dana Faber Canc Inst, Boston, MA USA. [Hoekstra-Weebers, Josette] Dutch Assoc Psychosocial Oncol, Amsterdam, Netherlands. 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2014 VL 23 SU 3 SI SI MA S4-0061 BP 18 EP 18 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA AS0YX UT WOS:000344003700025 ER PT J AU Fujisawa, D AF Fujisawa, Daisuke TI Schizophrenia and Cancer - Why is it Important? SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Fujisawa, Daisuke] Keio Univ, Sch Med, Dept Neuropsychiat, Tokyo, Japan. [Fujisawa, Daisuke] Massachusetts Gen Hosp, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2014 VL 23 SU 3 SI SI MA S13-0266 BP 41 EP 42 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA AS0YX UT WOS:000344003700058 ER PT J AU Greenberg, D AF Greenberg, Donna TI Psychotic Disorder in Cancer Patients Seen Through the US National Comprehensive Cancer Center guidelines for Distress: Implications for Differential Diagnosis and Facilitating Care of Cancer Patients with Chronic Psychotic Disorder SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Greenberg, Donna] Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Boston, MA USA. [Greenberg, Donna] Massachusetts Gen Hosp, Dept Psychiat, Ctr Canc, Boston, MA 02114 USA. [Greenberg, Donna] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2014 VL 23 SU 3 SI SI MA S13-0249 BP 41 EP 41 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA AS0YX UT WOS:000344003700057 ER PT J AU Irwin, K AF Irwin, Kelly TI Breast Cancer and Schizophrenia: Disparities in Outcomes and Opportunities for Improvement SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Irwin, Kelly] Harvard Univ, Sch Med, Boston, MA USA. [Irwin, Kelly] 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2014 VL 23 SU 3 SI SI MA S13-0579 BP 42 EP 42 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA AS0YX UT WOS:000344003700060 ER PT J AU Wakefield, CE McLoone, JK Tucker, K Patenaude, AF Doolan, EJ Cohn, RJ AF Wakefield, Claire E. McLoone, Jordana K. Tucker, Kathy Patenaude, Andrea F. Doolan, Emma J. Cohn, Richard J. TI Are Childhood Cancer Survivors and Their Parents Interested in Receiving Genetics-related Information and Services? A Multi-perspective, Mixed Methods Study SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Wakefield, Claire E.; McLoone, Jordana K.; Doolan, Emma J.; Cohn, Richard J.] Sydney Childrens Hosp, Kids Canc Ctr, Behav Sci Unit, Randwick, NSW, Australia. [Wakefield, Claire E.; McLoone, Jordana K.; Doolan, Emma J.; Cohn, Richard J.] Univ New S Wales, UNSW Med, Sch Womens & Childrens Hlth, Sydney, NSW, Australia. [Tucker, Kathy] Prince Wales Hosp, Dept Med Oncol, Randwick, NSW 2031, Australia. [Tucker, Kathy] Univ New S Wales, Prince Wales Clin Sch, Sydney, NSW, Australia. [Patenaude, Andrea F.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care,Dept Psych, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2014 VL 23 SU 3 SI SI MA G-0086 BP 91 EP 92 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA AS0YX UT WOS:000344003700130 ER PT J AU Fasciano, K Souza, P Bielaczyc, A Englander, S AF Fasciano, Karen Souza, Phoebe Bielaczyc, Anne Englander, Susan TI Building Connection and Creating Community Through the Development of a Young Adult Cancer Conference SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Fasciano, Karen; Souza, Phoebe; Bielaczyc, Anne; Englander, Susan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fasciano, Karen] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2014 VL 23 SU 3 SI SI MA P1-0240 BP 191 EP 192 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA AS0YX UT WOS:000344003700278 ER PT J AU Oktay, J Nedjat-Haiem, F Davis, C AF Oktay, Julianne Nedjat-Haiem, Frances Davis, Cindy TI Implementing Distress Screening: Social Workers' Experiences SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Oktay, Julianne] Univ Maryland, Baltimore, MD 21201 USA. [Nedjat-Haiem, Frances] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Davis, Cindy] Univ Tennessee, Knoxville, TN 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2014 VL 23 SU 3 SI SI MA P1-0199 BP 239 EP 239 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA AS0YX UT WOS:000344003700357 ER PT J AU Blashill, AJ Wilhelm, S AF Blashill, Aaron J. Wilhelm, Sabine TI Body Image Distortions, Weight, and Depression in Adolescent Boys: Longitudinal Trajectories Into Adulthood SO PSYCHOLOGY OF MEN & MASCULINITY LA English DT Article DE body image distortion; body mass index; depression; males; weight ID COMORBIDITY SURVEY REPLICATION; DYSMORPHIC DISORDER; CHINESE ADOLESCENTS; PERCEIVED WEIGHT; EATING PATHOLOGY; YOUNG ADULTHOOD; RISK-FACTORS; PREVALENCE; MUSCULARITY; PERCEPTION AB Depressive symptoms are common among the U.S. population, yet research into prospective risk factors of depression among men is limited. Distorted body image is also prevalent among adolescent boys, and may be linked with elevated depression; however, longitudinal associations have rarely been measured. Thus, the aim of the current study was to assess the prospective relationship between forms of body image distortion and depressive symptoms among adolescent boys, into adulthood. Data were extracted from the National Longitudinal Study of Adolescent Health. Participants were 2,139 U.S. adolescent boys (M age = 16) who were followed prospectively over 13 years (1996 to 2009), into adulthood. Longitudinal mixed-level modeling was used to assess the temporal prediction of body image distortion on symptoms of depression. Results revealed that boys who were average weight and viewed themselves as either very underweight (very underweight distorted; Cohen's d = .47) or overweight (overweight distorted; Cohen's d = .29) reported significantly higher levels of depressive symptoms compared to boys who accurately viewed their weight as average; this effect remained constant over the 13-year study period. These findings indicated that distortions in body image, particularly extreme distortions, are risk factors for elevated depressive symptoms among adolescent boys, and persist into early adulthood. C1 [Blashill, Aaron J.; Wilhelm, Sabine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. RP Blashill, AJ (reprint author), 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ablashill@partners.org FU NICHD NIH HHS [P01 HD031921]; NIMH NIH HHS [K23 MH096647] NR 53 TC 12 Z9 13 U1 2 U2 11 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1524-9220 EI 1939-151X J9 PSYCHOL MEN MASCULIN JI Psychol. Men Masculinity PD OCT PY 2014 VL 15 IS 4 BP 445 EP 451 DI 10.1037/a0034618 PG 7 WC Psychology, Social SC Psychology GA AR9BN UT WOS:000343866200013 PM 25383047 ER PT J AU Davis, CR Usher, N Dearing, E Barkai, AR Crowell-Doom, C Neupert, SD Mantzoros, CS Crowell, JA AF Davis, Cynthia R. Usher, Nicole Dearing, Eric Barkai, Ayelet R. Crowell-Doom, Cynthia Neupert, Shevaun D. Mantzoros, Christos S. Crowell, Judith A. TI Attachment and the Metabolic Syndrome in Midlife: The Role of Interview-Based Discourse Patterns SO PSYCHOSOMATIC MEDICINE LA English DT Article DE adult attachment; metabolic syndrome; adverse childhood experiences ID ADVERSE CHILDHOOD EXPERIENCES; WORKING MODELS; SOCIAL RELATIONSHIPS; PATIENT-ADHERENCE; MEDICAL-TREATMENT; MAJOR DEPRESSION; HEALTH BEHAVIOR; CHRONIC DISEASE; CENTRAL OBESITY; LIFE-COURSE AB Objective Adult attachment discourse patterns and current family relationship quality were examined as correlates of health behaviors and number of metabolic syndrome (MetS) criteria met, and as mediators of the link between childhood adversity and these health outcomes. Methods A sample of 215 white/European American and black/African American adults aged 35 to 55 years were examined using a cross-sectional study design. Discourse was assessed with the Adult Attachment Interview, using coherence (a marker of attachment security), unresolved trauma/loss (a marker of disorganized cognitions related to trauma or loss), and idealization (minimizing stressful experiences and their impact) scores. Relationship quality, adverse childhood experiences, and current depressive symptoms were assessed, as were health behaviors of diet, exercise, and smoking. MetS includes obesity, elevated blood pressure, elevated fasting glucose, high triglycerides, and low high-density lipoprotein cholesterol. Results Using path analysis and including childhood adversity severity and depressive symptoms in the model, both Adult Attachment Interview coherence and unresolved trauma/loss were directly linked to the number of MetS criteria (r = 0.186 and r = 0.170, respectively). Idealization was indirectly linked to MetS through poor diet (r = 0.183). The final model explained 21% of the variance in scores for the number of MetS criteria met. Conclusions Insecure adult attachment is associated with increased risk of MetS. C1 [Davis, Cynthia R.; Usher, Nicole; Crowell-Doom, Cynthia; Crowell, Judith A.] Judge Baker Childrens Ctr, Boston, MA USA. [Dearing, Eric] Boston Coll, Boston, MA USA. [Barkai, Ayelet R.] Cambridge Hlth Alliance, Dept Psychiat, Cambridge, MA USA. [Neupert, Shevaun D.] N Carolina State Univ, Dept Psychol, Raleigh, NC 27695 USA. [Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA USA. [Crowell, Judith A.] SUNY Stony Brook, Sch Med, Dept Psychiat, Stony Brook, NY 11794 USA. RP Crowell, JA (reprint author), SUNY Stony Brook, Div Child & Adolescent Psychiat, Putnam Hall South Campus, Stony Brook, NY 11794 USA. EM judith.crowell@stonybrookmedicine.edu FU National Institute of Aging [R01 AG 032030]; National Institute of Diabetes and Digestive and Kidney Diseases [81913]; Harvard Clinical and Translational Science Center from National Center for Research Resources [UL1 RR025758] FX This research was supported by the National Institute of Aging (Grant No. R01 AG 032030, to J.A. Crowell), National Institute of Diabetes and Digestive and Kidney Diseases (Grant No. 81913, to C. S. Mantzoros), and Harvard Clinical and Translational Science Center (Grant No. UL1 RR025758, to C. S. Mantzoros) from the National Center for Research Resources. The authors have no conflicts of interest to disclose. NR 112 TC 1 Z9 1 U1 5 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD OCT PY 2014 VL 76 IS 8 BP 611 EP 621 DI 10.1097/PSY.0000000000000107 PG 11 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AR9HK UT WOS:000343883900005 PM 25264975 ER PT J AU Fan, VS Locke, ER Diehr, P Wilsdon, A Enright, P Yende, S Avdalovic, M Barr, G Kapur, VK Thomas, R Krishnan, JA Lovasi, G Thielke, S AF Fan, Vincent S. Locke, Emily R. Diehr, Paula Wilsdon, Anthony Enright, Paul Yende, Sachin Avdalovic, Mark Barr, Graham Kapur, Vishesh K. Thomas, Rachel Krishnan, Jerry A. Lovasi, Gina Thielke, Stephen TI Disability and Recovery of Independent Function in Obstructive Lung Disease: The Cardiovascular Health Study SO RESPIRATION LA English DT Article DE Chronic airflow obstruction; Activities of daily living; Disability ID AIR-FLOW OBSTRUCTION; PULMONARY-DISEASE; OLDER-ADULTS; PHYSICAL-ACTIVITY; CONTROLLED-TRIAL; COPD; REHABILITATION; EXERCISE; OUTCOMES; STATES AB Background: Chronic obstructive lung disease frequently leads to disability. Older patients may experience transitions between states of disability and independence over time. Objective: To identify factors associated with transition between states of disability and independent function in obstructive lung disease. Methods: We analyzed data on 4,394 participants in the Cardiovascular Health Study who completed prebronchodilator spirometry. We calculated the 1-year probability of developing and resolving impairment in >= 1 instrumental activity of daily living (IADL) or >= 1 activity of daily living (ADL) using transition probability analysis. We identified factors associated with resolving disability using relative risk (RR) regression. Results: The prevalence of IADL impairment was higher with moderate (23.9%) and severe (36.9%) airflow obstruction compared to normal spirometry (22.5%; p < 0.001). Among participants with severe airflow obstruction, 23.5% recovered independence in IADLs and 40.5% recovered independence in ADLs. In the adjusted analyses, airflow obstruction predicted the development of IADL, but not ADL impairment. Participants with severe airflow obstruction were less likely to resolve IADL impairment [RR 0.67 and 95% confidence interval (CI) 0.49-0.94]. Compared to the most active individuals (i.e. who walked >= 28 blocks per week), walking less was associated with a decreased likelihood of resolving IADL impairment (7-27 blocks: RR 0.81 and 95% CI 0.69-0.86 and < 7 blocks: RR 0.73 and 95% CI 0.61-0.86). Increased strength (RR 1.16 and 95% CI 1.05-1.29) was associated with resolving IADL impairment. Conclusions: Disability is common in older people, especially in those with severe airflow obstruction. Increased physical activity and muscle strength are associated with recovery. Research is needed on interventions to improve these factors among patients with obstructive lung disease and disability. (C) 2014 S. Karger AG, Basel C1 [Fan, Vincent S.; Locke, Emily R.; Thomas, Rachel] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Fan, Vincent S.; Kapur, Vishesh K.] Univ Washington, Dept Med, Seattle, WA USA. [Diehr, Paula; Wilsdon, Anthony] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Thielke, Stephen] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Diehr, Paula] Univ Arizona, Tucson, AZ USA. [Yende, Sachin] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA. [Avdalovic, Mark] Univ Calif Davis, Div Pulm & Crit Care, Sacramento, CA 95817 USA. [Barr, Graham] Columbia Univ, Med Ctr, New York, NY USA. [Lovasi, Gina] Columbia Univ, Dept Epidemiol, New York, NY USA. [Krishnan, Jerry A.] Univ Illinois Hosp & Hlth Sci Syst, Chicago, IL USA. RP Fan, VS (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-152, Seattle, WA 98108 USA. EM Vincent.fan@va.gov RI Lovasi, Gina/C-2781-2009; OI Lovasi, Gina/0000-0003-2613-9599; Kapur, Vishesh/0000-0002-5417-1097 FU Merck; Glaxo-Smith Kline; Novartis; National Institutes of Health (NIH; US-EPA); Alpha1 Foundation; NIH; Department of Veterans Affairs (VA); PCORI; VA Puget Sound Health Care System, Seattle, Washington, USA FX Dr. Avdalovic received research support from Merck, Glaxo-Smith Kline and Novartis. Dr. Barr received grants or contracts from the National Institutes of Health (NIH; US-EPA) and the Alpha1 Foundation; in-kind contribution from Cenestra Health, travel reimbursement from Boeringher Ingleheim and royalties from UpToDate. Dr. Fan received grants from the NIH and Department of Veterans Affairs (VA) and has served as a consultant to Uptake Medical. Dr. Krishnan received grants from the NIH and PCORI and royalties from UpToDate. No other authors have any financial interests to report, and none of the authors report any conflicts of interest with the material in the manuscript. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of VA or the United States government. This material is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, Washington, USA. NR 46 TC 1 Z9 1 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0025-7931 EI 1423-0356 J9 RESPIRATION JI Respiration PD OCT PY 2014 VL 88 IS 4 BP 329 EP 338 DI 10.1159/000363772 PG 10 WC Respiratory System SC Respiratory System GA AR8IS UT WOS:000343819400011 PM 25228204 ER PT J AU Stamp, LK Merriman, TR Barclay, ML Singh, JA Roberts, RL Wright, DFB Dalbeth, N AF Stamp, Lisa K. Merriman, Tony R. Barclay, Murray L. Singh, Jasvinder A. Roberts, Rebecca L. Wright, Daniel F. B. Dalbeth, Nicola TI Impaired response or insufficient dosage?-Examining the potential causes of "inadequate response" to allopurinol in the treatment of gout SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE Gout; Allopurinol; Oxypurinol; Drug resistance ID URATE-LOWERING THERAPY; XANTHINE-OXIDASE; SERUM URATE; ALDEHYDE OXIDASE; HYPERURICEMIA; OXYPURINOL; DISEASE; BENZBROMARONE; TRANSPORTER; POPULATION AB Objectives: Gout is one of the most common forms of arthritis. It is well established that urate-lowering therapy that aims for a serum urate less than at least 0.36 mmol/l (6 mg/dl) is required for the successful management of gout. Allopurinol, a xanthine oxidase (XO) inhibitor, is the most commonly used urate-lowering therapy. However, many patients fail to achieve the target serum urate on allopurinol; these patients can be considered to have "inadequate response" to allopurinol. Herein, we examine the potential mechanisms and implications of inadequate response to allopurinol. Methods: The literature was reviewed for potential causes for failure to reach target serum urate in patients receiving allopurinol. Results: The two most common causes of inadequate response to allopurinol are poor adherence and under-dosing of allopurinol. Adherent patients who fail to achieve target serum urate on standard doses of allopurinol form a group that could be considered to be "partially resistant" to allopurinol. There are four potential mechanisms for partial allopurinol resistance: decreased conversion of allopurinol to oxypurinol; increased renal excretion of oxypurinol; abnormality in XO structure and/or function such that oxypurinol is rendered less effective and/or drug interactions. Conclusions: It is important to determine the reasons for failure to achieve treatment targets with allopurinol, particularly as newer agents become available. The knowledge of the mechanisms for inadequate response may help guide the clinician towards making a therapeutic choice that is more likely to result in achieving the serum urate target. (C) 2014 Elsevier Inc. All rights reserved. C1 [Stamp, Lisa K.] Univ Otago, Dept Med, Christchurch 8140, New Zealand. [Merriman, Tony R.] Univ Otago, Dept Biochem, Dunedin, New Zealand. [Barclay, Murray L.] Christchurch Hosp, Dept Clin Pharmacol, Christchurch, New Zealand. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Div Rheumatol, Birmingham, AL USA. [Roberts, Rebecca L.] Univ Otago, Dept Surg Sci, Dunedin, New Zealand. [Wright, Daniel F. B.] Univ Otago, Sch Pharm, Dunedin, New Zealand. [Dalbeth, Nicola] Univ Auckland, Dept Med, Auckland, New Zealand. RP Stamp, LK (reprint author), Univ Otago, Dept Med, POB 4345, Christchurch 8140, New Zealand. EM lisa.stamp@cdhb.health.nz OI Merriman, Tony/0000-0003-0844-8726 FU Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) [U19 HS021110]; National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) [P50 AR060772, U34 AR062891]; National Institute of Aging (NIA) [U01 AG018947]; National Cancer Institute (NCI) [U10 CA149950]; Patient Centered Outcomes Research Institute (PCORI) [CE-1304-6631]; Division of Rheumatology at the University of Alabama at Birmingham FX This article is the result of work supported by a grant from the Division of Rheumatology at the University of Alabama at Birmingham. JAS is supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) U19 HS021110, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) P50 AR060772 and U34 AR062891, National Institute of Aging (NIA) U01 AG018947, National Cancer Institute (NCI) U10 CA149950, the resources and the use of facilities at the VA Medical Center at Birmingham, Alabama and research contract CE-1304-6631 from the Patient Centered Outcomes Research Institute (PCORI). NR 31 TC 9 Z9 10 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0049-0172 EI 1532-866X J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD OCT PY 2014 VL 44 IS 2 BP 170 EP 174 DI 10.1016/j.semarthrit.2014.05.007 PG 5 WC Rheumatology SC Rheumatology GA AR8WM UT WOS:000343852200007 PM 24925693 ER PT J AU Arias, SA Zhang, Z Hillerns, C Sullivan, AF Boudreaux, ED Miller, I Camargo, CA AF Arias, Sarah A. Zhang, Zi Hillerns, Carla Sullivan, Ashley F. Boudreaux, Edwin D. Miller, Ivan Camargo, Carlos A. TI Using Structured Telephone Follow-up Assessments to Improve Suicide-Related Adverse Event Detection SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID REPORTING SYSTEM; PATIENT SAFETY; RISK AB Adverse event (AE) detection and reporting practices were compared during the first phase of the Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE), a suicide intervention study. Data were collected using a combination of chart reviews and structured telephone follow-up assessments postenrollment. Beyond chart reviews, structured telephone follow-up assessments identified 45% of the total AEs in our study. Notably, detection of suicide attempts significantly varied by approach with 53 (18%) detected by chart review, 173 (59%) by structured telephone follow-up assessments, and 69 (23%) marked as duplicates. Findings provide support for utilizing multiple methods for more robust AE detection in suicide research. C1 [Arias, Sarah A.; Sullivan, Ashley F.; Camargo, Carlos A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Zhang, Zi] Commonwealth Massachusetts, Ctr Hlth Informat & Anal, Boston, MA USA. [Zhang, Zi; Hillerns, Carla] Univ Massachusetts, Off Survey Res, Ctr Hlth Policy & Res, Sch Med, Shrewsbury, MA USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Miller, Ivan] Butler Hosp, Providence, RI 02906 USA. RP Arias, SA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM sarias1@mgh.harvard.edu OI Boudreaux, Edwin/0000-0002-3223-6371; Arias, Sarah/0000-0003-1832-8824 FU NIMH NIH HHS [U01MH088278, U01 MH088278] NR 28 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 EI 1943-278X J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD OCT PY 2014 VL 44 IS 5 BP 537 EP 547 DI 10.1111/sltb.12088 PG 11 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AS3LT UT WOS:000344180000006 PM 24588679 ER PT J AU Creaney, J Dick, IM Meniawy, TM Leong, SL Leon, JS Demelker, Y Segal, A Musk, AW Lee, YCG Skates, SJ Nowak, AK Robinson, BWS AF Creaney, Jenette Dick, Ian M. Meniawy, Tarek M. Leong, Su Lyn Leon, Justine S. Demelker, Yvonne Segal, Amanda Musk, A. W. (Bill) Lee, Y. C. Gary Skates, Steven J. Nowak, Anna K. Robinson, Bruce W. S. TI Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma SO THORAX LA English DT Article ID TO-LYMPHOCYTE RATIO; PLEURAL MESOTHELIOMA; DIAGNOSIS; CANCER; EFFUSIONS; CYTOLOGY; FAMILY; BLOOD AB Background Pleural malignant mesothelioma (MM) is a deadly tumour predominantly associated with asbestos exposure. A reliable diagnostic and prognostic marker for MM will significantly enhance clinical care and is an area of intense research. Soluble mesothelin is the most studied and an FDA-approved biomarker for MM. A recent report showed promising results using fibulin-3 as a new diagnostic marker. The aim of this study was to compare the utility of fibulin-3 versus mesothelin, singly or in combination. Methods Fibulin-3 and soluble mesothelin were determined by ELISA in the plasma and pleural fluid of 153 patients presenting with a pleural effusion including 82 with MM, 36 with non-MM malignant effusions and 35 with benign effusions. Biomarker concentrations were determined in the plasma of an additional 49 cases with benign asbestos-related disease. Results Mesothelin provides better diagnostic accuracy than fibulin-3 for MM whether measured in plasma or pleural effusion: area under the curve (AUC) for plasma was 0.822 (95% CI 0.76 to 0.87) compared with 0.671 (0.61 to 0.73), respectively, and for pleural fluid AUC was 0.815 (0.74 to 0.87) compared with 0.588 (0.51 to 0.67), respectively. Effusion fibulin-3 was an independent significant prognostic factor for survival in MM patients; HR 2.08 (1.14 to 3.82), p=0.017. MM patients with effusion fibulin-3 levels below the median survived significantly longer than those with levels above the median (14.1 vs 7.9 months, p=0.012). Mesothelin and neutrophil to lymphocyte ratio were not significant prognostic markers. Conclusions Soluble mesothelin is a superior diagnostic biomarker for MM compared with fibulin-3, whereas fibulin-3 provides superior prognostic information compared with mesothelin. C1 [Creaney, Jenette; Dick, Ian M.; Meniawy, Tarek M.; Leong, Su Lyn; Leon, Justine S.; Demelker, Yvonne; Musk, A. W. (Bill); Nowak, Anna K.; Robinson, Bruce W. S.] Univ Western Australia, Natl Ctr Asbestos Related Dis, Sch Med & Pharmacol, Nedlands, WA 6009, Australia. [Creaney, Jenette; Leong, Su Lyn; Leon, Justine S.; Demelker, Yvonne; Robinson, Bruce W. S.] Sir Charles Gairdner Hosp, Australian Mesothelioma Tissue Bank, Nedlands, WA 6009, Australia. [Segal, Amanda] Queen Elizabeth II Med Ctr, PathWest Lab Med WA, Nedlands, WA, Australia. [Musk, A. W. (Bill); Lee, Y. C. Gary; Robinson, Bruce W. S.] Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA 6009, Australia. [Lee, Y. C. Gary] Univ Western Australia, Ctr Asthma Allergy & Resp Res, Sch Med & Pharmacol, Nedlands, WA 6009, Australia. [Skates, Steven J.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Nowak, Anna K.] Sir Charles Gairdner Hosp, Dept Med Oncol, Nedlands, WA 6009, Australia. RP Creaney, J (reprint author), Univ Western Australia, Natl Ctr Asbestos Related Dis, Sch Med & Pharmacol, Nedlands, WA 6009, Australia. EM jenette.creaney@uwa.edu.au RI Robinson, Bruce/N-1900-2014; Nowak, Anna/B-2487-2013 OI Nowak, Anna/0000-0002-9317-9526 FU National Health and Medical Research Council [1063067] FX National Health and Medical Research Council (1063067). NR 26 TC 29 Z9 29 U1 1 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 EI 1468-3296 J9 THORAX JI Thorax PD OCT PY 2014 VL 69 IS 10 BP 895 EP 902 DI 10.1136/thoraxjnl-2014-205205 PG 8 WC Respiratory System SC Respiratory System GA AR9KW UT WOS:000343893500006 PM 25037982 ER PT J AU Pease, SE Segal, RA AF Pease, Sarah E. Segal, Rosalind A. TI Preserve and protect: maintaining axons within functional circuits SO TRENDS IN NEUROSCIENCES LA English DT Review DE axon injury; axon maintenance; axon survival; neurodegeneration; neurotrophins; Wallerian degeneration ID NICOTINAMIDE ADENINE-DINUCLEOTIDE; PROMOTES WALLERIAN DEGENERATION; UBIQUITIN-PROTEASOME SYSTEM; AMYLOID PRECURSOR PROTEIN; NERVE GROWTH-FACTOR; SELF-DESTRUCTION; CELL-DEATH; SUPERFAMILY PROTEIN; SYMPATHETIC NEURONS; SURVIVAL RESPONSE AB During development, neural circuits are initially generated by exuberant innervation and are rapidly refined by selective preservation and elimination of axons. The establishment and maintenance of functional circuits therefore requires coordination of axon survival and degeneration pathways. Both developing and mature circuits rely on interdependent mitochondrial and cytoskeletal components to maintain axonal health and homeostasis; injury or diseases that impinge on these components frequently cause pathologic axon loss. Here, we review recent findings that identify mechanisms of axonal preservation in the contexts of development, injury, and disease. C1 [Pease, Sarah E.; Segal, Rosalind A.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Pease, Sarah E.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Pease, Sarah E.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. RP Pease, SE (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM rosalind_segal@dfci.harvard.edu FU National Institutes of Health [R01NS050674]; Barr Weaver Award; Harvard/Massachusetts Institute of Technology (MIT) Joint Research Grant in Basic Neuroscience; Edward R. and Anne G. Lefler Center Predoctoral Fellowship FX Our research is supported by the National Institutes of Health grant R01NS050674, the Barr Weaver Award, and the Harvard/Massachusetts Institute of Technology (MIT) Joint Research Grant in Basic Neuroscience to R.A.S., and by the Edward R. and Anne G. Lefler Center Predoctoral Fellowship to S.E.P. We thank Dr Katharina Cosker, Sara Fenstermacher, and Maria Pazyra-Murphy for critical reading of the manuscript. NR 103 TC 7 Z9 7 U1 2 U2 10 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD OCT PY 2014 VL 37 IS 10 BP 572 EP 582 DI 10.1016/j.tins.2014.07.007 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AR8RM UT WOS:000343842200008 PM 25167775 ER PT J AU Rundek, T Brown, SC Wang, KF Dong, CH Farrell, MB Heller, GV Gornik, HL Hutchisson, M Needleman, L Benenati, JF Jaff, MR Meier, GH Perese, S Bendick, P Hamburg, NM Lohr, JM LaPerna, L Leers, SA Lilly, MP Tegeler, C Alexandrov, AV Katanick, SL AF Rundek, Tatjana Brown, Scott C. Wang, Kefeng Dong, Chuanhui Farrell, Mary Beth Heller, Gary V. Gornik, Heather L. Hutchisson, Marge Needleman, Laurence Benenati, James F. Jaff, Michael R. Meier, George H. Perese, Susana Bendick, Phillip Hamburg, Naomi M. Lohr, Joann M. LaPerna, Lucy Leers, Steven A. Lilly, Michael P. Tegeler, Charles Alexandrov, Andrei V. Katanick, Sandra L. TI Accreditation status and geographic location of outpatient vascular testing facilities among Medicare beneficiaries: The VALUE (Vascular Accreditation, Location & Utilization Evaluation) Study SO VASCULAR MEDICINE LA English DT Article DE Geographic disparities; Intersocietal Accreditation Commission (IAC); Medicare beneficiaries; Vascular Accreditation; Location & Utilization Evaluation (VALUE) Study; Vascular laboratory testing accreditation; Vascular testing AB Objective: There is limited information on the accreditation status and geographic distribution of vascular testing facilities in the US. The Centers for Medicare & Medicaid Services (CMS) provide reimbursement to facilities regardless of accreditation status. The aims were to: (1) identify the proportion of Intersocietal Accreditation Commission (IAC) accredited vascular testing facilities in a 5% random national sample of Medicare beneficiaries receiving outpatient vascular testing services; (2) describe the geographic distribution of these facilities. Methods: The VALUE (Vascular Accreditation, Location & Utilization Evaluation) Study examines the proportion of IAC accredited facilities providing vascular testing procedures nationally, and the geographic distribution and utilization of these facilities. The data set containing all facilities that billed Medicare for outpatient vascular testing services in 2011 (5% CMS Outpatient Limited Data Set (LDS) file) was examined, and locations of outpatient vascular testing facilities were obtained from the 2011 CMS/Medicare Provider of Services (POS) file. Results: Of 13,462 total vascular testing facilities billing Medicare for vascular testing procedures in a 5% random Outpatient LDS for the US in 2011, 13% (n=1730) of facilities were IAC accredited. The percentage of IAC accredited vascular testing facilities in the LDS file varied significantly by US region, p<0.0001: 26%, 12%, 11%, and 7% for the Northeast, South, Midwest, and Western regions, respectively. Conclusions: Findings suggest that the proportion of outpatient vascular testing facilities that are IAC accredited is low and varies by region. Increasing the number of accredited vascular testing facilities to improve test quality is a hypothesis that should be tested in future research. C1 [Rundek, Tatjana; Dong, Chuanhui] Univ Miami, Dept Neurol, Miller Sch Med, Miami, FL USA. [Rundek, Tatjana; Brown, Scott C.; Wang, Kefeng] Univ Miami, Miller Sch Med, Dept Publ Hlth Sci, Miami, FL 33136 USA. [Farrell, Mary Beth; Heller, Gary V.; Hutchisson, Marge; Katanick, Sandra L.] IAC, Ellicott City, MD USA. [Gornik, Heather L.] Cleveland Clin, Dept Vasc Med, Cleveland, OH 44106 USA. [Needleman, Laurence] Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiol, Philadelphia, PA 19107 USA. [Benenati, James F.] Baptist Hosp Miami, Baptist Cardiac & Vasc Inst, Miami, FL USA. [Jaff, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Meier, George H.] Univ Cincinnati, Dept Vasc Surg, Acad Hlth Ctr, Cincinnati, OH USA. [Perese, Susana] Univ So Calif, Keck Sch Med, Dept Vasc Surg, Los Angeles, CA 90033 USA. [Bendick, Phillip] William Beaumont Hosp, Vasc Lab, Royal Oak, MI 48072 USA. [Hamburg, Naomi M.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Lohr, Joann M.] Good Samaritan Outpatient Ctr, Cincinnati, OH USA. [LaPerna, Lucy] Riverside Radiol Associates, Columbus, OH USA. [Leers, Steven A.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Lilly, Michael P.] Univ Maryland, Sch Med, Vasc Lab, Baltimore, MD 21201 USA. [Tegeler, Charles] Wake Forest Baptist Hlth, Winston Salem, NC USA. [Alexandrov, Andrei V.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. RP Brown, SC (reprint author), Univ Miami, Miller Sch Med, Dept Publ Hlth Sci, 1120 NW 14th St Clin Res Bldg CRB Rm 1065, Miami, FL 33136 USA. EM sbrown@med.miami.edu OI Alexandrov, Andrei V/0000-0001-8871-1023 FU Intersocietal Accreditation Commission, 'Utilization of Vascular Testing in Medicare Beneficiaries: The Role of Ultrasound Laboratory Accreditation'; NINDS [K24 NS 062737]; National Institute of Neurological Disorders and Stroke [K24 NS 062737]; Intersocietal Accreditation Commission FX This project was supported by a grant from the Intersocietal Accreditation Commission, 'Utilization of Vascular Testing in Medicare Beneficiaries: The Role of Ultrasound Laboratory Accreditation', awarded to Dr Tatjana Rundek (PI). Its contents are solely the responsibility of the authors and do not necessarily represent the views of the IAC. Dr Rundek has been supported by the NINDS K24 NS 062737 award that allowed for protected time for this research.; FundRef Funding Sources: National Institute of Neurological Disorders and Stroke (Grant / Award Number: 'K24 NS 062737') Intersocietal Accreditation Commission (Grant / Award Number: 'Utilization of Vascular Testing in Medicare Beneficiaries: The Role of Ultrasound Laboratory Accreditation'). NR 13 TC 1 Z9 1 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X EI 1477-0377 J9 VASC MED JI Vasc. Med. PD OCT PY 2014 VL 19 IS 5 BP 376 EP 384 DI 10.1177/1358863X14547561 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AR8ZL UT WOS:000343859800006 PM 25179647 ER PT J AU Van de Bittner, GC Ricq, EL Hooker, JM AF Van de Bittner, Genevieve C. Ricq, Emily L. Hooker, Jacob M. TI A Philosophy for CNS Radiotracer Design SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; LATE-STAGE FLUORINATION; IN-VIVO; HUMAN BRAIN; HISTONE DEACETYLASE; PET LIGANDS; F-18; RECEPTORS; REPRODUCIBILITY; INHIBITORS AB CONSPECTUS: Decades after its discovery, positron emission tomography (PET) remains the premier tool for imaging neurochemistry in living humans. Technological improvements in radiolabeling methods, camera design, and image analysis have kept PET in the forefront. In addition, the use of PET imaging has expanded because researchers have developed new radiotracers that visualize receptors, transporters, enzymes, and other molecular targets within the human brain. However, of the thousands of proteins in the central nervous system (CNS), researchers have successfully imaged fewer than 40 human proteins. To address the critical need for new radiotracers, this Account expounds on the decisions, strategies, and pitfalls of CNS radiotracer development based on our current experience in this area. We discuss the five key components of radiotracer development for human imaging: choosing a biomedical question, selection of a biological target, design of the radiotracer chemical structure, evaluation of candidate radiotracers, and analysis of preclinical imaging. It is particularly important to analyze the market of scientists or companies who might use a new radiotracer and carefully select a relevant biomedical question(s) for that audience. In the selection of a specific biological target, we emphasize how target localization and identity can constrain this process and discuss the optimal target density and affinity ratios needed for binding-based radiotracers. In addition, we discuss various PET test-retest variability requirements for monitoring changes in density, occupancy, or functionality for new radiotracers. In the synthesis of new radiotracer structures, high-throughput, modular syntheses have proved valuable, and these processes provide compounds with sites for late-stage radioisotope installation. As a result, researchers can manage the time constraints associated with the limited half-lives of isotopes. In order to evaluate brain uptake, a number of methods are available to predict bioavailability, blood-brain barrier (BBB) permeability, and the associated issues of nonspecific binding and metabolic stability. To evaluate the synthesized chemical library, researchers need to consider high-throughput affinity assays, the analysis of specific binding, and the importance of fast binding kinetics. Finally, we describe how we initially assess preclinical radiotracer imaging, using brain uptake, specific binding, and preliminary kinetic analysis to identify promising radiotracers that may be useful for human brain imaging. Although we discuss these five design components separately and linearly in this Account, in practice we develop new PET-based radiotracers using these design components nonlinearly and iteratively to develop new compounds in the most efficient way possible. C1 [Van de Bittner, Genevieve C.; Ricq, Emily L.; Hooker, Jacob M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. [Ricq, Emily L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. RP Hooker, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. EM hooker@nmr.mgh.harvard.edu FU National Institutes of Health [NIH R01:5R01DA030321]; Department of Energy (DOE) [DE-SC0008430] FX We acknowledge Aaron Keefe for creating the artwork in Figure 1, which illustrates the authors' fountain-based view of the radiotracer development process. We thank the members of the Hooker Lab for their insight and advice and Dr. Changning Wang for contribution of data. We acknowledge the National Institutes of Health (Grant NIH R01:5R01DA030321) and the Department of Energy (DOE Training Grant DE-SC0008430) for funding this work. NR 51 TC 14 Z9 14 U1 3 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0001-4842 EI 1520-4898 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD OCT PY 2014 VL 47 IS 10 BP 3127 EP 3134 DI 10.1021/ar500233s PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA AR5RG UT WOS:000343640600027 PM 25272291 ER PT J AU Nakagawa, A Lui, FE Wassaf, D Yefidoff-Freedman, R Casalena, D Palmer, MA Meadows, J Mozzarelli, A Ronda, L Abdulmalik, O Bloch, KD Safo, MK Zapol, WM AF Nakagawa, Akito Lui, Francine E. Wassaf, Dina Yefidoff-Freedman, Revital Casalena, Dominick Palmer, Michelle A. Meadows, Jacqueline Mozzarelli, Andrea Ronda, Luca Abdulmalik, Osheiza Bloch, Kenneth D. Safo, Martin K. Zapol, Warren M. TI Identification of a Small Molecule that Increases Hemoglobin Oxygen Affinity and Reduces SS Erythrocyte Sickling SO ACS CHEMICAL BIOLOGY LA English DT Article ID STRUCTURAL BASIS; SERUM-ALBUMIN; CELL-DISEASE; THIOL-GROUP; BINDING; 2,3-DIPHOSPHOGLYCERATE; CRYSTALLOGRAPHY; INHIBITION; DISULFIDES; REACTIVITY AB Small molecules that increase the oxygen affinity of human hemoglobin may reduce sickling of red blood cells in patients with sickle cell disease. We screened 38 700 compounds using small molecule microarrays and identified 427 molecules that bind to hemoglobin. We developed a high-throughput assay for evaluating the ability of the 427 small molecules to modulate the oxygen affinity of hemoglobin. We identified a novel allosteric effector of hemoglobin, di(5-(2,3-dihydro-1,4-benzodioxin-2-yl)-4H-1,2,4-triazol-3-yl)disulfide (TD-1). TD-1 induced a greater increase in oxygen affinity of human hemoglobin in solution and in red blood cells than did 5-hydroxymethyl-2-furfural (5-HMF), N-ethylmaleimide (NEM), or diformamidine disulfide. The three-dimensional structure of hemoglobin complexed with TD-1 revealed that monomeric units of TD-1 bound covalently to beta-Cys93 and beta-Cys112, as well as noncovalently to the central water cavity of the hemoglobin tetramer. The binding of TD-1 to hemoglobin stabilized the relaxed state (R3-state) of hemoglobin. TD-1 increased the oxygen affinity of sickle hemoglobin and inhibited in vitro hypoxia-induced sickling of red blood cells in patients with sickle cell disease without causing hemolysis. Our study indicates that TD-1 represents a novel lead molecule for the treatment of patients with sickle cell disease. C1 [Nakagawa, Akito; Lui, Francine E.; Yefidoff-Freedman, Revital; Bloch, Kenneth D.; Zapol, Warren M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Nakagawa, Akito; Lui, Francine E.; Yefidoff-Freedman, Revital; Bloch, Kenneth D.; Zapol, Warren M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wassaf, Dina; Casalena, Dominick; Palmer, Michelle A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Meadows, Jacqueline; Safo, Martin K.] Virginia Commonwealth Univ, Sch Pharm, Inst Struct Biol & Drug Discovery, Dept Med Chem, Richmond, VA 23219 USA. [Mozzarelli, Andrea] Univ Parma, Dept Pharm, I-43124 Parma, Italy. [Ronda, Luca] Univ Parma, Dept Neurosci, I-43124 Parma, Italy. [Abdulmalik, Osheiza] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. RP Zapol, WM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, 55 Fruit St, Boston, MA 02114 USA. EM wzapol@mgh.harvard.edu RI Mozzarelli, Andrea/C-3615-2014; OI Mozzarelli, Andrea/0000-0003-3762-0062; Ronda, Luca/0000-0002-5389-2669 FU National Institutes of Health/NIH Heart, Lung, and Blood Institute (NIH/NHLBI) [HL103186]; Foundation LeDucq; NIH [CA16059] FX The authors wish to acknowledge J. Winkler, PhD (University of Pennsylvania) for helpful discussions and advice, T. Asakura, MD PhD (The Children's Hospital of Philadelphia) for providing resources to evaluate in vitro sickling of SS RBCs under hypoxic conditions, S. Johnston, PhD, and J. Athanasopoulos, PhD (The Broad Institute), for evaluating the binding of TD-1 to blood. This work was supported by grants from the National Institutes of Health/NIH Heart, Lung, and Blood Institute (NIH/NHLBI) (HL103186, O.A.) and from the Foundation LeDucq (K.D.B.). Structural biology resources were provided, in part, by NIH award CA16059 to the VCU Massey Cancer Center (M.K.S.). NR 47 TC 9 Z9 9 U1 6 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD OCT PY 2014 VL 9 IS 10 BP 2318 EP 2325 DI 10.1021/cb500230b PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AR3ZD UT WOS:000343526900020 PM 25061917 ER PT J AU Kanzaria, HK Probst, MA Ponce, NA Hsia, RY AF Kanzaria, Hemal K. Probst, Marc A. Ponce, Ninez A. Hsia, Renee Y. TI The association between advanced diagnostic imaging and ED length of stay SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Academic-Emergency-Medicine (SAEM) CY MAY 13-17, 2014 CL Dallas, TX SP Soc Acad Emergency Med ID EMERGENCY-DEPARTMENT PATIENTS; NATIONALLY REPRESENTATIVE SAMPLE; MEDICAL-CARE SURVEY; TRENDS; VISITS; CT; RADIATION; RISK AB Objective: There has been a rise in advanced diagnostic imaging (ADI) use in the emergency department (ED). Increased utilization may contribute to longer length of stay (LOS), but prior reports have not considered improved methods for modeling skewed LOS data. Methods: The 2010 National Hospital Ambulatory Medical Care Survey data were analyzed by 5 common ED chief complaints. Generalized linear model (GLM) was compared to quantile and ordinary least squares (OLS) regression to evaluate the association between ADI and ED LOS. Receipt of computed tomography or magnetic resonance imaging was the primary exposure. Emergency department LOS was the primary outcome. Results: Of the 33,685 ED visits analyzed, 17% involved ADI. The median LOS for patients without ADI was 138 minutes compared to 252 minutes for those who received ADI. Overall, GLM offered the most unbiased estimates, although it provided similar adjusted point estimates to OLS for the marginal change in LOS associated with ADI. The effect of imaging differed by LOS quantile, especially for patients with abdominal pain, fever, and back symptoms. Conclusions: Generalized linear model offered an improved modeling approach compared to OLS and quantile regression. Consideration of such techniques may facilitate a more complete view of the effect of ADI on ED LOS. Published by Elsevier Inc. C1 [Kanzaria, Hemal K.] Univ Calif Los Angeles, Ctr Emergency Med, US Dept Vet Affairs, Robert Wood Johnson Fdn Clin Scholars program, Los Angeles, CA 90024 USA. [Probst, Marc A.] Mt Sinai Med Ctr, Dept Emergency Med, New York, NY 10029 USA. [Ponce, Ninez A.] Univ Calif Los Angeles, UCLA Ctr Hlth Policy Res, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA. [Hsia, Renee Y.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Emergency Med, San Francisco, CA 94143 USA. RP Kanzaria, HK (reprint author), Univ Calif Los Angeles, Ctr Emergency Med, US Dept Vet Affairs, Robert Wood Johnson Fdn Clin Scholars program, 10940 Wilshire Blvd,Suite 710, Los Angeles, CA 90024 USA. EM hkanzaria@mednet.ucla.edu OI Ponce, Ninez/0000-0001-5151-6718 FU NCRR NIH HHS [KL2RR024130]; NHLBI NIH HHS [5 K12 HL109005] NR 37 TC 5 Z9 5 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 0735-6757 EI 1532-8171 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD OCT PY 2014 VL 32 IS 10 BP 1253 EP 1258 DI 10.1016/j.ajem.2014.07.038 PG 6 WC Emergency Medicine SC Emergency Medicine GA AR1BU UT WOS:000343316000018 PM 25176565 ER PT J AU Steenkamp, MM Litz, BT AF Steenkamp, Maria M. Litz, Brett T. TI One-Size-Fits-All Approach to PTSD in the VA Not Supported by the Evidence SO AMERICAN PSYCHOLOGIST LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE PROCESSING THERAPY; PSYCHOTHERAPY; VETERANS; TRIAL C1 VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Steenkamp, MM (reprint author), Boston VA Med Ctr, 150 S Huntington Ave,13B-73, Jamaica Plain, MA 02130 USA. EM maria.steenkamp2@va.gov NR 7 TC 6 Z9 6 U1 0 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X EI 1935-990X J9 AM PSYCHOL JI Am. Psychol. PD OCT PY 2014 VL 69 IS 7 BP 706 EP 707 DI 10.1037/a0037360 PG 3 WC Psychology, Multidisciplinary SC Psychology GA AS1AZ UT WOS:000344010000008 PM 25265298 ER PT J AU Karlin, BE Cross, G AF Karlin, Bradley E. Cross, Gerald TI Enhancing Access, Fidelity, and Outcomes in the National Dissemination of Evidence-Based Psychotherapies SO AMERICAN PSYCHOLOGIST LA English DT Editorial Material ID COGNITIVE-BEHAVIORAL THERAPY; HEALTH-CARE-SYSTEM; VETERANS; IMPLEMENTATION; DEPRESSION C1 [Karlin, Bradley E.] Educ Dev Ctr Inc, New York, NY 10014 USA. [Karlin, Bradley E.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Cross, Gerald] US Dept Vet Affairs, Cent Off, Washington, DC USA. RP Karlin, BE (reprint author), Educ Dev Ctr Inc, 96 Morton St,7th Floor, New York, NY 10014 USA. EM bkarlin@edc.org NR 12 TC 3 Z9 3 U1 0 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X EI 1935-990X J9 AM PSYCHOL JI Am. Psychol. PD OCT PY 2014 VL 69 IS 7 BP 709 EP 711 DI 10.1037/a0037384 PG 4 WC Psychology, Multidisciplinary SC Psychology GA AS1AZ UT WOS:000344010000011 PM 25265301 ER PT J AU Amin, MB Lin, DW Gore, JL Srigley, JR Samaratunga, H Egevad, L Rubin, M Nacey, J Carter, HB Klotz, L Sandler, H Zietman, AL Holden, S Montironi, R Humphrey, PA Evans, AJ Epstein, JI Delahunt, B McKenney, JK Berney, D Wheeler, TM Chinnaiyan, AM True, L Knudsen, B Hammond, MEH AF Amin, Mahul B. Lin, Daniel W. Gore, John L. Srigley, John R. Samaratunga, Hema Egevad, Lars Rubin, Mark Nacey, John Carter, H. Ballentine Klotz, Laurence Sandler, Howard Zietman, Anthony L. Holden, Stuart Montironi, Rodolfo Humphrey, Peter A. Evans, Andrew J. Epstein, Jonathan I. Delahunt, Brett McKenney, Jesse K. Berney, Dan Wheeler, Thomas M. Chinnaiyan, Arul M. True, Lawrence Knudsen, Beatrice Hammond, M. Elizabeth H. TI The Critical Role of the Pathologist in Determining Eligibility for Active Surveillance as a Management Option in Patients With Prostate Cancer Consensus Statement With Recommendations Supported by the College of American Pathologists, International Society of Urological Pathology, Association of Directors of Anatomic and Surgical Pathology, the New Zealand Society of Pathologists, and the Prostate Cancer Foundation SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID NEEDLE-BIOPSY SPECIMENS; GLEASON GRADING SYSTEM; SMALL ACINAR PROLIFERATION; BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; BREAST-CANCER; PERINEURAL INVASION; CONSERVATIVE MANAGEMENT; UNITED-STATES; TUMOR VOLUME AB Context.-Prostate cancer remains a significant public health problem. Recent publications of randomized trials and the US Preventive Services Task Force recommendations have drawn attention to overtreatment of localized, low-risk prostate cancer. Active surveillance, in which patients undergo regular visits with serum prostate-specific antigen tests and repeat prostate biopsies, rather than aggressive treatment with curative intent, may address overtreatment of low-risk prostate cancer. It is apparent that a greater awareness of the critical role of pathologists in determining eligibility for active surveillance is needed. Objectives.-To review the state of current knowledge about the role of active surveillance in the management of prostate cancer and to provide a multidisciplinary report focusing on pathologic parameters important to the successful identification of patients likely to succeed with active surveillance, to determine the role of molecular tests in increasing the safety of active surveillance, and to provide future directions. Design.-Systematic review of literature on active surveillance for low-risk prostate cancer, pathologic parameters important for appropriate stratification, and issues regarding interobserver reproducibility. Expert panels were created to delineate the fundamental questions confronting the clinical and pathologic aspects of management of men on active surveillance. Results.-Expert panelists identified pathologic parameters important for management and the related diagnostic and reporting issues. Consensus recommendations were generated where appropriate. Conclusions.-Active surveillance is an important management option for men with low-risk prostate cancer. Vital to this process is the critical role pathologic parameters have in identifying appropriate candidates for active surveillance. These findings need to be reproducible and consistently reported by surgical pathologists with accurate pathology reporting. C1 [Amin, Mahul B.; Knudsen, Beatrice] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Sandler, Howard] Cedars Sinai Med Ctr, Dept Radiat Oncol, Los Angeles, CA 90048 USA. [Holden, Stuart] Cedars Sinai Med Ctr, Dept Urol, Los Angeles, CA 90048 USA. [Knudsen, Beatrice] Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA. [Lin, Daniel W.; Gore, John L.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [True, Lawrence] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Srigley, John R.] Trillium Hlth Partners, Mississauga, ON, Canada. [Srigley, John R.] McMaster Univ, Hamilton, ON, Canada. [Samaratunga, Hema] Aquesta Pathol, Toowong, Qld, Australia. [Samaratunga, Hema] Univ Queensland, Brisbane, Qld, Australia. [Egevad, Lars] Karolinska Univ Hosp, Karolinska Inst, Dept Pathol & Oncol, Solna, Sweden. [Rubin, Mark] Weill Med Coll Cornell Univ, Inst Precis Med, Ithaca, NY USA. [Rubin, Mark] Weill Med Coll Cornell Univ, Dept Pathol & Lab Med, Ithaca, NY USA. [Rubin, Mark] New York Presbyterian Hosp, New York, NY USA. [Nacey, John] Univ Otago, Wellington Sch Med & Hlth Sci, Dept Surg, Wellington, New Zealand. [Delahunt, Brett] Univ Otago, Wellington Sch Med & Hlth Sci, Dept Pathol & Mol Med, Wellington, New Zealand. [Carter, H. Ballentine] Johns Hopkins Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD USA. [Epstein, Jonathan I.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA. [Epstein, Jonathan I.] Johns Hopkins Sch Med, Dept Urol, Baltimore, MD USA. [Epstein, Jonathan I.] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA. [Klotz, Laurence] Sunnybrook Hlth Sci Ctr, Div Urol, Toronto, ON M4N 3M5, Canada. [Evans, Andrew J.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [Zietman, Anthony L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Montironi, Rodolfo] Polytech Univ Marche Reg, Dept Biomed Sci & Publ Hlth, Sect Pathol Anat, Ancona, Italy. [Humphrey, Peter A.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [McKenney, Jesse K.] Cleveland Clin Fdn, Pathol & Lab Med Inst, Cleveland, OH 44195 USA. [Berney, Dan] Royal London Hosp, Dept Cellular Pathol, London E1 1BB, England. [Wheeler, Thomas M.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Chinnaiyan, Arul M.] Univ Michigan, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA. [Hammond, M. Elizabeth H.] Univ Utah, Sch Med, Dept Pathol, Sect Electron Microscopy, Salt Lake City, UT USA. RP Amin, MB (reprint author), Cedars Sinai Med Ctr, Dept Pathol & Lab Med, 8700 Beverly Blvd S Tower Suite 8707, Los Angeles, CA 90048 USA. EM mahul.amin@cshs.org RI Samaratunga, Hemamali/D-1559-2013 OI Samaratunga, Hemamali/0000-0001-5796-1791 FU Myriad Genetics (Salt Lake City, Utah) FX Dr Berney receives a yearly grant from Myriad Genetics (Salt Lake City, Utah) to test the effectiveness of Prolaris. The other authors have no relevant financial interest in the products or companies described in this article. NR 180 TC 36 Z9 36 U1 1 U2 11 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 2014 VL 138 IS 10 BP 1387 EP 1405 DI 10.5858/arpa.2014-0219-SA PG 19 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA AR5PK UT WOS:000343636000021 PM 25092589 ER PT J AU Litz, BT Schorr, Y Delaney, E Au, T Papa, A Fox, AB Morris, S Nickerson, A Block, S Prigerson, HG AF Litz, Brett T. Schorr, Yonit Delaney, Eileen Au, Teresa Papa, Anthony Fox, Annie B. Morris, Sue Nickerson, Angela Block, Susan Prigerson, Holly G. TI A randomized controlled trial of an internet-based therapist-assisted indicated preventive intervention for prolonged grief disorder SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Internet-based intervention; Prolonged grief; Prevention; Cognitive behavior therapy ID BEREAVEMENT-RELATED DEPRESSION; POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; COMPLICATED GRIEF; MENTAL-DISORDERS; ANXIETY; METAANALYSIS; DISTINCT; RESILIENCE; PARENTS AB This trial assessed the feasibility, acceptability, tolerability, and efficacy of an Internet-based therapist-assisted cognitive-behavioral indicated prevention intervention for prolonged grief disorder (PGD) called Healthy Experiences After Loss (HEAL). Eighty-four bereaved individuals at risk for PGD were randomized to either an immediate treatment group (n = 41) or a waitlist control group (n = 43). Assessments were conducted at four time-points: prior to the wait-interval (for the waitlist group), pre-intervention, post-intervention, 6 weeks later, and 3 months later (for the immediate group only). Intent-to-treat analyses indicated that HEAL was associated with large reductions in prolonged grief (d = 1.10), depression (d =.71), anxiety (d =.51), and posttraumatic stress (d =.91). Also, significantly fewer participants in the immediate group met PGD criteria post-intervention than in the waitlist group. Pooled data from both groups also yielded significant reductions and large effect sizes in PGD symptom severity at each follow-up assessment. The intervention required minimal professional oversight and ratings of satisfaction with treatment and usability of the Internet interface were high. HEAL has the potential to be an effective, well-tolerated tool to reduce the burden of significant pre-clinical PGD. Further research is needed to refine HEAL and to assess its efficacy and mechanisms of action in a large-scale trial. Published by Elsevier Ltd. C1 [Litz, Brett T.; Schorr, Yonit] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Jamaica Plain, MA USA. [Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Delaney, Eileen] Naval Ctr Combat & Operat Stress Control, Bur Med & Surg, San Diego, CA USA. [Au, Teresa] Boston Univ, Boston, MA 02215 USA. [Papa, Anthony] Univ Nevada, Reno, NV 89557 USA. [Fox, Annie B.] VA Boston Healthcare Syst, Boston, MA USA. [Morris, Sue; Block, Susan] Dana Farber Canc Inst, Boston, MA USA. [Nickerson, Angela] Univ New S Wales, Sydney, NSW 2052, Australia. [Block, Susan] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Prigerson, Holly G.] Weill Cornell Med Coll, New York, NY USA. RP Litz, BT (reprint author), VA Boston Healthcare Syst 116B 4, 150 S Huntington Ave, Boston, MA 02130 USA. EM litzb@bu.edu FU NIMH NIH HHS [MH079884, R34 MH079884] NR 69 TC 14 Z9 14 U1 4 U2 27 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 OCT PY 2014 VL 61 BP 23 EP 34 DI 10.1016/j.brat.2014.07.005 PG 12 WC Psychology, Clinical SC Psychology GA AR1NB UT WOS:000343350800003 PM 25113524 ER PT J AU Germain, A Richardson, R Stocker, R Mammen, O Hall, M Bramoweth, AD Begley, A Rode, N Frank, E Haas, G Buysse, DJ AF Germain, Anne Richardson, Robin Stocker, Ryan Mammen, Oommen Hall, Martica Bramoweth, Adam D. Begley, Amy Rode, Noelle Frank, Ellen Haas, Gretchen Buysse, Daniel J. TI Treatment for insomnia in combat-exposed OEF/OIF/OND Military Veterans: Preliminary, randomized controlled trial SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Military Veterans; Insomnia; Stimulus control; Sleep restriction; Education ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; SLEEP QUALITY INDEX; TRAUMATIC BRAIN-INJURY; MENTAL-HEALTH PROBLEMS; SELF-HELP TREATMENT; PTSD CHECKLIST PCL; PSYCHOMETRIC PROPERTIES; PSYCHIATRIC-DISORDERS; OLDER-ADULTS AB Chronic insomnia is highly prevalent among military personnel returning from Iraq and Afghanistan. We evaluated the effects of a military version of a brief behavioral treatment of insomnia (BBTI-MV) compared to an information only control (IC) condition in combat-exposed Veterans of Operations Enduring/Iraqi Freedom or Operation New Dawn (OEF/OIF/OND) on insomnia, sleep quality, and daytime symptoms of anxiety and depression. Forty OEF/OIF/OND Veterans (Mean age = 38.4 years old, s.d. =11.69; 85% men; 77.5% white) were randomized to one of two conditions. BBTI-MV consisted of two in-person sessions and two telephone contacts delivered over four weeks, and included personalized recommendations to reduce insomnia. The IC condition also consisted of 2 in-person sessions two telephone contacts delivered over four weeks, and Veterans were encouraged to read written information about sleep-promoting behaviors. The Insomnia Severity Index, Pittsburgh Sleep Quality Index, PTSD Checklist, and Beck Depression and Anxiety Inventories were completed at baseline, post-treatment, and at the six-month follow-up. Both interventions were associated with clinically significant improvements in insomnia, although the magnitude of improvements in sleep and rates of treatment response and remission were greater for BBTI-MV compared to IC from pre- to post-treatment. Both BBTI-MV and the provision of information were associated with clinically significant improvements in insomnia among Veterans. Despite the preliminary nature of the findings and limitations inherent to small controlled trials, the findings suggest that both approaches may provide viable options in a stepped-care approach to the treatment of insomnia in retuning combat-exposed Veterans. Larger, confirmatory effectiveness trials are required. ClinicalTrials.gov Identifier: NCT00840255. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Germain, Anne; Mammen, Oommen; Hall, Martica; Bramoweth, Adam D.; Frank, Ellen; Haas, Gretchen; Buysse, Daniel J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Richardson, Robin; Stocker, Ryan; Begley, Amy; Rode, Noelle] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. [Bramoweth, Adam D.; Haas, Gretchen] VA Pittsburgh Healthcare Syst, VISN4 Mental Illness Res Educ & Clin Ctr MIRECC, Pittsburgh, PA USA. RP Germain, A (reprint author), 3811 OHara St,Sterling Plaza, Pittsburgh, PA 15213 USA. EM germax@upmc.edu RI Hall, Martica/D-2809-2012 OI Hall, Martica/0000-0003-0642-2098 FU NCRR NIH HHS [UL1 RR024153, UL1RR024153]; NIA NIH HHS [P01 AG020677, P01AG020677]; NIMH NIH HHS [MH080696, R34 MH080696] NR 75 TC 6 Z9 6 U1 0 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 OCT PY 2014 VL 61 BP 78 EP 88 DI 10.1016/j.brat.2014.07.016 PG 11 WC Psychology, Clinical SC Psychology GA AR1NB UT WOS:000343350800009 PM 25194223 ER PT J AU Loggers, ET Lee, S Chilson, K Back, AL Block, S Loberiza, FR AF Loggers, E. T. Lee, S. Chilson, K. Back, A. L. Block, S. Loberiza, F. R. TI Advance care planning among hematopoietic cell transplant patients and bereaved caregivers SO BONE MARROW TRANSPLANTATION LA English DT Article ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; HEMATOLOGIC MALIGNANCIES; AUTOLOGOUS TRANSPLANTATION; UNRELATED DONORS; SIGNIFICANT IMPROVEMENT; PSYCHOLOGICAL DISTRESS; RECIPIENT AGE; FREE SURVIVAL; OLDER-ADULTS AB Younger, healthier patients contemplating high-risk (but potentially curative) hematopoietic cell transplants (HCT) may not consider advance care planning (ACP). We investigated the effect of pre transplant ACP in surviving HCT patients and bereaved caregivers using retrospective, audiotaped telephone surveys. Subjects were identified between 2001 and 2003 via databases at two high-volume HCT centers. Transcripts were coded by two investigators, with differences resolved by consensus. HCT survivors (n = 18) were interviewed a median of 13 months after HCT for acute leukemia (7), lymphoma (5) or other (6); 50% had living wills, 72% had a formal proxy. Twelve (67%) had discussed mortality risk pre HCT with the medical team. Of those, 92% felt their hope and perception of the medical team's truthfulness was increased or unchanged (I/U) by the conversation, whereas all felt clinician commitment to transplant was I/U. Bereaved caregivers (n = 11) were interviewed a median of 10 months post death (median 31 days post HCT, range 13-152). Nine (82%) had discussed mortality risk pre-HCT with the medical team; 7 (78%) felt hope was I/U, all felt clinician commitment to transplant and truthfulness was I/U, and most felt ACP reduced burden (67%). ACP discussions with patients and caregivers pre-HCT did not affect hope and supported confidence in medical teams. C1 [Loggers, E. T.; Lee, S.; Chilson, K.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98101 USA. [Loggers, E. T.] Grp Hlth Cooperat Puget Sound, Group Hlth Res Inst, Seattle, WA USA. [Lee, S.; Back, A. L.] Univ Washington, Seattle, WA 98195 USA. [Block, S.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Loberiza, F. R.] Univ Nebraska Med Ctr, Div Oncol Hematol, Omaha, NE USA. RP Loggers, ET (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1730 Minor Ave,Suite 160, Seattle, WA 98101 USA. EM loggers.e@ghc.org FU [CA 098486] FX This work was supported by grant CA 098486, PI: Stephanie Lee. NR 38 TC 1 Z9 2 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 2014 VL 49 IS 10 BP 1317 EP 1322 DI 10.1038/bmt.2014.152 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA AR5ZC UT WOS:000343660300012 PM 25068417 ER PT J AU Cardoso, F Costa, A Norton, L Senkus, E Aapro, M Andre, F Barrios, CH Bergh, J Biganzoli, L Blackwell, KL Cardoso, MJ Cufer, T El Saghir, N Fallowfield, L Fenech, D Francis, P Gelmon, K Giordano, SH Gligorov, J Goldhirsch, A Harbeck, N Houssami, N Hudis, C Kaufman, B Krop, I Kyriakides, S Lin, UN Mayer, M Merjaver, SD Nordstrom, EB Pagani, O Partridge, A Penault-Llorca, F Piccart, MJ Rugo, H Sledge, G Thomssen, C van't Veer, L Vorobiof, D Vrieling, C West, N Xu, B Winer, E AF Cardoso, F. Costa, A. Norton, L. Senkus, E. Aapro, M. Andre, F. Barrios, C. H. Bergh, J. Biganzoli, L. Blackwell, K. L. Cardoso, M. J. Cufer, T. El Saghir, N. Fallowfield, L. Fenech, D. Francis, P. Gelmon, K. Giordano, S. H. Gligorov, J. Goldhirsch, A. Harbeck, N. Houssami, N. Hudis, C. Kaufman, B. Krop, I. Kyriakides, S. Lin, U. N. Mayer, M. Merjaver, S. D. Nordstrom, E. B. Pagani, O. Partridge, A. Penault-Llorca, F. Piccart, M. J. Rugo, H. Sledge, G. Thomssen, C. van't Veer, L. Vorobiof, D. Vrieling, C. West, N. Xu, B. Winer, E. TI ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2) SO BREAST LA English DT Article ID PHASE-II TRIAL; ISOLATED LOCOREGIONAL RECURRENCE; RANDOMIZED CONTROLLED-TRIAL; MIDDLE-INCOME COUNTRIES.; 2 MULTICENTER TRIALS; FIRST-LINE THERAPY; POSTMENOPAUSAL WOMEN; DOUBLE-BLIND; 1ST-LINE THERAPY; PRIMARY TUMOR C1 [Cardoso, F.] Champalimaud Canc Ctr, European Sch Oncol & Breast Unit, P-1400048 Lisbon, Portugal. [Costa, A.] European Sch Oncol, Milan, Italy. [Costa, A.] European Sch Oncol, Bellinzona, Switzerland. [Norton, L.] Mem Sloan Kettering Canc Ctr, Breast Canc Program, New York, NY 10021 USA. [Senkus, E.] Med Univ Gdansk, Dept Radiotherapy & Oncol, Gdansk, Poland. [Aapro, M.] Inst Multidisciplinaire Oncol, Div Oncol, Genolier, Switzerland. [Andre, F.] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France. [Barrios, C. H.] Pontificia Univ Catolica Rio Grande do Sul, Sch Med, Dept Med, Porto Alegre, RS, Brazil. [Bergh, J.] Karolinska Inst, Dept Oncol Radiumhemmet, Stockholm, Sweden. [Bergh, J.] Canc Ctr Karolinska, Stockholm, Sweden. [Bergh, J.] Karolinska Univ Hosp, Stockholm, Sweden. [Biganzoli, L.] Sandro Pitigliani Oncol Ctr, Dept Med Oncol, Prato, Italy. [Blackwell, K. L.] Duke Canc Inst, Breast Canc Clin Program, Durham, NC USA. [Cardoso, M. J.] Champalimaud Canc Ctr, Breast Unit, P-1400048 Lisbon, Portugal. [Cufer, T.] Univ Clin Golnik, Med Fac Ljubljana, Ljubljana, Slovenia. [El Saghir, N.] Amer Univ Beirut, Med Ctr, NK Basile Canc Inst Breast Ctr Excellence, Beirut, Lebanon. [Fallowfield, L.] Univ Sussex, Brighton & Sussex Med Sch, Falmer, England. [Fenech, D.] Europa Donna Malta, Breast Care Support Grp, Mtarfa, Malta. [Francis, P.] Peter MacCallum Canc Ctr, Div Canc Med, Melbourne, Vic, Australia. [Gelmon, K.] BC Canc Agcy, Vancouver, BC, Canada. [Giordano, S. H.] UT MD Anderson Canc Ctr, Dept Hlth Serv Res, Houston, TX USA. [Giordano, S. H.] UT MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX USA. [Gligorov, J.] IUC UPMC, APHP Tenon, Francilian Breast Intergrp, Paris, France. [Goldhirsch, A.] European Inst Oncol, Program Breast Hlth, Milan, Italy. [Harbeck, N.] Brustzentrum Univ Munchen, Munich, DE USA. [Houssami, N.] Univ Sydney, Sydney Med Sch, Sch Publ Hlth, Screening & Test Evaluat Program, Sydney, NSW 2006, Australia. [Hudis, C.] Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, New York, NY 10021 USA. [Kaufman, B.] Sheba Med Ctr, Tel Hashomer, Israel. [Krop, I.; Lin, U. N.; Winer, E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kyriakides, S.] Europa Donna Cyprus, Nicosa, Cyprus. [Mayer, M.] Adv BC org, New York, NY USA. [Merjaver, S. D.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Merjaver, S. D.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Nordstrom, E. B.] Europa Donna Sweden & Brostcancerforeningarnas Ri, BRO, Sundbyberg, Sweden. [Pagani, O.] Oncol Inst Southern Switzerland, Bellinzona, Switzerland. [Pagani, O.] Breast Unit Southern Switzerland, Bellinzona, Switzerland. [Partridge, A.] Dana Farber Canc Inst, Dept Med Oncol, Div Womens Canc, Boston, MA 02115 USA. [Penault-Llorca, F.] Ctr Comprehens Canc, Jean Perrin Ctr, Clermont Ferrand, France. [Piccart, M. J.] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium. [Rugo, H.] UCSF, Helen Diller Family Comprehens Canc Ctr, Dept Med, Breast Oncol Program, San Francisco, CA USA. [Sledge, G.] Indiana Univ, Med Ctr, Indianapolis, IN USA. [Thomssen, C.] Univ Halle Wittenberg, Dept Gynaecol, Halle, DE, Germany. [van't Veer, L.] UCSF, Helen Diller Family Comprehens Canc Ctr, Breast Oncol Program, San Francisco, CA USA. [Vorobiof, D.] Sandton Oncol Ctr, Johannesburg, South Africa. [Vrieling, C.] Clin Grangettes, Dept Radiotherapy, Geneva, Switzerland. [West, N.] Cardiff & Vale Univ, Hlth Board, Nursing Div, Cardiff, S Glam, Wales. [Xu, B.] Chinese Acad Med Sci, Canc Hosp, Dept Med Oncol, Beijing 100730, Peoples R China. [Xu, B.] Peking Union Med Coll, Beijing 100021, Peoples R China. RP Cardoso, F (reprint author), Champalimaud Canc Ctr, Breast Unit, Av Brasilia,S-N, P-1400048 Lisbon, Portugal. EM fatimacardoso@fundacaochampalimaud.pt OI Gligorov, Joseph/0000-0002-9900-6386; Cardoso, Maria Joao/0000-0002-8137-3700; Norton, Larry/0000-0003-3701-9250; Cardoso, Fatima/0000-0002-6692-2249 NR 130 TC 85 Z9 89 U1 1 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD OCT PY 2014 VL 23 IS 5 BP 489 EP 502 DI 10.1016/j.breast.2014.08.009 PG 14 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AR2IU UT WOS:000343408300001 PM 25244983 ER PT J AU Evans, CL AF Evans, C. L. TI Peering under the skin: measuring melanoma depth with ultrasound and optical coherence tomography SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Editorial Material ID TISSUES; LESIONS AB ORIGINAL ARTICLE, p 799 C1 Harvard Univ, Massachusetts Gen Hosp, Antithyroid hormone autoantibodies vitiligo, Wellman Ctr Photomed, Charlestown, MA 02129 USA. RP Evans, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Antithyroid hormone autoantibodies vitiligo, Wellman Ctr Photomed, CNY149-3210,13th St, Charlestown, MA 02129 USA. EM evans.conor@mgh.harvard.edu NR 8 TC 0 Z9 0 U1 3 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD OCT PY 2014 VL 171 IS 4 BP 690 EP 691 DI 10.1111/bjd.13353 PG 2 WC Dermatology SC Dermatology GA AS1AE UT WOS:000344007500009 PM 25319422 ER PT J AU Soumerai, JD Sohani, AR Abramson, JS AF Soumerai, Jacob D. Sohani, Aliyah R. Abramson, Jeremy S. TI Diagnosis and Management of Castleman Disease SO CANCER CONTROL LA English DT Article ID LYMPH-NODE HYPERPLASIA; DENDRITIC CELL-SARCOMA; OF-THE-LITERATURE; ANTI-CD20 MONOCLONAL-ANTIBODY; HYALINE-VASCULAR VARIANT; HIV-NEGATIVE PATIENTS; NON-HODGKIN-LYMPHOMA; LONG-TERM REMISSION; RITUXIMAB THERAPY; KAPOSIS-SARCOMA AB Background: Castleman disease is an uncommon lymphoproliferative disorder characterized as either unicentric or multicentric. Unicentric Castleman disease (UCD) is localized and carries an excellent prognosis, whereas multicentric Castleman disease (MCD) is a systemic disease occurring most commonly in the setting of HIV infection and is associated with human herpesvirus 8. MCD has been associated with considerable morbidity and mortality, and the therapeutic landscape for its management continues to evolve. Methods: The available medical literature on UCD and MCD was reviewed. The clinical presentation and pathological diagnosis of Castleman disease was reviewed, along with associated disorders such as certain malignancies and autoimmune complications. Results: Surgical resection remains the standard therapy for UCD, while systemic therapies are required for the management of MCD. Rituximab monotherapy is the mainstay of therapy; however, novel therapies targeting interleukin 6 may represent a treatment option in the near future. Antiviral strategies as well as single-agent and combination chemotherapy with glucocorticoids are established systemic therapies. The management of Castleman disease also requires careful attention to potential concomitant infections, malignancies, and associated syndromes. Conclusions: UCD and MCD constitute uncommon but well-defined clinicopathologic entities. Although UCD is typically well controlled with local therapy, MCD continues to pose formidable challenges in management. We address historical chemotherapy-based approaches to this disease as well as recently developed targeted therapies, including rituximab and siltuximab, that have improved the outcome for newly diagnosed patients. Ongoing research into the management of MCD is needed. C1 [Soumerai, Jacob D.; Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Lymphoma, Ctr Canc, Boston, MA 02114 USA. [Soumerai, Jacob D.; Sohani, Aliyah R.; Abramson, Jeremy S.] Harvard Univ, Sch Med, Boston, MA USA. [Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Abramson, JS (reprint author), Massachusetts Gen Hosp, Ctr Lymphoma, Ctr Canc, 55 Fruit St,Yawkey 9A, Boston, MA 02114 USA. EM jabramson@mgh.harvard.edu NR 102 TC 23 Z9 26 U1 1 U2 5 PU H LEE MOFFITT CANCER CENTER & RESEARCH INST PI TAMPA PA 12902 MAGNOLIA DR, TAMPA, FL 33612 USA SN 1073-2748 J9 CANCER CONTROL JI Cancer Control PD OCT PY 2014 VL 21 IS 4 BP 266 EP 278 PG 13 WC Oncology SC Oncology GA AR6KN UT WOS:000343692600002 PM 25310208 ER PT J AU McDermott, D Lebbe, C Hodi, FS Maio, M Weber, JS Wolchok, JD Thompson, JA Balch, CM AF McDermott, David Lebbe, Celeste Hodi, F. Stephen Maio, Michele Weber, Jeffrey S. Wolchok, Jedd D. Thompson, John A. Balch, Charles M. TI Durable benefit and the potential for long-term survival with immunotherapy in advanced melanoma SO CANCER TREATMENT REVIEWS LA English DT Review DE Advanced melanoma; CTLA-4; Immunotherapy; Long-term survival; PD-1; Targeted therapy ID DOSE RECOMBINANT INTERLEUKIN-2; EXPANDED ACCESS PROGRAM; IPILIMUMAB 10 MG/KG; METASTATIC MELANOMA; OPEN-LABEL; CANCER-IMMUNOTHERAPY; CLINICAL-EXPERIENCE; RESPONSE CRITERIA; PHASE-2 TRIAL; SOLID TUMORS AB Historically, the median overall survival for patients with stage IV melanoma was less than 1 year and the 5-year survival rate was similar to 10%. Recent advances in therapy have raised 5-year survival expectations to similar to 20%. Notably, a subset of melanoma patients who receive immunotherapy with high-dose interleukin-2, and now ipilimumab, can achieve long-term survival of at least 5 years. A major goal in melanoma research is to increase the number of patients who experience this overall survival benefit. In this review, we discuss the attributes of immunotherapy and newer targeted agents, and consider how combination strategies might improve the chances of achieving durable benefit and long-term survival. We also discuss three areas that we believe will be critical to making further advances in melanoma treatment. To better understand the clinical profile of patients who achieve long-term survival with immunotherapy, we first present data from ipilimumab clinical trials in which a subset of patients experienced durable responses. Second, we discuss the limitations of traditional metrics used to evaluate the benefits of immunotherapies. Third, we consider emerging issues that clinicians are currently facing when making treatment decisions regarding immunotherapy. A better understanding of these novel treatments may improve survival outcomes in melanoma, increase the number of patients who experience this overall survival benefit, and inform the future use of these agents in the treatment of other cancer types. (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-SA license. C1 [McDermott, David] Beth Israel Deaconess Med Ctr, Dept Hematol Oncol, Boston, MA 02215 USA. [Lebbe, Celeste] Univ Paris Diderot, Hop St Louis, AP HP, Dept Dermatol,CIC,U976, F-75010 Paris, France. [Hodi, F. Stephen] Dana Farber Canc Inst, Ctr Immunooncol, Melanoma Ctr, Boston, MA 02215 USA. [Maio, Michele] Univ Hosp Siena, Dept Oncol, I-53100 Siena, Italy. [Weber, Jeffrey S.] H Lee Moffitt Canc Ctr & Res Inst, Dept Cutaneous Oncol, Tampa, FL 33612 USA. [Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, Dept Med, Ludwig Ctr Canc Immunotherapy, New York, NY 10065 USA. [Thompson, John A.] Seattle Canc Care Alliance, Seattle, WA 98109 USA. [Balch, Charles M.] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA. RP McDermott, D (reprint author), Beth Israel Deaconess Med Ctr, Dept Hematol Oncol, 375 Longwood Ave,Mailstop MASCO 428, Boston, MA 02215 USA. EM dmcdermo@bidmc.harvard.edu; celeste.lebbe@sls.aphp.fr; Stephen_Hodi@dfci.harvard.edu; mmaiocro@gmail.com; jeffrey.weber@moffitt.org; wolchokj@mskcc.org; jat@uw.edu; charles.balch@utsouthwestern.edu OI coral, sandra/0000-0002-1308-3082 FU Bristol-Myers Squibb FX Professional medical writing and editorial assistance was provided by Jennifer DiNieri at StemScientific and was funded by Bristol-Myers Squibb. NR 66 TC 58 Z9 58 U1 3 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 EI 1532-1967 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD OCT PY 2014 VL 40 IS 9 BP 1056 EP 1064 DI 10.1016/j.ctrv.2014.06.012 PG 9 WC Oncology SC Oncology GA AR1RB UT WOS:000343361200003 PM 25060490 ER PT J AU Chan, AM Dykstra, AR Jayaram, V Leonard, MK Travis, KE Gygi, B Baker, JM Eskandar, E Hochberg, LR Halgren, E Cash, SS AF Chan, Alexander M. Dykstra, Andrew R. Jayaram, Vinay Leonard, Matthew K. Travis, Katherine E. Gygi, Brian Baker, Janet M. Eskandar, Emad Hochberg, Leigh R. Halgren, Eric Cash, Sydney S. TI Speech-Specific Tuning of Neurons in Human Superior Temporal Gyrus SO CEREBRAL CORTEX LA English DT Article DE audition; human single units; microelectrodes; speech perception; superior temporal gyrus ID HUMAN AUDITORY-CORTEX; POSITRON-EMISSION-TOMOGRAPHY; VISUAL WORD RECOGNITION; SPATIOTEMPORAL DYNAMICS; HIERARCHICAL ORGANIZATION; LOBE; BRAIN; ACTIVATION; RESPONSES; SOUNDS AB How the brain extracts words from auditory signals is an unanswered question. We recorded approximately 150 single and multi-units from the left anterior superior temporal gyrus of a patient during multiple auditory experiments. Against low background activity, 45% of units robustly fired to particular spoken words with little or no response to pure tones, noise-vocoded speech, or environmental sounds. Many units were tuned to complex but specific sets of phonemes, which were influenced by local context but invariant to speaker, and suppressed during self-produced speech. The firing of several units to specific visual letters was correlated with their response to the corresponding auditory phonemes, providing the first direct neural evidence for phonological recoding during reading. Maximal decoding of individual phonemes and words identities was attained using firing rates from approximately 5 neurons within 200 ms after word onset. Thus, neurons in human superior temporal gyrus use sparse spatially organized population encoding of complex acoustic-phonetic features to help recognize auditory and visual words. C1 [Chan, Alexander M.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Dykstra, Andrew R.] MIT, Harvard Mit Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. [Chan, Alexander M.; Dykstra, Andrew R.; Hochberg, Leigh R.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Jayaram, Vinay] Harvard Univ, Dept Neurosci, Cambridge, MA 02138 USA. [Leonard, Matthew K.; Travis, Katherine E.; Halgren, Eric] Univ Calif San Diego, Multimodal Imaging Lab, La Jolla, CA 92093 USA. [Halgren, Eric] Univ Calif San Diego, Dept Radiol & Neurosci, La Jolla, CA 92093 USA. [Gygi, Brian] Nottingham Hearing Biomed Res Unit, Natl Inst Hlth Res, Nottingham, England. [Baker, Janet M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Chan, AM (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM alexchan@post.harvard.edu OI Jayaram, Vinay/0000-0002-8581-4921 FU NIMH NIH HHS [T32 MH020002] NR 87 TC 14 Z9 14 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD OCT PY 2014 VL 24 IS 10 BP 2679 EP 2693 DI 10.1093/cercor/bht127 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AR2IT UT WOS:000343408200014 PM 23680841 ER PT J AU Cooke, CR Feemster, LC Wiener, RS O'Neil, ME Slatore, CG AF Cooke, Colin R. Feemster, Laura C. Wiener, Renda Soylemez O'Neil, Maya E. Slatore, Christopher G. TI Aggressiveness of Intensive Care Use Among Patients With Lung Cancer in the Surveillance, Epidemiology, and End Results-Medicare Registry SO CHEST LA English DT Article ID OF-LIFE CARE; POPULATION; OUTCOMES; BENEFICIARIES; TRENDS; UNITS AB BACKGROUND: Approximately 65% of elderly patients with lung cancer who are admitted to the ICU will die within 6 months. Efforts to improve end-of-life care for this population must first understand the patient factors that underlie admission to the ICU. METHODS: We performed a retrospective cohort study examining all fee-for-service inpatient claims in the Surveillance, Epidemiology, and End Results (SEER)-Medicare registry for elderly patients (aged. 65 years) who had received a diagnosis of lung cancer between 1992 and 2005 and who were hospitalized for reasons other than resection of their lung cancer. We calculated yearly rates of ICU admission per 1,000 hospitalizations via room and board codes or International Classification of Diseases, Ninth Revision, Clinical Modification and diagnosis-related group codes for mechanical ventilation, stratified the rates by receipt of mechanical ventilation and ICU type (medical/surgical/cardiac vs intermediate), and compared these rates over time. RESULTS: A total of 175,756 patients with lung cancer in SEER were hospitalized for a reason other than surgical resection of their tumor during the study period, 49,373 (28%) of whom had at least one ICU stay. The rate of ICU admissions per 1,000 hospitalizations increased over the study period from 140.7 in 1992 to 201.7 in 2005 (P < .001). The majority of the increase in ICU admissions (per 1,000 hospitalizations) between 1992 and 2005 occurred among patients who were not mechanically ventilated (118.2 to 173.3, P < .001) and among those who were in intermediate ICUs (20.0 to 61.9, P < .001), but increased only moderately in medical/surgical/cardiac units (120.7 to 139.9, P < .001). CONCLUSIONS: ICU admission for patients with lung cancer increased over time, mostly among patients without mechanical ventilation who were largely cared for in intermediate ICUs. C1 [Cooke, Colin R.] Univ Michigan, Ctr Healthcare Outcomes & Policy, Inst Healthcare Innovat & Policy, Div Pulm & Crit Care Med,Michigan Ctr Integrat Re, Ann Arbor, MI 48109 USA. [Feemster, Laura C.] VA Puget Sound Healthcare Syst, Div Pulm & Crit Care Med, Seattle, WA USA. [Feemster, Laura C.] Univ Washington, Sch Med, Seattle, WA USA. [Wiener, Renda Soylemez] Boston Univ, Sch Med, Boston, MA 02118 USA. [Wiener, Renda Soylemez] Edith Nourse Rogers Mem VA Hosp, Bedford, MA USA. [O'Neil, Maya E.; Slatore, Christopher G.] Portland VA Med Ctr, Hlth Serv Res, Portland, OR USA. [O'Neil, Maya E.; Slatore, Christopher G.] Portland VA Med Ctr, Hlth Serv Dev, Portland, OR USA. [Slatore, Christopher G.] Portland VA Med Ctr, Sect Pulm & Crit Care Med, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Dept Med, Div Pulm & Crit Care Med, Portland, OR 97201 USA. RP Cooke, CR (reprint author), Univ Michigan, Ctr Healthcare Outcomes & Policy, 2800 Plymouth Rd,Bldg 16,Room 127W, Ann Arbor, MI 48109 USA. EM cookecr@umich.edu OI Cooke, Colin/0000-0001-9713-5371; Wiener, Renda/0000-0001-7712-2135; Slatore, Christopher/0000-0003-0958-8122 FU Agency for Healthcare Research and Quality [K08 HS020672]; National Cancer Institute [K07 CA138772]; National Heart, Lung and Blood Institute [K23 HL111116]; Department of Veterans Affairs FX This work was supported in part by the Agency for Healthcare Research and Quality [Grant K08 HS020672 to Dr Cooke], the National Cancer Institute [Grant K07 CA138772 to Dr Wiener], the National Heart, Lung and Blood Institute [Grant K23 HL111116 to Dr Feemster], and the Department of Veterans Affairs [to Drs Wiener and Feemster]. NR 26 TC 9 Z9 9 U1 1 U2 4 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2014 VL 146 IS 4 BP 916 EP 923 DI 10.1378/chest.14-0477 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AR4QD UT WOS:000343570400020 PM 25117058 ER PT J AU Bowler, RP Kim, V Regan, E Williams, AAA Santorico, SA Make, BJ Lynch, DA Hokanson, JE Washko, GR Bercz, P Soler, X Marchetti, N Criner, GJ Ramsdell, J Han, MK Demeo, D Anzueto, A Comellas, A Crapo, JD Dransfield, M Wells, JM Hersh, CP MacIntyre, N Martinez, F Nath, HP Niewoehner, D Sciurba, F Sharafkhaneh, A Silverman, EK van Beek, EJR Wilson, C Wendt, C Wise, RA AF Bowler, Russell P. Kim, Victor Regan, Elizabeth Williams, Andre A. A. Santorico, Stephanie A. Make, Barry J. Lynch, David A. Hokanson, John E. Washko, George R. Bercz, Peter Soler, Xavier Marchetti, Nathaniel Criner, Gerard J. Ramsdell, Joe Han, MeiLan K. Demeo, Dawn Anzueto, Antonio Comellas, Alejandro Crapo, James D. Dransfield, Mark Wells, J. Michael Hersh, Craig P. MacIntyre, Neil Martinez, Fernando Nath, Hrudaya P. Niewoehner, Dennis Sciurba, Frank Sharafkhaneh, Amir Silverman, Edwin K. van Beek, Edwin J. R. Wilson, Carla Wendt, Christine Wise, Robert A. CA COPDGene Investigators TI Prediction of Acute Respiratory Disease in Current and Former Smokers With and Without COPD SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; GASTROESOPHAGEAL-REFLUX SYMPTOMS; EARLY-ONSET COPD; QUALITY-OF-LIFE; FAMILIAL AGGREGATION; ACUTE EXACERBATIONS; GENDER-DIFFERENCES; UNITED-STATES; LUNG-FUNCTION; PREVALENCE AB BACKGROUND: The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. METHODS: Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. RESULTS: At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV1), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George's Respiratory Questionnaire score). Risks were similar for those with and without COPD. CONCLUSIONS: Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD. C1 [Bowler, Russell P.; Regan, Elizabeth; Williams, Andre A. A.; Make, Barry J.; Lynch, David A.; Crapo, James D.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Wilson, Carla] Natl Jewish Hlth, Div Biostat & Bioinformat, Denver, CO 80206 USA. [Santorico, Stephanie A.] Univ Colorado Denver, Dept Math & Stat Sci, Denver, CO USA. [Kim, Victor; Bercz, Peter; Marchetti, Nathaniel; Criner, Gerard J.] Temple Univ, Sect Pulm & Crit Care Med, Dept Med, Philadelphia, PA 19122 USA. [Hokanson, John E.] Univ Colorado, Dept Med, Aurora, CO USA. [Hokanson, John E.] Univ Colorado, Dept Epidemiol, Aurora, CO USA. [Washko, George R.; Demeo, Dawn; Hersh, Craig P.; Silverman, Edwin K.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Channing Div Network Med, Boston, MA 02115 USA. [Soler, Xavier; Ramsdell, Joe] Univ Calif San Diego, Dept Med, Div Pulm & Crit Care Med, La Jolla, CA 92093 USA. [Han, MeiLan K.; Martinez, Fernando] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, Dept Med, San Antonio, TX 78229 USA. [Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Comellas, Alejandro] Univ Iowa, Iowa City, IA USA. [Dransfield, Mark; Wells, J. Michael; Nath, Hrudaya P.] Univ Alabama Birmingham, Birmingham, AL USA. [MacIntyre, Neil] Duke Univ, Med Ctr, Durham, NC USA. [Niewoehner, Dennis; Wendt, Christine] Univ Minnesota, Minneapolis, MN USA. [Sciurba, Frank] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Sharafkhaneh, Amir] Baylor Coll Med, Houston, TX 77030 USA. [van Beek, Edwin J. R.] Univ Edinburgh, Clin Res Imaging Ctr, Edinburgh, Midlothian, Scotland. [Wise, Robert A.] Johns Hopkins Univ, Baltimore, MD USA. RP Bowler, RP (reprint author), Natl Jewish Hlth, Dept Med, 1400 Jackson St,Room K715a, Denver, CO 80206 USA. EM Bowlerr@njhealth.org RI Coxson, Harvey/A-9861-2017; OI Coxson, Harvey/0000-0001-5750-9711; Comellas, Alejandro/0000-0003-1521-7520; Curtis, Jeffrey/0000-0001-5191-4847; Foreman, Marilyn/0000-0002-9405-7475 FU National Heart, Lung and Blood Institute [R01 HL 08 9856, R01 HL 08 9897]; National Center for Research Resources/National Institutes of Health [UL1 RR025780]; National Institute of Nursing Research [NR013377] FX This study was supported by the National Heart, Lung and Blood Institute [Grants R01 HL 08 9856 and R01 HL 08 9897], National Center for Research Resources/National Institutes of Health [Grant UL1 RR025780], and National Institute of Nursing Research [NR013377]. NR 39 TC 18 Z9 18 U1 0 U2 12 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2014 VL 146 IS 4 BP 941 EP 950 DI 10.1378/chest.13-2946 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AR4QD UT WOS:000343570400023 PM 24945159 ER PT J AU Beitler, JR Schoenfeld, DA Thompson, BT AF Beitler, Jeremy R. Schoenfeld, David A. Thompson, B. Taylor TI Preventing ARDS Progress, Promise, and Pitfalls SO CHEST LA English DT Review ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; KERATINOCYTE GROWTH-FACTOR; INTENSIVE-CARE-UNIT; LOWER TIDAL VOLUMES; MECHANICALLY VENTILATED PATIENTS; H1N1PDM09 VIRUS-INFECTION; CONTROLLED CLINICAL-TRIAL; SEPTIC SHOCK AB Advances in critical care practice have led to a substantial decline in the incidence of ARDS over the past several years. Low tidal volume ventilation, timely resuscitation and antimicrobial administration, restrictive transfusion practices, and primary prevention of aspiration and nosocomial pneumonia have likely contributed to this reduction. Despite decades of research, there is no proven pharmacologic treatment of ARDS, and mortality from ARDS remains high. Consequently, recent initiatives have broadened the scope of lung injury research to include targeted prevention of ARDS. Prediction scores have been developed to identify patients at risk for ARDS, and clinical trials testing aspirin and inhaled budesonide/formoterol for ARDS prevention are ongoing. Future trials aimed at preventing ARDS face several key challenges. ARDS has not been validated as an end point for pivotal clinical trials, and caution is needed when testing toxic therapies that may prevent ARDS yet potentially increase mortality. C1 [Beitler, Jeremy R.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Schoenfeld, David A.] Massachusetts Gen Hosp, Ctr Biostat, Dept Med, Boston, MA 02114 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Thompson, BT (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM tthompson1@partners.org FU National Institutes of Health [5-R01-HL60710-9, 1-P01-HL108801, 5-T32-HL007633] FX This work was funded in part by National Institutes of Health [Grants 5-R01-HL60710-9, 1-P01-HL108801, and 5-T32-HL007633]. NR 98 TC 7 Z9 7 U1 1 U2 17 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2014 VL 146 IS 4 BP 1102 EP 1113 DI 10.1378/chest.14-0555 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AR4QD UT WOS:000343570400042 PM 25288000 ER PT J AU Livio, S Strockbine, NA Panchalingam, S Tennant, SM Barry, EM Marohn, ME Antonio, M Hossain, A Mandomando, I Ochieng, JB Oundo, JO Qureshi, S Ramamurthy, T Tamboura, B Adegbola, RA Hossain, MJ Saha, D Sen, S Faruque, AS Alonso, PL Breiman, RF Zaidi, AKM Sur, D Sow, SO Berkeley, LY O'Reilly, CE Mintz, ED Biswas, K Cohen, D Farag, TH Nasrin, D Wu, YK Blackwelder, WC Kotloff, KL Nataro, JP Levine, MM AF Livio, Sofie Strockbine, Nancy A. Panchalingam, Sandra Tennant, Sharon M. Barry, Eileen M. Marohn, Mark E. Antonio, Martin Hossain, Anowar Mandomando, Inacio Ochieng, John B. Oundo, Joseph O. Qureshi, Shahida Ramamurthy, Thandavarayan Tamboura, Boubou Adegbola, Richard A. Hossain, Mohammed Jahangir Saha, Debasish Sen, Sunil Faruque, Abu Syed Golam Alonso, Pedro L. Breiman, Robert F. Zaidi, Anita K. M. Sur, Dipika Sow, Samba O. Berkeley, Lynette Y. O'Reilly, Ciara E. Mintz, Eric D. Biswas, Kousick Cohen, Dani Farag, Tamer H. Nasrin, Dilruba Wu, Yukun Blackwelder, William C. Kotloff, Karen L. Nataro, James P. Levine, Myron M. TI Shigella Isolates From the Global Enteric Multicenter Study Inform Vaccine Development SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE serotyping; Shigella; shigellosis; vaccines ID SHIGA BACILLUS DYSENTERY; FLEXNERI 2A; DIARRHEAL DISEASE; ORAL IMMUNIZATION; DEVELOPING-COUNTRIES; ENTEROTOXIN GENES; SERUM ANTIBODIES; YOUNG-CHILDREN; O-ANTIGEN; IN-VITRO AB Background. Shigella, a major diarrheal disease pathogen worldwide, is the target of vaccine development. The Global Enteric Multicenter Study (GEMS) investigated burden and etiology of moderate-to-severe diarrheal disease in children aged <60 months and matched controls without diarrhea during 3 years at 4 sites in Africa and 3 in Asia. Shigella was 1 of the 4 most common pathogens across sites and age strata. GEMS Shigella serotypes are reviewed to guide vaccine development. Methods. Subjects' stool specimens/rectal swabs were transported to site laboratories in transport media and plated onto xylose lysine desoxycholate and MacConkey agar. Suspect Shigella colonies were identified by biochemical tests and agglutination with antisera. Shigella isolates were shipped to the GEMS Reference Laboratory (Baltimore, MD) for confirmation and serotyping of S. flexneri; one-third of isolates were sent to the Centers for Disease Control and Prevention for quality control. Results. Shigella dysenteriae and S. boydii accounted for 5.0% and 5.4%, respectively, of 1130 Shigella case isolates; S. flexneri comprised 65.9% and S. sonnei 23.7%. Five serotypes/subserotypes comprised 89.4% of S. flexneri, including S. flexneri 2a, S. flexneri 6, S. flexneri 3a, S. flexneri 2b, and S. flexneri 1b. Conclusions. A broad-spectrum Shigella vaccine must protect against S. sonnei and 15 S. flexneri serotypes/subserotypes. A quadrivalent vaccine with O antigens from S. sonnei, S. flexneri 2a, S. flexneri 3a, and S. flexneri 6 can provide broad direct coverage against these most common serotypes and indirect coverage against all but 1 (rare) remaining subserotype through shared S. flexneri group antigens. C1 [Livio, Sofie; Panchalingam, Sandra; Tennant, Sharon M.; Barry, Eileen M.; Marohn, Mark E.; Sen, Sunil; Berkeley, Lynette Y.; Farag, Tamer H.; Nasrin, Dilruba; Wu, Yukun; Blackwelder, William C.; Kotloff, Karen L.; Nataro, James P.; Levine, Myron M.] Univ Maryland Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. [Strockbine, Nancy A.] Ctr Dis Control & Prevent, Escherichia & Shigella Reference Unit, Enter Dis Lab Branch, Atlanta, GA USA. [Strockbine, Nancy A.; O'Reilly, Ciara E.; Mintz, Eric D.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA USA. [Antonio, Martin; Adegbola, Richard A.; Hossain, Mohammed Jahangir; Saha, Debasish] Med Res Council Unit United Kingdom, Fajara, Gambia. [Hossain, Anowar; Faruque, Abu Syed Golam] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Mandomando, Inacio; Alonso, Pedro L.] Ctr Invest Saude Manhica, Manhica, Mozambique. [Mandomando, Inacio; Breiman, Robert F.] Univ Barcelona, Hosp Clinic, Ctr Recerca Salut Int Barcelona, E-08007 Barcelona, Spain. [Ochieng, John B.; Oundo, Joseph O.; Breiman, Robert F.] Ctr Dis Control & Prevent, Kenya Med Res Inst, Kisumu, Kenya. [Qureshi, Shahida; Zaidi, Anita K. M.] Aga Khan Univ, Dept Paediat & Child Hlth, Karachi, Pakistan. [Ramamurthy, Thandavarayan; Sur, Dipika] Natl Inst Cholera & Enter Dis, Kolkata, India. [Tamboura, Boubou; Sow, Samba O.] Ctr Dev Vaccins Mali, Bamako, Mali. [Breiman, Robert F.] US Ctr Dis Control & Prevent, Global Dis Detect Div, Kenya Off, Nairobi, Kenya. [Sur, Dipika] PATH, New Delhi, India. [Berkeley, Lynette Y.] US FDA, Rockville, MD 20857 USA. [Biswas, Kousick] US Dept Vet Affairs, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA. [Cohen, Dani] Tel Aviv Univ, Sackler Fac Med, Sch Publ Hlth, Dept Epidemiol & Prevent Med, Ramat Aviv, Israel. RP Levine, MM (reprint author), Univ Maryland Sch Med, Ctr Vaccine Dev, 685 West Baltimore St, Baltimore, MD 21201 USA. EM mlevine@medicine.umaryland.edu FU Bill & Melinda Gates Foundation [38774] FX This work was supported by grant 38774 from the Bill & Melinda Gates Foundation to M. M. L. NR 46 TC 51 Z9 52 U1 0 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2014 VL 59 IS 7 BP 933 EP 941 DI 10.1093/cid/ciu468 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AR2JY UT WOS:000343411900005 PM 24958238 ER PT J AU Wright, AJ Fishman, JA AF Wright, Alissa J. Fishman, Jay A. TI Central Nervous System Syndromes in Solid Organ Transplant Recipients SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE central nervous system; fungus; meningitis; organ transplant; virus ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HEPATITIS-C VIRUS; REVERSIBLE ENCEPHALOPATHY SYNDROME; ORTHOTOPIC LIVER-TRANSPLANTATION; IMMUNE RECONSTITUTION SYNDROME; (KPC)-PRODUCING K. PNEUMONIAE; HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTIOUS-DISEASES SOCIETY; DONOR-DERIVED INFECTIONS; HERPES-SIMPLEX-VIRUS AB Solid organ transplant recipients have a high incidence of central nervous system (CNS) complications, including both focal and diffuse neurologic deficits. In the immunocompromised host, the initial clinical evaluation must focus on both life-threatening CNS infections and vascular or anatomic lesions. The clinical signs and symptoms of CNS processes are modified by the immunosuppression required to prevent graft rejection. In this population, these etiologies often coexist with drug toxicities and metabolic abnormalities that complicate the development of a specific approach to clinical management. This review assesses the multiple risk factors for CNS processes in solid organ transplant recipients and establishes a timeline to assist in the evaluation and management of these complex patients. C1 [Wright, Alissa J.; Fishman, Jay A.] Massachusetts Gen Hosp, Transplant Infect Dis Program, Boston, MA 02114 USA. [Fishman, Jay A.] Harvard Univ, Sch Med, Transplant Ctr, Boston, MA USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp Transplant Ctr, 55 Fruit St,WH510A, Boston, MA 02114 USA. EM jfishman@partners.org NR 133 TC 5 Z9 5 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 OCT 1 PY 2014 VL 59 IS 7 BP 1001 EP 1011 DI 10.1093/cid/ciu428 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AR2JY UT WOS:000343411900016 PM 24917660 ER PT J AU Lo Re, V Wang, L Devine, S Baser, O Olufade, T AF Lo Re, Vincent, III Wang, Li Devine, Scott Baser, Onur Olufade, Temitope TI Hepatic Decompensation in Patients With HIV/Hepatitis B Virus (HBV)/Hepatitis C Virus (HCV) Triple Infection Versus HIV/HCV Coinfection and the Effect of Anti-HBV Nucleos(t)ide Therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE end-stage liver disease; hepatic decompensation; hepatitis B; hepatitis C; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; VETERANS AGING COHORT; VIRAL-HEPATITIS; HIV-INFECTION; AFFAIRS; EVENTS; SYSTEM; CARE AB The incidence rate of hepatic decompensation was higher in patients with human immunodeficiency virus (HIV)/hepatitis B virus (HBV)/hepatitis C virus (HCV) triple infection than in those with HIV/HCV coinfection (24.1 vs 10.8 events per 1000 person-years; hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.12-3.18). Compared with HIV/HCV-infected patients, the rate of decompensation was increased among HIV/HBV/HCV-infected patients receiving no anti-HBV therapy (HR, 2.48; 95% CI, 1.37-4.49) but not among those who did receive such therapy (HR, 1.09; 95% CI,.40-2.97) C1 [Lo Re, Vincent, III] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III] Univ Penn, Perelman Sch Med, Penn Ctr AIDS Res, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. [Wang, Li; Baser, Onur] STATinMED Res, Analyt Res, Dallas, TX USA. [Devine, Scott; Olufade, Temitope] Merck Sharpe & Dohme Corp, US Outcomes Res, Whitehouse Stn, NJ USA. [Baser, Onur] MEF Univ, Dept Econ Adm & Social Sci, Istanbul, Turkey. RP Lo Re, V (reprint author), Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, 836 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM vincentl@mail.med.upenn.edu RI Lo Re, Vincent/N-7817-2015 NR 25 TC 4 Z9 4 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2014 VL 59 IS 7 BP 1027 EP 1031 DI 10.1093/cid/ciu476 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AR2JY UT WOS:000343411900019 PM 24944235 ER PT J AU Lewis, A Kimberly, WT AF Lewis, Ariane Kimberly, W. Taylor TI Prediction of ventriculoperitoneal shunt placement based on type of failure during external ventricular drain wean SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Article DE Extraventricular drain; Hydrocephalus; Subarachnoid hemorrhage; Ventriculoperitoneal shunt ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; NORMAL-PRESSURE HYDROCEPHALUS; DEPENDENT HYDROCEPHALUS; CEREBROSPINAL-FLUID; REHABILITATION; COILING AB Objective: There are multiple etiologies for failure while weaning an external ventricular drain (EVD) after subarachnoid hemorrhage (SAH), but there is little data on the relationship between etiology of wean failure and ventriculoperitoneal shunt (VPS) placement. Methods: We performed a retrospective analysis of SAH patients who had an EVD placed between January 2008 and June 2012 at our institution. For each wean step (defined as raising or clamping the EVD), we recorded success or failure. We categorized failure as lowering or opening the EVD due to elevated intracranial pressure (ICP), clinical failure (due to headache or vomiting or altered mental status), leakage from the EVD site, or development of radiographic hydrocephalus. We evaluated the relationship between etiology of wean failure and subsequent need for VPS. Results: Of 116 patients with an EVD placed, 35 required VPS placement (30%). Patients who required VPS placement had a median of 2 (interquartile range (IQR) 1-4) wean failures and those who did not require VPS placement had a median of 1 (IQR 0-1) wean failure (p = 0.001). There was no significant relationship between age, sex, Hunt Hess score, Fisher score, Glasgow coma scale, aneurysm location, aneurysm size, aneurysm treatment method, vasospasm and need for VPS. There was a significant relationship between patients with at least one wean failure due to clinical changes or radiographic hydrocephalus and need for VPS (p = 0.007 and p = 0.029, respectively). After multivariate analysis, there was only a significant relationship between clinical changes and need for VPS (OR 2.76, CI 1.03-7.36, p = 0.04). Conclusion: There is a significant association between wean failure due to clinical changes and requirement for VPS placement after SAH. (C) 2014 Elsevier B.V. All rights reserved. C1 [Lewis, Ariane; Kimberly, W. Taylor] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. RP Kimberly, WT (reprint author), Lunder 644,55 Fruit St, Boston, MA 02114 USA. EM Ariane.kansas.lewis@gmail.com; wtkimberly@partners.org OI Lewis, Ariane/0000-0002-0756-7320 FU Andrew David Heitman Neurovascular Research Foundation FX This work was supported by the Andrew David Heitman Neurovascular Research Foundation (W.T.K.). The foundation had no role in study design, collection, analysis, interpretation of data, writing of the manuscript, or decision to submit the manuscript for publication. NR 21 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 EI 1872-6968 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD OCT PY 2014 VL 125 BP 109 EP 113 DI 10.1016/j.clineuro.2014.07.022 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AR1LO UT WOS:000343346900022 PM 25108289 ER PT J AU Brooks, GA Li, L Uno, H Hassett, MJ Landon, BE Schrag, D AF Brooks, Gabriel A. Li, Ling Uno, Hajime Hassett, Michael J. Landon, Bruce E. Schrag, Deborah TI Acute Hospital Care Is The Chief Driver Of Regional Spending Variation In Medicare Patients With Advanced Cancer SO HEALTH AFFAIRS LA English DT Article ID UNITED-STATES; HEALTH; SATISFACTION; OUTCOMES; QUALITY; COSTS AB The root causes of regional variation in medical spending are poorly understood and vary by clinical condition. To identify drivers of regional spending variation for Medicare patients with advanced cancer, we used linked Surveillance, Epidemiology, and End Results program (SEER)-Medicare data from the period 2004-10. We broke down Medicare spending into thirteen cancer-relevant service categories. We then calculated the contribution of each category to spending and regional spending variation. Acute hospital care was the largest component of spending and the chief driver of regional spending variation, accounting for 48 percent of spending and 67 percent of variation. In contrast, chemotherapy accounted for 16 percent of spending and 10 percent of variation. Hospice care constituted 5 percent of spending. However, variation in hospice spending was fully offset by opposing variation in other categories. Our analysis suggests that the strategy with the greatest potential to improve the value of care for patients with advanced cancer is to reduce reliance on acute hospital care for this patient population. C1 [Brooks, Gabriel A.; Hassett, Michael J.; Schrag, Deborah] Harvard Univ, Sch Med, Boston, MA 02163 USA. [Brooks, Gabriel A.; Li, Ling; Uno, Hajime; Hassett, Michael J.; Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. [Uno, Hajime] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Landon, Bruce E.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Brooks, GA (reprint author), Harvard Univ, Sch Med, Boston, MA 02163 USA. EM gabriel_brooks@dfci.harvard.edu FU Conquer Cancer Foundation of the American Society of Clinical Oncology; National Cancer Institute of the National Institutes of Health [R25CA92203] FX This study was presented as a research abstract at the AcademyHealth Annual Research Meeting in Baltimore, Maryland, June 24, 2013. Gabriel Brooks was supported by a Young Investigator Award from the Conquer Cancer Foundation of the American Society of Clinical Oncology and by a program grant from the National Cancer Institute of the National Institutes of Health (Grant No. R25CA92203). Contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. This study used the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, National Cancer Institute; the Office of Research, Development, and Information, Centers for Medicare and Medicaid Services; Information Management Services, Inc.; and the Surveillance, Epidemiology, and End Results program tumor registries in the creation of the SEER-Medicare database. NR 30 TC 17 Z9 17 U1 3 U2 6 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD OCT PY 2014 VL 33 IS 10 BP 1793 EP 1800 DI 10.1377/hlthaff.2014.0280 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AR2IE UT WOS:000343406500013 PM 25288424 ER PT J AU Jena, AB Schoemaker, L Bhattacharya, J AF Jena, Anupam B. Schoemaker, Lena Bhattacharya, Jay TI Exposing Physicians To Reduced Residency Work Hours Did Not Adversely Affect Patient Outcomes After Residency SO HEALTH AFFAIRS LA English DT Article ID LENGTH-OF-STAY; DUTY HOURS; ATTENTIONAL FAILURES; NATIONAL-SURVEY; MEDICAL ERRORS; CARE; INTERNS; MORTALITY; EDUCATION; REFORM AB In 2003, work hours for physicians-in-training (residents) were capped by regulation at eighty hours per week, leading to the hotly debated but unexplored issue of whether physicians today are less well trained as a result of these work-hour reforms. Using a unique database of nearly all hospitalizations in Florida during 2000-09 that were linked to detailed information on the medical training history of the physician of record for each hospitalization, we studied whether hospital mortality and patients' length-of-stay varied according to the number of years a physician was exposed to the 2003 duty-hour regulations during his or her residency. We examined this database of practicing Florida physicians, using a difference-in-differences analysis that compared trends in outcomes of junior physicians (those with one-year post-residency experience) pre- and post-2003 to a control group of senior physicians (those with ten or more years of post-residency experience) who were not exposed to these reforms during their residency. We found that the duty-hour reforms did not adversely affect hospital mortality and length-of-stay of patients cared for by new attending physicians who were partly or fully exposed to reduced duty hours during their own residency. However, assessment of the impact of the duty-hour reforms on other clinical outcomes is needed. C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Boston, MA 02163 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jena, Anupam B.; Bhattacharya, Jay] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Schoemaker, Lena; Bhattacharya, Jay] Stanford Univ, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Boston, MA 02163 USA. EM jena@hcp.med.harvard.edu FU Office of the Director, National Institutes of Health [1DP5OD017897-01]; National Institute on Aging [R21 AG041112-02] FX Support for this research was provided by the Office of the Director, National Institutes of Health (Grant No. 1DP5OD017897-01, Anupam B. Jena, principal investigator). Jay Bhattacharya acknowledges support from the National Institute on Aging (Grant No. R21 AG041112-02). NR 41 TC 1 Z9 1 U1 0 U2 2 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD OCT PY 2014 VL 33 IS 10 BP 1832 EP 1840 DI 10.1377/hlthaff.2014.0318 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AR2IE UT WOS:000343406500019 PM 25288430 ER PT J AU Jafari-Khouzani, K AF Jafari-Khouzani, Kourosh TI MRI Upsampling Using Feature-Based Nonlocal Means Approach SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Interpolation; magnetic resonance imaging (MRI); nonlocal means; super-resolution; upsampling ID IMAGE SUPERRESOLUTION; INTERPOLATION AB In magnetic resonance imaging (MRI), spatial resolution is limited by several factors such as acquisition time, short physiological phenomena, and organ motion. The acquired image usually has higher resolution in two dimensions (the acquisition plane) in comparison with the third dimension, resulting in highly anisotropic voxel size. Interpolation of these low resolution (LR) images using standard techniques, such as linear or spline interpolation, results in distorted edges in the planes perpendicular to the acquisition plane. This poses limitation on conducting quantitative analyses of LR images, particularly on their voxel-wise analysis and registration. We have proposed a new non-local means feature- based technique that uses structural information of a high resolution (HR) image with a different contrast and interpolates the LR image. In this approach, the similarity between voxels is estimated using a feature vector that characterizes the laminar pattern of the brain structures, resulting in a more accurate similarity measure in comparison with conventional patch-based approach. This technique can be applied to LR images with both anisotropic and isotropic voxel sizes. Experimental results conducted on brain MRI scans of patients with brain tumors, multiple sclerosis, epilepsy, as well as schizophrenic patients and normal controls show that the proposed method is more accurate, requires fewer computations, and thus is significantly faster than a previous state-of-the-art patch-based technique. We also show how the proposed method may be used to upsample regions of interest drawn on LR images. C1 [Jafari-Khouzani, Kourosh] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Jafari-Khouzani, Kourosh] Harvard Univ, Sch Med, Boston, MA USA. RP Jafari-Khouzani, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. EM kjafari@nmr.mgh.harvard.edu FU National Institutes of Health under Advanced Multimodal Neuroimaging Training Program [R90-DA023427, 5U01CA154601-03, 2P41EB015896-16, R01CA129371, K24CA125440A] FX Manuscript received April 05, 2014; accepted May 17, 2014. Date of publication June 12, 2014; date of current version September 29, 2014. This work was supported in part by the National Institutes of Health under Advanced Multimodal Neuroimaging Training Program under Grant R90-DA023427, Grant 5U01CA154601-03, Grant 2P41EB015896-16, Grant R01CA129371, and Grant K24CA125440A. NR 25 TC 7 Z9 7 U1 1 U2 18 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD OCT PY 2014 VL 33 IS 10 BP 1969 EP 1985 DI 10.1109/TMI.2014.2329271 PG 17 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 AR6OL UT WOS:000343702700006 PM 24951680 ER PT J AU Ou, YM Akbari, H Bilello, M Da, X Davatzikos, C AF Ou, Yangming Akbari, Hamed Bilello, Michel Da, Xiao Davatzikos, Christos TI Comparative Evaluation of Registration Algorithms in Different Brain Databases With Varying Difficulty: Results and Insights SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Brain magnetic resonance imaging (MRI); deformable image registration; evaluation; registration accuracy ID NONRIGID IMAGE REGISTRATION; BREAST MR-IMAGES; DEFORMABLE REGISTRATION; MUTUAL-INFORMATION; SUBJECT REGISTRATION; FRAMEWORK; ATLAS; SEGMENTATION; VALIDATION; SIMILARITY AB Evaluating various algorithms for the inter-subject registration of brain magnetic resonance images (MRI) is a necessary topic receiving growing attention. Existing studies evaluated image registration algorithms in specific tasks or using specific databases (e. g., only for skull-stripped images, only for single-site images, etc.). Consequently, the choice of registration algorithms seems task-and usage/parameter-dependent. Nevertheless, recent large-scale, often multi-institutional imaging-related studies create the need and raise the question whether some registration algorithms can 1) generally apply to various tasks/databases posing various challenges; 2) perform consistently well, and while doing so, 3) require minimal or ideally no parameter tuning. In seeking answers to this question, we evaluated 12 general-purpose registration algorithms, for their generality, accuracy and robustness. We fixed their parameters at values suggested by algorithm developers as reported in the literature. We tested them in 7 databases/tasks, which present one or more of 4 commonly-encountered challenges: 1) inter-subject anatomical variability in skull-stripped images; 2) intensity homogeneity, noise and large structural differences in raw images; 3) imaging protocol and field-of-view (FOV) differences in multi-site data; and 4) missing correspondences in pathology-bearing images. Totally 7,562 registrations were performed. Registration accuracies were measured by (multi-) expert-annotated landmarks or regions of interest (ROIs). To ensure reproducibility, we used public software tools, public databases (whenever possible), and we fully disclose the parameter settings. We show evaluation results, and discuss the performances in light of algorithms' similarity metrics, transformation models and optimization strategies. We also discuss future directions for the algorithm development and evaluations. C1 [Ou, Yangming; Akbari, Hamed; Bilello, Michel; Da, Xiao; Davatzikos, Christos] Univ Penn, Dept Radiol, CBICA, Philadelphia, PA 19104 USA. [Ou, Yangming] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Ou, YM (reprint author), Univ Penn, Dept Radiol, CBICA, Philadelphia, PA 19104 USA. RI Da, Xiao/F-8738-2015; Ou, Yangming/M-5931-2013 OI Da, Xiao/0000-0001-9898-8130; Ou, Yangming/0000-0002-7726-6208 FU NIA NIH HHS [R01 AG014971] NR 129 TC 22 Z9 22 U1 6 U2 16 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD OCT PY 2014 VL 33 IS 10 BP 2039 EP 2065 DI 10.1109/TMI.2014.2330355 PG 27 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 AR6OL UT WOS:000343702700012 PM 24951685 ER PT J AU Rigoni, R Maina, V Mantero, S Marrella, V Grassi, F Pesole, G Mora, JR Villa, A Cassani, B AF Rigoni, R. Maina, V. Mantero, S. Marrella, V. Grassi, F. Pesole, G. Mora, J. R. Villa, A. Cassani, B. TI Microbial signals control inflammation and autoimmunity induced by hypomorphic RAG defects SO IMMUNOLOGY LA English DT Meeting Abstract CT 9th European-Mucosal-Immunology-Group Meeting CY OCT, 2014 CL Univ Glasgow, Glasgow, SCOTLAND SP European Mucosal Immunol Grp HO Univ Glasgow C1 [Rigoni, R.; Maina, V.; Mantero, S.] Humanitas Res Hosp, Rozzano Mi, Italy. [Marrella, V.; Villa, A.; Cassani, B.] IRGB CNR, Rozzano Mi, Italy. [Grassi, F.] Inst Res Biomed, Bellinzona, Switzerland. [Pesole, G.] Univ Bari, Bari, Italy. [Mora, J. R.] Harvard Med Sc, Massachusetts Gen Hosp, Boston, MA 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 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD OCT PY 2014 VL 143 SU 1 SI SI MA 059 BP 29 EP 30 PG 2 WC Immunology SC Immunology GA AR7BB UT WOS:000343733800095 ER PT J AU Woodward, AM Argueso, P AF Woodward, Ashley M. Argueeso, Pablo TI Expression Analysis of the Transmembrane Mucin MUC20 in Human Corneal and Conjunctival Epithelia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE MUC20; transmembrane mucin; cornea; conjunctiva; epithelial cell ID OCULAR SURFACE EPITHELIA; MEMBRANE-ASSOCIATED MUCINS; MESSENGER-RNA EXPRESSION; HEPATOCYTE GROWTH-FACTOR; GENE-EXPRESSION; AUTOLOGOUS SERUM; CELL-SURFACE; IN-VITRO; CANCER; MUC16 AB PURPOSE. Cell surface mucins are a group of highly O-glycosylated transmembrane glycoproteins responsible for the protection of epithelial cells on mucosal surfaces. The aim of this study was to investigate the localization and regulation of mucin 20 (MUC20) at the ocular surface. METHODS. Localization of MUC20 in human corneal and conjunctival epithelia was evaluated by immunofluorescence microscopy. Immortalized corneal (HCLE) and conjunctival (HCjE) cell lines were grown at different stages of differentiation and subjected to quantitative PCR and Western blot analyses. Cell surface proteins on apical cell membranes were biotinylated and isolated by neutravidin chromatography. RESULTS. The MUC20 was detected throughout the entire human ocular surface epithelia, predominantly in cell membranes within intermediate cell layers. In conjunctiva, MUC20 also was observed in the cytoplasm of apical cells within the stratified squamous epithelium, but not in goblet cells. Quantitative PCR and immunoblotting demonstrated expression of MUC20 in HCLE and HCjE cells. Induction of differentiation with serum-containing medium resulted in upregulation of MUC20 mRNA and protein. Biotin labeling of the surface of stratified cultures revealed low levels of MUC20 protein on apical glycocalyces. Further, MUC20 was not detected in the cell culture media or in human tears, suggesting that the extracellular domain of MUC20 is not released from the ocular surface as described previously for other cell surface mucins. CONCLUSIONS. Our results indicate that MUC20 is a novel transmembrane mucin expressed by the human corneal and conjunctival epithelia, and suggest that differential expression of MUC20 during differentiation has a role in maintaining ocular surface homeostasis. C1 [Argueeso, Pablo] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Argueso, P (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM pablo_argueso@meei.harvard.edu FU National Institutes of Health/National Eye Institute (NIH/NEI; Bethesda, MD, USA) [R01 EY014847] FX Supported by National Institutes of Health/National Eye Institute (NIH/NEI; Bethesda, MD, USA) Grant R01 EY014847 (PA). NR 43 TC 6 Z9 6 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2014 VL 55 IS 10 BP 6132 EP 6138 DI 10.1167/iovs.14-15269 PG 7 WC Ophthalmology SC Ophthalmology GA AQ9DY UT WOS:000343147100002 PM 25168902 ER PT J AU Schroedl, F Kaser-Eichberger, A Schlereth, SL Bock, F Regenfuss, B Reitsamer, HA Lutty, GA Maruyama, K Chen, L Lutjen-Drecoll, E Dana, R Kerjaschki, D Alitalo, K De Stefano, ME Junghans, BM Heindl, LM Cursiefen, C AF Schroedl, Falk Kaser-Eichberger, Alexandra Schlereth, Simona L. Bock, Felix Regenfuss, Birgit Reitsamer, Herbert A. Lutty, Gerard A. Maruyama, Kazuichi Chen, Lu Luetjen-Drecoll, Elke Dana, Reza Kerjaschki, Dontscho Alitalo, Kari De Stefano, Maria Egle Junghans, Barbara M. Heindl, Ludwig M. Cursiefen, Claus TI Consensus Statement on the Immunohistochemical Detection of Ocular Lymphatic Vessels SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE immune privilege; immunocytochemistry; lymphatics ID CILIARY BODY; LYMPHANGIOGENESIS; EYE; MACROPHAGES; MARKERS; CORNEAL; ANGIOGENESIS; VASCULATURE; PODOPLANIN; EXPRESSION AB There is currently considerable controversy about existence and classification of "lymphatic vessels" in the eye. Some of the confusion is certainly caused by inappropriate use (or nonuse) of the correct immunohistochemical markers. Many experts in the field expressed the need for a consensus statement, and, in this perspective, authors offer arguments and solutions to reliably continue with immunohistochemical ocular lymphatic research. C1 [Schroedl, Falk; Kaser-Eichberger, Alexandra; Reitsamer, Herbert A.] Paracelsus Med Univ, Dept Ophthalmol & Optometry, A-5020 Salzburg, Austria. [Schroedl, Falk] Paracelsus Med Univ, Dept Anat, A-5020 Salzburg, Austria. [Schlereth, Simona L.; Bock, Felix; Regenfuss, Birgit; Heindl, Ludwig M.; Cursiefen, Claus] Univ Cologne, Dept Ophthalmol, D-50931 Cologne, Germany. [Lutty, Gerard A.] Johns Hopkins Univ, Wilmer Ophthalmol Inst, Baltimore, MD 21218 USA. [Maruyama, Kazuichi] Tohoku Univ, Grad Sch Med, Dept Ophthalmol, Sendai, Miyagi 980, Japan. [Chen, Lu] Univ Calif Berkeley, Program Vis Sci, Ctr Eye Dis & Dev, Berkeley, CA 94720 USA. [Chen, Lu] Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA. [Luetjen-Drecoll, Elke] Univ Erlangen Nurnberg, Dept Anat 2, Erlangen, Germany. [Dana, Reza] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Dana, Reza] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Kerjaschki, Dontscho] Med Univ Vienna, Dept Pathol, Vienna, Austria. [Alitalo, Kari] Univ Helsinki, Inst Biomed, Helsinki, Finland. [De Stefano, Maria Egle] Univ Roma La Sapienza, Dept Biol & Biotechnol Charles Darwin, Ist Pasteur, Fdn Cenci Bolognetti, I-00185 Rome, Italy. [Junghans, Barbara M.] Univ New S Wales, Sch Optometry & Vis Sci, Sydney, NSW, Australia. RP Schroedl, F (reprint author), Paracelsus Med Univ, Dept Ophthalmol & Optometry, Strubergasse 21, A-5020 Salzburg, Austria. EM falk.schroedl@pmu.ac.at RI Alitalo, Kari/J-5013-2014; OI Alitalo, Kari/0000-0002-7331-0902; Junghans, Barbara/0000-0002-2089-7965 FU NEI NIH HHS [R01 EY016151, R01 EY017392] NR 29 TC 17 Z9 20 U1 1 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2014 VL 55 IS 10 BP 6440 EP 6442 DI 10.1167/iovs.14-15638 PG 3 WC Ophthalmology SC Ophthalmology GA AQ9DY UT WOS:000343147100041 PM 25315233 ER PT J AU Lee, WJ Sobrin, L Lee, MJ Kang, MH Seong, M Cho, H AF Lee, Won June Sobrin, Lucia Lee, Min Jeong Kang, Min Ho Seong, Mincheol Cho, Heeyoon TI The Relationship Between Diabetic Retinopathy and Diabetic Nephropathy in a Population-Based Study in Korea (KNHANES V-2, 3) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE diabetic nephropathy; diabetic retinopathy; epidemiological study; KNHANES; microalbuminuria; overt nephropathy ID NUTRITION EXAMINATION SURVEY; CHRONIC KIDNEY-DISEASE; EURODIAB IDDM COMPLICATIONS; RISK-FACTORS; NATIONAL-HEALTH; RENAL-INSUFFICIENCY; MELLITUS PATIENTS; BLOOD-PRESSURE; US POPULATION; UNITED-STATES AB PURPOSE. To determine the risk factors for and relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN), including microalbuminuria and overt nephropathy, in a population-based study of diabetes mellitus (DM) patients in Korea. METHODS. This was a population-based, cross-sectional study. From the fifth (2011, 2012) Korea National Health and Nutrition Examination Survey (KNHANES), 971 participants with type 2 DM were included. The prevalence of DR and DN was determined. Multivariate logistic regression was performed to determine risk factors, including DR, associated with DN in the Korean population. RESULTS. In DM patients, we observed a prevalence of 20.0% for any DR and 3.8% for proliferative diabetic retinopathy (PDR). Microalbuminuria prevalence was 19.3% and overt nephropathy prevalence was 5.5%. The risk factors of microalbuminuria were presence of hypertension; higher systolic blood pressure, serum hemoglobin A1c (HbA1c), and serum blood urea nitrogen level; as well as the presence of PDR. The risk factors of overt nephropathy were long duration of DM; high levels of HbA1c, systolic blood pressure, total cholesterol, and serum creatinine; as well as the presence of DR CONCLUSIONS. Proliferative diabetic retinopathy is associated with microalbuminuria and DR is associated with overt nephropathy in Korean DM patients. Our findings suggest that when an ophthalmologist finds the presence of DR or PDR, timely evaluation of the patient's renal status should be recommended. C1 [Lee, Won June; Kang, Min Ho; Seong, Mincheol; Cho, Heeyoon] Hanyang Univ, Coll Med, Dept Ophthalmol, Seoul, South Korea. [Sobrin, Lucia; Cho, Heeyoon] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Lee, Min Jeong] Ajou Univ, Sch Med, Dept Nephrol, Suwon 441749, South Korea. RP Cho, H (reprint author), Hanyang Univ, Guri Hosp, Coll Med, Dept Ophthalmol, Gyongchun Ro 153, Guri City, Gyeonggi Provin, South Korea. EM hycho@hanyang.ac.kr NR 48 TC 5 Z9 5 U1 1 U2 7 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2014 VL 55 IS 10 BP 6547 EP 6553 DI 10.1167/iovs.14-15001 PG 7 WC Ophthalmology SC Ophthalmology GA AQ9DY UT WOS:000343147100057 PM 25205863 ER PT J AU Rusanescu, G Mao, JR AF Rusanescu, Gabriel Mao, Jianren TI Notch3 is necessary for neuronal differentiation and maturation in the adult spinal cord SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE Notch; chronic pain; spinal cord; stem cells; neuronal differentiation; neuronal progenitors; adult neurogenesis; calretinin; nociception; Notch3 ID NEURAL PROGENITOR CELLS; DROSOPHILA-MELANOGASTER; NEUROBLAST SEGREGATION; INTRACELLULAR DOMAIN; ALAGILLE-SYNDROME; NERVOUS-SYSTEM; DNA-SYNTHESIS; HUMAN JAGGED1; IN-VITRO; EXPRESSION AB Notch receptors are key regulators of nervous system development and promoters of neural stem cells renewal and proliferation. Defects in the expression of Notch genes result in severe, often lethal developmental abnormalities. Notch3 is generally thought to have a similar proliferative, anti-differentiation and gliogenic role to Notch1. However, in some cases, Notch3 has an opposite, pro-differentiation effect. Here, we show that Notch3 segregates from Notch1 and is transiently expressed in adult rat and mouse spinal cord neuron precursors and immature neurons. This suggests that during the differentiation of adult neural progenitor cells, Notch signalling may follow a modified version of the classical lateral inhibition model, involving the segregation of individual Notch receptors. Notch3 knockout mice, otherwise neurologically normal, are characterized by a reduced number of mature inhibitory interneurons and an increased number of highly excitable immature neurons in spinal cord laminae I-II. As a result, these mice have permanently lower nociceptive thresholds, similar to chronic pain. These results suggest that defective neuronal differentiation, for example as a result of reduced Notch3 expression or activation, may underlie human cases of intractable chronic pain, such as fibromyalgia and neuropathic pain. C1 [Rusanescu, Gabriel; Mao, Jianren] Massachusetts Gen Hosp, MGH Ctr Translat Pain Res, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. RP Rusanescu, G (reprint author), Massachusetts Gen Hosp, MGH Ctr Translat Pain Res, Dept Anesthesia Crit Care & Pain Med, 149 13th St, Charlestown, MA 02129 USA. EM grusanes@gmail.com FU NIH [P20DA26002, R01DE18214, R01DE18538] FX This work was supported by NIH grants P20DA26002, R01DE18214 and R01DE18538 (J.M). GR performed the research, GR and JM designed the study, analysed data and wrote the manuscript. NR 66 TC 9 Z9 9 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1582-4934 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD OCT PY 2014 VL 18 IS 10 BP 2103 EP 2116 DI 10.1111/jcmm.12362 PG 14 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AR7DE UT WOS:000343739200018 PM 25164209 ER PT J AU Mahal, BA Ziehr, DR Aizer, AA Hyatt, AS Lago-Hernandez, C Choueiri, TK Elfiky, AA Hu, JC Sweeney, CJ Beard, CJ D'Amico, AV Martin, NE Kim, SP Lathan, CS Trinh, QD Nguyen, PL AF Mahal, Brandon A. Ziehr, David R. Aizer, Ayal A. Hyatt, Andrew S. Lago-Hernandez, Carlos Choueiri, Toni K. Elfiky, Aymen A. Hu, Jim C. Sweeney, Christopher J. Beard, Clair J. D'Amico, Anthony V. Martin, Neil E. Kim, Simon P. Lathan, Christopher S. Quoc-Dien Trinh Nguyen, Paul L. TI Racial disparities in an aging population: The relationship between age and race in the management of African American men with high-risk prostate cancer SO JOURNAL OF GERIATRIC ONCOLOGY LA English DT Article DE Prostatic neoplasms; Healthcare disparities; Geriatrics; African American; Population health ID RADICAL PROSTATECTOMY; ANDROGEN DEPRIVATION; RADIATION-THERAPY; CARE; TRIAL; DIAGNOSIS; TIME; RADIOTHERAPY; CARCINOMA; RECEIPT AB Purpose: To evaluate the relationship between age and race on the receipt of definitive therapy among men with high-risk prostate cancer (CaP). Methods: We used the Surveillance, Epidemiology and End Results Program to identify 62,644 men with high-risk CaP (PSA >20 or Gleason 8-10 or stage >= cT3a) diagnosed from 2004 to 2010. Multivariable logistic regression analysis modeled the interaction between age and race and its association with receipt of definitive therapy on 57,674 patients (47,879 white men; 9,795 African American [AA] men) with complete data on the covariates of interest. Results: Among men age >= 70, AA men had a higher risk of CaP-specific mortality (PCSM) compared to white men after adjusting for sociodemographic and prostate cancer-specific factors (Adjusted HR 1.20; 95% CI 1.02-1.38; P = 0.02). Nevertheless, a significant interaction between race and age was found (P interaction = 0.01), such that the adjusted odds of receiving definitive treatment for AA vs. white was 0.67 (95% CI 0.62-0.73; P < 0.001) among men age <70, but was 0.60 (95% CI 0.55-0.66; P < 0.001) among men age >= 70, suggesting increased racial disparity in the receipt of definitive treatment among older men. Conclusion: AA men with high-risk CaP are less likely to receive definitive therapy than white men. This disparity is significantly larger among men age >= 70, despite excess PCSM among AA men in this group. With a rapidly expanding population of older minority men, this disparity should be urgently addressed to prevent increasing disparities in cancer care. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Mahal, Brandon A.; Ziehr, David R.; Lago-Hernandez, Carlos] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Aizer, Ayal A.] Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Hyatt, Andrew S.; Beard, Clair J.; D'Amico, Anthony V.; Martin, Neil E.; Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Hyatt, Andrew S.; Choueiri, Toni K.; Elfiky, Aymen A.; Sweeney, Christopher J.; Beard, Clair J.; D'Amico, Anthony V.; Martin, Neil E.; Lathan, Christopher S.; Nguyen, Paul L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Choueiri, Toni K.; Elfiky, Aymen A.; Sweeney, Christopher J.; Lathan, Christopher S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hu, Jim C.] UCLA Med Ctr, Dept Urol, Los Angeles, CA 90095 USA. [Kim, Simon P.] Yale Univ, Dept Urol, Canc Outcomes & Publ Policy Effectiveness Res Ctr, New Haven, CT 06510 USA. [Quoc-Dien Trinh] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 FU Prostate Cancer Foundation; Fitz's Cancer Warriors FX This work is supported by David and Cynthia Chapin, the Prostate Cancer Foundation, Fitz's Cancer Warriors, Hugh Simons in honor of Frank and Anne Simons, and a grant from an anonymous family foundation. NR 35 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1879-4068 EI 1879-4076 J9 J GERIATR ONCOL JI J. Geriatr. Oncol. PD OCT 1 PY 2014 VL 5 IS 4 BP 352 EP 358 DI 10.1016/j.jgo.2014.05.001 PG 7 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA AR6JU UT WOS:000343690800003 PM 24862107 ER PT J AU Raux, M Patel, VI Cochennec, F Mukhopadhyay, S Desgranges, P Cambria, RP Becquemin, JP LaMuraglia, GM AF Raux, Maxime Patel, Virendra I. Cochennec, Frederic Mukhopadhyay, Shankha Desgranges, Pascal Cambria, Richard P. Becquemin, Jean-Pierre LaMuraglia, Glenn M. TI A propensity-matched comparison of outcomes for fenestrated endovascular aneurysm repair and open surgical repair of complex abdominal aortic aneurysms SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 29-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg ID RANDOMIZED CONTROLLED-TRIAL; LONG-TERM DURABILITY; EXPERIENCE; MANAGEMENT; ENDOGRAFTS; MORTALITY; STENT AB Objective: The benefit of fenestrated endovascular aortic aneurysm repair (FEVAR) compared with open surgical repair (OSR) of complex abdominal aortic aneurysms (CAAAs) is unknown. This study compares 30-day outcomes of these procedures from two high-volume centers where FEVAR was undertaken for high-risk patients. Methods: Patients undergoing FEVAR with commercially available devices and OSR of CAAAs (total suprarenal/supravisceral clamp position) were propensity matched by demographic, clinical, and anatomic criteria to identify similar patient cohorts. Perioperative outcomes were evaluated using univariate and multivariate methods. Results: From July 2001 to August 2012, 59 FEVAR and 324 OSR patients were identified. After 1:4 propensity matching for age, gender, hypertension, congestive heart failure, coronary disease, chronic obstructive pulmonary disease, stroke, diabetes, preoperative creatinine, and anticipated/actual aortic clamp site, the study cohort consisted of 42 FEVARs and 147 OSRs. The most frequent FEVAR construct was two renal fenestrations, with or without a single mesenteric scallop, in 50% of cases. An average of 2.9 vessels were treated per patient. Univariate analysis demonstrated FEVAR had higher rates of 30-day mortality (9.5% vs 2%; P = .05), any complication (41% vs 23%; P = .01), procedural complications (24% vs 7%; P < .01), and graft complications (30% vs 2%; P < .01). Multivariable analysis showed FEVAR was associated with an increased risk of 30-day mortality (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.1-24; P = .04), any complication (OR, 2.3; 95% CI, 1.1-4.9; P = .01), and graft complications (OR, 24; 95% CI, 4.8-66; P < .01). Conclusions: FEVAR, in this two-center study, was associated with a significantly higher risk of perioperative mortality and morbidity compared with OSR for management of CAAAs. These data suggest that extension of the paradigm shift comparing EVAR with OSR for routine AAAs to patients with CAAAs is not appropriate. Further study to establish proper patient selection for FEVAR instead of OSR is warranted before widespread use should be considered. C1 [Raux, Maxime; Cochennec, Frederic; Desgranges, Pascal; Becquemin, Jean-Pierre] Univ Paris 12, Hop Henri Mondor, Dept Vasc & Endovasc Surg, F-94010 Creteil, France. [Raux, Maxime; Patel, Virendra I.; Mukhopadhyay, Shankha; Cambria, Richard P.; LaMuraglia, Glenn M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA USA. RP Patel, VI (reprint author), Massachusetts Gen Hosp, 15 Parkman St,Wang ACC 440, Boston, MA 02114 USA. EM vpate14@partners.org NR 23 TC 25 Z9 25 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2014 VL 60 IS 4 BP 858 EP 863 DI 10.1016/j.jvs.2014.04.011 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AR1BX UT WOS:000343316600005 PM 24835042 ER PT J AU Kashyap, VS Illig, KA Shames, ML Maldonado, TS Eliason, JL Clouse, WD AF Kashyap, Vikram S. Illig, Karl A. Shames, Murray L. Maldonado, Thomas S. Eliason, Jonathan L. Clouse, W. Darrin TI A Society changes its name: The Peripheral Vascular Surgery Society becomes the Vascular and Endovascular Surgery Society SO JOURNAL OF VASCULAR SURGERY LA English DT Letter C1 [Kashyap, Vikram S.] Univ Hosp Case Med Ctr, Div Vasc Surg & Endovasc Therapy, Cleveland, OH 44106 USA. [Illig, Karl A.; Shames, Murray L.] Univ S Florida, Div Vasc & Endovasc Surg, Tampa, FL USA. [Maldonado, Thomas S.] NYU, Langone Med Ctr, Div Vasc Surg, New York, NY USA. [Eliason, Jonathan L.] Univ Michigan, Vasc Surg Sect, Ann Arbor, MI 48109 USA. [Clouse, W. Darrin] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Kashyap, VS (reprint author), Univ Hosp Case Med Ctr, Div Vasc Surg & Endovasc Therapy, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2014 VL 60 IS 4 BP 1123 EP 1124 DI 10.1016/j.jvs.2014.07.001 PG 3 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AR1BX UT WOS:000343316600102 PM 25260483 ER PT J AU Katon, J Mattocks, K Zephyrin, L Reiber, G Yano, EM Callegari, L Schwarz, EB Goulet, J Shaw, J Brandt, C Haskell, S AF Katon, Jodie Mattocks, Kristin Zephyrin, Laurie Reiber, Gayle Yano, Elizabeth M. Callegari, Lisa Schwarz, Eleanor Bimla Goulet, Joseph Shaw, Jonathan Brandt, Cynthia Haskell, Sally TI Gestational Diabetes and Hypertensive Disorders of Pregnancy Among Women Veterans Deployed in Service of Operations in Afghanistan and Iraq SO JOURNAL OF WOMENS HEALTH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; HEALTH-CARE; GENDER-DIFFERENCES; MENTAL-HEALTH; UNITED-STATES; RISK-FACTORS; PREECLAMPSIA; DEPRESSION; DIAGNOSES; MELLITUS AB Objective: To determine the prevalence of gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP) among women Veterans using Department of Veterans Affairs (VA) maternity benefits previously deployed in service of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND), and whether pregnancy complications were associated with VA use following delivery. Methods: We identified the study population through linkage with the Department of Defense roster and VA administrative and clinical data. GDM and HDP were identified by International Classification of Diseases, Ninth Revision codes in VA inpatient or outpatient files. Similarly, we constructed a nationally representative sample of deliveries from the Nationwide Inpatient Sample. We calculated standardized incidence ratios (SIR) adjusted for age and year of delivery to compare rates of GDM and HDP. Proportional hazards regression was used to determine whether pregnancy complications were associated with use of VA following delivery. Results: Between 2001 and 2010, 2,288 women OEF/OIF/OND Veterans used VA maternity benefits; 5.2% had GDM and 9.6% had HDP. Compared with women delivering in the United States, women OEF/OIF/OND Veterans using VA maternity benefits had higher risk of developing GDM (SIR: 1.40; 95% confidence interval [CI] 1.16, 1.68) and HDP (SIR: 1.32; 95% CI 1.15, 1.51). Among women OEF/OIF/OND Veterans using VA maternity benefits, GDM (HR 1.01, 95% CI 0.83, 1.24) and HDP (HR 1.07, 95% CI 0.92, 1.25) were not associated with use of VA following delivery. Conclusions: Non-VA providers should be aware of their patients' Veteran status and the associated elevated risk for pregnancy complications. Within VA, focused efforts to optimize Veterans' preconception and postpartum health are needed. C1 [Katon, Jodie; Reiber, Gayle; Callegari, Lisa] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, HSR&D, Seattle, WA USA. [Katon, Jodie; Zephyrin, Laurie; Haskell, Sally] Off Womens Hlth Serv, VA Cent Off, Washington, DC USA. [Katon, Jodie; Reiber, Gayle; Callegari, Lisa] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Reiber, Gayle] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Mattocks, Kristin] VA Cent Western Massachusetts, Leeds, MA USA. [Mattocks, Kristin] Univ Massachusetts, Sch Med, Worcester, MA USA. [Zephyrin, Laurie] New York Harbor VA Healthcare Syst, New York, NY USA. [Zephyrin, Laurie] NYU, Dept Obstet & Gynecol, Langone Med Ctr, New York, NY 10016 USA. [Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, Los Angeles, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Callegari, Lisa] Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Schwarz, Eleanor Bimla] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Schwarz, Eleanor Bimla] Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. [Schwarz, Eleanor Bimla] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Goulet, Joseph] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Haskell, Sally] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Goulet, Joseph; Brandt, Cynthia; Haskell, Sally] VA Connecticut Healthcare Syst, West Haven, CT USA. [Shaw, Jonathan] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Shaw, Jonathan] Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. RP Katon, J (reprint author), VA Med Ctr, 1660 South Columbian Way S-152, Seattle, WA 98108 USA. EM jkaton@u.washington.edu OI Goulet, Joseph/0000-0002-0842-804X FU U.S. Department of Veteran Affairs, Office of Research and Development, Health Services Research and Development [DHI 07-065-2]; Office of Academic Affiliations' Associated Health Postdoctoral Fellowship [TPP 61-026]; VA Health Services Research and Development (HSR&D) Senior Career Scientist Award [RCS 98-353]; VA HSR&D Career Scientist Award [RCS 05-195] FX This material is based on work supported by the U.S. Department of Veteran Affairs, Office of Research and Development, Health Services Research and Development (DHI 07-065-2), an Office of Academic Affiliations' Associated Health Postdoctoral Fellowship to Dr. Katon (#TPP 61-026), a VA Health Services Research and Development (HSR&D) Senior Career Scientist Award to Dr. Reiber (grant RCS 98-353) and a VA HSR&D Career Scientist Award to Dr. Yano (grant RCS 05-195). The authors would like to thank Norman Silliker and Melissa Skanderson, at VA Connecticut Healthcare System, West Haven, CT, and Jeff Rodenbaugh, at VA Puget Sound Health Care System, for their work managing the data. 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. NR 52 TC 5 Z9 5 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD OCT 1 PY 2014 VL 23 IS 10 BP 792 EP 800 DI 10.1089/jwh.2013.4681 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA AR0DT UT WOS:000343237900005 PM 25090022 ER PT J AU Dusetzina, SB Winn, A Chambers, J Ellis, S Conti, RM Freedman, RA Alexander, GC Keating, NL Huskamp, HA AF Dusetzina, Stacie B. Winn, Aaron Chambers, James Ellis, Shellie Conti, Rena M. Freedman, Rachel A. Alexander, G. Caleb Keating, Nancy L. Huskamp, Haiden A. TI Payer-Level Differences in the Response to Regulatory Actions Regarding Withdrawal of Breast Cancer as an Indication for Bevacizumab SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Dusetzina, Stacie B.] Univ N Carolina, Sch Med, Div Gen Med & Clin Epidemiol, Chapel Hill, NC USA. [Dusetzina, Stacie B.; Winn, Aaron; Ellis, Shellie] Univ N Carolina, Sch Med, Dept Hlth Policy & Management, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Chambers, James] Tufts Med Ctr, Ctr Evaluat Value & Risk Hlth, Boston, MA USA. [Conti, Rena M.] Univ Chicago Hosp, Dept Pediat, Sect Pediat Hematol Oncol, Chicago, IL 60637 USA. [Conti, Rena M.] Univ Chicago, Ctr Hlth & Social Sci, Chicago, IL 60637 USA. [Freedman, Rachel A.] Dana Farber Canc Inst, Boston, MA USA. [Alexander, G. Caleb] Johns Hopkins Univ, Ctr Drug Safety & Effectiveness, Baltimore, MD 21218 USA. [Alexander, G. Caleb] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21218 USA. [Keating, Nancy L.; Huskamp, Haiden A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD OCT 1 PY 2014 VL 23 IS 10 MA P-19 BP 857 EP 857 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA AR0DT UT WOS:000343237900033 ER PT J AU Ercan, A Yu, E Finkelstein, J Nigrovic, PA AF Ercan, Altan Yu, Elaine Finkelstein, Joel Nigrovic, Peter A. TI IgG Fc Glycosylation Favoring Less Inflammatory Variants Is Regulated by Estradiol in Men SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Ercan, Altan; Nigrovic, Peter A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Rheumatol Immunol & Allergy, Cambridge, MA 02138 USA. [Yu, Elaine; Finkelstein, Joel] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD OCT 1 PY 2014 VL 23 IS 10 MA P-20 BP 857 EP 857 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA AR0DT UT WOS:000343237900034 ER PT J AU Gupta, A Mayer, EA Sanmiguel, CP Van Horn, J Tillisch, K Labus, JS AF Gupta, Arpana Mayer, Emeran A. Sanmiguel, Claudia P. Van Horn, John Tillisch, Kirsten Labus, Jennifer S. TI Morphological and Diffuse Tensor Imaging-Based Brain Signatures Discriminate Obese and Overweight from Lean Subjects: Examining Sex Differences Within the Brain SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Gupta, Arpana; Mayer, Emeran A.; Sanmiguel, Claudia P.; Tillisch, Kirsten; Labus, Jennifer S.] Univ Calif Los Angeles, Ingest Behav & Obes Program, Gail & Gerald Oppenheimer Family Ctr Neurobiol St, Los Angeles, CA USA. [Gupta, Arpana; Mayer, Emeran A.; Sanmiguel, Claudia P.; Tillisch, Kirsten; Labus, Jennifer S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gupta, Arpana; Mayer, Emeran A.; Sanmiguel, Claudia P.; Tillisch, Kirsten; Labus, Jennifer S.] Univ Calif Los Angeles, Div Digest Dis, Los Angeles, CA USA. [Mayer, Emeran A.] Univ Calif Los Angeles, Ahmanson Lovelace Brain Mapping Ctr, Los Angeles, CA USA. [Van Horn, John] Univ So Calif, Keck Sch Med, Inst Neuroimaging & Informat, Los Angeles, CA 90033 USA. [Tillisch, Kirsten] Greater Los Angeles Healthcare Syst, US Dept Vet Affairs, Integrat Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD OCT 1 PY 2014 VL 23 IS 10 MA P-30 BP 860 EP 860 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA AR0DT UT WOS:000343237900044 ER PT J AU Jacobs, EG Weiss, B Whitfield-Gabrieli, S Klibanski, A Goldstein, JM AF Jacobs, Emily G. Weiss, Blair Whitfield-Gabrieli, Sue Klibanski, Anne Goldstein, Jill M. TI Reproductive Aging Is Associated With Altered Prefrontal and Hippocampal Signaling During Working Memory SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Jacobs, Emily G.; Weiss, Blair; Goldstein, Jill M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Jacobs, Emily G.; Goldstein, Jill M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Whitfield-Gabrieli, Sue] MIT, Cambridge, MA 02139 USA. [Klibanski, Anne] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD OCT 1 PY 2014 VL 23 IS 10 MA P-38 BP 862 EP 862 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA AR0DT UT WOS:000343237900052 ER PT J AU Steensma, DP Shampo, MA Kyle, RA AF Steensma, David P. Shampo, Marc A. Kyle, Robert A. TI Bruce Beutler: Innate Immunity and Toll-Like Receptors SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 21 TC 1 Z9 1 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD OCT PY 2014 VL 89 IS 10 BP E101 EP E103 DI 10.1016/j.mayocp.2013.10.039 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AR0BW UT WOS:000343230500003 PM 25282435 ER PT J AU Richter, C Seco, J Hong, TS Duda, DG Bortfeld, T AF Richter, Christian Seco, Joao Hong, Ted S. Duda, Dan G. Bortfeld, Thomas TI Radiation-induced changes in hepatocyte-specific Gd-EOB-DTPA enhanced MRI: Potential mechanism SO MEDICAL HYPOTHESES LA English DT Article ID NECROSIS-FACTOR-ALPHA; ORGANIC ANION TRANSPORTERS; MESSENGER-RNA LEVELS; HEPATOCELLULAR-CARCINOMA; TNF-ALPHA; NUCLEAR FACTOR-1-ALPHA; IRRADIATION LEADS; CANCER-TREATMENT; CONTRAST AGENTS; HEPATIC-UPTAKE AB Liver irradiation leads to a decreased uptake of a hepatobiliary directed MRI contrast agent (Gd-EOB-DTPA) as shown in studies performed 1-6 months after proton therapy, stereotactic ablative body radiation therapy and brachytherapy. Therefore, Gd-EOB-DTPA enhanced MRI could potentially be used for in vivo verification of the delivered dose distribution. Achieving this would be highly desirable, especially for particle therapy, where the accuracy and precision of the spatial dose deposition is affected by uncertainties of the range of particles in patients. However, the empirically detected effect needs to be understood before it can be used as a surrogate imaging biomarker for in vivo treatment verification or even liver functionality. Here, we propose a model of the underlying molecular mechanism of this phenomenon and discuss its implications for radiation therapy. We model the multi-step process starting from the immediate response after liver irradiation to the delayed/subsequent signal decrease in Gd-EOB-DTPA enhanced MR'. The model is based on both: (a) Evidence from different previously published reports and (b) a detailed evaluation of intra-hepatic signaling using a pathway analysis to identify potential pathways that are critical in this process. The proposed model provides mechanistic understanding of the reduced signal intensity in Gd-EOBDTPA enhanced MRI occurring in irradiated liver. We think that establishing this comprehensive model will be of great interest for the field of radiation oncology and can trigger further research. For example, measuring the expression of involved cytokines and specific transport proteins in blood samples and biopsy derived tissue samples and correlating the results with MRI imaging could give important information and may even explain inter-patient variations in MRI signal decrease C1 [Richter, Christian] Tech Univ Dresden, Oncoray Natl Ctr Radiat Res Oncol, Fac Med, D-01307 Dresden, Germany. [Richter, Christian] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, D-01307 Dresden, Germany. [Richter, Christian] Tech Univ Dresden, Dept Radiat Oncol, Fac Med, D-01307 Dresden, Germany. [Richter, Christian] Helmholtz Zentrum Dresden Rossendorf, Dresden, Germany. [Richter, Christian] German Canc Consortium DKTK, Dresden, Germany. [Richter, Christian] German Canc Res Ctr, Heidelberg, Germany. [Seco, Joao; Hong, Ted S.; Duda, Dan G.; Bortfeld, Thomas] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Seco, Joao; Hong, Ted S.; Duda, Dan G.; Bortfeld, Thomas] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Richter, C (reprint author), Tech Univ Dresden, Oncoray Natl Ctr Radiat Res Oncol, Fac Med, Fetscherstr 74,PF 41, D-01307 Dresden, Germany. EM christian.richter@oncoray.de FU Federal Share of program [C06-CA059267]; German Federal Ministry of Education and Research (BMBF) [03Z1N51] FX This work was supported in part by the Federal Share of program income earned by Massachusetts General Hospital on C06-CA059267, Proton Therapy Research and Treatment Center. Additional, this study has been partly supported by the German Federal Ministry of Education and Research (BMBF) under contract number 03Z1N51. NR 43 TC 5 Z9 5 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 EI 1532-2777 J9 MED HYPOTHESES JI Med. Hypotheses PD OCT PY 2014 VL 83 IS 4 BP 477 EP 481 DI 10.1016/j.mehy.2014.08.004 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AR1KR UT WOS:000343344600009 PM 25175713 ER PT J AU Murphy, GF Wilson, BJ Girouard, SD Frank, NY Frank, MH AF Murphy, George F. Wilson, Brian J. Girouard, Sasha D. Frank, Natasha Y. Frank, Markus H. TI Stem cells and targeted approaches to melanoma cure SO MOLECULAR ASPECTS OF MEDICINE LA English DT Review DE Melanoma; Cancer stem cell; ABCB5; Vasculogenic mimicry; Immune evasion; Drug resistance; Therapy ID EPITHELIAL-MESENCHYMAL TRANSITION; CUTANEOUS MALIGNANT-MELANOMA; TUMOR-INITIATING CELLS; BREAST-CANCER CELLS; CLASS-I EXPRESSION; METASTATIC MELANOMA; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; VASCULOGENIC MIMICRY; AGGRESSIVE MELANOMA AB Melanoma stem cells, also known as malignant melanoma-initiating cells, are identifiable through expression of specific biomarkers such as ABCB5 (ATP-binding cassette, sub-family B (MDR/TAP), member 5), NGFR (nerve growth factor receptor, CD271) and ALDH (aldehyde dehydrogenase), and drive melanoma initiation and progression based on prolonged self-renewal capacity, vasculogenic differentiation and immune evasion. As we will review here, specific roles of these aggressive subpopulations have been documented in tumorigenic growth, metastatic dissemination, therapeutic resistance, and malignant recurrence. Moreover, recent findings have provided pre-clinical proof-of-concept for the potential therapeutic utility of the melanoma stem cell concept. Therefore, melanoma stem cell-directed therapeutic approaches represent promising novel strategies to improve therapy of this arguably most virulent human cancer. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Murphy, George F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Wilson, Brian J.; Frank, Markus H.] Childrens Hosp Boston, Transplantat Res Ctr, Boston, MA USA. [Wilson, Brian J.; Frank, Markus H.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Girouard, Sasha D.] Harvard Univ, Sch Med, Dermatol Residency Program, Boston, MA USA. [Frank, Natasha Y.] VA Boston Healthcare Syst, Dept Med, Boston, MA USA. RP Murphy, GF (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM gmurphy@rics.bwh.harvard.edu; markus.frank@childrens.harvard.edu RI Frank, Markus/O-1625-2014 OI Frank, Markus/0000-0002-1312-0488 FU NIH/NCI [R01CA113796, R01CA158467, R01CA138231, P50CA093683]; Department of Veterans Affairs VA Merit Review Awards [VA BLRD 1I01BX000516, VA RRD 1I01RX000989] FX This work was supported by the NIH/NCI Grants R01CA113796, R01CA158467, R01CA138231 and P50CA093683, and by the Department of Veterans Affairs VA Merit Review Awards VA BLR&D 1I01BX000516 and VA RR&D 1I01RX000989. NR 131 TC 6 Z9 8 U1 4 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0098-2997 EI 1872-9452 J9 MOL ASPECTS MED JI Mol. Asp. Med. PD OCT PY 2014 VL 39 SI SI BP 33 EP 49 DI 10.1016/j.mam.2013.10.003 PG 17 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA AR1XF UT WOS:000343377200003 PM 24145241 ER PT J AU Berg, H Blagoev, K AF Berg, Howard Blagoev, Krastan TI Perspectives on working at the physics-biology interface Preface SO PHYSICAL BIOLOGY LA English DT Editorial Material C1 [Berg, Howard] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Blagoev, Krastan] Natl Sci Fdn, Arlington, VA USA. [Blagoev, Krastan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Berg, H (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. FU NIAID NIH HHS [R01 AI016478] NR 1 TC 0 Z9 0 U1 1 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1478-3967 EI 1478-3975 J9 PHYS BIOL JI Phys. Biol. PD OCT PY 2014 VL 11 IS 5 AR 050301 DI 10.1088/1478-3975/11/5/050301 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AR6CM UT WOS:000343670600001 PM 25291971 ER PT J AU Thompson, JL Rosell, DR Slifstein, M Girgis, RR Xu, XY Ehrlich, Y Kegeles, LS Hazlett, EA Abi-Dargham, A Siever, LJ AF Thompson, Judy L. Rosell, Daniel R. Slifstein, Mark Girgis, Ragy R. Xu, Xiaoyan Ehrlich, Yosefa Kegeles, Lawrence S. Hazlett, Erin A. Abi-Dargham, Anissa Siever, Larry J. TI Prefrontal dopamine D1 receptors and working memory in schizotypal personality disorder: a PET study with [C-11]NNC112 SO PSYCHOPHARMACOLOGY LA English DT Article DE Schizotypal personality disorder; Schizophrenia; PET; Dopamine; Prefrontal cortex; Working memory ID IN-VIVO BINDING; NEUROPSYCHOLOGICAL PERFORMANCE; SCHIZOPHRENIA SPECTRUM; NAIVE PATIENTS; D-1 RECEPTORS; TASK; SPECIFICITY; SELECTIVITY; TOMOGRAPHY; IMPAIRMENT AB Schizotypal personality disorder (SPD) is associated with working memory (WM) impairments that are similar to those observed in schizophrenia. Imaging studies have suggested that schizophrenia is associated with alterations in dopamine D1 receptor availability in the prefrontal cortex (PFC) that may be related to the WM impairments that characterize this disorder. The aim of this study was to characterize prefrontal D1 receptor availability and its relation to WM performance in SPD. We used positron emission tomography (PET) and the radiotracer [C-11]NNC112 with 18 unmedicated SPD and 21 healthy control participants; as an index of D1 receptor availability, binding potential (BP) measures (BPF, BPND, and BPP) were calculated for prefrontal and striatal subregions. To assess WM, SPD participants completed the 2-back and Paced Auditory Serial Addition Test (PASAT). There were no significant group differences in PFC BP. BPF and BPP in the medial PFC were significantly negatively related to PASAT performance (r (s) = -0.551, p = .022 and r (s) = -0.488, p = .047, respectively), but BP was not related to 2-back performance. In contrast to what has been found in schizophrenia, SPD was not associated with significant alterations in prefrontal D1 receptor availability. Similar to previous schizophrenia findings, however, higher prefrontal D1 receptor availability was associated with poorer WM performance (as measured by the PASAT) in SPD. These findings suggest that schizophrenia and SPD may share a common pathophysiological feature related to prefrontal dopamine functioning that contributes to WM dysfunction, but that in SPD, alterations in D1 may occur only in a subset of individuals and/or to an extent that is minor relative to what occurs in schizophrenia. C1 [Thompson, Judy L.; Slifstein, Mark; Girgis, Ragy R.; Xu, Xiaoyan; Kegeles, Lawrence S.; Abi-Dargham, Anissa] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Rosell, Daniel R.; Ehrlich, Yosefa; Hazlett, Erin A.; Siever, Larry J.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Rosell, Daniel R.; Ehrlich, Yosefa; Hazlett, Erin A.; Siever, Larry J.] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Kegeles, Lawrence S.; Abi-Dargham, Anissa] Columbia Univ Coll Phys & Surg, Dept Radiol, New York, NY 10032 USA. [Thompson, Judy L.] Rutgers State Univ, Sch Hlth Related Profess, Scotch Plains, NJ 07076 USA. RP Thompson, JL (reprint author), Rutgers State Univ, Sch Hlth Related Profess, 1776 Raritan Rd, Scotch Plains, NJ 07076 USA. EM judy.thompson@rutgers.edu RI Girgis, Ragy/N-3271-2016 FU US Department of Veterans Affairs [7609-028]; National Institute of Mental Health [MH56140]; Veterans Affairs VISN 3 Mental Illness Research, Education and Clinical Center (MIRECC) FX We thank the research participants of this study and express gratitude for the expert assistance of Rawad Ayoub, Jennifer Bae, Felipe Castillo, John Castrillon, Elizabeth Hackett, Elisabeth Iskander, Olga Kambalov, and Ethan Rothstein. This work was supported by a Merit Review grant (7609-028) from the US Department of Veterans Affairs to Larry J. Siever, by grant MH56140 from the National Institute of Mental Health to Larry J. Siever, and by the Veterans Affairs VISN 3 Mental Illness Research, Education and Clinical Center (MIRECC). NR 39 TC 2 Z9 2 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 2014 VL 231 IS 21 BP 4231 EP 4240 DI 10.1007/s00213-014-3566-6 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AR6WO UT WOS:000343721600014 PM 24781514 ER PT J AU Graubert, T AF Graubert, Timothy TI AML Genomics: Introduction SO SEMINARS IN HEMATOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Hematol Malignancy Program, Boston, MA 02114 USA. RP Graubert, T (reprint author), Massachusetts Gen Hosp, Hematol Malignancy Program, Boston, MA 02114 USA. EM tgraubert@partners.org OI Graubert, Timothy/0000-0002-7710-1171 NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 EI 1532-8686 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2014 VL 51 IS 4 BP 249 EP 249 DI 10.1053/j.seminhematol.2014.08.008 PG 1 WC Hematology SC Hematology GA AR1KH UT WOS:000343343600001 PM 25311737 ER PT J AU Perry, AM Attar, EC AF Perry, Ashley M. Attar, Eyal C. TI New Insights in AML Biology From Genomic Analysis SO SEMINARS IN HEMATOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; PARTIAL TANDEM DUPLICATION; HEMATOPOIETIC STEM-CELLS; CHRONIC MYELOMONOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; BROMODOMAIN PROTEIN BRD4; METHYLTRANSFERASE GENE EZH2; TUMOR-SUPPRESSOR GENE; ADDITIONAL-SEX-COMBS; PML-RAR-ALPHA AB Advancements in sequencing techniques have led to the discovery of numerous genes not previously implicated in acute myeloid leukemia (AML) biology. Further in vivo studies are necessary to discern the biological impact of these mutations. Murine models, the most commonly used in vivo system, provide a physiologic context for the study of specific genes. These systems have provided deep insights into the role of genetic translocations, mutations, and dysregulated gene expression on leukemia pathogenesis. This review focuses on the phenotype of newly identified genes, including NPM1, IDH1/2, TET2, MLL, DNMT3A, EZH2, EED, and ASXL1, in mouse models and the implications on AML biology. (C) 2014 Elsevier Inc. All rights reserved. C1 [Perry, Ashley M.; Attar, Eyal C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Attar, EC (reprint author), Massachusetts Gen Hosp, 100 Blossom St, Boston, MA 02114 USA. EM eattar@partners.org NR 135 TC 4 Z9 4 U1 2 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 0037-1963 EI 1532-8686 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2014 VL 51 IS 4 BP 282 EP 297 DI 10.1053/j.seminhematol.2014.08.005 PG 16 WC Hematology SC Hematology GA AR1KH UT WOS:000343343600005 PM 25311741 ER PT J AU Graubert, T Stone, R AF Graubert, Timothy Stone, Richard TI AML Genomics for the Clinician SO SEMINARS IN HEMATOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; ADULT PATIENTS; GROUP-B; PROGNOSTIC-SIGNIFICANCE; CEBPA MUTATIONS; NPM1 MUTATIONS; YOUNG-ADULT; WILD-TYPE AB Acute myeloid leukemia (AML) is a heterogeneous disease, characterized by frequent resistance to available chemotherapeutic agents. The basic therapy for patients with AML has changed little over the past 30 years. Improvements in outcome in recent decades in younger adult cohorts have generally been ascribed to better supportive care (ie, transfusion and antimicrobial therapy); older adults with AML continue to fare poorly. The explosion of new knowledge regarding the AML genome has yet to be translated into therapeutic benefit, but analysis of specific molecular features in AML samples has enabled the field to more accurately parse out prognosis and assign appropriate therapies (eg, chemotherapy vs allogeneic stem cell transplantation) for groups of patients. Cytogenetic analysis, whether by metaphase or interphase analysis, has been the main tool used to divide patients into varying prognostic subsets, but it has been modified in recent years to include assessment of mutations in a small number of genes. In the past several years, new technologies have provided strategies to interrogate individual cancer genomes in a broad and in-depth fashion. The present article discusses the potential of these new technologies, particularly gene panel and whole-exome or whole-genome sequencing, to improve diagnosis, prognosis, and therapeutic outcome in AML. (C) 2014 Elsevier Inc. All rights reserved. C1 [Graubert, Timothy] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Stone, Richard] Dana Farber Canc Inst, Boston, MA USA. RP Graubert, T (reprint author), Massachusetts Gen Hosp, Ctr Canc, 10 North Grove St,Lawrence House 204, Boston, MA 02114 USA. EM tgraubert@partners.org OI Graubert, Timothy/0000-0002-7710-1171 NR 51 TC 6 Z9 6 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 EI 1532-8686 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2014 VL 51 IS 4 BP 322 EP 329 DI 10.1053/j.seminhematol.2014.08.006 PG 8 WC Hematology SC Hematology GA AR1KH UT WOS:000343343600008 PM 25311744 ER PT J AU Barshes, NR Rodriguez-Barradas, MC Bechara, CF Pisimisis, G Young, EJ Kougias, P AF Barshes, Neal R. Rodriguez-Barradas, Maria C. Bechara, Carlos F. Pisimisis, George Young, Edward J. Kougias, Panos TI Microbial Isolates and Their Antimicrobial Susceptibilities in Inframalleolar Foot Infections SO SURGICAL INFECTIONS LA English DT Article ID SURGICAL SERIES; OSTEOMYELITIS; ULCERS AB Background: Foot infections are especially common among diabetic individuals and often contribute to limb loss. We investigated the microbiology of foot infections in our hospital to further understand the microbes involved and to assist in identifying potential empiric oral antibiotic regimens for foot infections. Methods: All moderate/severe inframalleolar foot infections that were drained surgically at a single center during a single calendar year were included. Initial isolates obtained intra-operatively were reviewed. Results: A total of 39 patients underwent operative drainage, of whom 34 (87%) had diabetes mellitus. Fifty-two total specimens were obtained, consisting of 26 fluid swabs, 12 soft-tissue specimens, and 11 bone specimens. Nineteen (49%) of the specimens were obtained from toe wounds, 16 (41%) from forefoot wounds, two (5%) from midfoot wounds, and two (5%) from heel wounds. Most specimens (71%) were polymicrobial, yielding a mean of 2.2 isolates. In all, 100 individual isolates, encompassing 39 different bacterial organisms, were identified (55 gram-positive aerobes, 33 gram-negative aerobes, 11 anaerobes, and one fungus). Enterococcus species and Staphylococcus aureus were the most common bacteria, each representing 13% of isolates. Only 9% of isolates were methicillin-resistant S. aureus. Obtaining multiple specimens (e.g., both fluid and tissue) increased the yield for identification of organisms. Oral antibiotics provided adequate coverage for gram-positive organisms but not for gram-negative organisms. Conclusions: Foot infections are typically polymicrobial and may involve a wide variety of microbes. Initial gram-stain results could be used to choose better initial empiric antimicrobial therapy for such infections. C1 [Barshes, Neal R.; Bechara, Carlos F.; Pisimisis, George; Kougias, Panos] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E Debakey Dept Surg, Houston, TX 77030 USA. [Rodriguez-Barradas, Maria C.; Young, Edward J.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. RP Barshes, NR (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E Debakey Dept Surg, Div Vasc & Endovasc Surg, 2002 Holcombe Blvd OCL 112, Houston, TX 77030 USA. EM nbarshes@bcm.tmc.edu NR 8 TC 2 Z9 2 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-2964 EI 1557-8674 J9 SURG INFECT JI Surg. Infect. PD OCT 1 PY 2014 VL 15 IS 5 BP 585 EP 591 DI 10.1089/sur.2013.126 PG 7 WC Infectious Diseases; Surgery SC Infectious Diseases; Surgery GA AR0AO UT WOS:000343224800019 PM 24827989 ER PT J AU Schroeder, FA Wang, C Van de Bittner, GC Neelamegam, R Takakura, WR Karunakaran, A Wey, HY Reis, SA Gale, J Zhang, YL Holson, EB Haggarty, SJ Hooker, JM AF Schroeder, F. A. Wang, C. Van de Bittner, G. C. Neelamegam, R. Takakura, W. R. Karunakaran, A. Wey, H. Y. Reis, S. A. Gale, J. Zhang, Y. L. Holson, E. B. Haggarty, S. J. Hooker, J. M. TI PET Imaging Demonstrates Histone Deacetylase Target Engagement and Clarifies Brain Penetrance of Known and Novel Small Molecule Inhibitors in Rat SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Neuroimaging epigenetics; preclinical; translational; rodent; radiotracer ID CHROMATIN-MEDIATED NEUROPLASTICITY; HDAC INHIBITORS; VALPROIC ACID; SCHIZOPHRENIA; MECHANISMS; PLASTICITY; DISORDERS; CLOZAPINE; BEHAVIOR; BINDING AB Histone deacetylase (HDAC) enzymes have been demonstrated as critical components in maintaining chromatin homeostasis, CNS development, and normal brain function. Evidence in mouse models links HDAC expression to learning, memory, and mood-related behaviors; small molecule HDAC inhibitor tool compounds have been used to demonstrate the importance of specific HDAC subtypes in modulating CNS-disease-related behaviors in rodents. So far, no direct evidence exists to understand the quantitative changes in HDAC target engagement that are necessary to alter biochemistry and behavior in a living animal. Understanding the relationship between target engagement and in vivo effect is essential in refining new ways to alleviate disease. We describe here, using positron emission tomography (PET) imaging of rat brain, the in vivo target engagement of a subset of class I/IIb HDAC enzymes implicated in CNS-disease (HDAC subtypes 1, 2, 3, and 6). We found marked differences in the brain penetrance of tool compounds from the hydroxamate and benzamide HDAC inhibitor classes and resolved a novel, highly brain penetrant benzamide, CN147, chronic treatment with which resulted in an antidepressant-like effect in a rat behavioral test. Our work highlights a new translational path for understanding the molecular and behavioral consequences of HDAC target engagement. C1 [Schroeder, F. A.; Wang, C.; Van de Bittner, G. C.; Neelamegam, R.; Takakura, W. R.; Karunakaran, A.; Wey, H. Y.; Hooker, J. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. [Schroeder, F. A.; Reis, S. A.; Haggarty, S. J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Neurol, Chem Neurobiol Lab, Boston, MA 02114 USA. [Schroeder, F. A.; Reis, S. A.; Haggarty, S. J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Psychiat, Boston, MA 02114 USA. [Gale, J.; Zhang, Y. L.; Holson, E. B.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. RP Hooker, JM (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Suite 2301, Charlestown, MA 02129 USA. EM hooker@nmr.mgh.harvard.edu OI Haggarty, Stephen J./0000-0002-7872-168X FU National Institute of Drug Abuse (NIDA) of the National Institutes of Health [R01DA030321]; [R01DA028301] FX Research was supported by the National Institute of Drug Abuse (NIDA) of the National Institutes of Health under Grant Number R01DA030321 (J.M.H.; S.J.H) with additional support under Grant R01DA028301 (SJ.H.). NR 41 TC 5 Z9 5 U1 2 U2 9 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 OCT PY 2014 VL 5 IS 10 BP 1055 EP 1062 DI 10.1021/cn500162j PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA AR0QO UT WOS:000343276600020 PM 25188794 ER PT J AU O'Brien, EC Simon, DN Allen, LA Singer, DE Fonarow, GC Kowey, PR Thomas, LE Ezekowitz, MD Mahaffey, KW Chang, P Piccini, JP Peterson, ED AF O'Brien, Emily C. Simon, DaJuanicia N. Allen, Larry A. Singer, Daniel E. Fonarow, Gregg C. Kowey, Peter R. Thomas, Laine E. Ezekowitz, Michael D. Mahaffey, Kenneth W. Chang, Paul Piccini, Jonathan P. Peterson, Eric D. TI Reasons for warfarin discontinuation in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) SO AMERICAN HEART JOURNAL LA English DT Article ID STROKE PREVENTION; PREDICTING STROKE; PRIMARY-CARE; RISK FACTOR; THERAPY; ANTICOAGULATION; PROPHYLAXIS; PERSISTENCE; PATTERNS; ASPIRIN AB Background Warfarin reduces thromboembolic risks in atrial fibrillation (AF), but therapeutic durability remains a concern. Methods We used clinical data from ORBIT-AF, a nationwide outpatient AF registry conducted at 176 sites with follow-up data at 6 and 12 months, to examine longitudinal patterns of warfarin discontinuation. We estimated associations between patient and provider characteristics and report of any warfarin discontinuation using discrete time proportional odds models. Results Of 10,132 AF patients enrolled in ORBIT-AF from June 2010 to August 2011, 6,110 (60.3%) were prescribed warfarin, had follow-up data, and were not switched to an alternative oral anticoagulant enrolled from June 2010 to August 2011. Over 1 year, 617 patients (10.1% of baseline warfarin users) discontinued warfarin therapy. Among incident warfarin users (starting therapy within 1 year of baseline survey), warfarin discontinuation rates rose to 17.1%. The most commonly reported reasons for warfarin discontinuation were physician preference (47.7%), patient refusal/preference (21.1%), bleeding event (20.2%), frequent falls/frailty (10.8%), high bleeding risk (9.8%), and patient inability to adhere to/monitor therapy (4.7%). In multivariable analysis, the factors most strongly associated with warfarin discontinuation were bleeding hospitalization during follow-up (odds ratio 10.91, 95% CI 7.91-15.03), prior catheter ablation (1.83, 1.37-2.45), noncardiovascular/nonbleeding hospitalization (1.77, 1.40-2.24), cardiovascular hospitalization (1.64, 1.33-2.03), and permanent AF (0.25, 0.17-0.36). Conclusions Discontinuation of warfarin is common among patients with AF, particularly among incident users. Warfarin is most commonly discontinued because of physician preference, patient refusal, and bleeding events. C1 [O'Brien, Emily C.; Simon, DaJuanicia N.; Thomas, Laine E.; Piccini, Jonathan P.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC 27705 USA. [Allen, Larry A.] Univ Colorado, Sch Med, Aurora, CO USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Kowey, Peter R.; Ezekowitz, Michael D.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Mahaffey, Kenneth W.] Stanford Sch Med, Stanford, CA USA. [Chang, Paul] Janssen Sci Affairs, Raritan, NJ USA. RP O'Brien, EC (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA. EM emily.obrien@duke.edu NR 20 TC 20 Z9 20 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD OCT PY 2014 VL 168 IS 4 BP 487 EP 494 DI 10.1016/j.ahj.2014.07.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AQ8QZ UT WOS:000343096900014 PM 25262258 ER PT J AU Duval, S Keo, HH Oldenburg, NC Baumgartner, I Jaff, MR Peacock, JM Tretinyak, AS Henry, TD Luepker, RV Hirsch, AT AF Duval, Sue Keo, Hong H. Oldenburg, Niki C. Baumgartner, Iris Jaff, Michael R. Peacock, James M. Tretinyak, Alexander S. Henry, Timothy D. Luepker, Russell V. Hirsch, Alan T. TI The impact of prolonged lower limb ischemia on amputation, mortality, and functional status: The FRIENDS registry SO AMERICAN HEART JOURNAL LA English DT Article ID PERIPHERAL ARTERIAL-DISEASE; LOWER-EXTREMITY; VASCULAR-SURGERY; URGENT TREATMENT; UNITED-STATES; MINOR STROKE; RISK-FACTORS; MULTICENTER; POPULATION; MANAGEMENT AB Background Peripheral artery disease (PAD) is a major cause of cardiovascular ischemic events and amputation. Knowledge gaps exist in defining and measuring key factors that predict these events. The objective of this study was to assess whether duration of limb ischemia would serve as a major predictor of limb and patient survival. Methods The FReedom from Ischemic Events: New Dimensions for Survival (FRIENDS) registry enrolled consecutive patients with limb-threatening peripheral artery disease at a single tertiary care hospital. Demographic information, key clinical care time segments, functional status and use of revascularization, and pharmacotherapy data were collected at baseline, and vascular ischemic events, cardiovascular mortality, and all-cause mortality were recorded at 30 days and 1 year. Results A total of 200 patients with median (interquartile range) age of 76 years (65-84 years) were enrolled in the registry. Median duration of limb ischemia was 0.75 days for acute limb ischemia (ALI) and 61 days for chronic critical limb ischemia (CLI). Duration of limb ischemia of <12, 12 to 24, and >24 hours in patients with ALI was associated with much higher rates of first amputation (P = .0002) and worse amputation-free survival (P = .037). No such associations were observed in patients with CLI. Conclusions For individuals with ischemic symptoms <14 days, prolonged limb ischemia is associated with higher 30-day and 1-year amputation, systemic ischemic event rates, and worse amputation-free survival. No such associations are evident for individuals with chronic CLI. These data imply that prompt diagnosis and revascularization might improve outcomes for patients with ALI. C1 [Duval, Sue; Oldenburg, Niki C.; Hirsch, Alan T.] Univ Minnesota, Sch Med, Cardiovasc Div, Vasc Med Program, Minneapolis, MN 55455 USA. [Duval, Sue; Oldenburg, Niki C.; Hirsch, Alan T.] Univ Minnesota, Sch Med, Lillehei Heart Inst, Minneapolis, MN 55455 USA. [Keo, Hong H.] Kantonsspital Aarau AG, Div Angiol, Aarau, Switzerland. [Baumgartner, Iris] Univ Hosp Bern, Div Angiol, Swiss Cardiovasc Ctr, CH-3010 Bern, Switzerland. [Baumgartner, Iris] Univ Bern, Bern, Switzerland. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Peacock, James M.] Minnesota Dept Hlth, Hlth Promot & Chron Dis Div, Ctr Hlth Promot, St Paul, MN USA. [Tretinyak, Alexander S.] Appleton Med Ctr, Appleton, WI USA. [Henry, Timothy D.] Cedars Sinai Heart Inst, Los Angeles, CA USA. [Luepker, Russell V.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Hirsch, AT (reprint author), Univ Minnesota, Sch Med, Lillehei Heart Inst, Vasc Med Program, Minneapolis, MN 55455 USA. FU Swiss National Science Foundation [PBBEB-121067]; Abbott Vascular, Switzerland; Abbott Vascular, USA FX Dr Keo received a fellowship grant (PBBEB-121067) from the Swiss National Science Foundation and an investigator-initiated research grant from Abbott Vascular, Switzerland. Additional support for registry development was provided via an investigator-initiated grant to the University of Minnesota (Dr Hirsch) from Abbott Vascular, USA, and by contributions from the Minneapolis Heart Institute Foundation at the Abbott Northwestern Hospital, Minneapolis, MN, USA. NR 39 TC 10 Z9 12 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD OCT PY 2014 VL 168 IS 4 BP 577 EP 587 DI 10.1016/j.ahj.2014.06.013 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AQ8QZ UT WOS:000343096900025 PM 25262269 ER PT J AU Welles, CC Whooley, MA Karumanchi, SA Hod, T Thadhani, R Berg, AH Ix, JH Mukamal, KJ AF Welles, Christine C. Whooley, Mary A. Karumanchi, S. Ananth Hod, Tammy Thadhani, Ravi Berg, Anders H. Ix, Joachim H. Mukamal, Kenneth J. TI RE: "VITAMIN D DEFICIENCY AND CARDIOVASCULAR EVENTS IN PATIENTS WITH CORONARY HEART DISEASE: DATA FROM THE HEART AND SOUL STUDY" REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 [Welles, Christine C.; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Welles, Christine C.; Whooley, Mary A.] Vet Affairs Med Ctr, Sect Gen Med, San Francisco, CA 94121 USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Karumanchi, S. Ananth; Hod, Tammy] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Berg, Anders H.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Mukamal, Kenneth J.] Beth Israel Deconess Med Ctr, Div Gen Med & Primary Care, Boston, MA USA. RP Welles, CC (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM christywelles@gmail.com NR 2 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 2014 VL 180 IS 7 BP 758 EP 758 DI 10.1093/aje/kwu216 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AQ8DU UT WOS:000343054500012 PM 25150267 ER PT J AU Nomura, N Nunes, P Bouley, R Nair, AV Shaw, S Ueda, E Pathomthongtaweechai, N Lu, HAJ Brown, D AF Nomura, Naohiro Nunes, Paula Bouley, Richard Nair, Anil V. Shaw, Stanley Ueda, Erica Pathomthongtaweechai, Nutthapoom Lu, Hua A. Jenny Brown, Dennis TI High-throughput chemical screening identifies AG-490 as a stimulator of aquaporin 2 membrane expression and urine concentration SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE cell signaling; diabetes insipidus; drug screening; vasopressin; water channels; EGFR and JAK-2 inhibitor ID NEPHROGENIC DIABETES-INSIPIDUS; EPIDERMAL-GROWTH-FACTOR; RENAL EPITHELIAL-CELLS; COLLECTING DUCT CELLS; IN-VIVO; PHOSPHODIESTERASE INHIBITOR; WATER REABSORPTION; SURFACE EXPRESSION; APICAL MEMBRANE; PLASMA-MEMBRANE AB A reduction or loss of plasma membrane aquaporin 2 (AQP2) in kidney principal cells due to defective vasopressin (VP) signaling through the VP receptor causes excessive urine production, i.e., diabetes insipidus. The amount of AQP2 on the plasma membrane is regulated by a balance of exocytosis and endocytosis and is the rate limiting step for water reabsorption in the collecting duct. We describe here a systematic approach using high-throughput screening (HTS) followed by in vitro and in vivo assays to discover novel compounds that enhance vasopressin-independent AQP2 membrane expression. We performed initial chemical library screening with a high-throughput exocytosis fluorescence assay using LLC-PK1 cells expressing soluble secreted yellow fluorescent protein and AQP2. Thirty-six candidate exocytosis enhancers were identified. These compounds were then rescreened in AQP2-expressing cells to determine their ability to increase AQP2 membrane accumulation. Effective drugs were then applied to kidney slices in vitro. Three compounds, AG-490, beta-lapachone, and HA14-1 increased AQP2 membrane accumulation in LLC-PK1 cells, and both AG-490 and beta-lapachone were also effective in MDCK cells and principal cells in rat kidney slices. Finally, one compound, AG-490 (an EGF receptor and JAK-2 kinase inhibitor), decreased urine volume and increased urine osmolality significantly in the first 2-4 h after a single injection into VP-deficient Brattleboro rats. In conclusion, we have developed a systematic procedure for identifying new compounds that modulate AQP2 trafficking using initial HTS followed by in vitro assays in cells and kidney slices, and concluding with in vivo testing in an animal model. C1 [Nomura, Naohiro; Nunes, Paula; Bouley, Richard; Nair, Anil V.; Shaw, Stanley; Ueda, Erica; Pathomthongtaweechai, Nutthapoom; Lu, Hua A. Jenny; Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nomura, Naohiro; Nunes, Paula; Bouley, Richard; Nair, Anil V.; Shaw, Stanley; Ueda, Erica; Pathomthongtaweechai, Nutthapoom; Lu, Hua A. Jenny; Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. [Nomura, Naohiro; Nunes, Paula; Bouley, Richard; Nair, Anil V.; Pathomthongtaweechai, Nutthapoom; Lu, Hua A. Jenny; Brown, Dennis] Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. [Nomura, Naohiro; Nunes, Paula; Bouley, Richard; Nair, Anil V.; Pathomthongtaweechai, Nutthapoom; Lu, Hua A. Jenny; Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Program Membrane Biol, 185 Cambridge St,Suite 8-202, Boston, MA 02114 USA. EM brown.dennis@mgh.harvard.edu RI Nunes-Hasler, Paula/N-4337-2015 OI Nunes-Hasler, Paula/0000-0002-4598-685X FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK-096586]; NIDDK [DK-075940, DK-092619]; MGH/ECOR; Natural Sciences and Engineering Research Council of Canada; Japan Society for the Promotion of Science; Boston Area Diabetes and Endocrinology Research Center [DK-57521]; MGH Center for the Study of Inflammatory Bowel Disease (NIDDK) [DK-43351]; Medical Scholar's Program of the Faculty of Science, Mahidol University, Bangkok, Thailand FX This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant DK-096586 (to D. Brown). H. A. Lu was supported by NIDDK Grants DK-075940 and DK-092619 and an MGH/ECOR interim support fund. P. Nunes was supported by a doctoral-level scholarship from the Natural Sciences and Engineering Research Council of Canada. N. Nomura was supported by a grant for "Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation program" from Japan Society for the Promotion of Science. Additional support for the Program in Membrane Biology Microscopy Core comes from the Boston Area Diabetes and Endocrinology Research Center (DK-57521) and the MGH Center for the Study of Inflammatory Bowel Disease (NIDDK Grant DK-43351). N. Pathomthongtaweechai was supported during his stay in D. Brown's laboratory by the Medical Scholar's Program of the Faculty of Science, Mahidol University, Bangkok, Thailand. NR 43 TC 4 Z9 6 U1 0 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 EI 1522-1563 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD OCT 1 PY 2014 VL 307 IS 7 BP C597 EP C605 DI 10.1152/ajpcell.00154.2014 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA AR0FK UT WOS:000343244300004 PM 24944200 ER PT J AU Karasawa, H Yakabi, S Wang, L Stengel, A Rivier, J Tache, Y AF Karasawa, Hiroshi Yakabi, Seiichi Wang, Lixin Stengel, Andreas Rivier, Jean Tache, Yvette TI Brain somatostatin receptor 2 mediates the dipsogenic effect of central somatostatin and cortistatin in rats: role in drinking behavior SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE angiotensin receptor 1; brain; cortistatin; somatostatin agonists; water intake ID CENTRAL-NERVOUS-SYSTEM; FOOD-ASSOCIATED DRINKING; GROWTH-HORMONE; WATER-INTAKE; OCTAPEPTIDE ANALOG; CONTAINING NEURONS; CIRCADIAN-RHYTHMS; SUBFORNICAL ORGAN; BINDING-AFFINITY; RING SIZE AB Intracerebroventricular injection of stable somatostatin (SST) agonists stimulates food and water intake in rats. We investigated the receptor subtype(s) involved in the dipsogenic effect of intracerebroventricular injection of SST agonists, mechanisms of action, and role. In nonfasted and non-water-deprived male rats with chronic intracerebroventricular cannula, intake of water without food or food without water was monitored separately to avoid any interactions compared with intracerebroventricular vehicle. SST-14 and cortistatin (CST-14) (1 mu g/rat icv) increased water intake by 3.1- and 2.7-fold, respectively, while both peptides did not alter food intake at 1 h postinjection in the light phase. By contrast, the stable pan-somatostatin agonist ODT8-SST (1 mu g/rat icv) increased both water and food intake by 4.9- and 3.7-fold, respectively. S-346-011, a selective receptor 2 (sst(2)) agonist (1 mu g/rat icv) induced water ingestion, while sst(1) or sst(4) agonist, injected under the same conditions, did not. The sst(2) antagonist S-406-028 (1 mu g/rat icv) prevented the 1-h water intake induced by intracerebroventricular ODT8-SST and CST-14. Losartan (100 mu g/rat icv), an angiotensin receptor 1 (AT(1)) antagonist, completely blocked the water consumption induced by intracerebroventricular ODT8-SST, whereas intracerebroventricular injection of S-406-028 did not modify the intracerebroventricular ANG II-induced dipsogenic response. The sst(2) antagonist reduced by 40% the increase of the 3-h water intake in the early dark phase. These data indicate that SST-14 and CST-14 interact with sst(2) to exert a potent dipsogenic effect, which is mediated downstream by angiotensin-AT1 signaling. These data also indicate that sst(2) activation by brain SST-14 and/or CST-14 may play an important role in the regulation of drinking behavior. C1 [Karasawa, Hiroshi; Yakabi, Seiichi; Wang, Lixin; Stengel, Andreas; Tache, Yvette] Univ Calif Los Angeles, Dept Med, CURE Digest Dis Ctr, Div Digest Dis, Los Angeles, CA 90024 USA. [Karasawa, Hiroshi; Yakabi, Seiichi; Wang, Lixin; Stengel, Andreas; Tache, Yvette] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Rivier, Jean] Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA USA. RP Tache, Y (reprint author), Bldg 115,Rm 117B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [P30-DK-41303, R01-30110]; Veterans Administration Research Career Scientist Award FX This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grants P30-DK-41303 (Animal Core, to Y. Tache and L. Wang), and R01-30110, and by the Veterans Administration Research Career Scientist Award (to Y. Tache). NR 64 TC 2 Z9 2 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 EI 1522-1490 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD OCT 1 PY 2014 VL 307 IS 7 BP R793 EP R801 DI 10.1152/ajpregu.00248.2014 PG 9 WC Physiology SC Physiology GA AQ9XZ UT WOS:000343214000004 PM 25031229 ER PT J AU Do, C Barnes, JL Tan, CY Wagner, B AF Do, Catherine Barnes, Jeffrey L. Tan, Chunyan Wagner, Brent TI Type of MRI contrast, tissue gadolinium, and fibrosis SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE gadolinium/adverse effects; magnetic resonance imaging/adverse effects; nephrogenic fibrosing dermopathy; skin diseases; animals; fibrosis ID NEPHROGENIC SYSTEMIC FIBROSIS; KIDNEY-DISEASE; AGENTS; BIODISTRIBUTION; DERMOPATHY; SKIN; CONSEQUENCES; FIBROBLASTS; GADOTERIDOL; GADODIAMIDE AB It has been presupposed that the thermodynamic stability constant (K-therm) of gadolinium-based MRI chelates relate to the risk of precipitating nephrogenic systemic fibrosis. The present study compared low-K-therm gadodiamide with high-K-therm gadoteridol in cultured fibroblasts and rats with uninephrectomies. Gadolinium content was assessed using scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy in paraffin-embedded tissues. In vitro, fibroblasts demonstrated dose-dependent fibronectin generation, transforming growth factor-beta production, and expression of activated myofibroblast stress fiber protein alpha-smooth muscle actin. There were negligible differences with respect to toxicity or proliferation between the two contrast agents. In the rodent model, gadodiamide treatment led to greater skin fibrosis and dermal cellularity than gadoteridol. In the kidney, both contrast agents led to proximal tubule vacuolization and increased fibronectin accumulation. Despite large detectable gadolinium signals in the spleen, skin, muscle, and liver from the gadodiamide-treated group, contrast-induced fibrosis appeared to be limited to the skin and kidney. These findings support the hypothesis that low-Ktherm chelates have a greater propensity to elicit nephrogenic systemic fibrosis and demonstrate that certain tissues are resistant to these effects. C1 [Do, Catherine; Barnes, Jeffrey L.; Tan, Chunyan] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Barnes, Jeffrey L.; Wagner, Brent] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Wagner, B (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, 7703 Floyd Curl Dr,MC 7882, San Antonio, TX 78229 USA. EM wagnerb@uthscsa.edu OI Wagner, Brent/0000-0002-7063-0142 FU Veterans Administration VISN 17 New Investigator Award; Veterans Administration Career Development Award; Veterans Administration BLR&D Merit Review Award [I01 BX001958]; National Institute of Diabetes and Digestive and Kidney Disease Grant [DK-102085] FX This work was supported by a Veterans Administration VISN 17 New Investigator Award (to B. Wagner), a Veterans Administration Career Development Award (to B. Wagner), Veterans Administration BLR&D Merit Review Award I01 BX001958 (to B. Wagner), and National Institute of Diabetes and Digestive and Kidney Disease Grant DK-102085. NR 40 TC 9 Z9 9 U1 1 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT 1 PY 2014 VL 307 IS 7 BP F844 EP F855 DI 10.1152/ajprenal.00379.2014 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AR0CE UT WOS:000343231600010 PM 25100280 ER PT J AU Wei, Y Liao, Y Zavilowitz, B Ren, J Liu, W Chan, P Rohatgi, R Estilo, G Jackson, EK Wang, WH Satlin, LM AF Wei, Yuan Liao, Yi Zavilowitz, Beth Ren, Jin Liu, Wen Chan, Pokman Rohatgi, Rajeev Estilo, Genevieve Jackson, Edwin K. Wang, Wen-Hui Satlin, Lisa M. TI Angiotensin II type 2 receptor regulates ROMK- like K+ channel activity in the renal cortical collecting duct during high dietary K+ adaptation SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE angiotensin II; angiotensin II type 2 receptor; cortical collecting duct; renal outer medullary potassium channel; protein kinase A ID DEPENDENT PROTEIN-KINASE; NITRIC-OXIDE SYNTHASE; AT(2) RECEPTOR; RAT-KIDNEY; APICAL MEMBRANE; TYROSINE KINASE; GENE-EXPRESSION; MESSENGER-RNA; TUBULE; PHOSPHATASE AB The kidney adjusts K+ excretion to match intake in part by regulation of the activity of apical K+ secretory channels, including renal outer medullary K+ (ROMK)-like K+ channels, in the cortical collecting duct (CCD). ANG II inhibits ROMK channels via the ANG II type 1 receptor (AT(1)R) during dietary K+ restriction. Because AT(1)Rs and ANG II type 2 receptors (AT(2)Rs) generally function in an antagonistic manner, we sought to characterize the regulation of ROMK channels by the AT(2)R. Patchclamp experiments revealed that ANG II increased ROMK channel activity in CCDs isolated from high-K+ (HK)-fed but not normal K+ (NK)-fed rats. This response was blocked by PD-123319, an AT(2)R antagonist, but not by losartan, an AT(1)R antagonist, and was mimicked by the AT(2)R agonist CGP-42112. Nitric oxide (NO) synthase is present in CCD cells that express ROMK channels. Blockade of NO synthase with N-nitro-L-arginine methyl ester and free NO with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt completely abolished ANG II-stimulated ROMK channel activity. NO enhances the synthesis of cGMP, which inhibits phosphodiesterases (PDEs) that normally degrade cAMP; cAMP increases ROMK channel activity. Pretreatment of CCDs with IBMX, a broad-spectrum PDE inhibitor, or cilostamide, a PDE3 inhibitor, abolished the stimulatory effect of ANG II on ROMK channels. Furthermore, PKA inhibitor peptide, but not an activator of the exchange protein directly activated by cAMP (Epac), also prevented the stimulatory effect of ANG II. We conclude that ANG II acts at the AT(2)R to stimulate ROMK channel activity in CCDs from HK-fed rats, a response opposite to that mediated by the AT(1)R in dietary K+-restricted animals, via a NO/cGMP pathway linked to a cAMPPKA-PKA pathway. C1 [Wei, Yuan; Zavilowitz, Beth; Liu, Wen; Rohatgi, Rajeev; Satlin, Lisa M.] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA. [Rohatgi, Rajeev; Estilo, Genevieve; Satlin, Lisa M.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Chan, Pokman] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Ren, Jin; Jackson, Edwin K.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Ren, Jin; Jackson, Edwin K.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Wei, Yuan; Wang, Wen-Hui] New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA. [Rohatgi, Rajeev] James J Peters Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. [Wei, Yuan; Liao, Yi] NYU, Med Ctr, Dept Cell Biol, New York, NY 10016 USA. RP Wei, Y (reprint author), NYU, Med Ctr, Dept Cell Biol, 550 First Ave, New York, NY 10016 USA. EM yuan.wei@nyumc.org FU American Heart Association Scientist Development [0530092N]; NIH [DK-47402, DK-38470, DK-51391, P30-DK-079307]; Department of Veterans Affairs Merit Review [1I01BX000388] FX This work was supported by American Heart Association Scientist Development Grant 0530092N (to Y. Wei). W. H. Wang was supported by NIH Grant DK-47402, and L. M. Satlin was supported by NIH Grants DK-38470 and DK-51391. L. M. Satlin and E. K. Jackson were further supported by NIH Grant P30-DK-079307 (Pittsburgh Center for Kidney Research). R. Rohatgi was supported by Department of Veterans Affairs Merit Review 1I01BX000388. NR 66 TC 7 Z9 7 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT 1 PY 2014 VL 307 IS 7 BP F833 EP F843 DI 10.1152/ajprenal.00141.2014 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AR0CE UT WOS:000343231600009 PM 25100281 ER PT J AU Marchetti, N Garshick, E Kinney, GL McKenzie, A Stinson, D Lutz, SM Lynch, DA Crinerl, GJ Silverman, EK Crapo, JD AF Marchetti, Nathaniel Garshick, Eric Kinney, Gregory L. McKenzie, Alex Stinson, Douglas Lutz, Sharon M. Lynch, David A. Crinerl, Gerard J. Silverman, Edwin K. Crapo, James D. CA COPDGene Investigators TI Association between Occupational Exposure and Lung Function, Respiratory Symptoms, and High-Resolution Computed Tomography Imaging in COPDGene SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE COPD; occupational exposure; emphysema ID OBSTRUCTIVE PULMONARY-DISEASE; AFRICAN GOLD MINERS; DUST EXPOSURE; ALPHA(1)-ANTITRYPSIN DEFICIENCY; CONSTRUCTION WORKERS; GENERAL-POPULATION; US POPULATION; EMPHYSEMA; AIRWAYS; WOMEN AB Rationale: Although occupational exposure to dust and fumes is considered a risk factor for chronic obstructive pulmonary disease, this determination has been limited by reliance on spirometry alone to assess disease severity in predominantly male populations. Objectives: To determine the effect of occupational exposure on lung function, respiratory symptoms, and findings of emphysema and airway wall thickness measured using quantitative computed tomography in men and women. Methods: COPDGene is a multicenter study of current and former smokers that underwent standardized volumetric chest computed tomography scans to assess airways, % emphysema, and % gas trapping. Spirometry and a respiratory questionnaire including occupational history were also analyzed in 9,614 subjects (4,496 women). Logistic regression and analysis of covariance was used to assess associations with exposure. Measurements and Main Results: Occupational exposure to both dust and fumes was reported by 47.9% of men and 20.1% of women. Adjusting for age, race, body mass index, education, and current and lifetime smoking, the odds ratios for persons with dust and fume exposures for chronic cough, chronic phlegm, persistent wheeze, and Global Initiative for Chronic Obstructive Lung Disease stages 2 and higher chronic obstructive pulmonary disease were significantly elevated and similar for men (1.83, 1.84, 2.0, 1.61, respectively) and women (1.65, 1.82, 1.98, 1.90, respectively). The % predicted FEV1 was similarly lower in those with exposure in men (70.7 +/- 0.8 vs. 76.0 +/- 0.9; P < 0.001) and women (70.5 +/- 0.8 vs. 77.2 +/- 0.8; P < 0.001). Percent emphysema and gas trapping was greater in those exposed to dust and fumes in men and women. In men, but not in women, persons with exposure had a greater mean square root wall area of 10-mm internal perimeter airways. Conclusions: Occupational exposure to dust and fumes in men and women is similarly associated with airflow obstruction, respiratory symptoms, more emphysema, and gas trapping in men and women. C1 [Marchetti, Nathaniel; Crinerl, Gerard J.] Temple Univ, Sch Med, Dept Med, Philadelphia, PA USA. [Garshick, Eric] Brigham & Womens Hosp, Dept Med, VA Boston Healthcare Syst, Pulm & Crit Care Med Sect,Med Serv, Boston, MA 02115 USA. [Garshick, Eric] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Garshick, Eric] Harvard Univ, Sch Med, Boston, MA USA. [Kinney, Gregory L.] Univ Colorado, Sch Publ Hlth, Dept Epidemiol, Denver, CO 80202 USA. [McKenzie, Alex; Stinson, Douglas; Lynch, David A.] Natl Jewish Hlth, Denver, CO USA. [Lutz, Sharon M.; Crapo, James D.] Univ Colorado, Dept Biostat, Anschutz Med Campus, Denver, CO 80202 USA. [Silverman, Edwin K.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Marchetti, N (reprint author), 785 Parkinson Pavil,3401 North Broad St, Philadelphia, PA 19140 USA. EM nathaniel.marchetti@tuhs.temple.edu FU NIH [R01 HL089897, R01 HL089856] FX Supported by NIH grants R01 HL089897 (J.D.C.) and R01 HL089856 (E.K.S.). NR 38 TC 11 Z9 11 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2014 VL 190 IS 7 BP 756 EP 762 DI 10.1164/rccm.201403-0493OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AQ7TS UT WOS:000343022700009 PM 25133327 ER PT J AU Yu, GY Herazo-Maya, JD Nukui, T Romkes, M Parwani, A Juan-Guardela, BM Robertson, J Gauldie, J Siegfried, JM Kaminski, N Kass, DJ AF Yu, Guoying Herazo-Maya, Jose D. Nukui, Tomoko Romkes, Marjorie Parwani, Anil Juan-Guardela, Brenda M. Robertson, Jennifer Gauldie, Jack Siegfried, Jill M. Kaminski, Naftali Kass, Daniel J. TI Matrix Metalloproteinase-19 Promotes Metastatic Behavior In Vitro and Is Associated with Increased Mortality in Non-Small Cell Lung Cancer SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE MMP19; epithelial-mesenchymal transition; metastasis; non-small cell lung cancer; miR-30 ID IDIOPATHIC PULMONARY-FIBROSIS; TUMOR-MICROENVIRONMENT; HEMOPEXIN DOMAIN; PROSTATE-CANCER; EXPRESSION; INVASION; ANGIOGENESIS; PROGRESSION; SIGNATURES; MICRORNA AB Rationale: Lung cancer is the leading cause of cancer death in both men and women in the United States and worldwide. Matrix metalloproteinases (MMPs) have been implicated in the development and progression of lung cancer, but their role in the molecular pathogenesis of lung cancer remains unclear. We have found that MMP19, a relatively novel member of the MMP family, is overexpressed in lung tumors when compared with control subjects. Objectives: To test the hypothesis that MMP19 plays a significant role in the development and progression of non-small cell lung cancer (NSCLC). Methods: We have analyzed lung cancer gene expression data, immunostained lung tumors for MMP19, and performed in vitro assays to test the effects of MMP19 in NSCLC cells. Measurements and Main Results: We found that MMP19 gene and protein expression is increased in lung cancer tumors compared with adjacent and histologically normal lung tissues. In three independent datasets, increased MMP19 gene expression conferred a poorer prognosis in NSCLC. In vitro, we found that overexpression of MMP19 promotes epithelial-mesenchymal transition, migration, and invasiveness in multiple NSCLC cell lines. Overexpression of MMP19 with a mutation at the catalytic site did not impair epithelial-mesenchymal transition or expression of prometastasis genes. We also found that miR-30 isoforms, a microRNA family predicted to target MMP19, is markedly down-regulated in human lung cancer and regulates MMP19 expression. Conclusions: Taken together, these findings suggest that MMP19 is associated with the development and progression of NSCLC and may be a potential biomarker of disease severity and outcome. C1 [Yu, Guoying; Herazo-Maya, Jose D.; Juan-Guardela, Brenda M.; Kaminski, Naftali] Yale Univ, Sch Med, Sect Pulm Crit Care & Sleep Med, New Haven, CT USA. [Nukui, Tomoko; Romkes, Marjorie] Univ Pittsburgh, Div Hematol & Oncol, Pittsburgh, PA USA. [Kass, Daniel J.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Kass, Daniel J.] Univ Pittsburgh, Dorothy P & Richard P Simmons Ctr Interstitial Lu, Dept Med, Pittsburgh, PA USA. [Parwani, Anil] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Robertson, Jennifer; Gauldie, Jack] McMaster Univ, Dept Pathol & Lab Med, Hamilton, ON, Canada. [Siegfried, Jill M.] Univ Minnesota, Dept Pharmacol, Minneapolis, MN USA. [Kass, Daniel J.] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. RP Kass, DJ (reprint author), UPMC Montefiore, NW 628,3459 Fifth Ave, Pittsburgh, PA 15213 USA. EM kassd2@upmc.edu OI Kaminski, Naftali/0000-0001-5917-4601 FU Dorothy P. and Richard P. Simmons Endowed Chair for Pulmonary Research; National Institutes of Health [R01HL107883, P30CA047904]; Lung Cancer Genomics project, University of Pittsburgh Medical Center FX Supported by the Dorothy P. and Richard P. Simmons Endowed Chair for Pulmonary Research; National Institutes of Health grants R01HL107883 and P30CA047904; and the Lung Cancer Genomics project, University of Pittsburgh Medical Center. NR 58 TC 7 Z9 8 U1 0 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2014 VL 190 IS 7 BP 780 EP 790 DI 10.1164/rccm.201310-1903OC PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AQ7TS UT WOS:000343022700012 PM 25250855 ER PT J AU Berra, L Pinciroli, R Stowell, CP Wang, L Yu, BL Femandez, BO Feelisch, M Mietto, C Hod, EA Chipman, D Scherrer-Crosbie, MI Bloch, KD Zapol, WM AF Berra, Lorenzo Pinciroli, Riccardo Stowell, Christopher P. Wang, Lin Yu, Binlan Femandez, Bernadette O. Feelisch, Martin Mietto, Cristina Hod, Eldad A. Chipman, Daniel Scherrer-Crosbie, Marie Ile Bloch, Kenneth D. Zapol, Warren M. TI Autologous Transfusion of Stored Red Blood Cells Increases Pulmonary Artery Pressure SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE hemoglobins; pulmonary hypertension; nitric oxide; endothelium; echocardiography ID INHALED NITRIC-OXIDE; ENDOTHELIAL DYSFUNCTION; HEMORRHAGIC-SHOCK; STORAGE DURATION; FREE HEMOGLOBIN; OLDER; HYPERTENSION; DEFORMABILITY; VOLUNTEERS; PNEUMONIA AB Rationale: Transfusion of erythrocytes stored for prolonged periods is associated with increased mortality. Erythrocytes undergo hemolysis during storage and after transfusion. Plasma hemoglobin scavenges endogenous nitric oxide leading to systemic and pulmonary vasoconstriction. Objectives: We hypothesized that transfusion of autologous blood stored for 40 days would increase the pulmonary artery pressure in volunteers with endothelial dysfunction (impaired endothelial production of nitric oxide). We also tested whether breathing nitric oxide before and during transfusion could prevent the increase of pulmonary artery pressure. Methods: Fourteen obese adults with endothelial dysfunction were enrolled in a randomized crossover study of transfusing autologous, leukoreduced blood stored for either 3 or 40 days. Volunteers were transfused with 3-day blood, 40-day blood, and 40-day blood while breathing 80 ppm nitric oxide. Measurements and Main Results: The age of volunteers was 41 +/- 4 years (mean +/- SEM), and their body mass index was 33.4 +/- 1.3 kg/m(2). Plasma hemoglobin concentrations increased after transfusion with 40-day and 40-day plus nitric oxide blood but not after transfusing 3-day blood. Mean pulmonary artery pressure, estimated by transthoracic echocardiography, increased after transfusing 40-day blood (18 +/- 2 to 23 +/- 2 mm Hg; P < 0.05) but did not change after transfusing 3-day blood (17 +/- 2 to 18 +/- 2 mm Hg; P = 0.5). Breathing nitric oxide decreased pulmonary artery pressure in volunteers transfused with 40-day blood (17 +/- 2 to 12 +/- 1 mm Hg; P < 0.05). Conclusions: Transfusion of autologous leukoreduced blood stored for 40 days was associated with increased plasma hemoglobin levels and increased pulmonary artery pressure. Breathing nitric oxide prevents the increase of pulmonary artery pressure produced by transfusing stored blood. C1 [Berra, Lorenzo; Pinciroli, Riccardo; Yu, Binlan; Mietto, Cristina; Bloch, Kenneth D.; Zapol, Warren M.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Stowell, Christopher P.] Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02114 USA. [Wang, Lin; Scherrer-Crosbie, Marie Ile] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Femandez, Bernadette O.; Feelisch, Martin] Univ Southampton, Fac Med Clin & Expt Sci, Southampton, Hants, England. [Hod, Eldad A.] Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY USA. RP Berra, L (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Thier 503,55 Fruit St, Boston, MA 02114 USA. EM lberra@mgh.harvard.edu RI Feelisch, Martin/C-3042-2008; OI Feelisch, Martin/0000-0003-2320-1158; Fernandez, Bernadette/0000-0001-6337-0381 FU Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital; National Institutes of Health (NIH) [T32GM007592]; NIH [HL074352, K08-HL103756, R21 DK092909]; Foundation LeDucq; Faculty of Medicine, University of Southampton FX Supported by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital. Inhaled nitric oxide was supplied by iNO Therapeutics, Ikaria (Hampton, NJ). L.B. was supported by National Institutes of Health (NIH) grant Research Training for Anesthetists T32GM007592. K.D.B. was supported by NIH R01 grant HL074352 and a grant from the Foundation LeDucq. M.F. acknowledges support from the Faculty of Medicine, University of Southampton. E.A.H. has received grant support from NIH K08-HL103756. M.S.-C. was supported by NIH R21 DK092909. NR 37 TC 18 Z9 18 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2014 VL 190 IS 7 BP 800 EP 807 DI 10.1164/rccm.201405-0850OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AQ7TS UT WOS:000343022700014 PM 25162920 ER PT J AU Sullivan, AF Hasegawa, K Linnemann, RW Long, ADA Teuber, SS Turner, SJ Massaro, S Camargo, CA AF Sullivan, Ashley F. Hasegawa, Kohei Linnemann, Rachel W. Long, Aidan A. Teuber, Suzanne S. Turner, Stuart J. Massaro, Susan Camargo, Carlos A., Jr. CA MARC-36 Investigators TI An update on United States asthma centers: 2013 SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter C1 [Sullivan, Ashley F.; Hasegawa, Kohei; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02138 USA. [Linnemann, Rachel W.] Harvard Univ, Sch Med, Dept Pediat, Div Pediat Pulmonol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Long, Aidan A.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol,Med Sch, Boston, MA USA. [Teuber, Suzanne S.] Univ Calif Davis, Med Ctr, Dept Internal Med, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. [Turner, Stuart J.; Massaro, Susan] Novartis Pharmaceut, E Hanover, NJ USA. RP Sullivan, AF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02138 USA. EM ccarmargo@partners.org OI Pallin, Daniel/0000-0002-8517-9702 NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD OCT PY 2014 VL 113 IS 4 BP 484 EP 486 DI 10.1016/j.anai.2014.07.013 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA AQ8VG UT WOS:000343113400024 PM 25129486 ER PT J AU Bhattacharrya, S Miller, J Ropper, AH AF Bhattacharrya, Shamik Miller, Julie Ropper, Allan H. TI The Case for Case Reports SO ANNALS OF NEUROLOGY LA English DT Article AB Case reports have seemingly fallen upon hard times. Once esteemed by William Osler and C. Miller Fisher, these reports are now considered anachronistic. Nonetheless, case reports remain valuable and formed the largest proportion of publications written last year by residents in our training program (the Partners Neurology Residency). Although they are easy to produce, it is reasonable to ask if these modern exercises are of equal significance to the narratives of migraine by John Graham in the 1950s or descriptions of Parkinson disease by James Parkinson in 1817. Even a brief reading of currently published case reports raises doubts about the value of many of them but also emphasizes their utility. We argue here that the case report format remains of considerable merit, especially to the aspiring academic clinician. C1 [Bhattacharrya, Shamik; Miller, Julie; Ropper, Allan H.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Bhattacharrya, Shamik; Miller, Julie] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Bhattacharrya, S (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM sbhattacharyya3@partners.org OI Bhattacharyya, Shamik/0000-0001-8047-3622 NR 5 TC 2 Z9 2 U1 2 U2 4 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 OCT PY 2014 VL 76 IS 4 BP 484 EP 486 DI 10.1002/ana.24267 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AQ8FB UT WOS:000343058400004 PM 25178674 ER PT J AU Cardoso, F Costa, A Norton, L Senkus, E Aapro, M Andre, F Barrios, CH Bergh, J Biganzoli, L Blackwell, KL Cardoso, MJ Cufer, T El Saghir, N Fallowfield, L Fenech, D Francis, P Gelmon, K Giordano, SH Gligorov, J Goldhirsch, A Harbeck, N Houssami, N Hudis, C Kaufman, B Krop, I Kyriakides, S Lin, UN Mayer, M Merjaver, SD Nordstrom, EB Pagani, O Partridge, A Penault-Llorca, F Piccart, MJ Rugo, H Sledge, G Thomssen, C van't Veer, L Vorobiof, D Vrieling, C West, N Xu, B Winer, E AF Cardoso, F. Costa, A. Norton, L. Senkus, E. Aapro, M. Andre, F. Barrios, C. H. Bergh, J. Biganzoli, L. Blackwell, K. L. Cardoso, M. J. Cufer, T. El Saghir, N. Fallowfield, L. Fenech, D. Francis, P. Gelmon, K. Giordano, S. H. Gligorov, J. Goldhirsch, A. Harbeck, N. Houssami, N. Hudis, C. Kaufman, B. Krop, I. Kyriakides, S. Lin, U. N. Mayer, M. Merjaver, S. D. Nordstrom, E. B. Pagani, O. Partridge, A. Penault-Llorca, F. Piccart, M. J. Rugo, H. Sledge, G. Thomssen, C. van't Veer, L. Vorobiof, D. Vrieling, C. West, N. Xu, B. Winer, E. TI ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2) SO ANNALS OF ONCOLOGY LA English DT Article ID PHASE-II TRIAL; ISOLATED LOCOREGIONAL RECURRENCE; 1ST-LINE HORMONAL TREATMENT; RANDOMIZED CONTROLLED-TRIAL; MIDDLE-INCOME COUNTRIES.; (ESO)-MBC TASK-FORCE; 2 MULTICENTER TRIALS; FIRST-LINE THERAPY; POSTMENOPAUSAL WOMEN; DOUBLE-BLIND C1 [Cardoso, F.] Champalimaud Canc Ctr, European Sch Oncol, Lisbon, Portugal. [Cardoso, F.] Champalimaud Canc Ctr, Breast Unit, Lisbon, Portugal. [Costa, A.] European Sch Oncol, Milan, Italy. [Costa, A.] European Sch Oncol, Bellinzona, Switzerland. [Norton, L.] Mem Sloan Kettering Canc Ctr, Breast Canc Program, New York, NY 10021 USA. [Senkus, E.] Med Univ Gdansk, Dept Oncol & Radiotherapy, Gdansk, Poland. [Aapro, M.] Inst Multidisciplinaire Oncol, Div Oncol, Genolier, Switzerland. [Andre, F.] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France. [Barrios, C. H.] PUCRS Sch Med, Dept Med, Porto Alegre, RS, Brazil. [Bergh, J.] Karolinska Inst, Dept Oncol, Radiumhemmet, Stockholm, Sweden. [Bergh, J.] Canc Ctr Karolinska, Stockholm, Sweden. [Bergh, J.] Karolinska Univ Hosp, Stockholm, Sweden. [Biganzoli, L.] Sandro Pitigliani Oncol Ctr, Dept Med Oncol, Prato, Italy. [Blackwell, K. L.] Duke Canc Inst, Breast Canc Clin Program, Durham, NC USA. [Cardoso, M. J.] Champalimaud Canc Ctr, Breast Unit, Lisbon, Portugal. [Cufer, T.] Univ Clin Golnik, Med Fac Ljubljana, Ljubljana, Slovenia. [El Saghir, N.] Amer Univ Beirut Med Ctr, NK Basile Canc Inst Breast Ctr Excellence, Beirut, Lebanon. [Fallowfield, L.] Univ Sussex, Brighton & Sussex Med Sch, Falmer, England. [Fenech, D.] Europa Donna Malta, Breast Care Support Grp, Mtarfa, Malta. [Francis, P.] Peter MacCallum Canc Ctr, Div Canc Med, Melbourne, Vic, Australia. [Gelmon, K.] BC Canc Agcy, Vancouver, BC, Canada. [Giordano, S. H.] UT MD Anderson Canc Ctr, Dept Hlth Serv Res, Houston, TX USA. [Giordano, S. H.] UT MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX USA. [Gligorov, J.] AROME, Francilian Breast Intergrp, IUC UPMC, APHP Tenon, Paris, France. [Goldhirsch, A.] European Inst Oncol, Program Breast Hlth, Milan, Italy. [Harbeck, N.] Univ Munich, Brustzentrum, Munich, Denmark. [Houssami, N.] Univ Sydney, Sydney Med Sch, Sch Publ Hlth, Screening & Test Evaluat Program, Sydney, NSW 2006, Australia. [Hudis, C.] Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, New York, NY 10021 USA. [Kaufman, B.] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Krop, I.; Lin, U. N.; Winer, E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kyriakides, S.] Europa Donna Cyprus, Nicosa, Cyprus. [Mayer, M.] AdvancedBC Org, New York, NY USA. [Merjaver, S. D.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Merjaver, S. D.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Nordstrom, E. B.] BRO, Europa Donna Sweden & Brostcanc Foreningarnas Rik, Sundbyberg, Sweden. [Pagani, O.] Oncol Inst Southern Switzerland, Bellinzona, Switzerland. [Pagani, O.] Breast Unit Southern Switzerland, Bellinzona, Switzerland. [Partridge, A.] Dana Farber Canc Inst, Div Womens Canc, Dept Med Oncol, Boston, MA 02115 USA. [Penault-Llorca, F.] Ctr Comprehens Canc, Jean Perrin Ctr, Clermont Ferrand, France. [Piccart, M. J.] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium. [Rugo, H.] UCSF Helen Diller Family Comprehens Canc Ctr, Breast Oncol Program, Dept Med, San Francisco, CA USA. [Sledge, G.] Indiana Univ Med CTR, Indianapolis, IN USA. [Thomssen, C.] Univ Halle Wittenberg, Dept Gynaecol, D-06108 Halle, Germany. [van't Veer, L.] UCSF Helen Diller Family Comprehens Canc Ctr, Breast Oncol Program, San Francisco, CA USA. [Vorobiof, D.] Sandton Oncol Ctr, Johannesburg, South Africa. [Vrieling, C.] Clin Grangettes, Dept Radiotherapy, Geneva, Switzerland. Cardiff & Vale Univ, Hlth Board, Nursing Div, Cardiff, S Glam, Wales. [West, N.; Xu, B.] Chinese Acad Med Sci, Canc Hosp, Dept Med Oncol, Beijing 100730, Peoples R China. [West, N.; Xu, B.] Peking Union Med Coll, Beijing 100021, Peoples R China. RP Cardoso, F (reprint author), Champalimaud Canc Ctr, Av. Brasilia S-N, P-1400048 Lisbon, Portugal. EM fatimacardoso@fundacaochampalimaud.pt OI Norton, Larry/0000-0003-3701-9250 NR 130 TC 120 Z9 129 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2014 VL 25 IS 10 BP 1871 EP 1888 DI 10.1093/annonc/mdu385 PG 18 WC Oncology SC Oncology GA AQ8BG UT WOS:000343045500002 PM 25234545 ER PT J AU Heymach, JV Lockwood, SJ Herbst, RS Johnson, BE Ryan, AJ AF Heymach, J. V. Lockwood, S. J. Herbst, R. S. Johnson, B. E. Ryan, A. J. TI EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer SO ANNALS OF ONCOLOGY LA English DT Article DE vandetanib; docetaxel; EGFR; KRAS; lung cancer ID ENDOTHELIAL GROWTH-FACTOR; FACTOR-RECEPTOR; MOLECULAR PREDICTORS; PLUS DOCETAXEL; THYROID-CANCER; DOUBLE-BLIND; GEFITINIB; TRIAL; ERLOTINIB; CARBOPLATIN AB Background: ZODIAC was a randomized phase III study of second-line treatment in patients with advanced non-small cell lung cancer (NSCLC) that evaluated the addition of vandetanib to docetaxel. The study showed a statistically significant improvement in progression-free survival and objective response rate, but not in overall survival for unselected patients. This study evaluated epidermal growth factor receptor (EGFR) gene mutation, copy number gain, and protein expression, and KRAS gene mutation, in pretreatment tumor samples as potential biomarkers predicting benefit from vandetanib as second-line treatment of NSCLC. Patients and methods: After progression following first-line chemotherapy, 1391 patients with locally advanced or metastatic (stage IIIB/IV) NSCLC were randomized 1 : 1 to receive vandetanib (100 mg/day) plus docetaxel (75 mg/m(2) every 21 days) or placebo plus docetaxel in the ZODIAC study. Archival tumor samples (n = 570) were collected from consenting patients (n = 958) for predefined, prospective biomarker analyses. Results: Of evaluable samples, 14% were EGFR mutation positive, 35% were EGFR FISH positive, 88% were EGFR protein expression positive, and 13% were KRAS mutation positive. Compared with the overall study population, in which progression-free survival (PFS) [ hazard ratio (HR) = 0.79] but not OS (HR = 0.91) were significantly improved with vandetanib, there was greater relative clinical benefit for patients with EGFR mutation-positive tumors [ PFS HR 0.51, confidence interval (CI) 0.25-1.06 and OS HR 0.46, CI 0.14-1.57] and EGFR FISH-positive tumors (PFS HR 0.61, CI 0.39-0.94 and OS HR 0.48, CI 0.28-0.84). Similarly, patients with EGFR mutation or FISH-positive tumor samples who received vandetanib had an increased chance of objective tumor response (odds ratios 3.34, CI 0.8-13.89, and 3.90, CI 1.02-14.82, respectively). There did not appear to be benefit for vandetanib in patients with KRAS mutation-positive tumors. Conclusions: High EGFR gene copy number or activating EGFR mutations may identify patient subgroups who receive increased clinical benefit from vandetanib in combination with docetaxel in second-line NSCLC. C1 [Heymach, J. V.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Lockwood, S. J.] AstraZeneca, Oncol iMED, Macclesfield, Cheshire, England. [Herbst, R. S.] Yale Univ, Sect Med Oncol, Yale Canc Ctr, New Haven, CT USA. [Herbst, R. S.] Yale Univ, Smilow Canc Hosp, New Haven, CT USA. [Johnson, B. E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Johnson, B. E.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. [Ryan, A. J.] Univ Oxford, Dept Oncol, Oxford OX3 7DQ, England. RP Ryan, AJ (reprint author), Univ Oxford, Dept Oncol, Old Rd Campus Res Bldg,Roosevelt Dr, Oxford OX3 7DQ, England. EM anderson.ryan@oncology.ox.ac.uk RI Ryan, Anderson/O-7701-2015 OI Ryan, Anderson/0000-0001-6241-7969 FU AstraZeneca FX The study was funded by AstraZeneca. NR 35 TC 8 Z9 8 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2014 VL 25 IS 10 BP 1941 EP 1948 DI 10.1093/annonc/mdu269 PG 8 WC Oncology SC Oncology GA AQ8BG UT WOS:000343045500009 PM 25057173 ER PT J AU Wanebo, HJ Lee, J Burtness, BA Ridge, JA Ghebremichael, M Spencer, SA Psyrri, D Pectasides, E Rimm, D Rosen, FR Hancock, MR Tolba, KA Forastiere, AA AF Wanebo, H. J. Lee, J. Burtness, B. A. Ridge, J. A. Ghebremichael, M. Spencer, S. A. Psyrri, D. Pectasides, E. Rimm, D. Rosen, F. R. Hancock, M. R. Tolba, K. A. Forastiere, A. A. TI Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303) SO ANNALS OF ONCOLOGY LA English DT Article DE cetuximab; induction chemotherapy; chemoradiation; head-neck ID FACTOR RECEPTOR EXPRESSION; OROPHARYNGEAL CANCER; HUMAN-PAPILLOMAVIRUS; SURVIVAL; NUCLEAR AB Background: E2303 evaluated cetuximab, paclitaxel, and carboplatin used as induction therapy and concomitant with radiation therapy in patients with stage III/IV head and neck squamous cell carcinoma (HNSCC) determining pathologic complete response (CR), event-free survival (EFS), and toxicity. Patients and methods: Patients with resectable stage III/IV HNSCC underwent induction therapy with planned primary site restaging biopsies (at week 8 in clinical complete responders and at week 14 if disease persisted). Chemoradiation (CRT) began week 9. If week 14 biopsy was negative, patients completed CRT (68-72 Gy); otherwise, resection was carried out. p16 protein expression status was correlated with response/survival. Results: Seventy-four patients were enrolled; 63 were eligible. Forty-four (70%) were free of surgery to the primary site, progression, and death 1-year post-treatment. Following induction, 41 (23 CR) underwent week 8 primary site biopsy and 24 (59%) had no tumor (pathologic CR). Week 14 biopsy during chemoradiation (50 Gy) in 34 (15 previously positive biopsy; 19 no prior biopsy) was negative in 33. Thus 90% of eligible patients completed CRT. Overall survival and EFS were 78% and 55% at 3 years, respectively. Disease progression in 23 patients (37%) was local only in 10 (16%), regional in 5 (8%), local and regional in 2 (3%), and distant in 5 patients (8%). There were no treatment-related deaths. Toxicity was primarily hematologic or radiation-related. p16 AQUA score was not associated with response/survival. Conclusions: Induction cetuximab, paclitaxel, and carboplatin followed by the same drug CRT is safe and induces high primary site response and promising survival. C1 [Wanebo, H. J.] Landmark Med Ctr, Dept Surg, Woonsocket, RI 02895 USA. [Lee, J.; Ghebremichael, M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Burtness, B. A.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Ridge, J. A.] Fox Chase Canc Ctr, Dept Surg, Philadelphia, PA 19111 USA. [Spencer, S. A.] Univ Alabama Birmingham, Dept Radiat Oncol, Birmingham, AL USA. [Psyrri, D.; Pectasides, E.; Rimm, D.] Yale Univ, Dept Med, New Haven, CT 06520 USA. [Rosen, F. R.] John H Stroger Hosp Cook Cty, Dept Med Oncol, Chicago, IL USA. [Hancock, M. R.] Porter Mem Hosp, Dept Med Oncol, Denver, CO USA. [Tolba, K. A.] Univ Miami, Dept Med, Miami, FL USA. [Forastiere, A. A.] Johns Hopkins Univ, Dept Med Oncol, Baltimore, MD USA. [Forastiere, A. A.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Wanebo, HJ (reprint author), Landmark Med Ctr, Div Surg Oncol, Dept Surg, 206 Cass Ave, Woonsocket, RI 02895 USA. EM hwanebo@chartercare.org FU Eastern Cooperative Oncology Group; Public Health Service Grants [CA23318, CA66636, CA21115, CA27525, CA16116]; National Cancer Institute, NIH; Department of Health and Human Services FX The work was sponsored by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair) and supported in part by Public Health Service Grants (CA23318, CA66636, CA21115, CA27525, CA16116) and from the National Cancer Institute, NIH, and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 15 TC 12 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2014 VL 25 IS 10 BP 2036 EP 2041 DI 10.1093/annonc/mdu248 PG 6 WC Oncology SC Oncology GA AQ8BG UT WOS:000343045500024 PM 25009013 ER PT J AU Ou, SHI Pasi, J AF Ou, S. -H. I. Pasi, J. TI Reply to the letter to the editor 'Clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLC' by Ou et al. SO ANNALS OF ONCOLOGY LA English DT Letter ID CELL LUNG-CANCER; RESISTANCE C1 [Ou, S. -H. I.] Univ Calif Irvine, Med Ctr, Chao Family Comprehens Canc Ctr, Orange, CA USA. [Pasi, J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ou, SHI (reprint author), Univ Calif Irvine, Med Ctr, Chao Family Comprehens Canc Ctr, Orange, CA USA. EM siou@uci.edu NR 7 TC 0 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2014 VL 25 IS 10 BP 2093 EP 2093 DI 10.1093/annonc/mdu258 PG 1 WC Oncology SC Oncology GA AQ8BG UT WOS:000343045500034 PM 25035278 ER PT J AU Kim, KM Cambria, RP Isselbacher, EM Baker, JN LaMuraglia, GM Stone, JR MacGillivray, TE AF Kim, Karen M. Cambria, Richard P. Isselbacher, Eric M. Baker, Joshua N. LaMuraglia, Glenn M. Stone, James R. MacGillivray, Thomas E. TI Contemporary Surgical Approaches and Outcomes in Adults With Kommerell Diverticulum SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 25-29, 2014 CL Orlando, FL SP Soc Thorac Surg ID ABERRANT SUBCLAVIAN ARTERY; ENDOVASCULAR AORTIC REPAIR; OF-THE-LITERATURE; ANEURYSM; MANAGEMENT; SPECIMENS; SURGERY; ARCH AB Background. Surgery in patients with Ko mmerell diverticulum (KD) is controversial. Although the presence of symptoms is an accepted indication, the KD itself may be a risk factor for dissection and rupture, although size criteria for operation are undefined. Methods. A retrospective review of 19 adult patients who underwent surgical treatment of KD between March 2004 and June 2013 was performed. Mean age was 48 years (range, 32 to 68 years). Fifteen patients were female, 15 were symptomatic, and 13 had a right aortic arch. Sixteen patients with aberrant subclavian artery underwent a two-stage procedure involving subclavian-common carotid artery transposition or bypass followed by aortic resection, including origin of the KD, with interposition graft reconstruction. Aortic resection was performed with left heart bypass (n = 10) or deep hypothermic circulatory arrest (n = 9). Results. There were no deaths or strokes. Complications after aberrant subclavian artery revascularization were transient ptosis (n = 3), graft occlusion (n = 1), recurrent laryngeal nerve injury (n = 1), phrenic nerve injury (n = 1), and reintubation (n = 1). Complications after aortic resection were intraoperative type A dissection (n = 1), phrenic nerve injury (n = 1), chylothorax (n = 1), and transient neurologic dysfunction (n = 1). Mean hospital stay after aberrant subclavian artery revascularization was 2 +/- 2 days and after aortic resection, 6.4 +/- 2.4 days. Of 18 available pathology specimens, all 18 showed medial degeneration. Mean follow-up was 3.3 years. Conclusions. This is the largest reported single-center experience with the surgical management of KD in adults, verifying its safety and efficacy. The high percentage of KD with medial degeneration suggests asymptomatic patients with an enlarged KD also may benefit from resection. (C) 2014 by The Society of Thoracic Surgeons C1 Massachusetts Gen Hosp, Div Gen Surg, Dept Surg, Div Cardiol,Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Vasc Surg, Dept Surg, Div Cardiol,Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Dept Surg, Div Cardiol,Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP MacGillivray, TE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Cox 650, Boston, MA 02114 USA. EM tmacgillivray@partners.org NR 27 TC 5 Z9 5 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2014 VL 98 IS 4 BP 1347 EP 1354 DI 10.1016/j.athoracsur.2014.05.045 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AQ9DM UT WOS:000343143400036 PM 25134861 ER PT J AU Pantoja, JL Ge, L Zhang, ZH Morrel, WG Guccione, JM Grossi, EA Ratcliffe, MB AF Pantoja, Joe Luis Ge, Liang Zhang, Zhihong Morrel, William G. Guccione, Julius M. Grossi, Eugene A. Ratcliffe, Mark B. TI Posterior Papillary Muscle Anchoring Affects Remote Myofiber Stress and Pump Function: Finite Element Analysis SO ANNALS OF THORACIC SURGERY LA English DT Article ID ISCHEMIC MITRAL REGURGITATION; POSTEROLATERAL MYOCARDIAL-INFARCTION; LEFT-VENTRICLE; DILATED CARDIOMYOPATHY; VALVE ANNULOPLASTY; HEART-FAILURE; REPAIR; MODEL; REVASCULARIZATION; BORDERZONE AB Background. The role of posterior papillary muscle anchoring (PPMA) in the management of chronic ischemic mitral regurgitation (CIMR) is controversial. We studied the effect of anchoring point direction and relocation displacement on left ventricular (LV) regional myofiber stress and pump function. Methods. Previously described finite element models of sheep 16 weeks after posterolateral myocardial infarction (MI) were used. True-sized mitral annuloplasty (MA) ring insertion plus different PPM anchoring techniques were simulated. Anchoring points tested included both commissures and the central anterior mitral annulus; relocation displacement varied from 10% to 40% of baseline diastolic distance from the PPM to the anchor points on the annulus. For each reconstruction scenario, myofiber stress in the MI, border zone, and remote myocardium as well as pump function were calculated. Results. PPMA caused reductions in myofiber stress at end-diastole and end-systole in all regions of the left ventricle that were proportional to the relocation displacement. Although stress reduction was greatest in the MI region, it also occurred in the remote region. The maximum 40% displacement caused a slight reduction in LV pump function. However, with the correction of regurgitation by MA plus PPMA, there was an overall increase in forward stroke volume. Finally, anchoring point direction had no effect on myofiber stress or pump function. Conclusions. PPMA reduces remote myofiber stress, which is proportional to the absolute distance of relocation and independent of anchoring point. Aggressive use of PPMA techniques to reduce remote myofiber stress may accelerate reverse LV remodeling without impairing LV function. (C) 2014 by The Society of Thoracic Surgeons C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. Univ Calif San Francisco, Dept Bioengn, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, San Francisco, CA USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. NYU, Dept Cardiothorac Surg, New York, NY USA. New York Harbor Vet Affairs Med Ctr, New York, NY USA. RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA. EM mark.ratcliffe@med.va.gov OI Morrel, William/0000-0001-6371-1094; GROSSI, eugene/0000-0002-2066-7035 FU National Institutes of Health [R01-HL-63348]; AHA [13MSRF17090108] FX This study was supported by National Institutes of Health grant R01-HL-63348 (MBR) and by AHA grant 13MSRF17090108. This support is gratefully acknowledged. NR 37 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2014 VL 98 IS 4 BP 1355 EP 1362 DI 10.1016/j.athoracsur.2014.04.077 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AQ9DM UT WOS:000343143400037 PM 25130075 ER PT J AU Sparks, JA Chen, CY Hiraki, LT Malspeis, S Costenbader, KH Karlson, EW AF Sparks, Jeffrey A. Chen, Chia-Yen Hiraki, Linda T. Malspeis, Susan Costenbader, Karen H. Karlson, Elizabeth W. TI Contributions of Familial Rheumatoid Arthritis or Lupus and Environmental Factors to Risk of Rheumatoid Arthritis in Women: A Prospective Cohort Study SO ARTHRITIS CARE & RESEARCH LA English DT Article ID ALCOHOL-CONSUMPTION; AUTOIMMUNE-DISEASES; ASSOCIATION; AGGREGATION; SMOKING; HISTORY; HEALTH; AUTOANTIBODIES; ERYTHEMATOSUS; HERITABILITY AB Objective. We assessed the contributions of familial rheumatoid arthritis (RA) or lupus and environmental factors to the risk of RA. Methods. Among 121,700 women in the Nurses' Health Study, 65,457 provided data on familial RA/lupus. Among these, 493 RA cases (301 seropositive and 192 seronegative) were validated. We estimated hazard ratios (HRs) for RA comparing those with and without familial RA/lupus, adjusting for environmental factors (smoking, alcohol, body mass index [BMI], parity, breastfeeding, menopause, hormone use, early menarche, and menstrual regularity) using Cox proportional hazards models. Population attributable risks (PARs) for RA within this cohort were calculated for familial RA/lupus, smoking, alcohol, BMI, parity, and breastfeeding. Results. Familial RA/lupus was significantly associated with RA (HR 3.67), seropositive RA (HR 3.90), and seronegative RA (HR 3.95). After adjusting for environmental factors, familial RA/lupus was significantly associated with RA (HR 3.59, 95% confidence interval 2.94-4.37). Smoking >10 pack-years, overweight, BMI, and premenopause status remained significantly associated with RA after adjusting for familial RA/lupus. For RA in this cohort, the PAR for smoking, BMI, alcohol, parity, or breastfeeding collectively was 41%; the PAR due to heredity from familial RA/lupus was 21%. Conclusion. In this large, prospective cohort, women with familial RA/lupus had a 4-fold increased risk for RA that remained significant after adjusting for environmental factors. A large proportion of RA risk was attributable to environmental factors, even among those with familial RA/lupus. C1 [Sparks, Jeffrey A.; Malspeis, Susan; Costenbader, Karen H.; Karlson, Elizabeth W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chen, Chia-Yen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hiraki, Linda T.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. RP Sparks, JA (reprint author), Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, 45 Francis St, Boston, MA 02115 USA. EM jasparks@partners.org OI Sparks, Jeffrey/0000-0002-5556-4618 FU NIH [CA-087969, CA-049449, CA-050385, CA-067262]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR-049880, AR-052403, AR-047782] FX Supported by the NIH (grants CA-087969, CA-049449, CA-050385, and CA-067262) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grants AR-049880, AR-052403, and AR-047782). NR 43 TC 7 Z9 7 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD OCT PY 2014 VL 66 IS 10 BP 1438 EP 1446 DI 10.1002/acr.22366 PG 9 WC Rheumatology SC Rheumatology GA AQ7PP UT WOS:000343011800002 PM 25103278 ER PT J AU Yazdany, J Tonner, C Schmajuk, G Lin, GA Trivedi, AN AF Yazdany, Jinoos Tonner, Chris Schmajuk, Gabriela Lin, Grace A. Trivedi, Amal N. TI Receipt of Glucocorticoid Monotherapy Among Medicare Beneficiaries With Rheumatoid Arthritis SO ARTHRITIS CARE & RESEARCH LA English DT Article ID MODIFYING ANTIRHEUMATIC DRUGS; HEALTH ADMINISTRATIVE DATABASES; EULAR RECOMMENDATIONS; ELDERLY-PATIENTS; ET-AL; CARE; MANAGEMENT; ARTICLE; UPDATE; SAFETY AB Objective. Using disease-modifying antirheumatic drugs (DMARDs) improves outcomes in rheumatoid arthritis (RA) and is a nationally endorsed quality measure. We investigated the prevalence and predictors of receiving glucocorticoids alone for the treatment of RA in a nationwide sample of Medicare beneficiaries. Methods. Among individuals ages >= 65 years with RA enrolled in the Part D prescription drug benefit in 2009, we compared those with >= 1 DMARD claim to those receiving glucocorticoid monotherapy, defined as no DMARD claim and an annual glucocorticoid supply of >= 180 days or an annual dose of >= 900 mg of prednisone or equivalent. We fit multivariable models to determine the sociodemographic and clinical factors associated with glucocorticoid monotherapy. Results. Of 8,125 beneficiaries treated for RA, 10.2% (n = 825) received glucocorticoids alone. Beneficiaries with low incomes were more likely to receive glucocorticoids alone (12.3%; 95% confidence interval [95% CI] 10.9-13.8% versus 9.4%; 95% CI 8.6-10.1%), as were those living in certain US regions. More physician office visits and hospitalizations were associated with glucocorticoid monotherapy. Individuals who had no contact with a rheumatologist were significantly more likely to receive glucocorticoids alone (17.5%; 95% CI 16.0-19.0% versus 8.5%; 95% CI 7.4-9.5% for those with no rheumatology visits versus 1-4 visits). Conclusion. Approximately 1 in 10 Medicare beneficiaries treated for RA received glucocorticoids without DMARDs in 2009. Compared to DMARD users, glucocorticoid users were older, had lower incomes, were more likely to live in certain US regions, and were less likely to have seen a rheumatologist, suggesting persistent gaps in quality of care despite expanded drug coverage under Part D. C1 [Yazdany, Jinoos; Tonner, Chris] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Yazdany, Jinoos; Tonner, Chris; Schmajuk, Gabriela; Lin, Grace A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Schmajuk, Gabriela] San Francisco VA Med Ctr, San Francisco, CA USA. [Trivedi, Amal N.] Providence VA Med Ctr, Providence, RI USA. [Trivedi, Amal N.] Brown Univ, Providence, RI 02912 USA. RP Yazdany, J (reprint author), Univ Calif San Francisco, Div Rheumatol, Box 0920, San Francisco, CA 94143 USA. EM jinoos.yazdany@ucsf.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [K23-AR-060259, P60-AR-053308]; University of California, San Francisco Resource Evaluation and Allocation Committee Grant Program; Rosalind Russell Medical Research Center for Arthritis; Informed Medical Decisions Foundation FX Supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases (awards K23-AR-060259, P60-AR-053308), the University of California, San Francisco Resource Evaluation and Allocation Committee Grant Program, and the Rosalind Russell Medical Research Center for Arthritis.; Dr. Lin has received consulting fees, speaking fees, and/or honoraria (less than $10,000) from Informed Medical Decisions Foundation. NR 28 TC 4 Z9 4 U1 0 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 OCT PY 2014 VL 66 IS 10 BP 1447 EP 1455 DI 10.1002/acr.22312 PG 9 WC Rheumatology SC Rheumatology GA AQ7PP UT WOS:000343011800003 PM 25244314 ER PT J AU Frank, RM Saccomanno, MF McDonald, LS Moric, M Romeo, AA Provencher, MT AF Frank, Rachel M. Saccomanno, Maristella F. McDonald, Lucas S. Moric, Mario Romeo, Anthony A. Provencher, Matthew T. TI Outcomes of Arthroscopic Anterior Shoulder Instability in the Beach Chair Versus Lateral Decubitus Position: A Systematic Review and Meta-Regression Analysis SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Review ID TERM-FOLLOW-UP; INFERIOR GLENOHUMERAL INSTABILITY; SUTURE ANCHOR TECHNIQUE; HILL-SACHS LESION; GLENOID BONE LOSS; BANKART REPAIR; RISK-FACTORS; BIOMECHANICAL ANALYSIS; CAPSULAR PLICATION; ABSORBABLE TACKS AB Purpose: This study aimed to systematically review the clinical outcomes and recurrence rates after arthroscopic anterior shoulder stabilization in the beach chair (BC) and lateral decubitus (LD) positions. Methods: The authors performed a systematic review of multiple medical databases using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All English-language literature from 1990 to 2013 reporting clinical outcomes after arthroscopic anterior shoulder stabilization with suture anchors or tacks with a minimum 2-year follow-up period were reviewed by 2 independent reviewers. Data on recurrent instability rate, return to activity/sport, range of motion, and subjective outcome measures were collected. Study methodological quality was evaluated with the Modified Coleman Methodology Score (MCMS) and the Quality Appraisal Tool (QAT). To quantify the structured review of observational data, meta-analytic statistical methods were used. Results: Sixty-four studies (38 BC position, 26 LD position) met inclusion criteria. A total of 3,668 shoulders were included, with 2,211 of patients in the BC position (average age, 26.7 +/- 3.8 years; 84.5% male sex) and 1,457 patients in the LD position (average age, 26.0 +/- 3.0 years; 82.7% male sex). The average follow-up was 49.8 +/- 29.5 months in the BC group compared with 38.7 +/- 23.3 months in the LD group. Average overall recurrent instability rates were 14.65 +/- 8.4% in the BC group (range, 0% to 38%) compared with 8.5% +/- 7.1% in the LD group (range, 0% to 30%; P = .002). The average postoperative loss in external rotation motion (in abduction) was reported in 19 studies in the BC group and in 13 studies in the LD group, with an average loss of 2.4 degrees +/- 1.0 degrees and 3.6 degrees +/- 2.6 degrees in each group, respectively (P > .05). Conclusions: Excellent clinical outcomes with low recurrence rates can be obtained after arthroscopic anterior shoulder stabilization in either the BC or the LD position; however, lower recurrence rates are noted in the LD position. Additional long-term randomized clinical trials comparing these positions are needed to better understand the potential advantages and disadvantages of each position. C1 [Frank, Rachel M.; Moric, Mario; Romeo, Anthony A.] Rush Univ, Med Ctr, Div Sports Med, Dept Orthopaed Surg, Chicago, IL 60612 USA. [McDonald, Lucas S.] Naval Med Ctr San Diego, San Diego, CA USA. [Provencher, Matthew T.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Div Sports Med & Surg, Boston, MA 02114 USA. [Saccomanno, Maristella F.] Catholic Univ, Dept Orthoped, Rome, Italy. RP Frank, RM (reprint author), Rush Univ, Med Ctr, 1611 Harrison St, Chicago, IL 60612 USA. EM rmfrank3@gmail.com OI Moric, Mario/0000-0003-2844-8168; Romeo, Anthony/0000-0003-4848-3411 NR 129 TC 9 Z9 9 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 EI 1526-3231 J9 ARTHROSCOPY JI Arthroscopy PD OCT PY 2014 VL 30 IS 10 BP 1349 EP 1365 DI 10.1016/j.arthro.2014.05.008 PG 17 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AQ9EK UT WOS:000343149500024 PM 25000864 ER PT J AU Ryu, SY Qian, WJ Camp, DG Smith, RD Tompkins, RG Davis, RW Xiao, WZ AF Ryu, So Young Qian, Wei-Jun Camp, David G. Smith, Richard D. Tompkins, Ronald G. Davis, Ronald W. Xiao, Wenzhong TI Detecting differential protein expression in large-scale population proteomics SO BIOINFORMATICS LA English DT Article ID MASS-SPECTROMETRY DATA; V-PROTEIN; BINDING-PROTEIN; QUANTIFICATION; SIMIAN-VIRUS-5; DDB1; COMPLEX; INJURY; RATES; STAT1 AB Motivation: Mass spectrometry (MS)-based high-throughput quantitative proteomics shows great potential in large-scale clinical biomarker studies, identifying and quantifying thousands of proteins in biological samples. However, there are unique challenges in analyzing the quantitative proteomics data. One issue is that the quantification of a given peptide is often missing in a subset of the experiments, especially for less abundant peptides. Another issue is that different MS experiments of the same study have significantly varying numbers of peptides quantified, which can result in more missing peptide abundances in an experiment that has a smaller total number of quantified peptides. To detect as many biomarker proteins as possible, it is necessary to develop bioinformatics methods that appropriately handle these challenges. Results: We propose a Significance Analysis for Large-scale Proteomics Studies (SALPS) that handles missing peptide intensity values caused by the two mechanisms mentioned above. Our model has a robust performance in both simulated data and proteomics data from a large clinical study. Because varying patients' sample qualities and deviating instrument performances are not avoidable for clinical studies performed over the course of several years, we believe that our approach will be useful to analyze large-scale clinical proteomics data. C1 [Ryu, So Young; Davis, Ronald W.; Xiao, Wenzhong] Stanford Univ, Stanford Genome Technol Ctr, Stanford, CA 94305 USA. [Qian, Wei-Jun; Camp, David G.; Smith, Richard D.] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. [Qian, Wei-Jun; Camp, David G.; Smith, Richard D.] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. [Ryu, So Young; Tompkins, Ronald G.; Xiao, Wenzhong] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Xiao, WZ (reprint author), Stanford Univ, Stanford Genome Technol Ctr, Stanford, CA 94305 USA. RI Smith, Richard/J-3664-2012 OI Smith, Richard/0000-0002-2381-2349 FU National Institutes of Health [T32-GM007035, R01-GM101401, P41-GM103493]; Shriners Research Grant [85500-BOS]; DOE [DE-AC05-76RL01830] FX Funding: This research was supported by National Institutes of Health grants (T32-GM007035 to R.G.T., R01-GM101401 to R.G.T. and W.X., P41-GM103493 to R.D.S.) and Shriners Research Grant (85500-BOS to W.X.). The experimental work described herein was performed in the Environmental Molecular Sciences Laboratory (EMSL), a US Department of Energy (DOE) national scientific user facility located at PNNL in Richland, Washington. PNNL is a multi-program national laboratory operated by Battelle Memorial Institute for the DOE under Contract DE-AC05-76RL01830. NR 25 TC 6 Z9 6 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD OCT 1 PY 2014 VL 30 IS 19 BP 2741 EP 2746 DI 10.1093/bioinformatics/btu341 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA AQ8NM UT WOS:000343082900007 PM 24928210 ER PT J AU Levinson, DF Mostafavi, S Milaneschi, Y Rivera, M Ripke, S Wray, NR Sullivan, PF AF Levinson, Douglas F. Mostafavi, Sara Milaneschi, Yuri Rivera, Margarita Ripke, Stephan Wray, Naomi R. Sullivan, Patrick F. TI Genetic Studies of Major Depressive Disorder: Why Are There No Genome-wide Association Study Findings and What Can We Do About It? SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 [Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Mostafavi, Sara] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA. [Milaneschi, Yuri] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Milaneschi, Yuri] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Milaneschi, Yuri] GGZ inGeest, Amsterdam, Netherlands. [Rivera, Margarita] Kings Coll London, MRC, Social Genet & Dev Psychiat Ctr, Inst Psychiat, London WC2R 2LS, England. [Rivera, Margarita] Univ Granada, Ctr Invest Biomed Red Salud Mental, Biomed Res Ctr, Inst Neurosci,Sect Psychiat, Granada, Spain. [Ripke, Stephan] Broad Inst, Program Med & Populat Genet, Cambridge, England. [Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. RP Levinson, DF (reprint author), Stanford Univ, 401 Quarry Rd,Rm 3322, Stanford, CA 94305 USA. EM dflev@stanford.edu RI Wray, Naomi/C-8639-2015 OI Wray, Naomi/0000-0001-7421-3357 FU NIMH NIH HHS [U01 MH094411, U01 MH094421] NR 10 TC 35 Z9 35 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2014 VL 76 IS 7 BP 510 EP 512 DI 10.1016/j.biopsych.2014.07.029 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AQ8QJ UT WOS:000343094000002 PM 25201436 ER PT J AU O'Dushlaine, C Ripke, S Ruderfer, DM Hamilton, SP Fava, M Iosifescu, DV Kohane, IS Churchill, SE Castro, VM Clements, CC Blumenthal, SR Murphy, SN Smoller, JW Perlis, RH AF O'Dushlaine, Colm Ripke, Stephan Ruderfer, Douglas M. Hamilton, Steven P. Fava, Maurizio Iosifescu, Dan V. Kohane, Isaac S. Churchill, Susanne E. Castro, Victor M. Clements, Caitlin C. Blumenthal, Sarah R. Murphy, Shawn N. Smoller, Jordan W. Perlis, Roy H. TI Rare Copy Number Variation in Treatment-Resistant Major Depressive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Antidepressant; copy number; deletion; duplication; pharmacogenetic; pharmacogenomic; rare genetic variation ID STAR-ASTERISK-D; ASSOCIATION; SCHIZOPHRENIA; RISK; IDENTIFICATION; VARIANTS; SAMPLE; GENES; LOCI; TOOL AB Background: While antidepressant treatment response appears to be partially heritable, no consistent genetic associations have been identified. Large, rare copy number variants (CNVs) play a role in other neuropsychiatric diseases, so we assessed their association with treatment-resistant depression (TRD). Methods: We analyzed data from two genome-wide association studies comprising 1263 Caucasian patients with major depressive disorder. One was drawn from a large health system by applying natural language processing to electronic health records (i2b2 cohort). The second consisted of a multicenter study of sequential antidepressant treatments, Sequenced Treatment Alternatives to Relieve Depression. The Birdsuite package was used to identify rare deletions and duplications. Individuals without symptomatic remission, despite two antidepressant treatment trials, were contrasted with those who remitted with a first treatment trial. Results: CNV data were derived for 778 subjects in the i2b2 cohort, including 300 subjects (37%) with TRD, and 485 subjects in Sequenced Treatment Alternatives to Relieve Depression cohort, including 152 (31%) with TRD. CNV burden analyses identified modest enrichment of duplications in cases (empirical p = .04 for duplications of 100-200 kilobase) and a particular deletion region spanning gene PABPC4L (empirical p = .02, 6 cases: 0 controls). Pathway analysis suggested enrichment of CNVs intersecting genes regulating actin cytoskeleton. However, none of these associations survived genome-wide correction. Conclusions: Contribution of rare CNVs to TRD appears to be modest, individually or in aggregate. The electronic health record-based methodology demonstrated here should facilitate collection of larger TRD cohorts necessary to further characterize these effects. C1 [O'Dushlaine, Colm; Ripke, Stephan; Smoller, Jordan W.; Perlis, Roy H.] Broad Inst Massachusetts, Inst Technol, Stanley Ctr Psychiat Res, Cambridge, England. [O'Dushlaine, Colm; Ripke, Stephan; Smoller, Jordan W.; Perlis, Roy H.] Harvard Univ, Cambridge, MA 02138 USA. [Fava, Maurizio; Clements, Caitlin C.; Blumenthal, Sarah R.; Smoller, Jordan W.; Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hamilton, Steven P.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Ruderfer, Douglas M.; Iosifescu, Dan V.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Kohane, Isaac S.; Churchill, Susanne E.; Castro, Victor M.; Murphy, Shawn N.] Massachusetts Gen Hosp, Partners HealthCare Syst, Boston, MA 02114 USA. [Castro, Victor M.; Murphy, Shawn N.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Castro, Victor M.; Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, Dept Psychiat, 185 Cambridge St, Boston, MA 02114 USA. EM rperlis@partners.org RI Ruderfer, Douglas/M-5795-2016; OI Ruderfer, Douglas/0000-0002-2365-386X; Hamilton, Steven/0000-0001-8106-6260 FU National Institute of Mental Health [R01MH086026, R01MH072802]; Stanley Center for Psychiatric Research; National Institutes of Health/National Library of Medicine [2U54LM008748]; Healthrageous; Pamlab; Perfect Health; Pfizer; Proteus Biomedical; Psybrain; RIDventures; UBC/Medco; Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; Bristol-Myers Squibb Company; Cephalon; Eli Lilly Company; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis; Organon, Inc.; PamLab, LLC; Pfizer, Inc; Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals, Inc.; Wyeth-Ayerst Laboratories; Mount Sinai School of Medicine from Astra-Zeneca; Brainsway; Euthymics Bioscience, Inc.; Neosync; Shire FX Dr. Perlis is supported by National Institute of Mental Health R01MH086026 and by the Stanley Center for Psychiatric Research. Dr. O'Dushlaine is supported by funding from the Stanley Center for Psychiatric Research. Sequenced Treatment Alternatives to Relieve Depression genotyping was supported by National Institute of Mental Health R01MH072802 to Dr. Hamilton. The i2b2 platform (Dr. Kohane) is supported by award number 2U54LM008748 from the National Institutes of Health/National Library of Medicine.; Dr. Perlis has received consulting fees or served on scientific advisory boards for Genomind, Healthrageous, Pamlab, Perfect Health, Pfizer, Proteus Biomedical, Psybrain, and RIDventures, and received patent fees/royalties from Concordant Rater Systems (now UBC/Medco).; Dr. Fava reports the following: Research Support: Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; Bristol-Myers Squibb Company; Cephalon; Eli Lilly & Company; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis; Organon, Inc.; PamLab, LLC; Pfizer, Inc; Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals, Inc.; and Wyeth-Ayerst Laboratories. Advisory/Consulting: Aspect Medical Systems; Astra-Zeneca; Bayer AG; Biovail Pharmaceuticals, Inc.; BrainCells, Inc.; Bristol-Myers Squibb Company; Cephalon; Compellis; Cypress Pharmaceuticals; Dov Pharmaceuticals; Eli Lilly & Company; EPIX Pharmaceuticals; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Grunenthal GmBH; Janssen Pharmaceutica; Jazz Pharmaceuticals; J & J Pharmaceuticals; Knoll Pharmaceutical Company; Lundbeck; MedAvante, Inc.; Neuronetics; Novartis; Nutrition 21; Organon, Inc.; PamLab, LLC; Pfizer, Inc.; PharmaStar; Pharmavite; Roche; Sanofi/Synthelabo; Sepracor; Solvay Pharmaceuticals, Inc.; Somaxon; Somerset Pharmaceuticals; and Wyeth-Ayerst Laboratories. Speaking: Astra-Zeneca; Boehringer-Ingelheim; Bristol-Myers Squibb Company; Cephalon; Eli Lilly & Company; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Novartis; Organon, Inc.; Pfizer, Inc.; PharmaStar; and Wyeth-Ayerst Laboratories. Equity Holdings: Compellis and MedAvante. Royalty/patent, other income: none.; In the past 3 years, Dr. Iosifescu has consulted for CNS Response, Otsuka, and Servier, and he has received research support through Mount Sinai School of Medicine from Astra-Zeneca; Brainsway; Euthymics Bioscience, Inc.; Neosync; and Shire. NR 32 TC 11 Z9 11 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2014 VL 76 IS 7 BP 536 EP 541 DI 10.1016/j.biopsych.2013.10.028 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AQ8QJ UT WOS:000343094000007 PM 24529801 ER PT J AU Srinivasan, PP Kim, LA Mettu, PS Cousins, SW Comer, GM Izatt, JA Farsiu, S AF Srinivasan, Pratul P. Kim, Leo A. Mettu, Priyatham S. Cousins, Scott W. Comer, Grant M. Izatt, Joseph A. Farsiu, Sina TI Fully automated detection of diabetic macular edema and dry age-related macular degeneration from optical coherence tomography images SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID NERVE-FIBER LAYER; SD-OCT IMAGES; RETINAL LAYERS; SEGMENTATION; THICKNESS; CLASSIFICATION; DIAGNOSIS; PATHOLOGY; EYES; RETINOPATHY AB We present a novel fully automated algorithm for the detection of retinal diseases via optical coherence tomography (OCT) imaging. Our algorithm utilizes multiscale histograms of oriented gradient descriptors as feature vectors of a support vector machine based classifier. The spectral domain OCT data sets used for cross-validation consisted of volumetric scans acquired from 45 subjects: 15 normal subjects, 15 patients with dry age-related macular degeneration (AMD), and 15 patients with diabetic macular edema (DME). Our classifier correctly identified 100% of cases with AMD, 100% cases with DME, and 86.67% cases of normal subjects. This algorithm is a potentially impactful tool for the remote diagnosis of ophthalmic diseases. (C)2014 Optical Society of America C1 [Srinivasan, Pratul P.; Izatt, Joseph A.; Farsiu, Sina] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. [Srinivasan, Pratul P.; Farsiu, Sina] Duke Univ, Dept Comp Sci, Durham, NC 27708 USA. [Kim, Leo A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Mettu, Priyatham S.; Cousins, Scott W.; Izatt, Joseph A.; Farsiu, Sina] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. [Comer, Grant M.] Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48105 USA. [Farsiu, Sina] Duke Univ, Dept Elect & Comp Engn, Durham, NC 27708 USA. RP Srinivasan, PP (reprint author), Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. EM pratul.srinivasan@duke.edu FU NIH [R01 EY022691]; U.S. Army Medical Research Acquisition Activity Contract [W81XWH-12-1-0397]; Duke University Pratt Undergraduate Fellowship Program; Juvenile Diabetes Research Foundation; NEI [K12-EY16335, K12 EY016333-08]; Massachusetts Lions Eye Research Fund FX This research was supported by the NIH R01 EY022691 (SF), the U.S. Army Medical Research Acquisition Activity Contract W81XWH-12-1-0397 (JAI), the Duke University Pratt Undergraduate Fellowship Program (PPS), the Juvenile Diabetes Research Foundation (GMC), the NEI K12-EY16335 (LAK), the NEI K12 EY016333-08 (PSM), and the Massachusetts Lions Eye Research Fund (LAK). We would like to thank Professors Magali Saint-Geniez and Kevin McHugh of Harvard University for their collaboration and invaluable feedback. NR 40 TC 21 Z9 21 U1 1 U2 12 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD OCT 1 PY 2014 VL 5 IS 10 BP 3568 EP 3577 DI 10.1364/BOE.5.003568 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AQ9BI UT WOS:000343135200025 PM 25360373 ER PT J AU Turcotte, R Alt, C Mortensen, LJ Lin, CP AF Turcotte, Raphael Alt, Clemens Mortensen, Luke J. Lin, Charles P. TI Characterization of multiphoton microscopy in the bone marrow following intravital laser osteotomy SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID HEMATOPOIETIC STEM; OPTICAL-PROPERTIES; PROGENITOR CELLS; CRANIAL WINDOW; LONG-TERM; ABLATION; PULSES; MECHANISMS; TRACKING; SURGERY AB The bone marrow is an important site where all blood cells are formed from hematopoietic stem cells and where hematologic malignancies such as leukemia emerge. It is also a frequent site for metastasis of solid tumors such as breast cancer and prostate cancer. Intravital microscopy is a powerful tool for studying the bone marrow with single cell and sub-cellular resolution. To improve optical access to this rich biological environment, plasma-mediated laser ablation with sub-microjoule femtosecond pulses was used to thin cortical bone. By locally removing a superficial layer of bone (local laser osteotomy), significant improvements in multiphoton imaging were observed in individual bone marrow compartments in vivo. This work demonstrates the utility of scanning laser ablation of hard tissue with sub-microjoule pulses as a preparatory step to imaging. (C) 2014 Optical Society of America C1 [Turcotte, Raphael; Alt, Clemens; Mortensen, Luke J.; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Adv Microscopy Program,Ctr Syst Biol, Boston, MA 02114 USA. [Turcotte, Raphael; Alt, Clemens; Mortensen, Luke J.; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Turcotte, Raphael] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Turcotte, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Adv Microscopy Program,Ctr Syst Biol, CPZN 8238,185 Cambridge Str, Boston, MA 02114 USA. EM lin@helix.mgh.harvard.edu OI Mortensen, Luke/0000-0002-4331-4099 FU HSCI [DP-0079-11-00]; NIH [EB017274]; FRQNT PhD Fellowship; Wellman Center for Photomedicine Graduate Student Fellowship; PCBC [U01HL099997] FX This work was supported by the HSCI grant DP-0079-11-00 and the NIH grant EB017274. RT was supported by a FRQNT PhD Fellowship and a Wellman Center for Photomedicine Graduate Student Fellowship. The authors would also like to acknowledge funding support from PCBC (U01HL099997). NR 42 TC 5 Z9 5 U1 1 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD OCT 1 PY 2014 VL 5 IS 10 BP 3578 EP 3588 DI 10.1364/BOE.5.003578 PG 11 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AQ9BI UT WOS:000343135200026 PM 25360374 ER PT J AU Wang, H Dong, Y Zhang, J Xu, Z Wang, G Swain, CA Zhang, Y Xie, Z AF Wang, H. Dong, Y. Zhang, J. Xu, Z. Wang, G. Swain, C. A. Zhang, Y. Xie, Z. TI Isoflurane induces endoplasmic reticulum stress and caspase activation through ryanodine receptors SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE endoplasmic reticulum; inhalation anaesthetics, isoflurane; receptors, ryanodine ID BETA-PROTEIN-LEVELS; ANESTHETIC ISOFLURANE; ALZHEIMERS-DISEASE; INDUCED APOPTOSIS; CELL-DEATH; VOLATILE ANESTHETICS; NEURONAL APOPTOSIS; INTRACELLULAR CA2+; COGNITIVE DECLINE; PRECURSOR PROTEIN AB Background. Isoflurane has been reported to induce caspase-3 activation, which may induce neurotoxicity and contribute to the pathogenesis of Alzheimer's disease. However, the underlying mechanism is largely unknown, especially whether or not isoflurane can induce ryanodine receptors (RyRs)-associated endoplasmic reticulum (ER) stress, leading to caspase-3 activation. We therefore assessed the effects of isoflurane on RyRs-associated ER stress. Methods. We treated primary neurones from wild-type (C57BL/6J) mice with 1% and 2% isoflurane for 1, 3, or 6 h. We then measured levels of C/EBP homologous protein (CHOP) and caspase-12, two ER stress markers, using immunocytochemistry staining and western blotting analysis. Dantrolene (5 mu M), the antagonist of RyRs, was used to investigate the role of RyRs in the isoflurane-induced ER stress and caspase-3 activation. Results. Isoflurane 2% for 6 h treatment increased the levels of CHOP (876% vs 100%, P=0.00009) and caspase-12 (276% vs 100%, P=0.006), and induced caspase-3 activation in the neurones. The administration of 2% isoflurane for 3 h (shorter duration), however, only increased the levels of CHOP (309% vs 100%, P=0.003) and caspase-12 (266% vs 100%, P=0.001), without causing caspase-3 activation. The isoflurane-induced ER stress (CHOP: F=16.64, P=0.0022; caspase-12: F=6.13, P=0.0383) and caspase-3 activation (F=32.06, P=0.0005) were attenuated by the dantrolene treatment. Conclusions. These data imply that isoflurane might induce caspase-3 activation by causing ER stress through RyRs, and dantrolene could attenuate the isoflurane-induced ER stress and caspase-3 activation. Further investigations of the potential neurotoxicity of isoflurane are needed. C1 [Wang, H.; Dong, Y.; Zhang, J.; Xu, Z.; Swain, C. A.; Zhang, Y.; Xie, Z.] Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Geriatr Anaesthesia Res Unit, 149 13th St,Room 4310, Charlestown, MA 02129 USA. [Wang, H.; Dong, Y.; Zhang, J.; Xu, Z.; Swain, C. A.; Zhang, Y.; Xie, Z.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Wang, H.; Wang, G.] Tianjin Med Univ, Gen Hosp, Dept Anaesthesiol, Tianjin Res Inst Anaesthesiol, Tianjin 300052, Peoples R China. [Zhang, J.] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Anaesthesiol, Wuhan 430030, Peoples R China. RP Xie, Z (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Geriatr Anaesthesia Res Unit, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@partners.org FU National Institutes of Health, Bethesda, MD [R21AG029856, R21AG038994, R01 GM088801, R01 AG041274]; Investigator-initiated Research grant from Alzheimer's Association, Chicago, IL; Cure Alzheimer's Fund, Wellesley, MA FX This research was supported by R21AG029856, R21AG038994, R01 GM088801, and R01 AG041274 from National Institutes of Health, Bethesda, MD, Investigator-initiated Research grant from Alzheimer's Association, Chicago, IL, and Cure Alzheimer's Fund, Wellesley, MA to Z. Xie. NR 55 TC 7 Z9 10 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 EI 1471-6771 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD OCT PY 2014 VL 113 IS 4 BP 695 EP 707 DI 10.1093/bja/aeu053 PG 13 WC Anesthesiology SC Anesthesiology GA AQ8OQ UT WOS:000343087400023 PM 24699520 ER PT J AU De Souza, MJ Williams, NI Nattiv, A Joy, E Misra, M Loucks, AB Matheson, G Olmsted, MP Barrack, M Mallinson, RJ Gibbs, JC Goolsby, M Nichols, JF Drinkwater, B Sanborn, C Agostini, R Otis, CL Johnson, MD Hoch, AZ Alleyne, JMK Wadsworth, LT Koehler, K VanHeest, J Harvey, P Kelly, AKW Fredericson, M Brooks, GA O'Donnell, E Callahan, LR Putukian, M Costello, L Hecht, S Rauh, MJ McComb, J AF De Souza, Mary Jane Williams, Nancy I. Nattiv, Aurelia Joy, Elizabeth Misra, Madhusmita Loucks, Anne B. Matheson, Gordon Olmsted, Marion P. Barrack, Michelle Mallinson, Rebecca J. Gibbs, Jenna C. Goolsby, Marci Nichols, Jeanne F. Drinkwater, Barbara Sanborn, Charlotte (Barney) Agostini, Rosemary Otis, Carol L. Johnson, Mimi D. Hoch, Anne Zeni Alleyne, Julia M. K. Wadsworth, L. Tyler Koehler, Karsten VanHeest, Jaci Harvey, Paula Kelly, Amanda K. Weiss Fredericson, Michael Brooks, George A. O'Donnell, Emma Callahan, Lisa R. Putukian, Margot Costello, Lauren Hecht, Suzanne Rauh, Mitchell J. McComb, Jacalyn TI Misunderstanding the Female Athlete Triad: Refuting the IOC Consensus Statement on Relative Energy Deficiency in Sport (RED-S) SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Editorial Material ID PEDIATRIC OFFICIAL POSITIONS; BONE-MINERAL DENSITY; INTERNATIONAL-CONFERENCE HELD; ANOREXIA-NERVOSA; EXERCISING WOMEN; HYPOTHALAMIC AMENORRHEA; MENSTRUAL DYSFUNCTION; SECRETORY DYNAMICS; ADOLESCENT GIRLS; LH PULSATILITY C1 [De Souza, Mary Jane; Williams, Nancy I.; Mallinson, Rebecca J.; Koehler, Karsten] Penn State Univ, Dept Kinesiol, University Pk, PA 16802 USA. [Nattiv, Aurelia] Univ Calif Los Angeles, Div Sports Med, Los Angeles, CA USA. [Nattiv, Aurelia] Univ Calif Los Angeles, Dept Orthopaed Surg, Los Angeles, CA USA. [Joy, Elizabeth] Intermt Healthcare, Salt Lake City, UT USA. [Misra, Madhusmita] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Loucks, Anne B.] Ohio Univ, Athens, OH 45701 USA. [Matheson, Gordon] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Olmsted, Marion P.; Alleyne, Julia M. K.; Harvey, Paula; O'Donnell, Emma] Univ Toronto, Toronto, ON, Canada. [Barrack, Michelle] Calif State Univ Northridge, Northridge, CA 91330 USA. [Gibbs, Jenna C.] Univ Waterloo, Waterloo, ON N2L 3G1, Canada. [Goolsby, Marci; Callahan, Lisa R.] Hosp Special Surg, New York, NY 10021 USA. [Nichols, Jeanne F.] Univ Calif San Diego, San Diego, CA 92103 USA. [Sanborn, Charlotte (Barney)] Texas Womans Univ, Denton, TX 76204 USA. [Agostini, Rosemary] Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. [Otis, Carol L.] WTA Tour Player Dev, Portland, OR USA. [Johnson, Mimi D.] Univ Washington, Seattle, WA 98195 USA. [Hoch, Anne Zeni] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Wadsworth, L. Tyler] Adv Orthoped & Sports Med, St Louis, MO USA. [VanHeest, Jaci] Univ Connecticut, Storrs, CT USA. [Kelly, Amanda K. Weiss] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Fredericson, Michael] Stanford Univ, Stanford, CA 94305 USA. [Brooks, George A.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Putukian, Margot; Costello, Lauren] Princeton Univ, Princeton, NJ 08544 USA. [Hecht, Suzanne] Univ Minnesota, Minneapolis, MN USA. [Rauh, Mitchell J.] San Diego State Univ, San Diego, CA 92182 USA. [McComb, Jacalyn] Texas Tech Univ, Lubbock, TX 79409 USA. RP De Souza, MJ (reprint author), Penn State Univ, Dept Kinesiol, Womens Hlth & Exercise Lab, Noll Lab 104, University Pk, PA 16802 USA. EM mjd34@psu.edu OI O'Donnell, Emma/0000-0002-4037-4213; Brooks, George A./0000-0002-1389-1629 FU NICHD NIH HHS [R01 HD060827] NR 60 TC 7 Z9 7 U1 11 U2 37 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-3674 EI 1473-0480 J9 BRIT J SPORT MED JI Br. J. Sports Med. PD OCT PY 2014 VL 48 IS 20 BP 1461 EP 1465 DI 10.1136/bjsports-2014-093958 PG 5 WC Sport Sciences SC Sport Sciences GA AQ8UV UT WOS:000343111200002 PM 25037200 ER PT J AU Zhao, JJ Carrasco, RD AF Zhao, Jian-Jun Carrasco, Ruben D. TI Crosstalk between microRNA30a/b/c/d/e-5p and the Canonical Wnt Pathway: Implications for Multiple Myeloma therapy SO CANCER RESEARCH LA English DT Review ID BORTEZOMIB-INDUCED APOPTOSIS; BETA-CATENIN; COLORECTAL-CANCER; MICRORNA EXPRESSION; DOWN-REGULATION; IN-VITRO; ARMADILLO/BETA-CATENIN; ANTITUMOR-ACTIVITY; DRUG-RESISTANCE; GENE-EXPRESSION AB Dysregulation of transcription via the Wnt/beta-catenin signaling pathway underlies the pathogenesis of a wide variety of frequent human cancers. These include epithelial carcinomas such as colorectal cancer and hematologic malignancies such as multiple myeloma. Thus, the Wnt/beta-catenin pathway potentially offers an attractive target for cancer therapy. This approach, however, has thus far proved challenging because the pathway plays a number of critical roles in physiologic homeostasis and because drugs that broadly target the pathway have unacceptable side effects. miRNAs function as regulators of gene expression and have also been implicated in the pathogenesis of multiple myeloma and other human cancers, offering the promise of novel therapeutic approaches if they can be applied effectively in vivo. Because BCL9 is a critical transcriptional coactivator of beta-catenin that is aberrantly expressed in many human cancers but is of low abundance in normal tissues_ENREF_5, the Wnt/beta-catenin/BCL9 complex has emerged as a promising and most likely relatively safe therapeutic target in cancers with dysregulated Wnt/beta-catenin activity. This review discusses recent advances in the biology of Wnt inhibitors and the appealing possibility of a functional link between BCL9 and miRNA30a/b/c/d/e-5p that could be exploited for multiple myeloma therapy. (C)2014 AACR. C1 [Zhao, Jian-Jun; Carrasco, Ruben D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Carrasco, Ruben D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Carrasco, RD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM ruben_carrasco@dfci.harvard.edu FU Multiple Myeloma Research Foundation (MMRF) research fellowship; MMRF senior faculty award; NCI, NIH [1R01CA151391-01] FX J-J. Zhao was supported by a Multiple Myeloma Research Foundation (MMRF) research fellowship. R.D. Carrasco was supported by an MMRF senior faculty award and by research grant 1R01CA151391-01 from the NCI, NIH. NR 94 TC 10 Z9 10 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2014 VL 74 IS 19 BP 5351 EP 5358 DI 10.1158/0008-5472.CAN-14-0994 PG 8 WC Oncology SC Oncology GA AQ8WP UT WOS:000343118900001 PM 25228654 ER PT J AU Werner, B Gallagher, RE Paietta, EM Litzow, MR Tallman, MS Wiernik, PH Slack, JL Willman, CL Sun, ZX Traulsen, A Dingli, D AF Werner, Benjamin Gallagher, Robert E. Paietta, Elisabeth M. Litzow, Mark R. Tallman, Martin S. Wiernik, Peter H. Slack, James L. Willman, Cheryl L. Sun, Zhuoxin Traulsen, Arne Dingli, David TI Dynamics of Leukemia Stem-like Cell Extinction in Acute Promyelocytic Leukemia SO CANCER RESEARCH LA English DT Article ID TRANS-RETINOIC ACID; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; NORTH-AMERICAN INTERGROUP; ACUTE MYELOID-LEUKEMIA; CYCLIC NEUTROPENIA; RECEPTOR-ALPHA; MESSENGER-RNA; SELF-RENEWAL; DIFFERENTIATION; CANCER AB Many tumors are believed to be maintained by a small number of cancer stem-like cells, where cure is thought to require eradication of this cell population. In this study, we investigated the dynamics of acute promyelocytic leukemia (APL) before and during therapy with regard to disease initiation, progression, and therapeutic response. This investigation used a mathematical model of hematopoiesis and a dataset derived from the North American Intergroup Study INT0129. The known phenotypic constraints of APL could be explained by a combination of differentiation blockade of PML-RAR alpha-positive cells and suppression of normal hematopoiesis. All-trans retinoic acid (ATRA) neutralizes the differentiation block and decreases the proliferation rate of leukemic stem cells in vivo. Prolonged ATRA treatment after chemotherapy can cure patients with APL by eliminating the stem-like cell population over the course of approximately one year. To our knowledge, this study offers the first estimate of the average duration of therapy that is required to eliminate stem-like cancer cells from a human tumor, with the potential for the refinement of treatment strategies to better manage human malignancy. (C)2014 AACR. C1 [Werner, Benjamin; Traulsen, Arne] Max Planck Inst Evolut Biol, Dept Evolut Theory, D-24306 Plon, Germany. [Gallagher, Robert E.; Paietta, Elisabeth M.] Montefiore Med Ctr, New York, NY USA. [Litzow, Mark R.; Dingli, David] Mayo Clin, Div Hematol, Rochester, MN USA. [Litzow, Mark R.; Dingli, David] Mayo Clin, Dept Internal Med, Rochester, MN USA. [Tallman, Martin S.] Northwestern Univ, Chicago, IL 60611 USA. [Wiernik, Peter H.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Slack, James L.] Mayo Clin Arizona, Div Hematol, Scottsdale, AZ USA. [Willman, Cheryl L.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Sun, Zhuoxin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Sun, Zhuoxin] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Dingli, David] Mayo Clin, Dept Mol Med, Rochester, MN USA. RP Dingli, D (reprint author), Mayo Clin, 200 First St SW, Rochester, MN 55905 USA. EM dingli.david@mayo.edu RI Traulsen, Arne/A-4955-2009; OI Traulsen, Arne/0000-0002-0669-5267; Werner, Benjamin/0000-0002-6857-8699 FU Public Health Service Grants from National Cancer Institute [CA21115, CA14958, CA13650, CA17145, CA86726, CA56771]; NIH; Department of Health and Human Services FX This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD, and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants CA21115, CA14958, CA13650, CA17145, CA86726, and CA56771 from the National Cancer Institute, NIH, and the Department of Health and Human Services. NR 50 TC 3 Z9 3 U1 1 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 OCT 1 PY 2014 VL 74 IS 19 BP 5386 EP 5396 DI 10.1158/0008-5472.CAN-14-1210 PG 11 WC Oncology SC Oncology GA AQ8WP UT WOS:000343118900006 PM 25082816 ER PT J AU Thapa, D Meng, P Bedolla, RG Reddick, RL Kumar, AP Ghosh, R AF Thapa, Dinesh Meng, Peng Bedolla, Roble G. Reddick, Robert L. Kumar, Addanki P. Ghosh, Rita TI NQO1 Suppresses NF-kappa B-p300 Interaction to Regulate Inflammatory Mediators Associated with Prostate Tumorigenesis SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; NAD(P)HQUINONE OXIDOREDUCTASE 1; IKK-ALPHA; OXIDATIVE STRESS; TRANSGENIC ADENOCARCINOMA; ANDROGEN DEPRIVATION; GENE-EXPRESSION; CANCER CELLS; P53; THERAPY AB NADPH reductase NAD(P) H: quinone oxidoreductase 1 (NQO1) is needed to maintain a cellular pool of antioxidants, and this enzyme may contribute to tumorigenesis on the basis of studies in NQO1-deficient mice. In this work, we sought deeper insights into how NQO1 contributes to prostate carcinogenesis, a setting in which oxidative stress and inflammation are established contributors to disease development and progression. In the TRAMP mouse model of prostate cancer, NQO1 was highly expressed in tumor cells. NQO1 silencing in prostate cancer cells increased levels of nuclear IKK alpha and NF-kappa B while decreasing the levels of p53, leading to interactions between NF-kappa B and p300 that reinforce survival signaling. Gene expression analysis revealed upregulation of a set of immune-associated transcripts associated with inflammation and tumorigenesis in cells in which NQO1 was attenuated, with IL8 confirmed functionally in cell culture as one key NQO1-supported cytokine. Notably, NQO1-silenced prostate cancer cells were more resistant to androgen deprivation. Furthermore, NQO1 inhibition increased migration, including under conditions of androgen deprivation. These results reveal a molecular link between NQO1 expression and proinflammatory cytokine signaling in prostate cancer. Furthermore, our results suggest that altering redox homeostasis through NQO1 inhibition might promote androgen-independent cell survival via opposing effects on NF-kappa B and p53 function. (C) 2014 AACR. C1 [Thapa, Dinesh; Meng, Peng; Bedolla, Roble G.; Kumar, Addanki P.; Ghosh, Rita] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Urol, San Antonio, TX 78229 USA. [Reddick, Robert L.] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Pathol, San Antonio, TX 78229 USA. [Reddick, Robert L.; Kumar, Addanki P.; Ghosh, Rita] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Kumar, Addanki P.; Ghosh, Rita] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Pharmacol, San Antonio, TX 78229 USA. [Kumar, Addanki P.; Ghosh, Rita] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Mol Med, San Antonio, TX 78229 USA. [Kumar, Addanki P.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Ghosh, R (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Urol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM ghoshr@uthscsa.edu FU [5R01CA149516]; [CTSA UL1 TR000149]; [1R01AT7448]; [CPRIT PDF RP101491] FX This work was supported by 5R01CA149516 (R. Ghosh), CTSA UL1 TR000149 (R. Ghosh), 1R01AT7448 (to A.P. Kumar), and CPRIT PDF RP101491 (D. Thapa). NR 49 TC 10 Z9 11 U1 2 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 OCT 1 PY 2014 VL 74 IS 19 BP 5644 EP 5655 DI 10.1158/0008-5472.CAN-14-0562 PG 12 WC Oncology SC Oncology GA AQ8WP UT WOS:000343118900028 PM 25125658 ER PT J AU Potash, J Anderson, KC AF Potash, Jesse Anderson, Kenneth C. TI AACR Cancer Progress Report 2014: Transforming Lives Through Research SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 [Potash, Jesse; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2014 VL 20 IS 19 BP 4977 EP 4977 DI 10.1158/1078-0432.CCR-14-2104 PG 1 WC Oncology SC Oncology GA AQ8XU UT WOS:000343123800001 PM 25228533 ER PT J AU Egloff, AM Lee, JW Langer, CJ Quon, H Vaezi, A Grandis, JR Seethala, RR Wang, L Shin, DM Argiris, A Yang, DH Mehra, R Ridge, JA Patel, UA Burtness, BA Forastiere, AA AF Egloff, Ann Marie Lee, Ju-Whei Langer, Corey J. Quon, Harry Vaezi, Alec Grandis, Jennifer R. Seethala, Raja R. Wang, Lin Shin, Dong M. Argiris, Athanassios Yang, Donghua Mehra, Ranee Ridge, John Andrew Patel, Urjeet A. Burtness, Barbara A. Forastiere, Arlene A. TI Phase II Study of Cetuximab in Combination with Cisplatin and Radiation in Unresectable, Locally Advanced Head and Neck Squamous Cell Carcinoma: Eastern Cooperative Oncology Group Trial E3303 SO CLINICAL CANCER RESEARCH LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR EXPRESSION; CONCURRENT CHEMOTHERAPY; RANDOMIZED-TRIAL; PLUS CETUXIMAB; DNA-REPAIR; CANCER; THERAPY; RADIOTHERAPY; INHIBITION AB Purpose: Treatment with cisplatin or cetuximab combined with radiotherapy each yield superior survival in locally advanced squamous cell head and neck cancer (LA-SCCHN) compared with radiotherapy alone. Eastern Cooperative Oncology Group Trial E3303 evaluated the triple combination. Experimental Design: Patients with stage IV unresectable LA-SCCHN received a loading dose of cetuximab (400 mg/m(2)) followed by 250 mg/m(2)/week and cisplatin 75 mg/m(2) q 3 weeks x3 cycles concurrent with standard fractionated radiotherapy. In the absence of disease progression or unacceptable toxicity, patients continued maintenance cetuximab for 6 to 12 months. Primary endpoint was 2-year progression-free survival (PFS). Patient tumor and blood correlates, including tumor human papillomavirus (HPV) status, were evaluated for association with survival. Results: A total of 69 patients were enrolled; 60 proved eligible and received protocol treatment. Oropharyngeal primaries constituted the majority (66.7%), stage T4 48.3% and N2-3 91.7%. Median radiotherapy dose delivered was 70 Gy, 71.6% received all three cycles of cisplatin, and 74.6% received maintenance cetuximab. Median PFS was 19.4 months, 2-year PFS 47% [95% confidence interval (CI), 33%-61%]. Two-year overall survival (OS) was 66% (95% CI, 53%-77%); median OS was not reached. Response rate was 66.7%. Most common grade >= 3 toxicities included mucositis (55%), dysphagia (46%), and neutropenia (26%); one attributable grade 5 toxicity occurred. Only tumor HPV status was significantly associated with survival. HPV was evaluable in 29 tumors; 10 (all oropharyngeal) were HPV positive. HPV+ patients had significantly longer OS and PFS (P = 0.004 and P = 0.036, respectively). Conclusions: Concurrent cetuximab, cisplatin, and radiotherapy were well tolerated and yielded promising 2-year PFS and OS in LA-SCCHN with improved survival for patients with HPV+ tumors. (C) 2014 AACR. C1 [Egloff, Ann Marie; Vaezi, Alec; Grandis, Jennifer R.; Seethala, Raja R.; Wang, Lin; Argiris, Athanassios] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Lee, Ju-Whei] Dana Farber Canc Inst, Boston, MA 02115 USA. [Langer, Corey J.; Yang, Donghua; Mehra, Ranee; Ridge, John Andrew; Burtness, Barbara A.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Quon, Harry] Univ Penn, Philadelphia, PA 19104 USA. [Shin, Dong M.] Emory Univ, Atlanta, GA 30322 USA. [Patel, Urjeet A.] Northwestern Univ, Chicago, IL 60611 USA. [Forastiere, Arlene A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Forastiere, Arlene A.] Sydney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Egloff, AM (reprint author), Univ Pittsburgh, Inst Eye & Ear, Dept Otolaryngol, Suite 500,200 Lothrop St, Pittsburgh, PA 15213 USA. EM egloffam@upmc.edu FU Public Health Service [CA23318, CA66636, CA21115, CA27525, CA39229, CA15488, CA16116, CA137140]; National Cancer Institute, NIH; Department of Health and Human Services FX This work was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA27525, CA39229, CA15488, CA16116, and CA137140 and from the National Cancer Institute, NIH and the Department of Health and Human Services. NR 48 TC 13 Z9 14 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2014 VL 20 IS 19 BP 5041 EP 5051 DI 10.1158/1078-0432.CCR-14-0051 PG 11 WC Oncology SC Oncology GA AQ8XU UT WOS:000343123800010 PM 25107914 ER PT J AU Willey, A Anderson, RR Sakamoto, FH AF Willey, Andrea Anderson, R. Rox Sakamoto, Fernanda H. TI Temperature-Modulated Photodynamic Therapy for the Treatment of Actinic Keratosis on the Extremities: A Pilot Study SO DERMATOLOGIC SURGERY LA English DT Article ID APPLIED 5-AMINOLEVULINIC ACID; PROTOPORPHYRIN IX PRODUCTION; RENAL-TRANSPLANT RECIPIENTS; 5-PERCENT IMIQUIMOD CREAM; NORMAL MOUSE SKIN; CUTANEOUS CIRCULATION; BLOOD-FLOW; BLUE-LIGHT; FOLLOW-UP; IN-VITRO AB BACKGROUND The efficacy of photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA) for the treatment of actinic keratosis (AKs) is lower on the distal extremities compared with the head and neck areas. The strong temperature dependence of porphyrin synthesis in biologic tissue suggests that heating skin during incubation may improve the efficacy of PDT, particularly in areas where biologic temperatures are naturally lower. The aim of this study was to evaluate the efficacy and tolerability of temperature-modulated PDT for the treatment of AKs on the extremities. METHODS In this IRB-approved, single-center study, the upper or lower extremities of 20 subjects were treated with 20% ALA under occlusion, followed by 10 J/cm(2), 417-nm blue light. One of the 2 extremities treated was heated during the 1-hour incubation. Outcome measures included lesion counts, tolerability, and global improvement at baseline, 1 week, and 2 and 6 months after treatment. RESULTS The median temperatures of the heated and control sides were 38.8 degrees C and 29.4 degrees C, respectively. The median clearance for the heated side was significantly greater than the control side at 2 and 6 months (p < .0001). Typical PDT side effects were greater on the heated side compared with the control yet were well tolerated by all subjects. CONCLUSION Warming the skin during incubation of ALA seems to improve the efficacy of PDT in the treatment of AKs on the extremities and is well tolerated when heat application is controlled within the limits of safety. C1 [Willey, Andrea] Surg & Aesthet Dermatol, Sacramento, CA USA. [Willey, Andrea] Univ Calif Davis, Dept Dermatol, Sacramento, CA 95817 USA. [Anderson, R. Rox; Sakamoto, Fernanda H.] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Anderson, R. Rox; Sakamoto, Fernanda H.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Willey, A (reprint author), 2277 Fair Oaks Blvd,Suite 402, Sacramento, CA 95825 USA. EM andrea.willey@mac.com FU DUSA Pharmaceuticals, Inc. FX A. Wiley's employer received a research grant, equipment loan, and study drug from DUSA Pharmaceuticals, Inc. A. Willey is a member of the scientific advisory board for DUSA pharmaceuticals. The other authors have indicated no significant interest with commercial supporters. NR 52 TC 13 Z9 14 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD OCT PY 2014 VL 40 IS 10 BP 1094 EP 1102 DI 10.1097/01.DSS.0000452662.69539.57 PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA AQ8AE UT WOS:000343041700005 PM 25207759 ER PT J AU Phillips, LS Ratner, RE Buse, JB Kahn, SE AF Phillips, Lawrence S. Ratner, Robert E. Buse, John B. Kahn, Steven E. TI We Can Change the Natural History of Type 2 Diabetes SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; INTENSIVE INSULIN THERAPY; LIFE-STYLE INTERVENTION; PREVENTION PROGRAM OUTCOMES; RANDOMIZED CONTROLLED-TRIAL; BETA-CELL DYSFUNCTION; ALL-CAUSE MORTALITY; 10-YEAR FOLLOW-UP; GLYCEMIC CONTROL; CLINICAL INERTIA AB As diabetes develops, we currently waste the first similar to 10 years of the natural history. If we found prediabetes and early diabetes when they first presented and treated them more effectively, we could prevent or delay the progression of hyperglycemia and the development of complications. Evidence for this comes from trials where lifestyle change and/or glucose-lowering medications decreased progression from prediabetes to diabetes. After withdrawal of these interventions, there was no "catch-up"-cumulative development of diabetes in the previously treated groups remained less than in control subjects. Moreover, achieving normal glucose levels even transiently during the trials was associated with a substantial reduction in subsequent development of diabetes. These findings indicate that we can change the natural history through routine screening to find prediabetes and early diabetes, combined with management aimed to keep glucose levels as close to normal as possible, without hypoglycemia. We should also test the hypothesis with a randomized controlled trial. C1 [Phillips, Lawrence S.] Atlanta VA Med Ctr, Decatur, GA 30033 USA. [Phillips, Lawrence S.] Emory Univ Sch Med, Div Endocrinol & Metab, Dept Med, Atlanta, GA USA. [Ratner, Robert E.] Amer Diabet Assoc, Alexandria, VA USA. [Buse, John B.] Univ North Carolina Sch Med, Dept Med, Div Endocrinol & Metab, Chapel Hill, NC USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Kahn, Steven E.] Univ Washington Sch Med, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. RP Phillips, LS (reprint author), Atlanta VA Med Ctr, Decatur, GA 30033 USA. EM lawrence.phillips@emory.edu OI Kahn, Steven/0000-0001-7307-9002 FU National Institutes of Health [DK066204, UL1 RR025008]; VA award HSRD IIR [07-138]; Cystic Fibrosis Foundation [PHILLI12A0]; National Center for Advancing Translational Sciences [UL1TR000083]; U.S. Department of Veterans Affairs; ADA; [P30 DK017047] FX This work was supported in part by National Institutes of Health awards DK066204 and UL1 RR025008, VA award HSR&D IIR 07-138, and a Cystic Fibrosis Foundation award PHILLI12A0 (L.S.P.); the National Center for Advancing Translational Sciences (UL1TR000083) (J.B.B.); P30 DK017047 (S.E.K.); the U.S. Department of Veterans Affairs (L.S.P. and S.E.K.); and the ADA (R.E.R.). NR 80 TC 11 Z9 11 U1 0 U2 9 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 OCT PY 2014 VL 37 IS 10 BP 2668 EP 2676 DI 10.2337/dc14-0817 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AR4UM UT WOS:000343582400018 PM 25249668 ER PT J AU Delahanty, LM Pan, Q Jablonski, KA Aroda, VR Watson, KE Bray, GA Kahn, SE Florez, JC Perreault, L Franks, PW AF Delahanty, Linda M. Pan, Qing Jablonski, Kathleen A. Aroda, Vanita R. Watson, Karol E. Bray, George A. Kahn, Steven E. Florez, Jose C. Perreault, Leigh Franks, Paul W. CA Diabet Prevention Program Res Grp TI Effects of Weight Loss, Weight Cycling, and Weight Loss Maintenance on Diabetes Incidence and Change in Cardiometabolic Traits in the Diabetes Prevention Program SO DIABETES CARE LA English DT Article ID LIFE-STYLE INTERVENTION; RISK-FACTORS; OBESE WOMEN; HYPERTENSION; PATTERNS; DISEASE AB OBJECTIVE This study examined specific measures of weight loss in relation to incident diabetes and improvement in cardiometabolic risk factors. RESEARCH DESIGN AND METHODS This prospective, observational study analyzed nine weight measures, characterizing baseline weight, short-versus long-term weight loss, short-versus long-term weight regain, and weight cycling, within the Diabetes Prevention Program (DPP) lifestyle intervention arm (n = 1,000) for predictors of incident diabetes and improvement in cardiometabolic risk factors over 2 years. RESULTS Although weight loss in the first 6 months was protective of diabetes (hazard ratio [HR] 0.94 per kg, 95% CI 0.90, 0.98; P < 0.01) and cardiometabolic risk factors (P < 0.01), weight loss from 0 to 2 years was the strongest predictor of reduced diabetes incidence (HR 0.90 per kg, 95% CI 0.87, 0.93; P < 0.01) and cardiometabolic risk factor improvement (e. g., fasting glucose: beta = -0.57 mg/dL per kg, 95% CI 20.66, 20.48; P < 0.01). Weight cycling (defined as number of 5-lb [2.25-kg] weight cycles) ranged 0-6 times per participant and was positively associated with incident diabetes (HR 1.33, 95% CI 1.12, 1.58; P < 0.01), fasting glucose (beta = 0.91 mg/dL per cycle; P = 0.02), HOMA-IR (beta = 0.25 units per cycle; P = 0.04), and systolic blood pressure (beta = 0.94 mmHg per cycle; P = 0.01). After adjustment for baseline weight, the effect of weight cycling remained statistically significant for diabetes risk (HR 1.22, 95% CI 1.02, 1.47; P = 0.03) but not for cardiometabolic traits. CONCLUSIONS Two-year weight loss was the strongest predictor of reduced diabetes risk and improvements in cardiometabolic traits. C1 [Delahanty, Linda M.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. [Delahanty, Linda M.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Pan, Qing; Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Aroda, Vanita R.] MedStar Hlth Res Inst, Hyattsville, MD USA. [Aroda, Vanita R.] Georgetown Univ, Sch Med, Washington, DC USA. [Watson, Karol E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Bray, George A.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Perreault, Leigh] Univ Colorado, Dept Med, Div Endocrinol Metab & Diabet, Aurora, CO USA. [Franks, Paul W.] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Delahanty, LM (reprint author), Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. EM dppmail@bsc.gwu.edu OI Franks, Paul/0000-0002-0520-7604; Kahn, Steven/0000-0001-7307-9002 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) [U01-DK-048489]; NIDDK; Indian Health Service; Office of Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; Office of Research on Women's Health; American Diabetes Association; McKesson BioServices Corp.; Matthews Media Group, Inc.; Henry M. Jackson Foundation; NIH [R01-DK072014, R01-DK072041]; Department of Clinical Sciences, Lund University; Department of Nutrition, Harvard University FX The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) provided funding to the clinical centers and the coordinating center for the design and conduct of the study and the collection, management, analysis, and interpretation of the data (U01-DK-048489). The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women's Health, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also partly supported by the intramural research program of the NIDDK. LifeScan Inc., Health o meter, Hoechst Marion Roussel, Inc., Merck-Medco Managed Care, Inc., Merck and Co., Nike Sports Marketing, Slimfast Foods Co., and Quaker Oats Co. donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices Corp., Matthews Media Group, Inc., and the Henry M. Jackson Foundation provided support services under subcontract with the coordinating center. A complete list of centers, investigators, and staff can be found in the Supplementary Data online. K.A.J. (the DPP Genetics Program) has a research grant from NIH (R01-DK072014). J.C.F. has received NIH grants (R01-DK072041). P.W.F. is supported by the Department of Clinical Sciences, Lund University and the Department of Nutrition, Harvard University. P. W. F. has received speaking honoraria from academic and nonprofit organizations. NR 17 TC 15 Z9 15 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2014 VL 37 IS 10 BP 2738 EP 2745 DI 10.2337/dc14-0018 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AR4UM UT WOS:000343582400027 PM 25024396 ER PT J AU Anderson, RJ Bahn, GD Emanuele, NV Marks, JB Duckworth, WC AF Anderson, Robert J. Bahn, Gideon D. Emanuele, Nicholas V. Marks, Jennifer B. Duckworth, William C. CA VADT Study Grp TI Blood Pressure and Pulse Pressure Effects on Renal Outcomes in the Veterans Affairs Diabetes Trial (VADT) SO DIABETES CARE LA English DT Article ID CHRONIC KIDNEY-DISEASE; GLYCEMIC CONTROL; GLUCOSE CONTROL; COMPLICATIONS; MORTALITY; MELLITUS; RISK AB OBJECTIVE Blood pressure (BP) control for renal protection is essential for patients with type 2 diabetes. Our objective in this analysis of Veterans Affairs Diabetes Trial (VADT) data was to learn whether on-study systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) affected renal outcomes measured as albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). RESEARCH DESIGN AND METHODS The VADT was a prospective, randomized study of 1,791 veterans with type 2 diabetes to determine whether intensive glucose control prevented major cardiovascular events. In this post hoc study, time-varying covariate survival analyses and hazard ratios (HR) were used to determine worsening of renal outcomes. RESULTS Compared with SBP 105-129 mmHg, the risk of ACR worsening increased significantly for SBP 130-139 mmHg (HR 1.88 [95% CI 1.28-2.77]; P = 0.001) and for SBP >= 140 mmHg (2.51 [1.66-3.78]; P < 0.0001). Compared with a PP range of 40-49 mmHg, PP < 40 was associated with significantly lowered risk of worsening ACR (0.36 [0.15-0.87]; P = 0.022) and PP >= 60 with significantly increased risk (2.38 [1.58-3.59]; P < 0.0001). Analyses of BP ranges associated with eGFR worsening showed significantly increased risk with rising baseline SBP and an interaction effect between SBP >= 140 mmHg and on-study A1C. These patients were 15% more likely than those with SBP <140 mmHg to experience eGFR worsening (1.15 [1.00-1.32]; P = 0.045) for each 1% (10.9 mmol/mol) A1C increase. CONCLUSIONS SBP >= 130 mmHg and PP >60 mmHg were associated with worsening ACR. The results suggest that treatment of SBP to <130 mmHg may lessen ACR worsening. The interaction between SBP >= 140 mmHg and A1C suggests that the effect of glycemic control on reducing progression of renal disease may be greater in hypertensive patients. C1 [Anderson, Robert J.] Vet Affairs Med Ctr, Omaha, NE 68105 USA. [Bahn, Gideon D.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Cooperat Studies Program, Coordinating Ctr, Hines, IL 60141 USA. [Emanuele, Nicholas V.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. [Emanuele, Nicholas V.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Med Serv, Hines, IL 60141 USA. [Marks, Jennifer B.] Vet Affairs Med Ctr, Endocrinol Sect, Med Serv, Miami, FL 33125 USA. [Duckworth, William C.] Vet Affairs Med Ctr, Res Serv, Phoenix, AZ USA. RP Anderson, RJ (reprint author), Vet Affairs Med Ctr, Omaha, NE 68105 USA. EM robert.anderson4@va.gov FU Veterans Affairs Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development; American Diabetes Association; National Eye Institute of the National Institutes of Health FX This study was supported by the Veterans Affairs Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development. Additional support was received from the American Diabetes Association and the National Eye Institute of the National Institutes of Health. NR 24 TC 4 Z9 5 U1 0 U2 2 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 OCT PY 2014 VL 37 IS 10 BP 2782 EP 2788 DI 10.2337/dc14-0284 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AR4UM UT WOS:000343582400032 PM 25048382 ER PT J AU Lipkin, EW Schwartz, AV Anderson, AM Davis, C Johnson, KC Gregg, EW Bray, GA Berkowitz, R Peters, AL Hodges, A Lewis, C Kahn, SE AF Lipkin, Edward W. Schwartz, Ann V. Anderson, Andrea M. Davis, Cralen Johnson, Karen C. Gregg, Edward W. Bray, George A. Berkowitz, Robert Peters, Anne L. Hodges, Amelia Lewis, Cora Kahn, Steven E. CA Look AHEAD Res Grp TI The Look AHEAD Trial: Bone Loss at 4-Year Follow-up in Type 2 Diabetes SO DIABETES CARE LA English DT Article ID X-RAY ABSORPTIOMETRY; OBESE OLDER-ADULTS; LIFE-STYLE INTERVENTION; WEIGHT-LOSS; MINERAL DENSITY; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; LUMBAR SPINE; EXERCISE; ROSIGLITAZONE AB OBJECTIVE To determine whether an intensive lifestyle intervention (ILI) designed to sustain weight loss and improve physical fitness in overweight or obese persons with type 2 diabetes was associated with bone loss after 4 years of follow-up. RESEARCH DESIGN AND METHODS This randomized controlled trial of intensive weight loss compared an ILI with a diabetes support and education (DSE) group among 1,309 overweight or obese subjects. Bone mineral density was assessed at baseline and after 1 year and 4 years of intervention. RESULTS ILI was effective in producing significant weight loss (5.3% vs. 1.8% in ILI and DSE, respectively; P < 0.01) and increased fitness (6.4% vs. -0.8%) at year 4. Inmen, ILI participants had a greater rate of bone loss during the first year (-1.66% vs. -0.09% per year in ILI and DSE, respectively). Differences between groups were diminished by one-half after 4 years (-0.88% vs. -0.05% per year in ILI and DSE, respectively) but remained significant (P < 0.01). The difference in rate of hip bone loss between groups over 4 years was related to increased weight loss in ILI. Among women, the rate of bone loss did not differ between ILI and DSE after 4 years. CONCLUSIONS A 4-year weight loss intervention was significantly associated with a modest increase in bone loss at the hip in men but not in women. C1 [Lipkin, Edward W.; Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. [Lipkin, Edward W.; Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Anderson, Andrea M.; Davis, Cralen; Hodges, Amelia] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Gregg, Edward W.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. [Bray, George A.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Berkowitz, Robert] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Peters, Anne L.] Univ So Calif, Keck Sch Med, Dept Med, Div Endocrinol, Los Angeles, CA 90033 USA. [Lewis, Cora] Univ Alabama Birmingham, Dept Prevent Med, Birmingham, AL USA. RP Lipkin, EW (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. EM ewl@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU Department of Health and Human Services through National Institutes of Health [DK-57136, DK-57149, DK-56990, DK-57177, DK-57171, DK-57151, DK-57182, DK-57131, DK-57002, DK-57078, DK57154, DK-57178, DK-57219, DK-57008, DK-57135, DK-56992]; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; Johns Hopkins Medical Institutions Bayview General Clinical Research Center (GCRC) [M01-RR-02719]; Massachusetts General Hospital Mallinckrodt GCRC; Massachusetts Institute of Technology GCRC [M01-RR-01066]; University of Colorado Health Sciences Center GCRC [M01-RR-00051]; Clinical Nutrition Research Unit [P30-DK-48520]; University of Tennessee at Memphis GCRC [M01-RR-0021140]; University of Pittsburgh GCRC [M01-RR-000056]; Clinical Translational Research Center - Clinical and Translational Science Award [UL1-RR-024153]; National Institutes of Health [DK-046204]; VA Puget Sound Health Care System Medical Research Service; Department of Veterans Affairs; Frederic C. Bartter GCRC [M01-RR-01346] FX This study is supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health: DK-57136, DK-57149, DK-56990, DK-57177, DK-57171, DK-57151, DK-57182, DK-57131, DK-57002, DK-57078, DK57154, DK-57178, DK-57219, DK-57008, DK-57135, and DK-56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; and the Centers for Disease Control and Prevention. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (IHS) provided personnel, medical oversight, and use of facilities. The opinions expressed in this article are those of the authors and do not necessarily reflect the views of the IHS or other funding sources.; Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (GCRC) (M01-RR-02719), the Massachusetts General Hospital Mallinckrodt GCRC and the Massachusetts Institute of Technology GCRC (M01-RR-01066), the University of Colorado Health Sciences Center GCRC (M01-RR-00051) and Clinical Nutrition Research Unit (P30-DK-48520), the University of Tennessee at Memphis GCRC (M01-RR-0021140), the University of Pittsburgh GCRC (M01-RR-000056), the Clinical Translational Research Center funded by a Clinical and Translational Science Award (UL1-RR-024153) and a National Institutes of Health grant (DK-046204), the VA Puget Sound Health Care System Medical Research Service, the Department of Veterans Affairs, and the Frederic C. Bartter GCRC (M01-RR-01346). NR 36 TC 5 Z9 5 U1 1 U2 5 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 OCT PY 2014 VL 37 IS 10 BP 2822 EP 2829 DI 10.2337/dc14-0762 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AR4UM UT WOS:000343582400037 PM 25048381 ER PT J AU Sinner, MF Stepas, KA Moser, CB Krijthe, BP Aspelund, T Sotoodehnia, N Fontes, JD Janssens, ACJW Kronmal, RA Magnani, JW Witteman, JC Chamberlain, AM Lubitz, SA Schnabel, RB Vasan, RS Wang, TJ Agarwal, SK McManus, DD Franco, OH Yin, XY Larson, MG Burke, GL Launer, LJ Hofman, A Levy, D Gottdiener, JS Kaab, S Couper, D Harris, TB Astor, BC Ballantyne, CM Hoogeveen, RC Arai, AE Soliman, EZ Ellinor, PT Stricker, BHC Gudnason, V Heckbert, SR Pencina, MJ Benjamin, EJ Alonso, A AF Sinner, Moritz F. Stepas, Katherine A. Moser, Carlee B. Krijthe, Bouwe P. Aspelund, Thor Sotoodehnia, Nona Fontes, Joao D. Janssens, A. Cecile J. W. Kronmal, Richard A. Magnani, Jared W. Witteman, Jacqueline C. Chamberlain, Alanna M. Lubitz, Steven A. Schnabel, Renate B. Vasan, Ramachandran S. Wang, Thomas J. Agarwal, Sunil K. McManus, David D. Franco, Oscar H. Yin, Xiaoyan Larson, Martin G. Burke, Gregory L. Launer, Lenore J. Hofman, Albert Levy, Daniel Gottdiener, John S. Kaeaeb, Stefan Couper, David Harris, Tamara B. Astor, Brad C. Ballantyne, Christie M. Hoogeveen, Ron C. Arai, Andrew E. Soliman, Elsayed Z. Ellinor, Patrick T. Stricker, Bruno H. C. Gudnason, Vilmundur Heckbert, Susan R. Pencina, Michael J. Benjamin, Emelia J. Alonso, Alvaro TI B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies SO EUROPACE LA English DT Article DE Atrial fibrillation; Risk prediction; Epidemiology; Biomarker; B-type natriuretic peptide; C-reactive protein ID ASSOCIATION CONSENSUS CONFERENCE; NT-PROBNP; INFLAMMATION; MANAGEMENT; BNP; RECLASSIFICATION; DISCRIMINATION; BIOMARKERS; REDUCTION; DYSPNEA AB Aims B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information. Methods and results We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n=5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n=4467; Rotterdam Study (RS), n=3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n=1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95% confidence interval (CI), 1.56-1.76], P < 0.0001 and 1.18 (95% CI, 1.11-1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, chi(2)=17.0; CRP, chi(2)=10.5; BNP and CRP, chi(2)=13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95% CI, 0.022-0.032), a relative IDI of 41.5%, and a continuous NRI of 0.389 (95% CI, 0.322-0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS. Conclusion B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers. C1 [Sinner, Moritz F.; Kaeaeb, Stefan] Univ Munich, Univ Hosp Munich, Dept Med 1, D-81377 Munich, Germany. [Stepas, Katherine A.; Moser, Carlee B.; Yin, Xiaoyan; Pencina, Michael J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Krijthe, Bouwe P.; Janssens, A. Cecile J. W.; Witteman, Jacqueline C.; Franco, Oscar H.; Hofman, Albert; Arai, Andrew E.; Stricker, Bruno H. C.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Krijthe, Bouwe P.; Janssens, A. Cecile J. W.; Witteman, Jacqueline C.; Hofman, Albert; Stricker, Bruno H. C.] NCHA, NL-2300 RC Leiden, Netherlands. [Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, IS-201 Kopavogur, Iceland. [Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, IS-101 Reykjavik, Iceland. [Sotoodehnia, Nona] Univ Washington, Dept Med, Div Cardiol, Seattle, WA 98195 USA. [Sotoodehnia, Nona] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. [Fontes, Joao D.; Magnani, Jared W.; Vasan, Ramachandran S.; Wang, Thomas J.; McManus, David D.; Yin, Xiaoyan; Larson, Martin G.; Levy, Daniel; Benjamin, Emelia J.] NHLBI, Framingham, MA 01702 USA. [Fontes, Joao D.; Magnani, Jared W.; Vasan, Ramachandran S.; Wang, Thomas J.; McManus, David D.; Yin, Xiaoyan; Larson, Martin G.; Levy, Daniel; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA 01702 USA. [Kronmal, Richard A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Magnani, Jared W.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Chamberlain, Alanna M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Schnabel, Renate B.] Univ Heart Ctr, Dept Gen & Intervent Cardiol, D-20246 Hamburg, Germany. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Agarwal, Sunil K.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. [McManus, David D.] Univ Massachusetts, Dept Med, Worcester, MA 01605 USA. [McManus, David D.] Univ Massachusetts, Dept Quantitat Hlth Sci, Worcester, MA 01605 USA. [McManus, David D.] Worcester Polytech Inst, Dept Biomed Engn, Worcester, MA 01609 USA. [Burke, Gregory L.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Framingham, MA 01702 USA. [Gottdiener, John S.] Univ Maryland, Med Ctr, Div Cardiol, Baltimore, MD 21201 USA. [Kaeaeb, Stefan] Deutsch Zentrum Herz Kreislauferkrankungen DZHK, Munich Heart Alliance, D-80802 Munich, Germany. [Couper, David] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Astor, Brad C.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Ballantyne, Christie M.; Hoogeveen, Ron C.] Baylor Coll Med, Houston, TX 77030 USA. [Ballantyne, Christie M.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA. [Arai, Andrew E.] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA. [Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC 27157 USA. [Stricker, Bruno H. C.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Stricker, Bruno H. C.] Inspectorate Hlth Care, NL-3500 GR The Hague, Netherlands. [Stricker, Bruno H. C.] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands. [Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. RP Benjamin, EJ (reprint author), NHLBI, Framingham, MA 01702 USA. EM emelia@bu.edu; alonso@umn.edu RI Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008; Alonso, Alvaro/A-4917-2010; OI Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund, Thor/0000-0002-7998-5433; Alonso, Alvaro/0000-0002-2225-8323; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU US National Institutes of Health, Bethesda, MD [1RC1HL101056] FX This work was supported by the US National Institutes of Health, Bethesda, MD [1RC1HL101056]. Details on additional funding are available in the supplemental material. NR 37 TC 30 Z9 31 U1 1 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 EI 1532-2092 J9 EUROPACE JI Europace PD OCT PY 2014 VL 16 IS 10 BP 1426 EP 1433 DI 10.1093/europace/euu175 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AR1EL UT WOS:000343326200003 PM 25037055 ER PT J AU Ozcan, C Strom, JB Newell, JB Mansour, MC Ruskin, JN AF Ozcan, Cevher Strom, Jordan B. Newell, John B. Mansour, Moussa C. Ruskin, Jeremy N. TI Incidence and predictors of atrial fibrillation and its impact on long-term survival in patients with supraventricular arrhythmias SO EUROPACE LA English DT Article DE Atrial fibrillation; Supraventricular tachycardia; Ablation; Survival; Predictors ID NODAL REENTRANT TACHYCARDIA; FOLLOW-UP; RISK-FACTORS; CATHETER ABLATION; NATURAL-HISTORY; HEART; FLUTTER; PREVALENCE; MANAGEMENT; PATHOPHYSIOLOGY AB Aims To determine the incidence and predictors of atrial fibrillation (AF) and its impact on survival in patients with other forms of supraventricular arrhythmias (SVAs) including atrial flutter (AFL), atrial tachycardia (AT), atrioventricular reentrant (AVRT), andAV nodal reentrant tachycardia (AVNRT). We hypothesized that SVAmay increase risk of AF and concomitant AF may influence long-term survival. Methods and results All patients who underwent catheter ablation for SVA from 2000 to 2010 were included in this study. The patients were identified retrospectively and the vital status determined prospectively. Observed survival in the study cohort was compared with survival rates in the age-and sex-matched general population. The study group included 1573 patients (mean age 50.5 +/- 18 years, 47% female) with AVNRT (38.5%), AFL (29.6%), AVRT (22.6%) and AT (9.3%). The patients were followed for a mean of 35 months (median 23 months). Atrial fibrillation was documented in 424 patients (27%) with a higher incidence inmales (35 vs. 18%). Atrial fibrillationwas present in 19.6% of patients before the ablation and developed in 9.07% after ablation. Atrial fibrillation commonly occurred in patientswith AFL (57.5%), AT (27.4%), AVRT (13.5%), and AVNRT (9.7%). Older age, prolonged PR interval, dilated left atrium, low left ventricular ejection fraction and presence of AFL were independent predictors for concomitant AF. Long-term survival was worse in the presence of AF. Conclusion The incidence of AF is high in patients with other forms of SVA. The most common association is between AFL and AF. Long-term survival is decreased in those who have concomitant AF, although AF did not emerge as an independent predictor of mortality when adjusted for other covariates. C1 [Ozcan, Cevher; Strom, Jordan B.; Newell, John B.; Mansour, Moussa C.; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Inst Heart Stroke & Vasc Care, Boston, MA 02114 USA. [Ozcan, Cevher] SUNY Buffalo, Sch Med & Biomed Sci, Div Cardiovasc Med, Buffalo, NY 14260 USA. RP Ruskin, JN (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Inst Heart Stroke & Vasc Care, Boston, MA 02114 USA. EM jruskin@partners.org FU Deane Institute for Integrated Research in Atrial Fibrillation and Stroke at the Massachusetts General Hospital, Boston, MA, USA FX This work was supported in part by the Deane Institute for Integrated Research in Atrial Fibrillation and Stroke at the Massachusetts General Hospital, Boston, MA, USA. NR 32 TC 7 Z9 7 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 EI 1532-2092 J9 EUROPACE JI Europace PD OCT PY 2014 VL 16 IS 10 BP 1508 EP 1514 DI 10.1093/europace/euu129 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AR1EL UT WOS:000343326200013 PM 24906607 ER PT J AU Karnes, RJ Joniau, S Blute, ML Van Poppel, H AF Karnes, R. Jeffrey Joniau, Steven Blute, Michael L. Van Poppel, Hendrik TI Caveat Emptor SO EUROPEAN UROLOGY LA English DT Editorial Material ID ASSISTED RADICAL PROSTATECTOMY; OUTCOMES; MEN C1 [Karnes, R. Jeffrey] Mayo Clin, Rochester, MN 55905 USA. [Joniau, Steven; Van Poppel, Hendrik] Univ Hosp, Leuven, Belgium. [Blute, Michael L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Karnes, RJ (reprint author), Mayo Clin, Dept Urol, Rochester, MN 55905 USA. EM karnes.r@mayo.edu NR 10 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD OCT PY 2014 VL 66 IS 4 BP 673 EP 675 DI 10.1016/j.eururo.2014.03.012 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA AQ9GK UT WOS:000343156500019 PM 24674148 ER PT J AU Heng, DYC Wells, JC Rini, BI Beuselinck, B Lee, JL Knox, JJ Bjarnason, GA Pal, SK Kollmannsberger, CK Yuasa, T Srinivas, S Donskov, F Bamias, A Wood, LA Ernst, DS Agarwal, N Vaishampayan, UN Rha, SY Kim, JJ Choueiri, TK AF Heng, Daniel Y. C. Wells, J. Connor Rini, Brian I. Beuselinck, Benoit Lee, Jae-Lyun Knox, Jennifer J. Bjarnason, Georg A. Pal, Sumanta Kumar Kollmannsberger, Christian K. Yuasa, Takeshi Srinivas, Sandy Donskov, Frede Bamias, Aristotelis Wood, Lori A. Ernst, D. Scott Agarwal, Neeraj Vaishampayan, Ulka N. Rha, Sun Young Kim, Jenny J. Choueiri, Toni K. TI Cytoreductive Nephrectomy in Patients with Synchronous Metastases from Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium SO EUROPEAN UROLOGY LA English DT Article DE Cytoreductive nephrectomy; Metastatic renal cell carcinoma; Targeted therapy ID INTERFERON-ALPHA; TARGETED THERAPY; SURVIVAL; VALIDATION; SUNITINIB; CANCER; MODEL; ERA AB Background: The benefit of cytoreductive nephrectomy (CN) for overall survival (OS) is unclear in patients with synchronous metastatic renal cell carcinoma (mRCC) in the era of targeted therapy. Objective: To determine OS benefit of CN compared with no CN in mRCC patients treated with targeted therapies. Design, setting, and participants: Retrospective data from patients with synchronous mRCC (n = 1658) from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were used to compare 982 mRCC patients who had a CN with 676 mRCC patients who did not. Outcome measurements and statistical analysis: OS was compared and hazard ratios (HRs) adjusted for IMDC poor prognostic criteria. Results and limitations: Patients who had CN had better IMDC prognostic profiles versus those without (favorable, intermediate, or poor in 9%, 63%, and 28% vs 1%, 45%, and 54%, respectively). The median OS of patients with CN versus without CN was 20.6 versus 9.5mo (p < 0.0001). When adjusted for IMDC criteria to correct for imbalances, the HR of death was 0.60 (95% confidence interval, 0.52-0.69; p < 0.0001). Patients estimated to survive < 12 mo may receive marginal benefit from CN. Patients who have four or more of the IMDC prognostic criteria did not benefit from CN. Data were collected retrospectively. Conclusions: CN is beneficial in synchronous mRCC patients treated with targeted therapy, even after adjusting for prognostic factors. Patients with estimated survival times <12 mo or four or more IMDC prognostic factors may not benefit from CN. This information may aid in patient selection as we await results from randomized controlled trials. Patient summary: We looked at the survival outcomes of metastatic renal cell carcinoma patients who did or did not have the primary tumor removed. We found that most patients benefited from tumor removal, except for those with four or more IMDC risk factors. (C) 2014 Published by Elsevier B.V. on behalf of European Association of Urology. C1 [Heng, Daniel Y. C.; Wells, J. Connor] Tom Baker Canc Clin, Calgary, AB, Canada. [Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Beuselinck, Benoit] Univ Hosp Leuven, Leuven, Belgium. [Lee, Jae-Lyun] Asan Med Ctr, Seoul, South Korea. [Knox, Jennifer J.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Bjarnason, Georg A.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Pal, Sumanta Kumar] City Hope Comprehens Canc Cente, Duarte, CA USA. [Kollmannsberger, Christian K.] BCCA Vancouver Canc Ctr, Vancouver, BC, Canada. [Yuasa, Takeshi] Japanese Fdn Canc Res, Canc Inst Hosp, Tokyo, Japan. [Srinivas, Sandy] Stanford Med Ctr, Stanford, CA USA. [Donskov, Frede] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Bamias, Aristotelis] Univ Athens, Dept Clin Therapeut, Athens 11528, Greece. [Wood, Lori A.] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Ernst, D. Scott] London Reg Canc Ctr, London, ON N6A 4L6, Canada. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Vaishampayan, Ulka N.] Karmanos Canc Inst, Detroit, MI USA. [Rha, Sun Young] Yonsei Univ, Coll Med, Seoul, South Korea. [Kim, Jenny J.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Heng, DYC (reprint author), Univ Calgary, Tom Baker Canc Ctr, 1331 29th St NW, Calgary, AB T2N 4N2, Canada. EM daniel.heng@albertahealthservices.ca OI Bjarnason, Georg Arnold/0000-0001-6903-5357; Donskov, Frede/0000-0002-8449-863X FU GlaxoSmithKline; Pfizer; Novartis; Bayer Korea FX Daniel Y.C. Heng certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Daniel Y.C. Heng is a consultant for Pfizer, Novartis, and Bayer/Onyx. Brian A. Rini is a consultant for Pfizer, GlaxoSmithKline, Aveo, and Bayer/Onyx. He receives research funding from GlaxoSmithKline and Pfizer. Jennifer J. Knox is a consultant for Aveo and receives research funding from Pfizer. Georg A. Bjarnason is a consultant and receives research funding and honoraria from Pfizer. Christian K. Kollmannsberger is a consultant for Pfizer, Novartis, and GlaxoSmithKline. He receives honoraria and research funding from Pfizer, Novartis, and GlaxoSmithKline. Sandy Srinivas is a consultant for Pfizer, Novartis, and Genentech. Frede Donskov receives research funding from Novartis. Lori A. Wood is a consultant for Pfizer and Novartis; she receives research funding from Pfizer, Novartis, and GlaxoSmithKline. Ulka Vaishampayan receives honoraria and research funding from Pfizer, Novartis, and GlaxoSmithKline. Sun Young Rha is a consultant for Pfizer, Novartis, and GlaxoSmithKline, and receives research funding from Novartis and Bayer Korea. Toni K. Choueiri is a consultant for Aveo, Pfizer, Novartis, GlaxoSmithKline, Genentech, and Bayer/Onyx, and receives research funding from Pfizer. NR 17 TC 69 Z9 70 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD OCT PY 2014 VL 66 IS 4 BP 704 EP 710 DI 10.1016/j.eururo.2014.05.034 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AQ9GK UT WOS:000343156500026 PM 24931622 ER PT J AU Valerio, M Ahmed, HU Emberton, M Lawrentschuk, N Lazzeri, M Montironi, R Nguyen, PL Trachtenberg, J Polascik, TJ AF Valerio, Massimo Ahmed, Hashim U. Emberton, Mark Lawrentschuk, Nathan Lazzeri, Massimo Montironi, Rodolfo Nguyen, Paul L. Trachtenberg, John Polascik, Thomas J. TI The Role of Focal Therapy in the Management of Localised Prostate Cancer: A Systematic Review SO EUROPEAN UROLOGY LA English DT Review DE Brachytherapy; Cryotherapy; High-intensity focused; ultrasound; Laser therapy; Photodynamic therapy; Prostate cancer ID INTENSITY-FOCUSED ULTRASOUND; ASSISTED RADICAL PROSTATECTOMY; TUMOR VOLUME; FOLLOW-UP; PATHOLOGICAL CHARACTERISTICS; CLINICAL-SIGNIFICANCE; TRANSPERINEAL BIOPSY; ACTIVE SURVEILLANCE; PATIENT SELECTION; ABLATIVE THERAPY AB Context: The incidence of localised prostate cancer is increasing worldwide. In light of recent evidence, current, radical, whole-gland treatments for organ-confined disease have being questioned with respect to their side effects, cancer control, and cost. Focal therapy may be an effective alternative strategy. Objective: To systematically review the existing literature on baseline characteristics of the target population; preoperative evaluation to localise disease; and perioperative, functional, and disease control outcomes following focal therapy. Evidence acquisition: Medline (through PubMed), Embase, Web of Science, and Cochrane Review databases were searched from inception to 31 October 2012. In addition, registered but not yet published trials were retrieved. Studies evaluating tissue-preserving therapies in men with biopsy-proven prostate cancer in the primary or salvage setting were included. Evidence synthesis: A total of 2350 cases were treated to date across 30 studies. Most studies were retrospective with variable standards of reporting, although there was an increasing number of prospective registered trials. Focal therapy was mainly delivered to men with low and intermediate disease, although some high-risk cases were treated that had known, unilateral, significant cancer. In most of the cases, biopsy findings were correlated to specific preoperative imaging, such as multiparametric magnetic resonance imaging or Doppler ultrasound to determine eligibility. Follow-up varied between 0 and 11.1 yr. In treatmentnai "ve prostates, pad-free continence ranged from 95% to 100%, erectile function ranged from 54% to 100%, and absence of clinically significant cancer ranged from 83% to 100%. In focal salvage cases for radiotherapy failure, the same outcomes were achieved in 87.2-100%, 29-40%, and 92% of cases, respectively. Biochemical disease-free survival was reported using a number of definitions that were not validated in the focal-therapy setting. Conclusions: Our systematic review highlights that, when focal therapy is delivered with intention to treat, the perioperative, functional, and disease control outcomes are encouraging within a short-to medium-term follow-up. Focal therapy is a strategy by which the overtreatment burden of the current prostate cancer pathway could be reduced, but robust comparative effectiveness studies are now required. (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved. C1 [Valerio, Massimo; Ahmed, Hashim U.; Emberton, Mark] UCL, Div Surg & Intervent Sci, London W1P 7NN, England. [Valerio, Massimo; Ahmed, Hashim U.; Emberton, Mark] Univ Coll Hosp NHS Fdn Trust, Dept Urol, London, England. [Valerio, Massimo] Univ Vaudois, Ctr Hosp, Dept Urol, Lausanne, Switzerland. [Lawrentschuk, Nathan] Univ Melbourne, Dept Surg, Melbourne, Vic, Australia. [Lawrentschuk, Nathan] Austin Hosp, Ludwig Inst Canc Res, Melbourne, Vic 3084, Australia. [Lazzeri, Massimo] Ist Sci San Raffaele, Osped San Raffaele Turro, Dept Urol, I-20132 Milan, Italy. [Montironi, Rodolfo] Polytech Univ Marche Reg, Sch Med, United Hosp, Sect Pathol Anat, Ancona, Italy. [Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Trachtenberg, John] Univ Hlth Network, Dept Surg Oncol, Div Urol, Toronto, ON, Canada. [Trachtenberg, John] Univ Toronto, Dept Surg, Toronto, ON, Canada. [Polascik, Thomas J.] Duke Univ, Med Ctr, Dept Surg, Div Urol, Durham, NC 27710 USA. [Polascik, Thomas J.] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA. RP Valerio, M (reprint author), UCL, Div Surg & Intervent Sci, London W1P 7NN, England. EM massimo.valerio@chuv.ch OI Lazzeri, Massimo/0000-0002-4411-3715; Lawrentschuk, Nathan/0000-0001-8553-5618 FU SICPA foundation; Medical Research Council (UK); Pelican Cancer Foundation charity; Prostate Cancer UK; St Peters Trust charity; Prostate Cancer Research Centre; Wellcome Trust; National Institute of Health Research-Health Technology Assessment program; US National Institutes of Health National Cancer Institute; UK National Institute of Health Research UCLH/UCL Comprehensive Biomedical Research Centre; USHIFU; GSK; Oncura/GE Healthcare; Steba Biotech FX Massimo Valerio certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: The SICPA foundation supports the ongoing fellowship and PhD program of M. Valerio. M. Emberton and H. U. Ahmed would like to acknowledge funding from the Medical Research Council (UK), the Pelican Cancer Foundation charity, Prostate Cancer UK, St Peters Trust charity, Prostate Cancer Research Centre, the Wellcome Trust, National Institute of Health Research-Health Technology Assessment program, and the US National Institutes of Health National Cancer Institute. M. Emberton receives funding in part from the UK National Institute of Health Research UCLH/UCL Comprehensive Biomedical Research Centre. M. Emberton and H. U. Ahmed receive funding from USHIFU, GSK and Advanced Medical Diagnostics for clinical trials. M. Emberton is a paid consultant to Steba Biotech and USHIFU. Both have previously received consultancy payments from Oncura/GE Healthcare and Steba Biotech. NR 112 TC 76 Z9 77 U1 5 U2 26 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD OCT PY 2014 VL 66 IS 4 BP 732 EP 751 DI 10.1016/j.eururo.2013.05.048 PG 20 WC Urology & Nephrology SC Urology & Nephrology GA AQ9GK UT WOS:000343156500033 PM 23769825 ER PT J AU Zhang, P Brusic, V AF Zhang, Ping Brusic, Vladimir TI Mathematical modeling for novel cancer drug discovery and development SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Review DE cancer; computational models; drug discovery; mathematical modeling ID CARCINOMA IN-SITU; HETEROGENEOUS DATA SOURCES; METASTATIC BREAST-CANCER; COMPUTER-AIDED DIAGNOSIS; SYSTEMS BIOLOGY; IMMUNE-SYSTEM; TUMOR-GROWTH; CELLULAR-AUTOMATA; SOMATIC MUTATION; RISK-FACTORS AB Introduction: Mathematical modeling enables: the in silk classification of cancers, the prediction of disease outcomes, optimization of therapy, identification of promising drug targets and prediction of resistance to anticancer drugs. In silica pre-screened drug targets can be validated by a small number of carefully selected experiments. Areas covered: This review discusses the basics of mathematical modeling in cancer drug discovery and development. The topics include in silk discovery of novel molecular drug targets, optimization of immunotherapies, personalized medicine and guiding preclinical and clinical trials. Breast cancer has been used to demonstrate the applications of mathematical modeling in cancer diagnostics, the identification of high-risk population, cancer screening strategies, prediction of tumor growth and guiding cancer treatment. Expert opinion: Mathematical models are the key components of the toolkit used in the fight against cancer. The combinatorial complexity of new drugs discovery is enormous, making systematic drug discovery, by experimentation, alone difficult if not impossible. The biggest challenges include seamless integration of growing data, information and knowledge, and making them available for a multiplicity of analyses. Mathematical models are essential for bringing cancer drug discovery into the era of Omics, Big Data and personalized medicine. C1 [Zhang, Ping] CSIRO Computat Informat, Marsfield, NSW, Australia. [Brusic, Vladimir] Canc Vaccine Ctr, Dana Farber Canc Inst, Boston, MA 02215 USA. [Brusic, Vladimir] Boston Univ, Dept Comp Sci, Metropolitan Coll, Boston, MA 02215 USA. RP Brusic, V (reprint author), Canc Vaccine Ctr, Dana Farber Canc Inst, Boston, MA 02215 USA. EM vladimir_brusic@dfci.hanrard.edu NR 152 TC 6 Z9 6 U1 6 U2 47 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1746-0441 EI 1746-045X J9 EXPERT OPIN DRUG DIS JI Expert. Opin. Drug Discov. PD OCT PY 2014 VL 9 IS 10 BP 1133 EP 1150 DI 10.1517/17460441.2014.941351 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AQ8IO UT WOS:000343069400004 PM 25062617 ER PT J AU Kornblit, B Maloney, DG Storer, BE Maris, MB Vindelov, L Hari, P Langston, AA Pulsipher, MA Bethge, WA Chauncey, TR Lange, T Petersen, FB Hubel, K Woolfrey, AE Flowers, MED Storb, R Sandmaier, BM AF Kornblit, Brian Maloney, David G. Storer, Barry E. Maris, Michael B. Vindelov, Lars Hari, Parameswaran Langston, Amelia A. Pulsipher, Michael A. Bethge, Wolfgang A. Chauncey, Thomas R. Lange, Thoralf Petersen, Finn B. Huebel, Kai Woolfrey, Ann E. Flowers, Mary E. D. Storb, Rainer Sandmaier, Brenda M. TI A randomized phase II trial of tacrolimus, mycophenolate mofetil and sirolimus after non-myeloablative unrelated donor transplantation SO HAEMATOLOGICA LA English DT Article ID VERSUS-HOST-DISEASE; STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; LOW-DOSE METHOTREXATE; GVHD PROPHYLAXIS; COMPARING METHOTREXATE; CYCLOSPORINE; COMBINATION; RISK AB The study is a randomized phase II trial investigating graft-versus-host disease prophylaxis after non-myeloablative (90 mg/m(2) fludarabine and 2 Gy total body irradiation) human leukocyte antigen matched unrelated donor transplantation. Patients were randomized as follows: arm 1 - tacrolimus 180 days and mycophenolate mofetil 95 days (n=69); arm 2 - tacrolimus 150 days and mycophenolate mofetil 180 days (n=71); arm 3 - tacrolimus 150 days, mycophenolate mofetil 180 days and sirolimus 80 days (n=68). All patients had sustained engraftment. Grade II-IV acute graft-versus-host disease rates in the 3 arms were 64%, 48% and 47% at Day 150, respectively (arm 3 vs. arm 1 (hazard ratio 0.62; P=0.04). Owing to the decreased incidence of acute graft-versus-host disease, systemic steroid use was lower at Day 150 in arm 3 (32% vs. 55% in arm 1 and 49% in arm 2; overall P=0.009 by hazard ratio analysis). The Day 150 incidence of cytomegalovirus reactivation was lower in arm 3 (arm 1, 54%; arm 2, 47%; arm 3, 22%; overall P=0.002 by hazard ratio analysis). Non-relapse mortality was comparable in the three arms at two years (arm 1, 26%; arm 2, 23%; arm 3, 18%). Toxicity rates and other outcome measures were similar between the three arms. The addition of sirolimus to tacrolimus and mycophenolate mofetil is safe and associated with lower incidence of acute graft-versus-host disease and cytomegalovirus reactivation. C1 [Kornblit, Brian; Maloney, David G.; Storer, Barry E.; Woolfrey, Ann E.; Flowers, Mary E. D.; Storb, Rainer; Sandmaier, Brenda M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Maloney, David G.; Woolfrey, Ann E.; Flowers, Mary E. D.; Storb, Rainer; Sandmaier, Brenda M.] Univ Washington, Dept Med, Div Oncol, Seattle, WA 98195 USA. [Storer, Barry E.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Maris, Michael B.] Colorado Blood Canc Inst, Denver, CO USA. [Vindelov, Lars] Univ Copenhagen, Rigshosp, DK-1168 Copenhagen, Denmark. [Hari, Parameswaran] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Langston, Amelia A.] Emory Univ, Atlanta, GA 30322 USA. [Pulsipher, Michael A.] Univ Utah, Sch Med, Huntsman Canc Inst, Div Hematol & Hematol Malignancies, Salt Lake City, UT USA. [Bethge, Wolfgang A.] Univ Tubingen, Med Ctr, Tubingen, Germany. [Chauncey, Thomas R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Lange, Thoralf] Univ Leipzig, D-04109 Leipzig, Germany. [Petersen, Finn B.] LDS Hosp, Salt Lake City, UT USA. [Huebel, Kai] Univ Cologne, Cologne, Germany. RP Sandmaier, BM (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. EM bsandmai@fhcrc.org OI Hari, Parameswaran/0000-0002-8800-297X FU National Institutes of Health, Bethesda, MD [CA018029, CA015704]; Danish Cancer Society [DP08135, R56-A2960-12-S2]; Froken Amalie Jorgensens Mindelegat; Anders Hasselbalchs Fond; Lundbeck Foundation [R32-A2730]; Rigshospitalet FX Research funding was provided by the National Institutes of Health, Bethesda, MD, grants, CA018029 and CA015704. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health nor its subsidiary Institutes and Centers. BK was supported by a fellowship from the Danish Cancer Society (DP08135), Froken Amalie Jorgensens Mindelegat and Anders Hasselbalchs Fond. Research funding for LV was provided by the Danish Cancer Society (R56-A2960-12-S2), the Lundbeck Foundation (R32-A2730) and Rigshospitalet. NR 40 TC 12 Z9 12 U1 0 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD OCT 1 PY 2014 VL 99 IS 10 BP 1624 EP 1631 DI 10.3324/haematol.2014.108340 PG 8 WC Hematology SC Hematology GA AQ7ZC UT WOS:000343038500027 PM 25085357 ER PT J AU Rosen, AK Chen, Q Borzecki, AM Shin, M Itani, KMF Shwartz, M AF Rosen, Amy K. Chen, Qi Borzecki, Ann M. Shin, Marlena Itani, Kamal M. F. Shwartz, Michael TI Using Estimated True Safety Event Rates versus Flagged Safety Event Rates: Does It Change Hospital Profiling and Payment? SO HEALTH SERVICES RESEARCH LA English DT Article DE Patient safety measurement; quality of care; AHRQ Patient Safety Indicators (PSIs); hospital profiling ID POSITIVE PREDICTIVE-VALUE; INDICATOR; QUALITY; IMPACT; CARE; EXPERIENCE; VALIDITY AB Objective. To assess whether use of the AHRQ Patient Safety Indicator (PSI) composite measure versus modified composite measures leads to changes in hospital profiles and payments. Data Sources/Study Setting. Retrospective analysis of 2010 Veterans Health Administration discharge data. Study Design. We used the AHRQ PSI software (v4.2) to obtain PSI-flagged events and composite scores for all 151 hospitals in the database (n = 517,814 hospitalizations). We compared the AHRQ PSI composite to two modified composites that estimated "true safety events" from previous chart abstraction findings: one with modified numerators based on the positive predictive value (PPV) of each PSI, and one with similarly modified numerators but whose denominators were based on the expected fraction of PSI-eligible cases that remained after removing those PSIs that were present-on-admission (POA). Principal Findings. Although a small percentage (5-6 percent) of hospitals changed outlier status based on modified PSI composites, some of these changes were substantial; 30 and 19 percent of hospitals changed >= 20 ranks after adjustment for PPVs and POA flags, respectively. We estimate that 33 percent of hospitals would see a change of at least 10 percent in performance payments. Conclusions. Changes in hospital profiles and payments would be substantial for some hospitals if the PSI composite score used weights reflecting the relative prevalence of true versus flagged events. C1 [Rosen, Amy K.; Chen, Qi; Shin, Marlena; Shwartz, Michael] VA Boston Healthcare Syst, CHOIR, Boston, MA 02130 USA. [Rosen, Amy K.; Itani, Kamal M. F.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02130 USA. [Borzecki, Ann M.] Bedford VA Med Ctr, CHOIR, Bedford, MA USA. [Borzecki, Ann M.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Bedford, MA USA. [Itani, Kamal M. F.] VA Boston Healthcare Syst, Dept Surg, Boston, MA 02130 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. [Shwartz, Michael] Boston Univ, Sch Management, Dept Operat & Technol Management, Boston, MA 02215 USA. RP Rosen, AK (reprint author), VA Boston Healthcare Syst, CHOIR, 150 S Huntington Ave, Boston, MA 02130 USA. EM akrosen@bu.edu FU VA Health Services Research and Development Service [SDR 07-002] FX Joint Acknowledgment/Disclosure Statement: This research was supported by funding from the VA Health Services Research and Development Service grant number SDR 07-002 (P.I. Rosen). NR 38 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2014 VL 49 IS 5 BP 1426 EP 1445 DI 10.1111/1475-6773.12180 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AQ7OA UT WOS:000343006400003 PM 24779721 ER PT J AU Garrido, MM Kelley, AS Paris, J Roza, K Meier, DE Morrison, RS Aldridge, MD AF Garrido, Melissa M. Kelley, Amy S. Paris, Julia Roza, Katherine Meier, Diane E. Morrison, R. Sean Aldridge, Melissa D. TI Methods for Constructing and Assessing Propensity Scores SO HEALTH SERVICES RESEARCH LA English DT Article DE Observational data/quasi-experiments; administrative data uses; patient outcomes/function ID VARIABLE SELECTION; CAUSAL INFERENCE; BALANCE; MODELS; SERVICES; BIAS; CARE AB Objectives. To model the steps involved in preparing for and carrying out propensity score analyses by providing step-by-step guidance and Stata code applied to an empirical dataset. Study Design. Guidance, Stata code, and empirical examples are given to illustrate (1) the process of choosing variables to include in the propensity score; (2) balance of propensity score across treatment and comparison groups; (3) balance of covariates across treatment and comparison groups within blocks of the propensity score; (4) choice of matching and weighting strategies; (5) balance of covariates after matching or weighting the sample; and (6) interpretation of treatment effect estimates. Empirical Application. We use data from the Palliative Care for Cancer Patients (PC4C) study, a multisite observational study of the effect of inpatient palliative care on patient health outcomes and health services use, to illustrate the development and use of a propensity score. Conclusions. Propensity scores are one useful tool for accounting for observed differences between treated and comparison groups. Careful testing of propensity scores is required before using them to estimate treatment effects. C1 [Garrido, Melissa M.; Kelley, Amy S.; Morrison, R. Sean; Aldridge, Melissa D.] James J Peters VA Med Ctr, GRECC, Bronx, NY 10468 USA. [Garrido, Melissa M.; Kelley, Amy S.; Paris, Julia; Roza, Katherine; Meier, Diane E.; Morrison, R. Sean; Aldridge, Melissa D.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Meier, Diane E.] Icahn Sch Med Mt Sinai, Ctr Adv Palliat Care, New York, NY 10029 USA. [Morrison, R. Sean] Hertzberg Palliat Care Inst, Natl Palliat Care Res Ctr, New York, NY USA. RP Garrido, MM (reprint author), James J Peters VA Med Ctr, GRECC, Bronx, NY 10468 USA. EM melissa.garrido@mssm.edu FU NCI/NINR [5R01CA116227]; National Palliative Care Research Center; Department of Veterans Affairs HSRD CDA [11-201/CDP 12-255]; National Institute on Aging [1K23AG040774-01A1, K24 AG022345]; American Federation for Aging Research; Doris Duke Charitable Foundation Clinical Research Program FX Joint Acknowledgment/Disclosure Statement: This work was funded by NCI/NINR 5R01CA116227 (PI: Diane E. Meier) and partially supported by the National Palliative Care Research Center. Dr. Garrido is supported by Department of Veterans Affairs HSR&D CDA 11-201/CDP 12-255, Dr. Kelley is supported by National Institute on Aging (1K23AG040774-01A1) and the American Federation for Aging Research, Ms. Paris and Ms. Roza are supported by the Doris Duke Charitable Foundation Clinical Research Program, and Dr. Morrison is supported by a Mid-Career Investigator Award in Patient Oriented Research from the National Institute on Aging (K24 AG022345). Dr. Meier directs the Center to Advance Palliative Care, and Dr. Morrison directs the National Center for Palliative Care Research. The authors wish to thank Peter May and two anonymous reviewers for helpful comments on previous drafts of this paper. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 44 TC 59 Z9 61 U1 3 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2014 VL 49 IS 5 BP 1701 EP 1720 DI 10.1111/1475-6773.12182 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AQ7OA UT WOS:000343006400017 PM 24779867 ER PT J AU Yu, Y Triebwasser, MP Wong, EKS Schramm, EC Thomas, B Reynolds, R Mardis, ER Atkinson, JP Daly, M Raychaudhuri, S Kavanagh, D Seddon, JM AF Yu, Yi Triebwasser, Michael P. Wong, Edwin K. S. Schramm, Elizabeth C. Thomas, Brett Reynolds, Robyn Mardis, Elaine R. Atkinson, John P. Daly, Mark Raychaudhuri, Soumya Kavanagh, David Seddon, Johanna M. TI Whole-exome sequencing identifies rare, functional CFHvariants in families with macular degeneration SO HUMAN MOLECULAR GENETICS LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; COMPLEMENT FACTOR-H; HIGH-RISK; BINDING-AFFINITY; HUMAN RETINA; MUTATIONS; VARIANT; DISEASE; MEMBRANE; PROTEIN AB We sequenced the whole exome of 35 cases and 7 controls from 9 age-related macular degeneration (AMD) families in whom known common genetic risk alleles could not explain their high disease burden and/or their early-onset advanced disease. Two families harbored novel rare mutations in CFH(R53C and D90G). R53C segregates perfectly with AMD in 11 cases (heterozygous) and 1 elderly control (reference allele) (LOD = 5.07, P = 6.7 x 10(-7)). In an independent cohort, 4 out of 1676 cases but none of the 745 examined controls or 4300 NHBLI Exome Sequencing Project (ESP) samples carried the R53C mutation (P = 0.0039). In another family of six siblings, D90G similarly segregated with AMD in five cases and one control (LOD = 1.22, P = 0.009). No other sample in our large cohort or the ESP had this mutation. Functional studies demonstrated that R53C decreased the ability of FH to perform decay accelerating activity. D90G exhibited a decrease in cofactor-mediated inactivation. Both of these changes would lead to a loss of regulatory activity, resulting in excessive alternative pathway activation. This study represents an initial application of the whole-exome strategy to families with early-onset AMD. It successfully identified high impact alleles leading to clearer functional insight into AMD etiopathogenesis. C1 [Yu, Yi; Reynolds, Robyn; Seddon, Johanna M.] Tufts Med Ctr, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA 02111 USA. [Triebwasser, Michael P.; Schramm, Elizabeth C.; Atkinson, John P.] Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63110 USA. [Wong, Edwin K. S.; Kavanagh, David] Newcastle Univ, Inst Med Genet, Int Ctr Life, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Thomas, Brett; Daly, Mark] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Mardis, Elaine R.] Washington Univ, Genome Inst, St Louis, MO USA. [Daly, Mark; Raychaudhuri, Soumya] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Raychaudhuri, Soumya] Partners HealthCare Ctr Personalized Genet Med, Boston, MA USA. [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Univ Manchester, Fac Med & Human Sci, Manchester, Lancs, England. [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. [Seddon, Johanna M.] Tufts Univ, Sackler Sch Grad Med Sci, Boston, MA 02111 USA. RP Seddon, JM (reprint author), Tufts Med Ctr, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA 02111 USA. EM jseddon@tuftsmedicalcenter.org RI Wong, Edwin/B-8599-2014; Kavanagh, David/E-8498-2011 OI Kavanagh, David/0000-0003-4718-0072 FU NIH [R01-EY11309, K08AR055688, U01HG0070033, F30HL103072, R01-AI041592, U54HG00307910, U54 HL112303]; Edward N. & Della L.Thome Memorial Foundation; Doris Duke Clinical Scientist Development Award; Facility of the Rheumatic Diseases Core; NIH-Arthritis and Musculoskeletal and Skin Diseases [P30 AR48335]; Massachusetts Lions Eye Research Fund, Inc.; Foundation Fighting Blindness; Macular Vision Research Foundation; Research to Prevent Blindness Challenge Grant; American Macular Degeneration Foundation; Arnold and Mabel Beckman Initiative for Macular Research; Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine; Ruth L. Kirschstein National Research Service Award (National Heart, Lung and Blood Institute) FX This research was supported in part by NIH grants R01-EY11309 (J.M.S.), K08AR055688 (S.R.), U01HG0070033 (S.R.), F30HL103072 (M.T.), R01-AI041592 (J.P.A. and E.C.S.), U54HG00307910 (E.M.), U54 HL112303 (J.P.A.); Edward N. & Della L.Thome Memorial Foundation (J.P.A.); the Doris Duke Clinical Scientist Development Award; the Facility of the Rheumatic Diseases Core supported by NIH-Arthritis and Musculoskeletal and Skin Diseases P30 AR48335 (J.P.A.), Massachusetts Lions Eye Research Fund, Inc. (J.M.S.); the Foundation Fighting Blindness (J.M.S.); the Macular Vision Research Foundation (J.M.S.); Research to Prevent Blindness Challenge Grant to the New England Eye Center, Department of Ophthalmology, Tufts University School of Medicine; American Macular Degeneration Foundation (J.M.S.); The Arnold and Mabel Beckman Initiative for Macular Research (E.M., S.R., J.M.S.) and the Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine. D.K. is a Wellcome Intermediate Clinical Fellow. E.K.S.W. is a Medical Research Council clinical research training fellow. M.T. is a Ruth L. Kirschstein National Research Service Award recipient (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 Institutes of Health. NR 47 TC 28 Z9 29 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 1 PY 2014 VL 23 IS 19 BP 5283 EP 5293 DI 10.1093/hmg/ddu226 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AQ9OM UT WOS:000343185200022 PM 24847005 ER PT J AU Li, QY Stram, A Chen, C Kar, S Gayther, S Pharoah, P Haiman, C Stranger, B Kraft, P Freedman, ML AF Li, Qiyuan Stram, Alexander Chen, Constance Kar, Siddhartha Gayther, Simon Pharoah, Paul Haiman, Christopher Stranger, Barbara Kraft, Peter Freedman, Matthew L. TI Expression QTL-based analyses reveal candidate causal genes and loci across five tumor types SO HUMAN MOLECULAR GENETICS LA English DT Article ID PROSTATE-CANCER SUSCEPTIBILITY; GENOME-WIDE ASSOCIATION; COLORECTAL-CANCER; GENOTYPE IMPUTATION; MYC ENHANCER; RISK; CHROMATIN; BREAST; CELLS; GROWTH AB The majority of trait-associated loci discovered through genome-wide association studies are located outside of known protein coding regions. Consequently, it is difficult to ascertain the mechanism underlying these variants and to pinpoint the causal alleles. Expression quantitative trait loci (eQTLs) provide an organizing principle to address both of these issues. eQTLs are genetic loci that correlate with RNA transcript levels. Large-scale data sets such as the Cancer Genome Atlas (TCGA) provide an ideal opportunity to systematically evaluate eQTLs as they have generated multiple data types on hundreds of samples. We evaluated the determinants of gene expression (germline variants and somatic copy number and methylation) and performed cis-eQTL analyses for mRNA expression and miRNA expression in five tumor types (breast, colon, kidney, lung and prostate). We next tested 149 known cancer risk loci for eQTL effects, and observed that 42(28.2%) were significantly associated with at least one transcript. Lastly, we described a fine-mapping strategy for these 42 eQTL target gene associations based on an integrated strategy that combines the eQTL level of significance and the regulatory potential as measured by DNasel hypersensitivity. For each of the risk loci, our analyses suggested 1 to 81 candidate causal variants that may be prioritized for downstream functional analysis. In summary, our study provided a comprehensive landscape of the genetic determinants of gene expression in different tumor types and ranked the genes and loci for further functional assessment of known cancer risk loci. C1 [Li, Qiyuan; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [Li, Qiyuan] Xiamen Univ, Coll Med, Xiamen, Peoples R China. [Li, Qiyuan; Freedman, Matthew L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Stram, Alexander; Haiman, Christopher] Univ So Calif, Los Angeles, CA USA. [Chen, Constance; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kar, Siddhartha; Pharoah, Paul] Univ Cambridge, Strangeways Res Lab, Cambridge, England. [Gayther, Simon] Univ So Calif, Keck Sch Med, Dept Prevent Med, Log Angeles, CA USA. [Stranger, Barbara] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA. RP Freedman, ML (reprint author), D710A,44 Binney St, Boston, MA 02115 USA. EM freedman@broadinstitute.org OI Stranger, Barbara/0000-0001-9021-7331 FU Elucidating Loci Involved in Prostate Cancer Susceptibility ELLIPSE [U19 CA148537]; Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) project [U19 CA148065]; Fundamental Research Funds for the Central Universities [ZK10121]; GAME-ON Network; National Natural Science Foundation of China [31371289]; AAPC WG-seq grant; Mayer Foundation; H.L. Snyder Medical Foundation; Kohlberg Foundation; A. David Mazzone Awards Program; Howard Hughes Medical Institute; Claudia Adams Barr award FX This work was supported by the Elucidating Loci Involved in Prostate Cancer Susceptibility ELLIPSE (U19 CA148537) and Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) project (U19 CA148065). M.L.F., P.K. and C.A.H. on behalf of the GAME-ON Network; the National Natural Science Foundation of China (31371289) (Q.L.) the Fundamental Research Funds for the Central Universities (ZK10121) (Q.L.); AAPC WG-seq grant (C.A.H. and M.L.F.); the Mayer Foundation (M.L.F.), the H.L. Snyder Medical Foundation (M.L.F.), the Kohlberg Foundation, and the A. David Mazzone Awards Program (M.L.F.). M.L.F. was a Howard Hughes Medical Institute Physician-Scientist Early Career Awardee (www.hhmi.org) and a recipient of a 2009 Claudia Adams Barr award (www.dana-farber.org). NR 40 TC 26 Z9 27 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 1 PY 2014 VL 23 IS 19 BP 5294 EP 5302 DI 10.1093/hmg/ddu228 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AQ9OM UT WOS:000343185200023 PM 24907074 ER PT J AU Li, PL Fujimoto, K Bourguingnon, L Yukl, S Deeks, S Wong, JK AF Li, Peilin Fujimoto, Katsuya Bourguingnon, Lilly Yukl, Steven Deeks, Steven Wong, Joseph K. TI Exogenous and endogenous hyaluronic acid reduces HIV infection of CD4(+) T cells SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN-KINASE-C; SEXUAL TRANSMISSION; CD44; INHIBITOR; OPPORTUNITIES; PROLIFERATION; PROPAGATION; ACTIVATION; RECEPTORS AB Preventing mucosal transmission of HIV is critical to halting the HIV epidemic. Novel approaches to preventing mucosal transmission are needed. Hyaluronic acid (HA) is a major extracellular component of mucosa and the primary ligand for the cell surface receptor CD44. CD44 enhances HIV infection of CD4(+) T cells, but the role of HA in this process is not clear. To study this, virions were generated with CD44 (HIVCD44) or without CD44 (HIVmock). Exogenous HA reduced HIV infection of unstimulated CD4(+) T cells in a CD44-dependent manner. Conversely, hyaluronidase-mediated reduction of endogenous HA on the cell surface enhanced HIV binding to and infection of unstimulated CD4(+) T cells. Exogenous HA treatment reduced activation of protein kinase C alpha via CD44 on CD4(+) T cells during infection with HIVCD44. These results reveal new roles for HA during the interaction of HIV with CD4(+) T cells that may be relevant to mucosal HIV transmission and could be exploitable as a future strategy to prevent HIV infection. C1 [Li, Peilin; Fujimoto, Katsuya; Bourguingnon, Lilly; Yukl, Steven; Wong, Joseph K.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Li, Peilin; Yukl, Steven; Deeks, Steven; Wong, Joseph K.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. RP Li, PL (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, 4150 Clement St, San Francisco, CA 94121 USA. EM Peilin.li@ucst.edu FU National Institutes of Health [1R21AI104445-01A1, R56AI091573-01]; Department of Veterans Affairs [1 IK2 CX000520-01, 5101 BX001048] FX This work was supported by the National Institutes of Health (grants 1R21AI104445-01A1 (PL) and R56AI091573-01 (JKW)), and the Department of Veterans Affairs (1 IK2 CX000520-01 (SY) and Merit Review Award 5101 BX001048 (JKW)). NR 53 TC 4 Z9 4 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 EI 1440-1711 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD OCT PY 2014 VL 92 IS 9 BP 770 EP 780 DI 10.1038/icb.2014.50 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA AR2BI UT WOS:000343388000008 PM 24957217 ER PT J AU Rauh-Hain, JA Hinchcliff, EM Oduyebo, T Worley, MJ Andrade, CA Schorge, JO George, S Muto, MG del Carmen, MG AF Rauh-Hain, Jose Alejandro Hinchcliff, Emily M. Oduyebo, Titilope Worley, Michael J., Jr. Andrade, Carolina A. Schorge, John O. George, Suzanne Muto, Micheal G. del Carmen, Marcela G. TI Clinical Outcomes of Women With Recurrent or Persistent Uterine Leiomyosarcoma SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Uterine leiomyosarcoma; Uterine cancer ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-II TRIAL; GEMCITABINE PLUS DOCETAXEL; PROGNOSTIC FACTORS; SURGICAL RESECTION; SURVIVAL; UTERUS; PULMONARY; SARCOMAS; THERAPY AB Objectives: This study aimed to identify prognostic factors influencing the outcome of recurrent or persistent uterine leiomyosarcoma (ULMS). Methods: All patients with recurrent or persistent ULMS who underwent treatment at the participating institutions between January 2000 and December 2010 were identified from the tumor registry. The Kaplan-Meier method was used to generate overall survival data. Factors predictive of outcome were compared using the log-rank test and Cox proportional hazards model. Results: One hundred fifteen (68.8%) patients who had recurrent/persistent disease were identified, 40 (34.8%) had persistent disease, and 75 (65.2%) had a recurrence. Median follow-up time was 24.9 months. The 5-year postrelapse survival rate was 15% and was not significantly different between women with recurrent or persistent disease (16% vs 13%; P = 0.1). Variables identified affecting the 5-year postrelapse survival rate included low number of mitosis at the time of diagnosis (<25, 25% vs 5%; P = 0.002), time to relapse from original diagnosis (<= 6 vs >6 months, 8% vs 22%; P = 0.003)), and surgical treatment (17% vs 12%; P = 0.01). Age, stage, chemotherapy at time of original diagnosis or at the time of relapse, site of recurrence, and single versus multiple sites of recurrence were not associated with survival. In a multivariate Cox regression model, only low number of mitosis (hazard ratio, 0.5; 95% confidence interval, 0.3-0.8, P = 0.02) was identified as a predictor of overall survival. Conclusions: The prognosis of patients with recurrent/persistent ULMS is, in general, poor. Women who have low number of mitosis at the time of diagnosis seemed to have better postrelapse survival. C1 [Rauh-Hain, Jose Alejandro; Hinchcliff, Emily M.; Andrade, Carolina A.; Schorge, John O.; del Carmen, Marcela G.] Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Hinchcliff, Emily M.; Oduyebo, Titilope; Worley, Michael J., Jr.; Muto, Micheal G.] Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. [George, Suzanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 29 TC 1 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD OCT PY 2014 VL 24 IS 8 BP 1434 EP 1440 DI 10.1097/IGC.0000000000000221 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AQ8QX UT WOS:000343096700014 PM 25248114 ER PT J AU Lee, LJ Bu, P Feltmate, C Viswanathan, AN AF Lee, Larissa J. Bu, Paula Feltmate, Colleen Viswanathan, Akila N. TI Adjuvant Chemotherapy With External Beam Radiation Therapy for High-Grade, Node-Positive Endometrial Cancer SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Stage IIIC endometrial cancer; Node-positive endometrial cancer; High-grade endometrial cancer; Radiation therapy; Chemotherapy ID PAPILLARY SEROUS CARCINOMA; CLEAR-CELL CARCINOMAS; SURVIVAL; OUTCOMES; DIFFERENCE; PROGNOSIS; PATTERNS; FAILURE AB Objective: The objective of this study was to evaluate clinical outcomes including disease-free survival (DFS) and overall survival (OS) for women with node-positive, high-grade adenocarcinoma of the uterus. Methods: Database review identified 73 patients with International Federation of Gynecology and Obstetrics stage IIIC 1/2 grade 3 endometrial cancer diagnosed from 1995 to 2009. Study inclusion required total abdominal hysterectomy/bilateral salpingo-oophorectomy and negative chest imaging. Histologic subtypes were endometrioid (22, 30%), papillary serous (20, 27%), clear cell (9, 12%), mixed (21, 29%), and undifferentiated (1, 1%). Adjuvant treatment was chemotherapy with external beam radiation therapy (EBRT) in 55 patients (75%), EBRT alone in 14 (19%), chemotherapy in 2 (3%), and no adjuvant therapy in 2 (3%). Results: With a median follow-up of 50 months, DFS/OS rates at 5 years were 44%/53%, respectively. Intraperitoneal relapse was more common in patients with positive cytology (30% vs 6%, P = 0.02) and nonendometrioid histology (16% vs 4%, P = 0.3). By histologic subtype, 5-year DFS/OS rates were 59%/82% for grade 3 endometrioid, 25%/30% for serous, 22%/17% for clear cell, and 50%/51% for mixed histology (P = 0.1/P < 0.001). The 5-year DFS/OS rates were 56%/68% for those who received both chemotherapy and EBRT. Among patients treated with adjuvant EBRT, pelvic control was 93%. Conclusions: For node-positive, high-grade endometrial cancer, patients with endometrioid and mixed histologic subtypes had better clinical outcomes than did those with serous and clear cell cancers. Distinct patterns of relapse were observed with a greater risk of intraperitoneal failure for nonendometrioid histologic subtypes. Future studies are needed to define the optimal chemotherapy regimen and radiation fields. C1 [Lee, Larissa J.; Bu, Paula; Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lee, Larissa J.; Feltmate, Colleen; Viswanathan, Akila N.] Harvard Univ, Sch Med, Boston, MA USA. [Feltmate, Colleen] Brigham & Womens Hosp, Dept Gynecol Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lee, LJ (reprint author), Brigham Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1 L2, Boston, MA 02115 USA. EM llee@lroc.harvard.edu NR 21 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD OCT PY 2014 VL 24 IS 8 BP 1441 EP 1448 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AQ8QX UT WOS:000343096700015 PM 25207463 ER PT J AU Sandberg, MA Pearce, EN Harper, S Weigel-DiFranco, C Hart, L Rosner, B Berson, EL AF Sandberg, Michael A. Pearce, Elizabeth N. Harper, Shyana Weigel-DiFranco, Carol Hart, Lois Rosner, Bernard Berson, Eliot L. TI The Relationship of Central Foveal Thickness to Urinary Iodine Concentration in Retinitis Pigmentosa With or Without Cystoid Macular Edema SO JAMA OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; RETINAL THICKNESS; INTRAVITREAL TRIAMCINOLONE; FOOD FREQUENCY; VISUAL-ACUITY; VITAMIN-A; ACETAZOLAMIDE; BLOOD; EXCRETION; BARRIER AB IMPORTANCE Current treatments for cystoid macular edema (CME) in retinitis pigmentosa (RP) are not always effective, may lead to adverse effects, and may not restore visual acuity. The present research lays the rationale for evaluating whether an iodine supplement could reduce CME in RP. OBJECTIVE To determine whether central foveal thickness (CFT) in the presence of CME is related to dietary iodine intake inferred from urinary iodine concentration (UIC) in nonsmoking adults with RP. DESIGN, SETTING, AND PARTICIPANTS We performed a cross-sectional observational study of 212 nonsmoking patients aged 18 to 69 years referred to our institution for RP with visual acuity of no worse than 20/200 in at least 1 eye. EXPOSURE Retinitis pigmentosa with or without CME. MAIN OUTCOMES AND MEASURES With the eye as the unit of analysis, the relationship of log CFT measured by optical coherence tomography to UIC measured from multiple spot samples and represented as a 3-level classification variable (<100, 100-199, and >= 200 mu g/L), assigning greater weight to patients with more reliable UIC estimates. RESULTS Analyses were limited to 199 patients after excluding 11 who failed to return urine samples for measuring UIC and 2 outliers for UIC. Of the 199 patients, 36.2% had CME in 1 or both eyes. Although log CFT was inversely related to UIC based on findings from all eyes (P = .02), regression of log CFT on UIC separately for eyes with and without CME showed a strong inverse significant relationship for the former group (P < .001) and no significant relationship for the latter group (P = .66) as tested. For the eyes with CME, CFT ranged from a geometric mean of 267 mu m for a median UIC of less than 100 mu g/L to a geometric mean of 172 mu m for a median UIC of 200 mu g/L or greater. In contrast, we found no significant association between CME prevalence and UIC based on the entire sample as tested (odds ratio, 1.01 [95% CI, 0.38-2.67]; P = .99). CONCLUSIONS AND RELEVANCE A higher UIC in nonsmoking adults with RP was significantly associated with less central foveal swelling in eyes with CME. Additional study is required to determine whether an iodine supplement can limit or reduce the extent of CME in patients with RP. C1 [Sandberg, Michael A.; Harper, Shyana; Weigel-DiFranco, Carol; Rosner, Bernard; Berson, Eliot L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Berman Gund Lab Study Retinal Deg, Boston, MA USA. [Pearce, Elizabeth N.] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Hart, Lois] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. RP Sandberg, MA (reprint author), Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM michael_sandberg@meei.harvard.edu FU National Eye Institute [EY019767]; Massachusetts Lions Eye Research Fund, Inc; Center Grant from the Foundation Fighting Blindness FX This study was supported by grant EY019767 from the National Eye Institute; by the Massachusetts Lions Eye Research Fund, Inc; and by a Center Grant from the Foundation Fighting Blindness. NR 45 TC 2 Z9 2 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD OCT PY 2014 VL 132 IS 10 BP 1209 EP 1214 DI 10.1001/jamaophthalmol.2014.1726 PG 6 WC Ophthalmology SC Ophthalmology GA AQ8FZ UT WOS:000343061000010 PM 24993773 ER PT J AU Hassett, MJ Neville, BA Weeks, JC AF Hassett, Michael J. Neville, Bridget A. Weeks, Jane C. TI The Relationship Between Quality, Spending, and Outcomes Among Women With Breast Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID REGIONAL-VARIATIONS; COMORBIDITY INDEX; CARE; SURVIVAL; COST; PERFORMANCE; STATISTICS; INDICATORS; MORTALITY AB Background Substantial shortcomings in the quality of breast cancer (BC) care have been identified. While breast cancer is responsible for the largest share of cancer care spending, little is known about the value of care provided to US women with BC. Methods For women aged 65 to 70 years diagnosed July 1997 through December 2005 with stage 0-III BC who were continuously enrolled in fee-for-service Medicare, we evaluated performance relative to 20 measures recommending for proven therapies and seven measures recommending against unnecessary therapies. Using health care service area as the unit of analysis, we characterized quality for recommended and unnecessary therapies, median per-patient cost in the year after diagnosis for Medicare parts A and B, and five-year overall survival. We analyzed the relationships between quality, cost, and survival. All statistical tests were two-sided. Results We assessed the care provided to 15 357 women and compiled quality, cost, and outcomes data for 99 regions. The median number of patients/region was 85 (interquartile range = 47-158); the five-year overall survival was 87.5%. Part B expenditure correlated positively with measures of recommended therapy (P = .027) and negatively with measures of unnecessary therapy (P = .004). Survival did not correlate with quality or cost. Regions demonstrating lower quality for both recommended and unnecessary therapy measures exhibited higher part A expenditure. Conclusions BC patients experience wide variation in quality, cost, and survival. Process measures that assess recommended and unnecessary therapies did not correlate with survival, but did shed light on spending for related and unrelated services. Additional efforts to identify factors that impact the relationships between quality, cost, and outcomes are needed. C1 [Hassett, Michael J.; Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Hassett, Michael J.; Weeks, Jane C.] Harvard Univ, Sch Med, Boston, MA USA. [Neville, Bridget A.] Ariadne Labs, Boston, MA USA. RP Hassett, MJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, 450 Brookline Ave, Boston, MA 02215 USA. EM michael_hassett@dfci.harvard.edu FU American Society of Clinical Oncology; Susan G. Komen for the Cure FX The American Society of Clinical Oncology (Career Development Award) and Susan G. Komen for the Cure (Career Catalyst Award) provided salary support to Dr. Hassett. NR 34 TC 2 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD OCT PY 2014 VL 106 IS 10 AR dju242 DI 10.1093/jnci/dju242 PG 9 WC Oncology SC Oncology GA AQ7ZA UT WOS:000343038200003 ER PT J AU Kehl, KL Arora, NK Schrag, D Ayanian, JZ Clauser, SB Klabunde, CN Kahn, KL Fletcher, RH Keating, NL AF Kehl, Kenneth L. Arora, Neeraj K. Schrag, Deborah Ayanian, John Z. Clauser, Steven B. Klabunde, Carrie N. Kahn, Katherine L. Fletcher, Robert H. Keating, Nancy L. TI Discussions About Clinical Trials Among Patients With Newly Diagnosed Lung and Colorectal Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CARE OUTCOMES RESEARCH; AGE-BASED DISPARITIES; DECISION-MAKING; BREAST-CANCER; PARTICIPATION; ENROLLMENT; OLDER; COMMUNICATION; PREFERENCES; EXPERIENCE AB Background Clinical trials are essential to establish the effectiveness of new cancer therapies, but less than 5% of adults with cancer enroll in trials. In addition to ineligibility or lack of available trials, barriers to enrollment may include limited patient awareness about the option of participation. Methods We surveyed a multiregional cohort of patients with lung or colorectal cancer (or their surrogates) three to six months after diagnosis. We assessed whether respondents reported learning that clinical trial participation might be an option, and, if so, with whom they discussed trials. We used logistic regression to assess the association of patient characteristics with discussing trial participation and enrolling in trials. All statistical tests were two-sided. Results Of 7887 respondents, 1114 (14.1%) reported discussing the possibility of clinical trial participation; most learned about trials from their physicians, and 287 patients (3.6% of all patients, 25.8% of trial discussants) enrolled. Among 2173 patients who received chemotherapy for advanced (stage III/IV lung or stage IV colorectal) cancer, 25.7% discussed trials, and 7.6% (29.5% of trial discussants) enrolled. Discussions were less frequent among older patients, African American or Asian vs white patients, and those with lower incomes and more comorbidity. Enrollment was higher among patients reporting shared vs physician-driven decisions (all P < .05). Conclusions In this population-based cohort, only 14% of patients discussed participation in clinical trials. Discussions were more frequent among advanced cancer patients but were still reported by a minority of patients. Strategies to expand access to trials and facilitate patient-provider communication about participation may accelerate development of better cancer therapeutics. C1 [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Arora, Neeraj K.; Clauser, Steven B.; Klabunde, Carrie N.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Schrag, Deborah] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Ayanian, John Z.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. [Fletcher, Robert H.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02115 USA. [Ayanian, John Z.; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU National Cancer Institute (NCI) (Dana Farber Cancer Institute) [U01 CA093344]; NCI (Dana Farber Cancer Institute/Cancer Research Network) [U01 CA093332]; NCI (Harvard Medical School/Northern California Cancer Center) [U01 CA093324]; NCI (RAND/UCLA) [U01 CA093348]; NCI (University of Alabama at Birmingham) [U01 CA093329]; NCI (University of Iowa) [U01 CA093339]; NCI (University of North Carolina) [U01 CA093326]; Department of Veterans Affairs [CRS 02-164]; [1R01CA164021-01A1] FX This work of the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium was supported by grants from the National Cancer Institute (NCI) to the Statistical Coordinating Center (Dana Farber Cancer Institute U01 CA093344) and the NCI-supported Primary Data Collection and Research Centers (Dana Farber Cancer Institute/Cancer Research Network U01 CA093332, Harvard Medical School/Northern California Cancer Center U01 CA093324, RAND/UCLA U01 CA093348, University of Alabama at Birmingham U01 CA093329, University of Iowa U01 CA093339, University of North Carolina U01 CA093326) and by a Department of Veterans Affairs grant to the Durham VA Medical Center CRS 02-164. Drs. Keating and Schrag were also supported by 1R01CA164021-01A1. NR 34 TC 5 Z9 5 U1 5 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD OCT PY 2014 VL 106 IS 10 AR dju216 DI 10.1093/jnci/dju216 PG 9 WC Oncology SC Oncology GA AQ7ZA UT WOS:000343038200001 ER PT J AU Waldron, L Riester, M Birrer, M AF Waldron, Levi Riester, Markus Birrer, Michael TI Molecular Subtypes of High-Grade Serous Ovarian Cancer: The Holy Grail? SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID DISTANT RECURRENCE; ENDOCRINE THERAPY; PAM50 RISK; CARCINOMA; SCORE C1 [Waldron, Levi] CUNY Hunter Coll, Sch Publ Hlth, New York, NY 10021 USA. [Riester, Markus] Novartis Inst BioMed Res, Cambridge, MA USA. [Birrer, Michael] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. RP Birrer, M (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM mbirrer@partners.org OI Waldron, Levi/0000-0003-2725-0694 NR 16 TC 1 Z9 1 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD OCT PY 2014 VL 106 IS 10 AR dju297 DI 10.1093/jnci/dju297 PG 2 WC Oncology SC Oncology GA AQ7ZA UT WOS:000343038200025 ER PT J AU Camargo, CA Ganmaa, D Sidbury, R Erdenedelger, K Radnaakhand, N Khandsuren, B AF Camargo, Carlos A., Jr. Ganmaa, D. Sidbury, Robert Erdenedelger, Kh. Radnaakhand, N. Khandsuren, B. TI Randomized trial of vitamin D supplementation for winter-related atopic dermatitis in children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Randomized controlled trial; vitamin D; nutritional supplement; atopic dermatitis; winter; children; Mongolia ID SERUM 25-HYDROXYVITAMIN D; ANTIMICROBIAL PEPTIDE EXPRESSION; ECZEMA PREVALENCE; ALLERGIC DISEASE; UNITED-STATES; SEVERITY; SCHOOLCHILDREN; INFANTS; LESIONS; HEALTH AB Background: Epidemiologic and preclinical data, and a small randomized trial in Boston, suggest that vitamin D supplementation may improve winter-related atopic dermatitis (AD). Objective: To determine the effect of vitamin D supplementation on winter-related AD. Methods: We performed a randomized, double-blind, placebo-controlled trial of Mongolian children with winter-related AD (clinicaltrials.gov identifier: NCT00879424). Baseline eligibility included age 2 to 17 years, AD score 10 to 72 using the Eczema Area and Severity Index (EASI), and winter-related AD (eg, history of AD worsening during the fall-to-winter transition). Subjects were enrolled in Ulaanbaatar during winter and randomly assigned to oral cholecalciferol (1000 IU/day) versus placebo for 1 month. All children and parents received emollient and patient education about AD and basic skin care. The main outcomes were changes in EASI score and in Investigator's Global Assessment. Results: The 107 enrolled children had a mean age of 9 years (SD 5), and 59% were male. Their median age of AD onset was 3 months (interquartile range 2 months to 1 year) and mean EASI score at baseline 21 (SD 9). One-month follow-up data were available for 104 (97%) children. Compared with placebo, vitamin D supplementation for 1 month produced a clinically and statistically significant improvement in EASI score (adjusted mean change: -6.5 vs -3.3, respectively; P = .04). Moreover, change in Investigator's Global Assessment favored vitamin D over placebo (P = .03). There were no adverse effects in either group. Conclusion: Vitamin D supplementation improved winter-related AD among Mongolian children, a population likely to have vitamin D deficiency in winter. C1 [Camargo, Carlos A., Jr.; Ganmaa, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Camargo, Carlos A., Jr.; Ganmaa, D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Ganmaa, D.; Erdenedelger, Kh.; Radnaakhand, N.; Khandsuren, B.] Hlth Sci Univ Mongolia, Ulaanbaatar, Mongol Peo Rep. [Erdenedelger, Kh.; Khandsuren, B.] Natl Dermatol Ctr, Ulaanbaatar, Mongol Peo Rep. [Sidbury, Robert] Seattle Childrens Hosp, Seattle, WA USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org FU Massachusetts General Hospital in Boston FX This trial was supported by Massachusetts General Hospital in Boston. Study agents and packaging were provided by Ddrops Company (Toronto, Ontario, Canada). Neither sponsor had any role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; nor in the preparation, review, or approval of the manuscript. NR 40 TC 36 Z9 37 U1 1 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 2014 VL 134 IS 4 BP 831 EP U420 DI 10.1016/j.jaci.2014.08.002 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA AQ9GC UT WOS:000343155700008 PM 25282565 ER PT J AU Dvorak, CC Hassan, A Slatter, MA Honig, M Lankester, AC Buckley, RH Pulsipher, MA Davis, JH Gungor, T Gabriel, M Bleesing, JH Bunin, N Sedlacek, P Connell, JA Crawford, DF Notarangelo, LD Pai, SY Hassid, J Veys, P Gennery, AR Cowan, MJ AF Dvorak, Christopher C. Hassan, Amel Slatter, Mary A. Hoenig, Manfred Lankester, Arjan C. Buckley, Rebecca H. Pulsipher, Michael A. Davis, Jeffrey H. Guengoer, Tayfun Gabriel, Melissa Bleesing, Jacob H. Bunin, Nancy Sedlacek, Petr Connell, James A. Crawford, David F. Notarangelo, Luigi D. Pai, Sung-Yun Hassid, Jake Veys, Paul Gennery, Andrew R. Cowan, Morton J. TI Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Severe combined immunodeficiency; hematopoietic cell transplantation; sibling donors; unrelated donors; umbilical cord blood; conditioning; serotherapy ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; COMBINED IMMUNE-DEFICIENCY; CORD BLOOD; B-CELLS; RECONSTITUTION; CHILDREN; ENGRAFTMENT; EXPERIENCE; CLEARANCE AB Background: Patients with severe combined immunodeficiency disease who have matched sibling donors (MSDs) can proceed to hematopoietic cell transplantation (HCT) without conditioning chemotherapy. Objective: We sought to determine whether the results of HCT without chemotherapy-based conditioning from matched unrelated donors (URDs), either from volunteer adults or umbilical cord blood, are comparable with those from MSDs. Methods: We performed a multicenter survey of severe combined immunodeficiency transplantation centers in North America, Europe, and Australia to compile retrospective data on patients who have undergone unconditioned HCT from either URDs (n = 37) or MSDs (n = 66). Results: Most patients undergoing URD HCT (92%) achieved donor T-cell engraftment compared with 97% for those with MSDs; however, estimated 5-year overall and event-free survival were worse for URD recipients (71% and 60%, respectively) compared with MSD recipients (92% and 89%, respectively; P < .01 for both). URD recipients who received pre-HCT serotherapy had similar 5-year overall survival (100%) to MSD recipients. The incidences of grade II to IV acute and chronic graft-versus-host disease were higher in URD (50% and 39%, respectively) compared with MSD (22% and 5%, respectively) recipients (P < .01 for both). In the surviving patients there was no difference in T-cell reconstitution at the last follow-up between the URD and MSD recipients; however, MSD recipients were more likely to achieve B-cell reconstitution (72% vs 17%, P < .001). Conclusion: Unconditioned URD HCT achieves excellent rates of donor T-cell engraftment similar to that seen in MSD recipients, and reconstitution rates are adequate. However, only a minority will have myeloid and B-cell reconstitution, and attention must be paid to graft-versus-host disease prophylaxis. This approach might be safer in children ineligible for intense regimens to spare the potential complications of chemotherapy. C1 [Dvorak, Christopher C.; Hassid, Jake; Cowan, Morton J.] Univ Calif San Francisco, Benioff Childrens Hosp, Div Pediat Allergy Immunol & Blood & Marrow Trans, San Francisco, CA 94143 USA. [Hassan, Amel; Veys, Paul] UCL Inst Child Hlth, Mol Immunol Unit, Ctr Immunodeficiency, London, England. [Slatter, Mary A.; Gennery, Andrew R.] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Hoenig, Manfred] Univ Med Ctr, Dept Pediat, Ulm, Germany. [Lankester, Arjan C.] Leiden Univ, Med Ctr, Dept Pediat, NL-2300 RA Leiden, Netherlands. [Buckley, Rebecca H.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27706 USA. [Buckley, Rebecca H.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27706 USA. [Pulsipher, Michael A.] Univ Utah, Sch Med, Div Hematol & Hematol Malignancies, Primary Childrens Hosp,Hunstman Canc Inst, Salt Lake City, UT USA. [Davis, Jeffrey H.] British Columbia Childrens Hosp, Hematol Oncol BMT Program, Vancouver, WA USA. [Guengoer, Tayfun] Univ Childrens Hosp, Stem Cell Transplantat Dept, Zurich, Switzerland. [Gabriel, Melissa] Childrens Hosp Westmead, Dept Oncol, Sydney, NSW, Australia. [Bleesing, Jacob H.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. [Bunin, Nancy] Childrens Hosp Philadelphia, Dept Pediat, Div Oncol, Philadelphia, PA 19104 USA. [Sedlacek, Petr] Teaching Hosp Motol, Dept Pediat Hematol & Oncol, Prague, Czech Republic. [Connell, James A.] Univ Michigan, Div Pediat Hematol Oncol, Ann Arbor, MI 48109 USA. [Crawford, David F.] Univ Oklahoma, Dept Pediat, Oklahoma City, OK USA. [Notarangelo, Luigi D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Notarangelo, Luigi D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Boston, MA USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Boston Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Dvorak, CC (reprint author), Univ Calif San Francisco, Benioff Childrens Hosp, Div Pediat Allergy Immunol & Blood & Marrow Trans, 505 Parnassus Ave,M 659, San Francisco, CA 94143 USA. EM dvorakc@peds.ucsf.edu RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 FU National Institute of Allergy and Infectious Diseases [1U54AI082973]; NIH Office of Rare Diseases Research, National Center for Advancing Translational Sciences FX Data collection for this study was facilitated in part through the CIBMTR (U24-CA76518; principal investigator: M. M. Horowitz) and the Primary Immune Deficiency Treatment Consortium (PIDTC) Annual Scientific Workshop (R13 AI094943). The PIDTC is a part of the National Institutes of Health Rare Diseases Clinical Research Network with the DMCC at the University of South Florida. Funding and/or programmatic support for this project has been provided by grant no. 1U54AI082973 from the National Institute of Allergy and Infectious Diseases and the NIH Office of Rare Diseases Research, National Center for Advancing Translational Sciences. The views expressed are those of the authors and do not represent the position of the NIAID, ORDR/NCATS, NIH, or the US Government. NR 37 TC 17 Z9 17 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 OCT PY 2014 VL 134 IS 4 BP 935 EP U263 DI 10.1016/j.jaci.2014.06.021 PG 24 WC Allergy; Immunology SC Allergy; Immunology GA AQ9GC UT WOS:000343155700023 PM 25109802 ER PT J AU Rudders, SA Arias, SA Camargo, CA AF Rudders, Susan A. Arias, Sarah A. Camargo, Carlos A., Jr. TI Trends in hospitalizations for food-induced anaphylaxis in US children, 2000-2009 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID EMERGENCY-DEPARTMENT VISITS; UNITED-STATES; ALLERGY C1 [Rudders, Susan A.] Brown Univ, Rhode Isl Hosp, Alpert Sch Med, Dept Pediat,Div Asthma & Allergy, Providence, RI 02912 USA. [Arias, Sarah A.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. RP Rudders, SA (reprint author), Brown Univ, Rhode Isl Hosp, Alpert Sch Med, Dept Pediat,Div Asthma & Allergy, Providence, RI 02912 USA. EM srudders@lifespan.org OI Arias, Sarah/0000-0003-1832-8824 NR 10 TC 15 Z9 15 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 2014 VL 134 IS 4 BP 960 EP 962 DI 10.1016/j.jaci.2014.06.018 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA AQ9GC UT WOS:000343155700027 PM 25109801 ER PT J AU Hedayat, M Massaad, MJ Lee, YN Conley, ME Orange, JS Ohsumi, TK Al-Herz, W Notarangelo, LD Geha, RS Chou, J AF Hedayat, Mona Massaad, Michel J. Lee, Yu Nee Conley, Mary Ellen Orange, Jordan S. Ohsumi, Toshiro K. Al-Herz, Waleed Notarangelo, Luigi D. Geha, Raif S. Chou, Janet TI Lessons in gene hunting: A RAG1 mutation presenting with agammaglobulinemia and absence of B cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID SEVERE COMBINED IMMUNODEFICIENCY; RECOMBINATION; IGM C1 [Hedayat, Mona; Massaad, Michel J.; Lee, Yu Nee; Notarangelo, Luigi D.; Geha, Raif S.; Chou, Janet] Harvard Univ, Sch Med, Childrens Hosp, Div Immunol, Boston, MA 02163 USA. [Hedayat, Mona; Massaad, Michel J.; Lee, Yu Nee; Notarangelo, Luigi D.; Geha, Raif S.; Chou, Janet] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Conley, Mary Ellen] Rockefeller Univ, St Giles Lab Human Genet Infect Dis, New York, NY 10021 USA. [Orange, Jordan S.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Ohsumi, Toshiro K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Al-Herz, Waleed] Kuwait Univ, Dept Pediat, Fac Med, Kuwait, Kuwait. RP Hedayat, M (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Immunol, Boston, MA 02163 USA. EM Janet.Chou@childrens.harvard.edu RI Notarangelo, Luigi/F-9718-2016; OI Notarangelo, Luigi/0000-0002-8335-0262; orange, jordan/0000-0001-7117-7725 FU NIAID NIH HHS [AI-094017, P01 AI076210, P01AI-076210, R03 AI094017] NR 12 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 2014 VL 134 IS 4 BP 983 EP 985 DI 10.1016/j.jaci.2014.04.037 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA AQ9GC UT WOS:000343155700036 PM 24985406 ER PT J AU Pfefferle, KJ Shemory, ST Dilisio, MF Fening, SD Gradisar, IM AF Pfefferle, Kiel J. Shemory, Scott T. Dilisio, Matthew F. Fening, Stephen D. Gradisar, Ian M. TI Risk Factors for Manipulation After Total Knee Arthroplasty: A Pooled Electronic Health Record Database Study SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total knee arthroplasty; arthrofibrosis; manipulation under anesthesia; knee stiffness; stiffness; manipulation ID TOTAL HIP; STIFFNESS; MOTION; REPLACEMENT; RANGE; MANAGEMENT; REVISION; PREVALENCE AB A commercially available software platform, Explorys (Explorys, Inc., Cleveland, OH), was used to mine a pooled electronic healthcare database consisting of the medical records of more than 27 million patients. A total of 229,420 patients had undergone a total knee arthroplasty; 3470 (1.51%) patients were identified to have undergone manipulation under anesthesia. Individual risk factors of being female, African American race, age less than 60, BMI >30 and nicotine dependence were determined to have relative risk of 1.25, 2.20, 3.46, 1.33 and 1.32 respectively. Depressive disorder, diabetes mellitus, opioid abuse/dependence and rheumatoid arthritis were not significant risk factors. African Americans under the age of 60 at time of TKA had the greatest incidence of MUA (5.17%) and relative risk of 3.73 (CI: 3.36, 4.13). (C) 2014 Elsevier Inc. All rights reserved. C1 [Pfefferle, Kiel J.; Shemory, Scott T.; Fening, Stephen D.] Summa Hlth Syst, Dept Orthopaed Surg, Akron, OH 44310 USA. [Dilisio, Matthew F.] Massachusetts Gen Hosp, Harvard Orthopaed Surg, Boston, MA 02114 USA. [Fening, Stephen D.] Austen BioInnovat Inst, Akron, OH USA. [Gradisar, Ian M.] Crystal Clin Orthoped Ctr, Akron, OH USA. RP Pfefferle, KJ (reprint author), Summa Hlth Syst, Dept Orthopaed Surg, 444 N Main St, Akron, OH 44310 USA. NR 29 TC 9 Z9 9 U1 1 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 2014 VL 29 IS 10 BP 2036 EP 2038 DI 10.1016/j.arth.2014.05.001 PG 3 WC Orthopedics SC Orthopedics GA AQ9HF UT WOS:000343159700029 PM 24927868 ER PT J AU Bengali, R Wellens, HJJ Jiang, YD AF Bengali, Raheel Wellens, Hein J. J. Jiang, Yandong TI Perioperative Management of the Wolff-Parkinson-White Syndrome SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Review DE Wolff-Parkinson-White; WPW; perioperative management; arrhythmia; diagnosis and treatment ID WIDE QRS COMPLEX; ACCESSORY ATRIOVENTRICULAR PATHWAYS; ALFENTANIL-MIDAZOLAM ANESTHESIA; SINOATRIAL NODE FUNCTION; BUNDLE-BRANCH BLOCK; SUPRAVENTRICULAR TACHYCARDIA; ATRIAL-FIBRILLATION; CARDIAC-ARRHYTHMIAS; CATHETER ABLATION; VENTRICULAR-TACHYCARDIA C1 [Bengali, Raheel; Jiang, Yandong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Wellens, Hein J. J.] Univ Maastricht, Maastricht, Netherlands. RP Bengali, R (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 422, Boston, MA 02114 USA. EM rbengali@partners.org NR 80 TC 4 Z9 4 U1 2 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-0770 EI 1532-8422 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD OCT PY 2014 VL 28 IS 5 BP 1375 EP 1386 DI 10.1053/j.jvca.2014.02.003 PG 12 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA AQ9PT UT WOS:000343188500033 PM 25027102 ER PT J AU Wierman, ME Arlt, W Basson, R Davis, SR Miller, KK Murad, MH Rosner, W Santoro, N AF Wierman, Margaret E. Arlt, Wiebke Basson, Rosemary Davis, Susan R. Miller, Karen K. Murad, Mohammad H. Rosner, William Santoro, Nanette TI Androgen Therapy in Women: A Reappraisal: An Endocrine Society Clinical Practice Guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HYPOACTIVE SEXUAL DESIRE; BREAST-CANCER RISK; BONE-MINERAL DENSITY; SURGICALLY MENOPAUSAL WOMEN; TANDEM MASS-SPECTROMETRY; POLYCYSTIC-OVARY-SYNDROME; HORMONE-BINDING GLOBULIN; PLACEBO-CONTROLLED TRIAL; VIRUS-INFECTED WOMEN; QUALITY-OF-LIFE AB Objective: To update practice guidelines for the therapeutic use of androgens in women. Participants: A Task Force appointed by the Endocrine Society, American Congress of Obestricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM), European Society of Endocrinology (ESE), and International Menopause Society (IMS) consisting of six experts, a methodologist, and a medical writer. Evidence: The Task Force commissioned two systematic reviews of published data and considered several other existing meta-analyses and trials. The GRADE methodology was used; the strength of a recommendation is indicated by a number "1" (strong recommendation, we recommend) or "2" (weak recommendation, we suggest). Consensus Process: Multiple e-mail communications and conference calls determined consensus. Committees of the Endocrine Society, ASRM, ACOG, ESE, and IMS reviewed and commented on the drafts of the guidelines. Conclusions: We continue to recommend against making a diagnosis of androgen deficiency syndrome in healthy women because there is a lack of a well-defined syndrome, and data correlating androgen levels with specific signs or symptoms are unavailable. We recommend against the general use of T for the following indications: infertility; sexual dysfunction other than hypoactive sexual desire disorder; cognitive, cardiovascular, metabolic, or bone health; or general well-being. We recommend against the routine use of dehydroepiandrosterone due to limited data concerning its effectiveness and safety in normal women or those with adrenal insufficiency. We recommend against the routine prescription of Tor dehydroepiandrosterone for the treatment of women with low androgen levels due to hypopituitarism, adrenal insufficiency, surgical menopause, pharmacological glucocorticoid administration, or other conditions associated with low androgen levels because there are limited data supporting improvement in signs and symptoms with therapy and no long-term studies of risk. Evidence supports the short-term efficacy and safety of high physiological doses of T treatment of postmenopausal women with sexual dysfunction due to hypoactive sexual desire disorder. Importantly, endogenous T levels did not predict response to therapy. At present, physiological T preparations for use in women are not available in many countries including the United States, and long-term safety data are lacking. We recommend that any woman receiving T therapy be monitored for signs and symptoms of androgen excess. We outline areas for future research. Ongoing improvement in androgen assays will allow a redefinition of normal ranges across the lifespan; this may help to clarify the impact of varying concentrations of plasma androgens on the biology, physiology, and psychology in women and lead to indications for therapeutic interventions. C1 [Wierman, Margaret E.] Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA. [Wierman, Margaret E.] Vet Affairs Res Serv, Denver, CO 80220 USA. [Arlt, Wiebke] Univ Birmingham, Sch Clin & Expt Med, Ctr Endocrinol Diabet & Metab, Birmingham B15 2TT, W Midlands, England. [Basson, Rosemary] Univ British Columbia, Dept Psychiat & OBGYN, Vancouver, BC V6T 1Z4, Canada. [Basson, Rosemary] Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada. [Davis, Susan R.] Monash Univ, Sch Publ Hlth & Prevent Med, Womens Hlth Res Program, Melbourne, Vic 3004, Australia. [Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Murad, Mohammad H.] Mayo Clin, Rochester, MN 55905 USA. [Rosner, William] Columbia Univ, Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY 10032 USA. [Santoro, Nanette] Univ Colorado, Sch Med, Aurora, CO 80045 USA. RP Wierman, ME (reprint author), Endocrine Soc, 2055 L St NW,Suite 600, Washington, DC 20036 USA. EM govt-prof@endocrine.org RI Arlt, Wiebke/B-6310-2009; Davis, Susan/A-3111-2009; OI Arlt, Wiebke/0000-0001-5106-9719; Davis, Susan R/0000-0002-2955-0415 FU NIH FX Margaret E. Wierman, MD, Chair-Financial or Business/Organizational Interests: none declared; Significant Financial Interest or Leadership Position: Vice President Clinical Scientist, The Endocrine Society. Wiebke Arlt, MD-Financial or Business/Organizational Interests: none declared; Significant Financial Interest or Leadership position: none declared. Rosemary Basson, PhD-Financial or Business/Organizational Interests: none declared; Significant Financial Interest or Leadership Position: Director, University of British Columbia Sexual Medicine, UBC Department of Psychiatry. Susan R. Davis, MBBS PhD-Financial or Business/Organizational Interests: none declared; Significant Financial Interest or Leadership Position: Board Member, the International Menopause Society. Karen K. Miller, MD-Financial or Business/Organizational Interests: NIH support for studies of androgens in women; Lawley Pharmaceuticals is providing Androfeme creme and matching placebo for an NIH-funded study; Significant Financial Interest or Leadership Position: none declared. Mohammed H. Murad, MD*-Financial or Business/Organizational Interests: Knowledge and Evaluation Research Unit (Mayo Clinic); Significant Financial Interest or Leadership Position: none declared. William Rosner, MD-Financial or Business/Organizational Interests: none declared; Significant Financial Interest or Leadership Position: none declared. Nanette Santoro, MD-Financial or Business/Organizational Interests: none declared; Significant Financial Interest or Leadership Position: none declared. NR 222 TC 43 Z9 44 U1 2 U2 22 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2014 VL 99 IS 10 BP 3489 EP 3510 DI 10.1210/jc.2014-2260 PG 22 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AR2NC UT WOS:000343423300044 PM 25279570 ER PT J AU Bilezikian, JP Brandi, ML Eastell, R Silverberg, SJ Udelsman, R Marcocci, C Potts, JT AF Bilezikian, John P. Brandi, Maria Luisa Eastell, Richard Silverberg, Shonni J. Udelsman, Robert Marcocci, Claudio Potts, John T., Jr. TI Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Fourth International Workshop SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article AB Objective: Asymptomatic primary hyperparathyroidism (PHPT) is routinely encountered in clinical practices of endocrinology throughout the world. This report distills an update of current information about diagnostics, clinical features, and management of this disease into a set of revised guidelines. Participants: Participants, representing an international constituency, with interest and expertise in various facets of asymptomatic PHPT constituted four Workshop Panels that developed key questions to be addressed. They then convened in an open 3-day conference September 19-21, 2013, in Florence, Italy, when a series of presentations and discussions addressed these questions. A smaller subcommittee, the Expert Panel, then met in closed session to reach an evidence-based consensus on how to address the questions and data that were aired in the open forum. Evidence: Preceding the conference, each question was addressed by a relevant, extensive literature search. All presentations and deliberations of the Workshop Panels and the Expert Panel were based upon the latest information gleaned from this literature search. Consensus Process: The expert panel considered all the evidence provided by the individual Workshop Panels and then came to consensus. Conclusion: In view of new findings since the last International Workshop on the Management of Asymptomatic PHPT, guidelines for management have been revised. The revised guidelines include: 1) recommendations for more extensive evaluation of the skeletal and renal systems; 2) skeletal and/or renal involvement as determined by further evaluation to become part of the guidelines for surgery; and 3) more specific guidelines for monitoring those who do not meet guidelines for parathyroid surgery. These guidelines should help endocrinologists and surgeons caring for patients with PHPT. A blueprint for future research is proposed to foster additional investigation into issues that remain uncertain or controversial. C1 [Bilezikian, John P.; Silverberg, Shonni J.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Brandi, Maria Luisa] Univ Florence, I-50121 Florence, Italy. [Eastell, Richard] Univ Sheffield, Sheffield S5 7AU, S Yorkshire, England. [Udelsman, Robert] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Marcocci, Claudio] Univ Pisa, I-56124 Pisa, Italy. [Potts, John T., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bilezikian, JP (reprint author), Coll Phys & Surg, Dept Med, 630 W 168th St, New York, NY 10032 USA. EM jpb2@columbia.edu FU NIDDK NIH HHS [K24 DK074457, R01 DK032333] NR 11 TC 132 Z9 135 U1 3 U2 11 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2014 VL 99 IS 10 BP 3561 EP 3569 DI 10.1210/jc.2014-1413 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AR2NC UT WOS:000343423300054 PM 25162665 ER PT J AU Marcocci, C Bollerslev, J Khan, AA Shoback, DM AF Marcocci, Claudio Bollerslev, Jens Khan, Aliya Aziz Shoback, Dolores Marie TI Medical Management of Primary Hyperparathyroidism: Proceedings of the Fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MILD PRIMARY HYPERPARATHYROIDISM; VITAMIN-D DEFICIENCY; PARATHYROID CELL-PROLIFERATION; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; CALCIUM INTAKE; SERUM-CALCIUM; ORAL ALENDRONATE; CONTROLLED-TRIAL; CINACALCET HCL AB Objective: Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The only available definitive therapy is parathyroidectomy, which is appropriate to consider in all patients. The purpose of this report is to provide an update on calcium and vitamin D supplementation and medical management for those patients with PHPT who cannot or do not want to undergo surgery. Methods: Questions were developed by the International Task Force on PHPT. A comprehensive literature search was undertaken, and relevant articles published between 2008 and 2013 were reviewed in detail. The questions were addressed by the panel of experts, and consensus was established at the time of the workshop. Conclusions: The recommended calcium intake in patients with PHPT should follow guidelines established for all individuals. It is not recommended to limit calcium intake in patients with PHPT who do not undergo surgery. Patients with low serum 25-hydroxyvitamin D should be repleted with doses of vitamin D aiming to bring serum 25-hydroxyvitamin D levels to >= 50 nmol/L (20 ng/mL) at a minimum, but a goal of >= 75 nmol/L (30 ng/mL) also is reasonable. Pharmacological approaches are available and should be reserved for those patients in whom it is desirable to lower the serum calcium, increase BMD, or both. For the control of hypercalcemia, cinacalcet is the treatment of choice. Cinacalcet reduces serum calcium concentrations to normal in many cases, but has only a modest effect on serum PTH levels. However, bone mineral density (BMD) does not change. To improve BMD, bisphosphonate therapy is recommended. The best evidence is for the use of alendronate, which improves BMD at the lumbar spine without altering the serum calcium concentration. To reduce the serum calcium and improve BMD, combination therapy with both agents is reasonable, but strong evidence for the efficacy of that approach is lacking. C1 [Marcocci, Claudio] Univ Pisa, Dept Clin & Expt Med, I-56124 Pisa, Italy. Univ Hosp Pisa, Endocrine Unit 2, I-56124 Pisa, Italy. [Bollerslev, Jens] Univ Oslo, Sect Specialized Endocrinol, Oslo Univ Hosp, Rikshosp, N-0027 Oslo, Norway. Univ Oslo, Fac Med, N-0027 Oslo, Norway. [Khan, Aliya Aziz] McMaster Univ, Dept Med, Div Endocrinol, Hamilton, ON L8N 4A6, Canada. [Khan, Aliya Aziz] McMaster Univ, Dept Med, Div Geriatr, Hamilton, ON L8N 4A6, Canada. [Shoback, Dolores Marie] Univ Calif San Francisco, Endocrine Res Unit, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Marcocci, C (reprint author), Univ Pisa, Endocrine Unit 2, Dept Clin & Expt Med, Via Paradisa 2, I-56124 Pisa, Italy. FU Amgen; NPS; Merck; Lilly FX Disclosure Summary: C.M., J.B., and D.M.S. have nothing to declare. A.A.K. received research funds from Amgen, NPS, and Merck and advisory board and speaker fees from Amgen, Merck, and Lilly. NR 70 TC 27 Z9 27 U1 0 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2014 VL 99 IS 10 BP 3607 EP 3618 DI 10.1210/jc.2014-1417 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AR2NC UT WOS:000343423300058 PM 25162668 ER PT J AU DeFronzo, RA Tripathy, D Abdul-Ghani, M Musi, N Gastaldelli, A AF DeFronzo, Ralph A. Tripathy, Devjit Abdul-Ghani, Muhammad Musi, Nicolas Gastaldelli, Amalia TI The Disposition Index Does Not Reflect beta-Cell Function in IGT Subjects Treated With Pioglitazone SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; TYPE-2 DIABETIC-PATIENTS; INSULIN-SECRETION; DOSE-RESPONSE; SENSITIVITY; CLEARANCE; METABOLISM; PREVENTION; RESISTANCE; INTOLERANCE AB Aims and Hypothesis: The insulin secretion/insulin resistance (IR) (disposition) index (Delta I/Delta G divided by IR, where Delta is change from baseline, I is insulin, and G is glucose) is commonly used as a measure of beta-cell function. This relationship is curvilinear and becomes linear when log transformed. Delta I is determined by 2 variables: insulin secretion rate (ISR) and metabolic clearance of insulin. We postulated that the characteristic curvilinear relationship would be lost if Delta plasma C-peptide (Delta CP) (instead of Delta plasma insulin) was plotted against insulin sensitivity. Methods: A total of 441 individuals with impaired glucose tolerance (IGT) from ACT NOW received an oral glucose tolerance test and were randomized to pioglitazone or placebo for 2.4 years. Results: Pioglitazone reduced IGT conversion to diabetes by 72% (P <.0001). Delta I/Delta G vs the Matsuda index of insulin sensitivity showed the characteristic curvilinear relationship. However, when Delta CP/Delta G or Delta ISR/Delta G was plotted against the Matsuda index, the curvilinear relationship was completely lost. This discordance was explained by 2 distinct physiologic effects that altered plasma insulin response in opposite directions: 1) increased ISR and 2) augmented metabolic clearance of insulin. The net result was a decline in the plasma insulin response to hyperglycemia during the oral glucose tolerance test. These findings demonstrate a physiologic control mechanism wherein the increase in ISR ensures adequate insulin delivery into the portal circulation to suppress hepatic glucose production while delivering a reduced but sufficient amount of insulin to peripheral tissues to maintain the pioglitazone-mediated improvement in insulin sensitivity without excessive hyperinsulinemia. Conclusions: These results demonstrate the validity of the disposition index when relating the plasma insulin response to insulin sensitivity but underscore the pitfall of this index when drawing conclusions about beta-cell function, because insulin secretion declined despite an increase in the plasma insulin response. C1 [DeFronzo, Ralph A.; Tripathy, Devjit; Abdul-Ghani, Muhammad; Musi, Nicolas; Gastaldelli, Amalia] Texas Diabet Inst, San Antonio, TX 78229 USA. [DeFronzo, Ralph A.; Tripathy, Devjit; Abdul-Ghani, Muhammad; Musi, Nicolas; Gastaldelli, Amalia] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [DeFronzo, Ralph A.; Tripathy, Devjit] South Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78229 USA. [Gastaldelli, Amalia] Inst Clin Physiol, Cardiometab Risk Unit, I-56124 Pisa, Italy. RP DeFronzo, RA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78229 USA. EM albarado@uthscsa.edu RI Gastaldelli, Amalia/H-3319-2014 OI Gastaldelli, Amalia/0000-0003-2594-1651 FU Takeda Pharmaceuticals North America FX This study was supported by an investigator-initiated and unrestricted research grant from Takeda Pharmaceuticals North America. Takeda played no role in the study design, data collection/analysis, or manuscript preparation/review. NR 26 TC 4 Z9 5 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2014 VL 99 IS 10 BP 3774 EP 3781 DI 10.1210/jc.2014-1515 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AR2NC UT WOS:000343423300079 PM 24937535 ER PT J AU Padhi, D Higano, CS Shore, ND Sieber, P Rasmussen, E Smith, MR AF Padhi, Desmond Higano, Celestia S. Shore, Neal D. Sieber, Paul Rasmussen, Erik Smith, Matthew R. TI Pharmacological Inhibition of Myostatin and Changes in Lean Body Mass and Lower Extremity Muscle Size in Patients Receiving Androgen Deprivation Therapy for Prostate Cancer SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN SENSITIVITY; MUSCULAR-DYSTROPHY; IIB INCREASES; GENE CAUSES; MDX MOUSE; RECEPTOR; MICE; CACHEXIA; CATTLE; MUTATIONS AB Context: Myostatin is a negative regulator of muscle growth. Androgen deprivation (ADT) is associated with muscle loss and increased body fat, and currently available therapies have limited efficacy to treat this complication. The antimyostatin peptibody (AMG 745/Mu-S) markedly attenuated muscle loss and decreased fat accumulation in orchiectomized mice. Objective: The objective of the study was to evaluate the safety, pharmacokinetics, and muscle efficacy of AMG 745 in men undergoing ADT for nonmetastatic prostate cancer. Methods: This was a randomized, blinded, placebo-controlled, multiple-dose, phase 1 study of AMG 745 given for 28 days. The end point of percentage change from baseline in lean body mass (LBM) as assessed by dual x-ray absorptiometry was prespecified. Results: Rates of adverse events (AMG 745 vs placebo) were the following: diarrhea (13% vs 9%), fatigue (13% vs 4%), contusion (10% vs 0%), and injection site bruising (6% vs 4%). Exposure increased linearly from 0.3 mg/kg to 3 mg/kg. AMG 745 significantly increased LBM in the 3 mg/kg vs the placebo groups on day 29 by 2.2% (+/- 0.8% SE, P = 0.008); in exploratory fat mass analysis, a decrease of -2.5% (+/- 1.0% SE, P = 0.021) was observed. Pharmacodynamic changes in muscle and fat were maintained at follow-up, 1 month after day 29. Conclusion: Four weekly sc doses of AMG 745 were well tolerated and were associated with increased LBM and decreased fat in the men receiving ADT for nonmetastatic prostate cancer. Results support further investigation of AMG 745 in clinical settings with muscle loss and atrophy. C1 [Padhi, Desmond] Amgen Inc, Dept Med Sci, Thousand Oaks, CA 91320 USA. [Rasmussen, Erik] Amgen Inc, Biostat, Thousand Oaks, CA 91320 USA. [Padhi, Desmond] Amgen Inc, Thousand Oaks, CA 91320 USA. [Higano, Celestia S.] Univ Washington, Dept Med, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Shore, Neal D.] Carolina Urol Res Ctr, Myrtle Beach, SC 29579 USA. [Sieber, Paul] Urol Associates Lancaster, Lancaster, PA 17604 USA. [Smith, Matthew R.] Massachusetts Gen Hosp Canc Ctr, Boston, MA 02114 USA. RP Padhi, D (reprint author), Amgen Inc, Dept Med Sci, One Amgen Ctr Dr, Thousand Oaks, CA 91320 USA. EM dpadhi@amgen.com FU Amgen FX This work was supported by Amgen. NR 45 TC 16 Z9 16 U1 2 U2 6 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2014 VL 99 IS 10 BP E1967 EP E1975 DI 10.1210/jc.2014-1271 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AR2NC UT WOS:000343423300018 PM 24971661 ER PT J AU Wesseling-Perry, K Wang, HJ Elashoff, R Gales, B Juppner, H Salusky, IB AF Wesseling-Perry, Katherine Wang, Hejing Elashoff, Robert Gales, Barbara Jueppner, Harald Salusky, Isidro B. TI Lack of FGF23 Response to Acute Changes in Serum Calcium and PTH in Humans SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-FACTOR 23; PARATHYROID-HORMONE SECRETION; SECONDARY HYPERPARATHYROIDISM; HEMODIALYSIS-PATIENTS; DIETARY PHOSPHORUS; GENE-EXPRESSION; PHOSPHATE; BONE; 1,25-DIHYDROXYVITAMIN-D; VOLUNTEERS AB Context: 1,25-Dihydroxyvitamin D (1,25D) administration and long-term increases in phosphate, PTH, and calcium concentrations are associated with increases in circulating fibroblast growth factor 23 (FGF23); however, whether or not acute changes in serum calcium modulate short-term FGF23 release is unknown. Objective/Design: To assess the direct effect of acute changes in calcium and PTH on circulating FGF23 levels. Setting: A university clinical and translational research center. Patients/Participants: Twelve healthy volunteers and 10 dialysis patients. Interventions: Calcium gluconate and sodium citrate were infused for 120 minutes on 2 consecutive days. Main Outcome Measures: Serum levels of ionized calcium, phosphorus, PTH, 1,25D, and plasma C-terminal FGF23 levels were obtained at 0, 13, 30, 60, 90, and 120 minutes during the infusions. Results: During the calcium infusion, serum calcium concentrations increased from 1.33 +/- 0.01 to 1.57 +/- 0.04 mmol/L (P < .05 from baseline) and from 1.20 +/- 0.05 to 1.50 +/- 0.03 mmol/L (P < .05 from baseline) in healthy subjects and in dialysis patients, respectively, whereas serum calcium values decreased from 1.33 +/- 0.01 to 1.03 +/- 0.02 mmol/L (P < .05 from baseline) and from 1.26 +/- 0.04 to 1.07 +/- 0.03 mmol/L (P < .05 from baseline) in the two groups, respectively during the sodium citrate infusion. PTH levels decreased from 35 (29, 57) to 8 (2,10) pg/mL (healthy subjects) (P < .05 from baseline) and from 292 (109, 423) to 44 (28, 86) pg/mL (dialysis patients) (P < .05 from baseline) during the calcium infusion and rose from 31 (25, 56) to 122 (95, 157) pg/mL and from 281 (117, 607) to 468 (169, 928) pg/mL (P < .05 from baseline) during sodium citrate infusion. Serum 1,25D levels and plasma FGF23 values remained unchanged during both infusions in both groups. Conclusions: Short-term changes in calcium and PTH levels do not affect FGF23 concentrations in either healthy volunteers or dialysis patients. C1 [Wesseling-Perry, Katherine; Wang, Hejing; Elashoff, Robert; Gales, Barbara; Salusky, Isidro B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wesseling-Perry, K (reprint author), Div Pediat Nephrol, A2-383 MDCC,10833 LeConte Blvd, Los Angeles, CA 90095 USA. EM kwesseling@mednet.ucla.edu FU U.S. Public Health Service Grants [DK-67563, DK-35423, DK-51081, DK-073039, UL1RR-033176]; Casey Lee Ball Foundation; National Kidney Foundation; American Society of Nephrology Norman Siegel Award FX This work was supported by U.S. Public Health Service Grants DK-67563, DK-35423, DK-51081, DK-073039, and UL1RR-033176 and funds from the Casey Lee Ball Foundation. K.W.-P. was a recipient of a fellowship award from the National Kidney Foundation and the American Society of Nephrology Norman Siegel Award. NR 21 TC 5 Z9 5 U1 1 U2 6 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2014 VL 99 IS 10 BP E1951 EP E1956 DI 10.1210/jc.2014-2125 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AR2NC UT WOS:000343423300016 PM 25062462 ER PT J AU Sun, XY Salat, D Upchurch, K Deason, R Kowall, N Budson, A AF Sun, Xiaoyan Salat, David Upchurch, Kristen Deason, Rebecca Kowall, Neil Budson, Andrew CA Alzheimers Dis Neuroimaging TI Destruction of White Matter Integrity in Patients With Mild Cognitive Impairment and Alzheimer Disease SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE diffusion tensor imaging; Alzheimer disease; mild cognitive impairment; fractional anisotropy; axial diffusivity; radial diffusivity; cholinergic pathway ID CHOLINERGIC PATHWAYS; GRAY-MATTER; IN-VIVO; DEMENTIA; BRAIN; HYPERINTENSITIES; SYSTEM; DIAGNOSIS; TRANSPORT; PATHOLOGY AB Background: Accumulating evidence shows that gradual loss of white matter integrity plays an important role in the development of Alzheimer disease (AD). Objective: The aim of this research was to study the microstructural integrity of white matter in AD in vivo. Methods: Global fractional anisotropy, global axial diffusivity (AxD), and global radial diffusivity (RD) were analyzed in subjects with normal controls (NC), mild cognitive impairment (MCI), and AD using Alzheimer's Disease Neuroimaging Initiative data (total N = 210). We further compared specific white matter tracts among the 3 groups. Results: Compared with the NC group, the MCI group had significantly increased global AxD and global RD. Compared with the NC and MCI groups, the AD group had significantly decreased global fractional anisotropy, increased global AxD, and increased global RD. With regard to specific white matter tracts, in the MCI group, we found increased AxD and increased RD in the external capsule, part of the lateral cholinergic pathway, in addition to the tracts connecting the limbic regions, predominantly in the left hemisphere. In the AD group, white matter abnormalities were widespread, including in the external capsule (cholinergic pathway) and limbic region tracts as well as tracts connecting anterior to posterior regions bilaterally. Conclusions: The radiographic manifestation of damaged white matter microstructural integrity in the cholinergic pathway in MCI patients may provide a rational basis for the use of cholinesterase inhibitor drugs in the MCI stage of AD. C1 [Sun, Xiaoyan; Upchurch, Kristen; Kowall, Neil; Budson, Andrew] VA Boston Healthcare Syst, Dept Neurol, Boston, MA 02130 USA. [Sun, Xiaoyan; Budson, Andrew] VA Boston Healthcare Syst, Ctr Translat Neurosci, Boston, MA 02130 USA. [Sun, Xiaoyan; Salat, David; Upchurch, Kristen; Kowall, Neil; Budson, Andrew] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Sun, Xiaoyan; Upchurch, Kristen; Kowall, Neil; Budson, Andrew] Boston Univ, Sch Med, Boston, MA 02118 USA. [Salat, David] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA 02130 USA. [Salat, David] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Deason, Rebecca] Texas State Univ, Dept Psychol, San Marcos, TX USA. RP Sun, XY (reprint author), VA Boston Healthcare Syst, Dept Neurol, Boston, MA 02130 USA. EM xysunny@hotmail.com RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU VA Special Fellowships in Advanced Geriatrics; National Institutes of Health [NIH]; ADNI (National Institutes of Health) [U01 AG024904]; DOD ADNI (Department of Defense) [W81XWH-12-2-0012]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; BioClinica, Inc; Biogen Idec, Inc; Bristol-Myers Squibb Company; Eisai, Inc; Elan Pharmaceuticals, Inc; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc; GE Healthcare; Innogenetics, NV; IXICO Ltd; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Medpace, Inc; Merck Co, Inc; Meso Scale Diagnostics, LLC; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer, Inc; Piramal Imaging; Servier; Synarc, Inc; Canadian Institutes of Health Research FX Supported by VA Special Fellowships in Advanced Geriatrics (salary for Dr Sun and Dr Upchurch). The infrastructure for this work was provided by the VA Boston Healthcare System and by Boston University Alzheimer's Disease Center (which is funded by the National Institutes of Health [NIH]). Data collection and sharing for this project were funded by the ADNI (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense Award Number W81XWH-12-2-0012). The ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; BioClinica, Inc; Biogen Idec, Inc; Bristol-Myers Squibb Company; Eisai, Inc; Elan Pharmaceuticals, Inc; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc; GE Healthcare; Innogenetics, NV; IXICO Ltd; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Medpace, Inc; Merck & Co, Inc; Meso Scale Diagnostics, LLC; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer, Inc; Piramal Imaging; Servier; Synarc, Inc; and support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to the NIH (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. The VADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. NR 49 TC 4 Z9 6 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD OCT PY 2014 VL 62 IS 7 BP 927 EP 933 DI 10.1097/JIM.0000000000000102 PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AR1DX UT WOS:000343324000019 PM 25046178 ER PT J AU Spencer, TJ Faraone, SV Tarko, L McDermott, K Biederman, J AF Spencer, Thomas J. Faraone, Stephen V. Tarko, Laura McDermott, Katie Biederman, Joseph TI Attention-Deficit/Hyperactivity Disorder and Adverse Health Outcomes in Adults SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Attention-deficit disorder with hyperactivity; health; risk; epidemiology ID DEFICIT HYPERACTIVITY DISORDER; CIGARETTE-SMOKING; CHILDHOOD EXPERIENCES; YOUNG-ADULTS; ADHD; ASSOCIATION; RISK; SYMPTOMS; SAMPLE; CHILDREN AB Whereas the adverse impact of attention-deficit/hyperactivity disorder (ADHD) on emotional and psychosocial well-being has been well investigated, its impact on physical health has not. The main aim of this study was to assess the impact of ADHD on lifestyle behaviors and measures of adverse health risk indicators. Subjects were 100 untreated adults with ADHD and 100 adults without ADHD of similar age and sex. Unhealthy lifestyle indicators included assessments of bad health habits, frequency of visits to healthcare providers, and follow through with recommended prophylactic tests. Assessments of adverse health risk indicators included measurements of cardiovascular and metabolic parameters, weight, body mass index, and waist circumference. No differences were identified in health habits between subjects with and without ADHD, but robust differences were found in a wide range of adverse health risk indicators. ADHD is associated with an adverse impact in health risk indicators well known to be associated with high morbidity and mortality. C1 [Spencer, Thomas J.; Tarko, Laura; McDermott, Katie; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Spencer, Thomas J.; Tarko, Laura; McDermott, Katie; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Adult ADHD, Boston, MA 02114 USA. [Spencer, Thomas J.; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY 13210 USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Warren 705,55 Fruit St, Boston, MA 02114 USA. EM tspencer@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU Shire; Pediatric Psychopharmacology Council Fund; Alcobra; Cephalon; Eli Lilly Company; Glaxo-Smith Kline; Heptares; Impax; Ironshore; Janssen Pharmaceutical; Lundbeck; McNeil Pharmaceutical; Novartis Pharmaceuticals; Pfizer; Shire Laboratories, Inc; Sunovion; VayaPharma; National Institute of Mental Health; Department of Defense; Massachusetts General Hospital (MGH) Corporate Sponsored Research and Licensing; Akili Interactive Labs; VAYA Pharma; SynapDx; National Institutes of Health (NIH); Otsuka; McNeil; Janssen; Novartis; Eli Lilly; Vaya Pharma/Enzymotec; NIH; MGH Psychiatry Academy; American Professional Society of ADHD and Related Disorders; ElMindA; The Children's Hospital of Southwest Florida/Lee Memorial Health System; AstraZeneca; Fundacion Dr. Manuel Camelo A.C. in Monterrey, Mexico; Department of Psychiatry at the MGH; Abbott; Alza; Boston University; Bristol Myers Squibb; Celltech; Eli Lilly and Co; Esai; Fundacion Areces (Spain); Forest; Glaxo; Gliatech; Hastings Center; Medice Pharmaceuticals (Germany); Merck; MMC Pediatric; National Association for Research on Schizophrenia and Depression; National Institute on Drug Abuse; New River; National Institute of Child Health and Human Development; Noven; Neurosearch; Organon; Pharmacia; Phase V Communications; Physicians Academy; The Prechter Foundation; Quantia Communications; Reed Exhibitions; Spanish Child Psychiatry Association; The Stanley Foundation; UCB Pharma Inc; Veritas; Wyeth FX This work was supported in part by a research grant from Shire (Dr Spencer) and by the Pediatric Psychopharmacology Council Fund.; Dr Thomas Spencer has received research support from, has been a speaker for or on a speaker bureau, or has been an advisor of on an advisory board of the following sources: Alcobra; Cephalon; Eli Lilly & Company; Glaxo-Smith Kline; Heptares; Impax; Ironshore; Janssen Pharmaceutical; Lundbeck; McNeil Pharmaceutical; Novartis Pharmaceuticals; Pfizer; Shire Laboratories, Inc; Sunovion; VayaPharma; the National Institute of Mental Health; and the Department of Defense. Dr Spencer receives research support from royalties and licensing fees on copyrighted ADHD scales through Massachusetts General Hospital (MGH) Corporate Sponsored Research and Licensing. Dr Spencer has a US Patent Application pending (provisional number 61/233.686), through MGH corporate licensing, on a method to prevent stimulant abuse.; In the past year, Dr Faraone received consulting income and/or research support from Akili Interactive Labs, VAYA Pharma, and SynapDx and research support from the National Institutes of Health (NIH). His institution is seeking a patent for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. In previous years, he received consulting fees, was on advisory boards, or participated in continuing medical education programs sponsored by Shire, Alcobra, Otsuka, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly. Dr Faraone receives royalties from books published by Guilford Press, Straight Talk about Your Child's Mental Health, and Oxford University Press, Schizophrenia: The Facts.; Dr Joseph Biederman is currently receiving research support from the following sources: The Department of Defense, Ironshore, Vaya Pharma/Enzymotec, and NIH. In 2013, Dr Joseph Biederman received an honorarium from the MGH Psychiatry Academy for a tuition-funded continuing medical education (CME) course. He received research support from American Professional Society of ADHD and Related Disorders, ElMindA, McNeil, and Shire. He has a US Patent Application pending (provisional number #61/233.686), through MGH corporate licensing, on a method to prevent stimulant abuse. Dr Biederman received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Shire and Sunovion; these royalties are paid to the Department of Psychiatry at MGH. In 2012, Dr Joseph Biederman received an honorarium from the MGH Psychiatry Academy and The Children's Hospital of Southwest Florida/Lee Memorial Health System for tuition-funded CME courses. In 2011, Dr Joseph Biederman gave a single unpaid talk for Juste Pharmaceutical Spain and received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course and honoraria for presenting at an international scientific conference on ADHD. He also received an honorarium from Cambridge University Press for a chapter publication. Dr Biederman received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Eli Lilly, Shire, and AstraZeneca; these royalties were paid to the Department of Psychiatry at MGH. In 2010, Dr Joseph Biederman received a speaker's fee from a single talk given at Fundacion Dr. Manuel Camelo A.C. in Monterrey, Mexico. Dr Biederman provided single consultations for Shionogi Pharma, Inc, and Cipher Pharmaceuticals, Inc; the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. Dr Biederman received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In previous years, Dr Joseph Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Boston University, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co, Esai, Fundacion Areces (Spain), Forest, Glaxo, Gliatech, Hastings Center, Janssen, McNeil, Medice Pharmaceuticals (Germany), Merck, MMC Pediatric, National Association for Research on Schizophrenia and Depression, National Institute on Drug Abuse, New River, National Institute of Child Health and Human Development, National Institute of Mental Health, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Phase V Communications, Physicians Academy, The Prechter Foundation, Quantia Communications, Reed Exhibitions, Shire, the Spanish Child Psychiatry Association, The Stanley Foundation, UCB Pharma Inc, Veritas, and Wyeth. NR 36 TC 11 Z9 12 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 2014 VL 202 IS 10 BP 725 EP 731 DI 10.1097/NMD.0000000000000191 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AR0FN UT WOS:000343244600004 PM 25211634 ER PT J AU Adams, JM McHugh, M AF Adams, Jeffrey M. McHugh, Matthew TI The Influence of Emerging Administrative Scientists An Interview With Matthew McHugh SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material AB This department highlights emerging nursing leaders and scientists who have demonstrated great promise in advancing innovation and patient care leadership in practice, policy, research, education and theory. This interview profiles Matthey McHugh, PhD, JD, MPH, RN, FAAN, The Rosemarie Greco Term Endowed Associate Professorship in Advocacy, an associate professor of nursing at University of Pennsylvania School of Nursing, and Robert Wood Johnson Foundation Nurse Faculty scholar. C1 [Adams, Jeffrey M.] Massachusetts Gen Hosp, Ctr Innovat Care Delivery, Boston, MA 02114 USA. [McHugh, Matthew] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, 275 Cambridge St,POB 432, Boston, MA 02114 USA. EM Jeff.adams@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD OCT PY 2014 VL 44 IS 10 BP 500 EP 501 DI 10.1097/NNA.0000000000000107 PG 2 WC Nursing SC Nursing GA AR1AV UT WOS:000343312200003 ER PT J AU Dello Russo, NM AF Dello Russo, Nicholas M. TI IMPLANTS STUDY IV SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter ID DENTAL IMPLANTS; SUCCESS; SURVIVAL; TIME C1 Massachusetts Gen Hosp, Div Dent, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Dello Russo, NM (reprint author), Massachusetts Gen Hosp, Div Dent, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 2014 VL 145 IS 10 BP 1012 EP 1013 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AQ8YV UT WOS:000343127800006 PM 25270698 ER PT J AU Levy, MH Smith, T Alvarez-Perez, A Back, A Baker, JN Block, S Codada, SN Dalal, S Dans, M Kutner, JS Kvale, E Misra, S Mitchell, W Sauer, TM Spiegel, D Sutton, L Taylor, RM Temel, J Tickoo, R Urba, SG Van Zyl, C Weinstein, SM Bergman, MA Scavone, JL AF Levy, Michael H. Smith, Thomas Alvarez-Perez, Amy Back, Anthony Baker, Justin N. Block, Susan Codada, Shirley N. Dalal, Shalini Dans, Maria Kutner, Jean S. Kvale, Elizabeth Misra, Sumathi Mitchell, William Sauer, Todd M. Spiegel, David Sutton, Linda Taylor, Robert M. Temel, Jennifer Tickoo, Roma Urba, Susan G. Van Zyl, Carin Weinstein, Sharon M. Bergman, Mary Anne Scavone, Jillian L. TI Palliative Care, Version 1.2014 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID END-OF-LIFE; CELL LUNG-CANCER; LATE REFERRALS; COMMUNICATION; ONCOLOGY; HOSPICE; DEATH; EXPECTATIONS; PROGNOSIS; OUTCOMES AB The NCCN Guidelines for Palliative Care provide interdisciplinary recommendations on palliative care for patients with cancer. These NCCN Guidelines Insights summarize the NCCN panel's discussions and guideline updates from 2013 and 2014. These include modifications/additions to palliative care screening and assessment protocols, new considerations for discussing the benefits and risks of anticancer therapy, and approaches to advance care planning. Recent updates focus on enhanced patient-centered care and seek to promote earlier integration of palliative care and advance care planning in oncology. C1 [Levy, Michael H.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Smith, Thomas] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21287 USA. [Alvarez-Perez, Amy] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Back, Anthony] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Baker, Justin N.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Block, Susan] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02215 USA. [Codada, Shirley N.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Dalal, Shalini] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Dans, Maria] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO 63110 USA. [Dans, Maria] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Kutner, Jean S.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Kvale, Elizabeth] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Misra, Sumathi] Vanderbilt Ingram Canc Ctr, Springhill, TN USA. [Mitchell, William] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Sauer, Todd M.] Univ Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Spiegel, David] Stanford Canc Inst, Stanford, CA USA. [Sutton, Linda] Duke Canc Inst, Durham, NC USA. [Taylor, Robert M.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Taylor, Robert M.] Solove Res Inst, Columbus, OH USA. [Temel, Jennifer] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Tickoo, Roma] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Urba, Susan G.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Van Zyl, Carin] City Hope Natl Med Ctr, Ctr Comprehens Canc, Monrovia, CA USA. [Weinstein, Sharon M.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. RP Levy, MH (reprint author), Fox Chase Canc Ctr, Philadelphia, PA USA. FU Eisai, Inc.; Millennium: The Takeda Oncology Company; Teva Pharmaceuticals; Bayer Health Care Pharmaceuticals Inc.; Celgene Corporation; Endo Pharmaceuticals and HealthTronics; Genentech; ARIAD; Pharmaceuticals, Inc FX Supported by educational grants from Eisai, Inc.; Millennium: The Takeda Oncology Company; Teva Pharmaceuticals; Bayer Health Care Pharmaceuticals Inc.; Celgene Corporation; Endo Pharmaceuticals and HealthTronics; Genentech; and ARIAD Pharmaceuticals, Inc. NR 66 TC 11 Z9 11 U1 1 U2 7 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2014 VL 12 IS 10 BP 1379 EP 1388 PG 10 WC Oncology SC Oncology GA AR0QE UT WOS:000343275600004 PM 25313178 ER PT J AU Denlinger, CS Ligibel, JA Are, M Baker, KS Demark-Wahnefried, W Dizon, D Friedman, DL Goldman, M Jones, L King, A Ku, GH Kvale, E Langbaum, TS Leonardi-Warren, K McCabe, MS Melisko, M Montoya, JG Mooney, K Morgan, MA Moslehi, JJ O'Connor, T Overholser, L Paskett, ED Peppercorn, J Raza, M Rodriguez, MA Syrjala, KL Urba, SG Wakabayashi, MT Zee, P McMillian, NR Freedman-Cass, DA AF Denlinger, Crystal S. Ligibel, Jennifer A. Are, Madhuri Baker, K. Scott Demark-Wahnefried, Wendy Dizon, Don Friedman, Debra L. Goldman, Mindy Jones, Lee King, Allison Ku, Grace H. Kvale, Elizabeth Langbaum, Terry S. Leonardi-Warren, Kristin McCabe, Mary S. Melisko, Michelle Montoya, Jose G. Mooney, Kathi Morgan, Mary Ann Moslehi, Javid J. O'Connor, Tracey Overholser, Linda Paskett, Electra D. Peppercorn, Jeffrey Raza, Muhammad Rodriguez, M. Alma Syrjala, Karen L. Urba, Susan G. Wakabayashi, Mark T. Zee, Phyllis McMillian, Nicole R. Freedman-Cass, Deborah A. TI Survivorship: Nutrition and Weight Management, Version 2.2014 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID BREAST-CANCER SURVIVORS; BODY-MASS INDEX; RANDOMIZED CONTROLLED-TRIALS; III COLON-CANCER; QUALITY-OF-LIFE; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; DIETARY PATTERNS; CARDIOVASCULAR-DISEASE; ADJUVANT CHEMOTHERAPY AB Healthy lifestyle habits have been associated with improved health outcomes and quality of life and, for some cancers, a reduced risk of recurrence and death. The NCCN Guidelines for Survivorship therefore recommend that cancer survivors be encouraged to achieve and maintain a healthy lifestyle, including attention to weight management, physical activity, and dietary habits. This section of the NCCN Guidelines focuses on recommendations regarding nutrition, weight management, and supplement use in survivors. Weight management recommendations are based on the survivor's body mass index and include discussions of nutritional, weight management, and physical activity principles, with referral to community resources, dietitians, and/or weight management programs as needed. C1 [Denlinger, Crystal S.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Ligibel, Jennifer A.] Dana Farber Brigham & Womens Canc Ctr, Milford, MA USA. [Are, Madhuri] Univ Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Baker, K. Scott; Syrjala, Karen L.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Demark-Wahnefried, Wendy] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Dizon, Don] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Friedman, Debra L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Goldman, Mindy] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Jones, Lee] Mem Sloan Kettering Canc Ctr, New York, NY USA. [King, Allison] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [King, Allison] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Ku, Grace H.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA USA. [Kvale, Elizabeth] Univ Alabama, Ctr Comprehens Canc, Tuscaloosa, AL 35487 USA. [Langbaum, Terry S.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Leonardi-Warren, Kristin; Overholser, Linda] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [McCabe, Mary S.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Melisko, Michelle] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Montoya, Jose G.] Stanford Canc Inst, Stanford, CA USA. [Mooney, Kathi] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Morgan, Mary Ann] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Moslehi, Javid J.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [O'Connor, Tracey] Roswell Pk Canc Inst, Buffalo, NY USA. [Paskett, Electra D.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Paskett, Electra D.] Solove Res Inst, Columbus, OH USA. [Peppercorn, Jeffrey] Duke Canc Inst, Durham, NC USA. [Raza, Muhammad] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Rodriguez, M. Alma] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Urba, Susan G.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Wakabayashi, Mark T.] City Hope Natl Med Ctr, Ctr Comprehens Canc, San Francisco, CA USA. [Zee, Phyllis] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. RP Denlinger, CS (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. OI King, Allison/0000-0002-1951-6176 FU NCI NIH HHS [UM1 CA173642] NR 53 TC 3 Z9 3 U1 1 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 OCT PY 2014 VL 12 IS 10 BP 1396 EP 1406 PG 11 WC Oncology SC Oncology GA AR0QE UT WOS:000343275600005 PM 25313179 ER PT J AU Pfister, DG Spencer, S Brizel, DM Burtness, B Busse, PM Caudell, JJ Cmelak, AJ Colevas, AD Dunphy, F Eisele, DW Gilbert, J Gillison, ML Haddad, RI Haughey, BH Hicks, WL Hitchcock, YJ Jimeno, A Kies, MS Lydiatt, WM Maghami, E Martins, R McCaffrey, T Mell, LK Mittal, BB Pinto, HA Ridge, JA Rodriguez, CP Samant, S Schuller, DE Shah, JP Weber, RS Wolf, GT Worden, F Yom, SS McMillian, NR Hughes, M AF Pfister, David G. Spencer, Sharon Brizel, David M. Burtness, Barbara Busse, Paul M. Caudell, Jimmy J. Cmelak, Anthony J. Colevas, A. Dimitrios Dunphy, Frank Eisele, David W. Gilbert, Jill Gillison, Maura L. Haddad, Robert I. Haughey, Bruce H. Hicks, Wesley L., Jr. Hitchcock, Ying J. Jimeno, Antonio Kies, Merrill S. Lydiatt, William M. Maghami, Ellie Martins, Renato McCaffrey, Thomas Mell, Loren K. Mittal, Bharat B. Pinto, Harlan A. Ridge, John A. Rodriguez, Cristina P. Samant, Sandeep Schuller, David E. Shah, Jatin P. Weber, Randal S. Wolf, Gregory T. Worden, Frank Yom, Sue S. McMillian, Nicole R. Hughes, Miranda TI Head and Neck Cancers, Version 2.2014 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID SQUAMOUS-CELL-CARCINOMA; INTENSITY-MODULATED RADIOTHERAPY; LOCALLY ADVANCED HEAD; QUALITY-OF-LIFE; COOPERATIVE-ONCOLOGY-GROUP; PROSPECTIVE RANDOMIZED-TRIAL; PHASE-II TRIAL; STANDARD FRACTIONATION RADIOTHERAPY; POSTOPERATIVE RADIATION-THERAPY; STAGE NASOPHARYNGEAL CARCINOMA AB This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to "Principles of Radiation Therapy" for each site and "Principles of Surgery," and the addition of a new section on "Principles of Dental Evaluation and Management." C1 [Pfister, David G.; Shah, Jatin P.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Spencer, Sharon] Univ Alabama, Ctr Comprehens Canc, Tuscaloosa, AL 35487 USA. [Brizel, David M.] Duke Canc Inst, Durham, NC USA. [Burtness, Barbara; Ridge, John A.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Busse, Paul M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Caudell, Jimmy J.; McCaffrey, Thomas] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Cmelak, Anthony J.; Gilbert, Jill] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Colevas, A. Dimitrios] Stanford Canc Inst, Stanford, CA USA. [Dunphy, Frank] Duke Canc Inst, Durham, NC USA. [Eisele, David W.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Gillison, Maura L.; Schuller, David E.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Gillison, Maura L.; Schuller, David E.] Solove Res Inst, Columbus, OH USA. [Haddad, Robert I.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Haughey, Bruce H.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Haughey, Bruce H.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Hicks, Wesley L., Jr.] Roswell Pk Canc Inst, Buffalo, NY USA. [Hitchcock, Ying J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Jimeno, Antonio] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Kies, Merrill S.; Weber, Randal S.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Lydiatt, William M.] Univ Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Maghami, Ellie] City Hope Natl Med Ctr, Ctr Comprehens Canc, Duarte, CA USA. [Martins, Renato] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Mell, Loren K.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Mittal, Bharat B.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Pinto, Harlan A.] Stanford Canc Inst, Stanford, CA USA. [Rodriguez, Cristina P.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Samant, Sandeep] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Wolf, Gregory T.; Worden, Frank] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Yom, Sue S.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. RP Pfister, DG (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. OI Shah, Jatin/0000-0002-6444-6592 NR 269 TC 50 Z9 51 U1 3 U2 14 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2014 VL 12 IS 10 BP 1454 EP 1487 PG 34 WC Oncology SC Oncology GA AR0QE UT WOS:000343275600010 PM 25313184 ER PT J AU San-Miguel, JF Hungria, VTM Yoon, SS Beksac, M Dimopoulos, MA Elghandour, A Jedrzejczak, WW Gunther, A Nakorn, TN Siritanaratkul, N Corradini, P Chuncharunee, S Lee, JJ Schlossman, RL Shelekhova, T Yong, K Tan, D Numbenjapon, T Cavenagh, JD Hou, J LeBlanc, R Nahi, H Qiu, LG Salwender, H Pulini, S Moreau, P Warzocha, K White, D Blade, J Chen, WM de la Rubia, J Gimsing, P Lonial, S Kaufman, JL Ocio, EM Veskovski, L Sohn, SK Wang, MC Lee, JH Einsele, H Sopala, M Corrado, C Bengoudifa, BR Binlich, F Richardson, PG AF San-Miguel, Jesus F. Hungria, Vania T. M. Yoon, Sung-Soo Beksac, Meral Dimopoulos, Meletios Athanasios Elghandour, Ashraf Jedrzejczak, Wieslaw Wiktor Guenther, Andreas Nakorn, Thanyaphong Na Siritanaratkul, Noppadol Corradini, Paolo Chuncharunee, Suporn Lee, Je-Jung Schlossman, Robert L. Shelekhova, Tatiana Yong, Kwee Tan, Daryl Numbenjapon, Tontanai Cavenagh, Jamie D. Hou, Jian LeBlanc, Richard Nahi, Hareth Qiu, Lugui Salwender, Hans Pulini, Stefano Moreau, Philippe Warzocha, Krzysztof White, Darrell Blade, Joan Chen, WenMing de la Rubia, Javier Gimsing, Peter Lonial, Sagar Kaufman, Jonathan L. Ocio, Enrique M. Veskovski, Ljupco Sohn, Sang Kyun Wang, Ming-Chung Lee, Jae Hoon Einsele, Hermann Sopala, Monika Corrado, Claudia Bengoudifa, Bourras-Rezki Binlich, Florence Richardson, Paul G. TI Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID INHIBITOR PANOBINOSTAT; COMBINATION THERAPY; TRIPLE COMBINATION; SINGLE-AGENT; LENALIDOMIDE; LBH589; TRANSPLANTATION; VORINOSTAT AB Background Panobinostat is a potent oral pan-deacetylase inhibitor that in preclinical studies has synergistic antimyeloma activity when combined with bortezomib and dexamethasone. We aimed to compare panobinostat, bortezomib, and dexamethasone with placebo, bortezomib, and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma. Methods PANORAMA1 is a multicentre, randomised, placebo-controlled, double-blind phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma who have received between one and three previous treatment regimens. Patients were randomly assigned (1:1) via an interactive web-based and voice response system, stratified by number of previous treatment lines and by previous use of bortezomib, to receive 21 day cycles of placebo or panobinostat (20 mg; on days 1, 3, 5, 8, 10, 12, orally), both in combination with bortezomib (1.3 mg/m(2) on days 1, 4, 8, 11, intravenously) and dexamethasone (20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, orally). Patients, physicians, and the investigators who did the data analysis were masked to treatment allocation; crossover was not permitted. The primary endpoint was progression-free survival (in accordance with modified European Group for Blood and Marrow Transplantation criteria and based on investigators' assessment) and was analysed by intention to treat. The study is ongoing, but no longer recruiting, and is registered at ClinicalTrials.gov, number NCT01023308. Findings 768 patients were enrolled between Jan 21, 2010, and Feb 29, 2012, with 387 randomly assigned to panobinostat, bortezomib, and dexamethasone and 381 to placebo, bortezomib, and dexamethasone. Median follow-up was 6.47 months (IQR 1.81-13.47) in the panobinostat group and 5.59 months (2.14-11.30) in the placebo group. Median progression-free survival was significantly longer in the panobinostat group than in the placebo group (11.99 months [95% CI 10.33-12.94] vs 8.08 months [7.56-9.23]; hazard ratio [HR] 0.63, 95% CI 0.52-0.76; p<0.0001). Overall survival data are not yet mature, although at the time of this analysis, median overall survival was 33.64 months (95% CI 31.34-not estimable) for the panobinostat group and 30.39 months (26.87-not estimable) for the placebo group (HR 0.87, 95% CI 0.69-1.10; p=0.26). The proportion of patients achieving an overall response did not differ between treatment groups (235[60.7%, 95% CI 55.7-65.6] for panobinostat vs 208 [54.6%, 49.4-59.7] for placebo; p=0.09); however, the proportion of patients with a complete or near complete response was significantly higher in the panobinostat group than in the placebo group (107[27.6%, 95% CI 23.2-32.4] vs 60 [15.7%, 12.2-19.8]; p=0.00006). Minimal responses were noted in 23 (6%) patients in the panobinostat group and in 42 (11%) in the placebo group. Median duration of response (partial response or better) was 13.14 months (95% CI 11.76-14.92) in the panobinostat group and 10.87 months (9.23-11.76) in the placebo group, and median time to response (partial response or better) was 1.51 months (1.41-1.64) in the panobinostat group and 2.00 months (1.61-2.79) in the placebo group. Serious adverse events were reported in 228 (60%) of 381 patients in the panobinostat group and 157 (42%) of 377 patients in the placebo group. Common grade 3-4 laboratory abnormalities and adverse events (irrespective of association with study drug) included thrombocytopenia (256 [67%] in the panobinostat group vs 118 [31%] in the placebo group), lymphopenia (202 [53%] vs 150 [40%]), diarrhoea (97 [26%] vs 30 [8%]), asthenia or fatigue (91 [24%] vs 45 [12%]), and peripheral neuropathy (67 [18%] vs 55 [15%]). Interpretation Our results suggest that panobinostat could be a useful addition to the treatment armamentarium for patients with relapsed or relapsed and refractory multiple myeloma. Longer follow up will be necessary to determine whether there is any effect on overall survival. C1 [San-Miguel, Jesus F.] Univ Navarra Clin, CIMA, Pamplona 31008, Spain. [Hungria, Vania T. M.] Santa Casa Misericordia Sao Paulo Hosp, Sao Paulo, Brazil. [Yoon, Sung-Soo] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Beksac, Meral] Ankara Univ, Sch Med, TR-06100 Ankara, Turkey. [Dimopoulos, Meletios Athanasios] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Elghandour, Ashraf] Univ Alexandria, Alexandria, Egypt. [Jedrzejczak, Wieslaw Wiktor] Med Univ Warsaw, Warsaw, Poland. [Guenther, Andreas] Univ Kiel, Kiel, Germany. [Nakorn, Thanyaphong Na] Chulalongkorn Univ, Bangkok, Thailand. [Nakorn, Thanyaphong Na] King Chulalongkorn Mem Hosp, Bangkok, Thailand. [Siritanaratkul, Noppadol] Siriraj Hosp, Bangkok, Thailand. [Corradini, Paolo] Univ Milan, Fdn IRCCS, Ist Nazl Tumori, Milan, Italy. [Chuncharunee, Suporn] Ramathibodi Hosp, Bangkok, Thailand. [Lee, Je-Jung] Chonnam Natl Univ, Hwasun Hosp, Hwasun, South Korea. [Schlossman, Robert L.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shelekhova, Tatiana] Saratov State Med Univ, Clin Profess Pathol & Haematol, Saratov, Russia. [Yong, Kwee] UCL, Inst Canc, London, England. [Tan, Daryl] Singapore Gen Hosp, Singapore, Singapore. [Numbenjapon, Tontanai] Phramongkutklao Hosp, Bangkok, Thailand. [Cavenagh, Jamie D.] St Bartholomews Hosp, Barts Hlth NHS Trust, London, England. [Hou, Jian] Chang Zheng Hosp, Shanghai, Peoples R China. [LeBlanc, Richard] Maisonneuve Rosemont Hosp, Montreal, PQ, Canada. [LeBlanc, Richard] Univ Montreal, Montreal, PQ, Canada. [Nahi, Hareth] Karolinska Univ Hosp, Stockholm, Sweden. [Qiu, Lugui] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China. [Qiu, Lugui] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China. [Qiu, Lugui] Peking Union Med Coll, Tianjin, Peoples R China. [Salwender, Hans] Asklepios Clin Altona, Hamburg, Germany. [Pulini, Stefano] Spirito Santo Hosp, Pescara, Italy. [Moreau, Philippe] Nantes Univ Hosp, Nantes, France. [Warzocha, Krzysztof] Inst Haematol & Transfus Med, Warsaw, Poland. [White, Darrell] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [White, Darrell] Dalhousie Univ, Halifax, NS, Canada. [Blade, Joan] Hosp Clin Barcelona, Inst Invest Biomed August Pi I Sunyer, Barcelona, Spain. [Chen, WenMing] Capital Med Univ, Beijing Chaoyang Hosp, Beijing, Peoples R China. [de la Rubia, Javier] Univ Hosp La Fe, Valencia, Spain. [de la Rubia, Javier] Univ Catolica San Vicente Martir, Valencia, Spain. [Gimsing, Peter] Rigshosp, DK-2100 Copenhagen, Denmark. [Gimsing, Peter] Univ Copenhagen, Copenhagen, Denmark. [Lonial, Sagar; Kaufman, Jonathan L.] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Ocio, Enrique M.] Univ Hosp, Salamanca, Spain. [Ocio, Enrique M.] Univ Salamanca, Canc Res Ctr, Inst Invest Biomed Salamanca, Inst Biol Mol & Celular Canc, E-37008 Salamanca, Spain. [Veskovski, Ljupco] Sahlgrens Univ Hosp, S-41345 Gothenburg, Sweden. [Sohn, Sang Kyun] Kyungpook Natl Univ, Taegu, South Korea. [Wang, Ming-Chung] Kaohsiung Chang Gung Mem Hosp, Kaohsiung, Taiwan. [Lee, Jae Hoon] Gachon Univ, Gil Med Ctr, Inchon, South Korea. [Einsele, Hermann] Univ Hosp Wurzburg, Wurzburg, Germany. [Sopala, Monika; Corrado, Claudia; Bengoudifa, Bourras-Rezki] Novartis Pharma AG, Basel, Switzerland. [Binlich, Florence] Novartis Pharma SAS, Rueil Malmaison, France. RP San-Miguel, JF (reprint author), Univ Navarra Clin, CIMA, Pamplona 31008, Spain. EM sanmiguel@unav.es RI richard, chrystelle/K-8595-2015; OI Sopala, Monika/0000-0001-9587-7953; nahi, hareth/0000-0003-4711-5094; Corradini, Paolo/0000-0002-9186-1353; Elghandour, ASHRAF/0000-0002-8841-048X FU Novartis Pharmaceuticals FX Novartis Pharmaceuticals. NR 28 TC 155 Z9 159 U1 9 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2014 VL 15 IS 11 BP 1195 EP 1206 DI 10.1016/S1470-2045(14)70440-1 PG 12 WC Oncology SC Oncology GA AQ8QY UT WOS:000343096800045 PM 25242045 ER PT J AU Liu, JF Barry, WT Birrer, M Lee, JM Buckanovich, RJ Fleming, GF Rimel, BJ Buss, MK Nattam, S Hurteau, J Luo, WX Quy, P Whalen, C Obermayer, L Lee, H Winer, EP Kohn, EC Ivy, SP Matulonis, UA AF Liu, Joyce F. Barry, William T. Birrer, Michael Lee, Jung-Min Buckanovich, Ronald J. Fleming, Gini F. Rimel, B. J. Buss, Mary K. Nattam, Sreenivasa Hurteau, Jean Luo, Weixiu Quy, Philippa Whalen, Christin Obermayer, Lisa Lee, Hang Winer, Eric P. Kohn, Elise C. Ivy, S. Percy Matulonis, Ursula A. TI Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study SO LANCET ONCOLOGY LA English DT Article ID NEGATIVE BREAST-CANCER; POLY(ADP-RIBOSE) POLYMERASE; EPITHELIAL OVARIAN; DOWN-REGULATION; MAINTENANCE THERAPY; PRIMARY PERITONEAL; FALLOPIAN-TUBE; OPEN-LABEL; TRIAL; BEVACIZUMAB AB Background Olaparib is a poly(ADP-ribose) polymerase inhibitor and cediranib is an anti-angiogenic agent with activity against VEGF receptor (VEGFR) 1, VEGFR2, and VEGFR3. Both oral agents have antitumour activity in women with recurrent ovarian cancer, and their combination was active and had manageable toxicities in a phase 1 trial. We investigated whether this combination could improve progression-free survival (PFS) compared with olaparib monotherapy in women with recurrent platinum-sensitive ovarian cancer. Methods In our randomised, open-label, phase 2 study, we recruited women (aged >= 18 years) who had measurable platinum-sensitive, relapsed, high-grade serous or endometrioid ovarian, fallopian tube, or primary peritoneal cancer, or those with deleterious germline BRCA1/2 mutations from nine participating US academic medical centres. We randomly allocated participants (1:1) according to permuted blocks, stratified by germline BRCA status and previous anti-angiogenic therapy, to receive olaparib capsules 400 mg twice daily or the combination at the recommended phase 2 dose of cediranib 30 mg daily and olaparib capsules 200 mg twice daily. The primary endpoint was progression-free survival analysed in the intention-to-treat population. The phase 2 trial is no longer accruing patients. An interim analysis was conducted in November, 2013, after 50% of expected events had occurred and efficacy results were unmasked. The primary analysis was performed on March 31, 2014, after 47 events (66% of those expected). The trial is registered with ClinicalTrials. gov, number NCT01116648. Findings Between Oct 26, 2011, and June 3, 2013, we randomly allocated 46 women to receive olaparib alone and 44 to receive the combination of olaparib and cediranib. Median PFS was 17.7 months (95% CI 14.7-not reached) for the women treated with cediranib plus olaparib compared with 9.0 months (95% CI 5.7-16.5) for those treated with olaparib monotherapy (hazard ratio 0.42, 95% CI 0.23-0.76; p=0.005). Grade 3 and 4 adverse events were more common with combination therapy than with monotherapy, including fatigue (12 patients in the cediranib plus olaparib group vs five patients in the olaparib monotherapy group), diarrhoea (ten vs none), and hypertension (18 vs none). Interpretation Cediranib plus olaparib seems to improve PFS in women with recurrent platinum-sensitive high-grade serous or endometrioid ovarian cancer, and warrants study in a phase 3 trial. The side-effect profile suggests such investigations should include assessments of quality of life and patient-reported outcomes to understand the effects of a continuing oral regimen with that of intermittent chemotherapy. C1 [Liu, Joyce F.; Quy, Philippa; Whalen, Christin; Obermayer, Lisa; Winer, Eric P.; Matulonis, Ursula A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Barry, William T.; Luo, Weixiu] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Birrer, Michael] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Lee, Jung-Min; Kohn, Elise C.] NCI, Ctr Canc Res, Womens Malignancies Branch, Bethesda, MD 20892 USA. [Kohn, Elise C.; Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Buckanovich, Ronald J.] Univ Michigan, Dept Med Oncol, Ann Arbor, MI 48109 USA. [Fleming, Gini F.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. [Rimel, B. J.] Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Los Angeles, CA 90048 USA. [Buss, Mary K.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Nattam, Sreenivasa] Ft Wayne Med Oncol & Hematol, Dept Oncol, Ft Wayne, IN USA. [Hurteau, Jean] North Shore Univ Hlth Syst, Evanston Hosp, Div Gynecol Oncol, Evanston, IL 60201 USA. RP Liu, JF (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM joyce_liu@dfci.harvard.edu FU Cancer Therapy Evaluation Program of the National Cancer Institute -American Recovery and Reinvestment Act (ARRA) through US National Institutes of Health [3 U01 CA062490-16S2]; CJL Charitable Foundation; Intramural Program of the Center for Cancer Research (CCR); CCR; Division of Cancer Treatment and Diagnosis, National Cancer Institute, US National Institutes of Health, Bethesda, MD, USA FX This study was funded by the Cancer Therapy Evaluation Program of the National Cancer Institute and supported by an American Recovery and Reinvestment Act (ARRA) grant through the US National Institutes of Health (3 U01 CA062490-16S2). WTB was supported by the CJL Charitable Foundation. J-ML was supported by the Intramural Program of the Center for Cancer Research (CCR), and ECK by the CCR and Division of Cancer Treatment and Diagnosis, National Cancer Institute, US National Institutes of Health, Bethesda, MD, USA. The funding source had no role in the conduct, data collection, or analysis of the study. NR 31 TC 115 Z9 117 U1 3 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2014 VL 15 IS 11 BP 1207 EP 1214 DI 10.1016/S1470-2045(14)70391-2 PG 8 WC Oncology SC Oncology GA AQ8QY UT WOS:000343096800046 PM 25218906 ER PT J AU Jurczyszyn, A Czepiel, J Gdula-Argasinska, J Czapkiewicz, A Biesiada, G Droozdz, M Perucki, W Castillo, JJ AF Jurczyszyn, Artur Czepiel, Jacek Gdula-Argasinska, Joanna Czapkiewicz, Anna Biesiada, Grazyna Drozdz, Miroslaw Perucki, William Castillo, Jorge J. TI Erythrocyte membrane fatty acids in multiple myeloma patients SO LEUKEMIA RESEARCH LA English DT Article DE Multiple myeloma; Fatty acids; Erythrocyte membrane; Gas chromatography; Cluster analysis ID FADS1-FADS2 GENE-CLUSTER; NON-HODGKINS-LYMPHOMA; THERAPEUTIC TARGET; DESATURASE ACTIVITY; CANCER-RISK; SYNTHASE; CELLS; BIOSYNTHESIS; INFLAMMATION; TISSUES AB Mounting data show that fatty acids (FA) and fatty acid synthase (FAS) function could be potential targets for multiple myeloma (MM) therapy. Our study aimed at comparing the FA composition of erythrocyte membranes of MM patients and healthy controls. MM patients had higher saturated FA and n-6 polyunsaturated FA (PUFA) and lower monounsaturated, n-3 PUFA and trans-FA indices than controls. The n-3/n-6 PUFA ratio was lower in MM patients and there was distinct clustering of variants of individual FA in MM patients. The FA content of erythrocyte membrane could serve as a diagnostic and/or predictive biomarker in MM. (C) 2014 The Authors. Published by Elsevier Ltd. All rights reserved. C1 [Jurczyszyn, Artur] Univ Hosp, Dept Hematol, PL-31501 Krakow, Poland. [Czepiel, Jacek; Biesiada, Grazyna] Jagiellonian Univ, Coll Med, Dept Infect Dis, Krakow, Poland. [Gdula-Argasinska, Joanna] Jagiellonian Univ, Coll Med, Fac Pharm, Dept Radioligands, Krakow, Poland. [Czapkiewicz, Anna] AGH Univ Sci & Technol, Fac Management, Krakow, Poland. [Drozdz, Miroslaw] St Anna Hosp, Miechow, Poland. [Perucki, William] Jagiellonian Univ, Coll Med, Students Sci Soc, Krakow, Poland. [Castillo, Jorge J.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Jurczyszyn, A (reprint author), Univ Hosp, Dept Hematol, Ul Kopernika 17, PL-31501 Krakow, Poland. EM mmjurczy@cyf-kr.edu.pl RI Czapkiewicz, Anna/K-9242-2015; OI Gdula-Argasinska, Joanna/0000-0003-3501-8350; Castillo, Jorge/0000-0001-9490-7532 FU National Science Centre, Poland [DEC-2011/01/B/NZ7/00038] FX This project was partially supported by National Science Centre, Poland to the author Joanna Gdula-Argasinska DEC-2011/01/B/NZ7/00038. NR 46 TC 10 Z9 11 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD OCT PY 2014 VL 38 IS 10 BP 1260 EP 1265 DI 10.1016/j.leukres.2014.08.009 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA AQ8TL UT WOS:000343105300022 PM 25192858 ER PT J AU Marutani, E Sakaguchi, M Chen, W Sasakura, K Liu, JF Xian, M Hanaoka, K Nagano, T Ichinose, F AF Marutani, Eizo Sakaguchi, Masahiro Chen, Wei Sasakura, Kiyoshi Liu, Jifeng Xian, Ming Hanaoka, Kenjiro Nagano, Tetsuo Ichinose, Fumito TI Cytoprotective effects of hydrogen sulfide-releasing N-methyl-D-aspartate receptor antagonists mediated by intracellular sulfane sulfur SO MEDCHEMCOMM LA English DT Article ID PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; RAT; MK-801; DEATH AB Hydrogen sulfide (H2S) exerts a host of biological effects ranging from cytotoxicity to cytoprotection. Cytotoxicity of H2S in neurodegenerative diseases may be mediated by N-methyl-D-aspartate receptor (NMDAR) activation. To exploit cytoprotective effects of H2S while minimizing its toxicity, we synthesized a series of H2S-releasing NMDAR antagonists and examined their effects against 1-methyl-4-phenylpyridinium (MPP+)-induced cell death, a cellular model of Parkinson's disease. We observed that cytoprotective effects of H2S-releasing NMDAR antagonists correlated with their ability to increase intracellular sulfane sulfur, but not H2S, levels. These studies suggest that H2S-donor compounds that increase intracellular sulfane sulfur levels are potentially useful neuroprotective agents against neurodegenerative diseases. C1 [Marutani, Eizo; Sakaguchi, Masahiro; Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Marutani, Eizo; Sakaguchi, Masahiro; Ichinose, Fumito] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Wei; Xian, Ming] Washington State Univ, Dept Chem, Pullman, WA 99164 USA. [Sasakura, Kiyoshi; Hanaoka, Kenjiro; Nagano, Tetsuo] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo 1130033, Japan. [Liu, Jifeng] Aberjona Labs Inc, Beverly, MA USA. RP Marutani, E (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM emarutani@mgh.harvard.edu FU National Institutes of Health (NIH) [HL101930]; ACS-Teva USA Scholar Award; NIH [HL116571] FX This work was supported by the National Institutes of Health (NIH) grant HL101930 to F. Ichinose and ACS-Teva USA Scholar Award, and NIH grant HL116571 to M. Xian. NR 22 TC 7 Z9 9 U1 1 U2 14 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 EI 2040-2511 J9 MEDCHEMCOMM JI MedChemComm PD OCT PY 2014 VL 5 IS 10 BP 1577 EP 1583 DI 10.1039/c4md00180j PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA AQ7TW UT WOS:000343023100020 PM 25431645 ER PT J AU Damato, AL Viswanathan, AN Don, SM Hansen, JL Cormack, RA AF Damato, Antonio L. Viswanathan, Akila N. Don, Sarah M. Hansen, Jorgen L. Cormack, Robert A. TI A system to use electromagnetic tracking for the quality assurance of brachytherapy catheter digitization SO MEDICAL PHYSICS LA English DT Article DE brachytherapy; quality assurance; electromagnetic tracking ID UNCERTAINTIES; ACCURACY AB Purpose: To investigate the use of a system using electromagnetic tracking (EMT), post-processing and an error-detection algorithm for detecting errors and resolving uncertainties in high-dose-rate brachytherapy catheter digitization for treatment planning. Methods: EMT was used to localize 15 catheters inserted into a phantom using a stepwise acquisition technique. Five distinct acquisition experiments were performed. Noise associated with the acquisition was calculated. The dwell location configuration was extracted from the EMT data. A CT scan of the phantom was performed, and five distinct catheter digitization sessions were performed. No a priori registration of the CT scan coordinate system with the EMT coordinate system was performed. CT-based digitization was automatically extracted from the brachytherapy plan DICOM files (CT), and rigid registration was performed between EMT and CT dwell positions. EMT registration error was characterized in terms of the mean and maximum distance between corresponding EMT and CT dwell positions per catheter. An algorithm for error detection and identification was presented. Three types of errors were systematically simulated: swap of two catheter numbers, partial swap of catheter number identification for parts of the catheters (mix), and catheter-tip shift. Error-detection sensitivity (number of simulated scenarios correctly identified as containing an error/number of simulated scenarios containing an error) and specificity (number of scenarios correctly identified as not containing errors/number of correct scenarios) were calculated. Catheter identification sensitivity (number of catheters correctly identified as erroneous across all scenarios/number of erroneous catheters across all scenarios) and specificity (number of catheters correctly identified as correct across all scenarios/number of correct catheters across all scenarios) were calculated. The mean detected and identified shift was calculated. Results: The maximum noise +/- 1 standard deviation associated with the EMT acquisitions was 1.0 +/- 0.1 mm, and the mean noise was 0.6 +/- 0.1 mm. Registration of all the EMT and CT dwell positions was associated with a mean catheter error of 0.6 +/- 0.2 mm, a maximum catheter error of 0.9 +/- 0.4 mm, a mean dwell error of 1.0 +/- 0.3 mm, and a maximum dwell error of 1.3 +/- 0.7 mm. Error detection and catheter identification sensitivity and specificity of 100% were observed for swap, mix and shift (>= 2.6 mm for error detection; >= 2.7 mm for catheter identification) errors. A mean detected shift of 1.8 +/- 0.4 mm and a mean identified shift of 1.9 +/- 0.4 mm were observed. Conclusions: Registration of the EMT dwell positions to the CT dwell positions was possible with a residual mean error per catheter of 0.6 +/- 0.2 mm and a maximum error for any dwell of 1.3 +/- 0.7 mm. These low residual registration errors show that quality assurance of the general characteristics of the catheters and of possible errors affecting one specific dwell position is possible. The sensitivity and specificity of the catheter digitization verification algorithm was 100% for swap and mix errors and for shifts >= 2.6 mm. On average, shifts >= 1.8 mm were detected, and shifts >= 1.9 mm were detected and identified. (C) 2014 American Association of Physicists in Medicine. C1 [Damato, Antonio L.; Viswanathan, Akila N.; Don, Sarah M.; Hansen, Jorgen L.; Cormack, Robert A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Damato, AL (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM adamato@lroc.harvard.edu FU Kaye Family Award FX The authors would like to thank Barbara Silver for reviewing this paper. This work was funded by Kaye Family Award. The authors report no conflicts of interest in conducting the research. NR 18 TC 10 Z9 10 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2014 VL 41 IS 10 AR 101702 DI 10.1118/1.4894710 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AQ7XF UT WOS:000343032400005 PM 25281941 ER PT J AU Li, XH Zhang, D Liu, B AF Li, Xinhua Zhang, Da Liu, Bob TI Longitudinal dose distribution and energy absorption in PMMA and water cylinders undergoing CT scans SO MEDICAL PHYSICS LA English DT Article DE computed tomography (CT); phantom; dose profile; width; energy absorption ID DOSIMETRY; EQUATIONS; PROFILES; LENGTH; SYSTEM; INDEX AB Purpose: The knowledge of longitudinal dose distribution provides the most direct view of the accumulated dose in computed tomography (CT) scanning. The purpose of this work was to perform a comprehensive study of dose distribution width and energy absorption with a wide range of subject sizes and beam irradiated lengths. Methods: Cumulative dose distribution along the z-axis was calculated based on the previously published CT dose equilibration data by Li, Zhang, and Liu [Med. Phys. 40, 031903 (10pp.) (2013)] and a mechanism for computing dose on axial lines by Li, Zhang, and Liu [Med. Phys. 39, 5347-5352 (2012)]. Full width at half maximum (FWHM), full width at tenth maximum (FWTM), the total energy (E) absorbed in a small cylinder of unit mass per centimeter square about the central or peripheral axis, and the energy (E-in) absorbed inside irradiated length (L) were subsequently extracted from the dose distribution. Results: Extensive results of FWHM, FWTM, and E-in/E were presented on the central and peripheral axes of infinitely long PMMA (diameters 6-50 cm) and water (diameters 6-55 cm) cylinders with L < 100 cm. FWHM was greater than the primary beam width only on the central axes of large phantoms and also with L ranging from a few centimeter to about 33 cm. FWTM generally increased with phantom diameter, and could be up to 32 cm longer than irradiated length, depending on L, phantom diameter and axis, but was insensitive to phantom material (PMMA or water). E-in/E increased with L and asymptotically approached unity for large L. As phantom diameter increased, E-in/E generally decreased, but asymptotically approached constant levels on the peripheral axes of large phantoms. A heuristic explanation of dose distribution width results was presented. Conclusions: This study enables the reader to gain a comprehensive view of dose distribution width and energy absorption and provides useful data for estimating doses to organs inside or beyond the irradiated region. The dose length product (DLP) presented by CT scanners is equal to neither E nor E-in. Both E and E-in can be evaluated using the equations and results presented in this paper and are robust with both constant and variable tube current scanning techniques. (C) 2014 American Association of Physicists in Medicine. C1 [Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA. Massachusetts Gen Hosp, Webster Ctr Adv Res & Educ Radiat, Dept Radiol, Boston, MA 02114 USA. RP Liu, B (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA. EM bliu7@mgh.harvard.edu NR 20 TC 4 Z9 4 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2014 VL 41 IS 10 AR 101912 DI 10.1118/1.4895825 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AQ7XF UT WOS:000343032400028 PM 28036935 ER PT J AU Lorsakul, A Li, QZ Trott, CM Hoog, C Petibon, Y Ouyang, JS Laine, AF El Fakhri, G AF Lorsakul, Auranuch Li, Quanzheng Trott, Cathryn M. Hoog, Christopher Petibon, Yoann Ouyang, Jinsong Laine, Andrew F. El Fakhri, Georges TI 4D numerical observer for lesion detection in respiratory-gated PET SO MEDICAL PHYSICS LA English DT Article DE numerical observer; channelized Hotelling observer; respiratory-gated PET imaging; detection task; image quality assessment ID MOTION CORRECTION; HOTELLING-OBSERVER; MODEL OBSERVERS; DETECTION PERFORMANCE; NOISE PROPERTIES; IMAGE QUALITY; EM ALGORITHM; LUNG-CANCER; RECONSTRUCTION; SPECT AB Purpose: Respiratory-gated positron emission tomography (PET)/computed tomography protocols reduce lesion smearing and improve lesion detection through a synchronized acquisition of emission data. However, an objective assessment of image quality of the improvement gained from respiratory-gated PET is mainly limited to a three-dimensional (3D) approach. This work proposes a 4D numerical observer that incorporates both spatial and temporal informations for detection tasks in pulmonary oncology. Methods: The authors propose a 4D numerical observer constructed with a 3D channelized Hotelling observer for the spatial domain followed by a Hotelling observer for the temporal domain. Realistic F-18-fluorodeoxyglucose activity distributions were simulated using a 4D extended cardiac torso anthropomorphic phantom including 12 spherical lesions at different anatomical locations (lower, upper, anterior, and posterior) within the lungs. Simulated data based on Monte Carlo simulation were obtained using GEANT4 application for tomographic emission (GATE). Fifty noise realizations of six respiratory-gated PET frames were simulated by GATE using a model of the Siemens Biograph mMR scanner geometry. PET sinograms of the thorax background and pulmonary lesions that were simulated separately were merged to generate different conditions of the lesions to the background (e.g., lesion contrast and motion). A conventional ordered subset expectation maximization (OSEM) reconstruction (5 iterations and 6 subsets) was used to obtain: (1) gated, (2) nongated, and (3) motion-corrected image volumes (a total of 3200 subimage volumes: 2400 gated, 400 nongated, and 400 motion-corrected). Lesion-detection signal-to-noise ratios (SNRs) were measured in different lesion-to-background contrast levels (3.5, 8.0, 9.0, and 20.0), lesion diameters (10.0, 13.0, and 16.0 mm), and respiratory motion displacements (17.6-31.3 mm). The proposed 4D numerical observer applied on multiple-gated images was compared to the conventional 3D approach applied on the nongated and motion-corrected images. Results: On average, the proposed 4D numerical observer improved the detection SNR by 48.6% (p < 0.005), whereas the 3D methods on motion-corrected images improved by 31.0% (p < 0.005) as compared to the nongated method. For all different conditions of the lesions, the relative SNR measurement (Gain = SNRObserved/SNRNongated) of the 4D method was significantly higher than one from the motion-corrected 3D method by 13.8% (p < 0.02), where Gain(4D) was 1.49 +/- 0.21 and Gain(3D) was 1.31 +/- 0.15. For the lesion with the highest amplitude of motion, the 4D numerical observer yielded the highest observer-performance improvement (176%). For the lesion undergoing the smallest motion amplitude, the 4D method provided superior lesion detectability compared with the 3D method, which provided a detection SNR close to the nongated method. The investigation on a structure of the 4D numerical observer showed that a Laguerre-Gaussian channel matrix with a volumetric 3D function yielded higher lesion-detection performance than one with a 2D-stack-channelized function, whereas a different kind of channels that have the ability to mimic the human visual system, i.e., difference-of-Gaussian, showed similar performance in detecting uniform and spherical lesions. The investigation of the detection performance when increasing noise levels yielded decreasing detection SNR by 27.6% and 41.5% for the nongated and gated methods, respectively. The investigation of lesion contrast and diameter showed that the proposed 4D observer preserved the linearity property of an optimal-linear observer while the motion was present. Furthermore, the investigation of the iteration and subset numbers of the OSEM algorithm demonstrated that these parameters had impact on the lesion detectability and the selection of the optimal parameters could provide the maximum lesion-detection performance. The proposed 4D numerical observer outperformed the other observers for the lesion-detection task in various lesion conditions and motions. Conclusions: The 4D numerical observer shows substantial improvement in lesion detectability over the 3D observer method. The proposed 4D approach could potentially provide a more reliable objective assessment of the impact of respiratory-gated PET improvement for lesion-detection tasks. On the other hand, the 4D approach may be used as an upper bound to investigate the performance of the motion correction method. In future work, the authors will validate the proposed 4D approach on clinical data for detection tasks in pulmonary oncology. (C) 2014 American Association of Physicists in Medicine. C1 [Lorsakul, Auranuch; Li, Quanzheng; Hoog, Christopher; Petibon, Yoann; Ouyang, Jinsong; El Fakhri, Georges] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Lorsakul, Auranuch; Laine, Andrew F.] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA. [Li, Quanzheng; Ouyang, Jinsong; El Fakhri, Georges] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Trott, Cathryn M.] Curtin Univ, Int Ctr Radio Astron Res, Bentley, WA 6102, Australia. [Trott, Cathryn M.] ARC Ctr Excellence All Sky Astrophys CAASTRO, Redfem, NSW 2016, Australia. RP El Fakhri, G (reprint author), Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM elfakhri@pet.mgh.harvard.edu RI Trott, Cathryn/B-5325-2013 OI Trott, Cathryn/0000-0001-6324-1766 FU National Institutes of Health (NIH) [R01HL110241, R01CA165221, R01HL118261]; Australian Research Council Centre of Excellence for All-sky Astrophysics (CAASTRO) [CE110001020] FX This work was supported in part by Grant Nos. R01HL110241, R01CA165221, R01HL118261, and R01HL118261 from the National Institutes of Health (NIH). Dr. Trott would like to acknowledge the Australian Research Council Centre of Excellence for All-sky Astrophysics (CAASTRO), through project number CE110001020. The authors would like to thank Dr. Nathaniel M. Alpert for his valuable suggestions. The contents of this article are solely the responsibility of the authors and do not represent the official views of the NIH. NR 60 TC 2 Z9 2 U1 0 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2014 VL 41 IS 10 AR 102504 DI 10.1118/1.4895975 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AQ7XF UT WOS:000343032400043 PM 25281979 ER PT J AU Fiskus, W Sharma, S Qi, J Shah, B Devaraj, SGT Leveque, C Portier, BP Iyer, S Bradner, JE Bhalla, KN AF Fiskus, Warren Sharma, Sunil Qi, Jun Shah, Bhavin Devaraj, Santhana G. T. Leveque, Christopher Portier, Bryce P. Iyer, Swaminathan Bradner, James E. Bhalla, Kapil N. TI BET Protein Antagonist JQ1 Is Synergistically Lethal with FLT3 Tyrosine Kinase Inhibitor (TKI) and Overcomes Resistance to FLT3-TKI in AML Cells Expressing FLT-ITD SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HISTONE DEACETYLASE INHIBITOR; THERAPEUTIC TARGET; P-TEFB; TRANSCRIPTIONAL REGULATION; SELECTIVE-INHIBITION; ACTIVATION; BROMODOMAIN; BRD4; DOMAIN AB Recently, treatment with bromodomain and extraterminal protein antagonist (BA) such as JQ1 has been shown to inhibit growth and induce apoptosis of human acute myelogenous leukemia (AML) cells, including those expressing FLT3-ITD. Here, we demonstrate that cotreatment with JQ1 and the FLT3 tyrosine kinase inhibitor (TKI) ponatinib or AC220 synergistically induce apoptosis of cultured and primary CD34(+) human AML blast progenitor cells (BPC) expressing FLT3-ITD. Concomitantly, as compared with each agent alone, cotreatment with JQ1 and the FLT3-TKI caused greater attenuation of c-MYC, BCL2, and CDK4/6. Simultaneously, cotreatment with JQ1 and the FLT3-TKI increased the levels of p21, BIM, and cleaved PARP, as well as mediated marked attenuation of p-STAT5, p-AKT, and p-ERK1/2 levels in AML BPCs. Conversely, cotreatment with JQ1 and FLT3-TKI was significantly less active against CD34(+) normal bone marrow progenitor cells. Knockdown of BRD4 by short hairpin RNA also sensitized AML cells to FLT3-TKI. JQ1 treatment induced apoptosis of mouse Ba/F3 cells ectopically expressing FLT3-ITD with or without FLT3-TKI-resistant mutations F691L and D835V. Compared with the parental human AML FLT3-ITD-expressing MOLM13, MOLM13-TKIR cells resistant to AC220 were markedly more sensitive to JQ1-induced apoptosis. Furthermore, cotreatment with JQ1 and the pan-histone deacetylase inhibitor (HDI) panobinostat synergistically induced apoptosis of FLT3-TKI-resistant MOLM13-TKIR and MV4-11-TKIR cells. Collectively, these findings support the rationale for determining the in vivo activity of combined therapy with BA and FLT3-TKI against human AML cells expressing FLT3-ITD or with BA and HDI against AML cells resistant to FLT3-TKI. (C)2014 AACR. C1 [Fiskus, Warren] Baylor Coll Med, Houston, TX 77030 USA. [Sharma, Sunil] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Qi, Jun; Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shah, Bhavin; Devaraj, Santhana G. T.; Leveque, Christopher; Portier, Bryce P.; Iyer, Swaminathan; Bhalla, Kapil N.] Houston Methodist Res Inst, Houston, TX USA. RP Bhalla, KN (reprint author), Houston Methodist Res Inst, 6670 Bertner Ave,R9-113, Houston, TX 77030 USA. EM knbhalla@tmhs.org FU NIH [R01 CA171338] FX This work was supported by a grant from the NIH awarded to K.N. Bhalla (R01 CA171338). NR 50 TC 36 Z9 37 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2014 VL 13 IS 10 BP 2315 EP 2327 DI 10.1158/1535-7163.MCT-14-0258 PG 13 WC Oncology SC Oncology GA AQ9AP UT WOS:000343132700006 PM 25053825 ER PT J AU Falcone, GJ Brouwers, HB Biffi, A Anderson, CD Battey, TWK Ayres, AM Vashkevich, A Schwab, KM Rost, NS Goldstein, JN Viswanathan, A Greenberg, SM Rosand, J AF Falcone, Guido J. Brouwers, H. Bart Biffi, Alessandro Anderson, Christopher D. Battey, Thomas W. K. Ayres, Alison M. Vashkevich, Anastasia Schwab, Kristin M. Rost, Natalia S. Goldstein, Joshua N. Viswanathan, Anand Greenberg, Steven M. Rosand, Jonathan TI Warfarin and Statins are Associated with Hematoma Volume in Primary Infratentorial Intracerebral Hemorrhage SO NEUROCRITICAL CARE LA English DT Article DE Cerebellar hemorrhage; Brainstem hemorrhage; ICH volume; Anticoagulation; Warfarin; Statins ID CEREBELLAR HEMORRHAGE; METAANALYSIS; MANAGEMENT; STROKE; MORTALITY; RISK AB Despite extensive studies of supratentorial intracerebral hemorrhage (ICH), limited data are available on determinants of hematoma volume in infratentorial ICH. We therefore aimed to identify predictors of infratentorial ICH volume and to evaluate whether location specificity exists when comparing cerebellar to brainstem ICH. We undertook a retrospective analysis of 139 consecutive infratentorial ICH cases (95 cerebellar and 44 brainstem ICH) prospectively enrolled in a single-center study of ICH. ICH volume was measured on the CT scan obtained upon presentation to the Emergency Department using an established computer-assisted method. We used linear regression to identify determinants of log-transformed ICH volume and logistic regression to evaluate their role in surgical evacuation. Median ICH volumes for all infratentorial, cerebellar, and brainstem ICH were nine [interquartile range (IQR), 3-23], ten (IQR, 3-25), and eight (IQR, 3-19) milliliters, respectively. Thirty-six patients were on warfarin treatment, 31 underwent surgical evacuation, and 65 died within 90 days. Warfarin was associated with an increase in ICH volume of 86 % [beta = 0.86, standard error (SE) = 0.29, p = 0.003] and statin treatment with a decrease of 69 % (beta = -69, SE = 0.26, p = 0.008). Among cerebellar ICH subjects, those on warfarin were five times more likely to undergo surgical evacuation (OR = 4.80, 95 % confidence interval 1.63-14.16, p = 0.005). Warfarin exposure increases ICH volume in infratentorial ICH. Further studies will be necessary to confirm the inverse relation observed between statins and ICH volume. C1 [Falcone, Guido J.; Brouwers, H. Bart; Biffi, Alessandro; Anderson, Christopher D.; Battey, Thomas W. K.; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Falcone, Guido J.; Brouwers, H. Bart; Biffi, Alessandro; Anderson, Christopher D.; Battey, Thomas W. K.; Ayres, Alison M.; Vashkevich, Anastasia; Schwab, Kristin M.; Rost, Natalia S.; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Falcone, Guido J.; Brouwers, H. Bart; Biffi, Alessandro; Anderson, Christopher D.; Battey, Thomas W. K.; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Dept Neurol, Boston, MA 02114 USA. [Falcone, Guido J.; Brouwers, H. Bart; Biffi, Alessandro; Anderson, Christopher D.; Battey, Thomas W. K.; Rost, Natalia S.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Falcone, Guido J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN-6818, Boston, MA 02114 USA. EM jrosand@partners.org RI Goldstein, Joshua/H-8953-2016; Falcone, Guido/L-2287-2016; OI Falcone, Guido/0000-0002-6407-0302; Anderson, Christopher/0000-0002-0053-2002 FU National Institutes of Health-the National Institute of Neurological Disorders and Stroke [R01NS073344, R01NS059727, 5K23NS059774]; American Heart Association [0755984T]; NIH-NINDS SPOTRIAS fellowship [P50NS061343]; American Brain Foundation FX All funding entities had no involvement in study design, data collection, analysis, interpretation, writing of the manuscript, and in the decision to submit for publication. The project described was supported by the National Institutes of Health-the National Institute of Neurological Disorders and Stroke (Grant Numbers R01NS073344, R01NS059727, 5K23NS059774) and the American Heart Association (Grant Number 0755984T). Dr. Brouwers was supported by the NIH-NINDS SPOTRIAS fellowship Grant P50NS061343. Dr. Anderson was supported by the American Brain Foundation. NR 22 TC 4 Z9 5 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 OCT PY 2014 VL 21 IS 2 BP 192 EP 199 DI 10.1007/s12028-013-9839-9 PG 8 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA AQ9AR UT WOS:000343132900004 PM 23839705 ER PT J AU Whalen, MJ AF Whalen, Michael J. TI Cerebrovascular Autoregulation in Diabetic Ketoacidosis: Time to Go With the (Microvascular Cerebral Blood) Flow! SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Editorial Material DE autoregulation; cerebral blood flow; children; diabetic ketoacidosis; diffuse correlation spectroscopy ID TRANSCRANIAL DOPPLER; SUBARACHNOID HEMORRHAGE; CHILDREN; EDEMA; HYPERTENSION; HYPEREMIA C1 [Whalen, Michael J.] Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Boston, MA 02114 USA. [Whalen, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. RP Whalen, MJ (reprint author), Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Boston, MA 02114 USA. FU NINDS NIH HHS [R01 NS064545] NR 16 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 EI 1947-3893 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD OCT PY 2014 VL 15 IS 8 BP 779 EP 780 DI 10.1097/PCC.0000000000000204 PG 2 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA AQ8CD UT WOS:000343049200022 PM 25280150 ER PT J AU Kaban, LB Padwa, B Mulliken, JB AF Kaban, Leonard B. Padwa, Bonnie Mulliken, John B. TI Mandibular Deformity in Hemifacial Microsomia: A Reassessment of the Pruzansky and Kaban Classification SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter C1 [Kaban, Leonard B.; Padwa, Bonnie; Mulliken, John B.] Massachusetts Gen Hosp, Boston Childrens Hosp, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM lkaban@partners.org NR 5 TC 1 Z9 1 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 2014 VL 134 IS 4 BP 657E EP 658E DI 10.1097/PRS.0000000000000547 PG 4 WC Surgery SC Surgery GA AQ8TM UT WOS:000343105400024 PM 25357063 ER PT J AU Salinas, HM Broelsch, GF Fernandes, JR McCormack, MC Meppelink, AM Randolph, MA Colwell, AS Austen, WG AF Salinas, Harry M. Broelsch, G. Felix Fernandes, Justin R. McCormack, Michael C. Meppelink, Amanda M. Randolph, Mark A. Colwell, Amy S. Austen, William G., Jr. TI Comparative Analysis of Processing Methods in Fat Grafting SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CELL-ASSISTED LIPOTRANSFER; ASPIRATED ADIPOSE-TISSUE; AUTOLOGOUS FAT; BREAST AUGMENTATION; SUPPORTIVE USE; STEM-CELLS; TRANSPLANTATION; CENTRIFUGATION; LIPOSUCTION; SURVIVAL AB Background: Centrifugation is a popular processing method, with an unclear mechanism of action. Hypotheses include fat concentration, reduced inflammatory response by removal of blood, and concentration of adipose-derived stem cells. The authors performed multiple experiments to determine the role of centrifugation and compared it with a different processing method (mesh/gauze technique). Methods: Lipoaspirate components were quantified after centrifugation at increasing speed to determine concentration efficacy. For comparison, the authors quantified the concentration efficacy of mesh/gauze. They also compared the number of adipose-derived stem cells isolated by either method. To determine the effects of each component, they compared fat alone to fat mixed with various spinoff components in a mouse model. They also compared centrifugation to mesh/gauze. Results: The adipocyte fraction remains constant above 5000 g, whereas 1200 g results in 91 percent concentrated fat. Mesh/gauze also results in 90 percent concentrated fat. The number of adipose-derived stem cells in 1 g of fat was 1603 +/- 2020 and 1857 +/- 1832 in the centrifuge and mesh/gauze groups, respectively (p = 0.86). Five "add-back" groups were created: fat plus oil, fat plus surgical tumescence, fat plus fresh tumescence, fat plus cell pellets and fresh tumescence, and fat plus cell pellets. The fat-only group had better retention than the groups mixed with tumescence, regardless of whether it was surgical, fresh, or had cell pellets. Oil did not affect grafts. Centrifugation at 1200 g was equivalent to mesh/gauze (0.73 +/- 0.12 g and 0.72 +/- 0.13 g, respectively). Conclusions: Centrifugation improves graft retention by concentration of the adipocyte fraction. The concentration efficacy of mesh/gauze is equivalent to centrifugation at 1200 g, with equivalent in vivo outcomes. C1 [Salinas, Harry M.; Broelsch, G. Felix; Fernandes, Justin R.; McCormack, Michael C.; Meppelink, Amanda M.; Randolph, Mark A.; Colwell, Amy S.; Austen, William G., Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Austen, WG (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 15 Parkman St,WAC 435, Boston, MA 02114 USA. EM wausten@partners.org NR 36 TC 11 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 2014 VL 134 IS 4 BP 675 EP 683 DI 10.1097/PRS.0000000000000524 PG 9 WC Surgery SC Surgery GA AQ8TM UT WOS:000343105400043 PM 24945949 ER PT J AU Eberlin, KR Leonard, DA Austen, WG Yaremchuk, MJ Mudgal, CS Winograd, JM Cetrulo, CL AF Eberlin, Kyle R. Leonard, David A. Austen, William G., Jr. Yaremchuk, Michael J. Mudgal, Chaitanya S. Winograd, Jonathan M. Cetrulo, Curtis L., Jr. TI The Volar Forearm Fasciocutaneous Extension: A Strategy to Maximize Vascular Outflow in Post-Burn Injury Hand Transplantation SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ELECTRICAL BURN INJURIES; FACIAL TRANSPLANTATION; MICROVASCULAR RECONSTRUCTION AB Patients with circumferential extremity burns may have a deficiency of cutaneous veins, which presents a challenge for both autologous reconstruction and vascularized composite allotransplantation. The authors present a 44-year-old, left-hand-dominant man with metacarpal level amputation of his left hand secondary to burn injury. Extensive prior debridement and skin grafting resulted in nearly total absence of cutaneous veins in the forearm. The patient underwent unilateral left hand transplantation with an allograft designed to include a volar forearm fasciocutaneous extension supplied by the radial artery and including the basilic vein to permit augmented venous drainage by means of anastomosis at the antecubital fossa. The volar forearm fasciocutaneous extension can increase vessel caliber and possibly improve reliability in the setting of hand transplantation and should be considered following severe burn injury. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Div Plast Surg, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Cambridge, MA 02138 USA. RP Cetrulo, CL (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Wang Ambulatory Care Ctr 435,55 Fruit St, Boston, MA 02114 USA. EM ccetrulo@partners.org NR 15 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 2014 VL 134 IS 4 BP 731 EP 735 DI 10.1097/PRS.0000000000000508 PG 5 WC Surgery SC Surgery GA AQ8TM UT WOS:000343105400048 PM 25357032 ER PT J AU Gfrerer, L Shubinets, V Hoyos, T Kong, YW Nguyen, C Pietschmann, P Morton, CC Maas, RL Liao, EC AF Gfrerer, Lisa Shubinets, Valeriy Hoyos, Tatiana Kong, Yawei Nguyen, Christina Pietschmann, Peter Morton, Cynthia C. Maas, Richard L. Liao, Eric C. TI Functional Analysis of SPECC1L in Craniofacial Development and Oblique Facial Cleft Pathogenesis SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID POPLITEAL PTERYGIUM SYNDROMES; NEURAL CREST CELLS; OROFACIAL CLEFTS; ZEBRAFISH PALATE; IRF6; MORPHOGENESIS; WOUDE; MOUSE; BIRTH; MICE AB Background: Oblique facial clefts, also known as Tessier clefts, are severe orofacial clefts, the genetic basis of which is poorly understood. Human genetics studies revealed that disruption in SPECC1L resulted in oblique facial clefts, demonstrating that oblique facial cleft malformation has a genetic basis. An important step toward innovation in treatment of oblique facial clefts would be improved understanding of its genetic pathogenesis. The authors exploit the zebrafish model to elucidate the function of SPECC1L by studying its homolog, specc1lb. Methods: Gene and protein expression analysis was carried out by reverse-transcriptase polymerase chain reaction and immunohistochemistry staining. Morpholino knockdown, mRNA rescue, lineage tracing and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assays were performed for functional analysis. Results: Expression of specc1lb was detected in epithelia juxtaposed to chondrocytes. Knockdown of specc1lb resulted in bilateral clefts between median and lateral elements of the ethmoid plate, structures analogous to the frontonasal process and the paired maxillary processes. Lineage tracing analysis revealed that cranial neural crest cells contributing to the frontonasal prominence failed to integrate with the maxillary prominence populations. Cells contributing to lower jaw structures were able to migrate to their destined pharyngeal segment but failed to converge to form mandibular elements. Conclusions: These results demonstrate that specc1lb is required for integration of frontonasal and maxillary elements and convergence of mandibular prominences. The authors confirm the role of SPECC1L in orofacial cleft pathogenesis in the first animal model of Tessier cleft, providing morphogenetic insight into the mechanisms of normal craniofacial development and oblique facial cleft pathogenesis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Cambridge, MA 02138 USA. Med Univ Vienna, Ctr Pathophysiol Infectiol & Immunol, Vienna, Austria. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol, Cambridge, MA 02138 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. RP Liao, EC (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM cliao@mgh.harvard.edu FU Shriners Hospital for Children; March of Dimes Basil O'Connor Award; Plastic Surgery Foundation; Doctoral Fellowship Programme of the Austrian Academy of Sciences; Howard Hughes Medical Institute Medical Student Award; Shriners Hospitals for Children Research Fellowship Award; National Institute of General Medical Sciences grant [PO1GM061354] FX The authors appreciate support by the Shriners Hospital for Children (to E. C. L.), the March of Dimes Basil O'Connor Award (to E. C. L.), the Plastic Surgery Foundation, the Doctoral Fellowship Programme of the Austrian Academy of Sciences (to L. G.), a Howard Hughes Medical Institute Medical Student Award (to V. S.), a Shriners Hospitals for Children Research Fellowship Award (to Y.K.), and National Institute of General Medical Sciences grant PO1GM061354 (to C. C. M.). They thank Renee Ethier for excellent care of their aquatics facility. Jenna Galloway and their laboratory colleagues provided valuable feedback and review of this article. NR 53 TC 8 Z9 8 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 2014 VL 134 IS 4 BP 748 EP 759 DI 10.1097/PRS.0000000000000517 PG 12 WC Surgery SC Surgery GA AQ8TM UT WOS:000343105400050 PM 25357034 ER PT J AU Gfrerer, L Maman, DY Tessler, O Austen, WG AF Gfrerer, Lisa Maman, Daniel Y. Tessler, Oren Austen, William G., Jr. TI Nonendoscopic Deactivation of Nerve Triggers in Migraine Headache Patients: Surgical Technique and Outcomes SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CORRUGATOR SUPERCILII MUSCLE; TOXIN TYPE-A; BOTULINUM TOXIN; OCCIPITAL NERVE; AURICULOTEMPORAL NERVE; COMPRESSION POINTS; ANATOMY; DECOMPRESSION; PATTERNS; PREVALENCE AB Background: Low efficacy, significant side effects, and refractory patients often limit the medical treatment of migraine headache. However, new surgical options have emerged. Dr. Bahman Guyuron and others report response rates between 68 and 95 percent after surgical deactivation of migraine trigger sites in select patients. In an effort to replicate and expand migraine trigger-site deactivation surgery as a treatment option, the authors' group and others have developed nonendoscopic algorithms. The exclusion of endoscopic techniques may be useful for surgeons with little experience or limited access to the endoscope and in patients with challenging anatomy. Methods: Forty-three consecutive trigger deactivation procedures in 35 patients were performed. Preoperative and 12-month postoperative migraine questionnaires and patient charts were reviewed. Response to surgery in terms of migraine symptom relief and adverse events were evaluated. Results: The overall positive response rate was 90.7 percent. Total elimination of migraine headaches was reported in 51.3 percent of those with a positive response, greater than 80 percent resolution of symptoms was reported in 20.5 percent, and 28.2 percent had resolution between 50 and 80 percent. No significant effect was reported following 9.3 percent of procedures. There were no major adverse events. Conclusions: Nonendoscopic trigger deactivation is a safe and effective treatment in select migraine headache patients. Although surgical techniques and understanding of the mechanisms of relief are evolving, results continue to be promising. This series confirms that excellent results can be attained without the endoscope. The authors continue to study these patients prospectively to improve patient selection and refine the protocol. C1 [Gfrerer, Lisa; Maman, Daniel Y.; Tessler, Oren; Austen, William G., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA USA. RP Austen, WG (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM wausten@partners.org NR 34 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 2014 VL 134 IS 4 BP 771 EP 778 DI 10.1097/PRS.0000000000000507 PG 8 WC Surgery SC Surgery GA AQ8TM UT WOS:000343105400052 PM 24945947 ER PT J AU Silva, PS Diala, PA Hamam, RN Arrigg, PG Shah, ST Murtha, TL Schlossman, DK Cavallerano, JD Sun, JK Aiello, LP AF Silva, Paolo S. Diala, Prisca A. Hamam, Rola N. Arrigg, Paul G. Shah, Sabera T. Murtha, Timothy L. Schlossman, Deborah K. Cavallerano, Jerry D. Sun, Jennifer K. Aiello, Lloyd P. TI VISUAL OUTCOMES FROM PARS PLANA VITRECTOMY VERSUS COMBINED PARS PLANA VITRECTOMY, PHACOEMULSIFICATION, AND INTRAOCULAR LENS IMPLANTATION IN PATIENTS WITH DIABETES SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE diabetes; pars plana vitrectomy; cataract surgery; phacoemulsification; diabetic retinopathy ID EXTRACAPSULAR CATARACT-EXTRACTION; RETINOPATHY; SURGERY; EYES AB Purpose:To compare visual acuity outcomes and diabetic retinopathy progression after pars plana vitrectomy (PPV) versus combined pars plana vitrectomy and phacoemulsification (PPVCE) in patients with diabetes.Methods:Retrospective review of 222 consecutive diabetic patients undergoing PPV or PPVCE.Results:A total of 251 eyes of 222 patients were evaluated (PPV = 122, PPVCE = 129). Four-year follow-up was 64% (161 eyes). Overall, patients undergoing PPVCE had better preoperative visual acuity (PPVCE = 20/80, PPV = 20/160, P = 0.03). At 4-year follow-up, visual acuity improved (PPV = +22, PPVCE = +11 letters) compared with baseline in both groups. After correcting for baseline differences in visual acuity, no statistically significant difference in final visual acuity was observed (PPVCE = 20/32, PPV = 20/50, P = 0.09). Results did not differ substantially by surgical indication (vitreous hemorrhage, traction retinal detachment, epiretinal membrane, and/or diabetic macular edema). Cataract progression occurred in 64%, and cataract surgery was performed in 39% of phakic eyes undergoing PPV. Rates of diabetic retinopathy progression, vitreous hemorrhage, and retinal detachment were not statistically different. Neovascular glaucoma developed in 2 patients (2%) after PPV and 6 patients (8%) after PPVCE (P = 0.07).Conclusion:In diabetic patients, equivalent visual acuity improvement over 4 years was observed after PPV or PPVCE. Visual outcomes and retinopathy progression rates were not significantly different after either intervention, suggesting that PPVCE may be appropriate when indicated in patients with diabetes. C1 [Silva, Paolo S.; Diala, Prisca A.; Hamam, Rola N.; Arrigg, Paul G.; Shah, Sabera T.; Murtha, Timothy L.; Schlossman, Deborah K.; Cavallerano, Jerry D.; Sun, Jennifer K.; Aiello, Lloyd P.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. [Silva, Paolo S.; Diala, Prisca A.; Arrigg, Paul G.; Shah, Sabera T.; Murtha, Timothy L.; Schlossman, Deborah K.; Cavallerano, Jerry D.; Sun, Jennifer K.; Aiello, Lloyd P.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Silva, PS (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM paoloantonio.silva@joslin.harvard.edu OI Hamam, Rola/0000-0001-8044-4215 NR 22 TC 5 Z9 5 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD OCT PY 2014 VL 34 IS 10 BP 1960 EP 1968 DI 10.1097/IAE.0000000000000171 PG 9 WC Ophthalmology SC Ophthalmology GA AQ8BX UT WOS:000343048200014 PM 24830822 ER PT J AU Gelman, SK Freund, KB Shah, VP Sarraf, D AF Gelman, Susan K. Freund, K. Bailey Shah, Vinnie P. Sarraf, David TI THE PEARL NECKLACE SIGN A Novel Spectral Domain Optical Coherence Tomography Finding in Exudative Macular Disease SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE neovascular age-related macular degeneration; Coats disease; diabetic macular edema; exudative maculopathy; hard exudate; lipid; retinal arterial macroaneurysm; spectral domain optical coherence tomography ID RETINAL VEIN OCCLUSION; HYPERREFLECTIVE FOCI; SD-OCT; DEGENERATION; EDEMA; ASSOCIATION; DETACHMENT; SPACES; LAYER AB Purpose:To report a novel spectral domain optical coherence tomography finding in exudative macular disease, called the pearl necklace sign.Methods:A retrospective case series of 21 eyes (20 patients) with chronic exudative maculopathy resulting from age-related macular degeneration, diabetic macular edema, branch retinal vein occlusion, retinal arterial macroaneurysm, and Coats disease. Spectral domain optical coherence tomography images were carefully evaluated and correlated with color fundus photography, near-infrared reflectance, and fluorescein angiography.Results:A unique spectral domain optical coherence tomography macular finding of hyperreflective dots in a contiguous ring around the inner wall of cystoid spaces in the outer plexiform layer of the retina that the authors refer to as the pearl necklace sign was seen in all patients. Visual acuity ranged from 20/30 to hand motions. The cystoid spaces and the hyperreflective dots resolved in certain cases after anti-vascular endothelial growth factor therapy and/or focal macular laser, but tended to recur.Conclusion:Because the pearl necklace configuration can be found adjacent to hard exudates in the outer plexiform layer, the authors speculate that the hyperreflective material is composed of lipoproteins or lipid-laden macrophages. This novel spectral domain optical coherence tomography sign gives further insight into the development and progression of hard lipoprotein exudates in exudative maculopathy. C1 [Gelman, Susan K.; Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90095 USA. [Gelman, Susan K.; Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Freund, K. Bailey; Shah, Vinnie P.] Vitreous Retina Macula Consultants New York, New York, NY USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM dsarraf@ucla.edu OI Freund, K. Bailey/0000-0002-7888-9773 FU Genentech, Inc; Regeneron Pharmaceuticals, Inc; Heidelberg Engineering; Optos plc; Regeneron Pharmaceuticals, Inc (IST grant) FX Financial disclosures are as follows: KBF: Genentech, Inc (advisor); Regeneron Pharmaceuticals, Inc (advisor); Heidelberg Engineering (advisor); Optos plc (advisor); DS: Heidelberg Engineering (speaker), Regeneron Pharmaceuticals, Inc (IST grant). NR 29 TC 7 Z9 7 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD OCT PY 2014 VL 34 IS 10 BP 2088 EP 2095 DI 10.1097/IAE.0000000000000207 PG 8 WC Ophthalmology SC Ophthalmology GA AQ8BX UT WOS:000343048200030 PM 25020214 ER PT J AU Baker, JF Pullman-Mooar, S Ibrahim, S AF Baker, Joshua F. Pullman-Mooar, Sally Ibrahim, Said TI Management of rheumatoid arthritis Incorporating patient perceptions and objective measures SO RHEUMATOLOGY LA English DT Editorial Material ID DISEASE-ACTIVITY C1 [Baker, Joshua F.; Pullman-Mooar, Sally] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Baker, Joshua F.] Univ Penn, Div Epidemiol, Philadelphia, PA 19104 USA. [Baker, Joshua F.; Pullman-Mooar, Sally] Philadelphia VA Med Ctr, Div Rheumatol, Philadelphia, PA USA. [Ibrahim, Said] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Baker, JF (reprint author), Univ Penn, Div Rheumatol, Hosp Univ Penn, 8 Penn Tower Bldg,34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bakerjo@uphs.upenn.edu FU NIAMS NIH HHS [K24 AR055259] NR 10 TC 2 Z9 3 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD OCT PY 2014 VL 53 IS 10 BP 1721 EP 1722 PG 2 WC Rheumatology SC Rheumatology GA AR2MU UT WOS:000343422400001 PM 24505124 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Predictors of pain medication use for arthroplasty pain after revision total knee arthroplasty SO RHEUMATOLOGY LA English DT Article DE total knee replacement; pain medication; narcotic; NSAIDs; predictors; revision TKA; opioid ID QUALITY-OF-LIFE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; TOTAL HIP-ARTHROPLASTY; INPATIENT REHABILITATION; UNITED-STATES; POOR PAIN; OUTCOMES; NSAIDS; RISK; REPLACEMENT AB Objective. Our objective was to study the use of pain medications for persistent knee pain and their predictors after revision total knee arthroplasty (TKA). Methods. We examined whether demographic (gender, age) and clinical characteristics [BMI, co-morbidity measured by the Deyo-Charlson index (a 5-point increase), anxiety and depression] predict the use of NSAIDs and narcotic pain medications 2 and 5 years after revision TKA. Multivariable logistic regression adjusted for these predictors as well as operative diagnosis, American Society of Anesthesiologists class and distance from the medical centre. Results. A total of 1533 patients responded to the 2-year questionnaire and 881 responded to the 5-year questionnaire. NSAID use was reported by 13.4% (206/1533) of patients at 2 years and 16.7% (147/881) at 5 years. Narcotic medication use was reported by 5.4% (83/1533) of patients at 2 years and 5.9% (52/881) at 5 years. Significant predictors of the use of NSAIDs for index TKA pain at 2 and 5 years were age >60-70 years [odds ratio (OR) 0.62 (95% CI 0.39, 0.98) and 0.46 (0.25, 0.85)] compared with age <= 60 years and a higher Deyo-Charlson index [OR 0.51 (95% CI 0.28, 0.93)] per 5-point increase at 5-year after revision TKA. Significant predictors of narcotic pain medication use for index TKA pain were age >60-70 years [OR 0.41 (0.21, 0.78)] and >70-80 years [0.40 (95% CI 0.22, 0.73)] at 2 years and depression [OR 4.58 (95% CI 1.58, 13.18)] at 5 years. Conclusion. Younger age and depression were risk factors for the use of NSAIDs and narcotic pain medications for index TKA pain at 2- and 5-years after revision TKA. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.; Lewallen, David G.] Univ Alabama Birmingham, Dept Med, Sch Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Lewallen, David G.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Dept Med, Sch Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU Mayo Clinic Orthopedic Surgery research funds, National Institutes of Health (NIH) Clinical Translational Science Award [1 KL2 RR024151-01]; Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs); National Institute of Aging; National Cancer Institute FX Funding: This material is the result of work supported by research grants from the Mayo Clinic Orthopedic Surgery research funds, National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) and the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, AL, USA. J.A.S. is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), National Institute of Aging and National Cancer Institute. NR 37 TC 6 Z9 6 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD OCT PY 2014 VL 53 IS 10 BP 1752 EP 1758 DI 10.1093/rheumatology/ket443 PG 7 WC Rheumatology SC Rheumatology GA AR2MU UT WOS:000343422400008 PM 24459220 ER PT J AU Chellali, A Zhang, L Sankaranarayanan, G Arikatla, VS Ahn, W Derevianko, A Schwaitzberg, SD Jones, DB DeMoya, M Cao, CGL AF Chellali, A. Zhang, L. Sankaranarayanan, G. Arikatla, V. S. Ahn, W. Derevianko, A. Schwaitzberg, S. D. Jones, D. B. DeMoya, M. Cao, C. G. L. TI Validation of the VBLaST peg transfer task: a first step toward an alternate training standard SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Surgical training; Virtual reality (VR); Virtual Basic Laparoscopic Surgical Trainer (VBLaST); Fundamentals of Laparoscopic Skills (FLS); Force feedback ID LAPAROSCOPIC SKILL TRAINER; VIRTUAL-REALITY; CONSTRUCT-VALIDATION; SIMULATOR; PERFORMANCE; PROGRAM; FACE; VALIDITY; FEEDBACK; SURGERY AB Background The FLS trainer lacks objective and automated assessments of laparoscopic performance and requires a large supply of relatively expensive consumables. Virtual reality simulation has a great potential as a training and assessment tool of laparoscopic skills and can overcome some limitations of the FLS trainer. This study was carried out to assess the value of our Virtual Basic Laparoscopic Surgical Trainer (VBLaST(C)) in the peg transfer task compared to the FLS trainer and its ability to differentiate performance between novice, intermediate, and expert groups. Methods Thirty subjects were divided into three groups: novices (PGY1-2, n = 10), intermediates (PGY3-4, n = 10), and experts (PGY5, surgical fellows and attendings, n = 10). All subjects performed ten trials of the peg transfer task on each simulator. Assessment of laparoscopic performance was based on FLS scoring while a questionnaire was used for subjective evaluation. Results The performance scores in the two simulators were correlated, though subjects performed significantly better in the FLS trainer. Experts performed better than novices only on the FLS trainer while no significant differences were observed between the other groups. Moreover, a significant learning effect was found on both trainers, with a greater improvement of performance on the VBLaST(R). Finally, 82.6 % of the subjects preferred the FLS over the VBLaST(R) for surgical training which could be attributed to the novelty of the VR technology and existing deficiencies of the user interface for the VBLaST(R). Conclusion This study demonstrated that the VBLaST(R) reproduced faithfully some aspects of the FLS peg transfer task (such as color, size, and shape of the peg board, etc.) while other aspects require additional development. Future improvement of the user interface and haptic feedback will enhance the value of the system as an alternative to the FLS as the standard training tool for laparoscopic surgery skills. C1 [Chellali, A.; Schwaitzberg, S. D.] Harvard Univ, Sch Med, Dept Surg, Cambridge Hlth Alliance, Cambridge, MA 02138 USA. [Chellali, A.] Univ Evry, Dept Comp Engn, IBISC Lab, Evry, France. [Zhang, L.] Tufts Univ, Dept Mech Engn, Medford, MA 02155 USA. [Sankaranarayanan, G.; Arikatla, V. S.; Ahn, W.] Rensselaer Polytech Inst, Ctr Modeling Simulat & Imaging Med, Troy, NY USA. [Derevianko, A.; DeMoya, M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Jones, D. B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, Boston, MA 02215 USA. [Cao, C. G. L.] Wright State Univ, Dept Biomed Ind & Human Factors Engn, Russ Engn Ctr 207, Dayton, OH 45435 USA. RP Cao, CGL (reprint author), Wright State Univ, Dept Biomed Ind & Human Factors Engn, Russ Engn Ctr 207, 3640 Colonel Glenn Hwy, Dayton, OH 45435 USA. EM caroline.cao@wright.edu FU National Institutes of Health (NIH) [NIBIB R01 EB010037-01]; NIBIB/NIH [R01EB010037] FX This project was supported by the National Institutes of Health (NIH) Grant NIBIB R01 EB010037-01. This work was supported by NIBIB/NIH Grant # R01EB010037. NR 26 TC 5 Z9 5 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 EI 1432-2218 J9 SURG ENDOSC JI Surg. Endosc. PD OCT PY 2014 VL 28 IS 10 BP 2856 EP 2862 DI 10.1007/s00464-014-3538-2 PG 7 WC Surgery SC Surgery GA AR0AC UT WOS:000343222600014 PM 24771197 ER PT J AU Govindan, JA Ruvkun, G AF Govindan, J. Amaranath Ruvkun, Gary TI Pathogens SO VIRULENCE LA English DT Editorial Material ID IMMUNE-SYSTEM; TRANSLATIONAL INHIBITION; TRIGGERED IMMUNITY; DANGER; ACTIVATION; ASYMPTOTE; EFFECTORS; EVOLUTION; ANIMALS; ELEGANS C1 [Govindan, J. Amaranath; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Govindan, J. Amaranath; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Govindan, JA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM govindan@molbio.mgh.harvard.edu NR 28 TC 0 Z9 0 U1 1 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 EI 2150-5608 J9 VIRULENCE JI Virulence PD OCT 1 PY 2014 VL 5 IS 7 BP 695 EP 696 DI 10.4161/viru.36667 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AR0BS UT WOS:000343229900001 PM 25513769 ER PT J AU Rajamuthiah, R Mylonakis, E AF Rajamuthiah, Rajmohan Mylonakis, Eleftherios TI Effector triggered immunity Activation of innate immunity in metazoans by bacterial effectors SO VIRULENCE LA English DT Review DE innate immunity; metazoans; animal cells; PAMP; MAMP; DAMP; PRR; translation inhibition; actin cytoskeleton; pore forming toxin ID PORE-FORMING TOXINS; WISKOTT-ALDRICH-SYNDROME; NF-KAPPA-B; RHO-GTPASES; TRANSLATIONAL INHIBITION; CAENORHABDITIS-ELEGANS; EPITHELIAL-CELLS; SYNDROME PROTEIN; PLASMA-MEMBRANE; RECEPTOR 2 AB Pathogenic bacteria produce virulence factors called effectors, which are important components of the infection process. Effectors aid in pathogenesis by facilitating bacterial attachment, pathogen entry into or exit from the host cell, immunoevasion, and immunosuppression. Effectors also have the ability to subvert host cellular processes, such as hijacking cytoskeletal machinery or blocking protein translation. However, host cells possess an evolutionarily conserved innate immune response that can sense the pathogen through the activity of its effectors and mount a robust immune response. This "effector triggered immunity" (ETI) was first discovered in plants but recent evidence suggest that the process is also well conserved in metazoans. We will discuss salient points of the mechanism of ETI in metazoans from recent studies done in mammalian cells and invertebrate model hosts. C1 [Rajamuthiah, Rajmohan; Mylonakis, Eleftherios] Brown Univ, Rhode Isl Hosp, Div Infect Dis, Alpert Med Sch, Providence, RI 02903 USA. [Rajamuthiah, Rajmohan; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Rajamuthiah, R (reprint author), Brown Univ, Rhode Isl Hosp, Div Infect Dis, Alpert Med Sch, Providence, RI 02903 USA. EM Rrajamuthiah@molbio.mgh.harvard.edu RI Raja Muthiah, Raj Mohan/D-3932-2014 OI Raja Muthiah, Raj Mohan/0000-0002-6956-3130 NR 79 TC 9 Z9 9 U1 2 U2 12 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 EI 2150-5608 J9 VIRULENCE JI Virulence PD OCT 1 PY 2014 VL 5 IS 7 BP 697 EP 702 DI 10.4161/viru.29091 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AR0BS UT WOS:000343229900002 PM 25513770 ER PT J AU Driver, TH Shlipak, MG Katz, R Goldenstein, L Sarnak, MJ Hoofnagle, AN Siscovick, DS Kestenbaum, B de Boer, IH Ix, JH AF Driver, Todd H. Shlipak, Michael G. Katz, Ronit Goldenstein, Leonard Sarnak, Mark J. Hoofnagle, Andrew N. Siscovick, David S. Kestenbaum, Bryan de Boer, Ian H. Ix, Joachim H. TI Low Serum Bicarbonate and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Serum bicarbonate; metabolic acidosis; chronic kidney disease (CKD); kidney function; renal disease; disease progression; kidney disease trajectory ID GLOMERULAR-FILTRATION-RATE; DIETARY ACID LOAD; METABOLIC-ACIDOSIS; CKD; DISEASE; ABNORMALITIES; ASSOCIATION; MORTALITY; OUTCOMES AB Background: Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear. Study Design: Retrospective cohort study. Setting & Participants: 5,810 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m(2) using the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation. Predictors: Serum bicarbonate concentrations. Outcomes: Rapid kidney function decline (eGFR decline > 5% per year) and incident reduced eGFR (eGFR < 60 mL/min/1.73 m(2) with minimum rate of eGFR loss of 1 mL/min/1.73 m(2) per year). Results: Average bicarbonate concentration was 23.2 +/- 1.8 mEq/L. 1,730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%-20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03-1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate level, 21 mEq/L relative to 23-24 mEq/L was 1.35 (95% CI, 1.05-1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83-1.62) for incident reduced eGFR. Limitations: Cause of metabolic acidosis cannot be determined in this study. Conclusions: Lower serum bicarbonate concentrations are associated independently with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with baseline eGFR. 60 mL/min/1.73 m(2). If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria or may have a causal role in the development of eGFR, 60 mL/min/1.73 m(2). (C) 2014 by the National Kidney Foundation, Inc. C1 [Driver, Todd H.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA USA. [Katz, Ronit; Hoofnagle, Andrew N.; Siscovick, David S.; Kestenbaum, Bryan; de Boer, Ian H.] Univ Washington, Div Nephrol, Kidney Res Inst, Seattle, WA USA. [Goldenstein, Leonard; Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, San Diego, CA 92161 USA. [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, San Diego, CA 92161 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. RP Ix, JH (reprint author), Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu FU National Institute on Aging [5R01AG027002-07]; National Institute of Diabetes and Digestive and Kidney Diseases [1R01DK098234-01A1]; UCSF-CTSI [TL1 TR000144]; National Heart, Lung, and Blood Institute; National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]; National Center for Research Resources [UL1-TR-000040, UL1-TR-001079]; Clinical and Translational Science Award [UL1-RR-024156] FX Support: Drs Shlipak and Sarnak are supported by grant 5R01AG027002-07 from the National Institute on Aging; Drs Ix and Shlipak, by grant 1R01DK098234-01A1 from the National Institute of Diabetes and Digestive and Kidney Diseases; and Dr Driver, by grant TL1 TR000144 from UCSF-CTSI. MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with MESA investigators; support for MESA is provided by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute: by grants UL1-TR-000040 and UL1-TR-001079 from the National Center for Research Resources, and Clinical and Translational Science Award UL1-RR-024156. None of the funding agencies had any role in the study design, collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication. NR 28 TC 23 Z9 24 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2014 VL 64 IS 4 BP 534 EP 541 DI 10.1053/j.ajkd.2014.05.008 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AQ4CN UT WOS:000342739900012 PM 24953891 ER PT J AU Goldenstein, L Driver, TH Fried, LF Rifkin, DE Patel, KV Yenchek, RH Harris, TB Kritchevsky, SB Newman, AB Sarnak, MJ Shlipak, MG Ix, JH AF Goldenstein, Leonard Driver, Todd H. Fried, Linda F. Rifkin, Dena E. Patel, Kushang V. Yenchek, Robert H. Harris, Tamara B. Kritchevsky, Stephen B. Newman, Anne B. Sarnak, Mark J. Shlipak, Michael G. Ix, Joachim H. CA Hlth ABC Study Investigators TI Serum Bicarbonate Concentrations and Kidney Disease Progression in Community-Living Elders: The Health, Aging, and Body Composition (Health ABC) Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article ID GLOMERULAR-FILTRATION-RATE; INJURY MOLECULE-1 KIM-1; METABOLIC-ACIDOSIS; SODIUM-BICARBONATE; FUNCTION DECLINE; LIPOCALIN NGAL; RENAL BIOPSY; OLDER-ADULTS; CKD; RISK AB Background: In populations with prevalent chronic kidney disease (CKD), lower serum bicarbonate levels are associated with more rapid CKD progression, but whether lower bicarbonate levels also are associated with risk of incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 and CKD progression among community-living persons with predominantly preserved kidney function is unknown. Study Design: Longitudinal observational cohort study. Setting & Participants: Well-functioning community-living elders aged 70-79 years at inception. Predictor: Serum bicarbonate level measured at the time of collection by arterialized venous blood sample using an arterial blood gas analyzer. Outcomes: Change in eGFR over 7 years, and new eGFR, 60 mL/min/1.73 m(2) with a rate of loss of at least 1 mL/min/1.73 m(2) per year. Measurements: Linear and logistic regressions were used to evaluate associations of baseline serum bicarbonate level with change in eGFR and incident eGFR < 60 mL/min/1.73 m(2). Results: At baseline, mean eGFR was 84 +/- 16 (SD) mL/min/1.73 m(2), and serum bicarbonate level was 25.2 +/- 1.9 mmol/L. Compared with participants with higher bicarbonate concentrations (23.0-28.0 mmol/L), those with bicarbonate concentrations < 23 mmol/L (n = 85 [8%]) lost eGFR 0.55 (95% CI, 0.13-0.97) mL/min/1.73 m(2) per year faster inmodels adjusted for demographics, CKDrisk factors, baseline eGFR, and urinealbumin-creatinine ratio. Among the 989 (92%) participantswith baseline eGFRs > 60 mL/min/1.73 m(2), 252 (25%) developed incident eGFRs < 60 mL/min/1.73 m(2) at follow-up. Adjusting for the same covariates, participants with bicarbonate concentrations, 23 mmol/L had nearly 2-fold greater odds of incident eGFRs < 60 mL/min/1.73 m(2) (OR, 1.72; 95% CI, 0.97-3.07) compared with those with higher bicarbonate concentrations. Limitations: Only 2 measurements of kidney function separated by 7 years and loss to follow-up due to intervening mortality in this elderly population. Conclusions: Lower serum bicarbonate concentrations are associated independently with decline in eGFR and incident eGFR < 60 mL/min/1.73 m(2) in community-living older persons. If confirmed, serum bicarbonate levels may give insight into kidney tubule health in persons with preserved eGFRs and suggest a possible new target for intervention to prevent CKD development. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. C1 [Goldenstein, Leonard; Rifkin, Dena E.; Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, San Diego, CA 92161 USA. [Goldenstein, Leonard; Rifkin, Dena E.; Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Driver, Todd H.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Fried, Linda F.] Vet Affairs Hosp, Nephrol Sect, Pittsburgh, PA USA. [Fried, Linda F.] Univ Pittsburgh, Dept Med, Div Nephrol, Pittsburgh, PA USA. [Fried, Linda F.; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Rifkin, Dena E.; Ix, Joachim H.] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, San Diego, CA 92161 USA. [Patel, Kushang V.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Yenchek, Robert H.] Univ Utah, Dept Med, Div Nephrol, Salt Lake City, UT 84112 USA. [Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Kritchevsky, Stephen B.] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Sarnak, Mark J.] Tufts Med Ctr, Dept Med, Div Nephrol, Boston, MA USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Ix, JH (reprint author), Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Institute of Diabetes and Digestive and Kidney Diseases [R01DK098234, T32DK069263]; National Institute on Aging [R01AG 027002, R01-AG028050, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institute of Nursing Research [R01-NR012459]; National Institutes of Health, NIA FX This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases by grants R01DK098234 (Drs Ix and Shlipak) and T32DK069263 (Dr Goldenstein); the National Institute on Aging by grants R01AG 027002 (Dr Sarnak) and R01-AG028050 (Dr Strotmeyer) and contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106; the National Institute of Nursing Research by grant R01-NR012459 (Dr Albert); and the Intramural Research Program of the National Institutes of Health, NIA. The funders of this study had no role in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication. NR 33 TC 15 Z9 16 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2014 VL 64 IS 4 BP 542 EP 549 DI 10.1053/j.ajkd.2014.05.009 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AQ4CN UT WOS:000342739900013 PM 24953890 ER PT J AU Lang, JS Scherzer, R Tien, PC Parikh, CR Anastos, K Estrella, MM Abraham, AG Sharma, A Cohen, MH Butch, AW Nowicki, M Grunfeld, C Shlipak, MG AF Lang, Joshua Scherzer, Rebecca Tien, Phyllis C. Parikh, Chirag R. Anastos, Kathryn Estrella, Michelle M. Abraham, Alison G. Sharma, Anjali Cohen, Mardge H. Butch, Anthony W. Nowicki, Marek Grunfeld, Carl Shlipak, Michael G. TI Serum Albumin and Kidney Function Decline in HIV-Infected Women SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Albumin; kidney function; HIV (human immunodeficiency virus); incident reduced estimated; glomerular filtration rate (eGFR); albuminuria; disease trajectory; chronic kidney disease (CKD) progression ID ALL-CAUSE MORTALITY; CYSTATIN-C; DIALYSIS PATIENTS; INTERAGENCY HIV; RENAL-DISEASE; RISK-FACTORS; INFLAMMATION; PROGRESSION; HYPOALBUMINEMIA; INDIVIDUALS AB Background: Serum albumin concentrations are a strong predictor of mortality and cardiovascular disease in human immunodeficiency virus (HIV)-infected individuals. We studied the longitudinal associations between serum albumin levels and kidney function decline in a population of HIV-infected women. Study Design: Retrospective cohort analysis. Setting & Participants: Study participants were recruited from the Women's Interagency HIV Study (WIHS), a large observational study designed to understand risk factors for the progression of HIV infection in women living in urban communities. 908 participants had baseline assessment of kidney function and 2 follow-up measurements over an average of 8 years. Predictor: The primary predictor was serum albumin concentration. Outcomes: We examined annual change in kidney function. Secondary outcomes included rapid kidney function decline and incident reduced estimated glomerular filtration rate (eGFR). Measurements: Kidney function decline was determined by cystatin C-based (eGFR(cys)) and creatinine-based eGFR (eGFR(cr)) at baseline and follow-up. Each model was adjusted for kidney disease and HIV-related risk factors using linear and relative risk regression. Results: After multivariate adjustment, each 0.5-g/dL decrement in baseline serum albumin concentration was associated with a 0.56-mL/min faster annual decline in eGFR(cys) (P < 0.001), which was attenuated only slightly to 0.55 mL/min/1.73 m(2) after adjustment for albuminuria. Results were similar whether using eGFR(cys) or eGFR(cr). In adjusted analyses, each 0.5-g/dL lower baseline serum albumin level was associated with a 1.71-fold greater risk of rapid kidney function decline (P < 0.001) and a 1.72-fold greater risk of incident reduced eGFR (P < 0.001). Limitations: The cohort is composed of only female participants from urban communities within the United States. Conclusions: Lower serum albumin levels were associated strongly with kidney function decline and incident reduced eGFRs in HIV-infected women independent of HIV disease status, body mass index, and albuminuria. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Lang, Joshua; Tien, Phyllis C.; Grunfeld, Carl; Shlipak, Michael G.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Scherzer, Rebecca] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Tien, Phyllis C.; Grunfeld, Carl; Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Parikh, Chirag R.] Yale Univ, Dept Med, Nephrol Sect, New Haven, CT 06520 USA. [Parikh, Chirag R.] Yale Univ, Program Appl Translat Res, New Haven, CT USA. [Anastos, Kathryn] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Anastos, Kathryn] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Estrella, Michelle M.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Abraham, Alison G.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Sharma, Anjali] Suny Downstate Med Ctr, Dept Med, Div Infect Dis, Brooklyn, NY 11203 USA. [Cohen, Mardge H.] Stroger Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge H.] Rush Univ, Dept Med, Chicago, IL 60612 USA. [Butch, Anthony W.] Univ Calif Los Angeles, Clin Immunol Res Lab, Los Angeles, CA USA. [Nowicki, Marek] Univ So Calif, Los Angeles, CA USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 111A1, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu FU National Institute on Aging [1R03AG034871-01, 5R01AG034853-04] FX Support: This study was supported by the National Institute on Aging (grants 1R03AG034871-01 [Principal Investigator (PI), Dr Shlipak] and 5R01AG034853-04 [PI, Dr Shlipak]). NR 26 TC 1 Z9 1 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2014 VL 64 IS 4 BP 584 EP 591 DI 10.1053/j.ajkd.2014.05.015 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AQ4CN UT WOS:000342739900018 PM 25059222 ER PT J AU Johansen, KL Dalrymple, LS Delgado, C Kaysen, GA Kornak, J Grimes, B Chertow, GM AF Johansen, Kirsten L. Dalrymple, Lorien S. Delgado, Cynthia Kaysen, George A. Kornak, John Grimes, Barbara Chertow, Glenn M. TI Comparison of Self-report-Based and Physical Performance-Based Frailty Definitions Among Patients Receiving Maintenance Hemodialysis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Frailty; physical performance; self-reported function; hemodialysis; physical activity; physical function; end-stage renal disease (ESRD) ID STAGE RENAL-DISEASE; BODY-COMPOSITION; WOMENS HEALTH; OLDER-ADULTS; PHENOTYPE; MORTALITY; CONSENSUS AB Background: A well-accepted definition of frailty includes measurements of physical performance, which may limit its clinical utility. Study Design: In a cross-sectional study, we compared prevalence and patient characteristics based on a frailty definition that uses self-reported function to the classic performance-based definition and developed a modified self-report-based definition. Setting & Participants: Prevalent adult patients receiving hemodialysis in 14 centers around San Francisco and Atlanta in 2009-2011. Index Tests: Self-report-based frailty definition in which a score lower than 75 on the Physical Function scale of the 36-Item Short Form Health Survey (SF-36) was substituted for gait speed and grip strength in the classic definition; modified self-report definition with optimized Physical Function score cutoff points derived in a development (one-half) cohort and validated in the other half. Reference Test: Performance-based frailty defined as 3 of the following: weight loss, weakness, exhaustion, low physical activity, and slow gait speed. Results: 387 (53%) patients were frail based on self-reported function, of whom 209 (29% of the cohort) met the performance-based definition. Only 23 (3%) met the performance-based definition of frailty only. The self-report definition had 90% sensitivity, 64% specificity, 54% positive predictive value, 93% negative predictive value, and 72.5% overall accuracy. Intracellular water per kilogram of body weight and serum albumin, prealbumin, and creatinine levels were highest among nonfrail individuals, intermediate among those who were frail by self-report, and lowest among those who also were frail by performance. Age, percentage of body fat, and C-reactive protein level followed an opposite pattern. The modified self-report definition had better accuracy (84%; 95% CI, 79%-89%) and superior specificity (88%) and positive predictive value (67%). Limitations: Our study did not address prediction of outcomes. Conclusions: Patients who meet the self-report-based but not the performance-based definition of frailty may represent an intermediate phenotype. A modified self-report definition can improve the accuracy of a questionnaire-based method of defining frailty. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Johansen, Kirsten L.; Dalrymple, Lorien S.; Delgado, Cynthia; Kaysen, George A.; Kornak, John; Grimes, Barbara; Chertow, Glenn M.] US Renal Data Syst, Nutr Special Studies Ctr, San Francisco, CA USA. [Johansen, Kirsten L.; Delgado, Cynthia] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94121 USA. [Johansen, Kirsten L.; Delgado, Cynthia] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. [Johansen, Kirsten L.; Kornak, John; Grimes, Barbara] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Dalrymple, Lorien S.; Kaysen, George A.] Univ Calif Davis, Univ Calif San Francisco, Div Nephrol, Davis, CA 95616 USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. RP Johansen, KL (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu FU National Institutes of Health [N01-DK-0005, K23 DK093584] FX Support: This work was supported by the National Institutes of Health (contract N01-DK-0005 to Dr Johansen and K23 DK093584 to Dr Dalrymple). The interpretation and reporting of the data presented here are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government. NR 19 TC 17 Z9 17 U1 0 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2014 VL 64 IS 4 BP 600 EP 607 DI 10.1053/j.ajkd.2014.03.016 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AQ4CN UT WOS:000342739900020 PM 24793033 ER PT J AU Nowak, J Seidel, C Berg, F Pietsch, T Friedrich, C von Hoff, K Rutkowski, S Warmuth-Metz, M AF Nowak, J. Seidel, C. Berg, F. Pietsch, T. Friedrich, C. von Hoff, K. Rutkowski, S. Warmuth-Metz, M. TI MRI Characteristics of Ependymoblastoma: Results from 22 Centrally Reviewed Cases SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Review ID PRIMITIVE NEUROECTODERMAL TUMORS; MULTICENTER TRIAL HIT91; ABUNDANT NEUROPIL; TRUE ROSETTES; EMBRYONAL TUMOR; POSTERIOR-FOSSA; BRAIN-TUMORS; MEDULLOBLASTOMA; CHILDREN; CLASSIFICATION AB BACKGROUND AND PURPOSE: Ependymoblastoma is a malignant embryonal tumor that develops in early childhood and has a dismal prognosis. Categorized by the World Health Organization as a subgroup of CNS-primitive neuroectodermal tumor, ependymoblastoma is histologically defined by "ependymoblastic rosettes." Because it is so rare, little is known about specific MR imaging characteristics of ependymoblastoma. We systematically analyzed and discussed MR imaging features of ependymoblastoma in a series of 22 consecutive patients. MATERIALS AND METHODS: Ependymoblastoma cases were obtained from the database of the German multicenter HIT trials between 2002 and 2013. All cases within this study were centrally reviewed for histopathology, MR imaging findings, and multimodal therapy. For systematic analysis of initial MR imaging scans at diagnosis, we applied standardized criteria for reference image evaluation of pediatric brain tumors. RESULTS: Ependymoblastomas are large tumors with well-defined tumor margins, iso- to hyperintense signal on T2WI, and diffusion restriction. Contrast enhancement is variable, with a tendency to mild or moderate enhancement. Subarachnoid spread is common in ependymoblastoma but can be absent initially. There was a male preponderance (1.75:1 ratio) for ependymoblastoma in our cohort. Mean age at diagnosis was 2.1 years. CONCLUSIONS: With this study, we add the largest case collection to the limited published database of MR imaging findings in ependymoblastoma, together with epidemiologic data. However, future studies are needed to systematically compare MR imaging findings of ependymoblastoma with other CNS-primitive neuroectodermal tumors and ependymoma, to delineate imaging criteria that might help distinguish these pediatric brain tumor entities. C1 [Nowak, J.; Seidel, C.; Berg, F.; Warmuth-Metz, M.] Univ Hosp Wurzburg, Reference Ctr Neuroradiol, D-97080 Wurzburg, Germany. [Seidel, C.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Berg, F.] Univ Witten Herdecke, Cologne Merheim Med Ctr, Dept Radiol & Neuroradiol, Cologne, Germany. [Pietsch, T.] Brain Tumor Reference Ctr, Dept Neuropathol, Bonn, Germany. [Friedrich, C.; von Hoff, K.; Rutkowski, S.] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany. RP Nowak, J (reprint author), Univ Hosp Wurzburg, Reference Ctr Neuroradiol, Josef Schneider Str 11, D-97080 Wurzburg, Germany. EM Nowak_jl@ukw.de FU German Childhood Cancer Foundation; HIT trial office FX Katja von Hoff-UNRELATED: Grants/Grants Pending: German Childhood Cancer Foundation.* Stefan Rutkowski-UNRELATED: Grants/Grants Pending: German Childhood Cancer Foundation,* Comments: funding of the HIT trial office, where patients' data have been collected, and supporting other studies of the HIT trial office. Monika Warmuth-Metz-UNRELATED: Grants/Grants Pending: German Childhood Cancer Foundation,* Comments: German Childhood Cancer Foundation is an association of parents with children with leukemia and tumors supporting the Radiological Reference Center; Consultancy: Roche, Oncoscience, Comments: for glioma studies separate from the HIT studies; Expert Testimony: Oncoscience, Comments: related to glioma studies other than the HIT studies; Travel/Accommodations/Meeting Expenses Unrelated to Activities Listed: Roche, Oncoscience. *Money paid to the institution. NR 34 TC 2 Z9 2 U1 0 U2 3 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 2014 VL 35 IS 10 BP 1996 EP 2001 DI 10.3174/ajnr.A4002 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AQ5YY UT WOS:000342885700026 PM 24948504 ER PT J AU Deshpande, BR Rao, SR Jentes, ES Hills, SL Fischer, M Gershman, MD Brunette, GW Ryan, ET LaRocque, RC AF Deshpande, Bhushan R. Rao, Sowmya R. Jentes, Emily S. Hills, Susan L. Fischer, Marc Gershman, Mark D. Brunette, Gary W. Ryan, Edward T. LaRocque, Regina C. CA Global TravEpiNet Consortium TI Use of Japanese Encephalitis Vaccine in US Travel Medicine Practices in Global TravEpiNet SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID YELLOW-FEVER; RISK; RECOMMENDATIONS; ASIA AB Few data regarding the use of Japanese encephalitis (JE) vaccine in clinical practice are available. We identified 711 travelers at higher risk and 7,578 travelers at lower risk for JE who were seen at US Global TravEpiNet sites from September of 2009 to August of 2012. Higher-risk travelers were younger than lower-risk travelers (median age = 29 years versus 40 years, P < 0.001). Over 70% of higher-risk travelers neither received JE vaccine during the clinic visit nor had been previously vaccinated. In the majority of these instances, clinicians determined that the JE vaccine was not indicated for the higher-risk traveler, which contradicts current recommendations of the Advisory Committee on Immunization Practices. Better understanding is needed of the clinical decision-making regarding JE vaccine in US travel medicine practices. C1 [Deshpande, Bhushan R.] Tufts Univ, Sch Arts & Sci, Medford, MA 02155 USA. [Rao, Sowmya R.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Jentes, Emily S.; Gershman, Mark D.; Brunette, Gary W.] Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Atlanta, GA USA. [Hills, Susan L.; Fischer, Marc] Ctr Dis Control & Prevent, Div Vector Borne Dis, Atlanta, GA USA. [Ryan, Edward T.; LaRocque, Regina C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP LaRocque, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, GRJ 504,55 Fruit St, Boston, MA 02114 USA. EM bhushan.deshpande@tufts.edu; srrao@partners.org; efj8@cdc.gov; shills@cdc.gov; mxf2@cdc.gov; dvj8@cdc.gov; fvd3@cdc.gov; etryan@partners.org; rclarocque@partners.org OI Vinetz, Joseph/0000-0001-8344-2004 FU US Centers for Disease Control and Prevention [U19CI000514, U01CK000175] FX This work was supported by US Centers for Disease Control and Prevention Grants U19CI000514 and U01CK000175. NR 12 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD OCT PY 2014 VL 91 IS 4 BP 694 EP 698 DI 10.4269/ajtmh.14-0062 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA AQ6XQ UT WOS:000342957600008 PM 25070999 ER PT J AU Weil, AA Begum, Y Chowdhury, F Khan, AI Leung, DT LaRocque, RC Charles, RC Ryan, ET Calderwood, SB Qadri, F Harris, JB AF Weil, Ana A. Begum, Yasmin Chowdhury, Fahima Khan, Ashraful I. Leung, Daniel T. LaRocque, Regina C. Charles, Richelle C. Ryan, Edward T. Calderwood, Stephen B. Qadri, Firdausi Harris, Jason B. TI Bacterial Shedding in Household Contacts of Cholera Patients in Dhaka, Bangladesh SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID O139 SYNONYM BENGAL; VIBRIO-CHOLERAE; ENDEMIC CHOLERA; FAMILY CONTACTS; RESPONSES; SUSCEPTIBILITY; INFECTION; TETRACYCLINE; PROPHYLAXIS; DIARRHEA AB Multiple Vibrio cholerae infections within the same household are common. Household contacts of patients with cholera were observed with daily clinical assessments and collection of rectal swab cultures for nine days after presentation of the index case. During the follow-up period, 71 (24%) of 294 household contacts developed a positive V. cholerae rectal swab, signifying bacterial shedding. The average length of bacterial shedding was 2.0 days (95% confidence interval 1.7-2.4). However, 16 (5%) of 294 contacts shed V. cholerae for >= 4 days. In a multivariate analysis, malnutrition was predictive of long-term shedding (odds ratio = 1.4, 95% confidence interval = 1.3-13, P = 0.02). High rates of V. cholerae infection and bacterial shedding among household contacts of cholera patients represent an opportunity for intervention to reduce V. cholerae transmission. C1 [Weil, Ana A.; LaRocque, Regina C.; Charles, Richelle C.; Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Begum, Yasmin; Chowdhury, Fahima; Khan, Ashraful I.; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, Dhaka 1000, Bangladesh. [Leung, Daniel T.] Univ Utah, Div Infect Dis, Salt Lake City, UT USA. RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Jackson 504, Boston, MA 02114 USA. EM aweil@partners.org; yasmin@icddrb.org; fchowdhury@icddrb.org; ashrafk@icddrb.org; Daniel.Leung@utah.edu; rclarocque@partners.org; rccharles@partners.org; etryan@partners.org; scalderwood@partners.org; fqadri@icddrb.org; jbharris@partners.org OI leung, daniel/0000-0001-8401-0801 FU National Institutes of Health [AI058935, R03 AI063079, R01AI03055, R01 AI099243, U01 AI077883, AI106878]; Training Grant in Vaccine Development and Public Health [TW005572]; Career Development Award [K08 AI089721, K08 AI100923]; Fogarty International Clinical Research Scholars award from the Fogarty International Center [R24 TW007988]; Swedish Agency for International Development and Cooperation, a Physician Scientist Early Career Award from the Howard Hughes Medical Institute; American Society for Tropical Medicine and Hygiene-Burroughs Wellcome Fund; Thrasher Research Fund Early Career Award; Partners Healthcare Center of Expertise in Global and Humanitarian Health Travel Grant FX This study was supported by grants from National Institutes of Health, including AI058935 (Edward T. Ryan and Stephen B. Calderwood), R03 AI063079 (Firdausi Qadri), R01AI03055 and R01 AI099243 (Jason B. Harris), and U01 AI077883 and AI106878 (Edward T. Ryan); a Training Grant in Vaccine Development and Public Health (TW005572) (Edward T. Ryan and Firdausi Qadri]; a Career Development Award (K08 AI089721 (Richelle C. Charles) and K08 AI100923 ([Daniel T. Leung); a Fogarty International Clinical Research Scholars award (R24 TW007988 (Firdausi Qadri and Ashraful I. Khan) from the Fogarty International Center; the Swedish Agency for International Development and Cooperation (Firdausi Qadri), a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (Regina C. LaRocque); a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society for Tropical Medicine and Hygiene-Burroughs Wellcome Fund (Daniel T. Leung); a Thrasher Research Fund Early Career Award (Daniel T. Leung); and a Partners Healthcare Center of Expertise in Global and Humanitarian Health Travel Grant (Ana A. Weil). NR 26 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD OCT PY 2014 VL 91 IS 4 BP 738 EP 742 DI 10.4269/ajtmh.14-0095 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA AQ6XQ UT WOS:000342957600015 PM 25114012 ER PT J AU Kamdar, N Hofer, I AF Kamdar, Nirav Hofer, Ira TI Safe and Scalable Device Design: A Call for Open Standards SO ANESTHESIOLOGY LA English DT Letter C1 [Kamdar, Nirav; Hofer, Ira] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kamdar, N (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM nkamdar@partners.org NR 2 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 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2014 VL 121 IS 4 BP 906 EP 906 DI 10.1097/ALN.0000000000000389 PG 1 WC Anesthesiology SC Anesthesiology GA AQ4CX UT WOS:000342741000031 PM 25247863 ER PT J AU Thoma, B Joshi, N Trueger, S Chan, TM Lin, M AF Thoma, Brent Joshi, Nikita Trueger, Seth Chan, Teresa M. Lin, Michelle TI Five Strategies to Effectively Use Online Resources in Emergency Medicine SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material ID SCHOLARSHIP; EDUCATION C1 [Thoma, Brent] Massachusetts Gen Hosp, Learning Lab, Dept Emergency Med, Boston, MA 02114 USA. [Thoma, Brent] Massachusetts Gen Hosp, Dept Emergency Med, Div Med Simulat, Boston, MA 02114 USA. [Thoma, Brent] Univ Saskatchewan, Saskatoon, SK, Canada. [Thoma, Brent; Joshi, Nikita; Chan, Teresa M.; Lin, Michelle] MedEdLIFE Res Collaborat, San Francisco, CA USA. [Joshi, Nikita] Stanford Univ, Div Emergency Med, Dept Surg, Palo Alto, CA 94304 USA. [Trueger, Seth] George Washington Univ, Dept Emergency Med, Washington, DC USA. [Chan, Teresa M.] McMaster Univ, Dept Med, Div Emergency Med, Hamilton, ON, Canada. [Lin, Michelle] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. RP Thoma, B (reprint author), Massachusetts Gen Hosp, Learning Lab, Dept Emergency Med, Boston, MA 02114 USA. EM brent.thoma@usask.ca OI Chan, Teresa/0000-0001-6104-462X; Trueger, N. Seth/0000-0001-8797-2192; Thoma, Brent/0000-0003-1124-5786 NR 19 TC 15 Z9 15 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2014 VL 64 IS 4 BP 392 EP 395 DI 10.1016/j.annemergmed.2014.05.029 PG 4 WC Emergency Medicine SC Emergency Medicine GA AQ5XW UT WOS:000342882900013 PM 24962889 ER PT J AU Deodhar, A Reveille, JD van den Bosch, F Braun, J Burgos-Vargas, R Caplan, L Clegg, DO Colbert, RA Gensler, LS van der Heijde, D van der Horst-Bruinsma, IE Inman, RD Maksymowych, WP Mease, PJ Raychaudhuri, S Reimold, A Rudwaleit, M Sieper, J Weisman, MH Landewe, RBM AF Deodhar, Atul Reveille, John D. van den Bosch, Filip Braun, Juergen Burgos-Vargas, Ruben Caplan, Liron Clegg, Daniel O. Colbert, Robert A. Gensler, Lianne S. van der Heijde, Desiree van der Horst-Bruinsma, Irene E. Inman, Robert D. Maksymowych, Walter P. Mease, Philip J. Raychaudhuri, Siba Reimold, Andreas Rudwaleit, Martin Sieper, Joachim Weisman, Michael H. Landewe, Robert B. M. TI The Concept of Axial Spondyloarthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID SOCIETY CLASSIFICATION CRITERIA; PLACEBO-CONTROLLED TRIAL; ANKYLOSING-SPONDYLITIS; DIAGNOSTIC-CRITERIA; DOUBLE-BLIND; SPONDYLARTHRITIS; EFFICACY; SAFETY; PREVALENCE C1 [Deodhar, Atul] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [van den Bosch, Filip] Ghent Univ Hosp, Ghent, Belgium. [Braun, Juergen] Rheumazentrum Ruhrgebiet, Herne, Germany. [Burgos-Vargas, Ruben] Hosp Gen Mexico City, Mexico City, DF, Mexico. [Burgos-Vargas, Ruben] Univ Nacl Autonoma Mexico, Mexico City 04510, DF, Mexico. [Caplan, Liron] Univ Colorado, Denver, CO 80202 USA. [Caplan, Liron] Denver VA Med Ctr, Denver, CO USA. [Clegg, Daniel O.] Univ Utah, Med Ctr, Salt Lake City, UT USA. [Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Gensler, Lianne S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [van der Heijde, Desiree] Leiden Univ, Med Ctr, Leiden, Netherlands. [van der Horst-Bruinsma, Irene E.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Inman, Robert D.] Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. [Inman, Robert D.] Univ Toronto, Toronto, ON, Canada. [Maksymowych, Walter P.] Alberta Heritage Fdn Med Res, Edmonton, AB, Canada. [Maksymowych, Walter P.] Univ Alberta, Edmonton, AB, Canada. [Mease, Philip J.] Seattle Rheumatol Associates, Seattle, WA USA. [Raychaudhuri, Siba] Univ Calif Davis, Sacramento, CA 95817 USA. [Reimold, Andreas] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Rudwaleit, Martin; Sieper, Joachim] Charite, Campus Benjamin Franklin, D-13353 Berlin, Germany. [Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Landewe, Robert B. M.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Landewe, Robert B. M.] Univ Amsterdam, Amsterdam, Netherlands. RP Deodhar, A (reprint author), Oregon Hlth & Sci Univ, Div Arthrit & Rheumat Dis, OP09,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM deodhara@ohsu.edu FU UCB; Novartis; AbbVie; Pfizer; MSD; Amgen; Celgene; AbbVie (Abbott); Bristol-Myers Squibb; Boehringer; Celltrion; Centocor; Chugai; EBEWE Pharma; Medac; MSD (Schering-Plough); Mundipharma; Pfizer (Wyeth); Roche; Sanofi-Aventis; Janssen; AstraZeneca; Augunex; Covagen; Daiichi; Eli Lilly; Galapagos NV; GlaxoSmithKline; Janssen Biologics; Merck; Novo Nordisk; Otsuka; Vertex; Quest; Biogen Idec; Crescendo; Genentech; Lilly; Abbott; Wyeth FX Dr. Deodhar has received consulting fees, speaking fees, and/or honoraria from UCB, Novartis, AbbVie, Pfizer, and MSD (less than $10,000 each), has served as an expert witness on behalf of UCB and AbbVie, and has received research grants from UCB, AbbVie, Novartis, Pfizer, and Amgen. Dr. van den Bosch has received consulting fees, speaking fees, and/or honoraria from AbbVie, Celgene, MSD, Pfizer, and UCB (less than $10,000 each). Dr. Braun has received consulting fees, speaking fees, and/or honoraria from AbbVie (Abbott), Amgen, Bristol-Myers Squibb, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB (less than $10,000 each). Dr. Burgos-Vargas has received consulting fees, speaking fees, and/or honoraria from AbbVie, Bristol-Myers Squibb, Janssen, Pfizer, Roche, and UCB (less than $10,000 each). Dr. Clegg has received consulting fees, speaking fees, and/or honoraria from Abbott (less than $10,000). Dr. Gensler has received consulting fees from UCB and AbbVie (less than $10,000 each). Dr. van der Heijde has received consulting fees, speaking fees, and/or honoraria from AbbVie, Amgen, AstraZeneca, Augunex, Bristol-Myers Squibb, Celgene, Chugai, Covagen, Daiichi, Eli Lilly, Galapagos NV, GlaxoSmithKline, Janssen Biologics, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, and Vertex (less than $10,000 each) and is the director of Imaging Rheumatology BV. Dr. Inman has received consulting fees from AbbVie, Amgen, Janssen, Pfizer, and UCB (less than $10,000 each). Dr. Maksymowych has received consulting fees, speaking fees, and/or honoraria from Pfizer, Eli Lilly, Merck, Janssen, and Quest (less than $10,000 each) and from AbbVie and UCB (more than $10,000 each). Dr. Mease has received consulting fees, speaking fees, and/or honoraria from Biogen Idec, Celgene, Covagen, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, and Vertex (less than $10,000 each) and from AbbVie, Amgen, Bristol-Myers Squibb, Pfizer, and UCB (more than $10,000 each). Dr. Raychaudhuri has received speaking fees or honoraria from Abbott, Amgen, and UCB (less than $10,000 each). Dr. Reimold has received consulting fees, speaking fees, and/or honoraria from UCB (less than $10,000). Dr. Rudwaleit has received consulting fees, speaking fees, and/or honoraria from AbbVie, Bristol-Myers Squibb, MSD, Pfizer, Roche, UCB, and Janssen (less than $10,000 each) and has served as an expert witness on behalf of UCB. Dr. Sieper has received consulting fees, speaking fees, and/or honoraria from AbbVie, Pfizer, Merck, UCB, and Novartis (less than $10,000 each). Dr. Weisman has received consulting fees from UCB (less than $10,000). Dr. Landewe has received consulting fees, speaking fees, and/or honoraria from AbbVie, Pfizer, UCB, Amgen, Wyeth, Merck, Novartis, and Janssen (less than $10,000 each) and is director of Rheumatology Consultancy BV. NR 23 TC 28 Z9 30 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2014 VL 66 IS 10 BP 2649 EP 2656 DI 10.1002/art.38776 PG 8 WC Rheumatology SC Rheumatology GA AQ4DZ UT WOS:000342744300001 PM 25154344 ER PT J AU van der Sijde, MR Ng, A Fu, JY AF van der Sijde, Marijke R. Ng, Aylwin Fu, Jingyuan TI Systems genetics: From GWAS to disease pathways SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review DE Post-GWAS; Systems genetics; Integrative approach; Disease mechanism; Network modelling; Causal inference ID GENOME-WIDE ASSOCIATION; PROTEIN ABUNDANCE; EXPRESSION QTLS; CROHNS-DISEASE; COMPLEX TRAITS; RISK-FACTORS; LOCI; IDENTIFICATION; ARCHITECTURE; GENES AB Most common diseases are complex, involving multiple genetic and environmental factors and their interactions. In the past decade, genome-wide association studies (GWAS) have successfully identified thousands of genetic variants underlying susceptibility to complex diseases. However, the results from these studies often do not provide evidence on how the variants affect downstream pathways and lead to the disease. Therefore, in the post-GWAS era the greatest challenge lies in combining GWAS findings with additional molecular data to functionally characterize the associations. The advances in various similar to omics techniques have made it possible to investigate the effect of risk variants on intermediate molecular levels, such as gene expression, methylation, protein abundance or metabolite levels. As disease aetiology is complex, no single molecular analysis is expected to fully unravel the disease mechanism. Multiple molecular levels can interact and also show plasticity in different physiological conditions, cell types and disease stages. There is therefore a great need for new integrative approaches that can combine data from different molecular levels and can help construct the causal inference from genotype to phenotype. Systems genetics is such an approach; it is used to study genetic effects within the larger scope of systems biology by integrating genotype information with various similar to omics datasets as well as with environmental and physiological variables. In this review, we describe this approach and discuss how it can help us unravel the molecular mechanisms through which genetic variation causes disease. This article is part of a Special Issue entitled: From Genome to Function. (C) 2014 Elsevier B.V. All rights reserved. C1 [van der Sijde, Marijke R.; Fu, Jingyuan] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands. [Ng, Aylwin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Ng, Aylwin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Ng, Aylwin] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. RP Fu, JY (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Genet, POB 30-001, NL-9700 RB Groningen, Netherlands. EM marijkevdsijde@gmail.com; ang@ccib.mgh.harvard.edu; fjingyuan@gmail.com FU Netherlands Organization for Scientific Research (NWO-VENI) [863.09.007]; Systems Biology Centre for Metabolism and Ageing (SBC-EBA) [853.00.110]; Massachusetts General Hospital Department of Medicine investigator start-up funding FX M.S. and J.F. are supported by the Netherlands Organization for Scientific Research (NWO-VENI grant 863.09.007 to J.F.) and the Systems Biology Centre for Metabolism and Ageing (SBC-EBA grant 853.00.110). A.N. is supported by the Massachusetts General Hospital Department of Medicine investigator start-up funding. NR 86 TC 21 Z9 21 U1 5 U2 34 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 EI 0006-3002 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD OCT PY 2014 VL 1842 IS 10 SI SI BP 1903 EP 1909 DI 10.1016/j.bbadis.2014.04.025 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AQ5RY UT WOS:000342867500004 PM 24798234 ER PT J AU Lage, K AF Lage, Kasper TI Protein-protein interactions and genetic diseases: The interactome SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review DE Protein-protein interaction; Complex human disease; Genetics and proteomics ID DE-NOVO MUTATIONS; INTERACTION NETWORK; SACCHAROMYCES-CEREVISIAE; INTERACTION DATABASE; CANDIDATE GENES; HUMAN GENOME; SYSTEMATIC IDENTIFICATION; FUNCTIONAL-ORGANIZATION; DROSOPHILA-MELANOGASTER; INTERACTION DATASETS AB Protein-protein interactions mediate essentially all biological processes. Despite the quality of these data being widely questioned a decade ago, the reproducibility of large-scale protein interaction data is now much improved and there is little question that the latest screens are of high quality. Moreover, common data standards and coordinated curation practices between the databases that collect the interactions have made these valuable data available to a wide group of researchers. Here, I will review how protein-protein interactions are measured, collected and quality controlled. I discuss how the architecture of molecular protein networks has informed disease biology, and how these data are now being computationally integrated with the newest genomic technologies, in particular genome-wide association studies and exome-sequencing projects, to improve our understanding of molecular processes perturbed by genetics in human diseases. This article is part of a Special Issue entitled: From Genome to Function. (C) 2014 Elsevier B.V. All rights reserved. C1 [Lage, Kasper] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lage, Kasper] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Lage, Kasper] Harvard Univ, Sch Med, Boston, MA USA. [Lage, Kasper] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Lage, K (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM lage.kasper@mgh.harvard.edu FU NICHD NIH HHS [P01 HD068250] NR 98 TC 23 Z9 23 U1 4 U2 32 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 EI 0006-3002 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD OCT PY 2014 VL 1842 IS 10 SI SI BP 1971 EP 1980 DI 10.1016/j.bbadis.2014.05.028 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AQ5RY UT WOS:000342867500011 PM 24892209 ER PT J AU Talcott, JA Manola, J Chen, RC Clark, JA Kaplan, I D'Amico, AV Zietman, AL AF Talcott, James A. Manola, Judith Chen, Ronald C. Clark, Jack A. Kaplan, Irving D'Amico, Anthony V. Zietman, Anthony L. TI Using patient-reported outcomes to assess and improve prostate cancer brachytherapy SO BJU INTERNATIONAL LA English DT Article DE prostate neoplasms; patient-reported outcomes; quality assessment/quality improvement; brachytherapy; urinary dysfunction ID QUALITY-OF-LIFE; EXTERNAL-BEAM IRRADIATION; BREAST-CANCER; CLINICAL-SIGNIFICANCE; THERAPY; URINARY; CARE; COMPLICATIONS; RADIOTHERAPY; SATISFACTION AB Objective To describe a successful quality improvement process that arose from unexpected differences in control groups' short-term patient-reported outcomes (PROs) within a comparative effectiveness study of a prostate brachytherapy technique intended to reduce urinary morbidity. Patients and Methods Patients planning prostate brachytherapy at one of three institutions were enrolled in a prospective cohort study. Patients were surveyed using a validated instrument to assess treatment-related toxicity before treatment and at pre-specified intervals. Unexpectedly, urinary PROs were worse in one of two standard brachytherapy technique control populations (US-BT1 and US-BT2). Therefore, we collaboratively reviewed treatment procedures, identified a discrepancy in technique, made a corrective modification, and evaluated the change. Results The patient groups were demographically and clinically similar. In the first preliminary analysis, US-BT2 patients reported significantly more short-term post-treatment urinary symptoms than US-BT1 patients. The study's treating physicians reviewed the US-BT1 and US-BT2 treatment protocols and found that they differed in whether they used an indwelling urinary catheter. After adopting the US-BT1 approach, short-term urinary morbidity in US-BT2 patients decreased significantly. Brachytherapy procedures were otherwise unchanged. Conclusion Many procedures in cancer treatments are not evaluated, resulting in practice variation and suboptimal outcomes. Patients, the primary medical consumers, provide little direct input in evaluations of their care. We used PROs, a sensitive and valid measure of treatment-related toxicity, for quality assessment and quality improvement (QA/QI) of prostate brachytherapy. This serendipitous patient-centred QA/QI process may be a useful model for empirically evaluating complex cancer treatment procedures and for screening for substandard care. C1 [Talcott, James A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Talcott, James A.] Continuum Canc Ctr New York, New York, NY 10011 USA. [Manola, Judith] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Ronald C.] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC USA. [Clark, Jack A.] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Clark, Jack A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Kaplan, Irving] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kaplan, Irving; D'Amico, Anthony V.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Talcott, James A.] Albert Einstein Coll Med, New York, NY USA. [Talcott, James A.; D'Amico, Anthony V.; Zietman, Anthony L.] Harvard Univ, Sch Med, Boston, MA USA. RP Talcott, JA (reprint author), Continuum Canc Ctr New York, Ctr Hlth Care Qual & Outcomes Res, 325 West 15th St, New York, NY 10011 USA. EM jtalcott@chpnet.org NR 38 TC 6 Z9 7 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD OCT PY 2014 VL 114 IS 4 BP 511 EP 516 DI 10.1111/bju.12464 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AQ7OF UT WOS:000343007100011 PM 24112602 ER PT J AU Shindiapina, P Brown, JR Danilov, AV AF Shindiapina, Polina Brown, Jennifer R. Danilov, Alexey V. TI A new hope: novel therapeutic approaches to treatment of chronic lymphocytic leukaemia with defects in TP53 SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE chronic lymphocytic leukaemia; TP53; B-cell receptor ID FLUDARABINE PLUS CYCLOPHOSPHAMIDE; HIGH-DOSE METHYLPREDNISOLONE; DEPENDENT CELLULAR CYTOTOXICITY; PREVIOUSLY UNTREATED PATIENTS; NATURAL-KILLER-CELL; KAPPA-B ACTIVATION; PHASE-III TRIAL; LRF CLL4 TRIAL; SALVAGE THERAPY; INDUCE REMISSIONS AB Chronic lymphocytic leukaemia (CLL) is an indolent B-cell malignancy with heterogeneous outcomes. Chromosomal abnormalities in CLL are predictive of the natural disease course; del(11q) and del(17p) are recognized as high risk genetic lesions. Del(17p) is associated with an impaired function of TP53, a key tumour suppressor, and is particularly problematic. Such patients respond poorly to chemo-immunotherapy and have significantly shorter survival compared to patients with standard and low-risk cytogenetics. While TP53 pathway defects are rare at initial diagnosis, their frequency increases in relapsed CLL. Until very recently, this group of patients represented an unmet clinical need with few therapeutic options. However, the advent of targeted therapies has expanded the drug armamentarium and introduced new hope for these highly refractory patients. Agents that target B-cell receptor signalling, BH3-mimetics and others induce apoptosis of the neoplastic B-cells in a TP53-independent manner. Their use in the clinic is associated with remarkable activity in patients with del(17p). In this review we discuss the frequency and clinical significance of del(17p) and genetic mutations leading to disrupted TP53, the putative role of other TP53 homologues, and the results of key clinical trials involving both conventional chemotherapy and novel agents. C1 [Shindiapina, Polina; Danilov, Alexey V.] Dartmouth Hitchcock Med Ctr, CLL Ctr, Lebanon, NH 03766 USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Danilov, AV (reprint author), Norris Cotton Canc Ctr, 1 Med Ctr Dr, Lebanon, NH 03766 USA. EM jennifer_brown@dfci.harvard.edu; Alexey.V.Danilov@hitchcock.org FU Lymphoma Research Foundation; Leukemia Lymphoma Society; American Cancer Society FX AVD is supported by the Lymphoma Research Foundation Clinical Investigator Career Development Award. JRB is supported by the Leukemia Lymphoma Society and the American Cancer Society and is a Scholar in Clinical Research of the Leukemia and Lymphoma Society. NR 122 TC 9 Z9 9 U1 2 U2 7 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 OCT PY 2014 VL 167 IS 2 BP 149 EP 161 DI 10.1111/bjh.13042 PG 13 WC Hematology SC Hematology GA AQ4TP UT WOS:000342792900003 PM 25040077 ER PT J AU Klein, AJ Feldman, DN Aronow, HD Gray, BH Gupta, K Gigliotti, OS Jaff, MR Bersin, RM White, CJ AF Klein, Andrew J. Feldman, Dmitriy N. Aronow, Herbert D. Gray, Bruce H. Gupta, Kamal Gigliotti, Osvaldo S. Jaff, Michael R. Bersin, Robert M. White, Christopher J. TI SCAI Expert Consensus Statement for Aorto-Iliac Arterial Intervention Appropriate Use SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE aorto-iliac disease; appropriate use; peripheral arterial disease ID INTER-SOCIETY-CONSENSUS; PERCUTANEOUS ENDOVASCULAR TREATMENT; TRANS-LUMINAL ANGIOPLASTY; PRIMARY STENT PLACEMENT; OCCLUSIVE DISEASE; ILIAC ARTERIES; AORTIC BIFURCATION; FOLLOW-UP; CLASS-C; RECONSTRUCTION AB Aorto-iliac arterial occlusive disease is common and may cause a spectrum of chronic symptoms from intermittent claudication to critical limb ischemia. Treatment is indicated for symptoms that have failed lifestyle and medical therapies or occasionally to facilitate other interventional procedures such as TAVR and/or placement of hemodynamic assist devices. It is widely accepted that TASC A, B, and C lesions are best managed with endovascular intervention. In experienced hands, most TASC D lesions may be treated by endovascular methods, and with the development of chronic total occlusion devices, many aorto-iliac occlusions may be recanalized safely by endovascular means. Interventional cardiologists should be well versed in the anatomy, as well as the treatment of aorto-iliac disease, given their need to traverse these vessels during transfemoral procedures. Overall, aorto-iliac occlusive disease is more commonly being treated with an endovascular-first approach, using open surgery as a secondary option. This document was developed to guide physicians in the clinical decision-making related to the contemporary application of endovascular intervention among patients with aorto-iliac arterial disease. (C) 2014 Wiley Periodicals, Inc. C1 [Klein, Andrew J.] St Louis Univ, Sch Med, Dept Med, St Louis VA Healthcare Syst,Div Cardiol, St Louis, MO 63104 USA. [Feldman, Dmitriy N.] New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Med, Div Cardiol, New York, NY USA. [Aronow, Herbert D.] St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA. [Gray, Bruce H.] Univ S Carolina, Sch Med, Dept Med Greenville, Greenville, SC USA. [Gupta, Kamal] Univ Kansas, Dept Med, Div Cardiol, Kansas City, KS USA. [Gigliotti, Osvaldo S.] Seton Heart Inst, Austin, TX USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Bersin, Robert M.] Swedish Heart & Vasc, Seattle, WA USA. [White, Christopher J.] Univ Queensland, Ochsner Clin Sch, Dept Med, John Ochsner Heart & Vasc Inst,Ochsner Med Ctr, New Orleans, LA USA. RP Klein, AJ (reprint author), B130 John Cochran VA Med Ctr, Cardiol Sect, 915 North Grand Blvd, St Louis, MO 63106 USA. EM andrew.klein3@va.gov RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 NR 39 TC 9 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT 1 PY 2014 VL 84 IS 4 BP 520 EP 528 DI 10.1002/ccd.25505 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AQ5DT UT WOS:000342826900004 PM 24740523 ER PT J AU Klein, AJ Pinto, DS Gray, BH Jaff, MR White, CJ Drachman, DE AF Klein, Andrew J. Pinto, Duane S. Gray, Bruce H. Jaff, Michael R. White, Christopher J. Drachman, Douglas E. TI SCAI Expert Consensus Statement for Femoral-Popliteal Arterial Intervention Appropriate Use SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE appropriate use; peripheral arterial disease; atherectomy; directional/rotational; endovascular intervention ID NITINOL STENT IMPLANTATION; RESILIENT RANDOMIZED-TRIAL; PACLITAXEL-ELUTING STENTS; CRITICAL LIMB ISCHEMIA; FOLLOW-UP; FEMOROPOPLITEAL LESIONS; BALLOON ANGIOPLASTY; OCCLUSIVE DISEASE; SUBINTIMAL ANGIOPLASTY; VIABAHN ENDOPROSTHESIS AB Successful endovascular intervention for femoral-popliteal (FP) arterial disease provides relief of claudication and offers limb-salvage in cases of critical limb ischemia. Technologies and operator technique have evolved to the point where we may now provide effective endovascular therapy for a spectrum of lesions, patients, and clinical scenarios. Endovascular treatment of this segment offers a significant alternative to surgical revascularization, and may confer improved safety for a wide range of patients, not solely those deemed high surgical risk. Although endovascular therapy of the FP segment has historically been hampered by high rates of restenosis, emerging technologies including drug-eluting stents, drug-coated balloons, and perhaps bio-absorbable stent platforms, provide future hope for more durable patency in complex disease. By combining lessons learned from clinical trials, international trends in clinical practice, and insights regarding emerging technologies, we may appropriately tailor our application of endovascular therapy to provide optimal care to our patients. This document was developed to guide physicians in the clinical decision-making related to the contemporary application of endovascular intervention among patients with FP arterial disease. (C) 2014 Wiley Periodicals, Inc. C1 [Klein, Andrew J.] St Louis VA Healthcare Syst, John Cochran VA Med Ctr, St Louis, MO USA. [Klein, Andrew J.] St Louis Sch Med, St Louis, MO USA. [Pinto, Duane S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Gray, Bruce H.] Univ S Carolina, Sch Med Greenville, Greenville, SC USA. [Jaff, Michael R.; Drachman, Douglas E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [White, Christopher J.] Ochsner Med Ctr, John Ochsner Heart & Vasc Inst, New Orleans, LA USA. RP Drachman, DE (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Gray Bigelow 800, Boston, MA 02114 USA. EM ddrachman@partners.org RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 FU Lutonix/BARD; iDEV; Atrium FX Dr. Klein has no relevant relationships with industry to declare. Dr. White has no relevant relationships to this topic to declare. Dr. Pinto is a consultant to Covidien and the Medicines Company. Dr. Gray has no relevant relationships to declare. Dr. Drachman receives research grant support from Lutonix/BARD, iDEV, and Atrium. Dr. Jaff is a noncompensated advisor for the following companies: Boston Scientific, Cordis Corporation, Covidien Vascular, and Medtronic Vascular. NR 43 TC 8 Z9 9 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT 1 PY 2014 VL 84 IS 4 BP 529 EP 538 DI 10.1002/ccd.25504 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AQ5DT UT WOS:000342826900005 PM 24753020 ER PT J AU Pietzsch, JB Geisler, BP Garner, AM Zeller, T Jaff, MR AF Pietzsch, Jan B. Geisler, Benjamin P. Garner, Abigail M. Zeller, Thomas Jaff, Michael R. TI Economic Analysis of Endovascular Interventions for Femoropopliteal Arterial Disease: A Systematic Review and Budget Impact Model for the United States and Germany SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE peripheral arterial disease; economics/cost-effectiveness; endovascular intervention; balloon; drug coated/eluting; balloon angioplasty; stent; drug eluting ID SUPERFICIAL FEMORAL-ARTERY; NITINOL STENT IMPLANTATION; RESILIENT RANDOMIZED-TRIAL; PACLITAXEL-ELUTING STENTS; BALLOON ANGIOPLASTY; POPLITEAL ARTERIES; PILOT TRIAL; FOLLOW-UP; LESIONS; RESTENOSIS AB Objectives: To study the economic impact on payers and providers of the four main endovascular strategies for the treatment of infrainguinal peripheral artery disease. Background: Bare metal stents (BMS), drug-eluting stents (DES), and drug-coated balloons (DCB) are associated with lower target lesion revascularization (TLR) probabilities than percutaneous transluminal angioplasty (PTA), but the economic impact is unknown. Methods: In December 2012, PubMed and Embase were systematically searched for studies with TLR as an endpoint. The 24-month probability of TLR for each treatment was weighted by sample size. A decision-analytic Markov model was used to assess the budget impact from payers' and facility-providers' perspectives of the four index procedure strategies (BMS, DES, DCB, and PTA). Base cases were developed for U. S. Medicare and the German statutory sickness fund perspectives using current 2013 reimbursement rates. Results: Thirteen studies with 2,406 subjects were included. The reported probability of TLR in the identified studies varied widely, particularly following treatment with PTA or BMS. The pooled 24-month probabilities were 14.3%, 19.3%, 28.1%, and 40.3% for DCB, DES, BMS, and PTA, respectively. The drug-eluting strategies had a lower projected budget impact over 24 months compared to BMS and PTA in both the U. S. Medicare (DCB: (sic)10,214; DES: (sic)12,904; uncoated balloons $ 13,114; BMS $ 13,802) and German public health care systems (DCB (sic)3,619; DES (sic)3,632; BMS (sic)4,026; PTA (sic)4,290). Conclusions: DCB and DES, compared to BMS and PTA, are associated with lower probabilities of target lesion revascularization and cost savings for U. S. and German payers. (C) 2014 Wiley Periodicals, Inc. C1 [Pietzsch, Jan B.; Geisler, Benjamin P.; Garner, Abigail M.] Wing Tech Inc, Menlo Pk, CA USA. [Zeller, Thomas] Univ Herzzentrums Freiburg Bad Krozingen, Bad Krozingen, Germany. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren 905, Boston, MA 02114 USA. EM mjaff@partners.org RI Geisler, Benjamin/A-9244-2010 OI Geisler, Benjamin/0000-0003-1704-6067 FU C.R. Bard; JJ Cordis; Biotronik; Straub Medical; Bayer-Medrad; IDEV; Cook; Abbott Vascular; ReCor FX Wing Tech Inc. (JBP, BPG, AMG) provided consulting services for Medtronic Inc. to construct the health-economic model. TZ serves on the advisory boards of Medtronic, W. L. Gore, Angioslide, Boston Scientific, Covidien, Spectranetics, Veryan, Northwind, and has received consulting fees/honoraria from C.R. Bard, J&J Cordis, Biotronik, Straub Medical, Bayer-Medrad, IDEV, Cook, Abbott Vascular, and ReCor. MRJ is a non-compensated advisor to Medtronic Vascular, and a Board member of VIVA Physicians, a 501(c)3 education and research organization. NR 25 TC 11 Z9 11 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT 1 PY 2014 VL 84 IS 4 BP 546 EP 554 DI 10.1002/ccd.25536 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AQ5DT UT WOS:000342826900007 PM 24782424 ER PT J AU Hennessy, KA Dynan, J AF Hennessy, Kerry Ann Dynan, Judy TI Improving Compliance With Personal Protective Equipment Use Through the Model for Improvement and Staff Champions SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article DE personal protective equipment; hazardous drugs; safe handling ID NURSES AB Although the known risks of exposure to hazardous drugs have been well documented and disseminated, certain barriers remain in the use of personal protective equipment (PPE) by nurses administering chemotherapy. At Dana-Farber Cancer Institute, a program was developed that incorporated not only monitoring and reporting compliance of the use of PPE, but also engaged the staff in audit and reporting activities. Compliance rates improved dramatically over time and have remained at high levels. C1 [Hennessy, Kerry Ann; Dynan, Judy] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hennessy, KA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM khennessy2@partners.org NR 11 TC 3 Z9 3 U1 0 U2 7 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD OCT PY 2014 VL 18 IS 5 BP 497 EP 500 DI 10.1188/14.CJON.497-500 PG 4 WC Oncology; Nursing SC Oncology; Nursing GA AQ8TN UT WOS:000343105500006 PM 25253103 ER PT J AU Cannon, CA Watson, LK Roth, MT LaVergne, S AF Cannon, Carol A. Watson, Lisa K. Roth, Matt T. LaVergne, Shirley TI Assessing the Learning Needs of Oncology Nurses SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article DE professional issues; cancer program development; management or evaluation; nursing education; continuing education ID CANCER SURVIVORS AB The Nurse Oncology Education Program (NOEP) is a nonprofit organization of the Texas Nurses Foundation that develops and provides education for nurses in all fields of practice on cancer prevention, detection, treatment, and survivorship. To meet the most current educational needs of nurses, NOEP conducts a biannual needs assessment survey to better understand its audience and inform its course development. The 2013 NOEP needs assessment survey used a convenience sample of licensed nurses throughout the United States. Nurses completed the online survey, and results revealed several priority areas for educational programs, including management of cancer symptoms and treatment side effects, complementary and alternative or integrative medicine, and screening recommendations. Time was noted as the largest barrier to educating patients and families about primary prevention practices. Results from this survey can be compared to those from previous surveys, particularly the 2009 and 2011 surveys, to determine changes in the demographics of NOEP's constituency, as well as consistencies in educational gaps. The results from the 2013 NOEP needs assessment survey offer valuable information about the learning needs of nurses across the country. The data can be used by the nurse educators and faculty who are responsible for providing cancer-specific education to nurses. C1 [Cannon, Carol A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Watson, Lisa K.; Roth, Matt T.] Nurse Oncol Educ Program, Austin, TX USA. [LaVergne, Shirley] Texas Hosp Assoc Fdn, Austin, TX USA. RP Cannon, CA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM cavcannon@gmail.com FU Cancer Prevention and Research Institute of Texas [542110131] FX Carol A. Cannon, BSN, RN, OCN (R), CHPN, is an oncology nurse at Massachusetts General Hospital in Boston; Lisa K. Watson, MLA, is a marketing and information specialist and Matt T. Roth, BA, is a former program support specialist, both at the Nurse Oncology Education Program in Austin, TX; and Shirley LaVergne, CMP, is a senior specialist at the Texas Hospital Association Foundation in Austin. The authors take full responsibility for the content of the article. Funding for the study was provided by a contract (No. 542110131) from the Cancer Prevention and Research Institute of Texas. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers or editorial staff. Cannon can be reached at cavcannon@gmail.com, with copy to editor at CJONEditor@ons.org. (Submitted November 2013. Revision submitted November 2013. Accepted for publication November 24, 2013.) NR 14 TC 1 Z9 1 U1 2 U2 4 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD OCT PY 2014 VL 18 IS 5 BP 577 EP 580 DI 10.1188/14.CJON.577-580 PG 4 WC Oncology; Nursing SC Oncology; Nursing GA AQ8TN UT WOS:000343105500015 PM 25253111 ER PT J AU Raje, N Faiman, B Harvey, RD Kurtin, SE Lonial, S Kumar, SK Cohen, AD Conde, MA Giralt, SA Recine, MS Tombler, ER Stadtmauer, E Jagannath, S Anderson, KC AF Raje, Noopur Faiman, Beth Harvey, R. Donald Kurtin, Sandra E. Lonial, Sagar Kumar, Shaji K. Cohen, Adam D. Conde, Miguel A. Giralt, Sergio A. Recine, Marie Sabo Tombler, Eugene R. Stadtmauer, Edward Jagannath, Sundar Anderson, Kenneth C. CA Managing Myeloma Continuing Educ I TI Identifying Professional Education Gaps and Barriers in Multiple Myeloma Patient Care: Findings of the Managing Myeloma Continuing Educational Initiative Advisory Committee SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Review DE CME; Continuing education; Guidelines; Management; Practice resources ID STEM-CELL TRANSPLANTATION; LENALIDOMIDE PLUS DEXAMETHASONE; MINIMAL RESIDUAL DISEASE; NURSE LEADERSHIP BOARD; CLINICAL-PRACTICE GUIDELINES; IMWG CONSENSUS PERSPECTIVES; SINGLE-AGENT CARFILZOMIB; HIGH-DOSE DEXAMETHASONE; NEWLY-DIAGNOSED MYELOMA; RISK STRATIFICATION AB Advances in the past decade and a half have led to unprecedented improved outcomes for patients with multiple myeloma (MM), and this disease appears to be transitioning to one more characteristic of a chronic disease in large part due to rapid translation of clinical insights into practice at the community level. Although evidence-based guidelines and consensus recommendations remain an important resource for managing cancer patients, they do not fill the gap between the principles of disease management today and the translation of tailoring treatment for individual patient needs. Thus, there is a continuing need for concise, focused educational activities and resources that facilitate improved knowledge and understanding of appropriate, individualized therapeutic strategies for assessing and caring for patients with MM. The next several years will truly be a time of shifting paradigms in the treatment of MM in which new agents will be approved, response criteria will be updated, and new approaches to risk assessment and monitoring minimal residual disease will evolve and enter practice. New groundbreaking therapeutic approaches, such as immunotherapy, might result in significant changes in how MM is treated and managed over the entire life cycle of the disease. Even the definition of the disease might be further amended as insights grow regarding who should be treated and who might benefit more from observation. As such, oncology clinicians will have to carefully review and update their management approaches accordingly even as they begin to focus even more on the survivorship needs of their MM patients. C1 [Raje, Noopur] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Faiman, Beth] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Harvey, R. Donald; Lonial, Sagar] Emory Univ, Sch Med, Atlanta, GA USA. [Kurtin, Sandra E.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. [Kumar, Shaji K.] Mayo Clin, Div Hematol, Rochester, MN USA. [Cohen, Adam D.; Stadtmauer, Edward] Hosp Univ Penn, Abramson Canc Ctr, Div Hematol Oncol, Philadelphia, PA USA. [Conde, Miguel A.] St Barnabas Hosp, Livingston, NJ USA. [Giralt, Sergio A.] Weill Cornell Coll Med, Mem Sloan Kettering Canc Ctr, Adult Bone Marrow Transplantat Serv, New York, NY USA. [Recine, Marie Sabo; Tombler, Eugene R.] MediCom Worldwide, Morrisville, PA USA. [Jagannath, Sundar] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Div Hematol Oncol, New York, NY 10029 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst, Boston, MA USA. RP Tombler, ER (reprint author), 101 Washington St, Morrisville, PA 19067 USA. EM gtomblet@medicaled.com RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 FU Millennium: The Takeda Oncology Company [12G2664]; Celgene Corporation [10429] FX The Managing Myeloma Continuing Education Initiative Advisory Group meeting which provided the opportunity to discuss the consensus points of this article was supported by educational grants from Millennium: The Takeda Oncology Company (grant # 12G2664), and Celgene Corporation (grant # 10429). NR 148 TC 3 Z9 3 U1 3 U2 11 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 EI 2152-2669 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD OCT PY 2014 VL 14 IS 5 BP 356 EP 369 DI 10.1016/j.clml.2014.04.011 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA AQ5WM UT WOS:000342879300003 PM 25066040 ER PT J AU Rasmussen-Torvik, LJ Stallings, SC Gordon, AS Almoguera, B Basford, MA Bielinski, SJ Brautbar, A Brilliant, MH Carrell, DS Connolly, JJ Crosslin, DR Doheny, KF Gallego, CJ Gottesman, O Kim, DS Leppig, KA Li, R Lin, S Manzi, S Mejia, AR Pacheco, JA Pan, V Pathak, J Perry, CL Peterson, JF Prows, CA Ralston, J Rasmussen, LV Ritchie, MD Sadhasivam, S Scott, SA Smith, M Vega, A Vinks, AA Volpi, S Wolf, WA Bottinger, E Chisholm, RL Chute, CG Haines, JL Harley, JB Keating, B Holm, IA Kullo, IJ Jarvik, GP Larson, EB Manolio, T McCarty, CA Nickerson, DA Scherer, SE Williams, MS Roden, DM Denny, JC AF Rasmussen-Torvik, L. J. Stallings, S. C. Gordon, A. S. Almoguera, B. Basford, M. A. Bielinski, S. J. Brautbar, A. Brilliant, M. H. Carrell, D. S. Connolly, J. J. Crosslin, D. R. Doheny, K. F. Gallego, C. J. Gottesman, O. Kim, D. S. Leppig, K. A. Li, R. Lin, S. Manzi, S. Mejia, A. R. Pacheco, J. A. Pan, V. Pathak, J. Perry, C. L. Peterson, J. F. Prows, C. A. Ralston, J. Rasmussen, L. V. Ritchie, M. D. Sadhasivam, S. Scott, S. A. Smith, M. Vega, A. Vinks, A. A. Volpi, S. Wolf, W. A. Bottinger, E. Chisholm, R. L. Chute, C. G. Haines, J. L. Harley, J. B. Keating, B. Holm, I. A. Kullo, I. J. Jarvik, G. P. Larson, E. B. Manolio, T. McCarty, C. A. Nickerson, D. A. Scherer, S. E. Williams, M. S. Roden, D. M. Denny, J. C. TI Design and Anticipated Outcomes of the eMERGE-PGx Project: A Multicenter Pilot for Preemptive Pharmacogenomics in Electronic Health Record Systems SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GENOME-WIDE ASSOCIATION; MEDICAL-RECORDS; PERSONALIZED MEDICINE; GENETIC-VARIANTS; RESEARCH NETWORK; AFRICAN-AMERICANS; EXTRACTION SYSTEM; PHENOME-WIDE; IMPLEMENTATION; CONSORTIUM AB We describe here the design and initial implementation of the eMERGE-PGx project. eMERGE-PGx, a partnership of the Electronic Medical Records and Genomics Network and the Pharmacogenomics Research Network, has three objectives: (i) to deploy PGRNseq, a next-generation sequencing platform assessing sequence variation in 84 proposed pharmacogenes, in nearly 9,000 patients likely to be prescribed drugs of interest in a 1- to 3-year time frame across several clinical sites; (ii) to integrate well-established clinically validated pharmacogenetic genotypes into the electronic health record with associated clinical decision support and to assess process and clinical outcomes of implementation; and (iii) to develop a repository of pharmacogenetic variants of unknown significance linked to a repository of electronic health record-based clinical phenotype data for ongoing pharmacogenomics discovery. We describe site-specific project implementation and anticipated products, including genetic variant and phenotype data repositories, novel variant association studies, clinical decision support modules, clinical and process outcomes, approaches to managing incidental findings, and patient and clinician education methods. C1 [Rasmussen-Torvik, L. J.; Rasmussen, L. V.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Stallings, S. C.] Vanderbilt Inst Clin & Translat Res, Nashville, TN USA. [Gordon, A. S.; Crosslin, D. R.; Kim, D. S.; Nickerson, D. A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Almoguera, B.; Connolly, J. J.; Keating, B.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Bielinski, S. J.] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA. [Brautbar, A.; Brilliant, M. H.] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. [Carrell, D. S.; Leppig, K. A.; Ralston, J.; Larson, E. B.] Grp Hlth Res Inst, Seattle, WA USA. [Doheny, K. F.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Ctr Inherited Dis Res, Baltimore, MD USA. [Gallego, C. J.; Jarvik, G. P.] Univ Washington, Div Med Genet, Seattle, WA 98195 USA. [Gottesman, O.; Mejia, A. R.; Bottinger, E.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Li, R.; Volpi, S.; Manolio, T.] NHGRI, Div Genom Med, Bethesda, MD 20892 USA. [Lin, S.] Marshfield Clin Res Fdn, Biomed Informat Res Ctr, Marshfield, WI USA. [Manzi, S.; Perry, C. L.; Wolf, W. A.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA USA. [Pacheco, J. A.; Pan, V.; Smith, M.; Chisholm, R. L.] Northwestern Univ, Feinberg Sch Med, Ctr Genet Med, Chicago, IL 60611 USA. [Pathak, J.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA. [Peterson, J. F.; Denny, J. C.] Vanderbilt Univ, Med Ctr, Dept Biomed Informat & Med, Nashville, TN USA. [Prows, C. A.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Human Genet, Cincinnati, OH 45229 USA. [Ritchie, M. D.] Penn State Univ, Dept Biochem & Mol Biol, State Coll, PA USA. [Sadhasivam, S.] Cincinnati Childrens Hosp Med Ctr, Dept Anesthesia, Cincinnati, OH 45229 USA. [Sadhasivam, S.; Vinks, A. A.; Harley, J. B.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. [Scott, S. A.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. Icahn Sch Med Mt Sinai, Mt Sinai Fac Practice Associates Primary Care Pro, New York, NY 10029 USA. [Prows, C. A.; Vinks, A. A.] Cincinnati Childrens Hosp Med Ctr, Div Clin Pharmacol, Cincinnati, OH 45229 USA. [Wolf, W. A.; Holm, I. A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Chute, C. G.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Haines, J. L.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA. [Harley, J. B.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Harley, J. B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Holm, I. A.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. [Kullo, I. J.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [McCarty, C. A.] Essentia Inst Rural Hlth, Duluth, MN USA. [Scherer, S. E.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Williams, M. S.] Geisinger Hlth Syst, Genom Med Inst, Danville, PA USA. [Roden, D. M.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. [Roden, D. M.; Denny, J. C.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. RP Rasmussen-Torvik, LJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. EM ljrtorvik@northwestern.edu RI Bielinski, Suzette/A-2238-2009; OI Bielinski, Suzette/0000-0002-2905-5430; Pan, Vivian/0000-0002-1666-9273; Rasmussen, Luke/0000-0002-4497-8049 FU Cincinnati Children's Hospital Medical Center/Harvard [U01HG006828]; Children's Hospital of Philadelphia [U01HG006830]; Essentia Institute of Rural Health [U01HG006389]; Geisinger Clinic [U01HG006382]; Group Health Cooperative [U01HG006375]; University of Washington [U01HG006375]; Mayo Clinic [U01HG006379]; Icahn School of Medicine at Mount Sinai [U01HG006380]; Northwestern University [U01HG006388]; Vanderbilt University [U01HG006378]; Vanderbilt serving as the coordinating center [U01HG006385]; Deep Resequencing Resources of the Pharmacogenomic Research Network [U01 HL069757, U19 GM61388, U01 GM097119]; National Human Genome Research Institute [5U01HG006507]; Mayo Clinic Center for Individualized Medicine; National Institutes of Health (Pharmacogenomics Research Network) [U19 GM61388]; Rochester Epidemiology Project [R01 GM28157, U01 HG005137, R01 CA138461, R01 AG034676]; Pharmacogenomics of Arrhythmia Therapy PGRN site grant from the National Institute of General Medical Sciences; National Heart, Lung, and Blood Institute [U19 HL65262]; [U01HG004438]; [HL069757] FX The eMERGE Network was funded through the following grants: U01HG006828 (Cincinnati Children's Hospital Medical Center/Harvard); U01HG006830 (Children's Hospital of Philadelphia); U01HG006389 (Essentia Institute of Rural Health); U01HG006382 (Geisinger Clinic); U01HG006375 (Group Health Cooperative and the University of Washington); U01HG006379 (Mayo Clinic)); U01HG006380 (Icahn School of Medicine at Mount Sinai); U01HG006388 (Northwestern University); U01HG006378 (Vanderbilt University); and U01HG006385 (Vanderbilt serving as the coordinating center). The development of the PGRN-Seq platform was supported by the Deep Resequencing Resources of the Pharmacogenomic Research Network: U01 HL069757, U19 GM61388, and U01 GM097119. The activities being performed at Johns Hopkins Center for Inherited Disease Research and Johns Hopkins DNA Diagnostic Lab are funded by grant U01HG004438. This work is also supported by grant (HL069757). One list of actionable genes was generated with funding from the National Human Genome Research Institute, 5U01HG006507. At Mayo Clinic this work was also supported in part by Mayo Clinic Center for Individualized Medicine and National Institutes of Health grants U19 GM61388 (the Pharmacogenomics Research Network), R01 GM28157, U01 HG005137, R01 CA138461, and R01 AG034676 (the Rochester Epidemiology Project). At Vanderbilt University, the work was also supported by the Pharmacogenomics of Arrhythmia Therapy PGRN site grant from the National Institute of General Medical Sciences and the National Heart, Lung, and Blood Institute (U19 HL65262), which also supports the site's participation in the Translational Pharmacogenetics Program and the Clinical Pharmacogenetics Implementation Consortium. NR 47 TC 53 Z9 54 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD OCT PY 2014 VL 96 IS 4 BP 482 EP 489 DI 10.1038/clpt.2014.137 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AQ3FN UT WOS:000342675400027 PM 24960519 ER PT J AU Tse, JY Stover, DG Chebib, I AF Tse, J. Y. Stover, D. G. Chebib, I. TI Simultaneous metastasis of melanoma and lung adenocarcinoma to hilar lymph nodes and pleural effusion after renal transplantation SO CYTOPATHOLOGY LA English DT Letter ID FINE-NEEDLE-ASPIRATION; SQUAMOUS-CELL CARCINOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; DIAGNOSIS; BIOPSY C1 [Tse, J. Y.; Chebib, I.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Tse, J. Y.; Chebib, I.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Stover, D. G.] Massachusetts Gen Hosp, Dana Farber Canc Inst Partners Canc Care, Ctr Canc, Dept Med Oncol, Boston, MA 02114 USA. RP Tse, JY (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, 55 Fruit St,WRN2, Boston, MA 02114 USA. EM jytse@partners.org OI Stover, Daniel/0000-0001-9003-8165 FU NCI NIH HHS [T32 CA009172] NR 6 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0956-5507 EI 1365-2303 J9 CYTOPATHOLOGY JI Cytopathology PD OCT PY 2014 VL 25 IS 5 BP 342 EP 344 DI 10.1111/cyt.12088 PG 3 WC Cell Biology; Pathology SC Cell Biology; Pathology GA AQ7HN UT WOS:000342983400010 PM 23899339 ER PT J AU Hoeppner, BB Hoeppner, SS Kelly, JF AF Hoeppner, Bettina B. Hoeppner, Susanne S. Kelly, John F. TI Do young people benefit from AA as much, and in the same ways, as adult aged 30+? A moderated multiple mediation analysis SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Young adults; Alcohol; Alcohol use disorder (AUD); Alcoholics Anonymous; Mediation; Mechanism of change ID BEHAVIOR-CHANGE; ALCOHOL-CONSUMPTION; 12-STEP ATTENDANCE; SELF-HELP; INPATIENT TREATMENT; PROJECT MATCH; USE DISORDERS; USE OUTCOMES; PARTICIPATION; ADOLESCENTS AB Background: Research has shown that participation in Alcoholics Anonymous (AA) confers significant recovery benefit to adults suffering from alcohol use disorder (AUD). Concerns persist, however, that AA may not work as well for younger adults, who tend to have shorter addiction histories, different social circumstances, and less spiritual/religious interest than adults. Methods: Secondary data analysis of Project MATCH, using a prospective, moderated multiple mediation analysis to test and compare six previously identified mechanisms of change in younger adults (n = 266) vs. adults aged 30+ (n = 1460). Nine clinical sites within the United States. Treatment-seeking adults (n = 1726) suffering from AUD who participated in 12 weeks of outpatient treatment and completed follow-ups at 3-, 9- and 15-months. AA attendance during treatment; mediators at 9 months; and outcomes [percentage of days abstinent (PDA) and drinks per drinking day (DDD)] at 15 months. Results: AA attendance was associated with improved drinking outcomes in both younger adults (PDA: F(1, 247)= 8.55, p < 0.01; DDD: F(1, 247)=15.93, p < 0.01) and adults aged 30+ (PDA: F(1, 1311) = 86.58, p < 0.01; DDD: F(1, 1311) = 11.96, p < 0.01). Only two of the six hypothesized pathways (i.e., decreases in pro-drinking social networks, self-efficacy in social situations) appeared to work in younger adults. Conclusion: Unidentified mechanisms of behavior change that are mobilized by AA participation appear to be at work in young people. Once identified, these mechanisms may shed new light on how exactly AA confers similar benefits for young people and, more broadly, may enhance our understanding of recovery-related change for young adults that could yield novel intervention targets. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Hoeppner, Bettina B.; Hoeppner, Susanne S.; Kelly, John F.] Harvard Univ, Massachusetts Gen Hosp, Ctr Addict Med, Sch Med, Boston, MA 02114 USA. RP Hoeppner, BB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Addict Med, Sch Med, 60 Staniford St, Boston, MA 02114 USA. EM bhoeppner@mgh.harvard.edu FU National Institute of Alcohol Abuse and Alcoholism [NIAAA R21 AA016762]; National Institute on Drug Abuse [K01 DA027097] FX This research was supported by a grant from the National Institute of Alcohol Abuse and Alcoholism (NIAAA R21 AA016762; Mechanisms and Moderators of Behavior Change in Alcoholics Anonymous) and a grant from the National Institute on Drug Abuse (K01 DA027097). The NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 65 TC 5 Z9 5 U1 2 U2 20 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 1 PY 2014 VL 143 BP 181 EP 188 DI 10.1016/j.drugalcdep.2014.07.023 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AQ5TI UT WOS:000342871100024 PM 25150401 ER PT J AU Vijayaraghavan, M Freitas, D Bangsberg, DR Miaskowski, C Kushel, MB AF Vijayaraghavan, Maya Freitas, Daniel Bangsberg, David R. Miaskowski, Christine Kushel, Margot B. TI Non-medical use of non-opioid psychotherapeutic medications in a community-based cohort of HIV-infected indigent adults SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Benzodiazepines; Muscle relaxants; Non-medical use; Prescription stimulants ID PRESCRIPTION DRUG OVERDOSES; CHRONIC PAIN; MENTAL-HEALTH; UNITED-STATES; OPIOID USE; ABUSE; PATTERNS; MISUSE AB Background: Non-opioid psychotherapeutic medications significantly increase the risk of opioid overdose-related deaths. We prospectively followed HIV-infected indigent adults sampled from the community to examine rates of and factors associated with non-medical use of benzodiazepines, muscle relaxants, and prescription stimulants. Methods: We interviewed participants quarterly for 2 years about alcohol and illicit substance use; depression; use of prescribed opioid analgesics, benzodiazepines and muscle relaxants; opioid analgesic misuse; and non-medical use (i.e., use without a prescription) of benzodiazepines, muscle relaxants, and prescription stimulants. Using mixed-effects multivariate logistic regression, we determined factors associated with non-medical use of benzodiazepines, muscle relaxants, and prescription stimulants. Results: Among the 296 participants at enrollment, 52.0% reported taking opioid analgesics that had been prescribed, 17.9% took benzodiazepines that had been prescribed, and 8.1% took muscle relaxants that had been prescribed. Over the 2-year study interval, 53.4% reported prescription opioid misuse, 25.3% reported non-medical use of benzodiazepines, 11.5% reported non-medical use of muscle relaxants, and 6.1% reported non-medical use of prescription stimulants. In rnultivariable analysis, opioid analgesic misuse in the past 90 days was associated with non-medical use of benzodiazepines, muscle relaxants, and prescription stimulants during the same time interval. Illicit substance use and depression were not associated with non-medical use of these medications. Conclusions: Prescription opioid analgesic misuse is associated with non-medical use of other psychotherapeutic medications. Health care providers should monitor for non-medical use of a broad array of psychoactive medications among high-risk populations to minimize harm. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Vijayaraghavan, Maya] Univ Calif San Diego, Moores UCSD Canc Ctr, San Diego, CA 92093 USA. [Bangsberg, David R.] Harvard Univ, Ctr Global Hlth, Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard,Sch Med, Boston, MA 02114 USA. [Miaskowski, Christine] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA. [Kushel, Margot B.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Kushel, MB (reprint author), San Francisco Gen Hosp, Div Gen Internal Med, Box 1364, San Francisco, CA 94143 USA. EM mvijayaraghavan@ucsd.edu; Daniel.Freitas@ucsf.edu; dbangsberg@partners.org; chris.miaskowski@nursing.ucsf.edu; mkushel@medsfgh.ucsf.edu FU National Institute on Drug Abuse [R01DA022550]; National Institute of Mental Health [R01MH54907]; University of California, San Francisco (UCSF); Clinical and Translational Institute grant; NIH/NCRR [UCSF-CTSI UL1 RR024131]; Tobacco-Related Disease Research Program [22XT-0020]; National Institute on Minority Health and Health Disparities [R25MD006832] FX This study was funded by a grant from the National Institute on Drug Abuse R01DA022550, and a grant from the National Institute of Mental Health R01MH54907. The Tenderloin Center for Clinical Research was supported by the University of California, San Francisco (UCSF), Clinical and Translational Institute grant, NIH/NCRR UCSF-CTSI UL1 RR024131. The funders had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. Dr. Vijayaraghavan is supported by an exploratory/developmental grant from Tobacco-Related Disease Research Program (22XT-0020). Mr. Freitas was supported by R25MD006832 from the National Institute on Minority Health and Health Disparities. Drs. Kushel and Vijayaraghavan had full access to the data and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 27 TC 3 Z9 3 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 1 PY 2014 VL 143 BP 263 EP 267 DI 10.1016/j.drugalcdep.2014.06.044 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AQ5TI UT WOS:000342871100036 PM 25107312 ER PT J AU Barrett, LF AF Barrett, Lisa Feldman TI The Conceptual Act Theory: A Precis SO EMOTION REVIEW LA English DT Article DE affect; conceptual act; Darwin; emotion; psychological construction ID PSYCHOLOGICAL CONSTRUCTION; FUNCTIONAL ARCHITECTURE; EMOTION; BRAIN; EXPERIENCE; SCIENCE AB According to the conceptual act theory, emotions emerge when physical sensations in the self and physical actions in others are meaningfully linked to situations during a process that can be called both cognitive and perceptual (creating emotional experiences, and emotion perceptions, respectively). There are key four hypotheses: (a) an emotion (like anger) is a conceptual category, populated with instances that are tailored to the environment; (b) each instance of emotion is constructed within the brain's functional architecture of domain-general core systems; (c) the workings of each system must be holistically understood within the momentary state of the brain, the body, and the surrounding context; (d) being emergent states, emotional episodes have functional features that physical states, alone, do not have. Similarities and differences to other theoretical approaches to emotion are discussed. C1 [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Barrett, LF (reprint author), Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. EM l.barrett@neu.edu FU National Institute of Health Director's Pioneer Award [DP1OD003312]; National Institute on Aging [R01AG030311]; National Institute of Mental Health [R21MH099605]; National Science Foundation [BCS-1052790]; U.S. Army Research Institute for the Behavioral and Social Sciences [W5J9CQ-11-C-0046, W5J9CQ-12-C-0049] FX Preparation of this manuscript was supported by a National Institute of Health Director's Pioneer Award (DP1OD003312), by grants from the National Institute on Aging (R01AG030311), the National Institute of Mental Health (R21MH099605), and the National Science Foundation (BCS-1052790), and by contracts from U.S. Army Research Institute for the Behavioral and Social Sciences (Contracts W5J9CQ-11-C-0046, W5J9CQ-12-C-0049) to Lisa Feldman Barrett. The views, opinions, and/or findings contained in this article are solely those of the author and should not be construed as an official Department of the Army or Department of Defense (DOD) position, policy, or decision. NR 32 TC 33 Z9 33 U1 2 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1754-0739 EI 1754-0747 J9 EMOT REV JI Emot. Rev. PD OCT PY 2014 VL 6 IS 4 BP 292 EP 297 DI 10.1177/1754073914534479 PG 6 WC Psychology, Multidisciplinary SC Psychology GA AQ7FE UT WOS:000342977200002 ER PT J AU Guidetti, A Prada, CP Laubach, JP Varga, C Maglio, ME McKenney, M Doss, D Schlossman, RL Mitsiades, C Hideshima, T Gorgun, GT Ghobrial, IM Raje, N Munshi, N Anderson, KC Richardson, PG AF Guidetti, Anna Prada, Claudia Paba Laubach, Jacob P. Varga, Cindy Maglio, Michelle E. McKenney, Mary Doss, Deborah Schlossman, Robert L. Mitsiades, Constantine Hideshima, Teru Gorgun, Gullu T. Ghobrial, Irene M. Raje, Noopur Munshi, Nikhil Anderson, Kenneth C. Richardson, Paul G. TI Pomalidomide for the treatment of relapsed and refractory multiple myeloma SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Article DE immunomodulatory drugs; multiple myeloma; pomalidomide; relapsed and refractory ID LOW-DOSE DEXAMETHASONE; LENALIDOMIDE PLUS DEXAMETHASONE; IMMUNOMODULATORY DRUGS; MOLECULAR-MECHANISMS; AGENTS LENALIDOMIDE; COMBINATION THERAPY; THALIDOMIDE ANALOGS; CYTOKINE PRODUCTION; ANTITUMOR-ACTIVITY; ANTICANCER AGENTS AB Introduction: Multiple myeloma patients who are refractory to lenalidomide and bortezomib have a dismal prognosis. Pomalidomide is a new immunomodulatory agent approved for the treatment of relapsed and refractory multiple myeloma (RRMM) that is unique in that it demonstrates promising activity but appears to be associated with lower toxicity than thalidomide or lenalidomide. Areas covered: We review the mechanisms of action of pomalidomide, evaluate preclinical data, summarize the results of dose-finding Phase I studies and describe Phase II/III studies of this drug in combination with dexamethasone and other agents. Data presented were gathered from multiple sources, including articles from PubMed, published abstracts from the annual meetings of the American Society of Hematology and American Society of Clinical Oncology and websites such as http://clinicaltrials.gov/. Expert opinion: The regulatory approval of pomalidomide represents an important addition to a hematologist's armamentarium for the treatment of RRMM. Pomalidomide is well tolerated and demonstrates a high level of anti-myeloma activity. Pomalidomide combined with dexamethasone should be considered as standard-of-care therapy for advanced RRMM following progression on both lenalidomide and bortezomib. Ongoing and future studies will characterize the activity of different combinations intended to improve treatment responses, and the potential role of pomalidomide as maintenance therapy. C1 [Guidetti, Anna] Univ Milan, Sch Med, Dept Pathophysiol & Transplantat, I-20122 Milan, Italy. [Prada, Claudia Paba; Laubach, Jacob P.; Schlossman, Robert L.; Munshi, Nikhil; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Varga, Cindy] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. [Maglio, Michelle E.; McKenney, Mary; Doss, Deborah] Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mitsiades, Constantine; Hideshima, Teru; Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Gorgun, Gullu T.] Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ghobrial, Irene M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Multiple Myeloma, Boston, MA 02114 USA. RP Richardson, PG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu RI Guidetti, Anna/E-6676-2017 OI Guidetti, Anna/0000-0002-4195-6397 FU Celgene Corp.; RJ Corman Multiple Myeloma Research Fund FX Medical writing support was provided by Sandralee Lewis of the Investigator Initiated Research Writing Group (part of the KnowledgePoint360 Group, an Ashfield Co.) and was funded by Celgene Corp. and the RJ Corman Multiple Myeloma Research Fund. NR 105 TC 0 Z9 1 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PD OCT PY 2014 VL 2 IS 10 BP 1089 EP 1108 DI 10.1517/21678707.2014.953480 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AQ7LO UT WOS:000342998800009 ER PT J AU Li, XF Shorter, D Kosten, TR AF Li, Xiaofan Shorter, Daryl Kosten, Thomas R. TI Buprenorphine in the treatment of opioid addiction: opportunities, challenges and strategies SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Editorial Material DE barriers; buprenorphine; integrated treatment model; office-based; opioid dependence ID INJECTION DEPOT FORMULATION; RANDOMIZED CONTROLLED-TRIAL; DAY DOSING REGIMENS; PRIMARY-CARE; IMPLEMENTING BUPRENORPHINE; PRESCRIBING BUPRENORPHINE; SUBLINGUAL BUPRENORPHINE; SUBSTITUTION TREATMENT; METHADONE-MAINTENANCE; TREATMENT OUTCOMES AB Introduction: Buprenorphine follows the success of methadone as another milestone in the history of treatment for opioid addiction. Buprenorphine can be used in an office-based setting where it is clearly effective, highly accepted by patients and has a favorable safety profile and less abuse potential. However, the adoption of buprenorphine treatment has been slow in the USA. Areas covered: This article first reviews the history of medication-assisted opioid addiction treatment and the current epidemic opioid addiction, followed by a review of the efficacy, pharmacology and clinical prescription of buprenorphine in office-based care. We then explore the possible barriers in using buprenorphine and the ways to overcome these barriers, including new formulations, educational programs and policy regulations that strike a balance between accessibility and reducing diversion. Expert opinion: Buprenorphine can align addiction treatment with treatments for other chronic medical illnesses. However, preventing diversion will require graduate and continuing medical education and integrated care models for delivery of buprenorphine to those in need. C1 [Li, Xiaofan] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Shorter, Daryl] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Div Alcohol & Addict Psychiat, Houston, TX 77030 USA. RP Shorter, D (reprint author), Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Michael E DeBakey Vet Affairs Med Ctr, 1 Baylor Plaza, Houston, TX 77030 USA. EM shorter@bcm.edu FU CSRD VA [IK2 CX000946] NR 85 TC 4 Z9 4 U1 4 U2 20 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 EI 1744-7666 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD OCT PY 2014 VL 15 IS 15 BP 2263 EP 2275 DI 10.1517/14656566.2014.955469 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AQ5UP UT WOS:000342874400012 PM 25171726 ER PT J AU Lu, FL Liu, YT Jiang, L Yamaguchi, S Zhang, Y AF Lu, Falong Liu, Yuting Jiang, Lan Yamaguchi, Shinpei Zhang, Yi TI Role of Tet proteins in enhancer activity and telomere elongation SO GENES & DEVELOPMENT LA English DT Article DE DNA methylation; demethylation; enhancer; embryonic stem cell; telomere ID EMBRYONIC STEM-CELLS; MOUSE ES CELLS; DNA METHYLATION; CPG ISLANDS; POSTNATAL-DEVELOPMENT; GENE-EXPRESSION; MAMMALIAN DNA; HUMAN GENOME; 5-HYDROXYMETHYLCYTOSINE; CHROMATIN AB DNA methylation at the C-5 position of cytosine (5mC) is one of the best-studied epigenetic modifications and plays important roles in diverse biological processes. Iterative oxidation of 5mC by the ten-eleven translocation (Tet) family of proteins generates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5fC and 5caC are selectively recognized and excised by thymine DNA glycosylase (TDG), leading to DNA demethylation. Functional characterization of Tet proteins has been complicated by the redundancy between the three family members. Using CRISPR/Cas9 technology, we generated mouse embryonic stem cells (ESCs) deficient for all three Tet proteins (Tet triple knockout [TKO]). Whole-genome bisulfite sequencing (WGBS) analysis revealed that Tet-mediated DNA demethylation mainly occurs at distally located enhancers and fine-tunes the transcription of genes associated with these regions. Functional characterization of Tet TKO ESCs revealed a role for Tet proteins in regulating the two-cell embryo (2C)-like state under ESC culture conditions. In addition, Tet TKO ESCs exhibited increased telomere sister chromatid exchange and elongated telomeres. Collectively, our study reveals a role for Tet proteins in not only DNA demethylation at enhancers but also regulating the 2C-like state and telomere homeostasis. C1 [Lu, Falong; Liu, Yuting; Jiang, Lan; Yamaguchi, Shinpei; Zhang, Yi] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Lu, Falong; Liu, Yuting; Jiang, Lan; Yamaguchi, Shinpei; Zhang, Yi] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Lu, Falong; Liu, Yuting; Jiang, Lan; Yamaguchi, Shinpei; Zhang, Yi] Boston Childrens Hosp, Div Hematol Oncol, Dept Pediat, Boston, MA 02115 USA. [Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yi] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Zhang, Y (reprint author), Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. EM yzhang@genetics.med.harvard.edu FU National Institutes of Health [U01DK089565]; Japan Society for the Promotion of Science (JSPS) FX We thank Dr. Hao Wu and Dr. Shogo Matoba for their helpful discussions; Dr. Li Shen, Dr. Wei Jiang, and Dr. Kumiko A. Iwabuchi for technical assistance; and Dr. Ana D'Alessio for generating the Tet2 antibody. We are grateful to Dr. Luis M. Tuesta and Dr. Hao Wu for critical reading of the manuscript. This project is supported by National Institutes of Health grant U01DK089565. S.Y. is supported by a post-doctoral fellowship from the Japan Society for the Promotion of Science (JSPS). Y.Z. is an investigator of the Howard Hughes Medical Institute. NR 71 TC 46 Z9 46 U1 4 U2 24 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD OCT 1 PY 2014 VL 28 IS 19 BP 2103 EP 2119 DI 10.1101/gad.248005.114 PG 17 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA AQ5ZX UT WOS:000342888200004 PM 25223896 ER PT J AU Gray, SW Martins, Y Feuerman, LZ Bernhardt, BA Biesecker, BB Christensen, KD Joffe, S Rini, C Veenstra, D McGuire, AL AF Gray, Stacy W. Martins, Yolanda Feuerman, Lindsay Z. Bernhardt, Barbara A. Biesecker, Barbara B. Christensen, Kurt D. Joffe, Steven Rini, Christine Veenstra, David McGuire, Amy L. CA CSER Consortium Outcomes Measures TI Social and behavioral research in genomic sequencing: approaches from the Clinical Sequencing Exploratory Research Consortium Outcomes and Measures Working Group SO GENETICS IN MEDICINE LA English DT Review DE behavior; genome sequencing; measures; outcomes; psychosocial ID SMOKING-CESSATION; PSYCHOMETRIC EVALUATION; CANCER SUSCEPTIBILITY; HUNTINGTONS-DISEASE; INFORMED-CONSENT; SCALE; RISK; VALIDATION; IMPACT; QUESTIONNAIRE AB The routine use of genomic sequencing in clinical medicine has the potential to dramatically alter patient care and medical outcomes. To fully understand the psychosocial and behavioral impact of sequencing integration into clinical practice, it is imperative that we identify the factors that influence sequencing-related decision making and patient outcomes. In an effort to develop a collaborative and conceptually grounded approach to studying sequencing adoption, members of the National Human Genome Research Institute's Clinical Sequencing Exploratory Research Consortium formed the Outcomes and Measures Working Group. Here we highlight the priority areas of investigation and psychosocial and behavioral outcomes identified by the Working Group. We also review some of the anticipated challenges to measurement in social and behavioral research related to genomic sequencing; opportunities for Instrument development; and the importance of qualitative, quantitative, and mixed-method approaches. This work represents the early, shared efforts of multiple research teams as we strive to understand individuals' experiences with genomic sequencing. The resulting body of knowledge will guide recommendations for the optimal use of sequencing in clinical practice. C1 [Gray, Stacy W.; Martins, Yolanda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gray, Stacy W.; Christensen, Kurt D.] Harvard Univ, Sch Med, Boston, MA USA. [Gray, Stacy W.; Christensen, Kurt D.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Feuerman, Lindsay Z.; McGuire, Amy L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. [Bernhardt, Barbara A.] Univ Penn, Sch Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Bernhardt, Barbara A.] Univ Penn, Penn Ctr Integrat Genet Healthcare Technol, Philadelphia, PA 19104 USA. [Biesecker, Barbara B.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Joffe, Steven] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Rini, Christine] Univ N Carolina, Chapel Hill, NC USA. [Rini, Christine] UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Veenstra, David] Univ Washington, Pharmaceut Outcomes Res & Policy Program, Dept Pharm, Seattle, WA 98195 USA. RP Gray, SW (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM stacyw_gray@dfci.harvard.edu OI Martins, Yolanda/0000-0002-3983-3531 FU National Human Genome Research Institute [1U01HG006485, 1U01HG006487, 1U01HG006492, 1U01HG006500, 1U01HG006507, 1U01HG005211, 1U01HG006546, 1U01HG007307, U01HG007303, 5R01HG006618, 5R01HG006615, 5R01HG006600, 5R21HG006596, 5R21HG006612, 5R21HG006613, 5R21HG006594, 1F32HG006993, R01 GM109743]; National Human Research Institute, National Institutes of Health; American Cancer Society [120529-MRSG-11-006-01-CPPB] FX This work was funded by the National Human Genome Research Institute grants 1U01HG006485, 1U01HG006487, 1U01HG006492, 1U01HG006500, 1U01HG006507, 1U01HG005211, 1U01HG006546, 1U01HG007307, U01HG007303, 5R01HG006618, 5R01HG006615, 5R01HG006600, 5R21HG006596, 5R21HG006612, 5R21HG006613, 5R21HG006594, 1F32HG006993, and R01 GM109743, Rettie AE; the Intramural Research Program of the National Human Research Institute, National Institutes of Health; and the American Cancer Society (120529-MRSG-11-006-01-CPPB). NR 75 TC 14 Z9 14 U1 4 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD OCT PY 2014 VL 16 IS 10 BP 727 EP 735 DI 10.1038/gim.2014.26 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA AQ5YM UT WOS:000342884500001 PM 24625446 ER PT J AU Kullgren, JT Harkins, KA Bellamy, SL Gonzales, A Tao, YY Zhu, JS Volpp, KG Asch, DA Heisler, M Karlawish, J AF Kullgren, Jeffrey T. Harkins, Kristin A. Bellamy, Scarlett L. Gonzales, Amy Tao, Yuanyuan Zhu, Jingsan Volpp, Kevin G. Asch, David A. Heisler, Michele Karlawish, Jason TI A Mixed-Methods Randomized Controlled Trial of Financial Incentives and Peer Networks to Promote Walking Among Older Adults SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE behavioral economics; eHealth; financial incentives; older adults; walking ID IMPROVE WARFARIN ADHERENCE; INCREASE PHYSICAL-ACTIVITY; HEALTH OUTCOMES; WEIGHT-LOSS; SUPPORT; PEDOMETER; PEOPLE; METAANALYSIS; POPULATIONS; MANAGEMENT AB Background. Financial incentives and peer networks could be delivered through eHealth technologies to encourage older adults to walk more. Methods. We conducted a 24-week randomized trial in which 92 older adults with a computer and Internet access received a pedometer, daily walking goals, and weekly feedback on goal achievement. Participants were randomized to weekly feedback only (Comparison), entry into a lottery with potential to earn up to $200 each week walking goals were met (Financial Incentive), linkage to four other participants through an online message board (Peer Network), or both interventions (Combined). Main outcomes were the proportion of days walking goals were met during the 16-week intervention and 8-week follow-up. We conducted a content analysis of messages posted by Peer Network and Combined arm participants. Results. During the 16-week intervention, there were no differences in the proportion of days walking goals were met in the Financial Incentive (39.7%; p = .78), Peer Network (24.9%; p = .08), and Combined (36.0%; p = .77) arms compared with the Comparison arm (36.0%). During 8 weeks of follow-up, the proportion of days walking goals were met was lower in the Peer Network arm (18.7%; p = .025) but not in the Financial Incentive (29.3%; p = .50) or Combined (24.8%; p = .37) arms, relative to the Comparison arm (34.5%). Messages posted by participants focused on barriers to walking and provision of social support. Conclusions. Financial incentives and peer networks delivered through eHealth technologies did not result in older adults walking more. C1 [Kullgren, Jeffrey T.; Heisler, Michele] VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA. [Kullgren, Jeffrey T.; Heisler, Michele] Univ Michigan, Ann Arbor, MI 48109 USA. [Harkins, Kristin A.; Bellamy, Scarlett L.; Tao, Yuanyuan; Zhu, Jingsan; Volpp, Kevin G.; Asch, David A.; Karlawish, Jason] Univ Penn, Philadelphia, PA 19104 USA. [Bellamy, Scarlett L.; Tao, Yuanyuan; Zhu, Jingsan; Volpp, Kevin G.; Asch, David A.; Karlawish, Jason] Ctr Hlth Incent & Behav Econ, Leonard Davis Inst Hlth Econ, Philadelphia, PA USA. [Bellamy, Scarlett L.; Tao, Yuanyuan; Zhu, Jingsan; Volpp, Kevin G.; Asch, David A.; Karlawish, Jason] Penn CMU Roybal P30 Ctr Behav Econ & Hlth, Philadelphia, PA USA. [Gonzales, Amy] Indiana Univ, Bloomington, IN USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Kullgren, JT (reprint author), VA Ann Arbor Healthcare Syst, VA Ctr Clin Management Res, POB 130170, Ann Arbor, MI 48113 USA. EM jkullgre@med.umich.edu RI Heisler, Michele/B-5774-2015 OI Heisler, Michele/0000-0002-6889-2063 FU National Institute on Aging (Multi PIs Volpp and Asch) [RC2103282621]; Department of Veterans Affairs; Robert Wood Johnson Foundation FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Grant RC2103282621 from the National Institute on Aging (Multi PIs Volpp and Asch). Support was also provided by the Department of Veterans Affairs and the Robert Wood Johnson Foundation. NR 46 TC 9 Z9 9 U1 1 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 EI 1552-6127 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD OCT PY 2014 VL 41 SU 1 BP 43S EP 50S DI 10.1177/1090198114540464 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AQ6MW UT WOS:000342928400006 PM 25274710 ER PT J AU Bonatti, R Silva, AFG Batatinha, AP Sobrado, LF Machado, AD Varone, BB Nearing, BD Belardinelli, L Verrier, RL AF Bonatti, Rodolfo Garcia Silva, Ana Flavia Batatinha, Americo Pereira Sobrado, Lucas F. Machado, Ananda Dianni Varone, Bruno B. Nearing, Bruce D. Belardinelli, Luiz Verrier, Richard L. TI Selective late sodium current blockade with GS-458967 markedly reduces ischemia-induced atrial and ventricular repolarization alternans and ECG heterogeneity SO HEART RHYTHM LA English DT Article DE Late I-Na; Atrial fibrillation; Atrial ischemia; Ventricular fibrillation; Ventricular ischemia; Heterogeneity; Depolarization; Repolarization; Antiarrhythmic drugs ID T-WAVE ALTERNANS; INTACT PORCINE HEART; CARDIAC-ARRHYTHMIA; FIBRILLATION; RANOLAZINE; POTENT; VULNERABILITY; MECHANISM; TRIAL; SUPPRESSION AB BACKGROUND Ischemic heart disease is associated with dual risk for atrial and ventricular arrhythmias. OBJECTIVE We examined whether selectively targeting late sodium channel current (I-Na) with 65-458967 (hereafter 65967) can reduce cardiac electrical instability and compared its effects to a clinically relevant dose of flecainide. METHODS Electrode catheters were positioned on the left atrial appendage and left ventricle of anesthetized pigs to monitor repolarization alternans and electrocardiographic heterogeneity before and during left circumflex coronary artery stenosis (75% flow reduction) before and after GS967 (0.4 mg/kg, intravenously [IV]) or ftecainide (1 mg/kg, IV, bolus over 2 minutes followed by 1 mg/(kg . h), IV, for 1 hour) administration. RESULTS Left circumflex coronary artery stenosis increased atrial repolarization alternans by 520% (from 9.4 +/- 1.2 to 58.3 +/- 11.3 mu V; P = .029) and 1-wave alternans by 1038% (from 30.7 +/- 8.2 to 349.3 +/- 103.8 mu V; P = .049). GS967 prevented ischemia-induced increases in alternans in the left atrium (9.3 +/- 5.6 mu V vs 58.3 +/- 11.3 mu V; P = .023) and Left ventricle (217.9 +/- 95.8 mu V vs 349.3 +/- 103.8 mu V; P < .001) (n = 7). GS967 reduced ischemia-induced increases in depolarization heterogeneity (atrium: from 45% to 28%; ventricle: from 92% to 51%) and repolarization heterogeneity (atrium: 43% to 23%; ventricle: 137% to 91%). GS967 did not alter heart rate, arterial blood pressure, PR and QT intervals, or QRS duration, but it mildly decreased contractility (left ventricular dP/dt) during ischemia, which was consistent with late I-Na inhibition. Flecainide (n = 7) amplified ischemia-induced increase in atrial and ventricular repolarization alternans, electrocardiographic heterogeneity, and ventricular fibrillation incidence. CONCLUSION Selective late IN, inhibition with 65967 exerts potent protective effects against ischemia-induced depolarization and repolarization abnormalities in both atria and ventricles. C1 [Bonatti, Rodolfo; Garcia Silva, Ana Flavia; Batatinha, Americo Pereira; Sobrado, Lucas F.; Machado, Ananda Dianni; Varone, Bruno B.] Univ Sao Paulo, Fac Med, Sao Paulo, Brazil. [Bonatti, Rodolfo; Garcia Silva, Ana Flavia; Batatinha, Americo Pereira; Sobrado, Lucas F.; Machado, Ananda Dianni; Varone, Bruno B.; Nearing, Bruce D.; Verrier, Richard L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Nearing, Bruce D.] Harvard Univ, Sch Med, Boston, MA USA. [Belardinelli, Luiz] Gilead Sci Inc, Foster City, CA 94404 USA. RP Verrier, RL (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, 99 Brookline Ave,RN-301, Boston, MA 02215 USA. EM rverrier@bidmc.harvard.edu FU Gilead Sciences; Lemann family; Colegio Bandeirantes; Harvard University's David Rockefeller Center for Latin American Studies FX This study was funded by a grant from Gilead Sciences to Beth Israel Deaconess Medical Center, Dr Verrier, P.I. Messrs Bonatti and Batatinha and Ms Silva have received support from the Lemann family, Dr Miguel Srougi, Colegio Bandeirantes, and Harvard University's David Rockefeller Center for Latin American Studies. Dr Belardinelli is an employee of Gilead Sciences. Dr Verrier and Dr Nearing have received royalties from George-town University and Beth Israel Deaconess Medical Center for intellectual property on the modified moving average method for T-wave alternans analysis, which was used in this study. NR 37 TC 17 Z9 18 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD OCT PY 2014 VL 11 IS 10 BP 1827 EP 1835 DI 10.1016/j.hrthm.2014.06.017 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AQ8VA UT WOS:000343112200030 PM 24953379 ER PT J AU Nevin, DT Morgan, CJ Graham, DY Genta, RM AF Nevin, Daniel T. Morgan, Christopher J. Graham, David Y. Genta, Robert M. TI Helicobacter pylori Gastritis in HIV-Infected Patients: A Review SO HELICOBACTER LA English DT Review DE Epidemiology; Helicobacter pylori; immune response; HIV; AIDS; immunocompromised host ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFLAMMATORY-BOWEL-DISEASE; ACTIVE ANTIRETROVIRAL THERAPY; PEPTIC-ULCER DISEASE; DELTA T-CELLS; LOW-PREVALENCE; POSITIVE PATIENTS; ENDOSCOPIC FINDINGS; SELECTIVE INCREASE; HYGIENE HYPOTHESIS AB BackgroundThe risk factors for acquiring Helicobacter pylori and Human Immunodeficiency Virus (HIV) infections are different: H.pylori is transmitted by gastro- or fecal-oral routes and is associated with low socioeconomic conditions, while HIV is transmitted through sexual intercourse, infected body fluids, and transplacentally. If the host responses to these infections were independent, the prevalence of H.pylori should be similar in HIV-infected and non-infected patients. Yet, several studies have detected a lower prevalence of H.pylori in patients with HIV infection, whereas other studies found either no differences or greater rates of H.pylori infection in HIV-positive subjects. ObjectiveTo review studies that addressed the issue of these two simultaneous infections and attempt to determine whether reliable conclusions can be drawn from this corpus of often contrasting evidence. MethodsElectronic literature search for relevant publications, followed by manual search of additional citations from extracted articles. ResultsThe initial search yielded 44 publications; after excluding case reports, reviews, narrowly focused articles, and duplicate reports, there remained 29 articles, which are the corpus of this review. With one exception, all studies reported higher rates of H.pylori infection in HIV-negative subjects. Five studies also examined the CD4 lymphocyte counts and found an inverse correlation between the degree of immunosuppression and the prevalence of active H.pylori infection. ConclusionsCurrent evidence suggests that it is likely that H.pylori needs a functional immune system to successfully and persistently colonize the human gastric mucosa. C1 [Nevin, Daniel T.; Morgan, Christopher J.; Genta, Robert M.] Miraca Life Sci Res Inst, Irving, TX USA. [Graham, David Y.] Houston VA Med Ctr, Houston, TX USA. [Graham, David Y.] Baylor Coll Med, Houston, TX 77030 USA. RP Genta, RM (reprint author), Miraca Life Sci, 6655 North MacArthur Blvd, Irving, TX 75039 USA. EM robert.genta@utsouthwestern.edu NR 48 TC 4 Z9 5 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1083-4389 EI 1523-5378 J9 HELICOBACTER JI Helicobacter PD OCT PY 2014 VL 19 IS 5 BP 323 EP 329 DI 10.1111/hel.12131 PG 7 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA AQ7JK UT WOS:000342989000001 PM 24773336 ER PT J AU Guinan, EC Palmer, CD Mancuso, CJ Brennan, L Stoler-Barak, L Kalish, LA Suter, EE Gallington, LC Huhtelin, DP Mansilla, M Schumann, RR Murray, JC Weiss, J Levy, O AF Guinan, Eva C. Palmer, Christine D. Mancuso, Christy J. Brennan, Lisa Stoler-Barak, Liat Kalish, Leslie A. Suter, Eugenie E. Gallington, Leighanne C. Huhtelin, David P. Mansilla, Maria Schumann, Ralf R. Murray, Jeffrey C. Weiss, Jerrold Levy, Ofer TI Identification of single nucleotide polymorphisms in hematopoietic cell transplant patients affecting early recognition of, and response to, endotoxin SO INNATE IMMUNITY LA English DT Article DE LPS-binding protein (LBP); bactericidal/permeability-increasing protein (BPI); bone marrow transplant; hematopoietic cell transplant (HCT); lipopolysaccharide (LPS); CD14; TNF ID BACTERICIDAL/PERMEABILITY-INCREASING PROTEIN; LIPOPOLYSACCHARIDE-BINDING PROTEIN; VERSUS-HOST-DISEASE; GRAM-NEGATIVE BACTERIA; TOLL-LIKE-RECEPTOR-4 ECTODOMAIN; CD14 POLYMORPHISMS; WILD-TYPE; GENE; MD-2; BPI AB Hematopoietic cell transplant (HCT) is a life-saving therapy for many malignant and non-malignant bone marrow diseases. Associated morbidities are often due to transplant-related toxicities and infections, exacerbated by regimen-induced immune suppression and systemic incursion of bacterial products. Patients undergoing myeloablative conditioning for HCT become endotoxemic and display blood/plasma changes consistent with lipopolysaccharide (LPS)-induced systemic innate immune activation. Herein, we addressed whether patients scheduled for HCT display differences in recognition/response to LPS ex vivo traceable to specific single nucleotide polymorphisms (SNPs). Two SNPs of LPS binding protein (LBP) were associated with changes in plasma LBP levels, with one LBP SNP also associating with differences in efficiency of extraction and transfer of endotoxin to myeloid differentiation factor-2 (MD-2), a step needed for activation of TLR4. None of the examined SNPs of CD14, bactericidal/permeability-increasing protein (BPI), TLR4 or MD-2 were associated with corresponding protein plasma levels or endotoxin delivery to MD-2, but CD14 and BPI SNPs significantly associated with differences in LPS-induced TNF-alpha release ex vivo and infection frequency, respectively. These findings suggest that specific LBP, CD14 and BPI SNPs might be contributory assessments in studies where clinical outcome may be affected by host response to endotoxin and bacterial infection. C1 [Guinan, Eva C.; Palmer, Christine D.; Mancuso, Christy J.; Stoler-Barak, Liat; Kalish, Leslie A.; Suter, Eugenie E.; Gallington, Leighanne C.; Levy, Ofer] Boston Childrens Hosp, Boston, MA 02215 USA. [Guinan, Eva C.; Palmer, Christine D.; Kalish, Leslie A.; Levy, Ofer] Harvard Univ, Sch Med, Boston, MA USA. [Guinan, Eva C.; Brennan, Lisa] Dana Farber Canc Inst, Boston, MA 02115 USA. [Palmer, Christine D.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA 02114 USA. [Huhtelin, David P.; Weiss, Jerrold] Univ Iowa, Iowa City, IA USA. [Huhtelin, David P.; Weiss, Jerrold] Vet Adm Med Ctr, Iowa City, IA USA. [Mansilla, Maria; Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Schumann, Ralf R.] Charite Univ Med Ctr, Inst Microbiol, Berlin, Germany. RP Levy, O (reprint author), Boston Childrens Hosp, Div Infect Dis, Boston, MA 02215 USA. EM ofer.levy@childrens.harvard.edu RI Gallington, Leighanne/G-9341-2011 OI Gallington, Leighanne/0000-0002-0383-7522 FU NIH [5R21 HL089659, 5U19 AI067751, R01 AI059372]; Dana Foundation Human Immunology Award; DartDose Center for Medical Countermeasures Against Radiation [1U19AI091173-01]; American Heart Association [11POST7660006]; Harvard Catalyst/The Harvard Clinical and Translational Science Center [8UL1TR000170-05]; Harvard University and its affiliated academic health centers FX This study was funded by collaborative research in the Guinan and Levy laboratories supported by NIH 5R21 HL089659 and 5U19 AI067751, a Dana Foundation Human Immunology Award, a DartDose Center for Medical Countermeasures Against Radiation (1U19AI091173-01) Pilot Award and by NIH R01 AI059372 to JW. CDP received salary support from the American Heart Association (11POST7660006). LAK was partially supported by Harvard Catalyst/The Harvard Clinical and Translational Science Center (8UL1TR000170-05), and financial contributions from Harvard University and its affiliated academic health centers. NR 47 TC 1 Z9 1 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1753-4259 EI 1753-4267 J9 INNATE IMMUN-LONDON JI Innate Immun. PD OCT PY 2014 VL 20 IS 7 BP 697 EP 711 DI 10.1177/1753425913505122 PG 15 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA AQ7HE UT WOS:000342982500003 PM 24107515 ER PT J AU Knapp, H Hagedorn, H Anaya, HD AF Knapp, Herschel Hagedorn, Hildi Anaya, Henry D. TI A five-year self-sustainability analysis of nurse-administered HIV rapid testing in Veterans Affairs primary care SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE HIV; AIDS; screening; diagnostic testing; rapid testing; point-of-care ID EMERGENCY-DEPARTMENT; ACCURACY; RISK AB In 2008, nurse-administered HIV oral rapid testing (RT) was introduced at the Veterans Affairs Primary Care Clinic in Downtown Los Angeles. Analysis at five years revealed variable yet increasing rates of HIV RT at that facility despite the fact that no post-launch support was provided by the implementation team. Qualitative interviews among stakeholders conducted at five years revealed the pre-existing implementation practices endemic to this clinic that facilitated this unprecedented success (e.g. history of positive quality improvement implementations, leadership support, clinician involvement at each step of the process to facilitate empowerment, ownership and feasible customisation of the implementation, cohesive communication among clinicians and leadership, training, efficient supply pathway, progressive performance feedback and ongoing encouragement). C1 [Knapp, Herschel; Anaya, Henry D.] US Dept Vet Affairs, Hlth Serv Res & Dev, Los Angeles, CA 90073 USA. [Hagedorn, Hildi] Minneapolis VA Healthcare Syst, QUERI Subst Use Disorders, Minneapolis, MN USA. [Hagedorn, Hildi] Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. RP Knapp, H (reprint author), US Dept Vet Affairs, Hlth Serv Res & Dev, 11301 Wilshire Blvd,111-G Bldg 500,Rm 4681, Los Angeles, CA 90073 USA. EM Herschel.Knapp@va.gov NR 18 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0956-4624 EI 1758-1052 J9 INT J STD AIDS JI Int. J. STD AIDS PD OCT PY 2014 VL 25 IS 12 BP 837 EP 843 DI 10.1177/0956462414521796 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AQ5CO UT WOS:000342821500001 PM 24480848 ER PT J AU Arnason, T Lauwers, GY AF Arnason, Thomas Lauwers, Gregory Y. TI Extruded Highly Proliferative Benign Mucous Neck Cells: A Peculiar Histologic Mimic of Poorly Cohesive Gastric Carcinoma SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE poorly cohesive; diffuse-type; gastric cancer; stomach; mimic; artifact ID SIGNET; STOMACH; BIOPSIES; BREAST AB Histologic mimics of poorly cohesive gastric carcinoma are uncommon but are important for pathologists to recognize. Here we report 2 cases of a novel histologic pattern mimicking poorly cohesive gastric carcinoma. In both cases, light microscopy revealed sheets of discohesive epithelial cells with prominent mitoses that have high proliferative activity, with a Ki67 proliferation index greater than 70%. One case was diagnosed as poorly cohesive carcinoma at an outside hospital and the other was referred in consultation as atypia of undetermined significance. Reexamination of the hematoxylin-eosin slides revealed morphologic clues that these sheets of discohesive cells represent artifactual extrusion of the highly proliferative neck zone from the surrounding benign mucosa. In contrast to poorly cohesive cancer, this artifact lacks all of the following diagnostic features: nuclear atypia, signet ring cell morphology, and intercellular stroma with infiltrating single cells between glands. Eight and 14 months later, both patients remain cancer free. C1 [Arnason, Thomas; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Arnason, Thomas; Lauwers, Gregory Y.] Harvard Univ, Sch Med, Boston, MA USA. [Arnason, Thomas] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS B3H 1V8, Canada. [Arnason, Thomas] Dalhousie Univ, Halifax, NS B3H 1V8, Canada. RP Arnason, T (reprint author), Queen Elizabeth 2 Hlth Sci Ctr, Div Anat Pathol, 7th Floor,MacKenzie Bldg,5788 Univ Ave, Halifax, NS B3H 1V8, Canada. EM thomas.arnason@cdha.nshealth.ca FU Royal College of Physicians and Surgeons of Canada; Dalhousie University FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Dr Arnason's fellowship funding was provided through scholarships from the Royal College of Physicians and Surgeons of Canada (Detweiler Traveling Fellowship) and Dalhousie University (McLoughlin Scholarship). NR 20 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 EI 1940-2465 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD OCT PY 2014 VL 22 IS 7 BP 623 EP 628 DI 10.1177/1066896913510030 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA AQ5ED UT WOS:000342828000005 PM 24275883 ER PT J AU Cipriani, NA Ryan, DP Nielsen, GP AF Cipriani, Nicole A. Ryan, Daniel P. Nielsen, G. Petur TI Primitive Myxoid Mesenchymal Tumor of Infancy With Rosettes: A New Finding and Literature Review SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE PMMTI; primitive myxoid mesenchymal tumor of infancy; rosettes ID OF-THE-LITERATURE; OSTEOSARCOMA AB Primitive myxoid mesenchymal tumor of infancy (PMMTI) is a relatively recently described tumor arising in infants and demonstrating a unique histomorphology. We present an unusual case of PMMTI with rosettes, a hitherto undescribed finding in the reported cases. We also present the cytogenetic and ultrastructural findings of this tumor and review the literature. As awareness of PMMTI increases, additional clinical data and histopathologic findings will aid in the morphologic and behavioral characterization of this neoplasm. C1 [Cipriani, Nicole A.; Nielsen, G. Petur] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cipriani, Nicole A.; Ryan, Daniel P.; Nielsen, G. Petur] Harvard Univ, Sch Med, Boston, MA USA. [Ryan, Daniel P.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. RP Cipriani, NA (reprint author), 5841 S Maryland Ave,MC 6101, Chicago, IL 60637 USA. EM ncipriani@gmail.com NR 10 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 EI 1940-2465 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD OCT PY 2014 VL 22 IS 7 BP 647 EP 651 DI 10.1177/1066896913509006 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA AQ5ED UT WOS:000342828000012 PM 24240695 ER PT J AU Thase, ME AF Thase, Michael E. TI Large-Scale Study Suggests Specific Indicators for Combined Cognitive Therapy and Pharmacotherapy in Major Depressive Disorder SO JAMA PSYCHIATRY LA English DT Editorial Material ID BEHAVIORAL-ANALYSIS SYSTEM; PSYCHOTHERAPY; COMBINATION; NEFAZODONE C1 [Thase, Michael E.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. RP Thase, ME (reprint author), Mood & Anxiety Disorders Treatment Res Program, 3535 Market St,Ste 670, Philadelphia, PA 19104 USA. EM thase@mail.med.upenn.edu NR 8 TC 2 Z9 2 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD OCT PY 2014 VL 71 IS 10 BP 1101 EP 1102 DI 10.1001/jamapsychiatry.2014.1524 PG 2 WC Psychiatry SC Psychiatry GA AQ6DW UT WOS:000342900200003 PM 25142013 ER PT J AU Anyanwu, CO Stewart, CL Werth, VP AF Anyanwu, Cynthia O. Stewart, Campbell L. Werth, Victoria P. TI Thalidomide-Induced Orofacial Neuropathy SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Letter ID CUTANEOUS LUPUS-ERYTHEMATOSUS C1 [Anyanwu, Cynthia O.; Werth, Victoria P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Anyanwu, Cynthia O.; Stewart, Campbell L.; Werth, Victoria P.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. RP Anyanwu, CO (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; National Institutes of Health (NIH) [K24-AR 02207] FX The authors acknowledge the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, and the National Institutes of Health (NIH K24-AR 02207) (V.P.W.). NR 9 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 EI 1536-7355 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD OCT PY 2014 VL 20 IS 7 BP 399 EP 400 PG 2 WC Rheumatology SC Rheumatology GA AQ8BJ UT WOS:000343046100015 PM 25275775 ER PT J AU Chiavetta, NM Martins, ARS Henriques, ICR Fregni, F AF Chiavetta, Noelle M. Martins, Ana R. S. Henriques, Ines C. R. Fregni, Felipe TI Differences in methodological quality between positive and negative published clinical trials SO JOURNAL OF ADVANCED NURSING LA English DT Article DE clinical trial; evidence-based nursing; methodological quality; nursing practice; nursing research; professional issues; publication bias ID RANDOMIZED CONTROLLED-TRIAL; INTENSIVE-CARE-UNIT; PUBLICATION BIAS; OLDER-PEOPLE; EDUCATION-PROGRAM; POSTPARTUM STRESS; NURSING-RESEARCH; PAIN MANAGEMENT; SLEEP QUALITY; OF-LIFE AB AimComparison of methodological quality differences in nursing clinical trials with positive and negative findings. BackgroundThe growth of nursing publications and increased reliance on data to guide clinical care make publication quality assessment imperative. One major concern is the tendency for more studies with positive findings to be published, potentially resulting in the publication of lower quality trials. DesignSecondary analysis of published trials to compare studies with positive and negative findings in terms of clinical trial quality and sample size calculation methodology. Data SourcesTwenty articles each from three major nursing journals (Journal of Clinical Nursing, Journal of Advanced Nursing and International Journal of Nursing Studies) for the years 2010-2012. We assessed article quality in terms of Jadad scores, methods and total sample size. Implications for NursingThis article underscores the importance of nurses and nursing students having the ability to assess the quality of published trials, so that they can make appropriate judgments on the implementation of care for patients as the use of evidence-based practice increases. ConclusionPotential differences in methodological quality between positive and negative trials may lead to positive trials with biased results, or discrimination against negative trials. The CONSORT is recommended, but use is still limited. Therefore, it is important to reinforce the use of these guidelines to supply readers with information on the quality of the published trials. The combination of authors publishing higher quality trials and deeper reader knowledge of quality assessment can have important clinical consequences. C1 [Chiavetta, Noelle M.; Fregni, Felipe] Spaulding Rehabil Hosp, Spaulding Neuromodulat Ctr, Boston, MA USA. [Chiavetta, Noelle M.; Martins, Ana R. S.; Fregni, Felipe] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Martins, Ana R. S.] Spaulding Rehabil Hosp, Spaulding Neuromodulat Ctr, Res Program, Boston, MA USA. [Henriques, Ines C. R.] Univ Coimbra, Fac Med, Coimbra, Portugal. [Fregni, Felipe] Harvard Univ, Sch Med, Boston, MA 02163 USA. RP Fregni, F (reprint author), Harvard Univ, Sch Med, Boston, MA 02163 USA. EM felipe.fregni@ppcr.hms.harvard.edu NR 93 TC 3 Z9 3 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-2402 EI 1365-2648 J9 J ADV NURS JI J. Adv. Nurs. PD OCT PY 2014 VL 70 IS 10 BP 2389 EP 2403 DI 10.1111/jan.12380 PG 15 WC Nursing SC Nursing GA AQ7IM UT WOS:000342986100020 PM 24660826 ER PT J AU Alizai, PH Schmid, S Otto, J Klink, CD Roeth, A Nolting, J Neumann, UP Klinge, U AF Alizai, Patrick Hamid Schmid, Sofie Otto, Jens Klink, Christian Daniel Roeth, Anjali Nolting, Jochen Neumann, Ulf Peter Klinge, Uwe TI Biomechanical analyses of prosthetic mesh repair in a hiatal hernia model SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE hiatal hernia; mesh; hiatal closure; porosity; anisotropy ID ANTIREFLUX SURGERY; ESOPHAGEAL HIATUS; PARAESOPHAGEAL HERNIAS; SURGICAL MESHES; RECURRENCE; FUNDOPLICATION; CLOSURE; PVDF; COMPLICATIONS; REINFORCEMENT AB Recurrence rate of hiatal hernia can be reduced with prosthetic mesh repair; however, type and shape of the mesh are still a matter of controversy. The purpose of this study was to investigate the biomechanical properties of four conventional meshes: pure polypropylene mesh (PP-P), polypropylene/poliglecaprone mesh (PP-U), polyvinylidenefluoride/polypropylene mesh (PVDF-I), and pure polyvinylidenefluoride mesh (PVDF-S). Meshes were tested either in warp direction (parallel to production direction) or perpendicular to the warp direction. A Zwick testing machine was used to measure elasticity and effective porosity of the textile probes. Stretching of the meshes in warp direction required forces that were up to 85-fold higher than the same elongation in perpendicular direction. Stretch stress led to loss of effective porosity in most meshes, except for PVDF-S. Biomechanical impact of the mesh was additionally evaluated in a hiatal hernia model. The different meshes were used either as rectangular patches or as circular meshes. Circular meshes led to a significant reinforcement of the hiatus, largely unaffected by the orientation of the warp fibers. In contrast, rectangular meshes provided a significant reinforcement only when warp fibers ran perpendicular to the crura. Anisotropic elasticity of prosthetic meshes should therefore be considered in hiatal closure with rectangular patches. (C) 2014 Wiley Periodicals, Inc. C1 [Alizai, Patrick Hamid; Schmid, Sofie; Otto, Jens; Klink, Christian Daniel; Roeth, Anjali; Nolting, Jochen; Neumann, Ulf Peter; Klinge, Uwe] RWTH Aachen Univ Hosp, Dept Gen Visceral & Transplantat Surg, D-52074 Aachen, Germany. [Roeth, Anjali] Harvard Univ, Sch Med, Dana Farber Canc Ctr, Div Genom Stabil & DNA Repair, Boston, MA USA. RP Alizai, PH (reprint author), RWTH Aachen Univ Hosp, Dept Gen Visceral & Transplantat Surg, D-52074 Aachen, Germany. EM palizai@ukaachen.de FU Ministry of Economics and Technology [ZIM/AiF KF2621701AJ0] FX Contract grant sponsor: Ministry of Economics and Technology; contract grant number: ZIM/AiF KF2621701AJ0 NR 37 TC 1 Z9 1 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4973 EI 1552-4981 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD OCT PY 2014 VL 102 IS 7 BP 1485 EP 1495 DI 10.1002/jbm.b.33128 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA AQ6ZS UT WOS:000342963000013 PM 24599834 ER PT J AU Manolagas, SC Kronenberg, HM AF Manolagas, Stavros C. Kronenberg, Henry M. TI Reproducibility of Results in Preclinical Studies: A Perspective From the Bone Field SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE GENETIC ANIMAL MODELS; BONE HISTOMORPHOMETRY; BONE QCT/MICROCT ID PARATHYROID-HORMONE; REDUCING WASTE; POSTMENOPAUSAL WOMEN; PUBLISHED RESEARCH; INCREASING VALUE; IN-VIVO; OSTEOPOROSIS; DESIGN; HISTOMORPHOMETRY; NOMENCLATURE AB The biomedical research enterprise-and the public support for it-is predicated on the belief that discoveries and the conclusions drawn from them can be trusted to build a body of knowledge which will be used to improve human health. As in all other areas of scientific inquiry, knowledge and understanding grow by layering new discoveries upon earlier ones. The process self-corrects and distills knowledge by discarding false ideas and unsubstantiated claims. Although self-correction is inexorable in the long-term, in recent years biomedical scientists and the public alike have become alarmed and deeply troubled by the fact that many published results cannot be reproduced. The chorus of concern reached a high pitch with a recent commentary from the NIH Director, Francis S. Collins, and Principal Deputy Director, Lawrence A. Tabak, and their announcement of specific plans to enhance reproducibility of preclinical research that relies on animal models. In this invited perspective, we highlight the magnitude of the problem across biomedical fields and address the relevance of these concerns to the field of bone and mineral metabolism. We also suggest how our specialty journals, our scientific organizations, and our community of bone and mineral researchers can help to overcome this troubling trend. (c) 2014 American Society for Bone and Mineral Research. C1 [Manolagas, Stavros C.] Univ Arkansas Med Sci, Div Endocrinol & Metab, Ctr Osteoporosis & Metab Bone Dis, Little Rock, AR 72205 USA. [Manolagas, Stavros C.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA USA. RP Manolagas, SC (reprint author), Univ Arkansas Med Sci, Div Endocrinol & Metab, 4301 W Markham,Slot 587, Little Rock, AR 72205 USA. EM manolagasstavros@uams.edu; kronenberg@helix.mgh.harvard.edu FU NIH [P01 AG13918, R01 AR56679, DK11794, DK56246]; Biomedical Laboratory Research and Development Service of the Veterans Administration Office of Research and Development [I01 BX001405] FX The authors' research is supported by the NIH (P01 AG13918, R01 AR56679 [to SCM]; DK11794 and DK56246 [to HMK]) and the Biomedical Laboratory Research and Development Service of the Veterans Administration Office of Research and Development (I01 BX001405 [to SCM]). We thank Leah Elrod for help with the preparation of the manuscript. NR 42 TC 14 Z9 14 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2014 VL 29 IS 10 BP 2131 EP 2140 DI 10.1002/jbmr.2293 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AQ4ZE UT WOS:000342809800001 PM 24916175 ER PT J AU Andrade, AC Magnavita, GM Allegro, JVBN Neto, CEBP Lucena, RDS Fregni, F AF Andrade, Agnes Carvalho Magnavita, Guilherme Moreira Brasil Nunes Allegro, Juleilda Valeria Borges Passos Neto, Carlos Eduardo Saldanha Lucena, Rita de Cassia Fregni, Felipe TI Feasibility of Transcranial Direct Current Stimulation Use in Children Aged 5 to 12 Years SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE tDCS; brain stimulation; language disorders ID NONINVASIVE BRAIN-STIMULATION; MAGNETIC STIMULATION; METAANALYSIS; DISORDERS; SAFETY; TRIAL; RTMS AB Transcranial direct current stimulation is a noninvasive brain stimulation technique that has been studied for the treatment of neuropsychiatric disorders in adults, with minimal side effects. The objective of this study is to report the feasibility, tolerability, and the short-term adverse effects of transcranial direct current stimulation in children from 5 to 12 years of age. It is a naturalistic study of 14 children who underwent 10 sessions of transcranial direct current stimulation as an alternative, off-label, and open-label treatment for various languages disorders. Frequency, intensity, adverse effects, and perception of improvement reported by parents were collected. The main side effects detected were tingling (28.6%) and itching (28.6%), acute mood changes (42.9%), and irritability (35.7%). Transcranial direct current stimulation is a feasible and tolerable technique in children, although studies regarding plastic and cognitive changes in children are needed to confirm its safety. In conclusion, this is a naturalistic report in which we considered transcranial direct current stimulation as feasible in children. C1 [Andrade, Agnes Carvalho; Magnavita, Guilherme Moreira; Brasil Nunes Allegro, Juleilda Valeria; Saldanha Lucena, Rita de Cassia] Univ Fed Bahia, Med Sch Bahia, Dept Neurosci, Salvador, BA, Brazil. [Borges Passos Neto, Carlos Eduardo] Univ Fed Bahia, Med Sch Bahia, Salvador, BA, Brazil. [Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Lab Neuromodulat,Dept Phys Med & Rehabil, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Lucena, RDS (reprint author), Dept Neurociencias, 32 Av Araujo Pinho, BR-40150110 Salvador, BA, Brazil. EM rcslucena@yahoo.com.br NR 28 TC 13 Z9 13 U1 1 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 EI 1708-8283 J9 J CHILD NEUROL JI J. Child Neurol. PD OCT PY 2014 VL 29 IS 10 BP 1360 EP 1365 DI 10.1177/0883073813503710 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AQ5CZ UT WOS:000342823700024 PM 24049057 ER PT J AU Suzuki, M Shin, M Simmer, JP Bartlett, JD AF Suzuki, M. Shin, M. Simmer, J. P. Bartlett, J. D. TI Fluoride Affects Enamel Protein Content via TGF-beta 1-mediated KLK4 Inhibition SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE amelogenin; matrix metalloproteinases; proteases; proteinases; signal transduction; cell stress; gene expression ID ENDOPLASMIC-RETICULUM STRESS; DENTAL FLUOROSIS; PEPTIDASE 4; EXPRESSION; BIOMINERALIZATION; KALLIKREIN-4; AMELOBLASTS; CLONING; CANCER; ORGAN AB Dental fluorosis is caused by chronic high-level fluoride (F-) exposure during enamel development, and fluorosed enamel has a higher than normal protein content. Matrix metalloproteinase 20 cleaves enamel matrix proteins during the secretory stage, and KLK4 further cleaves these proteins during the maturation stage so that the proteins can be reabsorbed from the hardening enamel. We show that transforming growth factor 1 (TGF-1) can induce Klk4 expression, and we examine the effect of F- on TGF-1 and KLK4 expression. We found that in vivo F- inhibits Klk4 but not Mmp20 transcript levels. LacZ-C57BL/6-Klk4(+/LacZ) mice have LacZ inserted in frame at the Klk4 translation initiation site so that the endogenous Klk4 promoter drives LacZ expression in the same temporal/spatial way as it does for Klk4. KLK4 protein levels in rat enamel and -galactosidase staining in LacZ-C57BL/6-Klk4(+/LacZ) mouse enamel were both significantly reduced by F- treatment. Since TGF-1 induces KLK4 expression, we tested and found that F- significantly reduced Tgf-1 transcript levels in rat enamel organ. These data suggest that F--mediated downregulation of TGF-1 expression contributes to reduced KLK4 protein levels in fluorosed enamel and provides an explanation for why fluorosed enamel has a higher than normal protein content. C1 [Suzuki, M.; Shin, M.; Bartlett, J. D.] Forsyth Inst, Dept Mineralized Tissue Biol, Cambridge, MA 02115 USA. [Suzuki, M.; Shin, M.; Bartlett, J. D.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Simmer, J. P.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Mineralized Tissue Biol, Cambridge, MA 02115 USA. EM jbartlett@forsyth.org FU National Institute of Dental and Craniofacial Research of the National Institutes of Health [R01DE018106, R01DE019775] FX We thank Justine Dobeck for histology expertise and Dr. Toshihiro Sugiyama for generously providing us with ameloblast-lineage cells. The research reported in this publication was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under award numbers R01DE018106 and R01DE019775. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 31 TC 7 Z9 9 U1 1 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD OCT PY 2014 VL 93 IS 10 BP 1022 EP 1027 DI 10.1177/0022034514545629 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AQ5DE UT WOS:000342824700014 PM 25074495 ER PT J AU Tirumani, SH Deaver, P Shinagare, AB Tirumani, H Hornick, JL George, S Ramaiya, NH AF Tirumani, Sree Harsha Deaver, Pamela Shinagare, Atul B. Tirumani, Harika Hornick, Jason L. George, Suzanne Ramaiya, Nikhil H. TI Metastatic pattern of uterine leiomyosarcoma: retrospective analysis of the predictors and outcome in 113 patients SO JOURNAL OF GYNECOLOGIC ONCOLOGY LA English DT Article DE Leiomyosarcoma; Neoplasm recurrence; Prognosis; Proportional Hazards Models ID SURVIVAL; SARCOMA; UTERUS AB Objective: To describe metastatic pattern of uterine leiomyosarcomas (ULMS) and correlate it with clinical and histopathologic parameters. Methods: we included 113 women (mean age, 53 years; range, 29 to 72 years) with histopathology-confirmed ULMS from 2000 to 2012. Distribution of metastases was noted from imaging by two radiologists in consensus. Predictors of development of metastases were analyzed with univariate and multivariate analysis. Impact of various clinical and histopathologic parameters on survival was compared using Log-rank test and Cox proportional hazard regression model. Results: Distant metastases were seen in 81.4% (92/113) of the patients after median interval of 7 months (interquartile range, 1 to 21). Lung was most common site of metastases (74%) followed by peritoneum (41%), bones (33%), and liver (27%). Local tumor recurrence was noted in 57 patients (50%), 51 of whom had distant metastases. Statistically significant correlation was noted between local recurrence and peritoneal metastases (p<0.001) and between lung and other common sites of hematogeneous metastases (p<0.05). Age, serosal involvement, local recurrence, and the International Federation of Gynecology and Obstetrics (FIGO) stage were predictive factors for metastases. At the time of reporting, 65% (74/113) of the patients have died; median survival was 45 months. Stage, local recurrence, and age were poor prognostic factors. Conclusion: ULMS metastasizes most frequently to lung, peritoneum, bone, and liver. Local recurrence was associated with peritoneal spread and lung metastases with other sites of hematogeneous metastases. Age, FIGO stage and local recurrence predicted metastatic disease and advanced stage, older age and local recurrence predicted poor outcome. C1 [Tirumani, Sree Harsha; Shinagare, Atul B.; Tirumani, Harika; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Tirumani, Sree Harsha; Deaver, Pamela; Shinagare, Atul B.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. [Hornick, Jason L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [George, Suzanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02215 USA. [George, Suzanne] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM stirumani@partners.org NR 23 TC 4 Z9 5 U1 1 U2 3 PU KOREAN SOC GYNECOLOGY ONCOLOGY & COLPOSCOPY PI SEOUL PA 102-HO, 55-5, NONHYEON-DONG, GANGNAM-GU, SEOUL, 135-010, SOUTH KOREA SN 2005-0380 EI 2005-0399 J9 J GYNECOL ONCOL JI J. Gynecol. Oncol. PD OCT PY 2014 VL 25 IS 4 BP 306 EP 312 DI 10.3802/jgo.2014.25.4.306 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AQ7TR UT WOS:000343022600011 PM 25142630 ER PT J AU Baskin, DG Hewitt, SM AF Baskin, Denis G. Hewitt, Stephen M. TI Improving the State of the Science of Immunohistochemistry: The Histochemical Society's Standards of Practice SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Editorial Material C1 [Baskin, Denis G.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, R&D Serv, Seattle, WA USA. [Baskin, Denis G.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Hewitt, SM (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788 FU Intramural NIH HHS; NIDDK NIH HHS [P30DK017047, P30 DK017047] NR 2 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD OCT PY 2014 VL 62 IS 10 BP 691 EP 692 DI 10.1369/0022155414538453 PG 2 WC Cell Biology SC Cell Biology GA AQ5GU UT WOS:000342836200001 PM 25085896 ER PT J AU Kartha, A Restuccia, JD Burgess, JF Benzer, J Glasgow, J Hockenberry, J Mohr, DC Kaboli, PJ AF Kartha, Anand Restuccia, Joseph D. Burgess, James F., Jr. Benzer, Justin Glasgow, Justin Hockenberry, Jason Mohr, David C. Kaboli, Peter J. TI Nurse Practitioner and Physician Assistant Scope of Practice in 118 Acute Care Hospitals SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID NONPHYSICIAN PROVIDERS; QUALITY IMPROVEMENT; PATIENT OUTCOMES; VETERANS; SERVICE; IMPACT; COLLABORATION; SATISFACTION; MODEL; UNIT AB BACKGROUND: Advanced practice providers (APPs), including nurse practitioners (NPs) and physician assistants (PAs) are cost-effective substitutes for physicians, with similar outcomes in primary care and surgery. However, little is understood about APP roles in inpatient medicine. OBJECTIVE: Describe APPs role in inpatient medicine. DESIGN: Observational cross-sectional cohort study. SETTING: One hundred twenty-four Veterans Health Administration (VHA) hospitals. PARTICIPANTS: Chiefs of medicine (COMs) and nurse managers. MEASUREMENTS: Surveys included inpatient medicine scope of practice for APPs and perceived healthcare quality. We conducted bivariate unadjusted and multivariable adjusted analyses. RESULTS: One hundred eighteen COMs (95.2%) and 198 nurse managers (75.0%) completed surveys. Of 118 medicine services, 56 (47.5%) employed APPs; 27 (48.2%) used NPs only, 15 (26.8%) PAs only, and 14 (25.0%) used both. Full-time equivalents for NPs was 0.5 to 7 (mean = 2.22) and PAs was 1 to 9 (mean = 2.23). Daily caseload was similar at 4 to 10 patients (mean = 6.5 patients). There were few significant differences between tasks. The presence of APPs was not associated with patient or nurse manager satisfaction. Presence of NPs was associated with greater overall inpatient and discharge coordination ratings by COMs and nurse managers, respectively; the presence of PAs was associated with lower overall inpatient coordination ratings by nurse managers. CONCLUSIONS: NPs and PAs work on half of VHA inpatient medicine services with broad, yet similar, scopes of practice. There were few differences between their roles and perceptions of care. Given their very different background, regulation, and reimbursement, this has implications for inpatient medicine services that plan to hire NPs or PAs. (c) 2014 Society of Hospital Medicine C1 [Kartha, Anand; Restuccia, Joseph D.; Burgess, James F., Jr.; Benzer, Justin; Mohr, David C.] VA Boston Healthcare Syst, CHOIR, Boston, MA USA. [Kartha, Anand] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Restuccia, Joseph D.] Boston Univ, Sch Management, Dept Operat & Technol Management, Boston, MA 02215 USA. [Burgess, James F., Jr.; Benzer, Justin; Mohr, David C.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Glasgow, Justin] Christiana Care Hlth Syst, Dept Internal Med, Wilmington, DE USA. [Glasgow, Justin; Hockenberry, Jason; Kaboli, Peter J.] Iowa City VA Healthcare Syst, Comprehens Access & Delivery Res & Evaluat CADRE, Iowa City, IA USA. [Hockenberry, Jason] Emory Univ, Rollins Sch Publ Hlth, Dept Hlth Policy & Management, Atlanta, GA 30322 USA. [Kaboli, Peter J.] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. RP Kartha, A (reprint author), Vet Adm Boston Healthcare Syst, 1400 VFW Pkwy,Mail Stop 111, West Roxbury, MA 02132 USA. EM anand.kartha@va.gov OI Benzer, Justin/0000-0001-5151-2127 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [IIR 08-067]; Comprehensive Access & Delivery Research and Evaluation (CADRE) Center at the Iowa City VAMC [CIN 13-412]; Center for Healthcare Organization and Implementation Research (CHOIR) at the Boston VA Healthcare System [HFP 04-145] FX The work reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (IIR 08-067) and the Comprehensive Access & Delivery Research and Evaluation (CADRE) Center at the Iowa City VAMC (CIN 13-412), and the Center for Healthcare Organization and Implementation Research (CHOIR) at the Boston VA Healthcare System (HFP 04-145). The funders did not play any role in the design and conduct of the study; in the collection, analysis, and interpretation of data; and in preparation, review, and approval of the manuscript. The authors do not have any conflicts of interest or financial relationships related to the content of this manuscript. The authors had full access to and take full responsibility for the integrity of the data and the accuracy of the data analysis. 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 41 TC 10 Z9 10 U1 1 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD OCT PY 2014 VL 9 IS 10 BP 615 EP 620 DI 10.1002/jhm.2231 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA AQ5ZE UT WOS:000342886300001 PM 25224593 ER PT J AU Breu, AC Herzig, SJ AF Breu, Anthony C. Herzig, Shoshana J. TI Differentiating DNI From DNR: Combating Code Status Conflation SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID RESUSCITATE; ORDERS AB Goals of care discussions, including those focused on code status, are meant to foster autonomous decision making. Unfortunately, these discussions often conflate decisions regarding the use of cardiopulmonary resuscitation for cardiac arrest and mechanical ventilation for prearrest respiratory failure. They also exclude discussions of outcomes, particularly those associated with prearrest respiratory failure. In doing so, they may fail in their intention of extending patient autonomy. (c) 2014 Society of Hospital Medicine C1 [Breu, Anthony C.] VA Boston Healthcare Syst, West Roxbury, MA 02132 USA. [Breu, Anthony C.; Herzig, Shoshana J.] Harvard Univ, Sch Med, Boston, MA USA. [Herzig, Shoshana J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. RP Breu, AC (reprint author), VA Boston Healthcare Syst, Med Serv 111, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM anthony.breu@va.gov FU National Institute on Aging [K23AG042459] FX Disclosures: Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. NR 12 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD OCT PY 2014 VL 9 IS 10 BP 669 EP 670 DI 10.1002/jhm.2234 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AQ5ZE UT WOS:000342886300010 PM 24978058 ER PT J AU Kim, AH Thompson, EA Governale, LS Santa, C Cahill, K Kieran, MW Chi, SN Ullrich, NJ Scott, RM Goumnerova, LC AF Kim, Albert H. Thompson, Elizabeth A. Governale, Lance S. Santa, Catalina Cahill, Kevin Kieran, Mark W. Chi, Susan N. Ullrich, Nicole J. Scott, R. Michael Goumnerova, Liliana C. TI Recurrence after gross-total resection of low-grade pediatric brain tumors: the frequency and timing of postoperative imaging SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE glioma; pediatric brain tumor; pilocytic astrocytoma; magnetic resonance imaging; recurrence; oncology ID BENIGN CEREBELLAR ASTROCYTOMAS; LONG-TERM; PILOCYTIC ASTROCYTOMAS; SURGICAL-MANAGEMENT; SURVEILLANCE; CHILDHOOD; CHILDREN; EXPERIENCE; EPILEPSY AB Object. Low-grade glial and glioneuronal brain tumors are frequently encountered in the pediatric population and can be effectively treated by resection. The authors aimed to use imaging to evaluate how often tumors recurred and to determine if recurrences were associated with any clinical symptoms, along with the financial costs of imaging, in patients with radiographically proven gross-total resection (GTR) at Boston Children's Hospital. These data were assessed to propose guidelines regarding postoperative surveillance. Methods. The authors performed a retrospective cohort analysis of the Pediatric Brain Tumor Program database from 1993 to 2003 to identify patients with glial or glioneuronal tumors initially evaluated at Boston Children's Hospital. Among the 888 patients evaluated for any type of brain tumor during this period, 67 patients had WHO Grade I glial or glioneuronal lesions with radiographically proven GTR and available follow-up data. The frequency and timing of postoperative imaging was compared with the institutional protocol. Recurrence-free survival was calculated using the Kaplan-Meier method Financial costs of imaging were available from 2001 to 2009 and were averaged to extrapolate the postoperative surveillance costs. Results. Among the 67 patients with GTR, 13 recurrences were detected radiographically with a mean time to recurrence of 32.4 months (range 2.9-128.5 months). The mean duration of follow-up after surgery was 6.6 years. The recurrence-free survival at 2 and 5 years after GTR for all low-grade glial and glioneuronal tumors was 0.90 (95% CI 0.82-0.97) and 0.82 (95% CI 0.73-0.92), respectively. No clinical symptoms were associated with any of the recurrences, and no deaths occurred. Under the institutional protocol of surveillance imaging, the estimated cost per recurrence at 5 years was $104,094 per patient. The proposed protocol would reduce the number of MR scans in the first 5 years from 10 to 5, providing a potential cost savings of $52,047 per recurrence. Conclusions. Given the slow-growing, clinically asymptomatic nature of low-grade glial and glioneuronal tumors coupled with the financial and psychological costs of repeated imaging, the authors propose a postoperative surveillance MRI schedule that is less intensive than current institutional practice. C1 [Kim, Albert H.; Thompson, Elizabeth A.] Washington Univ, Dept Neurosurg, St Louis, MO USA. [Governale, Lance S.] Ohio State Univ, Dept Neurosurg, Columbus, OH 43210 USA. [Santa, Catalina; Cahill, Kevin; Scott, R. Michael; Goumnerova, Liliana C.] Boston Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Ullrich, Nicole J.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Kieran, Mark W.; Chi, Susan N.; Ullrich, Nicole J.; Scott, R. Michael; Goumnerova, Liliana C.] Dana Farber Canc Inst, Pediat Neurooncol Ctr, Boston, MA 02115 USA. RP Goumnerova, LC (reprint author), Boston Childrens Hosp, 300 Longwood Ave,Hunnewell 2, Boston, MA 02115 USA. EM liliana.goumnerova@childrens.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU Brain Science Foundation Fellowship Grant FX This project was funded in part by a Brain Science Foundation Fellowship Grant (A.H.K.).The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. NR 15 TC 4 Z9 4 U1 0 U2 6 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 EI 1933-0715 J9 J NEUROSURG-PEDIATR JI J. Neurosurg.-Pediatr. PD OCT PY 2014 VL 14 IS 4 BP 356 EP 364 DI 10.3171/2014.6.PEDS1321 PG 9 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA AQ7CN UT WOS:000342970300006 PM 25062303 ER PT J AU Le, AQ Walcott, BP Redjal, N Coumans, JV AF Le, Andrew Q. Walcott, Brian P. Redjal, Navid Coumans, Jean-Valery TI Cervical osteophyte resulting in compression of the jugular foramen SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE spondylosis; cervical spine; jugular foramen; osteophyte ID DYSPHAGIA; OBSTRUCTION AB Jugular foramen syndrome is a condition characterized by unilateral paresis of cranial nerves IX, X, and XI in the setting of extrinsic compression. Here, the authors describe the case of a giant cervical osteophyte resulting in compression of the jugular foramen. A 74-year-old man who presented with progressive dysphagia and dysarthria was found to have right-sided tongue deviation, left palatal droop, and hypophonia. His dysphagia had progressed to the point that he had lost 25 kg over a 4-month period, necessitating a gastrostomy to maintain adequate nutrition. He underwent extensive workup for his dysphagia with several normal radiographic studies. Ultimately, CT scanning and postcontrast MRI revealed a posterior osteophyte arising from the C1-2 joint space and projecting into the right jugular foramen. This resulted in a jugular foramen syndrome in addition to delayed filling of the patient's right internal jugular vein distal to the osteophyte. Although rare, a posterior cervical osteophyte should be considered in cases of jugular foramen syndrome. C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurol Surg, 55 Fruit St,White Bldg,Rm 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 22 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 EI 1547-5646 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD OCT PY 2014 VL 21 IS 4 BP 565 EP 567 DI 10.3171/2014.6.SPINE13908 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AQ7CO UT WOS:000342970400009 PM 25014503 ER PT J AU Fusella, F Ferretti, R Recupero, D Rocca, S Di Savino, A Tornillo, G Silengo, L Turco, E Cabodi, S Provero, P Pandolfi, PP Sapino, A Tarone, G Brancaccio, M AF Fusella, Federica Ferretti, Roberta Recupero, Daniele Rocca, Stefania Di Savino, Augusta Tornillo, Giusy Silengo, Lorenzo Turco, Emilia Cabodi, Sara Provero, Paolo Pandolfi, Pier Paolo Sapino, Anna Tarone, Guido Brancaccio, Mara TI Morgana acts as a proto-oncogene through inhibition of a ROCK-PTEN pathway SO JOURNAL OF PATHOLOGY LA English DT Article DE breast cancer; chemoresistance; morgana; PTEN; ROCK ID NEGATIVE BREAST-CANCER; CENTROSOME DUPLICATION; TUMOR-SUPPRESSOR; ACTIVATION; MELUSIN; KINASE; CELLS; PHOSPHORYLATION; TUMORIGENESIS; MUTATIONS AB Morgana/CHP-1 is a ubiquitously expressed protein able to inhibit ROCK II kinase activity. We have previously demonstrated that morgana haploinsufficiency leads to multiple centrosomes, genomic instability, and higher susceptibility to tumour development. While a large fraction of human cancers has shown morgana down-regulation, a small subset of tumours was shown to express high morgana levels. Here we demonstrate that high morgana expression in different breast cancer subtypes correlates with high tumour grade, mitosis number, and lymph node positivity. Moreover, morgana overexpression induces transformation in NIH-3T3 cells and strongly protects them from various apoptotic stimuli. From a mechanistic point of view, we demonstrate that morgana causes PTEN destabilization, by inhibiting ROCK activity, hence triggering the PI3K/AKT survival pathway. In turn, morgana down-regulation in breast cancer cells that express high morgana levels increases PTEN expression and leads to sensitization of cells to chemotherapy. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Fusella, Federica; Ferretti, Roberta; Rocca, Stefania; Di Savino, Augusta; Tornillo, Giusy; Silengo, Lorenzo; Turco, Emilia; Cabodi, Sara; Provero, Paolo; Pandolfi, Pier Paolo; Tarone, Guido; Brancaccio, Mara] Univ Turin, Dept Biotechnol & Hlth Sci, Turin, Italy. [Recupero, Daniele; Sapino, Anna] Univ Turin, Dept Med Sci, Turin, Italy. [Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med,Dept Med & Pathol, Canc Genet Program,Div Genet,Beth Israel Deacones, Boston, MA 02215 USA. RP Brancaccio, M (reprint author), Ctr Mol Biotechnol, Via Nizza 52, I-10126 Turin, Italy. EM mara.brancaccio@unito.it OI Sapino, Anna/0000-0003-3542-9571 FU AIRC [IG 11456, IG 11346]; AIRC FX We would like to thank Flavio Cristofani and Antonellisa Sgarra for assistance with animal experiments; and Shuh Narumiya, Claudio Brancolini, Ferdinando Di Cunto, and Enzo Calautti for sharing DNA constructs. We also thank Radhika Srinivasan for manuscript revision. This work was supported by an AIRC 2011 (IG 11456) grant to MB and by an AIRC 2011 (IG 11346) grant to SC. AD was supported by a fellowship from AIRC (annual fellowship 'Marco Fabio Sartori'). NR 34 TC 6 Z9 6 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3417 EI 1096-9896 J9 J PATHOL JI J. Pathol. PD OCT PY 2014 VL 234 IS 2 BP 152 EP 163 DI 10.1002/path.4341 PG 12 WC Oncology; Pathology SC Oncology; Pathology GA AQ7EZ UT WOS:000342976700005 PM 24615293 ER PT J AU Sioletic, S Czaplinski, J Hu, L Fletcher, JA Fletcher, CDM Wagner, AJ Loda, M Demetri, GD Sicinska, ET Snyder, EL AF Sioletic, Stefano Czaplinski, Jeffrey Hu, Lan Fletcher, Jonathan A. Fletcher, Christopher D. M. Wagner, Andrew J. Loda, Massimo Demetri, George D. Sicinska, Ewa T. Snyder, Eric L. TI c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas SO JOURNAL OF PATHOLOGY LA English DT Article DE c-Jun; liposarcoma; soft tissue sarcoma; ENPP2; autotaxin ID LYSOPHOSPHATIDIC ACID RECEPTOR; HODGKIN LYMPHOMA-CELLS; BREAST-CANCER; DEDIFFERENTIATED LIPOSARCOMA; ADIPOCYTIC DIFFERENTIATION; LYSOPHOSPHOLIPASE-D; ANGIOGENIC FACTOR; AUTOTAXIN NPP-2; DNA-BINDING; IN-VITRO AB Genomic amplification of the c-Jun proto-oncogene has been identified in similar to 30% of dedifferentiated liposarcomas (DDLPS), but the functional contribution of c-Jun to the progression of DDLPS remains poorly understood. In previous work we showed that knock-down of c-Jun by RNA interference impaired the in vitro proliferation and in vivo growth of a DDLPS cell line (LP6) with genomic amplification of the c-Jun locus. Here, we used gene expression analysis and functional studies in a broad panel of cell lines to further define the role of c-Jun in DDLPS and other soft tissue sarcomas. We show that c-Jun knock-down impairs transition through the G(1) phase of the cell cycle in multiple DDLPS cell lines. We also found that high levels of c-Jun expression are both necessary and sufficient to promote DDLPS cell migration and invasion in vitro. Our data suggest that high levels of c-Jun enhance motility in part by driving the expression of ENPP2/Autotaxin. c-Jun over-expression has minimal effects on in vitro proliferation but substantially enhances the in vivo growth of weakly tumourigenic DDLPS cell lines. Finally, we provide evidence that c-Jun genomic amplification and over-expression may have similar functional consequences in other types of soft tissue sarcoma. Our data suggest a model in which relatively low levels of c-Jun are sufficient for in vitro proliferation, but high levels of c-Jun enhance invasiveness and capacity for in vivo tumour growth. These observations provide an explanation for the selective advantage provided by c-Jun genomic amplification in vivo and suggest that sarcomas with elevated c-Jun levels are likely to have a particularly high malignant potential. Data from exon array and RNA-Seq experiments have been deposited in the GEO database (Accession No. GSE57531). Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Sioletic, Stefano; Czaplinski, Jeffrey; Wagner, Andrew J.; Loda, Massimo; Demetri, George D.; Sicinska, Ewa T.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sioletic, Stefano; Czaplinski, Jeffrey; Wagner, Andrew J.; Demetri, George D.; Sicinska, Ewa T.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. [Czaplinski, Jeffrey; Loda, Massimo; Sicinska, Ewa T.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Hu, Lan] Dana Farber Canc Inst, Ctr Canc Computat Biol CCCB, Boston, MA 02115 USA. [Fletcher, Jonathan A.; Fletcher, Christopher D. M.; Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Snyder, Eric L.] Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA. [Snyder, Eric L.] Univ Calif San Francisco, Sch Med, Dept Anat, San Francisco, CA 94143 USA. RP Snyder, EL (reprint author), Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA. EM eric.snyder@ucsf.edu FU Ludwig Center at Dana Farber/Harvard Cancer Center; SPORE support from the National Cancer Institute (NCI) [SPORE 5U54CA168512-02]; Career Award for Medical Scientists from the Burroughs Wellcome Fund FX This study was supported by the Ludwig Center at Dana Farber/Harvard Cancer Center and by SPORE support from the National Cancer Institute (NCI; Grant No. SPORE 5U54CA168512-02, to GDD) and a Career Award for Medical Scientists from the Burroughs Wellcome Fund (to ELS). We thank Lisa Cameron for assistance in acquiring time-lapse images in the Confocal and Light Microscopy Core Facility at the Dana Farber Cancer Institute (DFCI). We thank the DFCI Flow Cytometry Core Facility for assistance with cell-cycle analysis. The authors are grateful to Drs Pedeutour, Kamijyo and Shinoda for sharing their cell lines. NR 52 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3417 EI 1096-9896 J9 J PATHOL JI J. Pathol. PD OCT PY 2014 VL 234 IS 2 BP 190 EP 202 DI 10.1002/path.4379 PG 13 WC Oncology; Pathology SC Oncology; Pathology GA AQ7EZ UT WOS:000342976700008 PM 24852265 ER PT J AU Anupindi, SA Grossman, AB Nimkin, K Mamula, P Gee, MS AF Anupindi, Sudha A. Grossman, Andrew B. Nimkin, Katherine Mamula, Petar Gee, Michael S. TI Imaging in the Evaluation of the Young Patient With Inflammatory Bowel Disease: What the Gastroenterologist Needs to Know SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Review DE children; imaging; inflammatory bowel disease; radiation dose ID PEDIATRIC CROHN DISEASE; BARIUM FOLLOW-THROUGH; MR ENTEROGRAPHY; RADIATION-EXPOSURE; COMPUTED-TOMOGRAPHY; CT ENTEROCLYSIS; TERMINAL ILEUM; CANCER-RISK; CHILDREN; ULTRASONOGRAPHY AB Imaging plays a pivotal role in the diagnosis and management of children and young adults with inflammatory bowel disease. The clinician is presented with numerous imaging options, and it can be challenging to decide which test is the best option. In this article we review the present imaging techniques available in the evaluation of inflammatory bowel disease, with emphasis on the advantages, disadvantages, and radiation burden of each test. Finally, we highlight a few common clinical scenarios and propose an imaging algorithm to approach these diagnostic challenges. C1 [Anupindi, Sudha A.] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. [Grossman, Andrew B.; Mamula, Petar] Childrens Hosp Philadelphia, Dept Pediat, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA. [Nimkin, Katherine; Gee, Michael S.] Massachusetts Gen Hosp, Div Pediat Imaging, Dept Radiol, Boston, MA 02114 USA. RP Anupindi, SA (reprint author), Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Dept Radiol, 34 St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM anupindi@email.chop.edu NR 59 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD OCT PY 2014 VL 59 IS 4 BP 429 EP 439 DI 10.1097/MPG.0000000000000475 PG 11 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA AQ2YG UT WOS:000342655300005 PM 24979661 ER PT J AU Medina, MA Salinas, HM Eberlin, KR Driscoll, DN Kwon, JY Austen, WG Cetrulo, CL AF Medina, Miguel A., III Salinas, Harry M. Eberlin, Kyle R. Driscoll, Daniel N. Kwon, John Y. Austen, William G., Jr. Cetrulo, Curtis L., Jr. TI Modified Free Radial Forearm Fascia Flap Reconstruction of Lower Extremity and Foot Wounds: Optimal Contour and Minimal Donor-Site Morbidity SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article DE radial forearm fascia flap; lower extremity; foot; wound; microsurgical ID FREE FASCIOCUTANEOUS FLAPS; OPEN TIBIAL FRACTURES; SUPRAFASCIAL DISSECTION; CHRONIC OSTEOMYELITIS; OUTCOMES; SELECTION; COVERAGE AB Background Free tissue transfer is commonly required for reconstruction of distal third lower extremity injuries. Injuries involving the dorsal surface of the foot require thin pliable flaps. Musculocutaneous flaps are often too bulky to accommodate shoe-wear. Fasciocutaneous flaps, while an improvement, need secondary contouring procedures. The modified radial forearm fascial flap (MRFFF) may offer an alternative. Methods Twelve patients with distal third lower extremity wounds were reconstructed with MRFFF + split thickness skin graft. The modification in flap design leaves fascia radial to the pedicle unharvested, preserving sensibility of the dorsoradial aspect of the hand. Flaps were covered with a skin graft after inset. Donor sites were closed primarily. Results Nine wounds were traumatic-five with exposed hardware, one burn, one diabetic ulcer, and one wound dehiscence following sarcoma resection + radiation. Out of 12, 11 limbs were salvaged at 1 to 2 years follow-up. All patients ambulated on the reconstructed leg and wore a shoe comfortably. Average time to weight bearing was 2 months. The donor site was limited to 25-cm scar on the volar forearm. No persistent motor/sensory deficits occurred in donor arms. Conclusion MRFFF is an excellent flap for reconstruction of the distal lower extremity. Flap contour allows excellent shoe-fitting without secondary revisions. Replacement of the adipocutaneous flap on MRFFF donor site eliminates the need for a conspicuous donor-site skin graft. The ulnar orientation of the harvested fascia prevents sensory loss in the dorsal hand. The MRFFF provides the ideal replacement of "like with like" for selected distal lower extremity wounds. C1 [Medina, Miguel A., III; Salinas, Harry M.; Eberlin, Kyle R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. [Driscoll, Daniel N.; Austen, William G., Jr.; Cetrulo, Curtis L., Jr.] Shriners Hosp Children, Dept Plast & Reconstruct Surg, Boston, MA USA. [Kwon, John Y.] Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Cetrulo, CL (reprint author), Massachusetts Gen Hosp, Div Plast Surg, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM ccetrulo@mgh.harvard.edu NR 21 TC 2 Z9 2 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0743-684X EI 1098-8947 J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD OCT PY 2014 VL 30 IS 8 BP 515 EP 521 DI 10.1055/s-0034-1383499 PG 7 WC Surgery SC Surgery GA AQ6KP UT WOS:000342921000002 PM 25184616 ER PT J AU Bhama, PK Patel, SA Khan, U Bhrany, AD Futran, ND AF Bhama, Prabhat K. Patel, Sapna A. Khan, Umer Bhrany, Amit D. Futran, Neal D. TI Head and Neck Free Flap Reconstruction in Patients Older than 80 Years SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article DE elderly; octogenarian; microvascular reconstruction; free flap; free tissue transfer ID FREE-TISSUE TRANSFER; ELDERLY-PATIENTS; MICROVASCULAR RECONSTRUCTION; PERIOPERATIVE COMPLICATIONS; CANCER PATIENTS; SURGERY; DEFECTS; AGE; OUTCOMES AB Background Free tissue transfer is a reliable method for reconstruction of head and neck defects. With the growing number of octogenarians in the population, it is important to understand how these patients respond to these procedures. Methods Through a retrospective chart review of patients who underwent a free-flap reconstruction from 2000 to 2010 at an academic medical center, 48 patients, aged 80 years and older, were compared with a control group consisting of 97 similar patients, aged younger than 80 years. We compared the intensive care unit (ICU) length of stay, overall hospital stay, and the incidence of perioperative complications between the cohorts. Results The average length of stay in the ICU was significantly longer for the octogenarian group as compared with the younger group (101 vs. 41 hours, p-value = 0.007). The average length of hospital stay was not significantly different between the two groups (difference = 40 hours, p-value = 0.102). The incidence of perioperative complication was 75% in the octogenarian group and 60% in the younger group (p-value = 0.095). There were two flap failures in the younger group, and none in the octogenarian group. There was a significantly higher rate of death within 30 days in the octogenarian group. Conclusions Microvascular free tissue transfer is a reliable and safe method of reconstruction of head and neck defects in patients over 80 years of age. Patients should be counseled about the potential risks of increased incidence of medical complications, ICU length of stay, and rate of perioperative death when recommended to undergo free tissue transfer reconstruction. C1 [Bhama, Prabhat K.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. [Bhama, Prabhat K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Patel, Sapna A.; Bhrany, Amit D.; Futran, Neal D.] Univ Washington, Med Ctr, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Khan, Umer] Seattle Childrens Res Inst, Seattle, WA USA. RP Patel, SA (reprint author), Univ Washington, Med Ctr, Dept Otolaryngol Head & Neck Surg, 1959 NE Pacific St Box 356515, Seattle, WA 98195 USA. EM sapnap@uw.edu NR 28 TC 6 Z9 6 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0743-684X EI 1098-8947 J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD OCT PY 2014 VL 30 IS 8 BP 523 EP 530 DI 10.1055/s-0034-1384664 PG 8 WC Surgery SC Surgery GA AQ6KP UT WOS:000342921000003 PM 25025506 ER PT J AU Benedict, C Traeger, L Dahn, JR Antoni, M Zhou, ES Bustillo, N Penedo, FJ AF Benedict, Catherine Traeger, Lara Dahn, Jason R. Antoni, Michael Zhou, Eric S. Bustillo, Natalie Penedo, Frank J. TI Sexual Bother in Men with Advanced Prostate Cancer Undergoing Androgen Deprivation Therapy SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Prostate Cancer; Androgen Deprivation; Androgen Ablation; Hormone Therapy; Sexual Function; Sexual Dysfunction; Sexual Bother; Erectile Dysfunction; Depressive Symptoms; Relationship Functioning; Quality of Life ID QUALITY-OF-LIFE; SCALE CES-D; RADICAL PROSTATECTOMY; FUNCTIONAL ASSESSMENT; OLDER-ADULTS; HIGH-RISK; HEALTH; VALIDATION; ADJUSTMENT; DEPRESSION AB IntroductionMen with advanced prostate cancer (APC) undergoing androgen deprivation therapy (ADT) often experience distressing sexual side effects. Sexual bother is an important component of adjustment. Factors associated with increased bother are not well understood. AimsThis study sought to describe sexual dysfunction and bother in APC patients undergoing ADT, identify socio-demographic and health/disease-related characteristics related to sexual bother, and evaluate associations between sexual bother and psychosocial well-being and quality of life (QOL). MethodsBaseline data of a larger psychosocial intervention study was used. Pearson's correlation and independent samples t-test tested bivariate relations. Multivariate regression analysis evaluated relations between sexual bother and psychosocial and QOL outcomes. Main Outcome MeasuresThe Expanded Prostate Cancer Index Composite sexual function and bother subscales, Center for Epidemiologic Studies Depression Scale, Functional Assessment of Cancer TherapyGeneral, and Dyadic Adjustment Scale were the main outcome measures. ResultsParticipants (N=80) were 70 years old (standard deviation [SD]=9.6) and reported 18.7 months (SD=17.3) of ADT. Sexual dysfunction (mean=10.1; SD=18.0) was highly prevalent. Greater sexual bother (lower scores) was related to younger age (=0.25, P=0.03) and fewer months of ADT (=0.22, P=0.05). Controlling for age, months of ADT, current and precancer sexual function, sexual bother correlated with more depressive symptoms (=-0.24, P=0.06) and lower QOL (=0.25, P=0.05). Contrary to hypotheses, greater sexual bother was related to greater dyadic satisfaction (=-0.35, P=0.03) and cohesion (=-0.42, P=0.01). ConclusionsThe majority of APC patients undergoing ADT will experience sexual dysfunction, but there is variability in their degree of sexual bother. Psychosocial aspects of sexual functioning should be considered when evaluating men's adjustment to ADT effects. Assessment of sexual bother may help identify men at risk for more general distress and lowered QOL. Psychosocial interventions targeting sexual bother may complement medical treatments for sexual dysfunction and be clinically relevant, particularly for younger men and those first starting ADT. Benedict C, Traeger L, Dahn JR, Antoni M, Zhou ES, Bustillo N, and Penedo FJ. Sexual bother in men with advanced prostate cancer undergoing androgen deprivation therapy. J Sex Med 2014;11:2571-2580. C1 [Benedict, Catherine] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10022 USA. [Traeger, Lara] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Dahn, Jason R.] Miami Vet Affairs Healthcare Syst, Mental Hlth & Behav Sci, Miami, FL USA. [Antoni, Michael; Bustillo, Natalie] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Antoni, Michael] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Zhou, Eric S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Penedo, Frank J.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. RP Benedict, C (reprint author), Mem Sloan Kettering Canc Ctr, 641 Lexington Ave,7th Floor, New York, NY 10022 USA. EM benedicc@mskcc.org NR 57 TC 9 Z9 9 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 EI 1743-6109 J9 J SEX MED JI J. Sex. Med. PD OCT PY 2014 VL 11 IS 10 BP 2571 EP 2580 DI 10.1111/jsm.12645 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA AQ6KD UT WOS:000342919400024 PM 25059094 ER PT J AU Sheng, J Larsen, A Heuberger, BD Blain, JC Szostak, JW AF Sheng, Jia Larsen, Aaron Heuberger, Benjamin D. Blain, J. Craig Szostak, Jack W. TI Crystal Structure Studies of RNA Duplexes Containing s(2)U:A and s(2)U:U Base Pairs SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MODIFIED URIDINE; WOBBLE POSITION; ACID; 2-THIOURIDINE; ANTICODON; ACCEPTOR; 4-THIOURIDINE; REPLICATION; THIOLATION; EFFICIENCY AB Structural studies of modified nucleobases in RNA duplexes are critical for developing a full understanding of the stability and specificity of RNA base pairing. 2-Thio-uridine (s(2)U) is a modified nucleobase found in certain tRNAs. Thermodynamic studies have evaluated the effects of s(2)U on base pairing in RNA, where it has been shown to stabilize U:A pairs and destabilize U:G wobble pairs. Surprisingly, no high-resolution crystal structures of s(2)U-containing RNA duplexes have yet been reported. We present here two high-resolution crystal structure of heptamer RNA duplexes (5'-uagcs(2)Ucc-3' paired with 3'-aucgAgg-5' and with 3'-aucgUgg-5') containing s(2)U:A and s(2)U:U pairs, respectively. For comparison, we also present the structures of their native counterparts solved under identical conditions. We found that replacing O2 with S2 stabilizes the U:A base pair without any detectable structural perturbation. In contrast, an s(2)U:U base pair is strongly stabilized in one specific U:U pairing conformation out of four observed for the native U:U base pair. This s(2)U:U stabilization appears to be due at least in part to an unexpected sulfur-mediated hydrogen bond. This work provides additional insights into the effects of 2-thio-uridine on RNA base pairing. C1 [Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Simches Res Ctr, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU National Institutes of Health, National Institute of General Medical Sciences; Howard Hughes Medical Institute; Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy [DE-AC02-05CH11231]; Simons Foundation FX We thank Dr. Jianhua Gan for help with structure determination; Dr. Garib Murshudov for help with JLigand; and Dr. Aaron E. Engelhart, Dr. Shenglong Zhang, and Dr. Li Li for helpful discussions. All diffraction data were collected at the Advanced Light Source (ALS) beamlines 8.2.1 and 8.2.2. The Berkeley Center for Structural Biology is supported in part by the National Institutes of Health, National Institute of General Medical Sciences, and the Howard Hughes Medical Institute. The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract DE-AC02-05CH11231. This work was supported in part by a grant from the Simons Foundation. J.W.S. is an Investigator of the Howard Hughes Medical Institute. NR 35 TC 11 Z9 12 U1 1 U2 11 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 OCT 1 PY 2014 VL 136 IS 39 BP 13916 EP 13924 DI 10.1021/ja508015a PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA AQ2IK UT WOS:000342608800071 PM 25188906 ER PT J AU Alloo, A Strazzula, L Rothschild, B Hawryluk, E Levine, D Hoang, MP Koga, H Hashimoto, T Kroshinsky, D AF Alloo, A. Strazzula, L. Rothschild, B. Hawryluk, E. Levine, D. Hoang, M. P. Koga, H. Hashimoto, T. Kroshinsky, D. TI Refractory antilaminin gamma 1 pemphigoid successfully treated with intravenous immunoglobulin and mycophenolate mofetil SO JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY LA English DT Letter ID SUBEPIDERMAL BLISTERING DISEASE; BASEMENT-MEMBRANE ZONE; BULLOSA-ACQUISITA; AUTOIMMUNE; ANTIGEN C1 [Alloo, A.; Rothschild, B.; Hawryluk, E.; Levine, D.; Kroshinsky, D.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Strazzula, L.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Hoang, M. P.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Koga, H.; Hashimoto, T.] Kurume Univ, Sch Med, Dept Dermatol, Fukuoka, Japan. RP Kroshinsky, D (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM dkroshinsky@partners.org NR 10 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0926-9959 EI 1468-3083 J9 J EUR ACAD DERMATOL JI J. Eur. Acad. Dermatol. Venereol. PD OCT PY 2014 VL 28 IS 10 BP 1401 EP 1403 DI 10.1111/jdv.12352 PG 3 WC Dermatology SC Dermatology GA AQ7OL UT WOS:000343007900020 PM 24397852 ER PT J AU Schoenfeld, D AF Schoenfeld, D. TI Optimizing phase II clinical trials: novel trial designs SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Article C1 [Schoenfeld, D.] Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA. [Schoenfeld, D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Schoenfeld, D (reprint author), Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1085-9489 EI 1529-8027 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD OCT PY 2014 VL 19 SU 2 BP S18 EP S20 DI 10.1111/jns.12081_3 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AQ4LG UT WOS:000342767900011 PM 25269733 ER PT J AU Bhatt, SP Wells, JM Dransfield, MT AF Bhatt, Surya P. Wells, J. Michael Dransfield, Mark T. TI Cardiovascular disease in COPD: a call for action SO LANCET RESPIRATORY MEDICINE LA English DT Editorial Material ID OBSTRUCTIVE PULMONARY-DISEASE; CLINICAL-PRACTICE GUIDELINE; AMERICAN-COLLEGE; RISK; MANAGEMENT; EXACERBATIONS; MORTALITY; EVENTS C1 [Bhatt, Surya P.; Wells, J. Michael; Dransfield, Mark T.] Univ Alabama Birmingham, UAB Lung Hlth Ctr, Birmingham, AL 35229 USA. [Wells, J. Michael; Dransfield, Mark T.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Bhatt, SP (reprint author), Univ Alabama Birmingham, UAB Lung Hlth Ctr, Birmingham, AL 35229 USA. EM mdrans99@uab.edu NR 15 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-2600 J9 LANCET RESP MED JI Lancet Resp. Med. PD OCT PY 2014 VL 2 IS 10 BP 783 EP 785 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AQ3KP UT WOS:000342692100014 PM 25298057 ER PT J AU Gordon, SB Bruce, NG Grigg, J Hibberd, PL Kurmi, OP Lam, KBH Mortimer, K Asante, KP Balakrishnan, K Balmes, J Bar-Zeev, N Bates, MN Breysse, PN Buist, S Chen, ZM Havens, D Jack, D Jindal, S Kan, HD Mehta, S Moschovis, P Naeher, L Patel, A Perez-Padilla, R Pope, D Rylance, J Semple, S Martin, WJ AF Gordon, Stephen B. Bruce, Nigel G. Grigg, Jonathan Hibberd, Patricia L. Kurmi, Om P. Lam, Kin-bong Hubert Mortimer, Kevin Asante, Kwaku Poku Balakrishnan, Kalpana Balmes, John Bar-Zeev, Naor Bates, Michael N. Breysse, Patrick N. Buist, Sonia Chen, Zhengming Havens, Deborah Jack, Darby Jindal, Surinder Kan, Haidong Mehta, Sumi Moschovis, Peter Naeher, Luke Patel, Archana Perez-Padilla, Rogelio Pope, Daniel Rylance, Jamie Semple, Sean Martin, William J., II TI Respiratory risks from household air pollution in low and middle income countries SO LANCET RESPIRATORY MEDICINE LA English DT Article ID PNEUMOCOCCAL CONJUGATE VACCINE; RADIOLOGICALLY-CONFIRMED PNEUMONIA; OBSTRUCTIVE PULMONARY-DISEASE; LUNG-CANCER RISK; POLYCYCLIC AROMATIC-HYDROCARBONS; SECONDHAND SMOKE EXPOSURE; PLACEBO-CONTROLLED-TRIAL; FINE PARTICULATE MATTER; ULTRAFINE CARBON-BLACK; SOLID-FUEL USE AB A third of the world's population uses solid fuel derived from plant material (biomass) or coal for cooking, heating, or lighting. These fuels are smoky, often used in an open fire or simple stove with incomplete combustion, and result in a large amount of household air pollution when smoke is poorly vented. Air pollution is the biggest environmental cause of death worldwide, with household air pollution accounting for about 3.5-4 million deaths every year. Women and children living in severe poverty have the greatest exposures to household air pollution. In this Commission, we review evidence for the association between household air pollution and respiratory infections, respiratory tract cancers, and chronic lung diseases. Respiratory infections (comprising both upper and lower respiratory tract infections with viruses, bacteria, and mycobacteria) have all been associated with exposure to household air pollution. Respiratory tract cancers, including both nasopharyngeal cancer and lung cancer, are strongly associated with pollution from coal burning and further data are needed about other solid fuels. Chronic lung diseases, including chronic obstructive pulmonary disease and bronchiectasis in women, are associated with solid fuel use for cooking, and the damaging effects of exposure to household air pollution in early life on lung development are yet to be fully described. We also review appropriate ways to measure exposure to household air pollution, as well as study design issues and potential effective interventions to prevent these disease burdens. Measurement of household air pollution needs individual, rather than fixed in place, monitoring because exposure varies by age, gender, location, and household role. Women and children are particularly susceptible to the toxic effects of pollution and are exposed to the highest concentrations. Interventions should target these high-risk groups and be of sufficient quality to make the air clean. To make clean energy available to all people is the long-term goal, with an intermediate solution being to make available energy that is clean enough to have a health impact. C1 [Gordon, Stephen B.; Mortimer, Kevin; Havens, Deborah] Univ Liverpool, Liverpool Sch Trop Med, Dept Clin Sci, Liverpool L3 5QA, Merseyside, England. [Bruce, Nigel G.; Pope, Daniel] Univ Liverpool, Dept Publ Hlth & Policy, Liverpool L3 5QA, Merseyside, England. [Grigg, Jonathan] Univ London, Blizard Inst, Ctr Paediat, London, England. [Hibberd, Patricia L.; Moschovis, Peter] Massachusetts Gen Hosp, Dept Pediat, Div Global Hlth, Boston, MA 02114 USA. [Hibberd, Patricia L.; Moschovis, Peter] Harvard Univ, Sch Med, Boston, MA USA. [Kurmi, Om P.; Chen, Zhengming] Univ Oxford, Nuffield Dept Populat Hlth, Clin Trials Serv Unit, Oxford, England. [Kurmi, Om P.; Chen, Zhengming] Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England. [Lam, Kin-bong Hubert] Univ Birmingham, Sch Hlth & Populat Sci, Inst Occupat & Environm Med, Birmingham, W Midlands, England. [Asante, Kwaku Poku; Jack, Darby] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA. [Balakrishnan, Kalpana] Sri Ramachandra Univ, Dept Environm Hlth Engn, Madras, Tamil Nadu, India. [Balmes, John] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Balmes, John] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Bar-Zeev, Naor; Rylance, Jamie] Univ Malawi, Coll Med, Malawi Liverpool Wellcome Trust, Clin Res Programme, Blantyre, Malawi. [Bar-Zeev, Naor] Univ Liverpool, Inst Infect & Global Hlth, Liverpool L69 3BX, Merseyside, England. [Bates, Michael N.] Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA. [Bates, Michael N.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. [Breysse, Patrick N.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. [Buist, Sonia] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Jindal, Surinder] Jindal Clin, Chandigarh, India. [Kan, Haidong] Fudan Univ, Sch Publ Hlth, Shanghai 200433, Peoples R China. [Mehta, Sumi] Hlth Effects Inst, Boston, MA USA. [Naeher, Luke] Univ Georgia, Coll Publ Hlth, Dept Environm Hlth Sci, Athens, GA 30602 USA. [Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India. [Perez-Padilla, Rogelio] Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico. [Semple, Sean] Univ Aberdeen, Royal Aberdeen Childrens Hosp, Scottish Ctr Indoor Air, Div Appl Hlth Sci, Aberdeen, Scotland. [Martin, William J., II] Ohio State Univ, Coll Publ Hlth, Div Environm Hlth Sci, Columbus, OH 43210 USA. RP Gordon, SB (reprint author), Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. EM stephen.gordon@lstmed.ac.uk; wjmartin@cph.osu.edu RI Balakrishnan, Kalpana/B-6653-2015; OI Balakrishnan, Kalpana/0000-0002-5905-1801; Mortimer, Kevin/0000-0002-8118-8871; Gordon, Stephen/0000-0001-6576-1116; Semple, Sean/0000-0002-0462-7295; Rylance, Jamie/0000-0002-2323-3611 FU Medical Research Council (BREATHE Partnership grant) FX We thank Jane Ardrey for collating, editing, and managing the production of this report, and we thank Shaun Pennington for technical assistance with figures and references. We thank Han Duijvendak and his team at HANDSTAND productions for photography. We acknowledge funding from the Medical Research Council (BREATHE Partnership grant) and input to the discussion of this Commission at the Collaboration for Applied Health Research and Delivery (CAHRD) meeting at the Liverpool School of Tropical Medicine, Liverpool, UK, on June 12-13, 2014. We thank James Jetter (US Environmental Protection Agency, NC, USA) for permission to use figure 3. NR 318 TC 69 Z9 73 U1 18 U2 90 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-2600 J9 LANCET RESP MED JI Lancet Resp. Med. PD OCT PY 2014 VL 2 IS 10 BP 823 EP 860 DI 10.1016/S2213-2600(14)70168-7 PG 38 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AQ3KP UT WOS:000342692100023 PM 25193349 ER PT J AU Flemming, JA Vagefi, PA Freise, CE Yao, FY Terrault, NA AF Flemming, Jennifer A. Vagefi, Parsia A. Freise, Chris E. Yao, Francis Y. Terrault, Norah A. TI Restricting Liver Transplant Recipients to Younger Donors Does Not Increase the Wait-List Time or the Dropout Rate: The Hepatitis C Experience SO LIVER TRANSPLANTATION LA English DT Article ID FIBROSIS PROGRESSION; CONSENSUS CONFERENCE; PATIENT SURVIVAL; AGE; VIRUS; GRAFT; RISK; INFECTION; CIRRHOSIS; ALCOHOL AB Older donor age is associated with lower graft and patient survival among all recipients of liver transplantation (LT). Among patients with hepatitis C virus (HCV), donor age is one of the strongest predictors of fibrosis severity and graft loss. We evaluated the implementation of a donor age restriction policy for LT patients with HCV at a single center and the effects that this policy had on wait-list (WL) and post-LT outcomes for HCV and non-HCV patients. This was a cohort study of 2388 WL patients and 1015 LT recipients between March 2002 and January 2013 and reflected 3 different eras of donor age policies. With the donor age restriction, the median donor age was reduced in LT recipients with HCV versus LT recipients without HCV (30 versus 48 years, P < 0.001) without differences in the WL time (10.6 versus 8.0 months, P = 0.23). According to a competing risks regression, those with HCV and those without HCV had lower subhazard ratios (SHRs) of dropout or death on the WL during the donor age restriction era versus the era without donor age restriction [SHR = 0.68 (P < 0.01) and SHR = 0.64 (P = 0.01), respectively]. No differences were seen in early post-LT survival for patients with or without HCV between eras (P = 0.7 and P = 0.88, respectively). In conclusion, we show that donor age restriction for HCV results in a lower donor age for HCV recipients without obvious adverse WL consequences. Although additional studies are needed, our results demonstrate the feasibility of donor age restriction for LT recipients with HCV, and such information may be relevant to programs with limited access to new antiviral therapies for which modifying the risk of severe disease remains of paramount importance. (C) 2014 AASLD. C1 [Flemming, Jennifer A.] Queens Univ, Dept Med, Kingston, ON K7L 3N6, Canada. [Flemming, Jennifer A.] Queens Univ, Div Canc Care & Epidemiol, Kingston, ON K7L 3N6, Canada. [Vagefi, Parsia A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Freise, Chris E.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Yao, Francis Y.; Terrault, Norah A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Terrault, NA (reprint author), Univ Calif San Francisco, Med Ctr, 513 Parnassus Ave,Room S-353, San Francisco, CA 94143 USA. EM norah.terrault@ucsf.edu FU Canadian Association for the Study of the Liver/Merck Fellowship in Hepatology FX This work was funded by the Canadian Association for the Study of the Liver/Merck Fellowship in Hepatology (to Jennifer A. Flemming). NR 21 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6465 EI 1527-6473 J9 LIVER TRANSPLANT JI Liver Transplant. PD OCT PY 2014 VL 20 IS 10 BP 1202 EP 1210 DI 10.1002/lt.23937 PG 9 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA AQ7PR UT WOS:000343012000008 PM 24961679 ER PT J AU Price, RA Elliott, MN Zaslavsky, AM Hays, RD Lehrman, WG Rybowski, L Edgman-Levitan, S Cleary, PD AF Price, Rebecca Anhang Elliott, Marc N. Zaslavsky, Alan M. Hays, Ron D. Lehrman, William G. Rybowski, Lise Edgman-Levitan, Susan Cleary, Paul D. TI Examining the Role of Patient Experience Surveys in Measuring Health Care Quality SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE patient experience; patient satisfaction; CAHPS; health care surveys; health care quality measurement; health care quality ID HOSPITAL PERFORMANCE-MEASURES; ACUTE MYOCARDIAL-INFARCTION; MEDICARE MANAGED CARE; CONSUMER ASSESSMENT; PSYCHOMETRIC PROPERTIES; CENTERED CARE; PHYSICIAN COMMUNICATION; CLINICAL-QUALITY; PROVIDER COMMUNICATION; PREVENTIVE SERVICES AB Patient care experience surveys evaluate the degree to which care is patient-centered. This article reviews the literature on the association between patient experiences and other measures of health care quality. Research indicates that better patient care experiences are associated with higher levels of adherence to recommended prevention and treatment processes, better clinical outcomes, better patient safety within hospitals, and less health care utilization. Patient experience measures that are collected using psychometrically sound instruments, employing recommended sample sizes and adjustment procedures, and implemented according to standard protocols are intrinsically meaningful and are appropriate complements for clinical process and outcome measures in public reporting and pay-for-performance programs. C1 [Price, Rebecca Anhang] RAND Corp, Arlington, VA 22202 USA. [Elliott, Marc N.] RAND Corp, Santa Monica, CA USA. [Zaslavsky, Alan M.] Harvard Univ, Sch Med, Boston, MA USA. [Hays, Ron D.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Lehrman, William G.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. [Rybowski, Lise] Severyn Grp, Ashburn, VA USA. [Edgman-Levitan, Susan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cleary, Paul D.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. RP Price, RA (reprint author), RAND Corp, 1200 South Hayes St, Arlington, VA 22202 USA. EM ranhangp@rand.org FU Agency for Health Care Research and Quality (AHRQ) [2U18HS016980, 2U18HSO16978]; Centers for Medicare & Medicaid Services (CMS); AHRQ; NIA [P30-AG021684]; NIMHD [P20MD000182] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Support for preparation of this manuscript comes from cooperative agreements from the Agency for Health Care Research and Quality (AHRQ; 2U18HS016980; 2U18HSO16978). The authors have been funded by the Centers for Medicare & Medicaid Services (CMS; RAP, MNE, AMZ, and PDC) and AHRQ (RAP, MNE, AMZ, RDH, LR, SEL, and PDC) as investigators in development and implementation of CAHPS surveys. RDH was also supported in part by grants from the NIA (P30-AG021684) and the NIMHD (P20MD000182). NR 109 TC 16 Z9 16 U1 5 U2 29 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 EI 1552-6801 J9 MED CARE RES REV JI Med. Care Res. Rev. PD OCT PY 2014 VL 71 IS 5 BP 522 EP 554 DI 10.1177/1077558714541480 PG 33 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AQ5KJ UT WOS:000342847000005 ER PT J AU Pouliot, GP Gutierrez, A AF Pouliot, Gayle P. Gutierrez, Alejandro TI Thymocyte transformation enhanced SO NATURE MEDICINE LA English DT Editorial Material ID TERT PROMOTER MUTATIONS; LEUKEMIA; MELANOMA; NOTCH1; MICE AB A new study identifies recurrent somatic duplications of a NOTCH 1-driven enhancer of MYC in human T cell leukemia. This enhancer is required for both normal and malignant T cell development. C1 [Pouliot, Gayle P.; Gutierrez, Alejandro] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Boston Childrens Hosp, Boston, MA 02115 USA. RP Pouliot, GP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Boston Childrens Hosp, 44 Binney St, Boston, MA 02115 USA. EM alejandro.gutierrez@childrens.harvard.edu OI Pouliot, Gayle/0000-0001-9730-143X NR 12 TC 0 Z9 0 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD OCT PY 2014 VL 20 IS 10 BP 1096 EP 1097 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AQ9RV UT WOS:000343194100011 PM 25295936 ER PT J AU Tsai, SDQ Iafrate, AJ Joung, JK AF Tsai, Shengdar Q. Iafrate, A. John Joung, J. Keith TI Towards a functional understanding of variants for molecular diagnostics using genome editing SO NATURE MEDICINE LA English DT Editorial Material ID GENERATION; MUTATIONS; NUCLEASES; CELLS C1 [Tsai, Shengdar Q.; Iafrate, A. John; Joung, J. Keith] Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Charlestown, MA 02129 USA. RP Tsai, SDQ (reprint author), Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Charlestown, MA 02129 USA. EM jjoung@mgh.harvard.edu NR 13 TC 3 Z9 3 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD OCT PY 2014 VL 20 IS 10 BP 1103 EP 1104 DI 10.1038/nm.3722 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AQ9RV UT WOS:000343194100015 PM 25295940 ER PT J AU Mayers, JR Wu, C Clish, CB Kraft, P Torrence, ME Fiske, BP Yuan, C Bao, Y Townsend, MK Tworoger, SS Davidson, SM Papagiannakopoulos, T Yang, A Dayton, TL Ogino, S Stampfer, MJ Giovannucci, EL Qian, ZR Rubinson, DA Ma, J Sesso, HD Gaziano, JM Cochrane, BB Liu, SM Wactawski-Wende, J Manson, JE Pollak, MN Kimmelman, AC Souza, A Pierce, K Wang, TJ Gerszten, RE Fuchs, CS Vander Heiden, MG Wolpin, BM AF Mayers, Jared R. Wu, Chen Clish, Clary B. Kraft, Peter Torrence, Margaret E. Fiske, Brian P. Yuan, Chen Bao, Ying Townsend, Mary K. Tworoger, Shelley S. Davidson, Shawn M. Papagiannakopoulos, Thales Yang, Annan Dayton, Talya L. Ogino, Shuji Stampfer, Meir J. Giovannucci, Edward L. Qian, Zhi Rong Rubinson, Douglas A. Ma, Jing Sesso, Howard D. Gaziano, John M. Cochrane, Barbara B. Liu, Simin Wactawski-Wende, Jean Manson, Joann E. Pollak, Michael N. Kimmelman, Alec C. Souza, Amanda Pierce, Kerry Wang, Thomas J. Gerszten, Robert E. Fuchs, Charles S. Vander Heiden, Matthew G. Wolpin, Brian M. TI Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development SO NATURE MEDICINE LA English DT Article ID INSULIN-RESISTANCE; CANCER CACHEXIA; POOLED ANALYSIS; LUNG-CANCER; WEIGHT-LOSS; ROC CURVE; K-RAS; RISK; MOUSE; METABOLOMICS AB Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months(1). PDAC has been linked with obesity and glucose intolerance(2-4), but whether changes in circulating metabolites are associated with early cancer progression is unknown. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from individuals with pancreatic cancer (cases) and matched controls from four prospective cohort studies. We find that elevated plasma levels of branched-chain amino acids (BCAAs) are associated with a greater than twofold increased risk of future pancreatic cancer diagnosis. This elevated risk was independent of known predisposing factors, with the strongest association observed among subjects with samples collected 2 to 5 years before diagnosis, when occult disease is probably present. We show that plasma BCAAs are also elevated in mice with early-stage pancreatic cancers driven by mutant Kras expression but not in mice with Kras-driven tumors in other tissues, and that breakdown of tissue protein accounts for the increase in plasma BCAAs that accompanies early-stage disease. Together, these findings suggest that increased whole-body protein breakdown is an early event in development of PDAC. C1 [Mayers, Jared R.; Torrence, Margaret E.; Fiske, Brian P.; Davidson, Shawn M.; Papagiannakopoulos, Thales; Dayton, Talya L.; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Mayers, Jared R.; Torrence, Margaret E.; Fiske, Brian P.; Davidson, Shawn M.; Papagiannakopoulos, Thales; Dayton, Talya L.; Vander Heiden, Matthew G.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Wu, Chen] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Etiol & Carcinogenesis, Beijing 100730, Peoples R China. [Wu, Chen] Peking Union Med Coll, Beijing 100021, Peoples R China. [Wu, Chen; Yuan, Chen; Ogino, Shuji; Qian, Zhi Rong; Rubinson, Douglas A.; Fuchs, Charles S.; Vander Heiden, Matthew G.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wu, Chen; Yuan, Chen; Bao, Ying; Townsend, Mary K.; Tworoger, Shelley S.; Ogino, Shuji; Stampfer, Meir J.; Giovannucci, Edward L.; Qian, Zhi Rong; Rubinson, Douglas A.; Ma, Jing; Sesso, Howard D.; Gaziano, John M.; Manson, Joann E.; Gerszten, Robert E.; Fuchs, Charles S.; Vander Heiden, Matthew G.; Wolpin, Brian M.] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Chen; Kraft, Peter; Tworoger, Shelley S.; Ogino, Shuji; Stampfer, Meir J.; Giovannucci, Edward L.; Ma, Jing; Sesso, Howard D.; Manson, Joann E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Clish, Clary B.; Souza, Amanda; Pierce, Kerry; Gerszten, Robert E.; Vander Heiden, Matthew G.] Broad Inst MIT & Harvard Univ, Cambridge, MA USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Bao, Ying; Townsend, Mary K.; Tworoger, Shelley S.; Stampfer, Meir J.; Giovannucci, Edward L.; Ma, Jing; Manson, Joann E.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Yang, Annan; Kimmelman, Alec C.] Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Stampfer, Meir J.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Sesso, Howard D.; Gaziano, John M.; Manson, Joann E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Gaziano, John M.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA USA. [Cochrane, Barbara B.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Liu, Simin] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Liu, Simin] Brown Univ, Dept Med, Providence, RI 02912 USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Pollak, Michael N.] McGill Univ, Dept Oncol, Montreal, PQ, Canada. [Pollak, Michael N.] McGill Univ, Dept Med, Montreal, PQ, Canada. [Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37235 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Vander Heiden, MG (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mvh@mit.edu; bwolpin@partners.org OI Tworoger, Shelley/0000-0002-6986-7046; Mayers, Jared/0000-0002-8607-1787 FU US National Institutes of Health (NIH) [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908, R01 CA49449, 1UM1 CA167552]; NIH [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; Nestle Research Center award; Robert T. and Judith B. Hale Fund for Pancreatic Cancer, Perry S. Levy Fund for Gastrointestinal Cancer Research and Pappas Family Research Fund for Pancreatic Cancer; Burroughs Wellcome Fund; Damon Runyon Cancer Research Foundation; Smith Family; Stern Family; NIH/NCI [K07 CA140790]; American Society of Clinical Oncology Conquer Cancer Foundation; Howard Hughes Medical Institute and Promises for Purple; Howard Hughes Medical Institute; Lustgarten Foundation; [F30 CA183474]; [R01 DK081572]; [P30-CA14051]; [P01-CA117969] FX We would like to acknowledge A. Deik and K. Bullock of the Broad Institute for assistance with LC-MS sample analyses and the Tang Histology facility in the Koch Institute Swanson Biotechnology Center for assistance processing mouse tissues. Cambridge Isotope Laboratories supplied 13C-BCAA diets for mouse labeling studies. We would like to thank C. Newgard and A. Goldberg for their thoughtful discussions regarding this manuscript. We would also like to thank the participants and staff of the Health Professionals Follow-Up Study (HPFS), Nurses' Health Study (NHS), Physicians' Health Study I (PHS) and Women's Health Initiative-Observational Study (WHI-OS) for their contributions as well as the cancer registries of the following states for their help: Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Indiana, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Nebraska, New Hampshire, New Jersey, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Virginia, Washington and Wyoming. NHS and HPFS are supported by US National Institutes of Health (NIH) grants P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908, R01 CA49449 and 1UM1 CA167552. PHS is supported by NIH grants CA 97193, CA 34944, CA 40360, HL 26490 and HL 34595. The WHI program is funded by the NIH through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and HHSN271201100004C. We acknowledge additional support from grant F30 CA183474 to J.R.M.; from a Nestle Research Center award to the Broad Institute; from R01 DK081572 grant to T.J.W. and R.E.G.; from the Robert T. and Judith B. Hale Fund for Pancreatic Cancer, Perry S. Levy Fund for Gastrointestinal Cancer Research and Pappas Family Research Fund for Pancreatic Cancer to C.S.F.; from the Burroughs Wellcome Fund, Damon Runyon Cancer Research Foundation, the Smith Family and the Stern Family to M.G.V.H.; and from NIH/NCI grant K07 CA140790, the American Society of Clinical Oncology Conquer Cancer Foundation, the Howard Hughes Medical Institute and Promises for Purple to B.M.W. M.G.V.H. additionally acknowledges support from P30-CA14051 and P01-CA117969, and major support for this project was provided by the Howard Hughes Medical Institute to B.M.W. and the Lustgarten Foundation to C.S.F., M.G.V.H. and B.M.W. NR 42 TC 78 Z9 80 U1 11 U2 49 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD OCT PY 2014 VL 20 IS 10 BP 1193 EP 1198 DI 10.1038/nm.3686 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AQ9RV UT WOS:000343194100031 PM 25261994 ER PT J AU Kang, JH Super, M Yung, CW Cooper, RM Domansky, K Graveline, AR Mammoto, T Berthet, JB Tobin, H Cartwright, MJ Watters, AL Rottman, M Waterhouse, A Mammoto, A Gamini, N Rodas, MJ Kole, A Jiang, A Valentin, TM Diaz, A Takahashi, K Ingber, DE AF Kang, Joo H. Super, Michael Yung, Chong Wing Cooper, Ryan M. Domansky, Karel Graveline, Amanda R. Mammoto, Tadanori Berthet, Julia B. Tobin, Heather Cartwright, Mark J. Watters, Alexander L. Rottman, Martin Waterhouse, Anna Mammoto, Akiko Gamini, Nazita Rodas, Melissa J. Kole, Anxhela Jiang, Amanda Valentin, Thomas M. Diaz, Alexander Takahashi, Kazue Ingber, Donald E. TI An extracorporeal blood-cleansing device for sepsis therapy SO NATURE MEDICINE LA English DT Article ID MANNOSE-BINDING LECTIN; RECOGNITION; SURVEILLANCE; RESISTANCE; MORTALITY; CELLS AB Here we describe a blood-cleansing device for sepsis therapy inspired by the spleen, which can continuously remove pathogens and toxins from blood without first identifying the infectious agent. Blood flowing from an infected individual is mixed with magnetic nanobeads coated with an engineered human opsonin mannose-binding lectin (MBL) that captures a broad range of pathogens and toxins without activating complement factors or coagulation. Magnets pull the opsonin-bound pathogens and toxins from the blood; the cleansed blood is then returned back to the individual. The biospleen efficiently removes multiple Gram-negative and Gram-positive bacteria, fungi and endotoxins from whole human blood flowing through a single biospleen unit at up to 1.25 liters per h in vitro. In rats infected with Staphylococcus aureus or Escherichia coli, the biospleen cleared >90% of bacteria from blood, reduced pathogen and immune cell infiltration in multiple organs and decreased inflammatory cytokine levels. In a model of endotoxemic shock, the biospleen increased survival rates after a 5-h treatment. C1 [Kang, Joo H.; Super, Michael; Yung, Chong Wing; Cooper, Ryan M.; Domansky, Karel; Graveline, Amanda R.; Berthet, Julia B.; Cartwright, Mark J.; Watters, Alexander L.; Rottman, Martin; Waterhouse, Anna; Gamini, Nazita; Rodas, Melissa J.; Kole, Anxhela; Valentin, Thomas M.; Diaz, Alexander; Ingber, Donald E.] Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Kang, Joo H.; Yung, Chong Wing; Cooper, Ryan M.; Mammoto, Tadanori; Tobin, Heather; Mammoto, Akiko; Jiang, Amanda; Ingber, Donald E.] Boston Childrens Hosp, Vasc Biol Program, Boston, MA USA. [Kang, Joo H.; Yung, Chong Wing; Cooper, Ryan M.; Mammoto, Tadanori; Tobin, Heather; Mammoto, Akiko; Jiang, Amanda; Takahashi, Kazue; Ingber, Donald E.] Harvard Univ, Sch Med, Boston, MA USA. [Kang, Joo H.; Ingber, Donald E.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Cooper, Ryan M.] Harvard MIT Hlth Sci & Technol Grad Program, Cambridge, MA USA. [Takahashi, Kazue] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ingber, DE (reprint author), Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. EM don.ingber@wyss.harvard.edu RI Rottman, Martin/I-3005-2012; OI Rottman, Martin/0000-0001-5953-3344; Berthet, Julia/0000-0002-6549-8116 FU Defense Advanced Research Projects Agency [N66001-11-1-4180, HR0011-13-C-0025]; Department of Defense/Center for Integration of Medicine and Innovative Technology; Wyss Institute for Biologically Inspired Engineering at Harvard University; Wyss Technology Development Fellowship from the Wyss Institute; Harvard University; National Science Foundation [ECS-0335765] FX This work was supported by Defense Advanced Research Projects Agency grant N66001-11-1-4180 and contract HR0011-13-C-0025, Department of Defense/Center for Integration of Medicine and Innovative Technology and the Wyss Institute for Biologically Inspired Engineering at Harvard University. We thank M. Montoya-Zavala and D. Breslau for micromachining,of the blood-cleansing microdevice and technical support; P. Snell and J. Tomolonis for microbiology assistance; A. Schulte for assistance in biospleen experiments; J. Weaver for help with scanning electron microscopy; R. Betensky for statistical analysis assistance; and A. Onderdonk, M. Puder, A. Nedder and their teams for assistance in developing the rat cecal contents sepsis model. We thank J. Fiering and his team for helpful discussions during the early phase of this project. J.H.K. is a recipient of a Wyss Technology Development Fellowship from the Wyss Institute and a professional development postdoctoral award from Harvard University. Scanning electron microscopy images were obtained at the Center for Nanoscale Systems at Harvard University; supported by the National Science Foundation under award no. ECS-0335765. NR 36 TC 47 Z9 49 U1 20 U2 89 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD OCT PY 2014 VL 20 IS 10 BP 1211 EP 1216 DI 10.1038/nm.3640 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AQ9RV UT WOS:000343194100034 PM 25216635 ER PT J AU Murugan, R Wen, XY Shah, N Lee, M Kong, L Pike, F Keener, C Unruh, M Finkel, K Vijayan, A Palevsky, PM Paganini, E Carter, M Elder, M Kellum, JA AF Murugan, Raghavan Wen, Xiaoyan Shah, Nilesh Lee, Minjae Kong, Lan Pike, Francis Keener, Christopher Unruh, Mark Finkel, Kevin Vijayan, Anitha Palevsky, Paul M. Paganini, Emil Carter, Melinda Elder, Michele Kellum, John A. CA Biol Markers Recovery Kidney TI Plasma inflammatory and apoptosis markers are associated with dialysis dependence and death among critically ill patients receiving renal replacement therapy SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE acute kidney injury; biomarkers; mortality; renal recovery; renal replacement therapy ID ACUTE KIDNEY INJURY; PREDICT MORTALITY; TRIAL NETWORK; APACHE-II; FAILURE; INTERLEUKIN-6; INTENSITY; SURGERY; SEPSIS; ARF AB Background. Survivors of critical illness complicated by acute kidney injury requiring renal replacement therapy (RRT) are at an increased risk of dialysis dependence and death but the mechanisms are unknown. Methods. In a multicenter, prospective, cohort study of 817 critically ill patients receiving RRT, we examined association between Day 1 plasma inflammatory [interleukin (IL)-1 beta, IL-6, IL-8, IL-10 and IL-18; macrophage migration inhibitory factor (MIF) and tumor necrosis factor]; apoptosis [tumor necrosis factor receptor (TNFR)-I and TNFR-II and death receptor (DR)-5]; and growth factor (granulocyte macrophage colony stimulating factor) biomarkers and renal recovery and mortality at Day 60. Renal recovery was defined as alive and RRT independent. Results. Of 817 participants, 36.5% were RRT independent and 50.8% died. After adjusting for differences in demographics, comorbid conditions; premorbid creatinine; nephrotoxins; sepsis; oliguria; mechanical ventilation; RRT dosing; and severity of illness, increased concentrations of plasma IL-8 and IL-18 and TNFR-I were independently associated with slower renal recovery [adjusted hazard ratio (AHR) range for all markers, 0.70-0.87]. Higher concentrations of IL-6, IL-8, IL-10 and IL-18; MIF; TNFR-I and DR-5 were associated with mortality (AHR range, 1.16-1.47). In an analysis of multiple markers simultaneously, increased IL-8 [AHR, 0.80, 95% confidence interval (95% CI) 0.70-0.91, P < 0.001] and TNFR-I (AHR, 0.63, 95% CI 0.50-0.79, P < 0.001) were associated with slower recovery, and increased IL-8 (AHR, 1.26, 95% CI 1.14-1.39, P < 0.001); MIF (AHR, 1.18, 95% CI 1.08-1.28, P < 0.001) and TNFR-I (AHR, 1.26, 95% CI 1.02-1.56, P < 0.03) were associated with mortality. Conclusions. Elevated plasma concentrations of inflammatory and apoptosis biomarkers are associated with RRT dependence and death. Our data suggest that future interventions should investigate broad-spectrum immune-modulation to improve outcomes. C1 [Murugan, Raghavan; Wen, Xiaoyan; Palevsky, Paul M.; Elder, Michele; Kellum, John A.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Ctr Crit Care Nephrol,CRISMA, Pittsburgh, PA 15260 USA. [Murugan, Raghavan; Wen, Xiaoyan; Shah, Nilesh; Lee, Minjae; Kong, Lan; Pike, Francis; Keener, Christopher; Carter, Melinda; Elder, Michele; Kellum, John A.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Clin Res Invest & Syst Modeling Acute Illness CRI, Pittsburgh, PA USA. [Shah, Nilesh; Pike, Francis; Keener, Christopher] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Lee, Minjae] Univ Texas Hlth Sci Ctr Houston, Ctr Clin & Translat Sci, Houston, TX 77030 USA. [Kong, Lan] Penn State Hershey Coll Med, Div Biostat & Bioinformat, Dept Publ Hlth Sci, Hershey, PA USA. [Unruh, Mark] Univ New Mexico, Div Nephrol, Dept Internal Med, Albuquerque, NM 87131 USA. [Finkel, Kevin] Univ Texas Med Sch Houston, Div Renal Dis & Hypertens, Houston, TX USA. [Vijayan, Anitha] Washington Univ, Div Renal Dis, St Louis, MO USA. [Palevsky, Paul M.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Paganini, Emil] Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Kellum, JA (reprint author), Univ Pittsburgh, Sch Med, Dept Crit Care Med, Ctr Crit Care Nephrol,CRISMA, Pittsburgh, PA 15260 USA. EM kellumja@ccm.upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU National Institute of Diabetes and Digestive, and Kidney Diseases (NIDDK) [R01DK070910]; National Center For Advancing Translational Sciences of the National Institutes of Health [KL2TR000146]; Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development (CSP) [530]; NIDDK [Y1-DK-3508]; [R01DK083961] FX BioMaRK was supported by a grant (R01DK070910) from the National Institute of Diabetes and Digestive, and Kidney Diseases (NIDDK). Additional support for J.K., X.W. and F.P. was provided by grant (R01DK083961) and for R.M. from the National Center For Advancing Translational Sciences of the National Institutes of Health under Award Number KL2TR000146. The VA/NIH ATN study was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development (CSP #530) and by NIDDK by interagency agreement Y1-DK-3508. NR 38 TC 20 Z9 21 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD OCT PY 2014 VL 29 IS 10 BP 1854 EP 1864 DI 10.1093/ndt/gfu051 PG 11 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA AQ6SE UT WOS:000342943300011 PM 24619058 ER PT J AU Groisser, BN Copen, WA Singhal, AB Hirai, KK Schaechter, JD AF Groisser, Benjamin N. Copen, William A. Singhal, Aneesh B. Hirai, Kelsi K. Schaechter, Judith D. TI Corticospinal Tract Diffusion Abnormalities Early After Stroke Predict Motor Outcome SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE stroke; motor recovery; diffusion tensor imaging (DTI); corticospinal tract (CST); upper limb; motor impairment; strength; dexterity; prognosis; prediction ID TRANSCRANIAL MAGNETIC STIMULATION; WHITE-MATTER TRACTOGRAPHY; TENSOR IMAGING DETECTS; ISCHEMIC-STROKE; WALLERIAN DEGENERATION; CEREBRAL-ISCHEMIA; RETINAL ISCHEMIA; PYRAMIDAL TRACT; RECOVERY; ANISOTROPY AB Background. Prognosis of long-term motor outcome of acute stroke patients with severe motor impairment is difficult to determine. Objective. Our primary goal was to evaluate the prognostic value of corticospinal tract (CST) injury on motor outcome of the upper limb compared with motor impairment level and lesion volume. Methods. In all, 10 acute stroke patients with moderately severe to severe motor impairment of the upper limb underwent diffusion tensor imaging (DTI) and testing of upper limb strength and dexterity at acute, subacute, and chronic poststroke time points. A density-weighted CST atlas was constructed using DTI tractography data from normal participants. This CST atlas was applied, using a largely automated process, to DTI data from patients to quantify CST injury at each time point. Differences in axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) of the ipsilesional CST relative to the contralesional CST were measured. Results. Acute loss in CST AD correlated most strongly and significantly with subacute and chronic strength and dexterity and remained significant after adjusting for acute motor impairment or lesion volume. Subacute loss in CST FA correlated most strongly with chronic dexterity, whereas subacute behavioral measures of limb strength correlated most strongly with chronic strength measures. Conclusions. Loss in acute CST AD and subacute CST FA are strong prognostic indicators of future motor functions of the upper limb for stroke patients with substantial initial motor impairment. DTI-derived measure of CST injury early after stroke may have utility in health care planning and in design of acute stroke clinical trials. C1 [Groisser, Benjamin N.; Hirai, Kelsi K.; Schaechter, Judith D.] MGH HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Groisser, Benjamin N.; Copen, William A.; Hirai, Kelsi K.; Schaechter, Judith D.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Singhal, Aneesh B.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Schaechter, JD (reprint author), MGH HST Athinoula A Martinos Ctr Biomed Imaging, 13th St,Bldg 149,Room 2301, Charlestown, MA 02129 USA. EM judith@nmr.mgh.harvard.edu FU Founders Affiliate of the American Heart Association [09GRNT2240036]; Biomedical Technology Program of the NIH-NCRR [P41RR14075]; NIH-NINDS [R01NS051412, 1R21NS077442] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by a grant from the Founders Affiliate of the American Heart Association (09GRNT2240036) and carried out using resources provided by the Biomedical Technology Program of the NIH-NCRR (P41RR14075) and the Harvard NeuroDiscovery Center. ABS was supported by grants from the NIH-NINDS (R01NS051412 and 1R21NS077442). NR 43 TC 20 Z9 22 U1 0 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 EI 1552-6844 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD OCT PY 2014 VL 28 IS 8 BP 751 EP 760 DI 10.1177/1545968314521896 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AQ5CK UT WOS:000342820800005 PM 24519021 ER PT J AU Hamani, C Pilitsis, J Rughani, AI Rosenow, JM Patil, PG Slavin, KS Abosch, A Eskandar, E Mitchell, LS Kalkanis, S AF Hamani, Clement Pilitsis, Julie Rughani, Anand I. Rosenow, Joshua M. Patil, Parag G. Slavin, Konstantin S. Abosch, Aviva Eskandar, Emad Mitchell, Laura S. Kalkanis, Steven TI Deep Brain Stimulation for Obsessive-Compulsive Disorder: Systematic Review and Evidence-Based Guideline Sponsored by the American Society for Stereotactic and Functional Neurosurgery and the Congress of Neurological Surgeons (CNS) and Endorsed by the CNS and American Association of Neurological Surgeons SO NEUROSURGERY LA English DT Review DE Deep brain stimulation; Guidelines; Obsessive-compulsive disorder; Neuromodulation; Psychiatry ID NUCLEUS-ACCUMBENS; ELECTRICAL-STIMULATION; INTERNAL CAPSULES; ANTERIOR LIMBS; PHARMACOTHERAPY; OUTCOMES; TARGET AB BACKGROUND: It is estimated that 40% to 60% of patients with obsessive-compulsive disorder (OCD) continue to experience symptoms despite adequate medical management. For this population of treatment-refractory patients, promising results have been reported with the use of deep brain stimulation (DBS). OBJECTIVE: To conduct a systematic review of the literature and develop evidence-based guidelines on DBS for OCD. METHODS: A systematic literature search was undertaken using the PubMed database for articles published between 1966 and October 2012 combining the following words: "deep brain stimulation and obsessive-compulsive disorder" or "electrical stimulation and obsessive-compulsive disorder." Of 353 articles, 7 were retrieved for full-text review and analysis. The quality of the articles was assigned to each study and the strength of recommendation graded according to the guidelines development methodology of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Guidelines Committee. RESULTS: Of the 7 studies, 1 class I and 2 class II double-blind, randomized, controlled trials reported that bilateral DBS is more effective in improving OCD symptoms than sham treatment. CONCLUSION: Based on the data published in the literature, the following recommendations can be made: (1) There is Level I evidence, based on a single class I study, for the use of bilateral subthalamic nucleus DBS for the treatment of medically refractory OCD. (2) There is Level II evidence, based on a single class II study, for the use of bilateral nucleus accumbens DBS for the treatment of medically refractory OCD. (3) There is insufficient evidence to make a recommendation for the use of unilateral DBS for the treatment of medically refractory OCD. C1 [Hamani, Clement] Toronto Western Hosp, Div Neurosurg, Ctr Addict & Mental Hlth, Toronto, ON M5T 2S8, Canada. [Pilitsis, Julie] Albany Med Coll, Dept Neurosurg, Albany, NY 12208 USA. [Pilitsis, Julie] Albany Med Coll, Ctr Neuropharmacol & Neurosci, Albany, NY 12208 USA. [Rughani, Anand I.] Maine Med Ctr, Neurosci Inst, Portland, ME 04102 USA. [Rosenow, Joshua M.] Northwestern Univ, Dept Neurosurg, Chicago, IL 60611 USA. [Patil, Parag G.] Univ Michigan, Dept Neurosurg, Ann Arbor, MI 48109 USA. [Patil, Parag G.] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. [Patil, Parag G.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Patil, Parag G.] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. [Slavin, Konstantin S.] Univ Chicago, Dept Neurosurg, Chicago, IL 60637 USA. [Abosch, Aviva] Univ Colorado, Dept Neurosurg, Denver, CO 80202 USA. [Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Mitchell, Laura S.] Congress Neurol Surg, Guidelines Dept, Schaumburg, IL USA. [Kalkanis, Steven] Henry Ford Hlth Syst, Dept Neurosurg, Detroit, MI USA. RP Hamani, C (reprint author), Toronto Western Hosp, Div Neurosurg, 399 Bathurst St,WW 4-437, Toronto, ON M5T 2S8, Canada. EM Clement.Hamani@uhn.on.ca RI Patil, Parag/D-1618-2016 FU Boston Scientific; St Jude; Medtronic; NIH FX Dr Hamani is a consultant for St. Jude Medical; Dr Pilitsis is a consultant for St. Jude Medical, Boston Scientific, and Medtronic and has grant support from Boston Scientific, St Jude, Medtronic, and the NIH; Dr Rosenow is a consultant for Boston Scientific; Dr Patil receives research support from Medtronic; Dr Abosch has an ad hoc consulting agreement with Medtronic; Dr Slavin is a consultant, advisory board member, and/or received honoraria from Medtronic, St. Jude Medical, Boston Scientific, Bioness, Greatbatch, Stimwave, and Nevro. The authors have no personal, financial, or institutional interest in any drugs, materials, or devices described in this article. NR 35 TC 21 Z9 21 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X EI 1524-4040 J9 NEUROSURGERY JI Neurosurgery PD OCT PY 2014 VL 75 IS 4 BP 327 EP 333 DI 10.1227/NEU.0000000000000499 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AQ3AY UT WOS:000342662300013 PM 25050579 ER PT J AU Ghogawala, Z Benzel, EC Heary, RF Riew, KD Albert, TJ Butler, WE Barker, FG Heller, JG McCormick, PC Whitmore, RG Freund, KM Schwartz, JS AF Ghogawala, Zoher Benzel, Edward C. Heary, Robert F. Riew, K. Daniel Albert, Todd J. Butler, William E. Barker, Fred G., II Heller, John G. McCormick, Paul C. Whitmore, Robert G. Freund, Karen M. Schwartz, J. Sanford TI Cervical Spondylotic Myelopathy Surgical Trial: Randomized, Controlled Trial Design and Rationale SO NEUROSURGERY LA English DT Article DE Cervical spondylotic myelopathy; Randomized clinical trial; Outcomes ID QUALITY-OF-LIFE; IMPORTANT DIFFERENCE; SURGERY PATIENTS; SPINE SURGERY; FUSION; LAMINOPLASTY; OUTCOMES; DISEASE; DECOMPRESSION; DISORDERS AB BACKGROUND: Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction in the world. There are significant practice variation and uncertainty as to the optimal surgical approach for treating CSM. OBJECTIVE: To determine whether ventral surgery is associated with superior Short Form-36 Physical Component Summary outcome at the 1-year follow-up compared with dorsal (laminectomy/fusion or laminoplasty) surgery for the treatment of CSM, to investigate whether postoperative sagittal balance is an independent predictor of overall outcome, and to compare health resource use for ventral and dorsal procedures. METHODS: The study is a randomized, controlled trial with a nonrandomized arm for patients who are eligible but decline randomization. Two hundred fifty patients (159 randomized) with CSM from 11 sites will be recruited over 18 months. The primary outcome is the Short Form-36 Physical Component Summary score. Secondary outcomes include disease-specific outcomes, overall health-related quality of life (EuroQOL 5-dimension questionnaire), and health resource use. EXPECTED OUTCOMES: This will be the first randomized, controlled trial to compare directly the health-related quality-of-life outcomes for ventral vs dorsal surgery for treating CSM. DISCUSSION: A National Institutes of Health-funded (1R13AR065834-01) investigator meeting was held before the initiation of the trial to bring multiple stakeholders together to finalize the study protocol. Study investigators, coordinators, and major stakeholders were able to attend and discuss strengths of, limitations of, and concerns about the study. The final protocol was approved for funding by the Patient-Centered Outcomes Research Institute (CE-1304-6173). The trial began enrollment on April 1, 2014. C1 [Ghogawala, Zoher; Whitmore, Robert G.] Lahey Hosp & Med Ctr, Dept Neurosurg, Alan & Jacqueline Stuart Spine Ctr, Burlington, MA 01805 USA. [Ghogawala, Zoher; Freund, Karen M.] Tufts Univ, Sch Med, Boston, MA 01805 USA. [Ghogawala, Zoher] Greenwich Hosp, Wallace Trials Ctr, Greenwich, CT USA. [Benzel, Edward C.] Cleveland Clin Fdn, Ctr Spine Hlth, Cleveland, OH 44195 USA. [Benzel, Edward C.] Cleveland Clin Fdn, Dept Neurosurg, Cleveland, OH 44195 USA. [Heary, Robert F.] Rutgers State Univ, New Jersey Med Sch, Dept Neurosurg, Newark, NJ 07102 USA. [Riew, K. Daniel] Washington Univ, Sch Med, Dept Orthoped Surg, St Louis, MO USA. [Albert, Todd J.] Thomas Jefferson Univ, Dept Orthoped Surg, Philadelphia, PA 19107 USA. [Albert, Todd J.] Rothman Inst, Philadelphia, PA USA. [Butler, William E.; Barker, Fred G., II] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA USA. [Butler, William E.; Barker, Fred G., II] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Heller, John G.] Emory Spine Ctr, Dept Orthoped Surg, Atlanta, GA USA. [McCormick, Paul C.] Columbia Univ, Med Ctr, Neurol Inst New York, Dept Neurol Surg, New York, NY USA. [Freund, Karen M.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Schwartz, J. Sanford] Univ Penn, Wharton Sch Business, Perelman Sch Med, Philadelphia, PA 19104 USA. [Schwartz, J. Sanford] Univ Penn, Leonard Davis Inst, Philadelphia, PA 19104 USA. RP Ghogawala, Z (reprint author), Lahey Hosp & Med Ctr, Dept Neurosurg, 41 Mall Rd, Burlington, MA 01805 USA. EM zoher.ghogawala@lahey.org FU NIH [1R13AR065834-01]; PCORI [CE-1304-6173] FX Funding was provided by the NIH (1R13AR065834-01) and PCORI (CE-1304-6173) to Dr Ghogawala. Dr Riew reports financial interest in Cerapedics, Medtronic, Spinal Dynamics, Amedica, Benvenue, Expanding Orthopedics, Nexgen, Osprey, Paradigm Spine, Spinal Kinetics, Spineology, Vertiflex, and Promethian Surgical Devices. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. NR 34 TC 8 Z9 8 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X EI 1524-4040 J9 NEUROSURGERY JI Neurosurgery PD OCT PY 2014 VL 75 IS 4 BP 334 EP 346 DI 10.1227/NEU.0000000000000479 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AQ3AY UT WOS:000342662300014 PM 24991714 ER PT J AU Potts, MB Siu, JJ Price, JD Salinas, RD Cho, MJ Ramos, AD Hahn, J Margeta, M Oldham, MC Lim, DA AF Potts, Matthew B. Siu, Jason J. Price, James D. Salinas, Ryan D. Cho, Mathew J. Ramos, Alexander D. Hahn, Junghyun Margeta, Marta Oldham, Michael C. Lim, Daniel A. TI Analysis of Mll1 Deficiency Identifies Neurogenic Transcriptional Modules and Brn4 as a Factor for Direct Astrocyte-to-Neuron Reprogramming SO NEUROSURGERY LA English DT Article DE Astrocytes; Brn4 (Pou3f4); Cell transdifferentiation; Epigenomics; Mll1; Neural stem cells; Neurogenesis ID HUMAN SOMATIC-CELLS; STEM-CELLS; SUBVENTRICULAR ZONE; ADULT BRAIN; POSTNATAL ASTROGLIA; DEFINED FACTORS; IN-VIVO; OLIGODENDROCYTES; EXPRESSION; NETWORK AB BACKGROUND: Mixed lineage leukemia-1 (Mll1) epigenetically regulates gene expression patterns that specify cellular identity in both embryonic development and adult stem cell populations. In the adult mouse brain, multipotent neural stem cells (NSCs) in the subventricular zone generate new neurons throughout life, and Mll1 is required for this postnatal neurogenesis but not for glial cell differentiation. Analysis of Mll1-dependent transcription may identify neurogenic genes useful for the direct reprogramming of astrocytes into neurons. OBJECTIVE: To identify Mll1-dependent transcriptional modules and to determine whether genes in the neurogenic modules can be used to directly reprogram astrocytes into neurons. METHODS: We performed gene coexpression module analysis on microarray data from differentiating wild-type and Mll1-deleted subventricular zone NSCs. Key developmental regulators belonging to the neurogenic modules were overexpressed in Mll1-deleted cells and cultured cortical astrocytes, and cell phenotypes were analyzed by immunocytochemistry and electrophysiology. RESULTS: Transcriptional modules that correspond to neurogenesis were identified in wild-type NSCs. Modules related to astrocytes and oligodendrocytes were enriched in Mll1-deleted NSCs, consistent with their gliogenic potential. Overexpression of genes selected from the neurogenic modules enhanced the production of neurons from Mll1-deleted cells, and overexpression of Brn4 (Pou3f4) in nonneurogenic cortical astroglia induced their transdifferentiation into electrophysiologically active neurons. CONCLUSION: Our results demonstrate that Mll1 is required for the expression of neurogenic but not gliogenic transcriptional modules in a multipotent NSC population and further indicate that specific Mll1-dependent genes may be useful for direct reprogramming strategies. C1 [Potts, Matthew B.; Siu, Jason J.; Price, James D.; Salinas, Ryan D.; Cho, Mathew J.; Ramos, Alexander D.; Lim, Daniel A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Potts, Matthew B.; Siu, Jason J.; Price, James D.; Salinas, Ryan D.; Cho, Mathew J.; Ramos, Alexander D.; Oldham, Michael C.; Lim, Daniel A.] Univ Calif San Francisco, Eli & Edythe Broad Inst Regenerat Med & Stem Cell, San Francisco, CA USA. [Hahn, Junghyun; Margeta, Marta] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Oldham, Michael C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Lim, Daniel A.] San Francisco VA Med Ctr, Surg Serv, San Francisco, CA USA. RP Lim, DA (reprint author), 35 Med Ctr Way, San Francisco, CA 94143 USA. EM limd@neurosurg.ucsf.edu OI Lim, Daniel/0000-0001-7221-3425; Margeta, Marta/0000-0001-6889-2488 FU VA BSLRD Merit Award [I01 BX000252]; National Institutes of Health [DP2 OD006505, R01-NS073765]; UCSF REAC/CTSI; National Institutes of Health NSRA [F32 NS073173]; UCSF Program for Breakthrough Biomedical Research; Sandler Foundation FX This work was supported by a VA BSLRD Merit Award (I01 BX000252), a National Institutes of Health New Innovator Award (DP2 OD006505), and a UCSF REAC/CTSI pilot award to Dr Lim; National Institutes of Health NSRA (F32 NS073173) to Dr Potts; a National Institutes of Health grant (R01-NS073765) to Dr Margeta; the UCSF Program for Breakthrough Biomedical Research, which is funded in part by the Sandler Foundation, to Dr Oldham; and facilities and resources provided by the San Francisco Veterans Affairs Medical Center. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. NR 50 TC 4 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X EI 1524-4040 J9 NEUROSURGERY JI Neurosurgery PD OCT PY 2014 VL 75 IS 4 BP 472 EP 482 DI 10.1227/NEU.0000000000000452 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AQ3AY UT WOS:000342662300041 PM 24887289 ER PT J AU Walker, RN Utech, A Velez, ME Schwartz, K AF Walker, Renee Nichole Utech, Anne Velez, Maria Eugenia Schwartz, Katie TI Delivered Volumes of Enteral Nutrition Exceed Prescribed Volumes SO NUTRITION IN CLINICAL PRACTICE LA English DT Article DE enteral nutrition; infusion pumps; energy intake ID RECEIVING MECHANICAL VENTILATION; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; ENERGY-EXPENDITURE; ACCURACY; ROUTE; PUMPS AB Background: Enteral nutrition (EN) provisions are typically calculated based on a 24-hour infusion period. However, feedings are often interrupted for daily activities, procedures, or gastrointestinal intolerance. The study's objective was to determine the delivered EN quantities provided to stable hospitalized patients, using cellular time and measured volumes to verify our EN calculation adjustment. Methods: A supply of consecutively numbered ready-to-hang (RTH) EN product was delivered to the bedside of 26 inpatients with established EN tolerance at goal rates on various types of nursing units. The dietitian weighed the volume remaining in the infusing product and recorded the measurement time. On the following days, the dietitian continued to weigh the infusing RTH product and the empty RTH bottles saved by nursing. The primary outcome was the difference between the prescribed and delivered EN provisions, which was calculated with a paired t test. Results: Patients received significantly more calories in the delivered enteral feeding (mean [SD], 1678 [385] kcal) than prescribed calories in the EN order (1489 [246 kcal]; t = 3.736, P = .001), adjusting for observed time. No significant differences were found between nursing units, product, and rate. Conclusion: EN delivered may actually exceed ordered amounts by 5%-21% (mean, 12%) with feeding pump inaccuracy as the primary contributing factor. This differs from what others have found. Our findings support using a volume-based ordering system vs a rate-based ordering system for more accurate EN delivery. C1 [Walker, Renee Nichole; Velez, Maria Eugenia; Schwartz, Katie] Michael E DeBakey Med Ctr, Houston, TX 77030 USA. [Utech, Anne] Vet Hlth Adm, Dept Vet Affairs, Houston, TX USA. [Utech, Anne; Velez, Maria Eugenia] Baylor Coll Med, Houston, TX 77030 USA. RP Walker, RN (reprint author), Michael E DeBakey Med Ctr, 2002 Holcombe Blvd,Rm 4a-340, Houston, TX 77030 USA. EM RNEW00@aol.com NR 13 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0884-5336 EI 1941-2452 J9 NUTR CLIN PRACT JI Nutr. Clin. Pract. PD OCT PY 2014 VL 29 IS 5 BP 662 EP 666 DI 10.1177/0884533614529998 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AQ5ME UT WOS:000342852500014 PM 25606647 ER PT J AU Field, AE Sonneville, KR Falbe, J Flint, A Haines, J Rosner, B Camargo, CA AF Field, Alison E. Sonneville, Kendrin R. Falbe, Jennifer Flint, Alan Haines, Jess Rosner, Bernard Camargo, Carlos A., Jr. TI Association of Sports Drinks with Weight Gain Among Adolescents and Young Adults SO OBESITY LA English DT Article ID SWEETENED BEVERAGE CONSUMPTION; SELF-REPORTED WEIGHT; PERFORMANCE; OBESITY; OVERWEIGHT; CHILDREN; SAMPLE; TRENDS; TRIAL; YOUTH AB ObjectiveSales of regular soda were declining, but sales of other sweetened beverages, such as sports drinks, were increasing. Our objective was to determine the prospective associations between sports drinks and body mass index (BMI) gains among adolescents and young adults. Methods4121 females and 3438 males in the Growing Up Today Study II, aged 9-16 in 2004, from across the United States were followed prospectively. Data were collected by questionnaire in 2004, 2006, 2008, and 2011. Servings per day of various beverages were assessed with a food frequency questionnaire. ResultsAmong the girls, each serving per day of sports drink predicted an increase of 0.3 BMI units (95% confidence interval (CI) CI 0.03-0.54) more than their peers over the next 2-3 years. Among the males, each serving of sports drinks predicted a 0.33 BMI (95% CI 0.09, 0.66) increase. In addition, boys who increased their intake over the 2-3 year interval gained significantly more than their peers during the same time interval. ConclusionsIntake of sports drinks predicted larger increases in BMI among both females and males. Our results suggest that school policies focused on obesity prevention should be augmented to restrict sports drinks. C1 [Field, Alison E.; Falbe, Jennifer] Boston Childrens Hosp, Dept Med, Div Adolescent Med, Boston, MA 02115 USA. [Field, Alison E.; Rosner, Bernard; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Field, Alison E.; Rosner, Bernard; Camargo, Carlos A., Jr.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Field, Alison E.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Falbe, Jennifer] Univ Calif Berkeley, Div Community Hlth & Human Dev, Berkeley, CA 94720 USA. [Flint, Alan] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Haines, Jess] Univ Guelph, Guelph, ON N1G 2W1, Canada. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Field, AE (reprint author), Boston Childrens Hosp, Dept Med, Div Adolescent Med, Boston, MA 02115 USA. EM Alison.Field@childrens.harvard.edu FU Breast Cancer Research Foundation; National Institutes of Health [R01-DK084001] FX Funding: This study was funded by the Breast Cancer Research Foundation and a grant (R01-DK084001) from the National Institutes of Health. NR 28 TC 7 Z9 7 U1 6 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD OCT PY 2014 VL 22 IS 10 BP 2238 EP 2243 DI 10.1002/oby.20845 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AQ4ET UT WOS:000342746800021 PM 25044989 ER PT J AU Gaskins, AJ Rich-Edwards, JW Colaci, DS Afeiche, MC Toth, TL Gillman, MW Missmer, SA Chavarro, JE AF Gaskins, Audrey J. Rich-Edwards, Janet W. Colaci, Daniela S. Afeiche, Myriam C. Toth, Thomas L. Gillman, Matthew W. Missmer, Stacey A. Chavarro, Jorge E. TI Prepregnancy and Early Adulthood Body Mass Index and Adult Weight Change in Relation to Fetal Loss SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ADVERSE PREGNANCY OUTCOMES; MATERNAL MEDICAL DISEASE; SPONTANEOUS-ABORTION; RISK-FACTORS; MISCARRIAGE; OBESITY; STILLBIRTH; METAANALYSIS; WOMEN; CONCEPTION AB OBJECTIVE: To examine prospectively the relationships of prepregnancy body mass index (BMI), BMI at age 18 years, and weight change since age 18 years with risk of fetal loss. METHODS: Our prospective cohort study included 25,719 pregnancies reported by 17,027 women in the Nurses' Health Study II between 1990 and 2009. In 1989, height, current weight, and weight at age 18 years were self-reported. Current weight was updated every 2 years thereafter. Pregnancies were self-reported, with case pregnancies lost spontaneously and comparison pregnancies ending in ectopic pregnancy, induced abortion, or live birth. RESULTS: Incident fetal loss was reported in 4,494 (17.5%) pregnancies. Compared with those of normal BMI, the multivariate relative risks of fetal loss were 1.07 (95% CI [confidence interval] 1.00-1.15) for overweight women, 1.10 (95% CI 0.98-1.23) for class I obese women, and 1.27 (95% CI 1.11-1.45) for class II and class III obese women (P trend <=.001). Body mass index at age 18 years was not associated with fetal loss (P trend=.59). Compared with women who maintained a stable weight (+/-4 kg) between age 18 years and before pregnancy, women who lost weight had a 20% (95% CI 9-29%) lower risk of fetal loss. This association was stronger among women who were overweight at age 18 years. CONCLUSION: Being overweight or obese before pregnancy was associated with higher risk of fetal loss. In women overweight or obese at age 18 years, losing 4 kg or more was associated with a lower risk of fetal loss. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA USA. Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. RP Gaskins, AJ (reprint author), Harvard Univ, Sch Publ Hlth, Bldg 2 3rd Floor, Boston, MA 02115 USA. EM agaskins@hsph.harvard.edu FU National Institutes of Health [T32DK007703-16, T32HD060454, UM1 CA176726] FX Supported by National Institutes of Health grants T32DK007703-16, T32HD060454, and UM1 CA176726. NR 39 TC 6 Z9 7 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2014 VL 124 IS 4 BP 662 EP 669 DI 10.1097/AOG.0000000000000478 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AQ4GZ UT WOS:000342753000003 PM 25198273 ER PT J AU Gaskins, AJ Afeiche, MC Wright, DL Toth, TL Williams, PL Gillman, MW Hauser, R Chavarro, JE AF Gaskins, Audrey J. Afeiche, Myriam C. Wright, Diane L. Toth, Thomas L. Williams, Paige L. Gillman, Matthew W. Hauser, Russ Chavarro, Jorge E. TI Dietary Folate and Reproductive Success Among Women Undergoing Assisted Reproduction SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID FOLIC-ACID; CARBON METABOLISM; UNITED-STATES; HEALTH; INFERTILITY; QUESTIONNAIRE; NUTRITION; PREGNANCY; VITAMINS; CANCER AB OBJECTIVE: To prospectively evaluate the associations of folate with assisted reproductive technology outcomes within a population in the United States. METHODS: This analysis included women (n=232) in a prospective cohort study at the Massachusetts General Hospital Fertility Center. Diet was assessed before assisted reproductive technology treatment using a validated food frequency questionnaire. Intermediate and clinical endpoints of assisted reproductive technology were abstracted from medical records. Generalized linear mixed models with random intercepts to account for multiple cycles per woman were used to evaluate the association of folate intake with assisted reproductive technology outcomes adjusting for calorie intake, age, body mass index, race, smoking status, infertility diagnosis, and protocol type. RESULTS: Among the 232 women (median age 35.2 years, median folate intake 1,778 micrograms/day), higher folate intake was associated with higher rates of implantation, clinical pregnancy, and live birth. The adjusted percentage (95% confidence interval [CI]) of initiated assisted reproductive technology cycles resulting in a live birth for women in increasing quartiles of folate intake were 30% (95% CI 21-42%), 47% (95% CI 35-59%), 42% (95% CI 30-35%) and 56% (95% CI 4367%) (P for trend=0.01). Live birth rates were 20% (95% CI 8-31%) higher among women in the highest quartile of supplemental folate intake (more than 800 micrograms/day) than among women in the lowest quartile (less than 400 micrograms/day). Higher supplemental folate intake was associated with higher fertilization rates and lower cycle failure rates before embryo transfer (P for trend=0.03 and 0.02). CONCLUSION: Higher intake of supplemental folate was associated with higher live birth rates after assisted reproductive technology treatment. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dept Populat Med, Cambridge, MA 02138 USA. Harvard Pilgrim Hlth Care Inst, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Gaskins, AJ (reprint author), Harvard Univ, Sch Publ Hlth, Bldg II 3rd Floor 655 Huntingt Ave, Boston, MA 02115 USA. EM ajg219@mail.harvard.edu FU NIH [R01-ES009718, R01-ES022955, P30-DK046200, T32-DK007703-16, T32-HD060454] FX Supported by NIH grants R01-ES009718, R01-ES022955, P30-DK046200, T32-DK007703-16, and T32-HD060454. NR 35 TC 12 Z9 13 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2014 VL 124 IS 4 BP 801 EP 809 DI 10.1097/AOG.0000000000000477 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AQ4GZ UT WOS:000342753000022 PM 25198264 ER PT J AU Suhler, EB Lim, LL Beardsley, RM Giles, TR Pasadhika, S Lee, ST de Saint Sardos, A Butler, NJ Smith, JR Rosenbaum, JT AF Suhler, Eric B. Lim, Lyndell L. Beardsley, Robert M. Giles, Tracy R. Pasadhika, Sirichai Lee, Shelly T. de Saint Sardos, Alexandre Butler, Nicholas J. Smith, Justine R. Rosenbaum, James T. TI Rituximab Therapy for Refractory Scleritis Results of a Phase I/II Dose-Ranging, Randomized, Clinical Trial SO OPHTHALMOLOGY LA English DT Article ID RHEUMATOID-ARTHRITIS; DOUBLE-BLIND; DISEASE; MULTICENTER AB Objective: To determine whether rituximab, a monoclonal antibody against the B-lymphocyte antigen CD20, is effective in the treatment of refractory noninfectious scleritis. Design: Prospective, dose-ranging, randomized, double-masked phase I/II clinical trial. Participants: Twelve patients with noninfectious scleritis refractory to systemic corticosteroid and >= 1 other systemic immunosuppressive agent were enrolled from January 2007 to March 2010. Intervention: Subjects were randomly assigned to 500 (n = 5) or 1000 mg (n = 7) dosing arms of rituximab intravenous infusions (500 or 1000 mg), given at study days 1 and 15. Initial responders with breakthrough inflammation after study week 24 were offered treatment with an additional cycle of 2 open-label rituximab 1000 mg infusions. Main Outcome Measures: Primary outcomes were reduction of inflammation, as measured with a validated scleritis disease grading scale (SGS) and reduction in corticosteroid dose by >= 50%. Patients were characterized as responders to study therapy if >= 1 of these endpoints showed improvement and neither showed evidence of worsening. Secondary outcomes were improvement in visual acuity, reduction in pain, and improvement in patient and physician-reported global health assessment. Results: Of 12 enrolled patients, 9 met the SGS endpoint at or before week 24, and 4 additionally were able to reduce corticosteroid dose by >= 50%. With regard to secondary outcome measures, 11 and 9 patients showed improvement in patient and physician global health scores, respectively, and 7 patients had reduction in pain. Of 9 initial responders, 7 experienced breakthrough inflammation after 24 weeks and were treated with a second cycle of rituximab infusions. Four patients had significant objective or subjective worsening within 8 weeks of receiving rituximab; this event was averted in subsequent patients by treatment with peri-infusional oral corticosteroid. No other significant adverse events were noted. No differences in efficacy, toxicity, or likelihood of retreatment were noted between the dosing arms. Conclusions: Rituximab was effective treatment for 9 of 12 enrolled patients with refractory, noninfectious scleritis at 24 weeks, although 7 required reinfusion with rituximab to maintain inflammatory control. The treatment was well-tolerated, and peri-infusional inflammatory exacerbations were managed successfully with oral corticosteroids. Further long-term studies are warranted to determine the safety and efficacy of rituximab in treating noninfectious scleritis and other ocular inflammatory diseases. (C) 2014 by the American Academy of Ophthalmology. C1 [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Suhler, Eric B.; Lim, Lyndell L.; Beardsley, Robert M.; Giles, Tracy R.; Pasadhika, Sirichai; Lee, Shelly T.; de Saint Sardos, Alexandre; Butler, Nicholas J.; Smith, Justine R.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Casey Eye Inst, Portland, OR 97201 USA. [Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med & Cell & Dev Biol, Portland, OR 97201 USA. [Smith, Justine R.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Dev Biol, Portland, OR 97201 USA. [Lim, Lyndell L.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia. [Smith, Justine R.] Flinders Univ S Australia, Adelaide, SA 5001, Australia. [Rosenbaum, James T.] Devers Eye Inst, Portland, OR USA. RP Suhler, EB (reprint author), Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM suhlere@ohsu.edu OI Lim, Lyndell/0000-0003-2491-685X FU Department of Veterans'Affairs; Genentech (San Francisco, CA); Research to Prevent Blindness grant (unrestricted grant to Casey Eye Institute); Rosenfeld Family Trust; William and Mary Bauman Foundation; Genentech; Abbott/Abbvie; Bristol-Myers-Squibb; EyeGate; LuxBio; Novartis FX E. B. S.: Research Supportd-Department of Veterans'Affairs; Supported in part by Genentech (San Francisco, CA). The funding organization had no role in the design or conduct of this research. Funded by a Research to Prevent Blindness grant (unrestricted grant to Casey Eye Institute), the Rosenfeld Family Trust (J. T. R.), and the William and Mary Bauman Foundation. The OHSU Uveitis Clinic has received research support from Genentech, Abbott/Abbvie, Bristol-Myers-Squibb, EyeGate, LuxBio, and Novartis. NR 23 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 2014 VL 121 IS 10 BP 1885 EP 1891 DI 10.1016/j.ophtha.2014.04.044 PG 7 WC Ophthalmology SC Ophthalmology GA AQ3ME UT WOS:000342697300017 PM 24953794 ER PT J AU Tunkel, DE Bauer, CA Sun, GH Rosenfeld, RM Chandrasekhar, SS Cunningham, ER Archer, SM Blakley, BW Carter, JM Granieri, EC Henry, JA Hollingsworth, D Khan, FA Mitchell, S Monfared, A Newman, CW Omole, FS Phillips, CD Robinson, SK Taw, MB Tyler, RS Waguespack, R Whamond, EJ AF Tunkel, David E. Bauer, Carol A. Sun, Gordon H. Rosenfeld, Richard M. Chandrasekhar, Sujana S. Cunningham, Eugene R., Jr. Archer, Sanford M. Blakley, Brian W. Carter, John M. Granieri, Evelyn C. Henry, James A. Hollingsworth, Deena Khan, Fawad A. Mitchell, Scott Monfared, Ashkan Newman, Craig W. Omole, Folashade S. Phillips, C. Douglas Robinson, Shannon K. Taw, Malcolm B. Tyler, Richard S. Waguespack, Richard Whamond, Elizabeth J. TI Clinical Practice Guideline: Tinnitus Executive Summary SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE tinnitus; hearing loss; quality of life; sound therapy; hearing aids; amplification AB The American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) has published a supplement to this issue featuring the new Clinical Practice Guideline: Tinnitus. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 13 recommendations developed address the evaluation of patients with tinnitus, including selection and timing of diagnostic testing and specialty referral to identify potential underlying treatable pathology. It will then focus on the evaluation and treatment of patients with persistent primary tinnitus, with recommendations to guide the evaluation and measurement of the impact of tinnitus and to determine the most appropriate interventions to improve symptoms and quality of life for tinnitus sufferers. C1 [Tunkel, David E.] Johns Hopkins Outpatient Ctr, Baltimore, MD 21287 USA. [Bauer, Carol A.] So Illinois Univ, Sch Med, Div Otolaryngol Head & Neck Surg, Springfield, IL USA. [Sun, Gordon H.] Partnership Hlth Analyt Res LLC, Los Angeles, CA USA. [Rosenfeld, Richard M.] Suny Downstate Med Ctr, Dept Otolaryngol, Brooklyn, NY 11203 USA. [Chandrasekhar, Sujana S.] New York Otol, New York, NY USA. [Cunningham, Eugene R., Jr.] Head & Neck Surg Fdn, Amer Acad Otolaryngol, Dept Res & Qual Improvement, Alexandria, VA USA. [Archer, Sanford M.] Univ Kentucky, Div Rhinol & Sinus Surg, Lexington, KY USA. [Archer, Sanford M.] Univ Kentucky, Div Facial Plast & Reconstruct Surg, Lexington, KY USA. [Blakley, Brian W.] Univ Manitoba, Dept Otolaryngol, Winnipeg, MB, Canada. [Carter, John M.] Tulane Univ, Dept Otolaryngol, New Orleans, LA 70118 USA. [Granieri, Evelyn C.] Columbia Univ, Div Geriatr Med & Aging, New York, NY USA. [Henry, James A.] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR USA. [Hollingsworth, Deena] ENT Specialists Northern Virginia, Falls Church, VA USA. [Khan, Fawad A.] Ochsner Hlth Syst, Kenner, LA USA. [Mitchell, Scott] Mitchell & Cavallo PC, Houston, TX USA. [Monfared, Ashkan] George Washington Univ, Dept Otol & Neurotol, Washington, DC USA. [Newman, Craig W.] Cleveland Clin, Lerner Coll Med, Dept Surg, Cleveland, OH 44106 USA. [Omole, Folashade S.] Morehouse Sch Med, East Point, GA USA. [Phillips, C. Douglas] New York Presbyterian Hosp, Weill Cornell Med Ctr, Dept Head & Neck Imaging, New York, NY USA. [Robinson, Shannon K.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Taw, Malcolm B.] Univ Calif Los Angeles, Dept Med, Ctr East West Med, Los Angeles, CA 90024 USA. [Tyler, Richard S.] Univ Iowa, Dept Otolaryngol Head & Neck Surg, Iowa City, IA 52242 USA. [Waguespack, Richard] Univ Alabama Birmingham, Sch Med, Dept Surg, Birmingham, AL 35294 USA. [Whamond, Elizabeth J.] Consumers United Evidence Based Healthcare, Fredericton, NB, Canada. RP Tunkel, DE (reprint author), Johns Hopkins Outpatient Ctr, Room 6231,601 North Caroline St,Rm 6231, Baltimore, MD 21287 USA. EM dtunkel@jhmi.edu OI Phillips, C. Douglas/0000-0003-1773-8899 FU American Academy of Otolaryngology-Head and Neck Surgery Foundation FX American Academy of Otolaryngology-Head and Neck Surgery Foundation. NR 8 TC 5 Z9 5 U1 1 U2 16 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 2014 VL 151 IS 4 BP 533 EP 541 DI 10.1177/0194599814547475 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AQ7HI UT WOS:000342982900004 PM 25274374 ER PT J AU Rogers, DJ Setlur, J Raol, N Maurer, R Hartnick, CJ AF Rogers, Derek J. Setlur, Jennifer Raol, Nikhila Maurer, Rie Hartnick, Christopher J. TI Evaluation of True Vocal Fold Growth as a Function of Age SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE vocal fold length; pediatric voice; pediatric laryngology ID PERTURBATION MEASURES; HORIZONTAL SECTIONS; VOICE FREQUENCY; LENGTH; DATABASE; CHILDREN; LARYNX; MORPHOMETRY; CONSISTENCY AB Objective. To evaluate change in true vocal fold length as a function of age. Study Design. Prospective study. Setting. Tertiary aerodigestive center. Subjects and Methods. In total, 205 patients (aged 1 month to 20 years), of whom 87 (42.4%) were female and 118 (57.6%) male, were included. Lengths of the total vocal fold (TVFL), membranous vocal fold (MVFL), and cartilaginous vocal fold (CVFL) were measured during direct laryngoscopy. Membranous-to-cartilaginous (M/C) ratios were calculated. Results. For patients younger than 1 year, mean (SD) MVFL was 4.4 (1.3) mm for females and 4.9 (1.8) mm for males. At age 17 years, mean (SD) MVFL was 12.3 (2.1) mm for females and 14.0 (1.4) mm for males. Mean TVFL, MVFL, and CVFL increased an average of 0.7 mm, 0.5 mm, and 0.2 mm per year in linear fashion, respectively (linear regression, P < .0001). The M/C ratio did not significantly change with age (P = .33). Mean TVFL, MVFL, and CVFL showed no statistical difference between males and females (P = .27, .11, and .75, respectively). Conclusion. This is the largest longitudinal pediatric study specifically examining vocal fold length as a function of age. Each length of the true vocal fold appeared to linearly increase for both females and males. The M/C ratio remained relatively constant, unlike previously reported data, possibly due to in vivo vs cadaveric measurements. These findings suggest that critical periods of development in females and males are not explainable by changes in vocal fold length alone, and other factors such as vocal fold layers need further exploration. C1 [Rogers, Derek J.; Raol, Nikhila; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Setlur, Jennifer] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Maurer, Rie] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. [Maurer, Rie] Harvard Catalyst, Boston, MA USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu NR 20 TC 3 Z9 3 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 2014 VL 151 IS 4 BP 681 EP 686 DI 10.1177/0194599814547489 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AQ7HI UT WOS:000342982900024 PM 25171926 ER PT J AU Corey, KE Stanley, TL Misdraji, J Scirica, C Pratt, J Hoppin, A Misra, M AF Corey, K. E. Stanley, T. L. Misdraji, J. Scirica, C. Pratt, J. Hoppin, A. Misra, M. TI Prevalence and outcome of non-alcoholic fatty liver disease in adolescents and young adults undergoing weight loss surgery SO PEDIATRIC OBESITY LA English DT Article DE Adolescence; non-alcoholic fatty liver disease; obesity; Roux-en-Y gastric bypass AB Background/ObjectiveWe evaluated the prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) in 27 adolescents referred for weight loss surgery (WLS). ResultsOn biopsy, 18 patients (66.7%) had NAFLD, and of those, 10 (37.0%) had NASH and 11 (40.7%) had fibrosis. Insulin, HbA1C and homeostatic model assessment of insulin resistance (HOMA-IR) were significantly higher in patients with NASH than those without NASH. Following WLS, 40% of patients with NASH had persistently elevated aminotransferase levels despite weight loss. ConclusionWe found that NASH is underdiagnosed in adolescents referred for WLS, and that hyperinsulinaemia, HOMA-IR and HbA1c can aid in identifying high-risk patients. C1 [Corey, K. E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Corey, K. E.; Stanley, T. L.; Misdraji, J.; Scirica, C.; Pratt, J.; Hoppin, A.; Misra, M.] Harvard Univ, Sch Med, Boston, MA USA. [Corey, K. E.; Scirica, C.; Pratt, J.; Hoppin, A.] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Stanley, T. L.; Misra, M.] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Stanley, T. L.; Misdraji, J.; Misra, M.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Misdraji, J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Corey, KE (reprint author), Massachusetts Gen Hosp, GI Associates Blake 4,55 Fruit St, Boston, MA 02114 USA. EM kcorey@partners.org FU American Association for the Study of Liver Disease Clinical and Translational Award; National Institutes of Health [T32HD052961, K23DK089910] FX Provided in part by American Association for the Study of Liver Disease Clinical and Translational Award (KEC), National Institutes of Health T32HD052961 to MM and K23DK089910 to T.L.S. NR 7 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-6310 EI 2047-6302 J9 PEDIATR OBES JI Pediatr. Obes. PD OCT PY 2014 VL 9 IS 5 BP E91 EP E93 DI 10.1111/j.2047-6310.2014.219.x PG 3 WC Pediatrics SC Pediatrics GA AQ7KA UT WOS:000342991900004 PM 24677740 ER PT J AU Jackson, JW VanderWeele, TJ Blacker, D Schneeweiss, S AF Jackson, John W. VanderWeele, Tyler J. Blacker, Deborah Schneeweiss, Sebastian TI Mediators of the Causal Pathway to Mortality in Older Adults Who Use Antipsychotics SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Jackson, John W.; Schneeweiss, Sebastian] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Jackson, John W.; Blacker, Deborah; Schneeweiss, Sebastian] Harvard Univ, Sch Med, Boston, MA USA. [Jackson, John W.; VanderWeele, Tyler J.; Blacker, Deborah; Schneeweiss, Sebastian] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Blacker, Deborah] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Schneeweiss, Sebastian/C-2125-2013 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 14 BP 8 EP 8 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600015 ER PT J AU Bateman, BT Franklin, JM Bykov, K Huybrechts, KF Fischer, MA Choudhry, NK AF Bateman, Brian T. Franklin, Jessica M. Bykov, Katsiaryna Huybrechts, Krista F. Fischer, Michael A. Choudhry, Niteesh K. TI Persistent Opioid Use Following Cesarean Delivery: Patterns and Predictors among Opioid Naive Women SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Bateman, Brian T.; Franklin, Jessica M.; Bykov, Katsiaryna; Huybrechts, Krista F.; Fischer, Michael A.; Choudhry, Niteesh K.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.; Franklin, Jessica M.; Bykov, Katsiaryna; Huybrechts, Krista F.; Fischer, Michael A.; Choudhry, Niteesh K.] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 36 BP 20 EP 20 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600037 ER PT J AU Bateman, BT Hernandez-Diaz, S Mogun, H Fischer, MA Huybrechts, KF AF Bateman, Brian T. Hernandez-Diaz, Sonia Mogun, Helen Fischer, Michael A. Huybrechts, Krista F. TI Statins during Pregnancy and the Risk of Congenital Malformations: A Cohort Study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Bateman, Brian T.; Mogun, Helen; Fischer, Michael A.; Huybrechts, Krista F.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.; Mogun, Helen; Fischer, Michael A.; Huybrechts, Krista F.] Harvard Univ, Sch Med, Boston, MA USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 42 BP 23 EP 24 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600043 ER PT J AU Chen, CY Stewart, GC Stevenson, LW Bhatt, DL Desai, M Seeger, JD Williams, L Jalbert, JJ Setoguchi, S AF Chen, Chih-Ying Stewart, Garrick C. Stevenson, Lynne W. Bhatt, Deepak L. Desai, Manisha Seeger, John D. Williams, Lauren Jalbert, Jessica J. Setoguchi, Soko TI Real-World Effectiveness of Primary ICDs Implanted during Unplanned Medicare Hospitalizations SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Chen, Chih-Ying; Seeger, John D.; Williams, Lauren; Jalbert, Jessica J.; Setoguchi, Soko] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Chen, Chih-Ying; Bhatt, Deepak L.; Seeger, John D.; Jalbert, Jessica J.; Setoguchi, Soko] Harvard Univ, Sch Med, Boston, MA USA. [Stewart, Garrick C.; Stevenson, Lynne W.; Bhatt, Deepak L.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Desai, Manisha] Stanford Univ, Sch Med, Quantitat Sci Unit, Palo Alto, CA 94304 USA. [Setoguchi, Soko] Duke Clin Res Inst, Durham, NC 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 50 BP 28 EP 28 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600051 ER PT J AU Hernandez-Diaz, S Bateman, B Huybrechts, K AF Hernandez-Diaz, Sonia Bateman, Brian Huybrechts, Krista TI Impact of Right Truncation in Studies of Drug Safety during Pregnancy SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bateman, Brian; Huybrechts, Krista] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian; Huybrechts, Krista] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 313 BP 165 EP 166 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600313 ER PT J AU Huybrechts, K Bateman, B Levin, R Mogun, H Hernandez-Diaz, S AF Huybrechts, Krista Bateman, Brian Levin, Raisa Mogun, Helen Hernandez-Diaz, Sonia TI Comparative Safety of Depression Treatments in Late Pregnancy for the Neonate SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Huybrechts, Krista; Bateman, Brian; Levin, Raisa; Mogun, Helen] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 314 BP 166 EP 166 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600314 ER PT J AU Kim, SC Glynn, R Liu, J Everett, B Goldfine, A AF Kim, Seoyoung C. Glynn, Robert Liu, Jun Everett, Brendan Goldfine, Allison TI Dipeptidyl Peptidase-4 Inhibitors Do Not Increase the Risk of Cardiovascular Events in Type 2 Diabetes SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Kim, Seoyoung C.; Glynn, Robert; Liu, Jun; Everett, Brendan] Brigham & Womens Hosp, Boston, MA 02115 USA. [Goldfine, Allison] Joslin Diabet Ctr, Boston, MA 02215 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 357 BP 188 EP 189 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600356 ER PT J AU Eguale, T Seger, DL Slight, SP Amato, MG Nanji, KC Maniam, N Dykes, PC Fiskio, JM Bates, DW AF Eguale, Tewodros Seger, Diane L. Slight, Sarah P. Amato, Mary G. Nanji, Karen C. Maniam, Nivethietha Dykes, Patricia C. Fiskio, Julie M. Bates, David W. TI Drug-Drug Interaction Alerts in Hospital Setting: Distribution, the Prevalence of Overrides, and Prescriber Determinants SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Eguale, Tewodros; Seger, Diane L.; Slight, Sarah P.; Amato, Mary G.; Nanji, Karen C.; Maniam, Nivethietha; Dykes, Patricia C.; Fiskio, Julie M.; Bates, David W.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Eguale, Tewodros; Bates, David W.] Harvard Univ, Sch Med, Boston, MA USA. [Eguale, Tewodros] McGill Univ, Dept Med, Montreal, PQ, Canada. [Seger, Diane L.; Maniam, Nivethietha; Dykes, Patricia C.; Fiskio, Julie M.; Bates, David W.] Partners Healthcare Syst Inc, Boston, MA USA. [Slight, Sarah P.] Univ Durham, Sch Med Pharm & Hlth, Durham, England. [Amato, Mary G.] MCPHS Univ, Boston, MA USA. [Nanji, Karen C.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 457 BP 241 EP 241 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600453 ER PT J AU Strosberg, JR Benson, AB Huynh, L Duh, MS Goldman, J Sahai, V Rademaker, AW Kulke, MH AF Strosberg, Jonathan R. Benson, Al B. Huynh, Lynn Duh, Mei Sheng Goldman, Jamie Sahai, Vaibhav Rademaker, Alfred W. Kulke, Matthew H. TI Above Standard Dose of Octreotide-LAR in Patients with Neuroendocrine Tumors (NET) for Control of Carcinoid Syndrome Symptoms: A Multi-Center Retrospective Chart Review Study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Strosberg, Jonathan R.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept GI Oncol, Tampa, FL 33612 USA. [Benson, Al B.; Sahai, Vaibhav; Rademaker, Alfred W.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Huynh, Lynn; Duh, Mei Sheng] Anal Grp Inc, Boston, MA USA. [Goldman, Jamie] Univ S Florida, Dept Internal Med, Tampa, FL 33612 USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 481 BP 253 EP 254 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600477 ER PT J AU Setoguchi, S Williams, L Chen, CY Wong, M Clard, M Cheung, W Lai, ECC AF Setoguchi, Soko Williams, Lauren Chen, Chih-Ying Wong, Monera Clard, Melissa Cheung, Winson Lai, Edward Chia-Cheng TI Cognitive Health, Willingness to Live, and Social Support but Not Physical Function May Be the Source of Healthy User Bias SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Setoguchi, Soko; Lai, Edward Chia-Cheng] Duke Clin Res Inst, Durhan, NC USA. [Williams, Lauren] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chen, Chih-Ying] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wong, Monera] Brown Univ, Providence, RI 02912 USA. [Clard, Melissa] British Columbia Canc Agcy, Vancouver, BC, Canada. [Cheung, Winson] Cheng Kong Univ, Tainan, Taiwan. NR 0 TC 0 Z9 0 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 OCT PY 2014 VL 23 SU 1 SI SI MA 490 BP 259 EP 259 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600486 ER PT J AU Broussard, CS Frey, MT Hernandez-Diaz, S Greene, MF Chambers, CD Sahin, L Sharp, BAC Honein, MA AF Broussard, Cheryl S. Frey, Meghan T. Hernandez-Diaz, Sonia Greene, Michael F. Chambers, Christina D. Sahin, Leyla Sharp, Beth A. Collins Honein, Margaret A. TI Developing a Systematic Approach to Safer Medication Use during Pregnancy: Summary of a Centers for Disease Control and Prevention-Convened Meeting SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Broussard, Cheryl S.; Frey, Meghan T.; Honein, Margaret A.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. [Frey, Meghan T.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Greene, Michael F.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Greene, Michael F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chambers, Christina D.] Univ Calif San Francisco, Dept Pediat, La Jolla, CA USA. [Chambers, Christina D.] Univ Calif San Francisco, Dept Family & Prevent Med, La Jolla, CA USA. [Sahin, Leyla] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Sharp, Beth A. Collins] Agcy Healthcare Res & Qual, Rockville, MD 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 594 BP 315 EP 315 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600590 ER PT J AU Lai, ECC Wong, M Iwata, I Zhang, YH Hsieh, CY Yang, YHK Setoguchi, S AF Lai, Edward Chia-Cheng Wong, Monera Iwata, Isao Zhang, Yinghong Hsieh, Cheng Yang Yang, Yea-Huei Kao Setoguchi, Soko TI Comparative Risk of Pneumonia among Different Cholinesterase Inhibitors SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Lai, Edward Chia-Cheng; Hsieh, Cheng Yang; Yang, Yea-Huei Kao] Natl Cheng Kung Univ, Inst Clin Pharm & Pharmaceut Sci, Tainan 70101, Taiwan. [Lai, Edward Chia-Cheng; Zhang, Yinghong; Setoguchi, Soko] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Wong, Monera] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Iwata, Isao] Univ N Carolina, Div Geriatr Med, Chapel Hill, NC USA. [Yang, Yea-Huei Kao] Natl Cheng Kung Univ, Hlth Outcome Res Ctr, Tainan 70101, Taiwan. [Hsieh, Cheng Yang] Tainan Sin Lau Hosp, Dept Neurol, Tainan, Taiwan. 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 642 BP 343 EP 343 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600638 ER PT J AU van den Ham, HA Klungel, OH Singer, DE Leufkens, HGM van Staa, TP AF van den Ham, Hendrika A. Klungel, Olaf H. Singer, Daniel E. Leufkens, Hubert G. M. van Staa, Tjeerd P. TI Comparison of ATRIA and CHA2DS2-VASc Risk Stratification Schemes for the Prediction of Stroke in the Individual Patient with Atrial Fibrillation and the Impact on Treatment Decisions SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [van den Ham, Hendrika A.; Klungel, Olaf H.; Leufkens, Hubert G. M.; van Staa, Tjeerd P.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands. [Singer, Daniel E.] Massachusetts Gen Hosp, Dept Epidemiol, Boston, MA 02114 USA. [van Staa, Tjeerd P.] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England. RI Klungel, Olaf/I-9563-2016 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 672 BP 359 EP 360 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600667 ER PT J AU Zhou, X Weiss, L Walker, AM Ananthakrishnan, AN Shen, R Sobel, RE Bate, A Reynolds, RF AF Zhou, X. Weiss, L. Walker, A. M. Ananthakrishnan, A. N. Shen, R. Sobel, R. E. Bate, A. Reynolds, R. F. TI What Does Natural Language Processing Add to the Structured Data Available in Medical Records? SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Zhou, X.; Weiss, L.; Shen, R.; Sobel, R. E.; Bate, A.; Reynolds, R. F.] Pfizer Inc, Epidemiol, Nyc, NY USA. [Walker, A. M.] WHISCON, Newton, MA USA. [Ananthakrishnan, A. N.] 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 739 BP 397 EP 398 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600734 ER PT J AU Funch, DP Ross, DS Gardstein, BM Norman, HS Sanders, LA Major-Pedersen, A Kring, SII Dore, DD AF Funch, Donnie P. Ross, Douglas S. Gardstein, Betsey M. Norman, Heather S. Sanders, Lauren A. Major-Pedersen, Atheline Kring, Sofia I. I. Dore, David D. TI Performance of Claims-Based Algorithms for Identifying Thyroid Cancer in Commercial Health Plan Enrollees Receiving Antidiabetic Therapies SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Funch, Donnie P.; Gardstein, Betsey M.; Norman, Heather S.; Sanders, Lauren A.; Dore, David D.] Optum, Epidemiol, Waltham, MA USA. [Ross, Douglas S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ross, Douglas S.] Harvard Univ, Sch Med, Boston, MA USA. [Major-Pedersen, Atheline] Novo Nordisk AS, Global Safety, DK-2880 Bagsvaerd, Denmark. [Kring, Sofia I. I.] Novo Nordisk AS, Epidemiol, Soborg, Denmark. [Dore, David D.] Brown Univ, Sch Publ Hlth, Providence, RI 02912 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 785 BP 422 EP 422 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600779 ER PT J AU Jalbert, JJ Nguyen, LL Gerhard-Herman, MD Jaff, MR Seeger, JD Kumamaru, H Williams, LA Liu, J Chen, CY Setoguchi, S AF Jalbert, Jessica J. Nguyen, Louis L. Gerhard-Herman, Marie D. Jaff, Michael R. Seeger, John D. Kumamaru, Hiraku Williams, Lauren A. Liu, Jun Chen, Chih-Ying Setoguchi, Soko TI How Do Routine Care Carotid Artery Stenting Patients Fare Compared to Those Enrolled in Trials? SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Jalbert, Jessica J.; Seeger, John D.; Kumamaru, Hiraku; Williams, Lauren A.; Liu, Jun; Chen, Chih-Ying; Setoguchi, Soko] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Jalbert, Jessica J.] LA SER Analyt, New York, NY USA. [Nguyen, Louis L.] Brigham & Womens Hosp, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. [Gerhard-Herman, Marie D.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Div Cardiovasc Med, Boston, MA 02114 USA. [Seeger, John D.] OptumInsight Epidemiol, Waltham, MA USA. [Setoguchi, Soko] Duke Clin Res Inst, Durham, NC 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 906 BP 487 EP 488 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600898 ER PT J AU Tsai, HT Keating, NL Yood, MU Van Den Eeden, SK Haque, R Cassidy-Bushrow, AE Smith, MR Potosky, AL AF Tsai, Huei-Ting Keating, Nancy L. Yood, Marianne Ulcickas Van Den Eeden, Stephen K. Haque, Reina Cassidy-Bushrow, Andrea E. Smith, Matthew R. Potosky, Arnold L. TI Risk of Diabetes among Patients Exposed to Primary Androgen Deprivation Therapy for Clinically Localized Prostate Cancer SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Tsai, Huei-Ting; Potosky, Arnold L.] Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Keating, Nancy L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Hlth Care Policy,Div Gen Internal Med, Boston, MA 02115 USA. [Yood, Marianne Ulcickas] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Van Den Eeden, Stephen K.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Haque, Reina] Kaiser Permanente So Calif, Div Res & Evaluat, Pasadena, CA 91101 USA. [Cassidy-Bushrow, Andrea E.] Henry Ford Hosp, Dept Publ Hlth Sci, Detroit, MI 48202 USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Genitorurinary Oncol Program, Boston, MA 02114 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2014 VL 23 SU 1 SI SI MA 923 BP 496 EP 496 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AQ4JZ UT WOS:000342763600913 ER PT J AU Adamson, B Attridge, RT AF Adamson, Braden Attridge, Russell T. TI Risk factors for resistant pathogens in community-dwelling pneumonia patients from 2001 to 2010. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy (ACCP) CY OCT 12-15, 2014 CL Austin, TX SP Amer Coll Clin Pharm C1 [Adamson, Braden] Univ Incarnate Word, Feik Sch Phamracy, Dept Pharm Practice, San Antonio, TX USA. [Attridge, Russell T.] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 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 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2014 VL 34 IS 10 MA 314 BP E260 EP E260 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AQ6JF UT WOS:000342916800257 ER PT J AU Lee, TC Attridge, RL Cota, JM Horlen, CK Attridge, RT AF Lee, Tina C. Attridge, Rebecca L. Cota, Jason M. Horlen, Cheryl K. Attridge, Russell T. TI Median potassium increases and the effect of patient-specific factors with potassium supplementation in hospitalized adults. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy (ACCP) CY OCT 12-15, 2014 CL Austin, TX SP Amer Coll Clin Pharm C1 [Lee, Tina C.; Cota, Jason M.; Horlen, Cheryl K.] Univ Incarnate Word, Feik Sch Pharm, San Antonio, TX USA. [Attridge, Rebecca L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Attridge, Russell T.] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 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 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2014 VL 34 IS 10 MA 294 BP E254 EP E254 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AQ6JF UT WOS:000342916800237 ER PT J AU Trester, M Wang, L Chao, S Maddix, D AF Trester, Marissa Wang, Lorraine Chao, Shirley Maddix, Daniel TI Comparing estimated glomerular filtration rates based on serum creatinine versus serum cystatin C and effect on renal dosing of medications. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy (ACCP) CY OCT 12-15, 2014 CL Austin, TX SP Amer Coll Clin Pharm C1 [Trester, Marissa; Wang, Lorraine; Chao, Shirley; Maddix, Daniel] San Francisco VA Med Ctr, Serv Pharm, San Francisco, CA 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 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2014 VL 34 IS 10 MA 178 BP E222 EP E223 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AQ6JF UT WOS:000342916800135 ER PT J AU Ikeda, AJ Grabowski, AM Lindsley, A Sadeghi-Demneh, E Reisinger, KD AF Ikeda, Andrea J. Grabowski, Alena M. Lindsley, Alida Sadeghi-Demneh, Ebrahim Reisinger, Kim D. TI A scoping literature review of the provision of orthoses and prostheses in resource-limited environments 2000-2010. Part two: Research and outcomes SO PROSTHETICS AND ORTHOTICS INTERNATIONAL LA English DT Review DE Prosthetics and orthotics in developing countries; developing countries; prosthetics and orthotics services in low-income countries; orthotics; prosthetics ID LOW-INCOME COUNTRIES; TRANS-TIBIAL AMPUTEES; FIELD FOLLOW-UP; PONSETI METHOD; TRANSTIBIAL PROSTHESES; CLUBFOOT DEFORMITY; FEMORAL AMPUTEES; DEVELOPING-WORLD; LIMB AMPUTEES; FEET AB Background: Despite the activities of many orthotic and prosthetic provision organizations in resource-limited environments, there is still a great need and there are several areas for improvement, as identified in Part One of this series. Objectives: Our goal was to examine outcomes and conclusions of research studies to produce an evidence base for determining factors that may lead to successful provision of orthoses and prostheses in resource-limited environments. Study design: Literature review. Methods: We conducted a scoping literature review of all information related to orthotic and prosthetic provision in resource-limited environments published from 2000 to 2010. We extracted measured outcomes reported in all types of articles and analyzed conclusions from research studies. Results: Reported outcomes included durability, cost, satisfaction, use/nonuse of device, amount of utilization, walking speed, discomfort, pain, fit, misalignment, capacity for service provision, number of devices produced or delivered, and number of graduates from training programs. Conclusions: There are many gaps in the evidence base, notably in measuring inclusion, participation, and quality of life for orthosis and prosthesis users in resource-limited environments. There is a paucity of reported outcomes for orthotics. Valid, reliable, and standard methods of data collection and reporting are needed to advance the field and enhance the evidence base. C1 [Ikeda, Andrea J.; Lindsley, Alida; Reisinger, Kim D.] San Francisco State Univ, Whirlwind Wheelchair Int, San Francisco, CA 94132 USA. [Grabowski, Alena M.] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA. [Sadeghi-Demneh, Ebrahim] Isfahan Univ Med Sci, Orthot & Prosthet Dept, Musculoskeletal Res Ctr, Esfahan, Iran. [Grabowski, Alena M.] US Dept Vet Affairs, Eastern Colorado Healthcare Syst, Denver, CO USA. RP Ikeda, AJ (reprint author), San Francisco State Univ, Whirlwind Wheelchair Int, 1600 Holloway Ave,SCI 251, San Francisco, CA 94132 USA. EM andrea@whirlwindwheelchair.org RI Sadeghi-Demneh, Ebrahim/E-8110-2012; OI Sadeghi-Demneh, Ebrahim/0000-0003-0590-8512; GRABOWSKI, ALENA/0000-0002-4432-618X FU US Department of Education, National Institute on Disability and Rehabilitation Research [H133A090020] FX This work was supported by the US Department of Education, National Institute on Disability and Rehabilitation Research (grant number H133A090020). NR 102 TC 3 Z9 3 U1 5 U2 16 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0309-3646 EI 1746-1553 J9 PROSTHET ORTHOT INT JI Prosthet. Orthot. Int. PD OCT PY 2014 VL 38 IS 5 BP 343 EP 362 DI 10.1177/0309364613490443 PG 20 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA AQ4NG UT WOS:000342774400001 PM 23942758 ER PT J AU Nanyes, DR Junco, SE Taylor, AB Robinson, AK Patterson, NL Shivarajpur, A Halloran, J Hale, SM Kaur, Y Hart, PJ Kim, CA AF Nanyes, David R. Junco, Sarah E. Taylor, Alexander B. Robinson, Angela K. Patterson, Nicolle L. Shivarajpur, Ambika Halloran, Jonathan Hale, Seth M. Kaur, Yogeet Hart, P. John Kim, Chongwoo A. TI Multiple polymer architectures of human polyhomeotic homolog 3 sterile alpha motif SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE SAM; Polyhomeotic; Polycomb group; chromatin; polymer ID TUMOR-SUPPRESSOR ACTIVITY; POLYCOMB-GROUP PROTEINS; SAM DOMAIN; SEX-COMB; REPRESSION; GENES; PHC3; SOFTWARE AB The self-association of sterile alpha motifs (SAMs) into a helical polymer architecture is a critical functional component of many different and diverse array of proteins. For the Drosophila Polycomb group (PcG) protein Polyhomeotic (Ph), its SAM polymerization serves as the structural foundation to cluster multiple PcG complexes, helping to maintain a silenced chromatin state. Ph SAM shares 64% sequence identity with its human ortholog, PHC3 SAM, and both SAMs polymerize. However, in the context of their larger protein regions, PHC3 SAM forms longer polymers compared with Ph SAM. Motivated to establish the precise structural basis for the differences, if any, between Ph and PHC3 SAM, we determined the crystal structure of the PHC3 SAM polymer. PHC3 SAM uses the same SAM-SAM interaction as the Ph SAM sixfold repeat polymer. Yet, PHC3 SAM polymerizes using just five SAMs per turn of the helical polymer rather than the typical six per turn observed for all SAM polymers reported to date. Structural analysis suggested that malleability of the PHC3 SAM would allow formation of not just the fivefold repeat structure but also possibly others. Indeed, a second PHC3 SAM polymer in a different crystal form forms a sixfold repeat polymer. These results suggest that the polymers formed by PHC3 SAM, and likely others, are dynamic. The functional consequence of the variable PHC3 SAM polymers may be to create different chromatin architectures. (C) 2014 Wiley Periodicals, Inc. C1 [Nanyes, David R.; Junco, Sarah E.; Taylor, Alexander B.; Robinson, Angela K.; Patterson, Nicolle L.; Shivarajpur, Ambika; Halloran, Jonathan; Hale, Seth M.; Kaur, Yogeet; Hart, P. John; Kim, Chongwoo A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Taylor, Alexander B.; Hart, P. John] Xray Crystallog Core Lab, San Antonio, TX 78229 USA. [Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. RP Kim, CA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, MSC 7760,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM chong@biochem.uthscsa.edu FU American Heart Association [0830111N]; American Cancer Society [RSG 08 285 01 GMC]; Department of Defense Breast Cancer Research Program [BC075278]; Welch Foundation [AQ-1813, AQ-1399]; NIH [1 F31 GM099418-01A1]; NIH-NCI [P30 CA054174-17] FX Grant sponsor: American Heart Association; Grant number: #0830111N (to C. A. K.); Grant sponsor: American Cancer Society; Grant number: RSG 08 285 01 GMC (to C. A. K.); Grant sponsor: Department of Defense Breast Cancer Research Program; Grant number: BC075278 (to C. A. K.); Grant sponsor: Welch Foundation; Grant numbers: AQ-1813 (to C. A. K.) and AQ-1399 (to P.J.H.); Grant sponsor: NIH; Grant numbers: 1 F31 GM099418-01A1 (to S.E.J.) and NIH-NCI P30 CA054174-17 (to P.J.H). NR 29 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-3585 EI 1097-0134 J9 PROTEINS JI Proteins PD OCT PY 2014 VL 82 IS 10 BP 2823 EP 2830 DI 10.1002/prot.24645 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AQ5LC UT WOS:000342849400044 PM 25044168 ER PT J AU Stanic, AK Kim, M Styer, AK Rueda, BR AF Stanic, Aleksandar K. Kim, Minji Styer, Aaron K. Rueda, Bo R. TI Dendritic Cells Attenuate the Early Establishment of Endometriosis-Like Lesions in a Murine Model SO REPRODUCTIVE SCIENCES LA English DT Article DE endometriosis; dendritic cells; T cells; immunocompetent syngeneic mouse model ID PERITONEAL-FLUID; MOUSE MODEL; T-CELLS; IN-VIVO; WOMEN; MACROPHAGES; RESPONSES; DISEASE; SERUM AB Complex interplay of innate and adaptive immune cells has been implicated in the establishment, maintenance, and progression of endometriosis. Defining the identity, activation state, and functional role of immune cells during lesion establishment will provide invaluable insight into the underlying mechanisms of disease. This study utilized a transgenic mouse model with conditional dendritic cell (DC) depletion (diphtheria toxin-treated B6.FVB-Itgax-hDTR-EGFP(tg)) and multiparametric flow cytometry to examine immune cell composition and activation state and to assess the functional role of DCs in endometriosis-like lesions. T cells and DCs were increased in lesions compared to native uteri and control splenocytes and demonstrated an activated phenotype (P < .05). Lesions in DC-depleted hosts demonstrated greater size (P < .001) and reduced expression of T-cell activation marker CD69 compared to controls (P < .05). Collectively, these results suggest that activated DCs within lesions activate T cells and result in the impairment of early lesion establishment. C1 [Stanic, Aleksandar K.; Kim, Minji; Styer, Aaron K.; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Stanic, Aleksandar K.; Styer, Aaron K.; Rueda, Bo R.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA USA. RP Styer, AK (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Their 9, Boston, MA 02114 USA. EM astyer@partners.org; brueda@partners.org OI Stanic-Kostic, Aleksandar/0000-0003-1946-6436 FU Vincent Memorial Research Funds FX The author(s) received the following financial support for the research, authorship, and/or publication of this article: Supported by Vincent Memorial Research Funds to BRR. NR 30 TC 7 Z9 8 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD OCT PY 2014 VL 21 IS 10 BP 1228 EP 1236 DI 10.1177/1933719114525267 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AQ5JK UT WOS:000342844000003 PM 24594835 ER PT J AU Mahaney-Price, AF Hilgeman, MM Davis, LL McNeal, SF Conner, CM Allen, RS AF Mahaney-Price, Ann F. Hilgeman, Michelle M. Davis, Lori L. McNeal, Sandre F. Conner, Charles M. Allen, Rebecca S. TI Living Will Status and Desire for Living Will Help Among Rural Alabama Veterans SO RESEARCH IN NURSING & HEALTH LA English DT Article DE living will; advance care planning; advance directive; end of life; rural; veterans ID ILLNESS RATING-SCALE; OF-LIFE CARE; ADVANCE DIRECTIVE COMPLETION; DECISION-MAKING; MEDICAL-CARE; END; COMMUNICATION; VALIDATION; DISABILITY; ADMISSION AB The purpose of this secondary analysis of data from an earlier intervention study to increase Veterans Administration health care enrollment in rural Alabama veterans was to determine the veterans' living will status, desire for help completing a living will, and relationships between these and demographic, health insurance, health self-report, cumulative illness, disability, and trust characteristics. Baseline data for 201 rural Alabama veterans were extracted from the larger study. Chi-square and t tests were used to analyze group differences in categorical and continuous variables. Logistic regression models were used to determine multivariate associations of variables with living will status and desire for help. Only 13% of participants had living wills. Of those without living wills, 40% expressed a desire for help completing a living will. African Americans were less likely to have living wills than were Caucasians. Participants with more than high school education were more likely to desire help completing living wills than were those with less education. With the exception of moderate-severe respiratory illness, moderate-severe illness was not associated with having a living will. With the exception of moderate-severe vascular illness, moderate-severe illness was not associated with desire for help completing a living will. The racial and educational disparities in living will status and desire for help and the number of participants who desired help completing a living will suggests a need for action to increase advance care planning among rural veterans. (C) 2014 Wiley Periodicals, Inc. C1 [Mahaney-Price, Ann F.] Tuscaloosa VA Med Ctr, Res & Dev Serv, Tuscaloosa, AL 35404 USA. [Hilgeman, Michelle M.] Univ Alabama, Res & Dev Serv, Tuscaloosa VA Med Ctr, Tuscaloosa Res & Educ Adv Corp,Ctr Mental Hlth &, Tuscaloosa, AL USA. [Davis, Lori L.] Tuscaloosa Res & Educ Adv Corp, Tuscaloosa VA Med Ctr, Res & Dev Serv, Tuscaloosa, AL USA. [Davis, Lori L.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [McNeal, Sandre F.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [Conner, Charles M.] Birmingham VA Med Ctr, Res Dept, Birmingham, AL USA. [Allen, Rebecca S.] Univ Alabama, Ctr Mental Hlth & Aging, Tuscaloosa, AL USA. RP Mahaney-Price, AF (reprint author), Tuscaloosa VA Med Ctr, Res & Dev Serv, 3701 Loop Rd East, Tuscaloosa, AL 35404 USA. EM amparnp@yahoo.com OI Allen, Rebecca Sue/0000-0002-2563-4996 FU Veterans Health Administration Office of Rural Health FX We are grateful for the support of the Veterans Health Administration Office of Rural Health (funding), Lawrence Biro (former VA VISN 7 Director), Maria Andrews, Tuscaloosa VA Medical Center Director, Alan Tyler, former Tuscaloosa VA Medical Center Director, Rica Lewis-Payton, former Birmingham VA Medical Center Director, and VA Research Services at the Tuscaloosa and Birmingham VA Medical Centers. A full list of participating Alabama Veteran Rural Health Initiative investigators and institutions is published elsewhere (see Hilgeman et al., 2014). NR 44 TC 2 Z9 2 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-6891 EI 1098-240X J9 RES NURS HEALTH JI Res. Nurs. Health PD OCT PY 2014 VL 37 IS 5 BP 379 EP 390 DI 10.1002/nur.21617 PG 12 WC Nursing SC Nursing GA AQ7FB UT WOS:000342976900007 PM 25156143 ER PT J AU Horton, LE Smith, AA Haas, GL AF Horton, Leslie E. Smith, Ashley A. Haas, Gretchen L. TI The nature and timing of social deficits in child and adolescent offspring of parents with schizophrenia: Preliminary evidence for precursors of negative symptoms? SO SCHIZOPHRENIA RESEARCH LA English DT Article DE High-risk; Schizophrenia; Social skills; Premorbid adjustment; Social anhedonia; Social amotivation; Negative symptoms ID ADULT SCHIZOPHRENIA; HIGH-RISK; ABNORMALITIES; ADJUSTMENT; ANHEDONIA AB Children with social dysfunction and a first-degree relative with schizophrenia are at elevated risk for schizophrenia; however, the nature of this dysfunction is unclear. It was hypothesized that familial high-risk (HR) children and adolescents (n = 17) would have social skill deficits relative to healthy controls (HC; n = 35). HR participants had a bimodal distribution of social skill scores (47% excellent; 53% poor). HR participants had worse social skills, assertion and empathy scores, suggesting possible developmental precursors to the social amotivation domain of negative symptoms. Characterizing HR children's social deficits could assist identification of those at risk for schizophrenia. (C) 2014 Elsevier B. V. All rights reserved. C1 [Horton, Leslie E.; Smith, Ashley A.; Haas, Gretchen L.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. [Haas, Gretchen L.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Horton, LE (reprint author), Univ Pittsburgh, Med Ctr, 3811 OHara St, Pittsburgh, PA 15213 USA. EM hortonle2@upmc.edu FU NARSAD Independent Investigator Grant [1098]; Department of Psychiatry of the University of Pittsburgh School of Medicine FX This work was supported, in part, by NARSAD Independent Investigator Grant #1098 to the senior author (G. Haas), and infrastructure support funding from the Department of Psychiatry of the University of Pittsburgh School of Medicine. We thank Dr. Matcheri S. Keshavan and Diana Mermon, MS, for their assistance in referral of some of the participants to this study. We thank Shelby Miller, Audrey Brie Latimore, Valerie Michael, and Nicole Pawloski for their assistance in data preparation efforts. NR 17 TC 0 Z9 0 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2014 VL 159 IS 1 BP 27 EP 30 DI 10.1016/j.schres.2014.07.007 PG 4 WC Psychiatry SC Psychiatry GA AQ8TY UT WOS:000343107400005 PM 25112161 ER PT J AU Mote, J Minzenberg, MJ Carter, CS Kring, AM AF Mote, Jasmine Minzenberg, Michael J. Carter, C. S. Kring, Ann M. TI Deficits in anticipatory but not consummatory pleasure in people with recent-onset schizophrenia spectrum disorders SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Anhedonia; Anticipatory pleasure; Consummatory pleasure; Psychosis; Schizophrenia ID NEGATIVE SYMPTOMS; ANHEDONIA; SCALE; EXPERIENCE; PSYCHOSIS; INDIVIDUALS; VALIDATION AB The majority of studies examining self-reported anticipatory and consummatory pleasure in schizophrenia, as measured on the Temporal Experience of Pleasure Scale (TEPS), have been conducted on chronically ill people with the disorder. In this study, people with a recent-onset schizophrenia spectrum diagnosis (first psychotic episode within one year of study participation) (n = 88) and people without a schizophrenia spectrum diagnosis (n = 66) were administered the TEPS. People with a schizophrenia spectrum diagnosis reported significantly lower scores of anticipatory, but not consummatory, pleasure on the TEPS compared to the control group. TEPS anticipatory pleasure scores were also significantly, negatively correlated with negative symptoms, but neither TEPS anticipatory nor consummatory pleasure scores were significantly correlated with functioning measures. Our results replicate previous findings with chronically ill people with schizophrenia on the TEPS. (C) 2014 Elsevier B. V. All rights reserved. C1 [Mote, Jasmine; Kring, Ann M.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [Minzenberg, Michael J.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Carter, C. S.] UC Davis Med Ctr, Imaging Res Ctr, Sacramento, CA 95817 USA. RP Mote, J (reprint author), Univ Calif Berkeley, Dept Psychol, 3210 Tolman Hall 1650, Berkeley, CA 94720 USA. EM mote@berkeley.edu; michael.minzenberg@ucsf.edu; cameron.carter@ucdmc.ucdavis.edu; akring@berkeley.edu FU National Institute of Mental Health [5R01MH059883-11]; National Science Foundation [DGE 1106400] FX This work was supported by the National Institute of Mental Health (5R01MH059883-11 to CSC). Jasmine Mote was supported by award number DGE 1106400 from the National Science Foundation. NR 26 TC 11 Z9 11 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2014 VL 159 IS 1 BP 76 EP 79 DI 10.1016/j.schres.2014.07.048 PG 4 WC Psychiatry SC Psychiatry GA AQ8TY UT WOS:000343107400013 PM 25139112 ER PT J AU Reddy, LF Green, MF Rizzo, S Sugar, CA Blanchard, JJ Gur, RE Kring, AM Horan, WP AF Reddy, L. Felice Green, Michael F. Rizzo, Shemra Sugar, Catherine A. Blanchard, Jack J. Gur, Raquel E. Kring, Ann M. Horan, William P. TI Behavioral approach and avoidance in schizophrenia: An evaluation of motivational profiles SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Motivation; Behavioral approach and avoidance; Social anhedonia; Negative symptoms; BIS/BAS ID CLINICAL-ASSESSMENT INTERVIEW; PSYCHIATRIC RATING-SCALE; NEGATIVE SYMPTOMS CAINS; INHIBITION SYSTEMS; EEG ASYMMETRY; MONTE-CARLO; ACTIVATION; ANHEDONIA; PERSONALITY; BIS AB Schizophrenia is associated with motivational deficits that interfere with a wide range of goal directed activities. Despite their clinical importance, our current understanding of these motivational impairments is limited. Furthermore, different types of motivational problems are commonly seen among individuals within the broad diagnosis of schizophrenia. The goal of the current study was to examine whether clinically meaningful subgroups could be identified based on approach and avoidance motivational tendencies. We measured these tendencies in 151 individuals with schizophrenia. Although prior studies demonstrate elevated BIS sensitivity in schizophrenia at the overall group level, none have explored various combinations of BIS/BAS sensitivities within this disorder. Cluster analyses yielded five subgroups with different combinations of low, moderate, or high BIS and BAS. The subgroups had interpretable differences in clinically rated negative symptoms and self-reported anhedonia/socio-emotional attitudes, which were not detectable with the more commonly used linear BIS/BAS scores. Two of the subgroups had significantly elevated negative symptoms but different approach/avoidance profiles: one was characterized by markedly low BIS, low BAS and an overall lack of social approach motivation; the other had markedly high BIS but moderate BAS and elevated social avoidance motivation. The two subgroups with relatively good clinical functioning showed patterns of BAS greater than BIS. Our findings indicate that there are distinct motivational pathways that can lead to asociality in schizophrenia and highlight the value of considering profiles based on combined patterns of BIS and BAS in schizophrenia. Published by Elsevier B.V. C1 [Reddy, L. Felice; Green, Michael F.; Horan, William P.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Reddy, L. Felice; Green, Michael F.; Rizzo, Shemra; Sugar, Catherine A.; Horan, William P.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Rizzo, Shemra; Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90024 USA. [Blanchard, Jack J.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Gur, Raquel E.] Univ Penn, Dept Psychiat, Neuropsychiat Sect, Philadelphia, PA 19104 USA. [Kring, Ann M.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. RP Reddy, LF (reprint author), VA Greater Los Angeles Healthcare Syst, MIRECC 210A,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIH [1R01MH082890, 1R01MH082783, RO1 MH08272, 1R01MH082839, 1R01MH082782] FX This work was supported in part by NIH grant 1R01MH082890 to Dr. Kring, grants 1R01MH082783 and RO1 MH08272 to Dr. Gur, grant 1R01MH082839 to Dr. Blanchard, and grant 1R01MH082782 to Dr. Horan. NR 46 TC 6 Z9 6 U1 6 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2014 VL 159 IS 1 BP 164 EP 170 DI 10.1016/j.schres.2014.07.047 PG 7 WC Psychiatry SC Psychiatry GA AQ8TY UT WOS:000343107400027 ER PT J AU Gray, BE McMahon, RP Green, MF Seidman, LJ Mesholam-Gately, RI Kern, RS Nuechterlein, KH Keefe, RS Gold, JM AF Gray, Bradley E. McMahon, Robert P. Green, Michael F. Seidman, Larry J. Mesholam-Gately, Raquelle I. Kern, Robert S. Nuechterlein, Keith H. Keefe, Richard S. Gold, James M. TI Detecting reliable cognitive change in individual patients with the MATRICS Consensus Cognitive Battery SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Reliable change; Regression; MCCB; MATRICS ID SCHIZOPHRENIA; REGRESSION AB Objective: Clinicians often need to evaluate the treatment response of an individual person and to know that observed change is true improvement or worsening beyond usual week-to-week changes. This paper gives clinicians tools to evaluate individual changes on the MATRICS Consensus Cognitive Battery (MCCB). We compare three different approaches: a descriptive analysis of MCCB test-retest performance with no intervention, a reliable change index (RCI) approach controlling for average practice effects, and a regression approach. Method: Data were gathered as part of the MATRICS PASS study (Nuechterlein et al., 2008). A total of 159 people with schizophrenia completed the MCCB at baseline and 4 weeks later. Data were analyzed using an RCI and a regression formula establishing confidence intervals. Results: The RCI and regression approaches agree within one point when baseline values are close to the sample mean. However, the regression approach offers more accurate limits for expected change at the tails of the distribution of baseline scores. Conclusions: Although both approaches have their merits, the regression approach provides the most accurate measure of significant change across the full range of scores. As the RCI does not account for regression to the mean and has confidence limits that remain constant across baseline scores, the RCI approach effectively gives narrower confidence limits around an inaccurately predicted average change value. Further, despite the high test-retest reliability of the MCCB, a change in an individual's score must be relatively large to be confident that it is beyond normal month-to-month variation. (C) 2014 Elsevier B. V. All rights reserved. C1 [Gray, Bradley E.; McMahon, Robert P.; Gold, James M.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21228 USA. [Green, Michael F.; Kern, Robert S.; Nuechterlein, Keith H.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Green, Michael F.; Kern, Robert S.; Nuechterlein, Keith H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Seidman, Larry J.; Mesholam-Gately, Raquelle I.] Harvard Univ, Massachusetts Mental Hlth Ctr, Beth Israel Deaconess Med Ctr, Publ Psychiat Div,Med Sch,Dept Psychiat, Boston, MA 02115 USA. [Keefe, Richard S.] Duke Univ, Sch Med, Dept Psychiat, Durham, NC 27710 USA. RP Gold, JM (reprint author), MPRC, POB 21247, Baltimore, MD 21228 USA. EM jgold@mprc.umaryland.edu FU NIMH [N01MH22006] FX This work was made possible by NIMH contract N01MH22006 provided to the University of California, Los Angeles (Drs. Marder, Green, and Fenton); and an option (Drs. Green and Nuechterlein) to the NIMH MATRICS initiative. NR 12 TC 5 Z9 5 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2014 VL 159 IS 1 BP 182 EP 187 DI 10.1016/j.schres.2014.07.032 PG 6 WC Psychiatry SC Psychiatry GA AQ8TY UT WOS:000343107400030 PM 25156338 ER PT J AU Redzic, JS Balaj, L van der Vos, KE Breakefield, XO AF Redzic, Jasmina S. Balaj, Leonora van der Vos, Kristan E. Breakefield, Xandra O. TI Extracellular RNA mediates and marks cancer progression SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE RNA; Extracellular vesicles; Cancer ID TUMOR-DERIVED MICROVESICLES; ENDOTHELIAL-CELL MIGRATION; HUMAN COLORECTAL-CANCER; MESSENGER-RNA; PROSTATE-CANCER; NONCODING RNAS; BREAST-CANCER; LUNG-CANCER; INTERCELLULAR COMMUNICATION; CEREBROSPINAL-FLUID AB Different types of RNAs identified thus far represent a diverse group of macromolecules that are involved in the regulation of different biological processes. RNA is generally thought to be localized primarily in the nucleus and cytoplasm; however, some types of RNA have been detected in the extracellular milieu. These extracellular RNA (exRNA) molecules are protected from degradation and it is now widely accepted that extracellular vesicles and ribonucleoprotein particles serve as transport vehicles for exRNA among cells. The functional consequence of this transfer of genetic information probably encompasses a broad range of normal developmental and physiologic processes in many organisms. This review will focus on the role of exRNA communication in cancer. We will focus on different types of RNA species identified and characterized within tumor-derived extracellular vesicles. Further, we will describe the role of exRNAs in cancer progression, as well as their potential for use as diagnostic biomarkers and therapeutic tools for monitoring and treating cancer, respectively. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Redzic, Jasmina S.] Univ Colorado, Denver Sch Med, Dept Neurosurg, Aurora, CO USA. [Balaj, Leonora; van der Vos, Kristan E.; Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Balaj, Leonora; van der Vos, Kristan E.; Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Balaj, Leonora; van der Vos, Kristan E.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Neurogenet Unit, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM jasmina.redzic@ucdenver.edu; Balaj.Leonora@mgh.harvard.edu; k.vd.vos@nki.nl; breakefield@hms.harvard.edu FU NIH/NCI [CA069246, U19 CA179563]; Voices Against Brain Tumor Foundation by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH; Richard Floor Biorepository Fund; FMD Fellowship (ECOR MGH); Dutch Scientific Organisation (NWO-Rubicon); NIH [2T32AG000222-21] FX We thank Ms. Suzanne McDavitt for skilled editorial assistance and Dr. Emanuele Cocucci for insights into EV trafficking. Funding was provided by NIH/NCI CA069246 and U19 CA179563 and Voices Against Brain Tumor Foundation (XOB) by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director. Funding was provided by the Richard Floor Biorepository Fund (XOB and LB). LB is supported by the FMD Fellowship (ECOR MGH). KEvdV is supported by the Dutch Scientific Organisation (NWO-Rubicon). Funding was provided by NIH 2T32AG000222-21 (JSR). NR 147 TC 15 Z9 15 U1 3 U2 21 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD OCT PY 2014 VL 28 BP 14 EP 23 DI 10.1016/j.semcancer.2014.04.010 PG 10 WC Oncology SC Oncology GA AQ7SQ UT WOS:000343019900003 PM 24783980 ER PT J AU Christianson, HC Svensson, KJ Belting, M AF Christianson, Helena C. Svensson, Katrin J. Belting, Mattias TI Exosome and microvesicle mediated phene transfer in mammalian cells SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE Endocytosis; Exosomes; Cancer; Phene transfer; Proteoglycans ID HEPARAN-SULFATE PROTEOGLYCANS; CLATHRIN-INDEPENDENT ENDOCYTOSIS; ENDOTHELIAL-CELLS; DENDRITIC CELLS; ACTIVATED PLATELETS; RECIPIENT CELLS; DOWN-MODULATE; TISSUE-FACTOR; LUNG-CANCER; IN-VIVO AB Extracellular vesicles (EVs), e.g. exosomes and microvesicles, emerge as new signaling organelles in the exchange of information between cells at the paracrine and systemic level. It is clear that these virus like particles carry complex biological information that can elicit a pleiotropic response in recipient cells with potential relevance in physiology as well as in cancer and other pathological conditions. Numerous studies convincingly show that the molecular composition of EVs closely reflects their cell or tissue of origin. Thus, the signaling status of donor cells, more specifically their endosomal compartments, may largely determine the biological output in recipient cells, a process that we then may conceptualize as vesicle mediated phene transfer. Whereas more conventional modes of cell-cell communication mostly depend on extracellular ligand concentration and cell-surface receptor availability, the magnitude of the EV signaling response relies on the capture and uptake by target cells, allowing release of the EV content. Numerous reports point at the intriguing possibility that, among thousands of mRNAs, miRNAs, and proteins, single EV constituents effectuate the biological response, e.g. stimulation of angiogenesis and cancer cell metastasis, in recipient cells; however, we find it conceivable that strategies targeted at general mechanisms of EV function should provide more rational avenues for therapeutic intervention directed at the EV system. Such strategies include manipulation of EV formation in the endolysosomal system, EV stability in the extracellular milieu, and EV entry into target cells. Here, we provide important insights into potential mechanisms of EV transport in mammalian cells and how these may be targeted. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Christianson, Helena C.; Svensson, Katrin J.; Belting, Mattias] Lund Univ, Ctr Canc, Dept Clin Sci, Sect Oncol Pathol, SE-22185 Lund, Sweden. [Belting, Mattias] Skane Univ Hosp, Dept Oncol, Lund, Sweden. [Svensson, Katrin J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Svensson, Katrin J.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. RP Belting, M (reprint author), Lund Univ, Ctr Canc, Dept Clin Sci, Sect Oncol & Pathol, Barngatan 2B, SE-22185 Lund, Sweden. EM mattias.belting@med.lu.se OI Svensson, Katrin J/0000-0001-5376-5128 FU Swedish Cancer Fund; Swedish Research Council; Skane University Hospital donation funds; Governmental funding of clinical research within the national health services (ALF); Gunnar Nilsson Foundation; Anna Lisa and Sven Eric Lundgren Foundation; Kamprad Foundation FX We apologize to all those authors whose important work could not be cited due to space restrictions. This work was supported by grants from the Swedish Cancer Fund; the Swedish Research Council; the Gunnar Nilsson, Anna Lisa and Sven Eric Lundgren, and Kamprad Foundations; the Skane University Hospital donation funds; and the Governmental funding of clinical research within the national health services (ALF). NR 77 TC 8 Z9 8 U1 1 U2 26 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD OCT PY 2014 VL 28 BP 31 EP 38 DI 10.1016/j.semcancer.2014.04.007 PG 8 WC Oncology SC Oncology GA AQ7SQ UT WOS:000343019900005 PM 24769057 ER PT J AU Miller, CB Espie, CA Epstein, DR Friedman, L Morin, CM Pigeon, WR Spielman, AJ Kyle, SD AF Miller, Christopher B. Espie, Colin A. Epstein, Dana R. Friedman, Leah Morin, Charles M. Pigeon, Wilfred R. Spielman, Arthur J. Kyle, Simon D. TI The evidence base of sleep restriction therapy for treating insomnia disorder SO SLEEP MEDICINE REVIEWS LA English DT Review DE Insomnia; Sleep; Cognitive behavioral therapy; Treatment; Psychological intervention; Sleep restriction therapy; Evidence base; Review ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; ECOLOGICAL MOMENTARY ASSESSMENT; PLACEBO-CONTROLLED TRIAL; OLDER-ADULTS; NONPHARMACOLOGIC TREATMENT; COMPARATIVE METAANALYSIS; CLINICAL MANAGEMENT; PRACTICE PARAMETERS; DAYTIME SYMPTOMS AB Sleep restriction therapy is routinely used within cognitive behavioral therapy to treat chronic insomnia. However, the efficacy for sleep restriction therapy as a standalone intervention has yet to be comprehensively reviewed. This review evaluates the evidence for the use of sleep restriction therapy in the treatment of chronic insomnia. The literature was searched using web-based databases, finding 1344 studies. Twenty-one were accessed in full (1323 were deemed irrelevant to this review). Nine were considered relevant and evaluated in relation to study design using a standardized study checklist and levels of evidence. Four trials met adequate methodological strength to examine the efficacy of therapy for chronic insomnia. Weighted effect sizes for self-reported sleep diary measures of sleep onset latency, wake time after sleep onset, and sleep efficiency were moderate-to-large after therapy. Total sleep time indicated a small improvement. Standalone sleep restriction therapy is efficacious for the treatment of chronic insomnia for sleep diary continuity variables. Studies are insufficient to evaluate the full impact on objective sleep variables. Measures of daytime functioning in response to therapy are lacking. Variability in the sleep restriction therapy implementation methods precludes any strong conclusions regarding the true impact of therapy. A future research agenda is outlined. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Miller, Christopher B.] Univ Sydney, Sydney Med Sch, Woolcock Inst Med Res, Ctr Integrated Res & Understanding Sleep, Sydney, NSW 2050, Australia. [Miller, Christopher B.] Univ Glasgow, Inst Neurosci & Psychol, Glasgow G12 8QQ, Lanark, Scotland. [Espie, Colin A.] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford OX1 2JD, England. [Espie, Colin A.] Univ Oxford, Circadian Neurosci Inst, Oxford OX1 2JD, England. [Epstein, Dana R.] Phoenix Vet Affairs Hlth Care Syst, Phoenix, AZ USA. [Epstein, Dana R.] Arizona State Univ, Coll Nursing & Hlth Innovat, Tempe, AZ 85287 USA. [Friedman, Leah] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Friedman, Leah] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Morin, Charles M.] Univ Laval, Quebec City, PQ, Canada. [Pigeon, Wilfred R.] Univ Rochester, Med Ctr, Sleep & Neurophysiol Res Lab, Rochester, NY 14627 USA. [Pigeon, Wilfred R.] US Dept Vet Affairs, Ctr Excellence Suicide Prevent, Washington, DC USA. [Spielman, Arthur J.] CUNY City Coll, Cognit Neurosci Doctoral Program, New York, NY USA. [Spielman, Arthur J.] Weill Cornell Med Coll, Ctr Sleep Med, New York, NY USA. [Kyle, Simon D.] Univ Manchester, Sch Psychol Sci, Manchester M13 9PL, Lancs, England. RP Miller, CB (reprint author), Univ Sydney, Sydney Med Sch, Woolcock Inst Med Res, POB M77,Missenden Rd, Sydney, NSW 2050, Australia. EM chris.miller@sydney.edu.au OI Miller, Christopher/0000-0002-2936-7717; Kyle, Simon/0000-0002-9581-5311 FU National Health and Medical Research Council (NHMRC, Australia) Centre for Integrated Research and Understanding of Sleep (CIRUS) [571421]; Sackler Institute of Psychobiological Research (University of Glasgow Sleep Centre, Scotland, UK); Chief Scientist Office (Scotland, UK) [CZG/2/503] FX This research was supported by the National Health and Medical Research Council (NHMRC, Australia) Centre for Integrated Research and Understanding of Sleep (CIRUS), grant no. 571421; the Sackler Institute of Psychobiological Research (University of Glasgow Sleep Centre, Scotland, UK); and the Chief Scientist Office (Scotland, UK) Grant # CZG/2/503. Authors Epstein, Friedman and Pigeon are employees of the United States Department of Veterans Affairs, which supported their work on this manuscript. The authors' views or opinions do not necessarily represent those of the Department of Veterans Affairs or the United States Government. NR 75 TC 10 Z9 10 U1 4 U2 24 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1087-0792 EI 1532-2955 J9 SLEEP MED REV JI Sleep Med. Rev. PD OCT PY 2014 VL 18 IS 5 BP 415 EP 424 DI 10.1016/j.smrv.2014.01.006 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AQ6XB UT WOS:000342956100007 PM 24629826 ER PT J AU Gilman, SE Loucks, EB AF Gilman, Stephen E. Loucks, Eric B. TI Another casualty of sibling fixed-effects analysis of education and health: An informative null, or null information? SO SOCIAL SCIENCE & MEDICINE LA English DT Editorial Material DE Cardiovascular disease; Educational attainment; Causal inference; Siblings; Disparities ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; SOCIOECONOMIC POSITION; CHILD-DEVELOPMENT; FAMILY FACTORS; ADULT HEALTH; DANISH TWINS; MORTALITY; RISK; ENVIRONMENT C1 [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gilman, Stephen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Loucks, Eric B.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. RP Gilman, SE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave, Boston, MA 02115 USA. EM sgilman@hsph.harvard.edu RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 FU NIA NIH HHS [1RC2AG036666, 1R01AG023397, R01 AG023397, RC2 AG036666] NR 55 TC 4 Z9 4 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD OCT PY 2014 VL 118 BP 191 EP 193 DI 10.1016/j.socscimed.2014.06.029 PG 3 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AQ5XC UT WOS:000342880900025 PM 25138687 ER PT J AU Tada, H Shiffman, D Smith, JG Sjogren, M Lubitz, SA Ellinor, PT Louie, JZ Catanese, JJ Engstrom, G Devlin, JJ Kathiresan, S Melander, O AF Tada, Hayato Shiffman, Dov Smith, J. Gustav Sjogren, Marketa Lubitz, Steven A. Ellinor, Patrick T. Louie, Judy Z. Catanese, Joseph J. Engstrom, Gunnar Devlin, James J. Kathiresan, Sekar Melander, Olle TI Twelve-Single Nucleotide Polymorphism Genetic Risk Score Identifies Individuals at Increased Risk for Future Atrial Fibrillation and Stroke SO STROKE LA English DT Article DE atrial fibrillation; polymorphism, single nucleotide; stroke ID FAMILIAL AGGREGATION; CHROMOSOME 4Q25; ISCHEMIC-STROKE; LIFETIME RISK; UNITED-STATES; VARIANTS; PREVALENCE; MARKERS; HEALTH; EPIDEMIOLOGY AB Background and Purpose-Atrial fibrillation (AF) is prevalent and there is a clinical need for biomarkers to identify individuals at higher risk for AF. Fixed throughout a life course and assayable early in life, genetic biomarkers may meet this need. Here, we investigate whether multiple single nucleotide polymorphisms together as an AF genetic risk score (AF-GRS) can improve prediction of one's risk for AF. Methods-In 27 471 participants of the Malmo Diet and Cancer Study, a prospective, community-based cohort, we used Cox models that adjusted for established AF risk factors to assess the association of AF-GRS with incident AF and ischemic stroke. Median follow-up was 14.4 years for incident AF and 14.5 years for ischemic stroke. The AF-GRS comprised 12 single nucleotide polymorphisms that had been previously shown to be associated with AF at genome-wide significance. Results-During follow-up, 2160 participants experienced a first AF event and 1495 had a first ischemic stroke event. Participants in the top AF-GRS quintile were at increased risk for incident AF (hazard ratio, 2.00; 95% confidence interval, 1.73-2.31; P=2.7x10(-21)) and ischemic stroke (hazard ratio, 1.23; 95% confidence interval, 1.04-1.46; P=0.02) when compared with the bottom quintile. Addition of the AF-GRS to established AF risk factors modestly improved both discrimination and reclassification (P<0.0001 for both). Conclusions-An AF-GRS can identify 20% of individuals who are at approximate to 2-fold increased risk for incident AF and at 23% increased risk for ischemic stroke. Targeting diagnostic or therapeutic interventions to this subset may prove clinically useful. C1 [Tada, Hayato; Lubitz, Steven A.; Ellinor, Patrick T.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Tada, Hayato; Lubitz, Steven A.; Ellinor, Patrick T.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Tada, Hayato; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Tada, Hayato; Ellinor, Patrick T.; Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Shiffman, Dov; Louie, Judy Z.; Catanese, Joseph J.; Devlin, James J.] Quest Diagnost, Sci & Innovat Grp, Alameda, CA 94502 USA. [Smith, J. Gustav] Lund Univ, Dept Cardiol, Lund, Sweden. [Sjogren, Marketa; Engstrom, Gunnar; Melander, Olle] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Melander, Olle] Skane Univ Hosp, Dept Internal Med, SE-20502 Malmo, Sweden. RP Shiffman, D (reprint author), Quest Diagnost, Sci & Innovat Grp, 1401 Harbor Bay Pkwy, Alameda, CA 94502 USA. EM dov.shiffman@celera.com; sekar@broadinstitute.org; olle.melander@med.lu.se OI Engstrom, Gunnar/0000-0002-8618-9152 FU Swedish Cancer Society; Swedish Medical Research Council; Swedish Dairy Association; Albert Pahlsson Foundation; Gunnar Nilsson Foundation; Malmo city council; Japanese Circulation Society; Swedish National Health Service; Swedish Heart and Lung Foundation; Skane University Hospital; National Institutes of Health (NIH) [1K23HL114724]; NIH; American Heart Association; Massachusetts General Hospital (MGH); Howard Goodman Fellowship from MGH; Donovan Family Foundation; European Research Council [StG-282255]; Swedish Research Council; Novo Nordisk Foundation; Skane University Hospital donation funds; Medical Faculty, Lund University; Governmental funding of clinical research within the National Health Services; Albert Pahlsson Research Foundation; Region Skane; King Gustav V; Queen Victoria Foundation; Marianne and Marcus Wallenberg Foundation; Quest Diagnostics FX The Malmo Diet and Cancer (MDC) study was made possible by grants from the Swedish Cancer Society, the Swedish Medical Research Council, the Swedish Dairy Association, the Albert Pahlsson and Gunnar Nilsson Foundations, and the Malmo city council. Dr Tada is supported by a grant from the Japanese Circulation Society to study in the United States. Dr Smith is supported by governmental funding of clinical research within the Swedish National Health Service and grants from the Swedish Heart and Lung Foundation and Skane University Hospital. Dr Lubitz is supported by a research grant from National Institutes of Health (NIH; 1K23HL114724). Dr Ellinor is supported by research grants from NIH and American Heart Association. Dr Kathiresan is supported by a Research Scholar award from the Massachusetts General Hospital (MGH), the Howard Goodman Fellowship from MGH, and the Donovan Family Foundation. Dr Melander is supported by the European Research Council (StG-282255), the Swedish Heart and Lung Foundation, Swedish Research Council; the Novo Nordisk Foundation, the Skane University Hospital donation funds; the Medical Faculty, Lund University; the Governmental funding of clinical research within the National Health Services, the Albert Pahlsson Research Foundation, Region Skane, the King Gustav V and Queen Victoria Foundation, and the Marianne and Marcus Wallenberg Foundation. Genotyping of the atrial fibrillation (AF) genetic risk score single nucleotide polymorphisms in the MDC study was performed at the Quest Diagnostics Science and Innovation genotyping facility in Alameda, CA. Drs Melander and Kathiresan are the recipients of an investigator-initiated grant from Quest Diagnostics to study the genetics of AF in MDC. NR 40 TC 33 Z9 33 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD OCT PY 2014 VL 45 IS 10 BP 2856 EP + DI 10.1161/STROKEAHA.114.006072 PG 16 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AQ4UH UT WOS:000342794700014 PM 25123217 ER PT J AU Hakimelahi, R Vachha, BA Copen, WA Papini, GDE He, JL Higazi, MM Lev, MH Schaefer, PW Yoo, AJ Schwamm, LH Gonzalez, RG AF Hakimelahi, Reza Vachha, Behroze A. Copen, William A. Papini, Giacomo D. E. He, Julian Higazi, Mahmoud M. Lev, Michael H. Schaefer, Pamela W. Yoo, Albert J. Schwamm, Lee H. Gonzalez, R. Gilberto TI Time and Diffusion Lesion Size in Major Anterior Circulation Ischemic Strokes SO STROKE LA English DT Article DE brain infarction; diffusion; magnetic resonance imaging; stroke ID TISSUE-PLASMINOGEN ACTIVATOR; FOCAL CEREBRAL-ISCHEMIA; DIFFUSION/PERFUSION MISMATCH; INTRAVENOUS ALTEPLASE; THROMBOLYTIC THERAPY; CONTROLLED-TRIAL; COLLATERAL FLOW; POOLED ANALYSIS; DEFUSE 2; MRI AB Background and Purpose-Major anterior circulation ischemic strokes caused by occlusion of the distal internal carotid artery or proximal middle cerebral artery or both account for about one third of ischemic strokes with mostly poor outcomes. These strokes are treatable by intravenous tissue-type plasminogen activator and endovascular methods. However, dynamics of infarct growth in these strokes are poorly documented. The purpose was to help understand infarct growth dynamics by measuring acute infarct size with diffusion-weighted imaging (DWI) at known times after stroke onset in patients with documented internal carotid artery/middle cerebral artery occlusions. Methods-Retrospectively, we included 47 consecutive patients with documented internal carotid artery/middle cerebral artery occlusions who underwent DWI within 30 hours of stroke onset. Prospectively, 139 patients were identified using the same inclusion criteria. DWI lesion volumes were measured and correlated to time since stroke onset. Perfusion data were reviewed in those who underwent perfusion imaging. Results-Acute infarct volumes ranged from 0.41 to 318.3 mL. Infarct size and time did not correlate (R-2=0.001). The majority of patients had DWI lesions that were <25% the territory at risk (<70 mL) whether they were imaged <8 or >8 hours after stroke onset. DWI lesions corresponded to areas of greatly reduced perfusion. Conclusions-Poor correlation between infarct volume and time after stroke onset suggests that there are factors more powerful than time in determining infarct size within the first 30 hours. The observations suggest that highly variable cerebral perfusion via the collateral circulation may primarily determine infarct growth dynamics. If verified, clinical implications include the possibility of treating many patients outside traditional time windows. C1 [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Neuroradiol Div, Boston, MA 02114 USA. [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Gonzalez, RG (reprint author), Harvard Univ, Sch Med, Neuroradiol Div, GRB 273A,55 Fruit St, Boston, MA 02114 USA. EM rggonzalez@mgh.harvard.edu OI Schwamm, Lee/0000-0003-0592-9145; Higazi, Mahmoud/0000-0003-3115-1939 FU Egyptian government; Minia University, Egypt FX Dr Higazi received grant support from the Egyptian government and Minia University, Egypt. NR 34 TC 13 Z9 13 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD OCT PY 2014 VL 45 IS 10 BP 2936 EP + DI 10.1161/STROKEAHA.114.005644 PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AQ4UH UT WOS:000342794700027 PM 25190444 ER PT J AU Knox, R Brennan-Minnella, AM Lu, FX Yang, DN Nakazawa, T Yamamoto, T Swanson, RA Ferriero, DM Jiang, XN AF Knox, Renatta Brennan-Minnella, Angela M. Lu, Fuxin Yang, Diana Nakazawa, Takanobu Yamamoto, Tadashi Swanson, Raymond A. Ferriero, Donna M. Jiang, Xiangning TI NR2B Phosphorylation at Tyrosine 1472 Contributes to Brain Injury in a Rodent Model of Neonatal Hypoxia-Ischemia SO STROKE LA English DT Article DE Fyn tyrosine kinase; hypoxia-ischemia, brain; NR2B NMDA receptor ID D-ASPARTATE RECEPTOR; NEURONAL CELL-DEATH; NMDA-RECEPTORS; NADPH OXIDASE; ACTIVATION; SUBUNIT; MICE; SUPEROXIDE; LOCALIZATION; 3-KINASE AB Background and Purpose-The NR2B subunit of the N-methyl-d-aspartate (NMDA) receptor is phosphorylated by the Src family kinase Fyn in brain, with tyrosine (Y) 1472 as the major phosphorylation site. Although Y1472 phosphorylation is important for synaptic plasticity, it is unknown whether it is involved in NMDA receptor-mediated excitotoxicity in neonatal brain hypoxia-ischemia (HI). This study was designed to elucidate the specific role of Y1472 phosphorylation of NR2B in neonatal HI in vivo and in NMDA-mediated neuronal death in vitro. Methods-Neonatal mice with a knockin mutation of Y1472 to phenylalanine (YF-KI) and their wild-type littermates were subjected to HI using the Vannucci model. Brains were scored 5 days later for damage using cresyl violet and iron staining. Western blotting and immunoprecipitation were performed to determine NR2B tyrosine phosphorylation. Expression of NADPH oxidase subunits and superoxide production were measured in vivo. NMDA-induced calcium response, superoxide formation, and cell death were evaluated in primary cortical neurons. Results-After neonatal HI, YF-KI mice have reduced expression of NADPH oxidase subunit gp91(phox) and p47(phox) and superoxide production, lower activity of proteases implicated in necrotic and apoptotic cell death, and less brain damage when compared with the wild-type mice. In vitro, YF-KI mutation diminishes superoxide generation in response to NMDA without effect on calcium accumulation and inhibits NMDA and glutamate-induced cell death. Conclusions-Upregulation of NR2B phosphorylation at Y1472 after neonatal HI is involved in superoxide-mediated oxidative stress and contributes to brain injury. C1 [Knox, Renatta; Lu, Fuxin; Yang, Diana; Ferriero, Donna M.; Jiang, Xiangning] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA. [Knox, Renatta; Ferriero, Donna M.] Univ Calif San Francisco, Biomed Sci Grad Program, San Francisco, CA 94158 USA. [Knox, Renatta] Univ Calif San Francisco, Med Scientist Training Program, San Francisco, CA 94158 USA. [Brennan-Minnella, Angela M.; Swanson, Raymond A.; Ferriero, Donna M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA. [Brennan-Minnella, Angela M.; Swanson, Raymond A.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94158 USA. [Nakazawa, Takanobu; Yamamoto, Tadashi] Univ Tokyo, Inst Med Sci, Div Oncol, Tokyo, Japan. RP Jiang, XN (reprint author), Univ Calif San Francisco, Dept Pediat, 675 Nelson Rising Lane Room 494, San Francisco, CA 94158 USA. EM xiangning.jiang@ucsf.edu FU National Institute of Neurological Disorders and Stroke [F31NS073145, R21NS059613, RO1NS084057, RO1NS081149, RO1NS33997] FX This work was funded by grants from National Institute of Neurological Disorders and Stroke: F31NS073145 (Dr Knox); R21NS059613 and RO1NS084057 (Dr Jiang); RO1NS081149 (Dr Swanson); and RO1NS33997 (Dr Ferriero). NR 25 TC 7 Z9 7 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD OCT PY 2014 VL 45 IS 10 BP 3040 EP 3047 DI 10.1161/STROKEAHA.114.006170 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AQ4UH UT WOS:000342794700042 PM 25158771 ER PT J AU Falcone, GJ Rosand, J AF Falcone, Guido J. Rosand, Jonathan TI Aspirin Should Be Discontinued After Lobar Intracerebral Hemorrhage SO STROKE LA English DT Editorial Material DE aspirin; cerebral hemorrhage; stroke ID CEREBRAL AMYLOID ANGIOPATHY C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Div Neurocrit Care & Emergency Neurol, Dept Neurol,J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Div Neurocrit Care & Emergency Neurol, 185 Cambridge St,CPZN 6810, Boston, MA 02114 USA. EM jrosand@partners.org RI Falcone, Guido/L-2287-2016 OI Falcone, Guido/0000-0002-6407-0302 FU NINDS NIH HHS [P50NS061343, R01NS059727] NR 8 TC 2 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD OCT PY 2014 VL 45 IS 10 BP 3151 EP 3152 DI 10.1161/STROKEAHA.114.005787 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AQ4UH UT WOS:000342794700065 PM 25205309 ER PT J AU Mathes, DW Solari, MG Gazelle, GS Butler, PEM Wu, A Nazzal, A Nielsen, GP Huang, CA Sachs, DH Lee, WPA Randolph, MA AF Mathes, David W. Solari, Mario G. Gazelle, Guy Scott Butler, Peter E. M. Wu, Anette Nazzal, Adam Nielsen, Gunnlauger P. Huang, Christene A. Sachs, David H. Lee, Wei Ping Andrew Randolph, Mark A. TI Stable mixed hematopoietic chimerism permits tolerance of vascularized composite allografts across a full major histocompatibility mismatch in swine SO TRANSPLANT INTERNATIONAL LA English DT Article DE bone marrow; chimera; fetal; swine; vascularized composite allograft ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; LARGE-ANIMAL-MODEL; STEM-CELL TRANSPLANTATION; IN-UTERO TRANSPLANTATION; MINIATURE SWINE; RENAL-ALLOGRAFTS; T-CELL; MULTILINEAGE CHIMERISM; MHC BARRIERS AB This study tested the hypothesis that vascularized composite allografts (VCA) could be accepted in a robust model of hematopoietic chimerism by injecting allogeneic bone marrow cells (BMC) into swine fetuses. Outbred Yorkshire sows and boars were screened to ensure the absence of the major histocompatibility (MHC) allele SLA(cc) of inbred MGH miniature swine and then mated. Bone marrow harvested from an SLA(cc) swine donor was T-cell depleted and injected intravenously into the fetuses between days 50-55 of gestation. After birth, the piglets were studied with flow cytometry to detect donor cells and mixed lymphocyte reactions (MLR) and cell-mediated lympholysis (CML) assays to assess their response to donor. Donor-matched VCAs from SLA(cc) donors were performed on four chimeric and two nonchimeric swine. The results showed donor cell engraftment and multilineage macrochimerism after the in utero transplantation of adult BMC, and chimeric animals were unresponsive to donor antigens in vitro. Both control VCAs were rejected by 21days and were alloreactive. Chimeric animals accepted the VCAs and never developed antidonor antibodies or alloreactivity to donor. These results confirm that the intravascular, in utero transplantation of adult BMC leads to donor cell chimerism and donor-specific tolerance of VCAs across a full MHC barrier in this animal model. C1 [Mathes, David W.] Univ Colorado, Sch Med, Div Plast Surg, Denver, CO USA. [Solari, Mario G.] Univ Pittsburgh, Sch Med, Div Plast Surg, Pittsburgh, PA USA. [Gazelle, Guy Scott] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Butler, Peter E. M.; Nazzal, Adam; Randolph, Mark A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. [Wu, Anette; Huang, Christene A.; Sachs, David H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Lab MGH East, Boston, MA 02114 USA. [Nielsen, Gunnlauger P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lee, Wei Ping Andrew] Johns Hopkins Med Inst, Dept Plast Surg, Baltimore, MD 21205 USA. RP Randolph, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 15 Parkman St,WAC435, Boston, MA 02114 USA. EM Randolph.mark@mgh.harvard.edu OI Butler, Peter/0000-0001-7419-1493 FU Plastic Surgery Education Foundation; Roche Laboratories Surgical Scientist Award from American Society of Transplant Surgeons; National Institutes of Health [5R01 HL63430, 1R01 CA79988-01A1]; Lifecell Fellowship of the Plastic Surgery Educational Foundation FX Supported by grants from the Plastic Surgery Education Foundation, The Roche Laboratories Surgical Scientist Award from the American Society of Transplant Surgeons, and partial support from National Institutes of Health grants 5R01 HL63430 and 1R01 CA79988-01A1. Dr. Mathes was supported by the Lifecell Fellowship of the Plastic Surgery Educational Foundation. NR 52 TC 7 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0934-0874 EI 1432-2277 J9 TRANSPL INT JI Transpl. Int. PD OCT PY 2014 VL 27 IS 10 BP 1086 EP 1096 DI 10.1111/tri.12380 PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA AQ5JX UT WOS:000342845400018 PM 24963743 ER PT J AU Thase, ME Kingdon, D Turkington, D AF Thase, Michael E. Kingdon, David Turkington, Douglas TI The promise of cognitive behavior therapy for treatment of severe mental disorders: a review of recent developments SO WORLD PSYCHIATRY LA English DT Article DE Cognitive behavior therapy; adjunctive therapy; severe mental disorders; schizophrenia; major depressive disorders; treatment refractory depression; bipolar disorder ID RANDOMIZED CONTROLLED-TRIAL; CHRONIC DEPRESSION; MAJOR DEPRESSION; ANALYSIS SYSTEM; BIPOLAR DISORDER; CHRONIC FORMS; PSYCHOSIS; PSYCHOTHERAPY; METAANALYSIS; SCHIZOPHRENIA AB Cognitive behavior therapy (CBT), as exemplified by the model of psychotherapy developed and refined over the past 40 years by A. T. Beck and colleagues, is one of the treatments of first choice for ambulatory depressive and anxiety disorders. Over the past several decades, there have been vigorous efforts to adapt CBT for treatment of more severe mental disorders, including schizophrenia and the more chronic and/or treatment refractory mood disorders. These efforts have primarily studied CBT as an adjunctive therapy, i.e., in combination with pharmacotherapy. Given the several limitations of state-of-the-art pharmacotherapies for these severe mental disorders, demonstration of clinically meaningful additive effects for CBT would have important implications for improving public health. This paper reviews the key developments in this important area of therapeutics, providing a summary of the current state of the art and suggesting directions for future research. C1 [Thase, Michael E.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Kingdon, David] Univ Southampton, Southampton, Hants, England. [Turkington, Douglas] NTW NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England. RP Thase, ME (reprint author), Univ Penn, Perelman Sch Med, 3535 Market St, Philadelphia, PA 19104 USA. NR 50 TC 16 Z9 17 U1 8 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1723-8617 EI 2051-5545 J9 WORLD PSYCHIATRY JI World Psychiatry PD OCT PY 2014 VL 13 IS 3 BP 244 EP 250 DI 10.1002/wps.20149 PG 7 WC Psychiatry SC Psychiatry GA AQ5LR UT WOS:000342851200007 PM 25273290 ER PT J AU Swann, AC AF Swann, Alan C. TI Non-pharmacological and pharmacological treatments act on the same brain SO WORLD PSYCHIATRY LA English DT Editorial Material ID BIPOLAR DISORDERS; DEPRESSION; THERAPY C1 Baylor Coll Med Mental Hlth Care Line, Dept Psychiat & Behav Sci, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Swann, AC (reprint author), Baylor Coll Med Mental Hlth Care Line, Dept Psychiat & Behav Sci, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1723-8617 EI 2051-5545 J9 WORLD PSYCHIATRY JI World Psychiatry PD OCT PY 2014 VL 13 IS 3 BP 262 EP 264 DI 10.1002/wps.20166 PG 4 WC Psychiatry SC Psychiatry GA AQ5LR UT WOS:000342851200016 PM 25273299 ER PT J AU Hedgire, SS Eberhardt, SC Borczuk, R McDermott, S Harisinghani, MG AF Hedgire, Sandeep S. Eberhardt, Steven C. Borczuk, Rachel McDermott, Shaunagh Harisinghani, Mukesh G. TI Interpretation and reporting multiparametric prostate MRI: a primer for residents and novices SO ABDOMINAL IMAGING LA English DT Article DE Prostate cancer; Multiparametric MRI; Interpretation and reporting of prostate MRI; Diffusion-weighted MRI; Dynamic contrast-enhanced MRI (DCE-MRI) ID CONTRAST-ENHANCED MRI; APPARENT DIFFUSION-COEFFICIENT; SEMINAL-VESICLE INVASION; PELVIC LYMPH-NODES; RADICAL PROSTATECTOMY; ACTIVE SURVEILLANCE; LOCAL RECURRENCE; ENDORECTAL COIL; EXTRACAPSULAR EXTENSION; SPATIAL-RESOLUTION AB Multiparametric MRI has developed as a tool for prostate cancer lesion detection, characterization, staging, surveillance, and imaging of local recurrence. Given the disease frequency and the growing importance of imaging, as reliance on PSA declines, radiologists involved in prostate MRI imaging must become proficient with the fundamentals of multiparametric prostate MRI (T2WI, DWI, DCE-MRI, and MR spectroscopy). Interpretation and reporting must yield accuracy, consistency, and add value to clinical care. This review provides a primer to novices and trainees learning about multiparametric prostate MRI. MRI technique is presented along with the use of particular MRI sequences. Relevant prostate anatomy is outlined and imaging features of prostate cancer with staging are discussed. Finally structured reporting is introduced, and some limitations of prostate MRI are discussed. C1 [Hedgire, Sandeep S.; Borczuk, Rachel; McDermott, Shaunagh; Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Eberhardt, Steven C.] Univ New Mexico, Dept Radiol, Albuquerque, NM 87106 USA. RP Hedgire, SS (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM hedgire.sandeep@mgh.harvard.edu NR 79 TC 3 Z9 3 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD OCT PY 2014 VL 39 IS 5 BP 1036 EP 1051 DI 10.1007/s00261-014-0097-x PG 16 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA AP9TB UT WOS:000342421700013 PM 24566965 ER PT J AU Wang, CL Davenport, MS Chinnugounder, S Schopp, JG Kani, K Zaidi, S Hippe, DS Paladin, AM Lalwani, N Bhargava, P Bush, WH AF Wang, Carolyn L. Davenport, Matthew S. Chinnugounder, Sankar Schopp, Jennifer G. Kani, Kimia Zaidi, Sadaf Hippe, Dan S. Paladin, Angelisa M. Lalwani, Neeraj Bhargava, Puneet Bush, William H. TI Errors of epinephrine administration during severe allergic-like contrast reactions: lessons learned from a bi-institutional study using high-fidelity simulation testing SO ABDOMINAL IMAGING LA English DT Article DE Epinephrine; Epinephrine error; Contrast reaction; High-fidelity simulation ID RADIOLOGY RESIDENTS; MEDIA REACTIONS; MANAGEMENT; EMERGENCIES; GUIDELINES; INJECTION; FREQUENCY; OVERDOSE; ASTHMA AB To determine the most common errors of epinephrine administration during severe allergic-like contrast reaction management using high-fidelity simulation surrogates. IRB approval and informed consent were obtained for this HIPAA-compliant bi-institutional prospective study of 40 radiology residents, fellows, and faculty who were asked to manage a structured high-fidelity severe allergic-like contrast reaction scenario (i.e., mild hives progressing to mild bronchospasm, then bronchospasm unresponsive to bronchodilators, and finally anaphylactic shock) on an interactive manikin. Intravenous (IV) and intramuscular epinephrine ampules were available to all participants, and the manikin had a functioning intravenous catheter for all scenarios. Video recordings of their performance were reviewed by experts in contrast reaction management, and errors in epinephrine administration were recorded and characterized. No participant (0/40) failed to give indicated epinephrine, but more than half (58% [23/40]) committed an error while doing so. The most common mistake was to administer epinephrine as the first-line treatment for mild bronchospasm (33% [13/40]). Other common errors were to administer IV epinephrine without a subsequent IV saline flush or concomitant IV fluids (25% [10/40]), administer an overdose of epinephrine (8% [3/40]), and administer epinephrine 1:1000 intravenously (8% [3/40]). Epinephrine administration errors are common. Many radiologists fail to administer albuterol as the first-line treatment for mild bronchospasm and fail to flush the IV catheter when administering IV epinephrine. High-fidelity contrast reaction scenarios can be used to identify areas for training improvement. C1 [Wang, Carolyn L.; Chinnugounder, Sankar; Kani, Kimia; Zaidi, Sadaf; Hippe, Dan S.; Paladin, Angelisa M.; Lalwani, Neeraj; Bush, William H.] Univ Washington, Seattle, WA 98195 USA. [Davenport, Matthew S.] Univ Michigan Hlth Syst, Dept Radiol, Ann Arbor, MI 48109 USA. [Schopp, Jennifer G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bhargava, Puneet] Univ Washington, Seattle, WA 98108 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Wang, CL (reprint author), Univ Washington, 1959 NE Pacific St,Box 357115, Seattle, WA 98195 USA. EM wangcl@uw.edu OI Hippe, Daniel/0000-0003-2427-4404; Bhargava, Puneet/0000-0002-3849-9666 NR 35 TC 3 Z9 3 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD OCT PY 2014 VL 39 IS 5 BP 1127 EP 1133 DI 10.1007/s00261-014-0141-x PG 7 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA AP9TB UT WOS:000342421700021 PM 25237003 ER PT J AU Lim, S Bae, JH Chun, EJ Kim, H Kim, SY Kim, KM Choi, SH Park, KS Florez, JC Jang, HC AF Lim, Soo Bae, Jae Hyun Chun, Eun Ju Kim, Haeryoung Kim, So Yeon Kim, Kyoung Min Choi, Sung Hee Park, Kyong Soo Florez, Jose C. Jang, Hak Chul TI Differences in pancreatic volume, fat content, and fat density measured by multidetector-row computed tomography according to the duration of diabetes SO ACTA DIABETOLOGICA LA English DT Article DE Pancreatic volume; Pancreatic fat; Type 2 diabetes; Multidetector-row computed tomography ID BETA-CELL FUNCTION; METABOLIC SYNDROME; GLUCOSE-TOLERANCE; IMAGE QUALITY; ECTOPIC FAT; CT; INSULIN; TYPE-1; ACIDS; MASS AB Pancreatic volume and fat content might be associated with beta-cell function or insulin resistance (IR). We investigated the difference in pancreatic volume and fat content between age- and body mass index (BMI)-matched normal subjects and patients with having different durations of type 2 diabetes (T2D). We compared pancreatic volume and fat parameters between 50 age- and BMI-matched normal subjects, 51 subjects with newly diagnosed type 2 diabetes (T2D-new), 53 subjects with T2D < 5 years (T2D < 5Y), and 52 subjects with T2D a parts per thousand yen5 years (T2Da parts per thousand yen5Y). Age and BMI were matched to range of +/- 2 years and +/- 0.5 kg/m(2), respectively. Pancreatic volume and fat were measured by multidetector-row computed tomography with 64 detector-row scanner. The difference in Hounsfield units between pancreas and spleen (HUp-s) was investigated for fat density. Anthropometric and biochemical parameters including the homeostasis model assessment of IR (HOMA-IR) and the insulinogenic index (IGI) were measured. Compared with normal subjects, patients with T2D had significantly smaller pancreatic volume, greater pancreatic fat, and lower HUp-s. Among the groups with T2D, pancreatic volume decreased and pancreatic fat percentage and HUp-s increased from the T2D-new to the T2D < 5Y and T2D > 5Y groups. Pancreatic volume and fat and HUp-s values were associated with HbA1c and triglyceride levels. Pancreatic volume was correlated with IGI while pancreatic fat and HUp-s values were correlated with HOMA-IR. The current study suggests that pancreatic volume and fat deposition might be associated with the development and progression of T2D in Korean subjects. C1 [Lim, Soo; Bae, Jae Hyun; Kim, Kyoung Min; Choi, Sung Hee; Park, Kyong Soo; Jang, Hak Chul] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Lim, Soo; Kim, Kyoung Min; Choi, Sung Hee; Jang, Hak Chul] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam 463707, South Korea. [Chun, Eun Ju] Seoul Natl Univ, Bundang Hosp, Dept Radiol, Songnam, South Korea. [Kim, Haeryoung] Seoul Natl Univ, Bundang Hosp, Dept Pathol, Songnam, South Korea. [Kim, So Yeon] Univ Ulsan, Coll Med, Dept Radiol, Seoul, South Korea. [Kim, So Yeon] Univ Ulsan, Coll Med, Res Inst Radiol, Asan Med Ctr, Seoul, South Korea. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Harvard Univ, Sch Med, Boston, MA USA. RP Jang, HC (reprint author), Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. EM janghak@snu.ac.kr RI Park, Kyong Soo/C-2265-2008; OI Park, Kyong Soo/0000-0003-3597-342X; CHOI, SUNG HEE/0000-0003-0740-8116 FU Korean Health Technology Research and Development project, Ministry of Health and Welfare, Republic of Korea [A090623, A092077]; Seoul National University Bundang Hospital Research Fund [03-2009-003] FX This study was supported by a Grant of the Korean Health Technology Research and Development project, Ministry of Health and Welfare, Republic of Korea (A090623 and A092077) and a Grant from the Seoul National University Bundang Hospital Research Fund (No. 03-2009-003). NR 40 TC 9 Z9 9 U1 0 U2 5 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 OCT PY 2014 VL 51 IS 5 BP 739 EP 748 DI 10.1007/s00592-014-0581-3 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP9VB UT WOS:000342427800006 PM 24671510 ER PT J AU Madanat, R Makinen, TJ Aro, HT Bragdon, C Malchau, H AF Madanat, Rami Makinen, Tatu J. Aro, Hannu T. Bragdon, Charles Malchau, Henrik TI Adherence of hip and knee arthroplasty studies to RSA standardization guidelines - A Systematic Review of Studies Published from 2007 to 2011 SO ACTA ORTHOPAEDICA LA English DT Article ID CROSS-LINKED POLYETHYLENE; ROENTGEN STEREOPHOTOGRAMMETRIC ANALYSIS; CEMENTED TIBIAL COMPONENTS; 5-YEAR FOLLOW-UP; RANDOMIZED RADIOSTEREOMETRIC ANALYSIS; CONSTRAINED ACETABULAR COMPONENT; MORSELIZED ALLOGRAFT BONE; FEMORAL-HEAD PENETRATION; COMPARING EARLY FIXATION; EARLY IMPLANT MIGRATION AB Background and purpose-Guidelines for standardization of radiostereometry (RSA) of implants were published in 2005 to facilitate comparison of outcomes between various research groups. In this systematic review, we determined how well studies have adhered to these guidelines. Methods-We carried out a literature search to identify all articles published between January 2000 and December 2011 that used RSA in the evaluation of hip or knee prosthesis migration. 2 investigators independently evaluated each of the studies for adherence to the 13 individual guideline items. Since some of the 13 points included more than 1 criterion, studies were assessed on whether each point was fully met, partially met, or not met. Results-153 studies that met our inclusion criteria were identified. 61 of these were published before the guidelines were introduced (2000-2005) and 92 after the guidelines were introduced (2006-2011). The methodological quality of RSA studies clearly improved from 2000 to 2011. None of the studies fully met all 13 guidelines. Nearly half (43) of the studies published after the guidelines demonstrated a high methodological quality and adhered at least partially to 10 of the 13 guidelines, whereas less than one-fifth (11) of the studies published before the guidelines had the same methodological quality. Commonly unaddressed guideline items were related to imaging methodology, determination of precision from double examinations, and also mean error of rigid-body fitting and condition number cutoff levels. Interpretation-The guidelines have improved methodological reporting in RSA studies, but adherence to these guidelines is still relatively low. There is a need to update and clarify the guidelines for clinical hip and knee arthroplasty RSA studies. C1 [Madanat, Rami; Makinen, Tatu J.] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Aro, Hannu T.] Turku Univ Hosp, FIN-20520 Turku, Finland. [Aro, Hannu T.] Univ Turku, Turku, Finland. [Madanat, Rami; Bragdon, Charles; Malchau, Henrik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harris Orthopaed Lab, Boston, MA USA. RP Madanat, R (reprint author), Univ Helsinki, Cent Hosp, Helsinki, Finland. EM rami.madanat@hus.fi FU Swedish Cultural Foundation in Finland; Jane and Aatos Erkko Foundation; Paulo Foundation; Finnish Medical Foundation FX HM is a stockowner and board member in RSA Biomedical Inc. This study was supported by grants from the Swedish Cultural Foundation in Finland, the Jane and Aatos Erkko Foundation, the Paulo Foundation, and the Finnish Medical Foundation. NR 161 TC 1 Z9 1 U1 2 U2 2 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1745-3674 EI 1745-3682 J9 ACTA ORTHOP JI Acta Orthop. PD OCT PY 2014 VL 85 IS 5 BP 447 EP 455 DI 10.3109/17453674.2014.934187 PG 9 WC Orthopedics SC Orthopedics GA AQ3ZO UT WOS:000342732200001 PM 24954489 ER PT J AU Mizunuma, M Neumann-Haefelin, E Moroz, N Li, YJ Blackwell, TK AF Mizunuma, Masaki Neumann-Haefelin, Elke Moroz, Natalie Li, Yujie Blackwell, T. Keith TI mTORC2-SGK-1 acts in two environmentally responsive pathways with opposing effects on longevity SO AGING CELL LA English DT Article DE aging; microbiome; mTORC2; rictor; serum- and glucocorticoid-regulated kinase; SKN-1/Nrf ID C. ELEGANS; CAENORHABDITIS-ELEGANS; LIFE-SPAN; STRESS-RESPONSE; RAPAMYCIN; METABOLISM; SKN-1; TOR; DAF-16/FOXO; INSULIN AB The nematode worm Caenorhabditiselegans provides a powerful system for elucidating how genetic, metabolic, nutritional, and environmental factors influence aging. The mechanistic target of rapamycin (mTOR) kinase is important in growth, disease, and aging and is present in the mTORC1 and mTORC2 complexes. In diverse eukaryotes, lifespan can be increased by inhibition of mTORC1, which transduces anabolic signals to stimulate protein synthesis and inhibit autophagy. Less is understood about mTORC2, which affects C.elegans lifespan in a complex manner that is influenced by the bacterial food source. mTORC2 regulates C.elegans growth, reproduction, and lipid metabolism by activating the SGK-1 kinase, but current data on SGK-1 and lifespan seem to be conflicting. Here, by analyzing the mTORC2 component Rictor (RICT-1), we show that mTORC2 modulates longevity by activating SGK-1 in two pathways that affect lifespan oppositely. RICT-1/mTORC2 limits longevity by directing SGK-1 to inhibit the stress-response transcription factor SKN-1/Nrf in the intestine. Signals produced by the bacterial food source determine how this pathway affects SKN-1 and lifespan. In addition, RICT-1/mTORC2 functions in neurons in an SGK-1-mediated pathway that increases lifespan at lower temperatures. RICT-1/mTORC2 and SGK-1 therefore oppose or accelerate aging depending upon the context in which they are active. Our findings reconcile data on SGK-1 and aging, show that the bacterial microenvironment influences SKN-1/Nrf, mTORC2 functions, and aging, and identify two longevity-related mTORC2 functions that involve SGK-regulated responses to environmental cues. C1 [Mizunuma, Masaki; Neumann-Haefelin, Elke; Moroz, Natalie; Blackwell, T. Keith] Harvard Univ, Sch Med, Joslin Diabet Ctr, Harvard Stem Cell Inst,Dept Genet, Boston, MA 02215 USA. [Mizunuma, Masaki] Hiroshima Univ, Grad Sch Adv Sci Matter, Dept Mol Biotechnol, Higashihiroshima 7398530, Japan. [Neumann-Haefelin, Elke; Li, Yujie] Univ Hosp Freiburg, Div Renal, D-79106 Freiburg, Germany. [Moroz, Natalie] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Div Biol Sci, Boston, MA 02115 USA. RP Mizunuma, M (reprint author), Hiroshima Univ, Grad Sch Adv Sci Matter, Dept Mol Biotechnol, Higashihiroshima 7398530, Japan. EM mmizu49120@hiroshima-u.ac.jp; keith.blackwell@joslin.harvard.edu FU JSPS; Japan Society for the Promotion of Science; NIH [GM062891]; Joslin Diabetes Center T32 training grant; NIDDK DRC award [DK036836]; DFG [KFO201]; European Social Fund; Ministry of Science, Research, and Arts Baden-Wurttemberg FX M. M. was supported by the JSPS Excellent Young Researchers Overseas Visit Program and by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science. Supported by NIH grant GM062891 to T. K. B., who is a Senior Scholar in Aging of the Ellison Medical Foundation, the Joslin Diabetes Center T32 training grant (N.M.), and an NIDDK DRC award (DK036836) to the Joslin Diabetes Center. E.N.H. was supported by grants from the DFG (KFO201), the European Social Fund, and the Ministry of Science, Research, and Arts Baden-Wurttemberg (Margarete von Wrangell Fellowship). NR 38 TC 14 Z9 14 U1 4 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD OCT PY 2014 VL 13 IS 5 BP 869 EP 878 DI 10.1111/acel.12248 PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA AQ2PY UT WOS:000342631100011 PM 25040785 ER PT J AU Lamming, DW Mihaylova, MM Katajisto, P Baar, EL Yilmaz, OH Hutchins, A Gultekin, Y Gaither, R Sabatini, DM AF Lamming, Dudley W. Mihaylova, Maria M. Katajisto, Pekka Baar, Emma L. Yilmaz, Omer H. Hutchins, Amanda Gultekin, Yetis Gaither, Rachel Sabatini, David M. TI Depletion of Rictor, an essential protein component of mTORC2, decreases male lifespan SO AGING CELL LA English DT Article DE aging; gender dimorphism; longevity; mTORC2; Rictor; Rapamycin ID COMPLEX 2; RAPAMYCIN; MICE; PHOSPHORYLATION; LONGEVITY; EXTENSION; SIROLIMUS; AKT/PKB; GROWTH; PKC AB Rapamycin, an inhibitor of the mechanistic target of rapamycin (mTOR), robustly extends the lifespan of model organisms including mice. We recently found that chronic treatment with rapamycin not only inhibits mTOR complex 1 (mTORC1), the canonical target of rapamycin, but also inhibits mTOR complex 2 (mTORC2) in vivo. While genetic evidence strongly suggests that inhibition of mTORC1 is sufficient to promote longevity, the impact of mTORC2 inhibition on mammalian longevity has not been assessed. RICTOR is a protein component of mTORC2 that is essential for its activity. We examined three different mouse models of Rictor loss: mice heterozygous for Rictor, mice lacking hepatic Rictor, and mice in which Rictor was inducibly deleted throughout the body in adult animals. Surprisingly, we find that depletion of RICTOR significantly decreases male, but not female, lifespan. While the mechanism by which RICTOR loss impairs male survival remains obscure, we find that the effect of RICTOR depletion on lifespan is independent of the role of hepatic mTORC2 in promoting glucose tolerance. Our results suggest that inhibition of mTORC2 signaling is detrimental to males, which may explain in part why interventions that decrease mTOR signaling show greater efficacy in females. C1 [Lamming, Dudley W.; Baar, Emma L.] Univ Wisconsin, Dept Med, Madison, WI 53705 USA. [Lamming, Dudley W.; Baar, Emma L.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Lamming, Dudley W.; Mihaylova, Maria M.; Katajisto, Pekka; Yilmaz, Omer H.; Hutchins, Amanda; Gultekin, Yetis; Gaither, Rachel; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Lamming, Dudley W.; Mihaylova, Maria M.; Katajisto, Pekka; Yilmaz, Omer H.; Hutchins, Amanda; Gultekin, Yetis; Gaither, Rachel; Sabatini, David M.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Lamming, Dudley W.; Mihaylova, Maria M.; Katajisto, Pekka; Yilmaz, Omer H.; Hutchins, Amanda; Gultekin, Yetis; Gaither, Rachel; Sabatini, David M.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Lamming, Dudley W.; Mihaylova, Maria M.; Katajisto, Pekka; Yilmaz, Omer H.; Hutchins, Amanda; Gultekin, Yetis; Gaither, Rachel; Sabatini, David M.] Broad Inst Harvard & MIT, Seven Cambridge Ctr, Cambridge, MA 02142 USA. [Lamming, Dudley W.; Mihaylova, Maria M.; Katajisto, Pekka; Yilmaz, Omer H.; Hutchins, Amanda; Gultekin, Yetis; Gaither, Rachel; Sabatini, David M.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP Lamming, DW (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,Room C3127 Res 151, Madison, WI 53705 USA. EM dlamming@medicine.wisc.edu; sabatini@wi.mit.edu RI Gultekin, Yetis/H-4194-2013; OI Lamming, Dudley/0000-0002-0079-4467 FU National Institute of Health; UW-Madison School of Medicine and Public Health; UW-Madison Department of Medicine; American Federation for Aging Research; Starr Foundation; Koch Institute Frontier Research Program; Ellison Medical Foundation; NIH/NIA [AG041765]; Damon Runyon Cancer Research Foundation [DRG-2146-13]; American Diabetes Association FX We would like to thank all the members of the Lamming and Sabatini labs. The Lamming lab is supported by a grant from the National Institute of Health and startup funds from the UW-Madison School of Medicine and Public Health and the UW-Madison Department of Medicine. The Sabatini lab is supported by grants from the National Institutes of Health and awards from the American Federation for Aging Research, Starr Foundation, Koch Institute Frontier Research Program, and the Ellison Medical Foundation to D. M. S. D. W. L is supported in part by a K99/R00 Pathway to Independence Award from the NIH/NIA (AG041765). M. M. is a Robert Black Fellow of the Damon Runyon Cancer Research Foundation, DRG-2146-13. P. K was supported by a mentor- based fellowship award from the American Diabetes Association. D. M. S. is an investigator of Howard Hughes Medical Institute. This work was supported using facilities and resources from the William S. Middleton Memorial Veterans Hospital. This work does not represent the views of the Department of Veterans Affairs or the United States Government. NR 32 TC 21 Z9 22 U1 4 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD OCT PY 2014 VL 13 IS 5 BP 911 EP 917 DI 10.1111/acel.12256 PG 7 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA AQ2PY UT WOS:000342631100015 PM 25059582 ER PT J AU Rigotti, NA Park, ER Streck, J Chang, YC Reyen, M McKool, K Winickoff, JP AF Rigotti, Nancy A. Park, Elyse R. Streck, Joanna Chang, Yuchiao Reyen, Michele McKool, Kathleen Winickoff, Jonathan P. TI An Intervention to Address Secondhand Tobacco Smoke Exposure Among Nonsmokers Hospitalized With Coronary Heart Disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article AB Secondhand tobacco smoke (SHS) exposure increases nonsmokers' risk of coronary heart disease and worsens outcomes after hospitalization for acute coronary syndrome, but it is rarely addressed in inpatient cardiac care. We developed and assessed a hospital-based intervention to increase nonsmokers' awareness of SHS as a cardiovascular risk factor. Nonsmokers admitted to 2 cardiac units of a large Boston, Massachusetts, hospital were surveyed before (May 2010 to January 2011) and after (November 2011 to March 2012) a system-level nurse-delivered intervention was implemented in October 2011. It consisted of a revised admission form that prompted nurses to document SHS exposure at admission, provide a pamphlet about SHS risks, and advise nonsmokers to make their home and car smoke free. The primary outcome was patients' short-term recall of advice to keep their home and car smoke free. The secondary outcome was patients' awareness of the cardiovascular risk of SHS exposure. We enrolled 190 nonsmokers before and 142 nonsmokers after implementation. Adjusting for group differences, patients admitted after the system change were more likely to recall being asked if a household member smokes (24% vs 10%, adjusted odds ratio [AOR] 3.6, 95% confidence interval [CI] 1.8 to 7.1, p = 0.0002) and being advised to keep their home and car smoke free (28% vs 2%, AOR 27.3, 95% CI 7.8 to 95.7, p <0.0001). After the intervention, more patients believed that SHS exposure increased cardiovascular risk for nonsmokers (42% vs 21%, AOR 2.6, 95% CI 1.6 to 4.4) and for themselves (39% vs 22%, AOR 2.2,95% CI 1.3 to 3.8). In conclusion, a system-level intervention in cardiac units successfully increased hospitalized nonsmokers' awareness of the cardiovascular risk of SHS exposure. (C) 2014 Elsevier Inc. All rights reserved. C1 [Rigotti, Nancy A.; Park, Elyse R.; Streck, Joanna; Reyen, Michele; McKool, Kathleen; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Rigotti, Nancy A.; Streck, Joanna; Chang, Yuchiao; Reyen, Michele] Massachusetts Gen Hosp, Med Serv, Div Gen Internal Med, Boston, MA 02114 USA. [Rigotti, Nancy A.; Park, Elyse R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Rigotti, Nancy A.; Park, Elyse R.] Partners HealthCare, Boston, MA USA. [Rigotti, Nancy A.; Streck, Joanna; Chang, Yuchiao] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Park, Elyse R.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Winickoff, Jonathan P.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. EM nrigotti@partners.org FU Flight Attendant Medical Research Institute, Miami, Florida [082472-CIA] FX This study was supported by a grant 082472-CIA from the Flight Attendant Medical Research Institute, Miami, Florida. NR 7 TC 2 Z9 2 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2014 VL 114 IS 7 BP 1040 EP 1045 DI 10.1016/j.amjcard.2014.07.017 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AQ3SP UT WOS:000342714100014 PM 25124185 ER PT J AU Kovach, AE DeLelys, ME Kelliher, AS Dillon, LJ Hasserjian, RP Ferry, JA Preffer, FI Sohani, AR AF Kovach, Alexandra E. DeLelys, Michelle E. Kelliher, Abigail S. Dillon, Laura J. Hasserjian, Robert P. Ferry, Judith A. Preffer, Frederic I. Sohani, Aliyah R. TI Diagnostic utility of cerebrospinal fluid flow cytometry in patients with and without prior hematologic malignancy SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMAS; LEPTOMENINGEAL DISEASE; HIGH-RISK; CYTOPATHOLOGY; IDENTIFICATION; SENSITIVITY; INVOLVEMENT; SPECIMENS AB Flow cytometry (FCM) is an adjunct study to routine analysis of cerebrospinal fluid (CSF) to investigate for involvement by a hematologic malignancy. However, in our experience, FCM only infrequently detects abnormalities in CSF. To help optimize resources without forfeiting clinically important data, we sought to determine evidence-based indications and criteria for performing FCM on CSF. FCM results of 316 consecutive CSF specimens were retrospectively reviewed and correlated with clinical history, total nucleated cell (TNC) counts, and results of concurrent cytologic review. Of 255 samples adequate for analysis, 54% were from patients with a prior history of hematologic malignancy, of which 12% (17 cases) were abnormal by FCM. Corresponding TNC counts among samples with abnormal FCM ranged from 0-1050 cells/mu L, and only 44% showed abnormal morphology on concurrent cytology. Of the remaining 46% of samples from patients with no known history of hematologic malignancy who had CSF sampling for neurological indications, only one (1%) was abnormal by FCM. This specimen had an elevated TNC count (39 cells/mu L) but lacked clearly abnormal findings on concurrent cytology. These results support the use of CSF FCM only in patients with a history of hematologic malignancy or, in the absence of such a history, in samples showing pleocytosis. If these criteria were applied to the current cohort using a TNC count cut-off of > 5 cells/mu L, 23% of samples would have been deferred from testing, resulting in decreased cost, improved efficiency, and reduction in the need for unnecessary testing without a negative impact on clinical care. Am. J. Hematol. 89:978-984, 2014. (c) 2014 Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Sohani, AR (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 219, Boston, MA 02114 USA. EM arsohani@partners.org NR 32 TC 1 Z9 1 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD OCT PY 2014 VL 89 IS 10 BP 978 EP 984 DI 10.1002/ajh.23806 PG 7 WC Hematology SC Hematology GA AQ3JR UT WOS:000342689200013 PM 25042070 ER PT J AU Goldberg, RA Shah, CP Wiegand, TW Heier, JS AF Goldberg, Roger A. Shah, Chirag P. Wiegand, Torsten W. Heier, Jeffrey S. TI Noninfectious Inflammation After Intravitreal Injection of Aflibercept: Clinical Characteristics and Visual Outcomes SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR INFLAMMATION; RANIBIZUMAB INJECTIONS; ENDOPHTHALMITIS; BEVACIZUMAB; TRIAMCINOLONE AB PURPOSE: To report the presenting features and clinical outcomes of a series of patients with noninfectious inflammation after intravitreal aflibercept injection. DESIGN: Noncomparative consecutive case series. METHODS: Medical records of patients who presented with noninfectious inflammation after intravitreal aflibercept injection between November 18, 2011 and June 30, 2013 were retrospectively reviewed. RESULTS: A total of 20 cases of postinjection inflammation were identified in 5356 aflibercept injections. The patients presented 1-13 days after aflibercept injection (median 3 days); all noted decreased vision, while 3 of 20 (15%) had pain and 2 of 20 (10%) had conjunctival injection. One patient had a hypopyon (0.5 mm), and the average anterior chamber cell was 1.8+ (range 0 to 4+). All eyes had some degree of vitritis (average 1.8+; range 0.5+ to 4+). Patients on average had received 6 prior aflibercept injections (range 0-16). Only 1 patient the first to present with inflammation in this series received an intravitreal tap (culture negative) and injection of antibiotics. All patients were managed with frequent topical steroids and were followed closely for signs of improvement. All but 1 patient regained their preinjection visual acuity (average: 33 days; range: 7-73 days). Four patients were subsequently rechallenged with aflibercept, and 1 developed inflammation again after 5 additional aflibercept injections. The overall incidence of inflammation after intravitreal aflibercept injection was 20 of 5356 injections (0.37%) or 19 of 844 patients (2.25%). However, a disproportionate number of cases clustered around 1 provider (17/20, 85%; P < .001 vs all other providers) and around the 2 office locations where this physician primarily worked (16/20, 75%; P < .001 vs 5 other offices). CONCLUSIONS: Noninfectious inflammation after intravitreal aflibercept injection typically presents without pain, conjunctival injection, or hypopyon, and responds to topical steroid therapy. The visual outcomes are generally favorable, though the return to baseline acuity can take many weeks. (C) 2014 by Elsevier Inc. All rights reserved. C1 [Goldberg, Roger A.; Shah, Chirag P.; Wiegand, Torsten W.; Heier, Jeffrey S.] Massachusetts Eye & Ear Infirm, Retina Serv, Ophthalm Consultants Boston, Boston, MA 02114 USA. RP Goldberg, RA (reprint author), Bay Area Retina Associates, 122 La Casa Via 223, Walnut Creek, CA 94598 USA. EM rgoldberg.eyemd@gmail.com OI Heier, Jeffrey/0000-0003-4625-3145 FU Alcon; Alimera; Allergan; Fovea; Genentech; Genzyme; Novartis; Ohr; Ophthotech; Regeneron; GlaxoSmithKline; Neovista; Notal Vision; Paloma; Center for Eye Research and Education Foundation, Boston, Massachusetts, USA FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST and have made the following disclosure(s): R.A.G., C.P.S., T.W.W.-Sub-investigator on studies with the following sponsors: Alcon, Alimera, Allergan, Fovea, Genentech, Genzyme, Partners, Novartis, Ohr, Ophthotech, Regeneron; JSH-Consultancy: Acucela, Aerpio, Allergan, Bausch & Lomb, Bayer, Endo Optiks, Fovea, Genentech, Genzyme, GlaxoSmithKline, Kanghong, Notal Vision, Oraya, Paloma, QLT, Regeneron, Sequenom; Research Grant: Alcon, Alimera, Allergan, Fovea, Genentech, Genzyme, GlaxoSmithKline, Neovista, Notal Vision, Novartis, Ophthotech, Paloma, Regeneron. Funding support was received from The Center for Eye Research and Education Foundation, Boston, Massachusetts, USA. Contributions of authors: All authors listed have made substantive intellectual contributions to this study including the conception and design, acquisition of data, analysis/interpretation of data, revisions, and final approval of the version to be published. NR 17 TC 10 Z9 10 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2014 VL 158 IS 4 BP 733 EP 737 DI 10.1016/j.ajo.2014.06.019 PG 5 WC Ophthalmology SC Ophthalmology GA AQ1PI UT WOS:000342552900011 PM 24983791 ER PT J AU Werdich, XQ Jakobiec, FA Curtin, HD Fay, A AF Werdich, Xiang Q. Jakobiec, Frederick A. Curtin, Hugh D. Fay, Aaron TI A Clinical, Radio logic, and Immunopathologic Study of Five Periorbital Intraosseous Cavernous Vascular Malformations SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PRIMARY HEMANGIOMA; VERTEBRAL HEMANGIOMAS; CAPILLARY HEMANGIOMA; FACIAL BONE; DIAGNOSIS; ZYGOMA; ORBIT; CLASSIFICATION; MANAGEMENT; ANOMALIES AB PURPOSE: To correlate the clinical, radiographic, histopathologic, and immunohistochemical features of 5 primary periorbital intraosseous cavernous vascular malformations. DESIGN: Retrospective interventional case series. METHODS: Clinical and operative records and radiographic images were reviewed. Histopathologic slides were evaluated with hematoxylin-eosin, trichrome, and elastin stains. Immunohistochemical studies were performed with a spectrum of monoclonal antibodies directed at antigens of vascular cells. RESULTS: Three men and 2 women ranged in age from 36 to 64 years. Vision was unaffected and there was no proptosis or globe displacement. The slow-growing lesions measured 13-25 mm in greatest diameter (mean 16.4 mm). Computed tomographic studies revealed that 2 lesions were situated in the maxillary bone, 2 in the frontal, and 1 in the zygoma, all anteriorly and with circumscribed, lucent, honeycombed, or sunburst characteristics. Histopathologically the lesions were composed of cavernous or telangiectatic channels; 1 showed advanced fibrotic vascular involution. Immunohistochemistry demonstrated CD31/34 positivity for vascular endothelium and D2-40 negativity for lymphatic endothelium. A typically thin mural myofibroblastic cuff was smooth muscle actin positive, weakly calponin positive, and desmin negative. Glucose transporter-1 and Ki-67 were negative in the endothelium. CONCLUSIONS: Intraosseous vascular lesions resemble orbital cavernous venous malformations (not true hemangiomas), except that their vascular walls are thinner owing to the constraints imposed by neighboring bone spicules, which limit the amount of interstitium from which mural myofibroblasts can be recruited. The bony trabeculae conferred the honeycomb or sunburst appearances observed radiographically. En bloc excision of these lesions was successful and avoided complications (mean follow-up, 46 months). (C) 2014 by Elsevier Inc. All rights reserved. C1 [Werdich, Xiang Q.; Jakobiec, Frederick A.] David G Cogan Lab Ophthalm Pathol, Boston, MA USA. [Curtin, Hugh D.] Dept Radiol, Boston, MA USA. [Werdich, Xiang Q.; Jakobiec, Frederick A.; Curtin, Hugh D.; Fay, Aaron] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Werdich, Xiang Q.; Jakobiec, Frederick A.; Curtin, Hugh D.; Fay, Aaron] Harvard Univ, Sch Med, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Suite 328,243 Charles St, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 55 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2014 VL 158 IS 4 BP 816 EP 826 DI 10.1016/j.ajo.2014.07.004 PG 11 WC Ophthalmology SC Ophthalmology GA AQ1PI UT WOS:000342552900023 PM 25034115 ER PT J AU Jakobiec, FA Rashid, A Lane, KA Kazim, M AF Jakobiec, Frederick A. Rashid, Alia Lane, Katherine A. Kazim, Michael TI Granulomatous Dacryoadenitis in Regional Enteritis (Crohn Disease) SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID NASOLACRIMAL DUCT OBSTRUCTION; ORBITAL MYOSITIS; NECROBIOTIC XANTHOGRANULOMA; ULCERATIVE-COLITIS; TUBERCULOUS DACRYOADENITIS; MULTIPLE-MYELOMA; LACRIMAL GLAND; RECALCITRANT; INFLAMMATION; DIAGNOSIS AB PURPOSE: To evaluate the clinical and immunopathologic features of 2 patients with bilateral dacryoadenitis associated with regional enteritis. DESIGN: Retrospective, clinicopathologic study. METHODS: Clinical records, photographs, and imaging studies were reviewed and microscopic sections of lacrimal gland biopsy samples were critically re-evaluated. The microscopic slides were stained with hematoxylin and eosin, special stains for organisms, and a range of immunohistochemical biomarkers, including CD3, CD4, CD5, CD8, CD20, CD68, CD138, CD1a, and immunoglobulins Ig G, IgG4, and IgA. RESULTS: Both patients were young women with a well-established diagnosis of regional enteritis. Histopathologic examination of biopsy samples disclosed moderate intraparenchymal fibrosis and lymphoplasmacytic infiltrates without lymphoid follicles. Small to medium intraparenchymal, noncaseating granulomas lacking multinucleated giant cells and, in 1 patient, CD68-positive and CD la-negative palisading granulomas in widened interlobular fibrous septa were detected. Vasculitis and IgG4 plasma cells were not observed. Additional immunohistochemical studies revealed that CD8 T lymphocytes (suppressor or cytotoxic subset) predominated over CD4-positive T lymphocytes (helper cells) surrounding the necrobiotic foci and were intermixed with the CD68-positive histiocytes in the absence of CD20 B lymphocytes. Special stains for organisms demonstrated negative results. CONCLUSIONS: Dacryoadenitis is the rarest form of ocular adnexal involvement in regional enteritis, which affects the orbit far more frequently than ulcerative colitis. It is a granulomatous process with the possibility of palisading necrobiotic foci. In contrast, ulcerative colitis causes an interstitial lymphocytic and nongranulomatous myositis. Sarcoidosis, Wegener granulomatosis, and pseudorheumatoid nodules must be ruled out. Treatment options entail a wide variety of agents with selection based on empirical considerations and tailored to the patient's symptoms. (C) 2014 by Elsevier Inc. All rights reserved. C1 [Jakobiec, Frederick A.; Rashid, Alia] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Rashid, Alia] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Lane, Katherine A.] Ophthalm Consultants Vermont, S Burlington, VT USA. [Kazim, Michael] New York Hosp, Edward S Harkness Eye Inst, New York, NY 10021 USA. [Kazim, Michael] Columbia Univ, New York, NY USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, 243 Charles St,Suite 328, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu OI Lane, Katherine/0000-0002-4110-5058 NR 40 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2014 VL 158 IS 4 BP 838 EP 844 DI 10.1016/j.ajo.2014.07.011 PG 7 WC Ophthalmology SC Ophthalmology GA AQ1PI UT WOS:000342552900026 PM 25036879 ER PT J AU Pachucki, MC Lovenheim, MF Harding, M AF Pachucki, Mark C. Lovenheim, Michael F. Harding, Matthew TI Within-Family Obesity Associations Evaluation of Parent, Child, and Sibling Relationships SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID BODY-MASS INDEX; PHYSICAL-ACTIVITY; ADULT OBESITY; FOOD PREFERENCES; ADOLESCENTS; TRAJECTORIES; AGGREGATION; PREVALENCE; PREDICTORS; OVERWEIGHT AB Background: How parent and sibling obesity status comparatively shape a child's obesity is unknown. Purpose: To investigate how the obesity status of different children within the same family is related to a parent or sibling's obesity. Methods: A national sample of adults in 10,244 American households was surveyed during 2011; data were analyzed in 2012-2013. Of these households, 1,948 adults had one or two children; provided sociodemographic information; and reported on adult and child height and weight, physical activity, and food environment. Logistic regression models were estimated in which the outcome of interest was child obesity status, with parent and sibling obesity as key predictors, adjusting for a range of both adult and child social and demographic confounders. Results: In one-child households, it was 2.2 times more likely (SE=0.5) that the child would be obese if a parent was obese. In households with two children, having an obese younger sibling was more strongly associated with elder-child obesity (OR=5.4, SE=1.9) than parent's obesity status (OR=2.3, SE=0.8). Having an obese elder sibling was associated with younger-child obesity (OR= 5.6, SE=1.9), and parent obesity status was no longer significant. Within-family sibling obesity was more strongly patterned between siblings of the same gender than between different genders, and child physical activity was significantly associated with obesity status. Conclusions: Considering offspring composition and sibling gender may be beneficial in childhood obesity prevention and intervention. (C) 2014 American Journal of Preventive Medicine C1 [Pachucki, Mark C.] Massachusetts Gen Hosp, MassGen Hosp Children, Mongan Inst Hlth Policy, Div Gen Acad Pediat, Boston, MA 02114 USA. [Pachucki, Mark C.] Harvard Univ, Sch Med, Boston, MA USA. [Lovenheim, Michael F.] Natl Bur Econ Res, Boston, MA USA. [Lovenheim, Michael F.] Cornell Univ, Dept Policy Anal & Management, Ithaca, NY USA. [Harding, Matthew] Duke Univ, Sanford Sch Publ Policy, Durham, NC USA. RP Pachucki, MC (reprint author), Mongan Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM mpachucki@mgh.harvard.edu FU Robert Wood Johnson Foundation [69294]; Robert Wood Johnson Foundation Health and Society at the University of California, Berkeley; University of California, San Francisco; Dr. Pachucki's fellowship FX This research was supported by funding from the Robert Wood Johnson Foundation Healthy Eating Research program (Grant No. 69294), and Dr. Pachucki's fellowship with the Robert Wood Johnson Foundation Health and Society Scholars Program at the University of California, Berkeley, and University of California, San Francisco. NR 43 TC 1 Z9 1 U1 1 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2014 VL 47 IS 4 BP 382 EP 391 DI 10.1016/j.amepre.2014.05.018 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA AP9GJ UT WOS:000342386700004 PM 25015563 ER PT J AU Tuerk, PW AF Tuerk, Peter W. TI Starting From Something: Augmenting Exposure Therapy and Methods of Inquiry SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; SOCIAL ANXIETY DISORDER; D-CYCLOSERINE; PROLONGED EXPOSURE; DOUBLE-BLIND; METAANALYSIS; PHOBIA; AUGMENTATION; ENHANCEMENT C1 [Tuerk, Peter W.] Vet Hlth Adm, Ralph H Johnson VA Med Ctr, Charleston, SC 29403 USA. [Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Mil Sci Div, Charleston, SC 29425 USA. RP Tuerk, PW (reprint author), Vet Hlth Adm, Ralph H Johnson VA Med Ctr, Charleston, SC 29403 USA. EM tuerk@musc.edu NR 19 TC 2 Z9 2 U1 2 U2 6 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 OCT PY 2014 VL 171 IS 10 BP 1034 EP 1037 DI 10.1176/appi.ajp.2014.14070880 PG 4 WC Psychiatry SC Psychiatry GA AQ3SM UT WOS:000342713800004 PM 25272341 ER PT J AU Hicks, CW Hodin, RA Savitt, L Bordeianou, L AF Hicks, Caitlin W. Hodin, Richard A. Savitt, Lieba Bordeianou, Liliana TI Does intramesorectal excision for ulcerative colitis impact bowel and sexual function when compared with total mesorectal excision? SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Ulcerative colitis; Intramesorectal excision; Total mesorectal excision; Ileal pouch anal anastomosis; Functional outcomes; Quality of life ID POUCH-ANAL ANASTOMOSIS; QUALITY-OF-LIFE; INCONTINENCE SEVERITY INDEX; ERECTILE FUNCTION IIEF; TERM-FOLLOW-UP; RESTORATIVE PROCTOCOLECTOMY; FECAL INCONTINENCE; INTERNATIONAL INDEX; RECTAL-CANCER; INSTRUMENT AB BACKGROUND: Proctectomy for ulcerative colitis (UC) can be performed via intramesorectal (IME) or total mesorectal excision (TME). METHODS: We compared patient-reported bowel and sexual function among IME versus TME UC patients (September 2000 to March 2011) using the Memorial Sloan-Kettering Cancer Center Bowel Function scale, Fecal Incontinence Quality of Life, Fecal Incontinence Severity Index, Female Sexual Function Instrument, and International Index of Erectile Dysfunction surveys. RESULTS: Eighty-nine IME versus TME patients (35 +/- 2 years, 57% male, 62% IME) had similar baseline characteristics, although IME patients had more open procedures (P <= .03). IME patients reported better fecal continence (P = .009) but similar fecal incontinence-related quality of life (P >= .44). For sexual function, there were no differences for either women (Female Sexual Function Instrument; P >= .20) or men (International Index of Erectile Dysfunction; P >= .22). CONCLUSIONS: IME appears to be associated with better fecal continence but no difference in overall bowel or sexual function compared with TME in patients with UC. (C) 2014 Elsevier Inc. All rights reserved. C1 [Hicks, Caitlin W.; Hodin, Richard A.; Savitt, Lieba; Bordeianou, Liliana] Massachusetts Gen Hosp, Dept Surg, Crohns & Colitis Ctr, Boston, MA 02114 USA. [Hicks, Caitlin W.] Johns Hopkins Univ Hosp, Dept Surg, Baltimore, MD 21287 USA. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Dept Surg, Crohns & Colitis Ctr, Boston, MA 02114 USA. EM lbordeianou@partners.org NR 37 TC 4 Z9 4 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD OCT PY 2014 VL 208 IS 4 BP 499 EP + DI 10.1016/j.amjsurg.2014.05.012 PG 10 WC Surgery SC Surgery GA AQ3II UT WOS:000342684800001 PM 25124292 ER PT J AU Sangji, NF AF Sangji, Naveen F. TI Repeal of the Sustainable Growth Rate: an overview for surgeons SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Sustainable growth rate; Medicare; Health policy; Physician payment; Advocacy; Repeal AB BACKGROUND: The Medicare sustainable growth rate (SGR) formula is used to control Medicare spending on physician services. Under the current SGR formula, physicians face an almost 24% cut to the Medicare fee schedule on April 1, 2015. The US House Way & Means and Energy & Commerce Committees and the Senate Finance Committee released jointly proposed legislation to permanently repeal the SGR, and transition Medicare physician payment to a value-based payment method. This review summarizes the key components of the proposed legislation, and discusses some of the political challenges ahead. DATA SOURCES: House Committees on Energy & Commerce and Ways & Means, and the Senate Committee on Finance staff write-ups. CONCLUSIONS: Physician Medicare reimbursement will move from a volume-based model to a value-based model over the next decade. Surgeons should remain engaged with the political process to ensure repeal of the SGR. (C) 2014 Elsevier Inc. All rights reserved. C1 [Sangji, Naveen F.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sangji, Naveen F.] Amer Coll Surg, Div Advocacy & Hlth Policy, Boston, MA USA. RP Sangji, NF (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM naveen.sangji@gmail.com FU E. A. Codman Fellowship at the Massachusetts General Hospital Department of Surgery FX The author was a Health Policy Fellow for the American College of Surgeons (ACS) Division of Advocacy and Health Policy (DAHP) at the time of submission of this manuscript. John Hedstrom, JD, Deputy Director of the ACS DAHP assisted with editing of the manuscript. She was funded through the E. A. Codman Fellowship at the Massachusetts General Hospital Department of Surgery. NR 1 TC 0 Z9 0 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD OCT PY 2014 VL 208 IS 4 BP 597 EP 600 DI 10.1016/j.amjsurg.2014.06.010 PG 4 WC Surgery SC Surgery GA AQ3II UT WOS:000342684800016 PM 25132628 ER PT J AU Mavros, MN Velmahos, GC Larentzakis, A Yeh, DD Fagenholz, P de Moya, M King, DR Lee, J Kaafarani, HMA AF Mavros, Michael N. Velmahos, George C. Larentzakis, Andreas Yeh, Daniel Dante Fagenholz, Peter de Moya, Marc King, David R. Lee, Jarone Kaafarani, Haytham M. A. TI Opening Pandora's box: understanding the nature, patterns, and 30-day outcomes of intraoperative adverse events SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Intraoperative adverse event; Accidental puncture or laceration; Outcomes ID QUALITY IMPROVEMENT PROGRAM; PATIENT SAFETY INDICATORS; SURGERY; COMPLICATIONS; RISK; ENTEROTOMY; MORBIDITY; REPAIR; CARE AB BACKGROUND: Little evidence exists regarding the characteristics of intraoperative adverse events (iAEs). METHODS: Administrative data, the American College of Surgeons - National Surgical Quality Improvement Project, and systematic review of operative reports were used to confirm iAEs in abdominal surgery patients. Standard American College of Surgeons - National Surgical Quality Improvement Project data were supplemented with variables including injury type/organ, phase of operation, adhesions, repair type, and intraoperative consultations. RESULTS: Two hundred twenty-seven iAEs (187 patients) were confirmed in 9,292 patients. Most common injuries were enterotomies during intestinal surgery (68%) and vessel injuries during hepatopancreaticobiliary surgery (61%); 108 iAEs (48%) specifically occurred during adhesiolysis. A third of the iAEs required organ/tissue resection or complex reconstruction. Because of iAEs, 20 intraoperative consults (11%) were requested and 9 of the 66 (16%) laparoscopic cases were converted to open. Thirty-day mortality and morbidity were 6% and 58%, respectively. The complications included perioperative transfusions (36%), surgical site infection (19%), systemic sepsis (13%), and failure to wean off the ventilator (12%). CONCLUSIONS: iAEs commonly occur in reoperative cases requiring lysis of adhesions and possibly lead to increased patient morbidity. Understanding iAEs is essential to prevent their occurrence and mitigate their adverse effects. (C) 2014 Elsevier Inc. All rights reserved. C1 [Mavros, Michael N.; Velmahos, George C.; Larentzakis, Andreas; Yeh, Daniel Dante; Fagenholz, Peter; de Moya, Marc; King, David R.; Lee, Jarone; Kaafarani, Haytham M. A.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Mavros, Michael N.; Velmahos, George C.; Larentzakis, Andreas; Yeh, Daniel Dante; Fagenholz, Peter; de Moya, Marc; King, David R.; Lee, Jarone; Kaafarani, Haytham M. A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Mavros, Michael N.] MedStar Washington Hosp Ctr, Dept Surg, Washington, DC 20010 USA. RP Kaafarani, HMA (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. EM hkaafarani@mgh.harvard.edu OI King, David/0000-0003-1028-1478 NR 21 TC 6 Z9 6 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD OCT PY 2014 VL 208 IS 4 BP 626 EP 631 DI 10.1016/j.amjsurg.2014.02.014 PG 6 WC Surgery SC Surgery GA AQ3II UT WOS:000342684800020 PM 24953016 ER PT J AU Liang, MK Li, LT Nguyen, MT Berger, RL Hicks, SC Kao, LS AF Liang, Mike K. Li, Linda T. Nguyen, Mylan T. Berger, Rachel L. Hicks, Stephanie C. Kao, Lillian S. TI Abdominal reoperation and mesh explantation following open ventral hernia repair with mesh SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Hernia; Ventral; Incisional; Umbilical; Reoperation; Mesh ID RANDOMIZED CONTROLLED-TRIAL; INCISIONAL HERNIA; SYNTHETIC MESH; SUTURE REPAIR; HERNIORRHAPHY; INFECTION; OUTCOMES; RISK AB BACKGROUND: This study sought to identify the incidence, indications, and predictors of abdominal reoperation and mesh explantation following open ventral hernia repair with mesh (OVHR). METHODS: A retrospective cohort study of all patients at a single institution who underwent an OVHR from 2000 to 2010 was performed. Patients who required subsequent abdominal reoperation or mesh explantation were compared with those who did not. Reasons for reoperation were recorded. The 2 groups were compared using univariate and multivariate analysis (MVA). RESULTS: A total of 407 patients were followed for a median (range) of 57 (1 to 143) months. Subsequent abdominal reoperation was required in 69 (17%) patients. The most common reasons for reoperation were recurrence and surgical site infection. Only the number of prior abdominal surgeries was associated with abdominal reoperation on MVA. Twenty-eight patients (6.9%) underwent subsequent mesh explantation. Only the Ventral Hernia Working Group grade was associated with mesh explantation on MVA. CONCLUSIONS: Abdominal reoperation and mesh explantation following OVHR are common. Overwhelmingly, surgical complications are themost common causes for reoperation and mesh explantation. (C) 2014 Elsevier Inc. All rights reserved. C1 [Liang, Mike K.; Nguyen, Mylan T.; Kao, Lillian S.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Li, Linda T.; Berger, Rachel L.] Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. [Hicks, Stephanie C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Liang, MK (reprint author), Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. EM ml3@bcm.edu RI Liang, Mike/L-8493-2015; OI Liang, Mike/0000-0001-7063-7291; Hicks, Stephanie/0000-0002-7858-0231 FU Center for Clinical and Translational Sciences - National Institutes of Health Clinical and Translational Award [UL1 TR000371]; National Center for Advancing Translational Sciences [KL2 TR000370] FX This work was supported by the Center for Clinical and Translational Sciences, which is funded by National Institutes of Health Clinical and Translational Award UL1 TR000371 and KL2 TR000370 from the National Center for Advancing Translational Sciences. 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 25 TC 11 Z9 11 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD OCT PY 2014 VL 208 IS 4 BP 670 EP 676 DI 10.1016/j.amjsurg.2013.10.024 PG 7 WC Surgery SC Surgery GA AQ3II UT WOS:000342684800029 PM 25241955 ER PT J AU Lowalekar, SK Cao, H Lu, XG Treanor, PR Thatte, HS AF Lowalekar, S. K. Cao, H. Lu, X. -G. Treanor, P. R. Thatte, H. S. TI Subnormothermic Preservation in Somah: A Novel Approach for Enhanced Functional Resuscitation of Donor Hearts for Transplant SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Basic (laboratory) research/science; diagnostic techniques and imaging: echocardiography; donors and donation; graft survival; heart (allograft) function/dysfunction; heart failure/injury; heart transplantation/cardiology; organ transplantation in general; translational research/science ID ISCHEMIA-REPERFUSION; PHOSPHOCREATINE; PRINCIPLES AB Organ preservation at 4 degrees C results in temporally irreversible injury to cellular structure and function. This study was designed to evaluate the possibility of storing hearts at ambient temperatures in novel organ preservation solution Somah to prevent damage and preserve optimum function by maintaining cellular energy over the temperature range of storage. Porcine hearts were stored in Celsior at 4 degrees C and Somah at 4 degrees C, 13 degrees C and 21 degrees C for 5h thereafter reperfused and reanimated in vitro for 3h. Heart weights, histopathology, ultrastructure and 2-dimensional echocardiography (2D-Echo) assessments showed preservation of structure in Somah groups. Tissue high-energy phosphate levels in Somah groups after storage were significantly greater than the Celsior hearts (p<0.05) and highest in the 21 degrees C Somah hearts. Upon reperfusion, myocardial O-2 consumption and lactate levels quickly achieved steady state in 21 degrees C hearts, but were delayed in Somah 4/13 degrees C groups and severely depressed in the Celsior group. Inotrope and electroconversion requirements were inversely related to storage temperature. In vitro 2D Echo demonstrated a discordantly attenuated function in the Celsior group, moderate functionality in 4 degrees C Somah group and superior reestablishment of performance in the Somah higher temperature groups. Hearts stored in Somah at 21 degrees C were metabolically and functionally superior to any other groups. C1 [Lowalekar, S. K.; Cao, H.; Lu, X. -G.; Thatte, H. S.] Harvard Univ, Sch Med, Dept Surg, Div Cardiothorac Surg, Boston, MA 02115 USA. [Lowalekar, S. K.; Cao, H.; Lu, X. -G.; Treanor, P. R.; Thatte, H. S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lowalekar, S. K.; Cao, H.; Lu, X. -G.; Thatte, H. S.] VA Boston Healthcare Syst, Boston, MA USA. RP Thatte, HS (reprint author), Harvard Univ, Sch Med, Dept Surg, Div Cardiothorac Surg, Boston, MA 02115 USA. EM hemant_thatte@hms.harvard.edu FU Department of Veterans Affairs Merit Grant award FX This work was supported by the Department of Veterans Affairs Merit Grant award (HST), and an unrestricted gift from Somahlution LLC (Jupiter, FL) to Boston VA Research Institute for research (HST). HST is a nonvested member of Somahlutions Scientific Advisory Board. Somahlution played no part in designing experiments, interpretation of data and in preparation of this manuscript. NR 26 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2014 VL 14 IS 10 BP 2253 EP 2262 DI 10.1111/ajt.12846 PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA AQ3BI UT WOS:000342663300011 PM 25154901 ER PT J AU Shinoda, K Akiyoshi, T Chase, CM Farkash, EA Ndishabandi, DK Raczek, CM Sebastian, DP Della Pelle, P Russell, PS Madsen, JC Colvin, RB Alessandrini, A AF Shinoda, K. Akiyoshi, T. Chase, C. M. Farkash, E. A. Ndishabandi, D. K. Raczek, C. M. Sebastian, D. P. Della Pelle, P. Russell, P. S. Madsen, J. C. Colvin, R. B. Alessandrini, A. TI Depletion of Foxp3(+) T Cells Abrogates Tolerance of Skin and Heart Allografts in Murine Mixed Chimeras Without the Loss of Mixed Chimerism SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Basic (laboratory) research/science; bone marrow/hematopoietic stem cell transplantation; heart transplantation/cardiology; immunobiology; major histocompatibility complex (MHC); tolerance: chimerism; tolerance: mechanisms ID BONE-MARROW-TRANSPLANTATION; INTRATHYMIC CLONAL DELETION; HOMEOSTATIC EXPANSION; MONOCLONAL-ANTIBODY; THYMIC IRRADIATION; REGULATORY CELLS; GENE-ACTION; MICE; INDUCTION; REJECTION AB The relative contribution of central and peripheral mechanisms to the generation and maintenance of allograft tolerance is of considerable interest. Here, we present new evidence that regulatory T cells (Foxp3(+)) maintain skin and heart allograft tolerance in mixed hematopoietic chimeric mice. Transient depletion of both donor- and recipient-derived Foxp3(+) cells was necessary and sufficient to induce decisive rejection of long-accepted skin and heart allografts. In contrast, stable hematopoietic chimerism remained, and there was no detectable induction of donor-specific reactivity to hematopoietic cells. Foxp3(+) cell depletion did not result in the rejection of skin grafts of only MHC-disparate donors (B6.C-H2(d)/bByJ), indicating that MHC antigens were not the target in the graft. We conclude that two different mechanisms of tolerance are present in mixed chimeras. Hematopoietic chimerism, resistant to Foxp3(+) depletion, is probably due to deletional tolerance to MHC antigens, as supported by previous studies. In contrast, regulatory tolerance mechanisms involving Foxp3(+) cells are required to control reactivity against non-MHC antigens not present on hematopoietic lineages. C1 [Shinoda, K.; Chase, C. M.; Russell, P. S.; Madsen, J. C.; Colvin, R. B.; Alessandrini, A.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Shinoda, K.; Chase, C. M.; Russell, P. S.; Madsen, J. C.; Alessandrini, A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Akiyoshi, T.; Farkash, E. A.; Ndishabandi, D. K.; Raczek, C. M.; Sebastian, D. P.; Della Pelle, P.; Colvin, R. B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Russell, P. S.; Madsen, J. C.; Alessandrini, A.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Colvin, R. B.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Alessandrini, A (reprint author), Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. EM aalessandrini@partners.org FU NIH [RO1 AI081734, RO1 HL071932]; Roche Organ Transplant Research Foundation FX This work was supported by NIH grants RO1 AI081734 (RBC) and RO1 HL071932 (JCM) and a grant from the Roche Organ Transplant Research Foundation (JCM). We thank Dr. David H. Sachs for helpful discussions and review of the manuscript. NR 33 TC 7 Z9 7 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2014 VL 14 IS 10 BP 2263 EP 2274 DI 10.1111/ajt.12851 PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA AQ3BI UT WOS:000342663300012 PM 25155089 ER PT J AU Pokharel, Y Nambi, V Martin, SS Hoogeveen, RC Nasir, K Khera, A Wong, ND Jones, PH Boone, J Roberts, AJ Ballantyne, CM Virani, SS AF Pokharel, Yashashwi Nambi, Vijay Martin, Seth S. Hoogeveen, Ron C. Nasir, Khurram Khera, Amit Wong, Nathan D. Jones, Peter H. Boone, Jeffrey Roberts, Arthur J. Ballantyne, Christie M. Virani, Salim S. TI Association between lipoprotein associated phospholipase A2 mass and subclinical coronary and carotid atherosclerosis in Retired National Football League players SO ATHEROSCLEROSIS LA English DT Article DE Coronary artery calcium; Carotid artery plaque; Lipoprotein associated phospholipase A(2); National football league; Subclinical atherosclerosis ID INTIMA-MEDIA THICKNESS; ACTIVATING-FACTOR ACETYLHYDROLASE; LOW-DENSITY-LIPOPROTEIN; HEART-DISEASE RISK; MYOCARDIAL-INFARCTION; COMPUTED-TOMOGRAPHY; METABOLIC SYNDROME; ARTERY-DISEASE; A(2) MASS; CALCIUM AB Objectives: Retired National Football League (NFL) players were reported to have high prevalence of cardiovascular risk factors. Lipoprotein Associated Phospholipase A(2) (LpPLA(2)) has shown to be associated with cardiovascular disease in the general population, but it is unknown whether such an association exists in retired NFL players. Our objective was to assess whether LpPLA(2) mass was associated with coronary artery calcium (CAC) and carotid artery plaque (CAP) in retired NFL players. Methods: LpPLA(2) mass was assessed using a dual monoclonal antibody immunoassay. CAC presence was defined as CAC score>0. CAP was defined as focal thickening >= 50% than that of the surrounding vessel wall with a minimal thickness of 1.2 mm on carotid ultrasound. Results: In 832 NFL players, the median (IQR) age and LpPLA2 levels were 54 (45-63) years and 142 (109-181) ng/mL respectively. LpPLA(2) mass was positively correlated with low-density lipoprotein (LDL) cholesterol and high-density lipoprotein cholesterol; negatively correlated with LDL particle concentration and body mass index; and not correlated with high-sensitivity C-reactive protein. CAC was present in 659 (79%) and CAP in 544 (65%) players. In a fully adjusted model, LpPLA(2) was not associated with CAC (ORper 1-SD increase, 0.85; 95% CI 0.71-1.02) or CAP (0.90, 0.75-1.08). LpPLA(2) was also not associated with CAC burden in those with CAC>0. Results were similar when highest and lowest LpPLA(2) tertiles were compared, and also in various subgroups. Conclusion: LpPLA2 mass was not associated with coronary or carotid subclinical atherosclerosis in retired NFL players. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Pokharel, Yashashwi; Nambi, Vijay; Hoogeveen, Ron C.; Jones, Peter H.; Ballantyne, Christie M.; Virani, Salim S.] Baylor Coll Med, Dept Med, Sect Cardiovasc Res, Houston, TX 77030 USA. [Pokharel, Yashashwi; Nambi, Vijay; Hoogeveen, Ron C.; Jones, Peter H.; Ballantyne, Christie M.; Virani, Salim S.] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA. [Nambi, Vijay; Virani, Salim S.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Martin, Seth S.; Nasir, Khurram] Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Baltimore, MD USA. [Nasir, Khurram] Baptist Hlth Med Grp, Ctr Prevent & Wellness Res, Miami Beach, FL USA. [Nasir, Khurram] Baptist Hlth South Florida, Baptist Cardiovasc Inst, Miami, FL USA. [Nasir, Khurram] Robert Stempel, Dept Epidemiol, W Palm Beach, FL USA. [Nasir, Khurram] Herbert Wertheim Coll Med, Dept Med, Miami, FL USA. [Khera, Amit] Univ Texas SW Med Ctr Dallas, Dept Med, Dallas, TX 75390 USA. [Wong, Nathan D.] Univ Calif Irvine, Heart Dis Prevent Program, Irvine, CA USA. [Boone, Jeffrey] Boone Heart Inst, Denver, CO USA. [Roberts, Arthur J.] Living Heart Fdn, Little Silver, NJ USA. [Virani, Salim S.] Michael E DeBakey VA Med Ctr Hlth Serv, Res & Dev Ctr Innovat, Hlth Policy Qual & Informat Program, Houston, TX USA. RP Pokharel, Y (reprint author), Baylor Coll Med, Dept Med, Sect Cardiovasc Res, 6565 Fannin St,Suite B160, Houston, TX 77030 USA. EM Yashashwi.pokharel@bcm.edu; vnambi@bcm.edu; smart100@jhmi.edu; ronh@bcm.edu; knasir1@jhmi.edu; Amit.Khera@UTSouthwestern.edu; ndwong@uci.edu; jones@bcm.edu; jeffboonemd@gmail.com; drrobertslhf@gmail.com; cmb@bcm.edu; virani@bcm.edu OI Virani, Salim/0000-0001-9541-6954 FU Pollin Fellowship in Preventive Cardiology; Marie Josee and Henry R. Kravis endowed fellowship; Abbott; Amarin; Amgen; Eli Lilly; GlaxoSmithKline; Genentech; Merck; Novartis; Pfizer; Regeneron; Roche; Sanofi-Synthelabo; NIH; AHA; Department of Veterans Affairs Health Services Research and Development Service Career Development Award; American Heart Association Beginning; American Diabetes Association Clinical Science and Epidemiology Award FX Martin: Supported by the Pollin Fellowship in Preventive Cardiology, as well as the Marie Josee and Henry R. Kravis endowed fellowship. Listed as a co-inventor on pending patent filed by Johns Hopkins University on a novel method for LDL cholesterol estimation.; Ballantyne: Grant/Research Support (All paid to institution, not individual): Abbott, Amarin, Amgen, Eli Lilly, GlaxoSmithKline, Genentech, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi-Synthelabo, NIH, AHA.; Virani: Supported by a Department of Veterans Affairs Health Services Research and Development Service Career Development Award, American Heart Association Beginning Grant-in-Aid, and the American Diabetes Association Clinical Science and Epidemiology Award. NR 43 TC 2 Z9 2 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD OCT PY 2014 VL 236 IS 2 BP 251 EP 256 DI 10.1016/j.atherosclerosis.2014.07.011 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AP9QP UT WOS:000342414700024 PM 25105582 ER PT J AU Zeidan, AM Lee, JW Prebet, T Greenberg, P Sun, ZX Juckett, M Smith, MR Paietta, E Gabrilove, J Erba, HP Katterling, RP Tallman, MS Gore, SD AF Zeidan, Amer M. Lee, Ju-Whei Prebet, Thomas Greenberg, Peter Sun, Zhuoxin Juckett, Mark Smith, Mitchell R. Paietta, Elisabeth Gabrilove, Janice Erba, Harry P. Katterling, Rhett P. Tallman, Martin S. Gore, Steven D. CA Eastern Cooperative Oncology Grp North Amer Leukemia Intergrp TI Platelet count doubling after the first cycle of azacitidine therapy predicts eventual response and survival in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukaemia but does not add to prognostic utility of the revised IPSS SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE myelodysplastic syndromes; azacitidine; revised international prognostic scoring system; French prognostic scoring system; prognostic models ID SCORING SYSTEM IPSS; RISK STRATIFICATION; TREATED PATIENTS; GROUP-B; LENALIDOMIDE; VALIDATION; COMBINATION; CANCER; TRIAL AB Reliable clinical or molecular predictors of benefit from azacitidine therapy in patients with myelodysplastic syndromes (MDS) are not defined. Doubling of platelet count at start of second cycle of azacitidine therapy compared to baseline was associated with achieving response and survival advantage in a Dutch cohort. To validate this observation, we analysed a larger cohort of North American patients, whose data was collected in a prospective clinical trial with a longer median follow-up. We found a significant association between platelet count doubling after first cycle of azacitidine therapy and probability of achieving objective response. Among patients with MDS or oligoblastic acute myeloid leukaemia (<30% bone marrow blasts, n=102), there was a statistically significant reduction in risk of death for patients who achieved platelet count doubling (n=23, median OS, 210months) compared to those who did not (n=79, median OS, 167months, adjusted hazard ratio (no/yes)=188, 95% confidence interval, 103-340, P=004). Nonetheless, the addition of this platelet count doubling variable did not improve the survival prediction provided by the revised International Prognostic Scoring System or the French Prognostic Scoring System. Identification of reliable and consistent predictors for clinical benefit for azacitidine therapy remains an unmet medical need and a top research priority. C1 [Zeidan, Amer M.; Gore, Steven D.] Yale Univ, Dept Med, New Haven, CT 06520 USA. [Lee, Ju-Whei; Sun, Zhuoxin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Prebet, Thomas] Aix Marseille Univ, Dept Hematol, Marseille, France. [Greenberg, Peter] Stanford Univ Canc Ctr, Div Hematol, Stanford, CA USA. [Juckett, Mark] Univ Wisconsin, Dept Oncol, Madison, WI USA. [Smith, Mitchell R.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Paietta, Elisabeth] Montefiore Med Ctr, North Div, Bronx, NY 10467 USA. [Gabrilove, Janice] Mt Sinai Sch Med, Dept Oncol, New York, NY USA. [Erba, Harry P.] Univ Alabama Birmingham, Dept Oncol, Birmingham, AL USA. [Katterling, Rhett P.] Mayo Clin, Rochester, MN USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, Dept Med Leukemia Serv, New York, NY 10021 USA. RP Zeidan, AM (reprint author), Yale Univ, Dept Med, 333 Cedar St,POB 208028, New Haven, CT 06520 USA. EM amer.zeidan@yale.edu FU American Society of Clinical Oncology (ASCO); MDS Clinical Research Consortium; Public Health Service [CA23318, CA66636, CA21115, CA16116, CA20176, CA27525, CA14958, CA31946, CA32102, CA17145, CA27057]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX Amer Zeidan is supported by a Young Investigator Award (YIA) from the American Society of Clinical Oncology (ASCO) and by an 'Evans Fellow' award from the MDS Clinical Research Consortium. This research was done while Amer Zeidan was at Johns Hopkins University, Baltimore, Maryland. This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA16116, CA20176, CA27525, CA14958, CA31946, CA32102, CA17145, CA27057 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 29 TC 10 Z9 11 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2014 VL 167 IS 1 BP 62 EP 68 DI 10.1111/bjh.13008 PG 7 WC Hematology SC Hematology GA AQ3IM UT WOS:000342685300007 PM 24995683 ER PT J AU Lee, MJ Wickner, P Fanning, L Schlossman, R Richardson, P Laubach, J Castells, M AF Lee, Min Jung Wickner, Paige Fanning, Laura Schlossman, Robert Richardson, Paul Laubach, Jacob Castells, Maria TI Lenalidomide desensitization for delayed hypersensitivity reactions in 5 patients with multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE allergy; multiple myeloma; myeloma therapy; desensitization; lenalidomide C1 [Lee, Min Jung; Wickner, Paige; Fanning, Laura; Castells, Maria] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Schlossman, Robert; Laubach, Jacob] Dana Farber Canc Inst, Boston, MA 02115 USA. [Richardson, Paul] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Lee, MJ (reprint author), Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA. EM mlee42@partners.org NR 10 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2014 VL 167 IS 1 BP 127 EP 131 DI 10.1111/bjh.12925 PG 5 WC Hematology SC Hematology GA AQ3IM UT WOS:000342685300014 PM 24824093 ER PT J AU Leidl, MC Choi, CJ Syed, ZA Melki, SA AF Leidl, Matthew C. Choi, Catherine J. Syed, Zeba A. Melki, Samir A. TI Intraocular pressure fluctuation and glaucoma progression: what do we know? SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Review ID OPEN-ANGLE GLAUCOMA; NORMAL-TENSION GLAUCOMA; VISUAL-FIELD PROGRESSION; CENTRAL CORNEAL THICKNESS; OCULAR PERFUSION-PRESSURE; INDEPENDENT RISK-FACTOR; DIURNAL-VARIATION; CONTACT-LENS; TREATED GLAUCOMA; IOP FLUCTUATION AB While mean intraocular pressure (IOP) has long been known to correlate with glaucomatous damage, the role of IOP fluctuation is less clearly defined. There is extensive evidence in the literature for and against the value of short-term and long-term IOP fluctuation in the evaluation and prognosis of patients with glaucoma. We present here the arguments made by both sides, as well as a discussion of the pitfalls of prior research and potential directions for future studies. Until a reliable method is developed that allows for constant IOP monitoring, many variables will continue to hinder us from drawing adequate conclusions regarding the significance of IOP variation. C1 [Leidl, Matthew C.] Nassau Univ Med Ctr, E Meadow, NY USA. [Choi, Catherine J.; Melki, Samir A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Syed, Zeba A.; Melki, Samir A.] Harvard Univ, Sch Med, Boston, MA USA. [Melki, Samir A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Melki, Samir A.] Boston Eye Grp, Brookline, MA 02446 USA. RP Melki, SA (reprint author), Boston Eye Grp, 1101 Beacon St, Brookline, MA 02446 USA. EM melki@bostonlaser.com NR 80 TC 9 Z9 9 U1 1 U2 14 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD OCT PY 2014 VL 98 IS 10 BP 1315 EP 1319 DI 10.1136/bjophthalmol-2013-303980 PG 5 WC Ophthalmology SC Ophthalmology GA AQ3HF UT WOS:000342681400003 PM 24627247 ER PT J AU Wang, XG Jia, YL Spain, R Potsaid, B Liu, JJ Baumann, B Hornegger, J Fujimoto, JG Wu, Q Huang, D AF Wang, Xiaogang Jia, Yali Spain, Rebecca Potsaid, Benjamin Liu, Jonathan J. Baumann, Bernhard Hornegger, Joachim Fujimoto, James G. Wu, Qiang Huang, David TI Optical coherence tomography angiography of optic nerve head and parafovea in multiple sclerosis SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID RETINAL BLOOD-FLOW; AMPLITUDE-DECORRELATION ANGIOGRAPHY; FIBER LAYER; NEURITIS; PARAMETERS AB Aims To investigate swept-source optical coherence tomography (OCT) angiography in the optic nerve head (ONH) and parafoveal regions in patients with multiple sclerosis (MS). Methods Fifty-two MS eyes and 21 healthy control (HC) eyes were included. There were two MS subgroups: 38 MS eyes without an optic neuritis (ON) history (MS -ON), and 14 MS eyes with an ON history (MS +ON). The OCT images were captured by high-speed 1050 nm swept-source OCT. The ONH flow index (FI) and parafoveal FI were quantified from OCT angiograms. Results The mean ONH FI was 0.160 +/- 0.010 for the HC group, 0.156 +/- 0.017 for the MS-ON group, and 0.140 +/- 0.020 for the MS+ON group. The ONH FI of the MS+ON group was reduced by 12.5% compared to HC eyes (p=0.004). A higher percentage of MS+ON eyes had abnormal ONH FI compared to HC patients (43% vs 5%, p=0.01). Mean parafoveal FIs were 0.126 +/- 0.007, 0.127 +/- 0.010, and 0.129 +/- 0.005 for the HC, MS-ON, and MS +ON groups, respectively, and did not differ significantly among them. The coefficient of variation (CV) of intravisit repeatability and intervisit reproducibility were 1.03% and 4.53% for ONH FI, and 1.65% and 3.55% for parafoveal FI. Conclusions Based on OCT angiography, the FI measurement is feasible, highly repeatable and reproducible, and it is suitable for clinical measurement of ONH and parafoveal perfusion. The ONH FI may be useful in detecting damage from ON and quantifying its severity. C1 [Wang, Xiaogang; Jia, Yali; Huang, David] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA. [Wang, Xiaogang; Wu, Qiang] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai 200030, Peoples R China. [Spain, Rebecca] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Neurol, Portland, OR 97239 USA. [Potsaid, Benjamin; Liu, Jonathan J.; Baumann, Bernhard; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Potsaid, Benjamin; Liu, Jonathan J.; Baumann, Bernhard; Fujimoto, James G.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Hornegger, Joachim] Univ Erlangen Nurnberg, Pattern Recognit Lab, D-91054 Erlangen, Germany. [Hornegger, Joachim] Univ Erlangen Nurnberg, SAOT, D-91054 Erlangen, Germany. RP Huang, D (reprint author), Oregon Hlth & Sci Univ, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM bjo@dr-huang.net OI Jia, Yali/0000-0002-2784-1905; Baumann, Bernhard/0000-0001-6419-1932 FU NIH [UL1TR000128, R01 EY023285, R01 EY013516, R01-EY11289, P30EY010572]; AFOSR [FA9550-10-1-0551, FA9550-12-1-0499]; German Research Foundation [DFG-HO-1791/11-1]; Research to Prevent Blindness FX This work was supported by NIH grants: Clinical and Translational Science Award Grant (UL1TR000128), R01 EY023285, R01 EY013516, R01-EY11289, and P30EY010572. Additional supports were AFOSR FA9550-10-1-0551, FA9550-12-1-0499, German Research Foundation DFG-HO-1791/11-1, and a grant from Research to Prevent Blindness. NR 25 TC 27 Z9 29 U1 0 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD OCT PY 2014 VL 98 IS 10 BP 1368 EP 1373 DI 10.1136/bjophthalmol-2013-304547 PG 6 WC Ophthalmology SC Ophthalmology GA AQ3HF UT WOS:000342681400014 PM 24831719 ER PT J AU Choy, E AF Choy, Edwin TI Sarcoma After 5 Years of Progression-Free Survival: Lessons From the French Sarcoma Group SO CANCER LA English DT Editorial Material ID SOFT-TISSUE SARCOMA; PROGNOSTIC-FACTORS; MANAGEMENT; RECURRENCE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Choy, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol Oncol, Mailstop Yawkey 7B,55 Fruit St, Boston, MA 02114 USA. EM echoy@partners.org NR 17 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2014 VL 120 IS 19 BP 2942 EP 2943 DI 10.1002/cncr.28834 PG 2 WC Oncology SC Oncology GA AQ2PP UT WOS:000342630000004 PM 24942785 ER PT J AU Pirl, WF Fann, JR Greer, JA Braun, I Deshields, T Fulcher, C Harvey, E Holland, J Kennedy, V Lazenby, M Wagner, L Underhill, M Walker, DK Zabora, J Zebrack, B Bardwell, WA AF Pirl, William F. Fann, Jesse R. Greer, Joseph A. Braun, Ilana Deshields, Teresa Fulcher, Caryl Harvey, Elizabeth Holland, Jimmie Kennedy, Vicki Lazenby, Mark Wagner, Lynne Underhill, Meghan Walker, Deborah K. Zabora, James Zebrack, Bradley Bardwell, Wayne A. TI Recommendations for the Implementation of Distress Screening Programs in Cancer Centers Report From the American Psychosocial Oncology Society (APOS), Association of Oncology Social Work (AOSW), and Oncology Nursing Society (ONS) Joint Task Force SO CANCER LA English DT Review DE psychosocial aspects; neoplasms; screening; standards; recommendations; distress screening; implementation; cancer; psychosocial; programs ID QUALITY-OF-LIFE; PATIENT HEALTH QUESTIONNAIRE; RANDOMIZED CONTROLLED-TRIAL; CELL LUNG-CANCER; PSYCHOLOGICAL DISTRESS; DEPRESSION SCALE; HOSPITAL ANXIETY; MOOD DISORDERS; CARE; THERMOMETER AB In 2015, the American College of Surgeons (ACoS) Commission on Cancer will require cancer centers to implement screening programs for psychosocial distress as a new criterion for accreditation. A joint task force from the American Psychosocial Oncology Society, the Association of Oncology Social Work, and the Oncology Nursing Society developed consensus-based recommendations to guide the implementation of this requirement. In this review, the authors provide recommendations regarding each of the 6 components necessary to meet the ACoS standard: 1) inclusion of psychosocial representation on the cancer committee, 2) timing of screening, 3) method/mode of screening, 4) tools for screening, 5) assessment and referral, and 6) documentation. (C) 2014 American Cancer Society. C1 [Pirl, William F.; Greer, Joseph A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 USA. [Fann, Jesse R.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Braun, Ilana] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Palliat Care & Psychosocial Oncol, Boston, MA 02114 USA. [Deshields, Teresa] Washington Univ, Dept Psychol, Sch Med, St Louis, MO 63130 USA. [Fulcher, Caryl] Duke Univ Hlth Syst, Dept Adv Clin Practice, Durham, NC USA. [Harvey, Elizabeth] Int Consulting Oncol LLC, New York, NY USA. [Holland, Jimmie] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. [Kennedy, Vicki] Canc Support Community, Washington, DC USA. [Lazenby, Mark] Yale Univ, Sch Nursing, Div Acute Care Hlth Syst, Orange, CT USA. [Wagner, Lynne] Northwestern Univ, Dept Med Social Sci, Chicago, IL 60611 USA. [Underhill, Meghan] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. [Walker, Deborah K.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. [Zabora, James] Life Canc, Fairfax, VA USA. [Zebrack, Bradley] Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA. [Bardwell, Wayne A.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Pirl, WF (reprint author), Harvard Univ, Sch Med, Yawkey 10B,55 Fruit St, Boston, MA 02114 USA. EM wpirl@partners.org FU Lilly Oncology FX Dr. Deshields reports Speakers' Bureau fees from Lilly Oncology. NR 59 TC 31 Z9 32 U1 2 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2014 VL 120 IS 19 BP 2946 EP 2954 DI 10.1002/cncr.28750 PG 9 WC Oncology SC Oncology GA AQ2PP UT WOS:000342630000006 PM 24798107 ER PT J AU Onega, T Beaber, EF Sprague, BL Barlow, WE Haas, JS Tosteson, ANA Schnall, MD Armstrong, K Schapira, MM Geller, B Weaver, DL Conant, EF AF Onega, Tracy Beaber, Elisabeth F. Sprague, Brian L. Barlow, William E. Haas, Jennifer S. Tosteson, Anna N. A. Schnall, Mitchell D. Armstrong, Katrina Schapira, Marilyn M. Geller, Berta Weaver, Donald L. Conant, Emily F. TI Breast Cancer Screening in an Era of Personalized Regimens A Conceptual Model and National Cancer Institute Initiative for Risk-Based and Preference-Based Approaches at a Population Level SO CANCER LA English DT Review DE screening; breast cancer; process of care; mammography; guidelines ID CARCINOMA IN-SITU; UNITED-STATES; FOLLOW-UP; MAMMOGRAPHY; CARE; WOMEN; OVERDIAGNOSIS; SOCIETY; QUALITY; TRENDS AB Breast cancer screening holds a prominent place in public health, health care delivery, policy, and women's health care decisions. Several factors are driving shifts in how population-based breast cancer screening is approached, including advanced imaging technologies, health system performance measures, health care reform, concern for "overdiagnosis," and improved understanding of risk. Maximizing benefits while minimizing the harms of screening requires moving from a "1-size-fits-all" guideline paradigm to more personalized strategies. A refined conceptual model for breast cancer screening is needed to align women's risks and preferences with screening regimens. A conceptual model of personalized breast cancer screening is presented herein that emphasizes key domains and transitions throughout the screening process, as well as multilevel perspectives. The key domains of screening awareness, detection, diagnosis, and treatment and survivorship are conceptualized to function at the level of the patient, provider, facility, health care system, and population/policy arena. Personalized breast cancer screening can be assessed across these domains with both process and outcome measures. Identifying, evaluating, and monitoring process measures in screening is a focus of a National Cancer Institute initiative entitled PROSPR (Population-based Research Optimizing Screening through Personalized Regimens), which will provide generalizable evidence for a risk-based model of breast cancer screening, The model presented builds on prior breast cancer screening models and may serve to identify new measures to optimize benefits-to-harms tradeoffs in population-based screening, which is a timely goal in the era of health care reform. (C) 2014 American Cancer Society. C1 [Onega, Tracy; Tosteson, Anna N. A.] Geisel Sch Med Dartmouth, Dept Community & Family Med, Lebanon, NH 03756 USA. [Onega, Tracy; Tosteson, Anna N. A.] Geisel Sch Med Dartmouth, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH 03756 USA. [Onega, Tracy; Tosteson, Anna N. A.] Norris Cotton Canc Ctr, Lebanon, NH USA. [Beaber, Elisabeth F.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Sprague, Brian L.; Geller, Berta; Weaver, Donald L.] Univ Vermont, Dept Surg, Burlington, VT 05405 USA. [Barlow, William E.] Canc Res & Biostat, Seattle, WA USA. [Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. [Schnall, Mitchell D.; Schapira, Marilyn M.; Conant, Emily F.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Armstrong, Katrina] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Onega, T (reprint author), Geisel Sch Med Dartmouth, Dept Community & Family Med, HB-7927,Rubin 8,One Med Ctr Dr, Lebanon, NH 03756 USA. EM Tracy.L.Onega@dartmouth.edu FU National Cancer Institute (NCI) [U01CA163304, U54CA163313-03, U54CA163307-01, U54CA163303-03] FX Supported by National Cancer Institute (NCI) grants U01CA163304, U54CA163313-03, U54CA163307-01, and U54CA163303-03. NR 42 TC 30 Z9 30 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2014 VL 120 IS 19 BP 2955 EP 2964 DI 10.1002/cncr.28771 PG 10 WC Oncology SC Oncology GA AQ2PP UT WOS:000342630000007 PM 24830599 ER PT J AU Boylan, MR Khalili, H Huang, ES Chan, AT AF Boylan, Matthew R. Khalili, Hamed Huang, Edward S. Chan, Andrew T. TI Measures of Adiposity Are Associated With Increased Risk of Peptic Ulcer SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Obesity; Peptic Ulcer Disease; Body Mass Index; Waist-To-Hip Ratio ID BODY-MASS INDEX; MALE HEALTH-PROFESSIONALS; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; ASPIRIN USE; GUT MICROBIOTA; OBESITY; QUESTIONNAIRE; POPULATION; SYMPTOMS AB BACKGROUND & AIMS: Obesity is associated with systemic inflammation, alterations in the intestinal microbiome, and decreased epithelial integrity. The association between obesity and peptic ulcer has not been investigated thoroughly. METHODS: We conducted a prospective cohort study of 47,120 men enrolled in the Health Professionals Follow-Up Study (mean age at baseline, 54 y). Biennially, we updated information on body mass index (BMI), physical activity, smoking, and use of nonsteroidal anti-inflammatory drugs or aspirin. Self-reported waist and hip measurements were validated among a subsample of participants. Self-reported cases of gastric and duodenal ulcers were confirmed by medical record review. Helicobacter pylori status was determined from endoscopic biopsy specimens, serum antibody measurements, and/or stool antigen assays documented in the medical record. We used Cox proportional hazards modeling to calculate hazard ratios and 95% confidence intervals (CIs). RESULTS: We documented 272 gastric and 320 duodenal ulcers over 24 years of follow-up evaluation. The multivariate-adjusted hazard ratio for gastric ulcer was 1.83 (95% CI, 1.20-2.78; P-trend < .01) for obese men (BMI, >= 30.0 kg/m(2)), compared with men with BMIs of 23.0 to 24.9 kg/m(2), and 1.88 (95% CI, 1.06-3.33; P-trend = .04) for men with waist-to-hip ratios (WHR) of 1.00 or higher, compared with men with a WHR of 0.85 to 0.89. The risk of duodenal ulcer was not associated with BMI (P-trend = .24) or WHR (P-trend = .68). In secondary analyses, increased BMI and WHR each were associated with increased risk of H pylori-negative, but not H pylori-positive, ulcers. The effect of BMI on ulcer risk did not change with use of aspirin or nonsteroidal anti-inflammatory drugs, alcohol consumption, physical activity, or smoking. CONCLUSIONS: In a large prospective cohort of male health professionals, central and total obesity were associated with increased risk of peptic ulcer-particularly gastric and H pylori-negative ulcers. C1 [Boylan, Matthew R.; Khalili, Hamed; Huang, Edward S.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Boylan, Matthew R.; Khalili, Hamed; Huang, Edward S.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Boylan, Matthew R.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Huang, Edward S.] Palo Alto Med Fdn, Dept Gastroenterol, Mountain View, CA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St,GRJ 825CA, Boston, MA 02114 USA. EM achan@mgh.harvard.edu FU National Institute for Diabetes and Digestive and Kidney Diseases/National Institutes of Health; American Gastroenterological Association; [UM1 CA167552]; [R01 DK095964]; [K24 DK098311]; [K23 DK099681] FX Funded by UM1 CA167552 (PI: Walter C. Willett, MD, DrPH, MPH), R01 DK095964 (A. T. C.), and K24 DK098311 (A. T. C.) from the National Institute for Diabetes and Digestive and Kidney Diseases/National Institutes of Health. Andrew Chan is a Damon Runyon Cancer Research Foundation Clinical Investigator. Hamed Khalili is supported by grant K23 DK099681 and a career development grant from the American Gastroenterological Association. NR 24 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2014 VL 12 IS 10 BP 1688 EP 1694 DI 10.1016/j.cgh.2014.03.021 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AQ2OA UT WOS:000342625000021 PM 24681076 ER PT J AU Bonilha, HS Simpson, AN Ellis, C Mauldin, P Martin-Harris, B Simpson, K AF Bonilha, Heather Shaw Simpson, Annie N. Ellis, Charles Mauldin, Patrick Martin-Harris, Bonnie Simpson, Kit TI The One-Year Attributable Cost of Post-stroke Dysphagia SO DYSPHAGIA LA English DT Article DE Deglutition; Deglutition disorders; Dysphagia; Cost; Stroke; Length of stay; Discharge severity ID RACIAL DISPARITIES; ACUTE STROKE; MORTALITY; DATABASE AB With the recent emphasis on evidence-based practice and healthcare reform, understanding the cost of dysphagia management has never been more important. It is helpful for clinicians to understand and objectively report the costs associated with dysphagia when they advocate for their services in this economy. Having carefully estimated cost of illness, inputs are needed for cost-effectiveness analyses that help support the value of treatments. This study sought to address this issue by examining the 1-year cost associated with a diagnosis of dysphagia post-stroke in South Carolina. Furthermore, this study investigated whether ethnicity and residence differences exist in the cost of dysphagia post-stroke. Data on 3,200 patients in the South Carolina Medicare database from 2004 who had ICD-9 codes for ischemic stroke, 434 and 436, were retrospectively included in this study. Differences between persons with and without dysphagia post-stroke were compared with respect to age, gender, ethnicity, mortality, length of stay, comorbidity, rurality, discharge disposition, and cost to Medicare. Univariate analyses and a gamma-distributed generalized linear multivariable model with a log link function were completed. We found that the 1-year cost to Medicare for persons with dysphagia post ischemic stroke was $4,510 higher than that for persons without dysphagia post ischemic stroke when controlling for age, comorbidities, ethnicity, and proportion of time alive. Univariate analysis revealed that rurality, ethnicity, and gender were not statistically significantly different in comparisons of individuals with or without dysphagia post-stroke. Post-stroke dysphagia significantly increases post-stroke medical expenses. Understanding the expenditures associated with post-stroke dysphagia is helpful for optimal allocation and use of resources. Such information is needed to conduct cost-effectiveness studies. C1 [Bonilha, Heather Shaw; Ellis, Charles; Martin-Harris, Bonnie] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Bonilha, Heather Shaw; Martin-Harris, Bonnie] Med Univ S Carolina, Evelyn Trammell Inst Voice & Swallowing, Charleston, SC 29425 USA. [Bonilha, Heather Shaw; Simpson, Annie N.; Martin-Harris, Bonnie] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Simpson, Annie N.; Simpson, Kit] Med Univ S Carolina, Dept Healthcare Leadership & Management, Charleston, SC 29425 USA. [Mauldin, Patrick] Med Univ S Carolina, Dept Med, Div Gen Med & Geriatr, Charleston, SC 29425 USA. [Martin-Harris, Bonnie] Ralph H Johnson VA Med Ctr, VA Ctr Dis Prevent & Hlth Intervent Diverse Popul, Charleston, SC USA. RP Bonilha, HS (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, 77 President St, Charleston, SC 29425 USA. EM bonilhah@musc.edu FU NIH/NCRR, South Carolina Translational Research Institute part of the NIH Clinical Translational Science Award Program [UL1 RR029880] FX Dr. Bonilha's effort on this project was supported by a career development award (NIH/NCRR grant No. UL1 RR029880) from the South Carolina Translational Research Institute part of the NIH Clinical Translational Science Award Program. NR 27 TC 8 Z9 10 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-051X EI 1432-0460 J9 DYSPHAGIA JI Dysphagia PD OCT PY 2014 VL 29 IS 5 BP 545 EP 552 DI 10.1007/s00455-014-9543-8 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA AQ0TG UT WOS:000342495000003 PM 24948438 ER PT J AU Darabad, RR Suzuki, T Richards, SM Jakobiec, FA Zakka, FR Barabino, S Sullivan, DA AF Darabad, Raheleh Rahimi Suzuki, Tomo Richards, Stephen M. Jakobiec, Frederick A. Zakka, Fouad R. Barabino, Stefano Sullivan, David A. TI Does estrogen deficiency cause lacrimal gland inflammation and aqueous-deficient dry eye in mice? SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE lacrimal gland; mice; estrogen; male; female; sex difference; inflammation; tear volume; gene expression ID HORMONE REPLACEMENT THERAPY; RESEMBLING SJOGRENS-SYNDROME; AROMATASE KNOCKOUT MOUSE; TEAR FUNCTION-TESTS; MRL LPR/LPR MICE; GENE-EXPRESSION; POSTMENOPAUSAL WOMEN; SEX STEROIDS; AUTOIMMUNE EXOCRINOPATHY; X-INACTIVATION AB Researchers have proposed that estrogen deficiency will lead to a Sjogren's syndrome (SjS)-like lacrimal gland inflammation, aqueous tear deficiency and dry eye. The purpose of this study was to determine whether this proposal is correct. Lacrimal glands were obtained from adult, age-matched wild type (WT) and aromatase knockout (ArKO) mice, in which estrogen synthesis is completely eliminated. Tissues were also obtained from autoimmune MRL/Mp-lprflpr (MRL/lpr) mice as inflammation controls. Tear volumes in WT and ArKO mice were measured and glands were processed for molecular biological and histological evaluation. Our results demonstrate that estrogen absence does not lead to a SjS-like inflammation in lacrimal tissue or to an aqueous-deficient dry eye. There was no upregulation of genes associated with inflammatory pathways in lacrimal glands of male or female ArKO mice. Such inflammatory activity was prominent in autoimmune MRL/Ipr tissues. We also found no evidence of inflammation in lacrimal gland tissue sections of estrogen-deficient mice, and tear volumes of ArKO males were actually increased as compared to those WT controls. Interestingly, our study did show that estrogen absence influences the expression of thousands of lacrimal gland genes, and that this impact is sex- and genotype-specific. Our findings demonstrate that estrogen absence is not a risk factor for the development of SjS-like lacrimal gland inflammation or for aqueous-deficient dry eye in mice. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Darabad, Raheleh Rahimi; Suzuki, Tomo; Richards, Stephen M.; Barabino, Stefano; Sullivan, David A.] Schepens Eye Res Inst, Boston, MA 02114 USA. [Darabad, Raheleh Rahimi; Suzuki, Tomo; Richards, Stephen M.; Jakobiec, Frederick A.; Zakka, Fouad R.; Barabino, Stefano; Sullivan, David A.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jakobiec, Frederick A.; Zakka, Fouad R.; Sullivan, David A.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Sullivan, DA (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM david.sullivan@schepens.harvard.edu FU NIH [R01EY05612]; Ocular Surface Research Fund FX This research was supported by NIH grant R01EY05612 and the Margaret S. Sinon Scholar in Ocular Surface Research Fund. NR 69 TC 4 Z9 4 U1 4 U2 10 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 OCT PY 2014 VL 127 BP 153 EP 160 DI 10.1016/j.exer.2014.07.017 PG 8 WC Ophthalmology SC Ophthalmology GA AQ1KI UT WOS:000342539900018 ER PT J AU Lam, TC Sahgal, A Chang, EL Lo, SS AF Lam, Tai-Chung Sahgal, Arjun Chang, Eric L. Lo, Simon S. TI Stereotactic radiosurgery for multiple brain metastases SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE brain metastases; gamma knife system; neurocognitive function; stereotactic radiosurgery; whole brain radiation therapy ID GAMMA-KNIFE RADIOSURGERY; CELL LUNG-CANCER; QUALITY-OF-LIFE; PROGNOSTIC-FACTORS; CLINICAL ARTICLE; BREAST-CANCER; RADIATION-THERAPY; SURGICAL RESECTION; INTRACRANIAL METASTASES; CEREBRAL METASTASES AB Stereotactic radiosurgery (SRS) alone has become one of the treatment options for patients with 1-4 metastases as the detrimental effects of whole brain radiation therapy on neurocognition and quality of life are becoming well known. Multiple randomized control trials also failed to show overall survival benefit of adding whole brain radiation therapy to SRS. However, the role of SRS in multiple brain metastases, especially those with >= 4 tumors, remains controversial. The literature is emerging, and the limited evidence suggests that the local control benefit is independent of the number of metastases, and that patients with more than four brain metastases have similar overall survival compared to those with 2-4 tumors. This review aims at summarizing the current evidence of SRS for multiple brain metastases, divided into limited (2-3) and multiple (>= 4) lesions. It also reviews the technical aspects and cost-effectiveness of SRS. C1 [Lam, Tai-Chung] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Sahgal, Arjun] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Radiat Oncol, Toronto, ON, Canada. [Chang, Eric L.] Univ So Calif, Keck Sch Med, Dept Radiat Oncol, Norris Canc Hosp,Keck Hosp,Los Angeles Cty Univ S, Los Angeles, CA 90033 USA. [Lo, Simon S.] Case Comprehens Canc Ctr, Univ Hosp Seidman Canc Ctr, Dept Radiat Oncol, Cleveland, OH 44106 USA. RP Lo, SS (reprint author), Case Comprehens Canc Ctr, Univ Hosp Seidman Canc Ctr, Dept Radiat Oncol, Cleveland, OH 44106 USA. EM Simon.Lo@UHhospitals.org FU Elekta AB FX S Lo has received travel expenses and honorarium from Varian Medical Systems and research support from Elekta AB. A Sahgal has received honorarium for educational seminars and research support for radiosurgery research by Elekta AB. EL Chang has received honorarium for educational seminars by Elekta AB. 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 89 TC 0 Z9 0 U1 1 U2 10 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD OCT PY 2014 VL 14 IS 10 BP 1153 EP 1172 DI 10.1586/14737140.2014.940325 PG 20 WC Oncology SC Oncology GA AQ3EQ UT WOS:000342672800008 PM 25034143 ER PT J AU Afeiche, MC Gaskins, AJ Williams, PL Toth, TL Wright, DL Hauser, R Chavarro, JE AF Afeiche, M. C. Gaskins, A. J. Williams, P. L. Toth, T. L. Wright, D. L. Hauser, R. Chavarro, J. E. TI DAIRY INTAKE IN WOMEN AND IN VITRO FERTILIZATION OUTCOMES. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 18-22, 2014 CL Honolulu, HI SP Amer Soc Reprod Med C1 [Afeiche, M. C.; Gaskins, A. J.; Chavarro, J. E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Williams, P. L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Toth, T. L.; Wright, D. L.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Toth, T. L.; Wright, D. L.] Harvard Univ, Sch Med, Boston, MA USA. [Hauser, R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2014 VL 102 IS 3 SU S MA P-530 BP E312 EP E313 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AQ0VG UT WOS:000342500201285 ER PT J AU Cardozo, ER Karmon, AE Gold, J Petrozza, JC Styer, AK AF Cardozo, E. R. Karmon, A. E. Gold, J. Petrozza, J. C. Styer, A. K. TI IMPACT OF DONOR BMI ON PREGNANCY OUTCOME IN OOCYTE DONATION CYCLES SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 18-22, 2014 CL Honolulu, HI SP Amer Soc Reprod Med C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol, 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2014 VL 102 IS 3 SU S MA P-360 BP E258 EP E258 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AQ0VG UT WOS:000342500201116 ER PT J AU Cardozo, ER Thomson, AP Karmon, AE Sabatini, ME AF Cardozo, E. R. Thomson, A. P. Karmon, A. E. Sabatini, M. E. TI THE ROLE OF DEMOGRAPHICS AND DIAGNOSIS ON FERTILITY PRESERVATION DECISION MAKING AMONG FEMALE CANCER PATIENTS OF REPRODUCTIVE AGE. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 18-22, 2014 CL Honolulu, HI SP Amer Soc Reprod Med C1 [Cardozo, E. R.; Thomson, A. P.; Karmon, A. E.; Sabatini, M. E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Reprod Med & IVF Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2014 VL 102 IS 3 SU S MA P-41 BP E153 EP E153 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AQ0VG UT WOS:000342500200455 ER PT J AU Chiu, YH Afeiche, MC Gaskins, AJ Williams, PL Wright, DL Petrozza, JC Tanrikut, C Hauser, R Chavarro, JE AF Chiu, Y. -H. Afeiche, M. C. Gaskins, A. J. Williams, P. L. Wright, D. L. Petrozza, J. C. Tanrikut, C. Hauser, R. Chavarro, J. E. TI FRUIT AND VEGETABLE INTAKE AND THEIR PESTICIDE RESIDUES IN RELATION TO SEMEN QUALITY AND FERTILZATION RATES AMONG SUBFERTILE MEN. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 18-22, 2014 CL Honolulu, HI SP Amer Soc Reprod Med C1 [Chiu, Y. -H.; Afeiche, M. C.; Gaskins, A. J.; Williams, P. L.; Hauser, R.; Chavarro, J. E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Wright, D. L.; Petrozza, J. C.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Petrozza, J. C.; Tanrikut, C.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2014 VL 102 IS 3 SU S MA O-20 BP E8 EP E9 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AQ0VG UT WOS:000342500200021 ER PT J AU Karmon, AE Cardozo, EE Souter, I Gold, J Petrozza, JC Styer, AK AF Karmon, A. E. Cardozo, E. E. Souter, I. Gold, J. Petrozza, J. C. Styer, A. K. TI DONOR TSH LEVEL IS ASSOCIATED WITH IN VITRO FERTILIZATION OUTCOME AMONG OOCYTE DONATION CYCLES. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 18-22, 2014 CL Honolulu, HI SP Amer Soc Reprod Med C1 [Karmon, A. E.; Cardozo, E. E.; Souter, I.; Gold, J.; Petrozza, J. C.; Styer, A. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2014 VL 102 IS 3 SU S MA O-120 BP E41 EP E41 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AQ0VG UT WOS:000342500200121 ER PT J AU Karmon, AE Rhee, J Wang, J Wright, DL Chavarro, JE Toth, TL AF Karmon, A. E. Rhee, J. Wang, J. Wright, D. L. Chavarro, J. E. Toth, T. L. TI ANESTHETIC AND ANALGESIC AGENTS USED DURING OOCYTE RETRIEVAL AND IN VITRO FERTILIZATION OUTCOME. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 18-22, 2014 CL Honolulu, HI SP Amer Soc Reprod Med C1 [Karmon, A. E.; Wright, D. L.; Toth, T. L.] Massachusetts Gen Hosp, Dept Ob Gyn, Boston, MA 02114 USA. [Rhee, J.; Wang, J.] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Chavarro, J. E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2014 VL 102 IS 3 SU S MA O-117 BP E40 EP E40 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AQ0VG UT WOS:000342500200117 ER PT J AU Karmon, AE Toth, TL Gaskins, AJ Afeiche, MC Tanrikut, C Hauser, R Chavarro, JC AF Karmon, A. E. Toth, T. L. Gaskins, A. J. Afeiche, M. C. Tanrikut, C. Hauser, R. Chavarro, J. C. TI MALE CAFFEINE AND ALCOHOL INTAKE IN RELATION TO IN VITRO FERTILIZATION OUTCOME AMONG FERTILITY PATIENTS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 18-22, 2014 CL Honolulu, HI SP Amer Soc Reprod Med C1 [Karmon, A. E.; Toth, T. L.] Massachusetts Gen Hosp, Vincent Obstetr & Gynecol, Boston, MA 02114 USA. [Gaskins, A. J.; Afeiche, M. C.; Chavarro, J. C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Tanrikut, C.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Hauser, R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2014 VL 102 IS 3 SU S MA O-19 BP E8 EP E8 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AQ0VG UT WOS:000342500200020 ER PT J AU Kiatpongsan, S Feibelmann, S Sepucha, K AF Kiatpongsan, S. Feibelmann, S. Sepucha, K. TI GAPS BETWEEN PHYSICIANS' PERCEPTIONS OF THE IMPORTANCE OF SHARED DECISION MAKING AND THEIR PRACTICE IN MENOPAUSAL SYMPTOM MANAGEMENT SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 18-22, 2014 CL Honolulu, HI SP Amer Soc Reprod Med C1 [Kiatpongsan, S.] Chulalongkorn Univ, Fac Med, Bangkok 10330, Thailand. [Kiatpongsan, S.] Harvard Interfac Initiat Hlth Policy, Cambridge, MA USA. [Kiatpongsan, S.; Feibelmann, S.; Sepucha, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sepucha, K.] 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2014 VL 102 IS 3 SU S MA O-132 BP E45 EP E45 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AQ0VG UT WOS:000342500200133 ER PT J AU Kim, HJ Bjonnes, A Saxena, R Welt, C AF Kim, H. -J. Bjonnes, A. Saxena, R. Welt, C. TI EVALUATING RISK VARIANTS FOR KOREAN WOMEN WITH POLYCYSTIC OVARY SYNDROME IN WOMEN OF EUROPEAN ETHNICITY SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 18-22, 2014 CL Honolulu, HI SP Amer Soc Reprod Med C1 [Kim, H. -J.] Seoul Natl Univ, Bundang Hosp, Songnam, Gyeongi, South Korea. [Bjonnes, A.; Saxena, R.; Welt, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2014 VL 102 IS 3 SU S MA P-388 BP E266 EP E267 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AQ0VG UT WOS:000342500201144 ER PT J AU Luke, B Stern, JE Kotelchuck, M Hornstein, MD Declercq, E Cohen, B Diop, H AF Luke, B. Stern, J. E. Kotelchuck, M. Hornstein, M. D. Declercq, E. Cohen, B. Diop, H. TI BIRTH OUTCOMES BY INFERTILITY TREATMENT: ANALYSES OF THE MASSACHUSETTS OUTCOMES STUDY OF ASSISTED REPRODUCTIVE TECHNOLOGIES (MOSART). SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 18-22, 2014 CL Honolulu, HI SP Amer Soc Reprod Med C1 [Luke, B.] Michigan State Univ, E Lansing, MI 48824 USA. [Stern, J. E.] BGeisel Sch Med Dartmouth, Lebanon, NH USA. [Kotelchuck, M.; Declercq, E.] MassGen Hosp Children, Boston, MA USA. [Hornstein, M. D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Declercq, E.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Cohen, B.; Diop, H.] Massachusetts Dept Publ Hlth, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2014 VL 102 IS 3 SU S MA O-48 BP E17 EP E17 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AQ0VG UT WOS:000342500200049 ER PT J AU Souter, I Chiu, YH Afeiche, M Hauser, R Chavarro, JE AF Souter, I. Chiu, Y. -H. Afeiche, M. Hauser, R. Chavarro, J. E. TI THE ASSOCIATION OF DIETARY FAT INTAKE AND ANTRAL FOLLICLE COUNT (AFC) AMONG WOMEN UNDERGOING INFERTILITY TREATMENTS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 18-22, 2014 CL Honolulu, HI SP Amer Soc Reprod Med C1 [Souter, I.; Hauser, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Chiu, Y. -H.; Afeiche, M.; Hauser, R.; Chavarro, J. E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Chavarro, J. E.] Harvard Univ, Sch Med, BWH Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2014 VL 102 IS 3 SU S MA O-267 BP E92 EP E92 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AQ0VG UT WOS:000342500200268 ER PT J AU Thomson, AP Cardozo, ER Sabatini, ME AF Thomson, A. P. Cardozo, E. R. Sabatini, M. E. TI COMPARING IVF OUTCOMES FOR CANCER PATIENTS FOLLOWING EMBRYO AND OOCYTE CRYOPRESERVATION WITH AGE-MATCHED CONTROLS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 18-22, 2014 CL Honolulu, HI SP Amer Soc Reprod Med C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol, 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2014 VL 102 IS 3 SU S MA P-42 BP E153 EP E153 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AQ0VG UT WOS:000342500200456 ER PT J AU Anderson, KC AF Anderson, Kenneth C. TI Multiple Myeloma Preface SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Hematol Oncol,Jerome Lipper Multiple Myeloma, Boston, MA 02215 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Hematol Oncol,Jerome Lipper Multiple Myeloma, 450 Brookline Ave, Boston, MA 02215 USA. EM kenneth_anderson@dfci.harvard.edu NR 0 TC 2 Z9 2 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2014 VL 28 IS 5 BP XI EP XII DI 10.1016/j.hoc.2014.08.001 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA AQ1EA UT WOS:000342523500001 PM 25212892 ER PT J AU Varga, C Laubach, J Hideshima, T Chauhan, D Anderson, KC Richardson, PG AF Varga, Cindy Laubach, Jacob Hideshima, Teru Chauhan, Dharminder Anderson, Kenneth C. Richardson, Paul G. TI Novel Targeted Agents in the Treatment of Multiple Myeloma SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Multiple myeloma; Second-generation proteasome inhibitors; Histone deacetylase inhibitors; Heat shock protein 90 inhibitors; PIK3/Akt/mTOR inhibitors; BET bromodomain inhibitors; Deubiquitinating enzyme inhibitors; Wnt ID HISTONE DEACETYLASE INHIBITORS; AURORA-A-KINASE; SMALL-MOLECULE INHIBITOR; OVERCOMES BORTEZOMIB RESISTANCE; FLUOROPHENYLALANINE ETHYL-ESTER; VIVO SYNERGISTIC CYTOTOXICITY; IN-VIVO; ANTITUMOR-ACTIVITY; PRECLINICAL MODELS; MONOCLONAL-ANTIBODY AB New, next-generation targeted treatment strategies are required to improve outcomes in patients with multiple myeloma (MM). Monoclonal antibodies, cell signaling inhibitors, and selective therapies targeting the bone marrow microenvironment have demonstrated encouraging results' with generally manageable toxicity in therapeutic trials of patients with relapsed and refractory disease, each critically informed by preclinical studies. A combination approach of these newer agents with immunomodulators and/or proteasome inhibitors as part of a treatment platform seems to improve the efficacy of anti-MM regimens, even in heavily pretreated patients. Future studies are required to better understand the complex mechanisms of drug resistance in MM. C1 [Varga, Cindy; Laubach, Jacob; Hideshima, Teru; Chauhan, Dharminder; Anderson, Kenneth C.; Richardson, Paul G.] Harvard Univ, Sch Med, Dept Hematol Oncol, Jerome Lipper Multiple Myeloma Ctr,Dana Farber Ca, Boston, MA 02215 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Mayer 228, Boston, MA 02215 USA. EM paul_richardson@dfci.harvard.edu NR 127 TC 4 Z9 4 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2014 VL 28 IS 5 BP 903 EP + DI 10.1016/j.hoc.2014.07.001 PG 25 WC Oncology; Hematology SC Oncology; Hematology GA AQ1EA UT WOS:000342523500009 PM 25212889 ER PT J AU Bae, J Munshi, NC Anderson, KC AF Bae, Jooeun Munshi, Nikhil C. Anderson, Kenneth C. TI Immunotherapy Strategies in Multiple Myeloma SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Multiple myeloma; Passive-specific immunotherapy; Active-specific immunotherapy ID CYTOTOXIC-T-LYMPHOCYTES; UNFOLDED PROTEIN RESPONSE; POTENTIAL THERAPEUTIC APPLICATION; RHAMM-R3 PEPTIDE VACCINATION; CELLULAR IMMUNE-RESPONSES; PULSED DENDRITIC CELLS; MONOCLONAL-ANTIBODY; IDIOTYPE VACCINATION; BONE-MARROW; IN-VIVO AB Multiple myeloma (MM) is a B-cell malignancy characterized by the clonal proliferation of malignant plasma cells, in the bone marrow and the development of osteolytic bone lesions. MM has emerged as a paradigm within the cancers for the success of drug discovery and translational medicine. This article discusses immunotherapy as an encouraging option for the goal of inducing effective and long-lasting therapeutic outcome. Divided into two distinct approaches, passive or active, immunotherapy, which targets tumor-associated antigens has shown promising results in multiple preclinical and clinical studies. C1 [Bae, Jooeun; Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Bae, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Jooeun_Bae@dfci.harvard.edu NR 131 TC 4 Z9 4 U1 2 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2014 VL 28 IS 5 BP 927 EP + DI 10.1016/j.hoc.2014.07.002 PG 18 WC Oncology; Hematology SC Oncology; Hematology GA AQ1EA UT WOS:000342523500010 PM 25212890 ER PT J AU Treon, SP Hunter, ZR Castillo, JJ Merlini, G AF Treon, Steven P. Hunter, Zachary R. Castillo, Jorge J. Merlini, Giampaolo TI Waldenstrom Macroglobulinemia SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Waldenstrom macroglobulinemia; Lymphoproliferative disorder; MYD88 L265P; CXCR4 WHIM mutations; Morbidity; Treatment options ID LYMPHOPLASMACYTIC LYMPHOMA/WALDENSTROM MACROGLOBULINEMIA; FLUDARABINE PLUS CYCLOPHOSPHAMIDE; CONSENSUS PANEL RECOMMENDATIONS; COLD-REACTING AUTOANTIBODIES; 2ND INTERNATIONAL WORKSHOP; COOPERATIVE-ONCOLOGY-GROUP; IGM MONOCLONAL GAMMOPATHY; L265P SOMATIC MUTATION; MANTLE-CELL LYMPHOMA; PHASE-II TRIAL AB Waldenstrom macroglobulinemia (WM) is an IgM-secreting B-cell lympho-proliferative disorder, with strong familial predisposition. MYD88 L265P and CXCR4 WHIM mutations are common in WM and support the growth and survival of WM cells. Clinical manifestations of disease are related to both tumor cell infiltration and paraprotein production. Current treatment includes monoclonal antibodies, alkylating agents, nucleoside analogs, proteasome inhibitors, immunomodulatory drugs, and signal inhibitors. Short- and long-term toxicities should be weighed in treatment decisions with use of these agents. Elucidation of the signaling pathways involved in WM is helping to advance targeted therapeutics for WM and includes efforts directed at MYD88 and CXCR4 signaling. C1 [Treon, Steven P.; Hunter, Zachary R.; Castillo, Jorge J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02215 USA. [Merlini, Giampaolo] Univ Hosp Policlin San Matteo, Amyloidosis Res & Treatment Ctr, Dept Mol Med, I-27100 Pavia, Italy. RP Treon, SP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, 450 Brookline Ave, Boston, MA 02215 USA. EM steven_treon@dfci.harvard.edu RI Merlini, Giampaolo/A-3817-2008; OI Merlini, Giampaolo/0000-0001-7680-3254; Castillo, Jorge/0000-0001-9490-7532; Hunter, Zachary/0000-0002-1689-1691 NR 137 TC 6 Z9 7 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2014 VL 28 IS 5 BP 945 EP + DI 10.1016/j.hoc.2014.06.003 PG 27 WC Oncology; Hematology SC Oncology; Hematology GA AQ1EA UT WOS:000342523500011 PM 25212891 ER PT J AU Touroutoglou, A Bickart, KC Barrett, LF Dickerson, BC AF Touroutoglou, Alexandra Bickart, Kevin C. Barrett, Lisa Feldman Dickerson, Bradford C. TI Amygdala Task-Evoked Activity and Task-Free Connectivity Independently Contribute to Feelings of Arousal SO HUMAN BRAIN MAPPING LA English DT Article DE amygdala; task-evoked activation; resting-state connectivity; individual differences; feelings of arousal ID MEDIAL PREFRONTAL NETWORKS; MACAQUE MONKEYS; FUNCTIONAL CONNECTIVITY; CORTICAL PROJECTIONS; DIFFERENTIAL CONNECTIONS; ANTERIOR INSULA; HUMAN BRAIN; CORTEX; EMOTION; ORGANIZATION AB Individual differences in the intensity of feelings of arousal while viewing emotional pictures have been associated with the magnitude of task-evoked blood-oxygen dependent (BOLD) response in the amygdala. Recently, we reported that individual differences in feelings of arousal are associated with task-free (resting state) connectivity within the salience network. There has not yet been an investigation of whether these two types of functional magnetic resonance imaging (MRI) measures are redundant or independent in their relationships to behavior. Here we tested the hypothesis that a combination of task-evoked amygdala activation and task-free amygdala connectivity within the salience network relate to individual differences in feelings of arousal while viewing of negatively potent images. In 25 young adults, results revealed that greater task-evoked amygdala activation and stronger task-free amygdala connectivity within the salience network each contributed independently to feelings of arousal, predicting a total of 45% of its variance. Individuals who had both increased task-evoked amygdala activation and stronger task-free amygdala connectivity within the salience network had the most heightened levels of arousal. Task-evoked amygdala activation and task-free amygdala connectivity within the salience network were not related to each other, suggesting that resting-state and task-evoked dynamic brain imaging measures may provide independent and complementary information about affective experience, and likely other kinds of behaviors as well. Hum Brain Mapp 35:5316-5327, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Touroutoglou, Alexandra] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Touroutoglou, Alexandra; Barrett, Lisa Feldman; Dickerson, Bradford C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Touroutoglou, Alexandra; Barrett, Lisa Feldman; Dickerson, Bradford C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. [Touroutoglou, Alexandra; Barrett, Lisa Feldman; Dickerson, Bradford C.] Massachusetts Gen Hosp, Div Psychiat Neuroimaging, Dept Psychiat, Boston, MA 02114 USA. [Bickart, Kevin C.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Frontotemporal Disorders Unit, Dept Neurol, Boston, MA 02114 USA. RP Dickerson, BC (reprint author), MGH Frontotemporal Disorders Unit, 149 13th St,Suite 2691, Boston, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu FU National Institutes of Health Director's Pioneer Award [DP1OD003312]; National Institute on Aging Grant [R01 AG030311-06A1] FX Contract grant sponsor: National Institutes of Health Director's Pioneer Award; Contract grant number: DP1OD003312; Contract grant sponsor: National Institute on Aging Grant; Contract grant number: R01 AG030311-06A1. NR 66 TC 9 Z9 9 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD OCT PY 2014 VL 35 IS 10 BP 5316 EP 5327 DI 10.1002/hbm.22552 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AQ3CV UT WOS:000342667400027 PM 24862171 ER PT J AU Oldenburg, CE Biello, KB Colby, D Closson, EF Mai, T Nguyen, T Nguyen, NA Mimiaga, MJ AF Oldenburg, Catherine E. Biello, Katie B. Colby, Donn Closson, Elizabeth F. Thi Mai Thi Nguyen Nguyen, Ngoc A. Mimiaga, Matthew J. TI Stigma related to sex work among men who engage in transactional sex with men in Ho Chi Minh City, Vietnam SO INTERNATIONAL JOURNAL OF PUBLIC HEALTH LA English DT Article DE HIV; Sex workers; Male sex workers; Vietnam; Depression; Stigma ID HIV-RELATED STIGMA; INTERNALIZED STIGMA; DISCRIMINATION; DEPRESSION; RISK; PREVENTION; HANOI; WOMEN; INDIA; ASSOCIATIONS AB Male sex workers (MSW) in Vietnam face high levels of stigma related to sex work, which may be associated with depression and increased vulnerability to HIV. In 2010, 300 MSW completed a behavioral and psychosocial survey. Multivariable models assessed factors associated with sex work-related stigma and the association between stigma and depression. Factors associated with increased stigma included having disclosed sexual orientation to healthcare workers (b 1.75, 95 % CI 0.69-2.80), meeting clients in the street/park (b 1.42, 95 % CI 0.32-2.52), and having been forced to have sex without a condom (b 2.36, 95 % CI 1.27-3.45). Factors associated with decreased stigma included meeting clients via the telephone or internet (b -1.26, 95 % CI -2.39 to -0.12) and receiving financial support from family or friends (b -1.31, 95 % CI -2.46 to -0.17). Stigma was significantly associated with increased odds of depression (AOR 1.07, 95 % CI 1.01-1.15). Addressing stigma and depression in HIV prevention interventions is crucial for tailoring these programs to MSWs' needs, and may result in decreased HIV spread. C1 [Oldenburg, Catherine E.; Biello, Katie B.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Biello, Katie B.; Closson, Elizabeth F.; Mimiaga, Matthew J.] Fenway Community Hlth Boston, Fenway Inst, Boston, MA USA. [Colby, Donn; Thi Mai; Thi Nguyen; Nguyen, Ngoc A.] Harvard Med Sch AIDS Initiat Vietnam, Ho Chi Minh City, Vietnam. [Colby, Donn] Ctr Appl Res Men & Hlth, Ho Chi Minh City, Vietnam. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Mimiaga, MJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM ceo242@mail.harvard.edu; mmimiaga@hsph.harvard.edu OI colby, donn/0000-0003-3931-5926 FU Harvard Catalyst-The Harvard Clinical and Translational Science Center; NIAID [T32AI007535] FX This study was conducted with the support of a pilot grant from Harvard Catalyst-The Harvard Clinical and Translational Science Center (PIs: Colby and Mimiaga). CEO is supported by NIAID T32AI007535 (PI: Seage). NR 35 TC 12 Z9 12 U1 3 U2 5 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1661-8556 EI 1661-8564 J9 INT J PUBLIC HEALTH JI Int. J. Public Health PD OCT PY 2014 VL 59 IS 5 BP 833 EP 840 DI 10.1007/s00038-014-0562-x PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AQ0UK UT WOS:000342498000021 PM 24858522 ER PT J AU Burke, RE Jones, J Ho, PM Bekelman, DB AF Burke, Robert E. Jones, Jacqueline Ho, P. Michael Bekelman, David B. TI Caregivers' Perceived Roles in Caring for Patients With Heart Failure: What Do Clinicians Need to Know? SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Caregiver; self-management; heart failure; qualitative ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; FAMILY CAREGIVERS; OLDER-ADULTS; INFORMAL CAREGIVERS; ALZHEIMERS-DISEASE; CARE; PROGRAM; HOME; INTERVENTION AB Background: Poor self-management of heart failure (HF) is an essential contributor to poor outcomes. Caregivers are involved in the care of HF patients, but caregiver interventions intended to improve the outcomes of patients have been largely unsuccessful. Improved knowledge of caregivers' desired roles in care may improve future interventions. Methods and Results: This qualitative study of 20 caregivers of BF patients recruited from an academic medical center used a general inductive approach, with insights from role theory, to analyze the data. Caregivers perceived themselves as health care managers and care plan enforcers, advocates for quality of life, and experts in the lived experience of HF at home. However, they encountered role strain (expectations of role exceed ability to perform role) and role conflict (incompatible or contradictory roles) when it seemed that these roles were incompatible with those that they felt the health care system saw them in. This resulted in expressions of anger and distrust towards the health care system. Conclusions: Clinicians caring for patients with BF can seek to better empower and enable this care. Involving caregivers in disease management research and assessing their roles before intervention may hold promise for enabling and empowering caregivers to improve outcomes of HF patients. C1 [Burke, Robert E.] Denver VA Med Ctr, Hosp Med Sect, Denver, CO 80220 USA. [Burke, Robert E.; Bekelman, David B.] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Denver, CO USA. [Jones, Jacqueline] Univ Colorado, Coll Nursing, Denver, CO 80202 USA. [Ho, P. Michael] Denver VA Med Ctr, Cardiol Sect, Denver, CO 80220 USA. [Ho, P. Michael] Univ Colorado, Sch Med, Dept Med, Denver, CO USA. [Bekelman, David B.] Denver VA Med Ctr, Res Sect, Denver, CO 80220 USA. [Bekelman, David B.] Denver VA Med Ctr, Geriatr Sect, Denver, CO 80220 USA. RP Burke, RE (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM robert.burke5@va.gov FU VA HSR&D Colorado Research to Improve Care Coordination REAP; Hartford/Jahnigen Center of Excellence at the University of Colorado; Dr Bekelman's VA Career Development Award [08-022] FX Dr Burke was supported by the VA HSR&D Colorado Research to Improve Care Coordination REAP. The original interviewers were supported by the Hartford/Jahnigen Center of Excellence at the University of Colorado and Dr Bekelman's VA Career Development Award (08-022). These funding sources had no role in the design, interpretation, or presentation of results. This report represents the views of the authors and not necessarily those of the US Department of Veterans Affairs. NR 42 TC 7 Z9 8 U1 3 U2 10 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD OCT PY 2014 VL 20 IS 10 BP 731 EP 738 DI 10.1016/j.cardfail.2014.07.011 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AQ2XN UT WOS:000342653400004 PM 25084216 ER PT J AU Houstis, NE Lewis, GD AF Houstis, Nicholas E. Lewis, Gregory D. TI Causes of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Searching for Consensus SO JOURNAL OF CARDIAC FAILURE LA English DT Review DE Exercise testing; VO(2)max; Fick; diagnostic criteria ID ISOLATED DIASTOLIC DYSFUNCTION; CARDIAC-OUTPUT; STROKE VOLUME; HYPERTROPHIC CARDIOMYOPATHY; VENTRICULAR-ARTERIAL; GAS-EXCHANGE; CHRONOTROPIC INCOMPETENCE; MYOCARDIAL RELAXATION; MECHANISTIC INSIGHTS; STARLING MECHANISM AB Exercise intolerance is one of the cardinal symptoms of heart failure with preserved ejection fraction (HFpEF). We review its mechanistic basis using evidence from exercise studies. One barrier to a consensus understanding of the pathophysiology is heterogeneity of the patient population. Therefore, we pay special attention to varying study definitions of the disease and their possible impact on the causal factors that are implicated. We then discuss the role of exercise testing and its potential to subtype IAPpEF in to more homogeneous mechanism-based subclasses. C1 [Houstis, Nicholas E.; Lewis, Gregory D.] Harvard Univ, Sch Med, Dept Med, Cardiol Div,Massachusetts Gen Hosp, Boston, MA USA. RP Lewis, GD (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Bigelow 800,Fruit St, Boston, MA 02114 USA. EM glewis@partners.org NR 109 TC 5 Z9 6 U1 2 U2 8 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD OCT PY 2014 VL 20 IS 10 BP 762 EP 778 DI 10.1016/j.cardfail.2014.07.010 PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AQ2XN UT WOS:000342653400008 PM 25108084 ER PT J AU Jing, Z Xing, J Chen, XZ Stetler, RA Weng, ZF Gan, Y Zhang, F Gao, YQ Chen, J Leak, RK Cao, GD AF Jing, Zheng Xing, Juan Chen, Xinzhi Stetler, Ruth A. Weng, Zhongfang Gan, Yu Zhang, Feng Gao, Yanqin Chen, Jun Leak, Rehana K. Cao, Guodong TI Neuronal NAMPT is released after cerebral ischemia and protects against white matter injury SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE NAMPT; NAMPT secretion; neuroprotection; oligodendrocytes; transient MCAO; white matter injury ID NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; BRAIN-INJURY; MOUSE MODEL; STROKE; LESIONS; CELLS; ACCUMULATION; TISSUE; THY-1; RAT AB Nicotinamide phosphoribosyltransferase (NAMPT) has been implicated in neuroprotection against ischemic brain injury, but the mechanism underlying its protective effect remains largely unknown. To further examine the protective effect of NAMPT against ischemic stroke and its potential mechanism of action, we generated a novel neuron-specific NAMPT transgenic mouse line. Transgenic mice and wild-type littermates were subjected to transient occlusion of the middle cerebral artery (MCAO) for 60 minutes. Neuron-specific NAMPT overexpression significantly reduced infarct volume by 65% (P=0.018) and improved long-term neurologic outcomes (P <= 0.05) compared with littermates. Interestingly, neuronal overexpression of NAMPT increased the area of myelinated fibers in the striatum and corpus callosum, indicating that NAMPT protects against white matter injury. The mechanism of protection appeared to be through extracellular release of NAMPT. First, NAMPT was secreted into the extracellular medium by primary cortical neurons exposed to ischemia-like oxygen-glucose deprivation (OGD) in vitro. Second, conditioned medium from NAMPT-overexpressing neurons exposed to OGD protected cultured oligodendrocytes from OGD. Third, the protective effects of conditioned medium were abolished by antibody-mediated NAMPT depletion, strongly suggesting that the protective effect is mediated by the extracellular NAMPT released into in the medium. These data suggest a novel neuroprotective role for secreted NAMPT in the protection of white matter after ischemic injury. C1 [Jing, Zheng; Xing, Juan; Chen, Xinzhi; Chen, Jun; Cao, Guodong] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Jing, Zheng; Xing, Juan; Chen, Xinzhi; Stetler, Ruth A.; Weng, Zhongfang; Gan, Yu; Zhang, Feng; Chen, Jun; Cao, Guodong] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA. [Gao, Yanqin] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15219 USA. RP Cao, GD (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, BST S505,3500 Terrace St, Pittsburgh, PA 15260 USA. EM caog@upmc.edu RI Gao, Yanqin/I-6790-2016; OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417 FU National Institutes of Health/NINDS [NS079345]; VA Merit Review [RX000199, BX002346]; Chinese Natural Science Foundation [81371306] FX This project was supported by National Institutes of Health/NINDS grants NS079345, (to GC), VA Merit Review grants RX000199 and BX002346 (to GC), and Chinese Natural Science Foundation grants 81371306 (to Yanqin Gao). NR 27 TC 16 Z9 16 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2014 VL 34 IS 10 BP 1613 EP 1621 DI 10.1038/jcbfm.2014.119 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA AQ1IV UT WOS:000342536000005 PM 25005877 ER PT J AU Walcott, BP AF Walcott, Brian P. TI BMP signaling modulation attenuates cerebral arteriovenous malformation formation in a vertebrate model SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE arteriovenous malformation; losartan; medical therapy; stroke; zebrafish ID MARFAN-SYNDROME; AORTIC-ANEURYSM; LOSARTAN; BRAIN; CELLS; GENE; MICE; SPECIFICATION; ANTAGONIST; RECEPTORS AB Cerebral arteriovenous malformations (AVMs) are vascular anomalies that carry a high risk of stroke and death. To test potential AVM therapies, a reverse genetics approach was used to model AVMs in zebrafish. Antisense morpholino oligonucleotides were used to knockdown activin receptor-like kinase I (alk1), which encodes a transforming growth factor (TGF)-beta family type I receptor implicated in a subset of human AVMs. Knockdown of alk1 caused a spectrum of morphologic, functional, and molecular defects that resemble those seen in human with AVMs. It was found that losartan, an angiotensin II receptor antagonist, attenuated abnormal blood vessel morphology and systemic manifestations of high-output arteriovenous shunting in vivo. SMAD1 phosphorylation was significantly decreased in alk1 morphants compared with uninjected organisms (0.189 +/- 0.0201, 0.429 +/- 0.0164, P = 0.0002). After treatment, morphant SMAD1 levels approached uninjected levels (0.326 +/- 0.0360, P = 0.0355) and were significantly higher than those seen in the morphant-control group (P = 0.0294). These data suggest that modulating the BMP signaling pathway with losartan, a drug in widespread clinical use in humans as an antihypertensive, may have the potential to be further evaluated as a therapeutic strategy for patients with AVMs. C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. [Walcott, Brian P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Walcott, Brian P.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Walcott, Brian P.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurol Surg, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU Brain Aneurysm Foundation; American Medical Association Seed Grant program; Congress of Neurological Surgeons FX Funding for this research was made in part by the Brain Aneurysm Foundation, the American Medical Association Seed Grant program, and the Congress of Neurological Surgeons. NR 39 TC 3 Z9 4 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2014 VL 34 IS 10 BP 1688 EP 1694 DI 10.1038/jcbfm.2014.134 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA AQ1IV UT WOS:000342536000014 PM 25052553 ER PT J AU Yien, YY Robledo, RF Schultz, IJ Takahashi-Makise, N Gwynn, B Bauer, DE Dass, A Yi, G Li, LT Hildick-Smith, GJ Cooney, JD Pierce, EL Mohler, K Dailey, TA Miyata, N Kingsley, PD Garone, C Hattangadi, SM Huang, H Chen, W Keenan, EM Shah, DI Schlaeger, TM DiMauro, S Orkin, SH Cantor, AB Palis, J Koehler, CM Lodish, HF Kaplan, J Ward, DM Dailey, HA Phillips, JD Peters, LL Paw, BH AF Yien, Yvette Y. Robledo, Raymond F. Schultz, Iman J. Takahashi-Makise, Naoko Gwynn, Babette Bauer, Daniel E. Dass, Abhishek Yi, Gloria Li, Liangtao Hildick-Smith, Gordon J. Cooney, Jeffrey D. Pierce, Eric L. Mohler, Kyla Dailey, Tamara A. Miyata, Non Kingsley, Paul D. Garone, Caterina Hattangadi, Shilpa M. Huang, Hui Chen, Wen Keenan, Ellen M. Shah, Dhvanit I. Schlaeger, Thorsten M. DiMauro, Salvatore Orkin, Stuart H. Cantor, Alan B. Palis, James Koehler, Carla M. Lodish, Harvey F. Kaplan, Jerry Ward, Diane M. Dailey, Harry A. Phillips, John D. Peters, Luanne L. Paw, Barry H. TI TMEM14C is required for erythroid mitochondrial heme metabolism SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CONGENITAL ERYTHROPOIETIC PORPHYRIA; CHROMATIN OCCUPANCY; IRON ASSIMILATION; GENE ACTIVATION; CHIP-SEQ; CELLS; DIFFERENTIATION; PROTEIN; LOCI; BIOSYNTHESIS AB The transport and intracellular trafficking of heme biosynthesis intermediates are crucial for hemoglobin production, which is a critical process in developing red cells. Here, we profiled gene expression in terminally differentiating murine fetal liver-derived erythroid cells to identify regulators of heme metabolism. We determined that TMEM14C, an inner mitochondrial membrane protein that is enriched in vertebrate hematopoietic tissues, is essential for erythropoiesis and heme synthesis in vivo and in cultured erythroid cells. In mice, TMEM14C deficiency resulted in porphyrin accumulation in the fetal liver, erythroid maturation arrest, and embryonic lethality due to profound anemia. Protoporphyrin IX synthesis in TMEM14C-deficient erythroid cells was blocked, leading to an accumulation of porphyrin precursors. The heme synthesis defect in TMEM14C-deficient cells was ameliorated with a protoporphyrin IX analog, indicating that TMEM14C primarily functions in the terminal steps of the heme synthesis pathway. Together, our data demonstrate that TMEM14C facilitates the import of protoporphyrinogen IX into the mitochondrial matrix for heme synthesis and subsequent hemoglobin production. Furthermore, the identification of TMEM14C as a protoporphyrinogen IX importer provides a genetic tool for further exploring erythropoiesis and congenital anemias. C1 [Yien, Yvette Y.; Schultz, Iman J.; Hildick-Smith, Gordon J.; Cooney, Jeffrey D.; Pierce, Eric L.; Chen, Wen; Keenan, Ellen M.; Shah, Dhvanit I.; Paw, Barry H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol, Boston, MA 02115 USA. [Robledo, Raymond F.; Gwynn, Babette; Peters, Luanne L.] Jackson Lab, Bar Harbor, ME 04609 USA. [Takahashi-Makise, Naoko; Li, Liangtao; Kaplan, Jerry; Ward, Diane M.] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. [Bauer, Daniel E.; Dass, Abhishek; Yi, Gloria; Hattangadi, Shilpa M.; Huang, Hui; Schlaeger, Thorsten M.; Orkin, Stuart H.; Cantor, Alan B.; Paw, Barry H.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Bauer, Daniel E.; Hattangadi, Shilpa M.; Orkin, Stuart H.; Cantor, Alan B.; Paw, Barry H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Mohler, Kyla; Dailey, Tamara A.; Dailey, Harry A.] Univ Georgia, Biomed & Hlth Sci Inst, Dept Microbiol, Athens, GA 30602 USA. [Mohler, Kyla; Dailey, Tamara A.; Dailey, Harry A.] Univ Georgia, Biomed & Hlth Sci Inst, Dept Biochem, Athens, GA 30602 USA. [Mohler, Kyla; Dailey, Tamara A.; Dailey, Harry A.] Univ Georgia, Biomed & Hlth Sci Inst, Dept Mol Biol, Athens, GA 30602 USA. [Miyata, Non; Koehler, Carla M.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90024 USA. [Kingsley, Paul D.; Palis, James] Univ Rochester, Sch Med & Dent, Dept Pediat, Ctr Pediat Biomed Res, Rochester, NY 14642 USA. [Garone, Caterina; DiMauro, Salvatore] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Hattangadi, Shilpa M.; Lodish, Harvey F.] MIT, Whitehead Inst, Cambridge, MA 02139 USA. [Hattangadi, Shilpa M.; Lodish, Harvey F.] MIT, Dept Biol, Cambridge, MA USA. [Phillips, John D.] Univ Utah, Sch Med, Div Hematol, Salt Lake City, UT USA. RP Paw, BH (reprint author), Brigham & Womens Hosp, Div Hematol, 1 Blackfan Circle,Karp 05-211, Boston, MA 02115 USA. EM luanne.peters@jax.org; bpaw@rics.bwh.harvard.edu OI Garone, Caterina/0000-0003-4928-1037 FU NIH center grant [P30 DK34854]; American Heart Association; Cooley's Anemia Foundation; March of Dimes Foundation [6-FY09-289]; NWO Dutch National Science Fund; American Physiological Society; NIH [K01 DK085217, K08 DK076848, T32 HL007574, F32 DK098866, K08 DK093705, P01 HD032062, R01 DK09361, DK020503, U54 DK083909, R01 DK096051, R01 GM61721, R01 DK052830, R01 HL088468, R01 DK070838, P01 HL032262] FX We thank James Bieker, Roslyn Orkin, David Williams, and Leonard Zon for critical feedback on the manuscript. We thank Caiyong Chen, Jacky Chung, and Amy Medlock for technical advice and helpful scientific discussions. We thank Mahnaz Paktinat for training on the use of the BD FACSCanto cell sorter, as mentioned in the Supplemental Methods, and Marie McConkey, Esther Obeng, and Benjamin Ebert for providing mouse tissues. We also thank Jonathan Thou for his assistance in analysis of confocal images. The DS19 MEL clones were obtained from Arthur Skoultchi (Albert Einstein College of Medicine). As detailed in the Supplemental Methods, fluorescence confocal microscopy was performed at the Harvard Digestive Disease Center Imaging Facility (Boston Children's Hospital, supported by NIH center grant P30 DK34854) with assistance from Ramiro Massol. This work was supported by grants from the American Heart Association (to J.D. Cooney), Cooley's Anemia Foundation (to D.I. Shah), the March of Dimes Foundation (6-FY09-289, to B.H. Paw), the NWO Dutch National Science Fund (to I.J. Schultz), the American Physiological Society (to E.M. Keenan), and the NIH (K01 DK085217, to D.I. Shah; K08 DK076848, to S.M. Hattangadi; T32 HL007574 and F32 DK098866, to Y.Y. Yien; K08 DK093705, to D.E. Bauer; P01 HD032062, to S. DiMauro; R01 DK09361, to J.D. Phillips; DK020503 and U54 DK083909, to J.D. Phillips; R01 DK096051, to H.A. Dailey; R01 GM61721, to C.M. Koehler; R01 DK052830, to J. Kaplan and D.M. Ward; R01 HL088468, to L.L. Peters; R01 DK070838, to B.H. Paw; and P01 HL032262, to A.B. Cantor, H.F. Lodish, S.H. Orkin, and B.H. Paw). NR 68 TC 11 Z9 11 U1 1 U2 14 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2014 VL 124 IS 10 BP 4294 EP 4304 DI 10.1172/JCI76979 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AQ2WG UT WOS:000342649900026 PM 25157825 ER PT J AU Loison, F Zhu, HY Karatepe, K Kasorn, A Liu, P Ye, KQ Zhou, JX Cao, SN Gong, HY Jenne, DE Remold-O'Donnell, E Xu, YF Luo, HBR AF Loison, Fabien Zhu, Haiyan Karatepe, Kutay Kasorn, Anongnard Liu, Peng Ye, Keqiang Zhou, Jiaxi Cao, Shannan Gong, Haiyan Jenne, Dieter E. Remold-O'Donnell, Eileen Xu, Yuanfu Luo, Hongbo R. TI Proteinase 3-dependent caspase-3 cleavage modulates neutrophil death and inflammation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CELL-DEATH; SERINE PROTEASES; POLYMORPHONUCLEAR LEUKOCYTES; CATHEPSIN-G; APOPTOSIS; ACTIVATION; MECHANISMS; ELASTASE; GRANULES; SERPINB1 AB Caspase-3 mediated spontaneous death in neutrophils is a prototype of programmed cell death and is critical for modulating physiopathological inflammatory responses; however, the underlying regulatory pathways remain ill defined. Here we determined that in aging neutrophils, the cleavage and activation of caspase-3 is independent of the canonical caspase-8 or caspase-9 mediated pathway. Instead, caspase-3 activation was mediated by serine protease proteinase 3 (PR3), which is present in the cytosol of aging neutrophils. Specifically, PR3 cleaved procaspase-3 at a site upstream of the canonical caspase-9 cleavage site. In mature neutrophils, PR3 was sequestered in granules and released during aging via lysosomal membrane permeabilization (LMP), leading to procaspase-3 cleavage and apoptosis. Pharmacological inhibition or knockdown of PR3 delayed neutrophil death in vitro and consistently delayed neutrophil death and augmented neutrophil accumulation at sites of inflammation in a murine model of peritonitis. Adoptive transfer of both WT and PR3-deficient neutrophils revealed that the delayed death of neutrophils lacking PR3 is due to an altered intrinsic apoptosis/survival pathway, rather than the inflammatory microenvironment. The presence of the suicide protease inhibitor SERPINB1 counterbalanced the protease activity of PR3 in aging neutrophils, and deletion of Serpinb1 accelerated neutrophil death. Taken together, our results reveal that PR3-mediated caspase-3 activation controls neutrophil spontaneous death. C1 [Loison, Fabien; Karatepe, Kutay; Kasorn, Anongnard; Luo, Hongbo R.] Harvard Univ, Sch Med, Dept Pathol, Dept Lab Med,Childrens Hosp Boston, Boston, MA 02115 USA. [Loison, Fabien; Karatepe, Kutay; Kasorn, Anongnard; Luo, Hongbo R.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Loison, Fabien] Mahidol Univ, Fac Sci, Dept Microbiol, Bangkok 10400, Thailand. [Zhu, Haiyan; Liu, Peng; Zhou, Jiaxi; Cao, Shannan; Gong, Haiyan; Xu, Yuanfu] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China. [Zhu, Haiyan; Liu, Peng; Zhou, Jiaxi; Cao, Shannan; Gong, Haiyan; Xu, Yuanfu] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China. [Zhu, Haiyan; Liu, Peng; Zhou, Jiaxi; Cao, Shannan; Gong, Haiyan; Xu, Yuanfu] Peking Union Med Coll, Tianjin, Peoples R China. [Kasorn, Anongnard] Srinakharinwirot Univ, Fac Med, Dept Community Med, Bangkok, Thailand. [Ye, Keqiang] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Jenne, Dieter E.] Helmholtz Zentrum Munchen, Comprehens Pneumol Ctr, Munich, Germany. [Remold-O'Donnell, Eileen] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. [Remold-O'Donnell, Eileen] Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. [Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Luo, HBR (reprint author), Enders Res Bldg,Room 811, Tianjin 300020, Peoples R China. EM xuyf@ihcams.ac.cn; Hongbo.Luo@childrens.harvard.edu FU National Basic Research Program of China [2012CB966403]; Chinese National Natural Sciences Foundation [31271484]; Tianjin Natural Science Foundation [12JCZDJC24600]; NIH grants [R01AI103142, R01HL092020, P01 HL095489]; FAMRI; European Union [261382]; NIH [R21AI103407] FX The authors thank Leslie Silberstein, Li Chai, John Lucky, and John Manis for helpful discussions and Catlyn Blanchard, Jia Zhong, and Li Zhao for preparing the mice. Y. Xu is supported by grant 2012CB966403 from the National Basic Research Program of China, grant 31271484 from the Chinese National Natural Sciences Foundation, and grant 12JCZDJC24600 from the Tianjin Natural Science Foundation. H.R. Luo is supported by NIH grants R01AI103142, R01HL092020, and P01 HL095489 and by a grant from the FAMRI. This work was also supported by European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement 261382 (INTRICATE) (to D.E. Jenne). E. Remold-O'Donnell is supported by NIH grant R21AI103407. NR 50 TC 18 Z9 18 U1 2 U2 11 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2014 VL 124 IS 10 BP 4445 EP 4458 DI 10.1172/JCI76246 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AQ2WG UT WOS:000342649900038 PM 25180606 ER PT J AU Zhu, QY Yamakuchi, M Ture, S Garcia-Hernandez, MD Ko, KA Modjeski, KL LoMonaco, MB Johnson, AB O'Donnell, CJ Takai, Y Morrell, CN Lowenstein, CJ AF Zhu, Qiuyu Yamakuchi, Munekazu Ture, Sara Garcia-Hernandez, Maria de la Luz Ko, Kyung Ae Modjeski, Kristina L. LoMonaco, Michael B. Johnson, Andrew B. O'Donnell, Christopher J. Takai, Yoshimi Morrell, Craig N. Lowenstein, Charles J. TI Syntaxin-binding protein STXBP5 inhibits endothelial exocytosis and promotes platelet secretion SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID VON-WILLEBRAND-FACTOR; WEIBEL-PALADE BODY; ETHYLMALEIMIDE-SENSITIVE-FACTOR; SYNAPTIC VESICLE CYCLE; THROMBUS FORMATION; NEUROTRANSMITTER RELEASE; MEMBRANE-FUSION; VENOUS THROMBOEMBOLISM; CARDIOVASCULAR-DISEASE; REGULATES EXOCYTOSIS AB In humans, vWF levels predict the risk of myocardial infarction and thrombosis; however, the factors that influence vWF levels are not completely understood. Recent genome-wide association studies (GWAS) have identified syntaxin-binding protein 5 (STXBP5) as a candidate gene linked to changes in vWF plasma levels, though the functional relationship between STXBPS and vWF is unknown. We hypothesized that STXBP5 inhibits endothelial cell exocytosis. We found that STXBP5 is expressed in human endothelial cells and colocalizes with and interacts with syntaxin 4. In human endothelial cells reduction of STXBP5 increased exocytosis of vWF and P-selectin. Mice lacking Stxbp5 had higher levels of vWF in the plasma, increased P-selectin translocation, and more platelet-endothelial interactions, which suggests that STXBP5 inhibits endothelial exocytosis. However, Stxbp5 KO mice also displayed hemostasis defects, including prolonged tail bleeding times and impaired mesenteric arteriole and carotid artery thrombosis. Furthermore, platelets from Stxbp5 KO mice had defects in platelet secretion and activation; thus, STXBP5 inhibits endothelial exocytosis but promotes platelet secretion. Our study reveals a vascular function for STXBP5, validates the functional relevance of a candidate gene identified by GWAS, and suggests that variation within STXBPS is a genetic risk for venous thromboembolic disease. C1 [Zhu, Qiuyu; Yamakuchi, Munekazu; Ture, Sara; Garcia-Hernandez, Maria de la Luz; Ko, Kyung Ae; Modjeski, Kristina L.; LoMonaco, Michael B.; Morrell, Craig N.; Lowenstein, Charles J.] Univ Rochester, Med Ctr, Dept Med, Aab Cardiovasc Res Inst, Rochester, NY 14642 USA. [Zhu, Qiuyu; Modjeski, Kristina L.] Univ Rochester, Sch Med & Dent, Dept Physiol & Pharmacol, Rochester, NY USA. [Yamakuchi, Munekazu] Kagoshima Univ, Grad Sch Med & Dent, Dept Lab & Vasc Med, Kagoshima 890, Japan. [Johnson, Andrew B.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, NIH, Framingham, MA USA. [Johnson, Andrew B.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiovasc, Boston, MA USA. [Takai, Yoshimi] Kobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Kobe, Hyogo 657, Japan. RP Lowenstein, CJ (reprint author), Box CVRI,601 Elmwood Ave, Rochester, NY 14642 USA. EM charles_lowenstein@urmc.rochester.edu RI Johnson, Andrew/G-6520-2013 FU NIH/NHLBI [R21 HL108372]; HHMI "Med-into-Grad" Fellowship in Cardiovascular Sciences at the Aab Cardiovascular Research Institute, University of Rochester; American Heart Association [14GRNT19020033, 0835446N, 13PRE17050105] FX We thank Jun Miyoshi for Stxbp5 KO mice, Sriram Neelamegham for XS-vWF protein, and David James for pMEX neo-3xFLAG-tomosyn (8)-ATG expression plasmid. This work was supported by NIH/NHLBI grant R21 HL108372 (to C.J. Lowenstein); by the HHMI "Med-into-Grad" Fellowship in Cardiovascular Sciences at the Aab Cardiovascular Research Institute, University of Rochester (to C.J. Lowenstein and Q Zhu); and by American Heart Association grants 14GRNT19020033 (to C.J. Lowenstein), 0835446N (to M. Yamakuchi), and 13PRE17050105 (to Q. Zhu). NR 87 TC 17 Z9 17 U1 2 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2014 VL 124 IS 10 BP 4503 EP 4516 DI 10.1172/JCI71245 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AQ2WG UT WOS:000342649900042 PM 25244095 ER PT J AU Kahl, BS Hong, FX Williams, ME Gascoyne, RD Wagner, LI Krauss, JC Habermann, TM Swinnen, LJ Schuster, SJ Peterson, CG Sborov, MD Martin, SE Weiss, M Ehmann, WC Horning, SJ AF Kahl, Brad S. Hong, Fangxin Williams, Michael E. Gascoyne, Randy D. Wagner, Lynne I. Krauss, John C. Habermann, Thomas M. Swinnen, Lode J. Schuster, Stephen J. Peterson, Christopher G. Sborov, Mark D. Martin, S. Eric Weiss, Matthias Ehmann, W. Christopher Horning, Sandra J. TI Rituximab Extended Schedule or Re-Treatment Trial for Low-Tumor Burden Follicular Lymphoma: Eastern Cooperative Oncology Group Protocol E4402 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; ANTI-CD20 MONOCLONAL-ANTIBODY; PHASE-II TRIAL; RANDOMIZED CONTROLLED-TRIAL; ADVANCED-STAGE; MAINTENANCE THERAPY; INDOLENT LYMPHOMA; FREE SURVIVAL; FOLLOW-UP; LOW-GRADE AB Purpose In low-tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival when compared with observation. It is not known whether MR provides superior long-term disease control compared with re-treatment rituximab (RR) administered on an as-needed basis. E4402 (RESORT) was a randomized clinical trial designed to compare MR against RR. Patients and Methods Eligible patients with previously untreated low-tumor burden FL received four doses of rituximab, and responding patients were randomly assigned to either RR or MR. Patients receiving RR were eligible for re-treatment at each disease progression until treatment failure. Patients assigned to MR received a single dose of rituximab every 3 months until treatment failure. The primary end point was time to treatment failure. Secondary end points included time to first cytotoxic therapy, toxicity, and health-related quality of life (HRQOL). Results A total of 289 patients were randomly assigned to RR or MR. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years for patients receiving RR and 4.3 years for those receiving MR (P = .54). Three-year freedom from cytotoxic therapy was 84% for those receiving RR and 95% for those receiving MR (P = .03). The median number of rituximab doses was four patients receiving RR and 18 for those receiving MR. There was no difference in HRQOL. Grade 3 to 4 toxicities were infrequent in both arms. Conclusion In low-tumor burden FL, a re-treatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy. (C) 2014 by American Society of Clinical Oncology C1 [Kahl, Brad S.] Univ Wisconsin, Madison, WI 53705 USA. [Peterson, Christopher G.] Aspirus Reg Canc Ctr, Wausau, WI USA. [Weiss, Matthias] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. [Hong, Fangxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Williams, Michael E.] Univ Virginia, Charlottesville, VA USA. [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Wagner, Lynne I.] Northwestern Univ, Chicago, IL 60611 USA. [Krauss, John C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Habermann, Thomas M.] Mayo Clin, Rochester, MN USA. [Sborov, Mark D.] Fairview Southdale Hosp, St Louis Pk, MN USA. [Swinnen, Lode J.] Johns Hopkins Univ, Baltimore, MD USA. [Schuster, Stephen J.] Univ Penn, Philadelphia, PA 19104 USA. [Ehmann, W. Christopher] Penn State Canc Inst, Hershey, PA USA. [Martin, S. Eric] Christiana Care Community Clin Oncol Program, Newark, DE USA. [Martin, S. Eric] Helen F Graham Canc Network, Newark, DE USA. [Horning, Sandra J.] Genentech Inc, San Francisco, CA 94080 USA. RP Kahl, BS (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, 1111 Highland Ave,4059 Wisconsin Inst Med Res, Madison, WI 53705 USA. EM bsk@medicine.wisc.edu FU Public Health Service Grants from National Cancer Institute, National Institutes of Health, and Department of Health and Human Services [CA21115, CA23318, CA66636, CA49957, CA21076, CA17145, CA13650] FX Supported in part by Public Health Service Grants No. CA21115, CA23318, CA66636, CA49957, CA21076, CA17145, and CA13650 from the National Cancer Institute, National Institutes of Health, and Department of Health and Human Services. NR 28 TC 40 Z9 41 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2014 VL 32 IS 28 BP 3096 EP + DI 10.1200/JCO.2014.56.5853 PG 9 WC Oncology SC Oncology GA AQ3EB UT WOS:000342671000004 PM 25154829 ER PT J AU Donahue, J AF Donahue, John TI Coronary Artery Disease in Offender Populations: Incarceration as a Risk Factor and a Point of Intervention SO JOURNAL OF CORRECTIONAL HEALTH CARE LA English DT Article DE coronary artery disease; incarceration; offenders; prevention programs ID STATE PRISON-INMATES; CARDIOVASCULAR-DISEASE; SUBSTANCE-ABUSE; HEART-DISEASE; UNITED-STATES; HEALTH-CARE; LIFE-STYLE; DISPARITIES; PREVENTION; MORTALITY AB Coronary artery disease (CAD) is a significant health problem and global burden. Research on antisocial behaviors has identified some groups of offenders as vulnerable to the development of cardiovascular disorders. This article reviews the relationship between criminal offending and CAD, with a particular emphasis on incarcerated populations. Existing research supports this link, with incarceration demonstrating substantial associations with numerous cardiac risk factors, development of cardiac problems, and cardiovascular disease mortality. Comprehensive multicomponent prevention programs, while often available in the community, have received little research attention in prison settings. In addition to clarifying the relationship between incarceration and heart disease, this article reviews various treatment and management responses made by prison officials. C1 Portland VA Med Ctr, VISN Northwest Mental Illness Res 20, Educ & Clin Ctr, Portland, OR 97239 USA. RP Donahue, J (reprint author), Portland VA Med Ctr, VISN Northwest Mental Illness Res 20, Educ & Clin Ctr, P3MIRECC,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM jdonahue81@gmail.com NR 44 TC 2 Z9 2 U1 3 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1078-3458 EI 1940-5200 J9 J CORRECT HEALTH CAR JI J. Correct. Health Care PD OCT PY 2014 VL 20 IS 4 BP 302 EP 312 DI 10.1177/1078345814541534 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AQ3BL UT WOS:000342663600005 PM 25038141 ER PT J AU Becker, SJE Makarawung, DJS Spit, SA King, JD Ring, D AF Becker, Stephanie J. E. Makarawung, Dennis J. S. Spit, Silke A. King, John D. Ring, David TI Disability in Patients With Trapeziometacarpal Joint Arthrosis: Incidental Versus Presenting Diagnosis SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Disability; incidental diagnosis; psychosocial factors; symptoms; trapeziometacarpal joint arthrosis ID THUMB CARPOMETACARPAL JOINT; HAND OSTEOARTHRITIS; PAIN; PREVALENCE; VALIDITY; ASSOCIATION; STRENGTH; GRIP AB Purpose To test the hypothesis that there is no difference in trapeziometacarpal (TMC) joint arthrosis-related symptoms and disability between patients seeking treatment for symptoms of TMC arthrosis and those with incidental TMC joint arthrosis. Methods We compared 64 patients presenting for care of TMC joint arthrosis with 64 with incidental TMC joint arthrosis. For both groups, the diagnosis was based on crepitation on examination. Bivariate and multivariate analyses assessed factors associated with symptoms and disability related to TMC joint arthrosis. Results In bivariate analysis, patients presenting for care of TMC joint arthrosis had significantly more symptoms and disability from TMC joint arthrosis than those with incidental TMC joint arthrosis. The best multivariate linear regression model for fewer TMC joint arthrosis-related symptoms and disability included patients with incidental TMC joint arthrosis, male sex, no other painful conditions, less catastrophic thinking, and fewer depressive symptoms and explained 74% of the variability. Having incidental TMC joint arthrosis (25%) and more adaptive coping strategies (less catastrophic thinking; 5%) were the most important contributors to fewer symptoms and less disability. Conclusions Future studies are merited to determine whether training in better coping strategies (eg, less catastrophic thinking and fewer depressive symptoms) can decrease symptoms and disability in patients with TMC joint arthrosis. Copyright (C) 2014 by the American Society for Surgery of the Hand. All rights reserved. C1 [Becker, Stephanie J. E.; Makarawung, Dennis J. S.; Spit, Silke A.; King, John D.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Sch Med, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Dept Orthopaed Surg,Yawkey Ctr,Sch Med, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org RI Becker, Stephanie/N-5761-2014 FU Anna Foundation; Genootschap Noorthey; Stichting Fonds Doctor Catharine van Tussenbroek; Stichting Vreedefonds, The Netherlands; University of Amsterdam-Academic Medical Center, Amsterdam, The Netherlands; Marco Polo Fonds, The Netherlands; Keck School of Medicine of the University of Southern California, California, United States 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. D.J.SM. is supported by a Dutch research grant from the University of Amsterdam-Academic Medical Center, Amsterdam, The Netherlands, for scientific research. S.A.S. is supported by a Dutch research grant from Marco Polo Fonds, The Netherlands, for scientific research. J.D.K. is supported by a summer research grant from the Keck School of Medicine of the University of Southern California, California, United States, for scientific research. NR 28 TC 8 Z9 8 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD OCT PY 2014 VL 39 IS 10 BP 2009 EP 2015 DI 10.1016/j.jhsa.2014.07.009 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AQ4AB UT WOS:000342733500019 PM 25194769 ER PT J AU Mellema, JJ Doornberg, JN Dyer, GSM Ring, D AF Mellema, Jos J. Doornberg, Job N. Dyer, George S. M. Ring, David TI Distribution of Coronoid Fracture Lines by Specific Patterns of Traumatic Elbow Instability SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Coronoid; fractures; mapping; elbow; injury ID TOMOGRAPHY AB Purpose To determine if specific coronoid fractures relate to specific overall traumatic elbow instability injury patterns and to depict any relationship on fracture maps and heat maps. Methods We collected 110 computed tomography (CT) studies from patients with coronoid fractures. Fracture types and pattern of injury were characterized based on anteroposterior and lateral radiographs, 2- and 3-dimensional CT scans, and intraoperative findings as described in operative reports. Using quantitative 3-dimensional CT techniques we were able to reconstruct the coronoid and reduce fracture fragments. Based on these reconstructions, fracture lines were identified and graphically superimposed onto a standard template in order to create 2-dimensional fracture maps. To further emphasize the fracture maps, the initial diagrams were converted into fracture heat maps following arbitrary units of measure. The Fisher exact test was used to evaluate the association between coronoid fracture types and elbow fracture-dislocation patterns. Results Forty-seven coronoid fractures were associated with a terrible triad fracture dislocation, 30 with a varus posteromedial rotational injury, 1 with a anterior olecranon fracture dislocation, 22 with a posterior olecranon fracture dislocation, and 7 with a posterior Monteggia injury associated with terrible triad fracture dislocation of the elbow. The association between coronoid fracture types and elbow fracture-dislocation patterns, as shown on 2-dimensional fracture and heat maps, was strongly significant. Conclusions Our fracture maps and heat maps support the observation that specific patterns of traumatic elbow instability have correspondingly specific coronoid fracture patterns. Knowledge of these patterns is useful for planning management because it directs exposure and fixation and helps identify associated ligament injuries and fractures that might benefit from treatment. Copyright (C) 2014 by the American Society for Surgery of the Hand. All rights reserved. C1 Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Univ Amsterdam, Acad Med Ctr, Orthotrauma Res Ctr Amsterdam, NL-1105 AZ Amsterdam, Netherlands. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Ring, David/0000-0002-6506-4879 NR 13 TC 10 Z9 13 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD OCT PY 2014 VL 39 IS 10 BP 2041 EP 2046 DI 10.1016/j.jhsa.2014.06.123 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AQ4AB UT WOS:000342733500024 PM 25070699 ER PT J AU Moradi, A Kachooei, AR Mudgal, CS AF Moradi, Ali Kachooei, Amir Reza Mudgal, Chaitanya S. TI Mallet Fracture SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID DISTAL INTERPHALANGEAL JOINT; KIRSCHNER WIRE TECHNIQUE; FINGER FRACTURES; OPERATIVE TREATMENT; AVULSION FRACTURES; EXTENSOR TENDON; FIXATION; SPLINT; COMPLICATIONS; PHALANX C1 Mashhad Univ Med Sci, Dept Orthoped Surg, Mashhad, Iran. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthoped, Boston, MA USA. RP Mudgal, CS (reprint author), Yawkey Ctr, Orthopaed Hand Serv, Dept Orthoped, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org NR 33 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD OCT PY 2014 VL 39 IS 10 BP 2067 EP 2069 DI 10.1016/j.jhsa.2014.06.022 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AQ4AB UT WOS:000342733500031 PM 25135247 ER PT J AU Peterson, SL Peterson, EL Wheatley, MJ AF Peterson, Steven L. Peterson, Emma L. Wheatley, Michael J. TI Management of Fingertip Amputations SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Fingertip; amputation; injury; replantation; classification ID PNB CLASSIFICATION; UPPER EXTREMITY; HAND INJURIES; ISLAND FLAPS; REPLANTATION; EXPERIENCE; NEUROMAS; OUTCOMES; CHILDREN; DIGITS AB Injuries to the fingertips are among the most common injuries to the hand and result in approximately 4.8 million emergency department visits per year. Most injuries are lacerations or crushes; amputations represent a small but complex spectrum of injury. Treatments available cover a broad range of techniques with no single recommended reference standard for treatment. Although there is no consensus on how these injuries should be treated, the goals of treatment should include minimization of pain, optimization of healing time, preservation of sensibility and length, prevention of painful neuromas, avoidance or limiting of nail deformity, minimization of time lost from work, and provision of an acceptable cosmetic appearance. In this review we present a variety of options in caring for these injuries to help achieve these goals, and the available data that support the various treatment plans. Copyright (C) 2014 by the American Society for Surgery of the Hand. All rights reserved. C1 [Peterson, Steven L.; Peterson, Emma L.; Wheatley, Michael J.] Portland VA Med Ctr, Operat Care Div, Portland, OR 97207 USA. RP Peterson, SL (reprint author), Portland VA Med Ctr, Hand Surg Sect, Operat Care Div, 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM slpdvmmd@aol.com NR 32 TC 2 Z9 3 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 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD OCT PY 2014 VL 39 IS 10 BP 2093 EP 2101 DI 10.1016/j.jhsa.2014.04.025 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AQ4AB UT WOS:000342733500036 PM 25257490 ER PT J AU Nishimura, Y Shingai, M Donau, OK Plishka, RJ Buckler-White, A Mascola, JR Nabel, GJ Nason, MC Montefiori, D Moldt, B Poignard, P Diskin, R Bjorkman, PJ Klein, F Mouquet, H Burton, DR Nussenzweig, MC Martin, MA AF Nishimura, Yoshiaki Shingai, Masashi Donau, Olivia K. Plishka, Ronald J. Buckler-White, Alicia Mascola, John R. Nabel, Gary J. Nason, Martha C. Montefiori, David Moldt, Brian Poignard, Pascal Diskin, Ron Bjorkman, Pamela J. Klein, Florian Mouquet, Hugo Burton, Dennis R. Nussenzweig, Michel C. Martin, Malcolm A. TI PREEXPOSURE PASSIVE TRANSFER PREDICTS PLASMA ANTIBODY LEVELS TO PREVENT HIV-1 AQUISITION SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Nishimura, Yoshiaki; Shingai, Masashi; Donau, Olivia K.; Plishka, Ronald J.; Buckler-White, Alicia; Martin, Malcolm A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Nason, Martha C.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Montefiori, David] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Moldt, Brian; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Moldt, Brian; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Moldt, Brian; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Ctr HIV AIDs Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Diskin, Ron; Bjorkman, Pamela J.] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Bjorkman, Pamela J.; Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. [Klein, Florian; Mouquet, Hugo; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. [Burton, Dennis R.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. RI poignard, pascal/N-6678-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0047-2565 EI 1600-0684 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 2014 VL 43 IS 5 MA 47 BP 398 EP 398 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA AQ3EZ UT WOS:000342673700060 ER PT J AU Hageman, MGJS Bossen, JKJ Smith, RM Ring, D AF Hageman, Michiel G. J. S. Bossen, Jeroen K. J. Smith, R. Malcolm Ring, David TI Predictors of Readmission in Orthopaedic Trauma Surgery SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE orthopaedic surgery; readmission; adverse event ID LENGTH-OF-STAY; HOSPITAL READMISSIONS; HIP FRACTURE; MEDICARE PATIENTS; GENERAL-SURGERY; RISK-FACTORS; CARE; QUALITY; RATES; REHOSPITALIZATIONS AB Objectives: This study of patients who had operative treatment of skeletal trauma addresses (1) the association between readmission within 30 days of discharge and comorbidities and (2) differences in factors associated with all-cause readmissions and those because of a surgical adverse event. Design: Retrospective study. Setting: Tertiary care referral center. Patients: Three thousand four hundred fifty-two operations for skeletal trauma between 2008 and 2012 with comorbidities quantified using the updated Charlson comorbidity index (CCI). Outcome Measurement: Readmission to the hospital within 30 days of surgery and the subset of readmissions because of adverse events related directly to surgery. Results: There was a significant association between readmission within 30 days of surgery and higher CCI (P < 0.001), older age (P < 0.001), and marital status (widowed) (P, 0.001). The factors associated with readmission related to an adverse event were identical. The best multivariable logistic regression models for all-cause 30-day readmission and 30-day readmission related to a surgical adverse event included CCI and older age in both models (odds ratio 1.1, P < 0.01, pseudo R-2 = 0.03). Conclusions: Older patients and patients with greater comorbidity are more likely to be readmitted within 30 days of surgery for musculoskeletal trauma, whether for a surgical adverse event or another reason. The best multivariable models predicted very little of the variability in readmission, which reflects the complexity of readmission and the difficulty reducing the risk to a few specific factors. C1 [Hageman, Michiel G. J. S.; Bossen, Jeroen K. J.; Smith, R. Malcolm; Ring, David] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Dutch faculty grant from the Vrije Universiteit Amsterdam for medical students; Marti-Keunig Eckhart Stichting; Anna Foundation; Spinoza Foundation FX J. K. J. Bossen is supported by a Dutch faculty grant from the Vrije Universiteit Amsterdam for medical students (small grant). M. G. J. S. Hageman is supported by a Dutch research grants from Marti-Keunig Eckhart Stichting, Anna Foundation, and Spinoza Foundation. NR 32 TC 4 Z9 4 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 EI 1531-2291 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD OCT PY 2014 VL 28 IS 10 BP E247 EP E249 PG 3 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA AQ4GG UT WOS:000342750900003 PM 24662992 ER PT J AU Faria, V Linnman, C Lebel, A Borsook, D AF Faria, Vanda Linnman, Clas Lebel, Alyssa Borsook, David TI Harnessing the Placebo Effect in Pediatric Migraine Clinic SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID PHARMACOLOGICAL-TREATMENT; YOUNG-CHILDREN; COMMUNICATION; ADOLESCENTS; DISEASE; ANXIETY; DRUGS; EXPECTANCIES; EXPECTATIONS; RELEVANCE C1 [Faria, Vanda; Linnman, Clas; Lebel, Alyssa; Borsook, David] Harvard Univ, Sch Med, Boston Childrens Hosp, Ctr Pain & Brain, Waltham, MA USA. [Faria, Vanda; Linnman, Clas; Lebel, Alyssa; Borsook, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Waltham, MA USA. [Faria, Vanda] Uppsala Univ, Dept Psychol, Uppsala, Sweden. [Lebel, Alyssa; Borsook, David] Harvard Univ, Sch Med, Boston Childrens Hosp, Chron Headache Program, Waltham, MA USA. RP Faria, V (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Ctr Pain & Brain,PAIN Grp, 9 Hope Ave, Waltham, MA USA. EM vanda.rochafaria@childrens.harvard.edu OI Linnman, Clas/0000-0001-8449-894X FU NCCIH NIH HHS [R21 AT007530-01, R21 AT007530]; NINDS NIH HHS [K24 NS064050, K24NS064050, R01 NS075018, R01NS0750182] NR 53 TC 6 Z9 6 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 2014 VL 165 IS 4 BP 659 EP 665 DI 10.1016/j.jpeds.2014.06.040 PG 7 WC Pediatrics SC Pediatrics GA AQ3LD UT WOS:000342694200006 PM 25063720 ER PT J AU McCormick, B Ottesen, RA Hughes, ME Javid, SH Khan, SA Mortimer, J Niland, JC Weeks, JC Edge, SB AF McCormick, Beryl Ottesen, Rebecca A. Hughes, Melissa E. Javid, Sara H. Khan, Seema A. Mortimer, Joanne Niland, Joyce C. Weeks, Jane C. Edge, Stephen B. TI Impact of Guideline Changes on Use or Omission of Radiation in the Elderly with Early Breast Cancer: Practice Patterns at National Comprehensive Cancer Network Institutions SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID LUMPECTOMY PLUS TAMOXIFEN; IRRADIATION; OLDER; AGE AB BACKGROUND: Breast radiation therapy (RT) is a care standard after breast-conservation surgery that improves local control and survival in women. In 2004, a phase III trial demonstrated radiation after breast-conservation surgery provided no survival and limited local control benefit to women aged 70 years and older with stage I, estrogen receptor-positive cancers who receive endocrine therapy. This led to breast-conservation surgery and endocrine therapy alone being incorporated as a category I option in the National Comprehensive Cancer Network (NCCN) Guidelines for older women in 2004. We examined factors associated with change in radiation use in elderly patients at 13 NCCN centers. STUDY DESIGN: We identified women treated at NCCN centers meeting age and stage criteria during 2000 to 2009. Factors considered a priori potentially associated with RT use were evaluated in univariate and multivariable models, including year of diagnosis, tumor and patient characteristics, axillary surgery, and treating institution. Date of diagnosis was classified as 2000 to 2004 vs 2005 to 2009, reflecting when guidelines changed. RESULTS: Among 1,292 eligible cases, 78% received RT. In multivariable analysis, diagnosis after 2004 (p = 0.0003), older age (p < 0.0001), higher comorbidity score (p = 0.0006), smaller tumors (p = 0.0146), and omission of axillary surgery (p < 0.0001) predicted RT omission. Ninety-four percent of women aged 70 to 74 years received RT in 2000, compared with 88% in 2009. For the same times and age 80 years and older, RT use was 80% vs 41%. Finally, RT use was associated with treating institution (p < 0.0001). CONCLUSIONS: After guideline changes for RT use in older women, NCCN centers demonstrated wide variation in implementing change. This suggests other factors are also influencing guideline uptake. (C) 2014 by the American College of Surgeons C1 [McCormick, Beryl] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Ottesen, Rebecca A.; Mortimer, Joanne; Niland, Joyce C.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Hughes, Melissa E.; Weeks, Jane C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Javid, Sara H.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Khan, Seema A.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Edge, Stephen B.] Baptist Canc Ctr, Memphis, TN USA. [Edge, Stephen B.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. RP McCormick, B (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM mccormib@mskcc.org NR 10 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD OCT PY 2014 VL 219 IS 4 BP 796 EP 802 DI 10.1016/j.jamcollsurg.2014.05.013 PG 7 WC Surgery SC Surgery GA AP9TJ UT WOS:000342422500027 PM 25127504 ER PT J AU Hwang, JH Fernando, ATP Faure, N Andrabi, S Hahn, WC Schaffhausen, BS Roberts, TM AF Hwang, Justin H. Fernando, Arun T. Pores Faure, Nathalie Andrabi, Shaida Hahn, William C. Schaffhausen, Brian S. Roberts, Thomas M. TI Polyomavirus Small t Antigen Interacts with Yes-Associated Protein To Regulate Cell Survival and Differentiation SO JOURNAL OF VIROLOGY LA English DT Article ID HIPPO PATHWAY; MIDDLE-T; SIGNALING PATHWAY; PHOSPHATASE 2A; TRANSCRIPTIONAL COACTIVATION; NEURONAL DIFFERENTIATION; MICRORNA BIOGENESIS; GROWTH-CONTROL; GENE-TRANSFER; DNA-DAMAGE AB Murine polyomavirus small t antigen (PyST) regulates cell cycle, cell survival, apoptosis, and differentiation and cooperates with middle T antigen (MT) to transform primary cells in vitro and in vivo. Like all polyomavirus T antigens, PyST functions largely via its interactions with host cell proteins. Here, we show that PyST binds both Yes-associated protein 1 (YAP1) and YAP2, integral parts of the Hippo signaling pathway, which is a subject of increasing interest in human cancer. The transcription factor TEAD, which is a known target of YAP, is also found in PyST complexes. PyST enhanced YAP association with protein phosphatase 2A (PP2A), leading to decreased YAP phosphorylation. PyST increased YAP levels by decreasing its degradation. This effect was mediated by a reduction in YAP association with beta-transducin repeat protein (beta TRCP), which is known to regulate YAP turnover in a phosphorylation-dependent manner. Genetic analysis has identified PyST mutants defective in YAP binding. These mutants demonstrated that YAP binding is important for PyST to block myoblast differentiation and to synergize with the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) to promote cell death in 3T3-L1 preadipocytes placed under differentiation conditions. In addition to YAP binding, both of these phenotypes require PyST binding to PP2A. IMPORTANCE The Hippo/YAP pathway is a highly conserved cascade important for tissue development and homeostasis. Defects in this pathway are increasingly being associated with cancer. Polyomavirus small t antigen is a viral oncogene that cooperates with middle T antigen in transformation. On its own, small t antigen controls cell survival and differentiation. By binding YAP, small t antigen brings it together with protein phosphatase 2A. This work shows how this association of small t antigen with YAP is important for its effects on cell phenotype. It also suggests that PyST can be used to characterize cellular processes that are regulated by YAP. C1 [Hwang, Justin H.; Faure, Nathalie; Schaffhausen, Brian S.] Tufts Univ, Sch Med, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. [Hwang, Justin H.; Schaffhausen, Brian S.] Tufts Univ, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. [Fernando, Arun T. Pores; Andrabi, Shaida; Roberts, Thomas M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Fernando, Arun T. Pores; Roberts, Thomas M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Andrabi, Shaida] Univ Kashmir, Dept Biochem, Kashmir, India. [Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hahn, William C.] Broad Inst Harvard, Cambridge, MA USA. [Hahn, William C.] MIT, Cambridge, MA 02139 USA. RP Schaffhausen, BS (reprint author), Tufts Univ, Sch Med, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. EM brian.schaffhausen@tufts.edu; thomas_roberts@dfci.harvard.edu FU NIH [CA50661, CA30002, CA34722] FX This work was supported by NIH grants CA50661 (W.C.H., T.M.R., and B.S.S.), CA30002 (T.M.R.), and CA34722 (B.S.S.). NR 71 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD OCT PY 2014 VL 88 IS 20 BP 12055 EP 12064 DI 10.1128/JVI.01399-14 PG 10 WC Virology SC Virology GA AQ3JH UT WOS:000342688000038 PM 25122798 ER PT J AU Dwojak, SM Bhattacharyya, N AF Dwojak, Sunshine M. Bhattacharyya, Neil TI Incremental and Comparative Health Care Expenditures for Head and Neck Cancer in the United States SO LARYNGOSCOPE LA English DT Article DE Head and neck cancer; healthcare expenditure; cost ID COST; POPULATION AB Objectives/HypothesisDetermine the incremental costs associated with head and neck cancer (HNCa) and compare the costs with other common cancers. Study DesignCross-sectional analysis of a healthcare expenditure database. MethodsThe Medical Expenditure Panel Survey is a national survey of US households. All cases of HNCa were extracted for 2006, 2008, and 2010. The incremental expenditures associated with HNCa were determined by comparing the healthcare expenditures of individuals with HNCa to the population without cancer, controlling for age, sex, education, insurance status, marital status, geographic region, and comorbidities. Healthcare expenditures for HNCa were then compared to individuals with lung cancer and colon cancer to determine relative healthcare expenditures. ResultsAn estimated 264,713 patients (annualized) with HNCa were identified. The mean annual healthcare expenditures per individual for HNCa were $23,408$3,397 versus $3,860$52 for those without cancer. The mean adjusted incremental cost associated with HNCa was $15,852 +/-$3,297 per individual (P<.001). Within this incremental cost, there was an increased incremental outpatient services cost of $3,495 +/-$1,044 (P=.001) and an increased incremental hospital inpatient cost of $6,783 +/-$2,894 (P=.020) associated with HNCa. The annual healthcare expenditures per individual fell in between those for lung cancer ($25,267 +/-$2,375, P=.607) and colon cancer ($16,975 +/-$1,291, P=.055). ConclusionsDespite its lower relative incidence, HNCa is associated with a significant incremental increase in annual healthcare expenditures per individual, which is comparable to or higher than other common cancers. In aggregate, the estimated annual costs associated with HNCa are $4.20 billion. C1 Brigham & Womens Hosp, Dept Otolaryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Dwojak, SM (reprint author), Brigham & Womens Hosp, Massachusetts Eye & Ear Infirm, Combined Harvard Program Otolaryngol, 45 Francis St, Boston, MA 02115 USA. EM sunshine_dwojak@meei.harvard.edu FU Triological Society Meeting, Miami, Florida, U.S.A. FX This article was the recipient of the Eastern Section Resident Research Award at the Triological Society Meeting, Miami, Florida, U.S.A., January 10, 2014. NR 11 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2014 VL 124 IS 10 BP 2305 EP 2308 DI 10.1002/lary.24795 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AQ4FQ UT WOS:000342749100022 PM 24939610 ER PT J AU Nouraei, SM Franco, RA Dowdall, JR Nouraei, SAR Mills, H Virk, JS Sandhu, GS Polkey, M AF Nouraei, S. Mahmoud Franco, Ramon A. Dowdall, Jayme R. Nouraei, S. A. Reza Mills, Heide Virk, Jag S. Sandhu, Guri S. Polkey, Mike TI Physiology-Based Minimum Clinically Important Difference Thresholds in Adult Laryngotracheal Stenosis SO LARYNGOSCOPE LA English DT Article DE Laryngotracheal stenosis; flow-volume loops; outcome measures; evidence-based medicine; minimum clinically important difference; pulmonary function test ID OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; DYSPNEA SCALE; HEALTH-STATUS; QUESTIONNAIRE; DYNAMICS; SCORE; COPD AB Objectives/HypothesisDelivering evidence-based patient care is predicated on the availability of objective and validated outcome measures. We aimed to calculate physiology-based minimum clinically important difference (MCID) values for adult laryngotracheal stenosis (LTS). Study DesignProspective observational study. MethodsPatient demographics, morbidities, and stenosis severity were assessed preoperatively. Flow-volume loops and Medical Research Council (MRC) dyspnea grades were measured in 21 males and 44 females before and 6 to 8 weeks after airway surgery, and before treating recurrent disease in 10 patients. Anchor and distribution-based methodologies were used to calculate MCIDs for treatment efficacy and disease recurrence respectively. ResultsThe mean age at treatment was 4616 years. The most common etiology was idiopathic subglottic stenosis (38%). Most lesions (66%) obstructed >70% of the lumen. There were strong correlations between treatment-related changes in total peak flow (TPF) (TPF) (peak expiratory flow+|peak inspiratory flow|) and the ratio of area under the flow-volume loop (AUC) to forced vital capacity (FVC) (AUC(Total)/FVC), and treatment-related changes in the MRC grade (MRC) (r=-0.76 and r=-0.82, respectively). Both TPF and AUC(Total)/FVC discriminated between effective (MRC <0) and ineffective (MRC 0) interventions, yielding MCID values of 4.2 L/s for TPF and 2.1 L-2/s for AUC(Total)/FVC, respectively. Ten patients required airway treatment for recurrent disease, and TPF and AUC(Total)/FVC levels had distribution-based MCID values of 0.9 and 0.6, respectively. ConclusionsFlow-volume loops provide a quantitative method of objectively assessing outcomes in LTS. TPF is the most convenient index for this purpose, but AUC(Total)/FVC provides marginally greater sensitivity and specificity. C1 [Nouraei, S. Mahmoud] Univ Mazandaran Sch Med Sci, Dept Cardiothorac Surg, Sari, Iran. [Nouraei, S. A. Reza; Mills, Heide; Virk, Jag S.; Sandhu, Guri S.] Charing Cross Hosp, Natl Ctr Airway Reconstruct, Dept Otolaryngol Head & Neck Surg, London, England. [Franco, Ramon A.; Dowdall, Jayme R.] Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. [Franco, Ramon A.; Dowdall, Jayme R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Polkey, Mike] Royal Brompton & Harefield NHS Fdn Trust, London, England. RP Nouraei, SAR (reprint author), Anglia Ruskin Univ, Postgrad Med Inst, Chelmsford CM1 1SQ, Essex, England. EM RN@cantab.net NR 26 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2014 VL 124 IS 10 BP 2313 EP 2320 DI 10.1002/lary.24641 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AQ4FQ UT WOS:000342749100024 PM 25265276 ER PT J AU Fontenot, TE Randolph, GW Friedlander, PL Masoodi, H Yola, IM Kandil, E AF Fontenot, Tatyana E. Randolph, Gregory W. Friedlander, Paul L. Masoodi, Hammad Yola, Ibrahim M. Kandil, Emad TI Gender, Race, and Electrophysiologic Characteristics of the Branched Recurrent Laryngeal Nerve SO LARYNGOSCOPE LA English DT Article DE Thyroid surgery; recurrent laryngeal nerve; vocal cord dysfunction ID ANTERIOR EXTRALARYNGEAL BRANCH; THYROID-SURGERY; MOTOR FIBERS; ANATOMY AB Objectives/HypothesisThe extralaryngeal branching of recurrent laryngeal nerves (RLN) conveys an increased risk of nerve injury during thyroid surgery. We hypothesized that racial and gender variations in prevalence of branched RLN exist. Study DesignA retrospective review of all patients who underwent thyroid surgery in a 4-year period in a single surgeon practice. MethodsThe RLN was routinely identified during thyroid surgery. Presence of RLN branching, its distance from the laryngeal nerve entry point (NEP), and functionality of the branches were ascertained. Patient demographics, rates of neural branching, and distance of bifurcation from the NEP were evaluated using statistical analysis. ResultsWe identified 719 RLNs at risk in 491 patients who underwent central neck surgery. Four hundred and five (82.5%) patients were female and 86 (17.5%) patients were male. There were 218 (44.4%) African American patients and 251 (51.1 %) Caucasian patients. In African American patients, 42.1% RLNs bifurcated compared to 33.2% RLNs in Caucasian (P=0.017) patients. The RLNs of African American and Caucasian patients bifurcated at comparable distances (P=0.30). In male patients, 39.1% RLNs bifurcated; whereas in female patients 36.2% RLNs bifurcated (P=0.53). On average, RLN bifurcation in female patients was at a longer distance from NEP compared to that of male patients (P=0.012). Electrophysiologic testing found motor fibers in all anterior branches and three posterior extralaryngeal RLN branches. ConclusionAfrican American patients have a higher rate of RLN bifurcation compared to Caucasian patients but no statistically significant difference in distance from NEP. Female patients tend to have longer branching variants of bifid RLNs. RLN motor fibers reside primarily in the anterior branch but may occur in the posterior branch. Level of Evidence4. Laryngoscope 124:2433-2437, 2014 C1 [Fontenot, Tatyana E.; Friedlander, Paul L.; Kandil, Emad] Tulane Univ, Sch Med, Dept Otolaryngol, New Orleans, LA 70112 USA. [Masoodi, Hammad; Kandil, Emad] Tulane Univ, Sch Med, Dept Surg, Endocrine Sect, New Orleans, LA 70112 USA. [Yola, Ibrahim M.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. [Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Thyroid & Parathyroid Surg, Boston, MA 02114 USA. RP Kandil, E (reprint author), Tulane Otolaryngol Head & Neck Surg, 1430 Tulane Ave,SL 59, New Orleans, LA 70112 USA. EM ekandil@tulane.edu OI Fontenot, Tatyana/0000-0001-7664-5014 NR 17 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2014 VL 124 IS 10 BP 2433 EP 2437 DI 10.1002/lary.24631 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AQ4FQ UT WOS:000342749100045 PM 24493270 ER PT J AU Seano, G Chiaverina, G Gagliardi, PA Blasio, L Puliafito, A Bouvard, C Sessa, R Tarone, G Sorokin, L Helley, D Jain, RK Serini, G Bussolino, F Primo, L AF Seano, Giorgio Chiaverina, Giulia Gagliardi, Paolo Armando di Blasio, Laura Puliafito, Alberto Bouvard, Claire Sessa, Roberto Tarone, Guido Sorokin, Lydia Helley, Dominique Jain, Rakesh K. Serini, Guido Bussolino, Federico Primo, Luca TI Endothelial podosome rosettes regulate vascular branching in tumour angiogenesis SO NATURE CELL BIOLOGY LA English DT Article ID GROWTH-FACTOR; TRANSFORMED FIBROBLASTS; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; BLOOD-VESSELS; TIP CELLS; F-ACTIN; INTEGRIN; MICE; INVADOPODIA AB The mechanism by which angiogenic endothelial cells break the physical barrier of the vascular basement membrane and consequently sprout to form new vessels in mature tissues is unclear. Here, we show that the angiogenic endothelium is characterized by the presence of functional podosome rosettes. These extracellular-matrix-degrading and adhesive structures are precursors of de novo branching points and represent a key feature in the formation of new blood vessels. VEGF-A stimulation induces the formation of endothelial podosome rosettes by upregulating integrin alpha(6)beta(1). In contrast, the binding of alpha(6)beta(1) integrin to the laminin of the vascular basement membrane impairs the formation of podosome rosettes by restricting alpha(6)beta(1) integrin to focal adhesions and hampering its translocation to podosomes. Using an ex vivo sprouting angiogenesis assay, transgenic and knockout mouse models and human tumour sample analysis, we provide evidence that endothelial podosome rosettes control blood vessel branching and are critical regulators of pathological angiogenesis. C1 [Seano, Giorgio; Chiaverina, Giulia; Gagliardi, Paolo Armando; di Blasio, Laura; Puliafito, Alberto; Sessa, Roberto; Serini, Guido; Bussolino, Federico; Primo, Luca] Univ Turin, Dept Oncol, I-10100 Turin, Italy. [Seano, Giorgio; Chiaverina, Giulia; Gagliardi, Paolo Armando; di Blasio, Laura; Puliafito, Alberto; Sessa, Roberto; Serini, Guido; Bussolino, Federico; Primo, Luca] IRCCS, Candiolo Canc Inst FPO, I-10060 Candiolo, Italy. [Seano, Giorgio; Jain, Rakesh K.] Harvard Univ, Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Sch Med, Boston, MA 02114 USA. [Bouvard, Claire] Univ Paris 05, UMR S 765, Sorbonne Paris Cite, F-75006 Paris, France. [Tarone, Guido] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Ctr Mol Biotechnol, I-10124 Turin, Italy. [Sorokin, Lydia] Univ Munster, Inst Physiol Chem & Pathobiochem, D-48149 Munster, Germany. [Helley, Dominique] Univ Paris 05, UMR S 970, Sorbonne Paris Cite, F-75006 Paris, France. RP Seano, G (reprint author), Univ Turin, Dept Oncol, I-10100 Turin, Italy. EM seano@steele.mgh.harvard.edu; luca.primo@ircc.it OI Seano, Giorgio/0000-0002-7294-302X; Serini, Guido/0000-0002-3502-8367; Gagliardi, Paolo Armando/0000-0002-4818-035X; di Blasio, Laura/0000-0002-1337-7654 FU Associazione Italiana per la Ricerca sul Cancro (AIRC) [10133, 14635, 13016, 13604, 15026]; AIRC 5x1000 [12182]; Converging Technologies Program, grant: 'Photonic Biosensors for Early Cancer Diagnostics'; Technological Platforms for Biotechnology: grant DRUIDI; Fondazione Cassa di Risparmio Torino (CRT); Fondazione Piemontese per la Ricerca sul Cancro-ONLUS; Fondo Investimenti per la Ricerca di Base [RBAP11BYNP]; University of Torino-Compagnia di San Paolo: RETHE grant; GeneRNet grant; NIH HHS/United States [P01 CA080124/CA/NCI]; Fondazione T. & L. de Beaumont Bonelli; Girardi Family FX A special thank you to E. Georges-Labouesse (CNRS/INSERM/ULP, Illkirch, France), who recently passed away, for kindly providing Tie2-dependent integrin alpha6 KO mice. We thank P. C. Marchisio (San Raffaele Scientific Institute, Milano, Italy) for discussion and insightful suggestions on the manuscript; D. R. Sherwood (Duke University Medical Center, Durham, USA) for critical reading of the manuscript; K. Tryggvason (Karolinska Institutet, Stockholm, Sweden) for providing laminin alpha4 null mice; R. Wedlich-Soldner (Max-Planck Institute of Biochemistry, Martinsried, Germany) and L. M. Machesky (Beatson Institute for Cancer Research, Glasgow, UK) for providing breeding pairs for the LifeAct-EGFP mouse colony and reagents; R. Falcioni (National Cancer Institute 'Regina Elena', Rome, Italy) for critical reading and reagents; E. De Luca and M. Gai (MBC, Torino, Italy) for their assistance in multiphoton microscopy; Y. Boucher and C. Smith (HMS, Boston, USA) for assistance in immunohistochemistry on human tissues; and E. Giraudo and F. Maione (IRCC, Candiolo, Italy) for their help in the treatment of RipTag2 mice. This work was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC) investigator grants IG (10133, F.B.; 14635, L.P.; 13016 G. Serini) and fellowships (13604 G. Seano; 15026 P.A.G.); AIRC 5x1000 (12182); Converging Technologies Program, grant: 'Photonic Biosensors for Early Cancer Diagnostics'; Technological Platforms for Biotechnology: grant DRUIDI; Fondazione Cassa di Risparmio Torino (CRT); Fondazione Piemontese per la Ricerca sul Cancro-ONLUS (Intramural Grant 5x1000 2008) (L.P.); Fondo Investimenti per la Ricerca di Base RBAP11BYNP (Newton) (F.B. and L.P.); University of Torino-Compagnia di San Paolo: RETHE grant (F.B.); GeneRNet grant (L.P.); P01 CA080124/CA/NCI NIH HHS/United States (R.K.J.); The 'Fondazione T. & L. de Beaumont Bonelli' and the Girardi Family (G. Seano). NR 45 TC 27 Z9 27 U1 0 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD OCT PY 2014 VL 16 IS 10 BP 931 EP 941 DI 10.1038/ncb3036 PG 11 WC Cell Biology SC Cell Biology GA AQ3RW UT WOS:000342712200003 PM 25218639 ER PT J AU Cremasco, V Woodruff, MC Onder, L Cupovic, J Nieves-Bonilla, JM Schildberg, FA Chang, J Cremasco, F Harvey, CJ Wucherpfennig, K Ludewig, B Carroll, MC Turley, SJ AF Cremasco, Viviana Woodruff, Matthew C. Onder, Lucas Cupovic, Jovana Nieves-Bonilla, Janice M. Schildberg, Frank A. Chang, Jonathan Cremasco, Floriana Harvey, Christopher J. Wucherpfennig, Kai Ludewig, Burkhard Carroll, Michael C. Turley, Shannon J. TI B cell homeostasis and follicle confines are governed by fibroblastic reticular cells SO NATURE IMMUNOLOGY LA English DT Article ID SECONDARY LYMPHOID ORGANS; BETA-DEFICIENT MICE; DENDRITIC CELLS; HUMORAL IMMUNITY; STROMAL CELLS; NODES; ANTIGEN; ORGANOGENESIS; ACTIVATION; MATURATION AB Fibroblastic reticular cells (FRCs) are known to inhabit T cell-rich areas of lymphoid organs, where they function to facilitate interactions between T cells and dendritic cells. However, in vivo manipulation of FRCs has been limited by a dearth of genetic tools that target this lineage. Here, using a mouse model to conditionally ablate FRCs, we demonstrated their indispensable role in antiviral T cell responses. Unexpectedly, loss of FRCs also attenuated humoral immunity due to impaired B cell viability and follicular organization. Follicle-resident FRCs established a favorable niche for B lymphocytes via production of the cytokine BAFF. Thus, our study indicates that adaptive immunity requires an intact FRC network and identifies a subset of FRCs that control B cell homeostasis and follicle identity. C1 [Cremasco, Viviana; Nieves-Bonilla, Janice M.; Schildberg, Frank A.; Chang, Jonathan; Cremasco, Floriana; Harvey, Christopher J.; Wucherpfennig, Kai; Turley, Shannon J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. [Woodruff, Matthew C.; Carroll, Michael C.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Woodruff, Matthew C.; Chang, Jonathan] Harvard Univ, Sch Med, Div Med Sci, Boston, MA 02115 USA. [Onder, Lucas; Cupovic, Jovana; Ludewig, Burkhard] Kantonal Hosp St Gallen, Inst Immunol, St Gallen, Switzerland. [Cremasco, Floriana] Univ Milan, Dept Pharmacol, Milan, Italy. [Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Turley, Shannon J.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. RP Turley, SJ (reprint author), Genentech Inc, San Francisco, CA 94080 USA. EM michael.carroll@childrens.harvard.edu; turley.shannon@gene.com FU US National Institutes of Health [5R01 DK074500-08, 2P01AI045757-15, R21 CA182598-01, R01 AI039246, P01 AI078897, R37 AI054636, T32 CA 070083-15]; Barr Foundation; Cancer Research Institute; Vontobel Foundation; Helmut Horten Foundation FX We thank L. Cameron for technical assistance at the Dana-Farber cancer Institute Confocal Imaging core. Supported by the US National Institutes of Health (5R01 DK074500-08, 2P01AI045757-15, R21 CA182598-01 to S.J.T.; R01 AI039246, P01 AI078897 and R37 AI054636 to M.C.C.; and T32 CA 070083-15 to V.C.), the Barr Foundation (S.J.T.), the Cancer Research Institute (V.C.), the Vontobel Foundation (to B.L.) and the Helmut Horten Foundation (to B.L.). NR 44 TC 45 Z9 45 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2014 VL 15 IS 10 BP 973 EP U222 DI 10.1038/ni.2965 PG 11 WC Immunology SC Immunology GA AQ1TR UT WOS:000342564800013 PM 25151489 ER PT J AU Levine, GN Jeong, YH Goto, S Anderson, JL Huo, Y Mega, JL Taubert, K Smith, SC AF Levine, Glenn N. Jeong, Young-Hoon Goto, Shinya Anderson, Jeffrey L. Huo, Yong Mega, Jessica L. Taubert, Kathryn Smith, Sidney C., Jr. TI World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI SO NATURE REVIEWS CARDIOLOGY LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; ELEVATION MYOCARDIAL-INFARCTION; ASSOCIATION TASK-FORCE; TREATMENT PLATELET REACTIVITY; ELUTING STENT IMPLANTATION; ACCF/AHA FOCUSED UPDATE; VERIFYNOW P2Y12 ASSAY; ST-SEGMENT ELEVATION; OUTCOMES PLATO TRIAL; BARE-METAL STENTS AB Guideline recommendations on the use of dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention (PCI) have been formulated by both the ACC/AHA and the ESC. These recommendations are based primarily on large, phase III, randomized, controlled trials of the P2Y(12) inhibitors clopidogrel, prasugrel, and ticagrelor. However, few East Asian patients have been included in the trials to assess the use of these agents, particularly the newer agents prasugrel and ticagrelor. Additionally, an increasing body of data suggests that East Asian patients have differing risk profiles for both thrombophilia and bleeding compared with white patients, and that a different 'therapeutic window' of on-treatment platelet reactivity might be appropriate in East Asian patients. Furthermore, a phenomenon referred to as the 'East Asian paradox' has been described, in which East Asian patients have a similar or even a lower rate of ischaemic events after PCI compared with white patients, despite a higher level of platelet reactivity during DAPT. Recognizing these concerns, the World Heart Federation has undertaken this evidence-based review and produced this expert consensus statement to determine the antiplatelet treatment strategies that are most appropriate for East Asian patients. C1 [Levine, Glenn N.] Baylor Coll Med, Houston, TX 77030 USA. [Levine, Glenn N.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Jeong, Young-Hoon] Gyeongsang Natl Univ Hosp, Jinju, South Korea. [Jeong, Young-Hoon] Gyeongsang Natl Univ, Sch Med, Jinju, South Korea. [Goto, Shinya] Tokai Univ, Sch Med, Dept Med Cardiol, Hiratsuka, Kanagawa 25912, Japan. [Anderson, Jeffrey L.] Univ Utah, Intermt Med Ctr, Sch Med, Salt Lake City, UT 84112 USA. [Huo, Yong] Peking Univ, Hosp 1, Dept Cardiol, Beijing, Peoples R China. [Mega, Jessica L.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Taubert, Kathryn] World Heart Federat, Geneva, Switzerland. [Smith, Sidney C., Jr.] Univ N Carolina, Div Cardiol, Chapel Hill, NC 27599 USA. RP Smith, SC (reprint author), Univ N Carolina, Div Cardiol, 160 Dent Circle,CB 7075, Chapel Hill, NC 27599 USA. EM scs@med.unc.edu FU Accumetrics; Boehringer-Ingelheim; Han-mi Pharmaceuticals; Haemonetics; Otsuka; AstraZeneca; Bayer; MSD; Pfizer/BMS; Sanofi-Aventis (France); Bayer Healthcare; Bristol-Myers Squibb; Daiichi Sankyo; Eli Lilly; Johnson Johnson; Nanosphere; Sanofi-Aventis FX Y.-H.J. has received honoraria for lectures from AstraZeneca, Daiichi Sankyo/Lilly, Haemonetics, Nanosphere, Otsuka, and Sanofi-Aventis; and research grants or support from Accumetrics, Boehringer-Ingelheim, Han-mi Pharmaceuticals, Haemonetics, and Otsuka. S. G. has received honoraria from Asteras, AstraZeneca, Bayer, Daiichi-Sankyo, Eisai, Medtronic-Japan, Mochida, MSD, Novartis, Otsuka, Pfizer, Sanofi-Aventis, Takeda, and Tanabe-Mitsubishi. He is an advisory board member for AstraZeneca, Bayer, MSD, and Pfizer/BMS. He is an investigator on a study or trial sponsored by AstraZeneca, Bayer, MSD, and Pfizer/BMS. J.L.A. served on an Acute Coronary Syndrome (ACS) Expert Panel to generate a position paper on advances in ACS therapy that was funded by an unrestricted educational grant from Sanofi-Aventis (France). J.L.M. served as an investigator on a study or trial sponsored by Accumetrics, AstraZeneca, Bayer Healthcare, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Johnson & Johnson, Nanosphere, and Sanofi-Aventis. G.N.L., Y.H., K. T., and S. C. S. declare no competing interests. NR 80 TC 43 Z9 49 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5002 EI 1759-5010 J9 NAT REV CARDIOL JI Nat. Rev. Cardiol. PD OCT PY 2014 VL 11 IS 10 BP 597 EP 606 DI 10.1038/nrcardio.2014.104 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AQ1UP UT WOS:000342568100007 PM 25154978 ER PT J AU Emblem, KE Farrar, CT Gerstner, ER Batchelor, TT Borra, RJH Rosen, BR Sorensen, AG Jain, RK AF Emblem, Kyrre E. Farrar, Christian T. Gerstner, Elizabeth R. Batchelor, Tracy T. Borra, Ronald J. H. Rosen, Bruce R. Sorensen, A. Gregory Jain, Rakesh K. TI Vessel calibre-a potential MRI biomarker of tumour response in clinical trials SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID CEREBRAL BLOOD-VOLUME; CONTRAST-ENHANCED MRI; ANTI-ANGIOGENIC THERAPY; POSITRON-EMISSION-TOMOGRAPHY; NEWLY-DIAGNOSED GLIOBLASTOMA; ARTERIAL INPUT FUNCTION; LONGITUDINAL IN-VIVO; MAGNETIC-RESONANCE; GRADIENT-ECHO; ANTIANGIOGENIC THERAPY AB Our understanding of the importance of blood vessels and angiogenesis in cancer has increased considerably over the past decades, and the assessment of tumour vessel calibre and structure has become increasingly important for in vivo monitoring of therapeutic response. The preferred method for in vivo imaging of most solid cancers is MRI, and the concept of vessel-calibre MRI has evolved since its initial inception in the early 1990s. Almost a quarter of a century later, unlike traditional contrast-enhanced MRI techniques, vessel-calibre MRI remains widely inaccessible to the general clinical community. The narrow availability of the technique is, in part, attributable to limited awareness and a lack of imaging standardization. Thus, the role of vessel-calibre MRI in early phase clinical trials remains to be determined. By contrast, regulatory approvals of antiangiogenic agents that are not directly cytotoxic have created an urgent need for clinical trials incorporating advanced imaging analyses, going beyond traditional assessments of tumour volume. To this end, we review the field of vessel-calibre MRI and summarize the emerging evidence supporting the use of this technique to monitor response to anticancer therapy. We also discuss the potential use of this biomarker assessment in clinical imaging trials and highlight relevant avenues for future research. C1 [Emblem, Kyrre E.] Oslo Univ Hosp, Intervent Ctr, N-0372 Oslo, Norway. [Farrar, Christian T.; Borra, Ronald J. H.; Rosen, Bruce R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02129 USA. [Farrar, Christian T.; Borra, Ronald J. H.; Rosen, Bruce R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Gerstner, Elizabeth R.; Batchelor, Tracy T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Jain, Rakesh K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab Tumor Biol,Dept Radiat Oncol, Boston, MA 02114 USA. [Sorensen, A. Gregory] Siemens Healthcare Hlth Serv, Malvern, PA 19355 USA. RP Emblem, KE (reprint author), Oslo Univ Hosp, Intervent Ctr, Sognsvannsveien 20, N-0372 Oslo, Norway. EM kyrre@nmr.mgh.harvard.edu RI Emblem, Kyrre/H-6691-2012 OI Emblem, Kyrre/0000-0002-6580-9519 FU National Cancer Institute, NIH, US Department of Human and Health Services [NCT00254943, T32-CA009502, NCT00756106, NCT00662506, S10 RR021110-01A1, P01CA80124]; South-Eastern Norway Regional Health Authority [2013069]; Sigrid Juselius Foundation; Instrumentarium Research Foundation; Academy of Finland; Paulo Foundation; Finnish Medical Foundation FX The authors thank J. Martin (Department of Chemical Engineering, Massachusetts Institute of Technology and the Edwin L. Steele Laboratory of Tumor Biology, Massachusetts General Hospital) and T. Stylianopoulos (Department of Mechanical and Manufacturing Engineering, University of Cyprus) for help with this manuscript. The authors apologize to the authors whose work we could not cite owing to limits on the number of references that we were able to include. The authors acknowledge funding support from the National Cancer Institute, NIH, US Department of Human and Health Services (grants NCT00254943 to K.E.E., T32-CA009502 to C.T.F., NCT00756106 to E.R.G., NCT00662506 to T.T.B., S10 RR021110-01A1 to B.R.R., NCT00254943 to A.G.S. and P01CA80124 to R.K.J.), and the South-Eastern Norway Regional Health Authority (grant 2013069 to K.E.E.). In addition, R.J.H.B. acknowledges funding from the Sigrid Juselius Foundation, the Instrumentarium Research Foundation, the Academy of Finland, the Paulo Foundation and the Finnish Medical Foundation. NR 180 TC 17 Z9 18 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD OCT PY 2014 VL 11 IS 10 BP 566 EP 584 DI 10.1038/nrclinonc.2014.126 PG 19 WC Oncology SC Oncology GA AQ1NP UT WOS:000342548400003 PM 25113840 ER PT J AU Furuyama, JK Nagarajan, R Roberts, CK Lee, CC Hahn, TJ Thomas, MA AF Furuyama, Jon K. Nagarajan, Rajakumar Roberts, Christian K. Lee, Cathy C. Hahn, Theodore J. Thomas, M. Albert TI A pilot validation of multi-echo based echo-planar correlated spectroscopic imaging in human calf muscles SO NMR IN BIOMEDICINE LA English DT Article DE multi-spin echo; 2D correlated spectroscopy; calf muscle; diabetes; intra-myocellular and extra-myocellular lipids; choline; unsaturation index ID MAGNETIC-RESONANCE SPECTROSCOPY; HUMAN BRAIN; IN-VIVO; SKELETAL-MUSCLE; LIPID-METABOLISM; MR SPECTROSCOPY; 3 T; SCANNER; SHIFT; TIMES AB A current limitation of MR spectroscopic imaging of multiple skeletal muscles is prolonged scan duration. A significant reduction in the total scan duration using the echo-planar correlated spectroscopic imaging (EP-COSI) sequence was accomplished using two bipolar readout trains with different phase-encoded echoes for one of two spatial dimensions within a single repetition time (TR). The second bipolar readout was used for spatially encoding the outer k-space, whereas the first readout was used for the central k-space only. The performance of this novel sequence, called multi-echo based echo-planar correlated spectroscopic imaging (ME-EPCOSI), was demonstrated by localizing specific key features in calf muscles and bone marrow of 11 healthy volunteers and five subjects with type 2 diabetes (T2D). A 3T MRI-MRS scanner equipped with a transmit-receive extremity coil was used. Localization of the ME-EPCOSI sequence was in good agreement with the earlier single-readout based EP-COSI sequence and the required scan time was reduced by a factor of two. In agreement with an earlier report using single-voxel based 2D MRS, significantly increased unsaturated pools of intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) and decreased IMCL and EMCL unsaturation indices (UIs) were observed in the soleus and tibialis anterior muscle regions of subjects with T2D compared with healthy controls. In addition, significantly decreased choline content was observed in the soleus of T2D subjects compared with healthy controls. Multi-voxel characterization of IMCL and EMCL ratios and UI in the calf muscle may be useful for the non-invasive assessment of altered lipid metabolism in the pathophysiology of T2D. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Furuyama, Jon K.; Nagarajan, Rajakumar; Thomas, M. Albert] Univ Calif Los Angeles, Dept Radiol Sci, Los Angeles, CA 90024 USA. [Roberts, Christian K.] Univ Calif Los Angeles, Sch Nursing, Translat Sci Sect, Exercise & Metab Dis Res Lab, Los Angeles, CA 90024 USA. [Lee, Cathy C.; Hahn, Theodore J.] VA Greater Los Angeles Healthcare Syst, GRECC, Los Angeles, CA USA. RP Thomas, MA (reprint author), Univ Calif Los Angeles, Dept Radiol Sci, Los Angeles, CA 90024 USA. EM athomas@mednet.ucla.edu RI Thomas, m. albert/A-6176-2012; Nagarajan, Rajakumar/A-7179-2013 FU NIH/NIDDK [5R01DK090406] FX This work was partially funded by an NIH/NIDDK grant (5R01DK090406). NR 33 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3480 EI 1099-1492 J9 NMR BIOMED JI NMR Biomed. PD OCT PY 2014 VL 27 IS 10 BP 1176 EP 1183 DI 10.1002/nbm.3171 PG 8 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA AQ4HO UT WOS:000342754700006 PM 25132520 ER PT J AU Sipos, F Muzes, G Furi, I Spisak, S Wichmann, B Germann, TM Constantinovits, M Krenacs, T Tulassay, Z Molnar, B AF Sipos, Ferenc Muzes, Gyoergyi Furi, Istvan Spisak, Sandor Wichmann, Barnabas Germann, Tiana M. Constantinovits, Miklos Krenacs, Tibor Tulassay, Zsolt Molnar, Bela TI Intravenous Administration of a Single-Dose Free-Circulating DNA of Colitic Origin Improves Severe Murine DSS-Colitis SO PATHOLOGY & ONCOLOGY RESEARCH LA English DT Article DE Free-circulating DNA; DSS-colitis; Toll-like receptor 9; Proinflammatory cytokines; Tissue regeneration ID SODIUM-INDUCED COLITIS; TOLL-LIKE RECEPTORS; INFLAMMATORY BOWEL DISEASES; ISOLATED LYMPHOID FOLLICLES; COLORECTAL-CANCER; PERIPHERAL-BLOOD; NUCLEIC-ACIDS; CELL-FREE; ULCERATIVE-COLITIS; CYTOKINE PROFILE AB In inflammatory bowel diseases the presence of free-circulating DNA (fcDNA) sequences in the sera is an established phenomenon, albeit its real biological function still remains unclear. In our study the immunobiologic effects of a single-dose, intravenously administered fcDNA of normal and colitic origin were assayed in DSS-colitic and control mice. In parallel with disease and histological activity evaluations changes of the TLR9 and inflammatory cytokine signaling gene expression profiles were assayed in isolated cells of the lamina propria. Intravenously administered colitis-derived fcDNA displayed a more prominent beneficial action regarding the clinical and histological severity of DSS-colitis than that of fcDNA of normal origin. Systemic administration of colitis-derived fcDNA significantly altered the expression of certain TLR9-related and proinflammatory cytokine genes in a clinically favorable manner. Presumably due to induction of severe colitis, the subsequent marked inflammatory environment may result changes in fcDNA with a potential to promote the downregulation of inflammation and improvement of tissue regeneration. Elucidating mechanisms of innate immune alterations by nucleic acids may provide further insight into the etiology of inflammatory bowel diseases, and develop the basis of novel nucleic acid-based immunotherapies. C1 [Sipos, Ferenc; Muzes, Gyoergyi; Furi, Istvan; Wichmann, Barnabas; Germann, Tiana M.; Constantinovits, Miklos; Tulassay, Zsolt; Molnar, Bela] Semmelweis Univ, Dept Internal Med 2, Cell Anal Lab, H-1088 Budapest, Hungary. [Spisak, Sandor] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Spisak, Sandor; Tulassay, Zsolt; Molnar, Bela] Hungarian Acad Sci, Mol Med Res Unit, Budapest, Hungary. [Krenacs, Tibor] Semmelweis Univ, Dept Pathol & Expt Oncol 1, H-1085 Budapest, Hungary. RP Sipos, F (reprint author), Semmelweis Univ, Dept Internal Med 2, Cell Anal Lab, Szentkiralyi St 46, H-1088 Budapest, Hungary. EM dr.siposf@gmail.com NR 58 TC 0 Z9 0 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1219-4956 EI 1532-2807 J9 PATHOL ONCOL RES JI Pathol. Oncol. Res. PD OCT PY 2014 VL 20 IS 4 BP 867 EP 877 DI 10.1007/s12253-014-9766-x PG 11 WC Oncology; Pathology SC Oncology; Pathology GA AQ1PZ UT WOS:000342554600014 PM 24723054 ER PT J AU Ansell, J Crowther, M Burnett, A Garcia, D Kaatz, S Lopes, RD Nutescu, E Oertel, L Schnurr, T Streiff, M Wirth, D Witt, D Wittkowsky, A AF Ansell, Jack Crowther, Mark Burnett, Allison Garcia, David Kaatz, Scott Lopes, Renato D. Nutescu, Edith Oertel, Lynn Schnurr, Terri Streiff, Michael Wirth, Diane Witt, Daniel Wittkowsky, Ann CA Anticoagulation Forum TI Comment on: Editorial by Husted et al "Non-vitamin K antagonist oral anticoagulants (NOACs): No longer new or novel" SO THROMBOSIS AND HAEMOSTASIS LA English DT Letter C1 [Ansell, Jack] Hofstra North Shore LIJ Sch Med, Hempstead, NY USA. [Crowther, Mark; Schnurr, Terri] St Josephs Healthcare, Hamilton, ON, Canada. [Crowther, Mark] McMaster Univ, Hamilton, ON, Canada. [Burnett, Allison] Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA. [Burnett, Allison] Univ New Mexico Hosp, Albuquerque, NM USA. [Garcia, David] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Kaatz, Scott] Michigan State Univ, Coll Human Med, Grand Rapids, MI USA. [Lopes, Renato D.] Duke Univ, Sch Med, Durham, NC USA. [Nutescu, Edith] Univ Illinois, Univ Illinois Hosp & Hlth Sci Syst, Chicago, IL USA. [Oertel, Lynn] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Streiff, Michael] Johns Hopkins Sch Med, Johns Hopkins Med Ctr, Baltimore, MD USA. [Wirth, Diane] Grady Mem, Delaware, OH USA. [Witt, Daniel] Univ Utah, Coll Pharm, Salt Lake City, UT 84112 USA. [Wittkowsky, Ann] Univ Washington, UW Med Dept Pharm, Seattle, WA 98195 USA. RP Ansell, J (reprint author), 15 Waterview Way, Long Branch, NJ 07740 USA. EM ansellje@gmail.com NR 2 TC 4 Z9 4 U1 0 U2 2 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 OCT PY 2014 VL 112 IS 4 BP 841 EP 841 DI 10.1160/TH14-04-0325 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AQ2YE UT WOS:000342655100028 PM 25119051 ER PT J AU Dos Reis, LL Tuttle, RM Alon, E Bergman, DA Bernet, V Brett, EM Cobin, R Doherty, G Harris, JR Klopper, J Lee, SL Lupo, M Milas, M Machac, J Mechanick, JI Orloff, L Randolph, G Ross, DS Smallridge, RC Terris, DJ Tufano, RP Mehra, S Scherl, S Clain, JB Urken, ML AF Dos Reis, Laura L. Tuttle, R. Michael Alon, Eran Bergman, Donald A. Bernet, Victor Brett, Elise M. Cobin, Rhoda Doherty, Gerard Harris, Jeffrey R. Klopper, Joshua Lee, Stephanie L. Lupo, Mark Milas, Mira Machac, Josef Mechanick, Jeffrey I. Orloff, Lisa Randolph, Gregory Ross, Douglas S. Smallridge, Robert C. Terris, David James Tufano, Ralph P. Mehra, Saral Scherl, Sophie Clain, Jason B. Urken, Mark L. TI What Is the Gold Standard for Comprehensive Interinstitutional Communication of Perioperative Information for Thyroid Cancer Patients? A Comparison of Existing Electronic Health Records with the Current American Thyroid Association Recommendations SO THYROID LA English DT Review ID SURGERY; SYSTEM AB Background: Appropriate management of well-differentiated thyroid cancer requires treating clinicians to have access to critical elements of the patient's presentation, surgical management, postoperative course, and pathologic assessment. Electronic health records (EHRs) provide an effective method for the storage and transmission of patient information, although most commercially available EHRs are not intended to be disease-specific. In addition, there are significant challenges for the sharing of relevant clinical information when providers involved in the care of a patient with thyroid cancer are not connected by a common EHR. In 2012, the American Thyroid Association (ATA) defined the critical elements for optimal interclinician communication in a position paper entitled, "The Essential Elements of Interdisciplinary Communication of Perioperative Information for Patients Undergoing Thyroid Cancer Surgery." Summary: We present a field-by-field comparison of the ATA's essential elements as applied to three contemporary electronic reporting systems: the Thyroid Surgery e-Form from Memorial Sloan-Kettering Cancer Center (MSKCC), the Alberta WebSMR from the University of Calgary, and the Thyroid Cancer Care Collaborative (TCCC). The MSKCC e-form fulfills 21 of 32 intraoperative fields and includes an additional 14 fields not specifically mentioned in the ATA's report. The Alberta WebSMR fulfills 45 of 82 preoperative and intraoperative fields outlined by the ATA and includes 13 additional fields. The TCCC fulfills 117 of 120 fields outlined by the ATA and includes 23 additional fields. Conclusions: Effective management of thyroid cancer is a highly collaborative, multidisciplinary effort. The patient information that factors into clinical decisions about thyroid cancer is complex. For these reasons, EHRs are particularly favorable for the management of patients with thyroid cancer. The MSKCC Thyroid Surgery e-Form, the Alberta WebSMR, and the TCCC each meet all of the general recommendations for effective reporting of the specific domains that they cover in the management of thyroid cancer, as recommended by the ATA. However, the TCCC format is the most comprehensive. The TCCC is a new Web-based disease-specific database to enhance communication of patient information between clinicians in a Health Insurance Portability and Accountability Act (HIPAA)-compliant manner. We believe the easy-to-use TCCC format will enhance clinician communication while providing portability of thyroid cancer information for patients. C1 [Dos Reis, Laura L.; Scherl, Sophie; Clain, Jason B.; Urken, Mark L.] Thyroid Head & Neck Canc Fdn, New York, NY 10003 USA. [Tuttle, R. Michael] Mem Sloan Kettering Canc Ctr, Serv Endocrinol, New York, NY 10021 USA. [Alon, Eran] Tel Aviv Univ Israel, Dept Otolarynol Head & Neck Surg, Sackler Sch Med, Chaim Sheba Med Ctr, Tel Hashomer, Israel. [Bergman, Donald A.; Brett, Elise M.; Mechanick, Jeffrey I.] Mt Sinai Hosp, Dept Endocrinol, New York, NY 10029 USA. [Machac, Josef] Mt Sinai Hosp, Dept Radiol, New York, NY 10029 USA. [Bernet, Victor; Smallridge, Robert C.] Mayo Clin, Dept Endocrinol, Jacksonville, FL 32224 USA. [Cobin, Rhoda] North Jersey Endocrine & Diabet, Ridgewood, NJ USA. [Doherty, Gerard] Boston Med Ctr, Dept Surg, Boston, MA USA. [Lee, Stephanie L.] Boston Med Ctr, Dept Med Endocrinol Diabet & Nutr, Boston, MA USA. [Harris, Jeffrey R.] Univ Alberta, Dept Otolaryngol Head & Neck Surg, Edmonton, AB, Canada. [Klopper, Joshua] Univ Colorado, Sch Med, Div Endocrinol Metab & Diabet, Aurora, CO USA. [Lupo, Mark] Thyroid & Endocrine Ctr Florida, Sarasota, FL USA. [Milas, Mira] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. [Orloff, Lisa] Standford Sch Med, Dept Otolaryngol, Stanford, CA USA. [Randolph, Gregory] Massachusetts Gen Hosp, Dept Otolaryngol, Boston, MA 02114 USA. [Ross, Douglas S.] Massachusetts Gen Hosp, Thyroid Associates, Boston, MA 02114 USA. [Terris, David James] Med Coll Georgia, Dept Otolaryngol, Augusta, GA 30912 USA. [Tufano, Ralph P.] Johns Hopkins, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA. [Mehra, Saral] Yale Univ, Sch Med, Dept Otolaryngol, New Haven, CT USA. [Urken, Mark L.] Mt Sinai Beth Israel, Dept Otolaryngol Head & Neck Surg, New York, NY USA. RP Dos Reis, LL (reprint author), Thyroid Head & Neck Canc Fdn, 10 Union Sq East,Suite 5B, New York, NY 10003 USA. EM ldosreis@thancfoundation.org FU Mount Sinai Health System FX We would like to acknowledge the Mount Sinai Health System for their generous support of this research project. NR 4 TC 3 Z9 3 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD OCT 1 PY 2014 VL 24 IS 10 BP 1466 EP 1472 DI 10.1089/thy.2014.0209 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AQ4DO UT WOS:000342742800005 PM 25036190 ER PT J AU Beaudenon-Huibregtse, S Alexander, EK Guttler, RB Hershman, JM Babu, V Blevins, TC Moore, P Andruss, B Labourier, E AF Beaudenon-Huibregtse, Sylvie Alexander, Erik K. Guttler, Richard B. Hershman, Jerome M. Babu, Varsha Blevins, Thomas C. Moore, Paul Andruss, Bernard Labourier, Emmanuel TI Centralized Molecular Testing for Oncogenic Gene Mutations Complements the Local Cytopathologic Diagnosis of Thyroid Nodules SO THYROID LA English DT Article ID NEEDLE-ASPIRATION BIOPSY; BRAF V600E MUTATION; FOLLICULAR VARIANT; TECHNOLOGY PLATFORM; BETHESDA SYSTEM; CARCINOMA; CANCER; SPECIMENS; IMPACT; METAANALYSIS AB Background: Molecular testing for oncogenic gene mutations and chromosomal rearrangements plays a growing role in the optimal management of thyroid nodules, yet lacks standardized testing modalities and systematic validation data. Our objective was to assess the performance of molecular cytology on preoperative thyroid nodule fine-needle aspirates (FNAs) across a broad range of variables, including independent collection sites, clinical practices, and anatomic pathology interpretations. Methods: Single-pass FNAs were prospectively collected from 806 nodules 1 cm or larger by ultrasonography at five independent sites across the United States. Specimens were shipped in a nucleic acid stabilization solution and tested at a centralized clinical laboratory. Seventeen genetic alterations (BRAF, KRAS, HRAS, and NRAS mutations, PAX8-PPARG and RET-PTC rearrangements) were evaluated by multiplex polymerase chain reaction and liquid bead array cytometry in 769 FNAs that met inclusion criteria. Cytology, histology, and clinical care followed local procedures and practices. All results were double-blinded. Results: Thirty-two specimens (4.2%) failed to yield sufficient nucleic acid to generate molecular data. A single genetic alteration was detected in 80% of cytology malignant cases, 21% of indeterminate, 7.8% of nondiagnostic, and 3.5% of benign cases. Among 109 nodules with surgical histology reference standard, oncogenic mutations were present in 50% of malignant nodules missed by cytology. There were 14 cancers not identified by cytology or molecular tests, including 5 carcinomas with histologic sizes less than 1 cm (3 multifocal) and 8 noninvasive follicular variants of papillary carcinoma (4 encapsulated). No mutations were detected in 89% of the nodules benign by histopathology with 6 false-positive molecular results in 5 adenomas (2-5.5 cm) and 1 cystic nodule with an incidental papillary microcarcinoma (0.15 cm). The posttest probability of thyroid cancer was 100% for nodules positive for BRAF or RET-PTC, 70% for RAS or PAX8-PPARG, and 88% for molecular cytology overall. Conclusions: Centralized and standardized molecular testing for genetic alterations associated with a high risk of malignancy efficiently complements the local cytopathologic diagnosis of thyroid nodule aspirates in the clinical setting. Actionable molecular cytology can improve the personalized surgical and medical management of patients with thyroid cancers, facilitating one-stage total thyroidectomy and reducing the number of unnecessary diagnostic surgeries. C1 [Beaudenon-Huibregtse, Sylvie; Andruss, Bernard; Labourier, Emmanuel] Asuragen Inc, Austin, TX 78744 USA. [Alexander, Erik K.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Alexander, Erik K.] Harvard Univ, Sch Med, Boston, MA USA. [Guttler, Richard B.] Santa Monica Thyroid Ctr, Santa Monica, CA USA. [Hershman, Jerome M.; Babu, Varsha] W Los Angeles Vet Affairs Med Ctr, Endocrinol & Diabet Div, Los Angeles, CA 90073 USA. [Hershman, Jerome M.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Blevins, Thomas C.] Texas Diabet & Endocrinol, Austin, TX USA. [Moore, Paul] Austin Diagnost Clin, Austin, TX USA. RP Labourier, E (reprint author), Asuragen Inc, 2150 Woodward St,Suite 100, Austin, TX 78744 USA. EM elabourier@asuragen.com OI Labourier, Emmanuel/0000-0001-8010-0674 FU Asuragen Inc. FX This study was sponsored by Asuragen Inc. S.B.H., B.A., and E.L. are employees of Asuragen. E. K. A. received compensation for his participation in Asuragen's clinical advisory board, and is a consultant to Genzyme, Inc. and Veracyte, Inc. The other authors have no conflicts of interest to declare. NR 35 TC 26 Z9 28 U1 1 U2 12 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD OCT 1 PY 2014 VL 24 IS 10 BP 1479 EP 1487 DI 10.1089/thy.2013.0640 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AQ4DO UT WOS:000342742800007 PM 24811481 ER PT J AU Weinger, K Beverly, EA Smaldone, A AF Weinger, Katie Beverly, Elizabeth A. Smaldone, Arlene TI Diabetes Self-Care and the Older Adult SO WESTERN JOURNAL OF NURSING RESEARCH LA English DT Article DE diabetes; self-care; education; depression; older adults ID SUBCUTANEOUS INSULIN INFUSION; NURSING-HOME RESIDENTS; RANDOMIZED-CONTROLLED-TRIAL; MULTIPLE DAILY INJECTIONS; DWELLING ELDERLY-WOMEN; POOR GLYCEMIC CONTROL; OPEN CROSSOVER TRIAL; OF-THE-LITERATURE; UNITED-STATES; COGNITIVE DYSFUNCTION AB The prevalence of diabetes is highest in older adults, a population that is increasing. Diabetes self-care is complex with important recommendations for nutrition, physical activity, checking glucose levels, and taking medication. Older adults with diabetes have unique issues that impact self-care. As people age, their health status, support systems, physical and mental abilities, and nutritional requirements change. Furthermore, comorbidities, complications, and polypharmacy complicate diabetes self-care. Depression is also more common among the elderly and may lead to deterioration in self-care behaviors. Because of concerns about cognitive deficits and multiple comorbidities, adults older than 65 years are often excluded from research trials. Thus, little clinical evidence is available and the most appropriate treatment approaches and how to best support older patients' self-care efforts are unclear. This review summarizes the current literature, research findings, and expert and consensus recommendations with their rationales. C1 [Weinger, Katie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Beverly, Elizabeth A.] Ohio Univ, Heritage Coll Osteopath Med, Athens, OH 45701 USA. [Smaldone, Arlene] Columbia Univ, Sch Nursing, New York, NY USA. RP Weinger, K (reprint author), Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM katie.weinger@joslin.harvard.edu FU National Institutes of Health [R01 DK060115, P30 DK36836] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the National Institutes of Health Grants R01 DK060115 and P30 DK36836. NR 118 TC 4 Z9 4 U1 3 U2 26 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0193-9459 EI 1552-8456 J9 WESTERN J NURS RES JI West. J. Nurs. Res. PD OCT PY 2014 VL 36 IS 9 SI SI BP 1272 EP 1298 DI 10.1177/0193945914521696 PG 27 WC Nursing SC Nursing GA AQ2OQ UT WOS:000342626900013 PM 24510969 ER PT J AU Safren, SA Thomas, BE Mayer, KH Biello, KB Mani, J Rajagandhi, V Periyasamy, M Swaminathan, S Mimiaga, MJ AF Safren, Steven A. Thomas, Beena E. Mayer, Kenneth H. Biello, Katie B. Mani, Jamuna Rajagandhi, Vijaylakshmi Periyasamy, Murugesan Swaminathan, Soumya Mimiaga, Matthew J. TI A Pilot RCT of an Intervention to Reduce HIV Sexual Risk and Increase Self-acceptance Among MSM in Chennai, India SO AIDS AND BEHAVIOR LA English DT Article DE MSM; Risk reduction; India; Self-acceptance ID MENTAL-HEALTH; PREVENTION; QUESTIONS; BEHAVIOR; VIOLENCE; WORKERS AB This is a 2-arm pilot randomized controlled trial (N = 96) of a behavioral intervention (4 group and 4 individual sessions) integrating risk reduction counseling with counseling to foster self-acceptance in MSM in India compared to enhanced standard of care (ESOC). Both conditions involved HIV and STI testing and counseling at baseline and 6-months, and assessments of condomless sex at baseline, 3-, and 6-months. A significant condition by time interaction suggested a difference in the rate of change in number of anal sex acts without condoms in the intervention versus ESOC (p < 0.0001). Post hoc contrasts suggested that the overall difference was due to intervention-response at 3-months. The incidence of bacterial STIs was 17.5 % in the intervention condition and a 28.6 % in ESOC. Addressing self-acceptance and related psychosocial concerns in the context sexual risk reduction counseling for MSM in India was feasible and acceptable. Testing the intervention for efficacy is justified. C1 [Safren, Steven A.; Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02163 USA. [Safren, Steven A.; Mayer, Kenneth H.; Biello, Katie B.; Mimiaga, Matthew J.] Inst Fenway Hlth, Boston, MA USA. [Thomas, Beena E.; Mani, Jamuna; Rajagandhi, Vijaylakshmi; Periyasamy, Murugesan; Swaminathan, Soumya] Indian Council Med Res, Natl Inst Res TB, Madras, Tamil Nadu, India. [Biello, Katie B.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Safren, SA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02163 USA. EM ssafren@mgh.harvard.edu FU NIMH NIH HHS [5K24MH094214, K24 MH094214, R-21 MH085314, R21 MH085314] NR 23 TC 3 Z9 3 U1 2 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD OCT PY 2014 VL 18 IS 10 BP 1904 EP 1912 DI 10.1007/s10461-014-0773-4 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AP9UF UT WOS:000342425000007 PM 24770985 ER PT J AU Mpunga, T Tapela, N Hedt-Gauthier, BL Milner, D Nshimiyimana, I Muvugabigwi, G Moore, M Shulman, DS Pepoon, JR Shulman, LN AF Mpunga, Tharcisse Tapela, Neo Hedt-Gauthier, Bethany L. Milner, Dan Nshimiyimana, Irenee Muvugabigwi, Gaspard Moore, Molly Shulman, David S. Pepoon, James R. Shulman, Lawrence N. TI Diagnosis of Cancer in Rural Rwanda: Early Outcomes of a Phased Approach to Implement Anatomic Pathology Services in Resource-Limited Settings SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Cancer; Pathology services; Butaro District Hospital; Rwanda; Capacity building; North-South partnerships ID DEVELOPING-WORLD; TELEPATHOLOGY; AFRICA; MODEL AB Objectives: Adequate pathology services are a prerequisite to accurate cancer diagnoses and tailoring appropriate treatment. Limitations in skilled personnel and infrastructure are among the challenges faced by developing countries. We describe a stepwise implementation of anatomic pathology laboratory services at Butaro District Hospital, designated as a Cancer Center of Excellence in rural Rwanda. Methods: The phased approach to developing pathology services up to December 2012 is described A retrospective review of specimens submitted to Butaro District Hospital between July I, 2012, and December 31, 2012, was conducted. Patient clinical characteristics and sociodemographics are also described Results: During the study period, a total of 437 tissue specimens were submitted. Among these, 143 (32.7%) were from male patients, 244 (55.8%) were confirmed as malignant, 163 (37.3%) were benign, 28 (6.4%) were inconclusive, and two (0.5%) results were not available at the time of analysis. The median time from specimen receipt at Butaro to final reporting was 32 days (range, 7-193 days; interquartile range, 23-44 days). Conclusions: Our experience demonstrates that anatomic pathology services can be established in resource-limited settings and local capacity can be built to support accurate diagnoses. Our approach included leveraging partnerships, volunteer experts, and task shifting and will be expanded to include telepathology. C1 [Mpunga, Tharcisse; Nshimiyimana, Irenee; Muvugabigwi, Gaspard] Minist Hlth, Kigali, Rwanda. [Mpunga, Tharcisse; Hedt-Gauthier, Bethany L.] Univ Rwanda, Coll Med & Hlth Sci, Kigali, Rwanda. [Tapela, Neo; Hedt-Gauthier, Bethany L.; Moore, Molly; Shulman, David S.; Pepoon, James R.] Partners Hlth Rwanda, Kigali, Rwanda. [Tapela, Neo; Milner, Dan; Pepoon, James R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hedt-Gauthier, Bethany L.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Shulman, Lawrence N.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mpunga, T (reprint author), Butaro Dist Hosp, POB 59, Musanze, Rwanda. EM dmpunga537@gmail.com FU Non-Communicable Diseases Writing Group; Harvard Medical School Department of Global Health and Social Medicine Research Core FX This study was supported by Partners In Health/Inshuti Mu Buzima and by the Non-Communicable Diseases Writing Group. B.L.H.-G. was supported by the Harvard Medical School Department of Global Health and Social Medicine Research Core. NR 14 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 2014 VL 142 IS 4 BP 541 EP 545 DI 10.1309/AJCPYPDES6Z8ELEY PG 5 WC Pathology SC Pathology GA AP9OR UT WOS:000342409600018 PM 25239422 ER PT J AU Lin, AE Krikov, S Riehle-Colarusso, T Frias, JL Belmont, J Anderka, M Geva, T Getz, KD Botto, LD AF Lin, Angela E. Krikov, Sergey Riehle-Colarusso, Tiffany Frias, Jaime L. Belmont, John Anderka, Marlene Geva, Tal Getz, Kelly D. Botto, Lorenzo D. CA Natl Birth Defects Prevention TI Laterality Defects in the National Birth Defects Prevention Study (1998-2007): Birth Prevalence and Descriptive Epidemiology SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE asplenia; cardiovascular malformations; congenital heart defects; dextrocardia; heterotaxy; isomerism; laterality defects; malposition; prevalence; race/ethnic disparities; situs ambiguous; situs inversus ID CONGENITAL HEART-DISEASE; PRIMARY CILIARY DYSKINESIA; ANOMALIES; HETEROTAXIA; CLASSIFICATION; ASYMMETRY; DIAGNOSIS; NEWBORNS; ATLANTA AB Little is known epidemiologically about laterality defects. Using data from the National Birth Defects Prevention Study (NBDPS), a large multi-site case-control study of birth defects, we analyzed prevalence and selected characteristics in children born with laterality defects born from 1998 to 2007. We identified 517 nonsyndromic cases (378 heterotaxy, 73.1%; 139 situs inversus totalis [SIT], 26.9%) resulting in an estimated birth prevalence of 1.1 per 10,000 live births (95% confidence interval 1.0-1.2). Prevalence did not differ significantly across sites, over time, or by inclusion of pregnancy termination. Laterality defects were more common among preterm cases compared to term cases, and in children born to mothers who were non-white or younger than 20 years compared to white mothers or those age 25-29 years. The distribution of associated cardiac and extra-cardiac defects, excluding the expected heterotaxy anomalies, varied by type of laterality defect. Cases with heterotaxy were significantly more likely than those with SIT to have double outlet right ventricle, atrioventricular canal defects, pulmonary stenosis, non-tetralogy of Fallot pulmonary atresia with ventricular septal defect, totally and partially anomalous pulmonary venous return; also more likely to have orofacial clefts, esophageal atresia, bowel atresias, and omphalocele, though not reaching statistical significance. Relatively more common among cases with SIT were Dandy-Walker malformation, anotia/microtia, and limb deficiency. The similarity in the demographic characteristics of heterotaxy and SIT supports the hypothesis that they are part of a continuum of abnormal left-right axis patterning. These findings on laterality defects may help guide clinical care, future research, and prevention strategies. (C) 2014 Wiley Periodicals, Inc. C1 [Lin, Angela E.] MassGen Hosp Children, Boston, MA 02114 USA. [Lin, Angela E.; Anderka, Marlene; Getz, Kelly D.] Massachusetts Ctr Birth Defects Res & Prevent, Boston, MA USA. [Krikov, Sergey; Botto, Lorenzo D.] Univ Utah, Dept Pediat, Div Med Genet, Salt Lake City, UT USA. [Riehle-Colarusso, Tiffany; Frias, Jaime L.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. [Frias, Jaime L.] McKing Consulting Corp, Fairfax, VA USA. [Belmont, John] Baylor Coll Med, Houston, TX 77030 USA. [Geva, Tal] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA. RP Lin, AE (reprint author), MassGen Hosp Children, 185 Cambridge St,CPZN 2222, Boston, MA 02114 USA. EM lin.angela@mgh.harvard.edu FU Centers for Disease Control and Prevention Centers of Excellence Award [U50/CCU925286] FX Grant sponsor: Centers for Disease Control and Prevention Centers of Excellence Award No.; Grant number: U50/CCU925286. NR 35 TC 17 Z9 18 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT PY 2014 VL 164 IS 10 BP 2581 EP 2591 DI 10.1002/ajmg.a.36695 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA AP7TM UT WOS:000342279600026 PM 25099286 ER PT J AU Farkas, MH Lew, DS Sousa, ME Bujakowska, K Chatagnon, J Bhattacharya, SS Pierce, EA Nandrot, EF AF Farkas, Michael H. Lew, Deborah S. Sousa, Maria E. Bujakowska, Kinga Chatagnon, Jonathan Bhattacharya, Shomi S. Pierce, Eric A. Nandrot, Emeline F. TI Mutations in Pre-mRNA Processing Factors 3, 8, and 31 Cause Dysfunction of the Retinal Pigment Epithelium SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PLURIPOTENT STEM-CELLS; RETINITIS-PIGMENTOSA; ALPHA-V-BETA-5 INTEGRIN; PHAGOCYTOSIS; MERTK; DEGENERATION; GENE; RPE; ROD; DYSTROPHY AB Mutations in the ubiquitously expressed pre-mRNA processing factors 3, 8, and 31 (PRPF3, PRPF8, and PRPF31) cause nonsyndromic dominant retinitis pigmentosa in humans, an inherited retinal degeneration. It is unclear what mechanisms, or which cell types of the retina, are affected. Transgenic mice with the human mutations in these genes display late-onset morphological changes in the retinal pigment epithelium (RPE). To determine whether the observed morphological changes are preceded by abnormal RPE function, we investigated its phagocytic function in Prpf3(T494M/T494M), prpf8(H2309P/H2309P), and Prpf31(+/-) mice. We observe decreased phagocytosis in primary RPE cultures from mutant mice, and this is replicated by sh RNA-mediated knockdown of PRPF31 in human ARPE-19 cells. The diurnal rhythmicity of phagocytosis is almost Lost, indicated by the marked attenuation of the phagocytic burst 2 hours after light onset. The strength of adhesion between RPE apical microvilli and photoreceptor outer segments also declined during peak adhesion in all mutants. In all models, at least one of the receptors involved in binding and internalization of shed photoreceptor outer segments was subjected to changes in Localization. Although the mechanism underlying these changes in RPE function is yet to be elucidated, these data are consistent with the mouse RPE being the primary cell affected by mutations in the RNA splicing factors, and these changes occur at an early age. C1 [Farkas, Michael H.; Sousa, Maria E.; Bujakowska, Kinga; Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst,, Boston, MA USA. [Lew, Deborah S.; Bujakowska, Kinga; Chatagnon, Jonathan; Bhattacharya, Shomi S.; Nandrot, Emeline F.] Univ Paris 06, Sorbonne Univ, Vis Inst, INSERM,U968,UMR S 968,CNRS,UMR 7210, Paris, France. [Bhattacharya, Shomi S.] UCL, Inst Ophthalmol, London, England. [Bhattacharya, Shomi S.] Andalusian Ctr Mol Biol & Regenerat Med CABIMER, Andalusian Ctr Mol Biol & Regenerat Med, Seville, Spain. RP Nandrot, EF (reprint author), Dept Therapeut, Inst Vis, 17 Rue Moreau, F-75012 Paris, France. EM eric_pierce@meei.harvard.edu; emeline.nandrot@inserm.fr OI Pierce, Eric/0000-0002-2354-4102 FU NIH National Eye Institute [EY020902, F32-EY020747]; Research to Prevent Blindness, United States; Agence Nationale de la Recherche, France, Chaire d'Excellence; Fondation Voir et Entendre and Fondation Bettencourt Schueller Young Investigator grants; Center National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale, France; Sorbonne Universites, Universite Pierre et Marie Curie-Paris 6; Centre National de la Recherche Scientifique; Department de Paris FX Supported by the NIH National Eye Institute grants EY020902 (E.A.P., subaward to S.S.B. and E.F.N.) and F32-EY020747 (M.H.F.); Research to Prevent Blindness, United States; Agence Nationale de la Recherche, France, Chaire d'Excellence (S.S.B.); Fondation Voir et Entendre and Fondation Bettencourt Schueller Young Investigator grants (E.F.N.); Center National de la Recherche Scientifique (CNRS) (E.F.N.). In addition, the Institut de la Vision is funded by Institut National de la Sante et de la Recherche Medicale, France; Sorbonne Universites, Universite Pierre et Marie Curie-Paris 6; Centre National de la Recherche Scientifique; and Department de Paris. NR 42 TC 7 Z9 7 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2014 VL 184 IS 10 BP 2641 EP 2652 DI 10.1016/j.ajpath.2014.06.026 PG 12 WC Pathology SC Pathology GA AP7SK UT WOS:000342276800006 PM 25111227 ER PT J AU Song, DL Grieco, S Li, YF Hunter, A Chu, S Zhao, LL Song, Y DeAngelis, RA Shi, LY Liu, Q Pierce, EA Nishina, PM Larnbris, JD Dunaief, JL AF Song, Deli Grieco, Steve Li, Yafeng Hunter, Allan Chu, Sally Zhao, Liangliang Song, Ying DeAngelis, Robert A. Shi, Lan-Ying Liu, Qin Pierce, Eric A. Nishina, Patsy M. Larnbris, John D. Dunaief, Joshua L. TI A Murine Rp1 Missense Mutation Causes Protein Mislocalization and Slowly Progressive Photoreceptor Degeneration SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID DOMINANT RETINITIS-PIGMENTOSA; MICROTUBULE-ASSOCIATED PROTEIN; GENE; DOUBLECORTIN; DISEASE; MICE; MAK AB Mutations in the RP1 gene can cause retinitis pigmentosa. We identified a spontaneous L66P mutation caused by two adjacent point mutations in the Rp1 gene in a colony of C57BL/6J mice. Mice homozygous for the L66P mutation exhibited slow, progressive photoreceptor degeneration throughout their Lifespan. Optical coherence tomography imaging found abnormal photoreceptor reflectivity at 1 month of age. Histology found shortening and disorganization of the photoreceptor inner and outer segments and progressive thinning of the outer nuclear layer. Electroretinogram a- and b-wave amplitudes were decreased with age. Western blot analysis found that the quantity and size of the mutated retinitis pigmentosa 1 (RP1) protein were normal. However, immunohistochemistry found that the mutant Rp1 protein partially mislocalized to the transition zone of the shortened axonemes. This mutation disrupted colocalization with cytoplasmic microtubules in vitro. In conclusion, the L66P mutation in the first doublecortin domain of the Rp1 gene impairs Rp1 protein localization and function, Leading to abnormalities in photoreceptor outer segment structure and progressive photoreceptor degeneration. This is the first missense mutation in Rp1 shown to cause retinal degeneration. It provides a unique, slowly progressive photoreceptor degeneration model that mirrors the slow degeneration kinetics in most patients with retinitis pigmentosa. C1 [Song, Deli; Grieco, Steve; Li, Yafeng; Hunter, Allan; Chu, Sally; Zhao, Liangliang; Song, Ying; Dunaief, Joshua L.] Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA. [DeAngelis, Robert A.; Larnbris, John D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Zhao, Liangliang] Jilin Univ, Hosp 2, Dept Ophthalmol, Changchun 130023, Peoples R China. [Shi, Lan-Ying; Nishina, Patsy M.] Jackson Lab, Bar Harbor, ME 04609 USA. [Liu, Qin; Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Dunaief, JL (reprint author), 305 Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA. EM jdunaief@upenn.edu OI Lambris, John/0000-0002-9370-5776; Pierce, Eric/0000-0002-2354-4102 FU NIH [R01 EY015240, EY016501, EY2063, A16870, EY12910]; Research to Prevent Blindness; F.M. Kirby Foundation, United States; Paul and Evanina Bell Mackall Foundation Trust; Cancer Center CORE grant [5P30CA034196]; Foundation Fighting Blindness USA FX Supported by NIH grants R01 EY015240 (J.L.D.), EY016501 (P.M.N.), EY2063 (J.D.L.), A16870 (J.D.L.), and EY12910 (E.A.P.); unrestricted funding from Research to Prevent Blindness; the F.M. Kirby Foundation, United States; a gift in memory of Dr. Lee F. Mauger; the Paul and Evanina Bell Mackall Foundation Trust; a Cancer Center CORE grant 5P30CA034196 (P.M.N.); the Foundation Fighting Blindness USA (Q.L.). D.S., S.G., and Y.L. contributed equally to this work. NR 27 TC 4 Z9 4 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2014 VL 184 IS 10 BP 2721 EP 2729 DI 10.1016/j.ajpath.2014.06.010 PG 9 WC Pathology SC Pathology GA AP7SK UT WOS:000342276800013 PM 25088982 ER PT J AU Lopez, L Peralta, CA Lee, A Al Hazzouri, AZ Haan, MN AF Lopez, Lenny Peralta, Carmen A. Lee, Anne Al Hazzouri, Adina Zeki Haan, Mary N. TI Impact of acculturation on cardiovascular risk factors among elderly Mexican Americans SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Hispanics; Acculturation; Cardiovascular risk factors ID HEALTH INTERVIEW SURVEY; NON-HISPANIC WHITES; UNITED-STATES; NATIONAL-HEALTH; HYPERTENSION; PREVALENCE; MORTALITY; DISEASE; LATINOS; ATHEROSCLEROSIS AB Purpose: Higher levels of acculturation among Latinos have been shown to be associated with a higher prevalence of cardiovascular (CV) risk factors in some studies of middle-age persons. The association of acculturation and prevalence of CV risk factors in elderly Latinos is less well established. Methods: Acculturation was measured using the validated bidimensional Acculturation Rating Scale for Mexican Americans-II. We conducted a cross-sectional analysis of the association of acculturation with prevalence of CV risk factors among 1789 elderly men and women from the Sacramento Area Latino Study on Aging using multivariate linear and logistic regression. We tested for the interaction of acculturation with risk factors by nativity status. Results: Median age was 69.8 years. Higher acculturation was associated with lower systolic blood pressure, lower low-density lipoprotein, higher high-density lipoprotein, and lower prevalence of CV disease after age and sex adjustment. Higher acculturation remained associated with lower level of low-density lipoprotein and higher level of high-density lipoprotein after full adjustment. Nativity status did not affect these results. Conclusions: Contrary to other reports in middle-aged persons, higher levels of acculturation were associated with better lipid profiles and no significant differences in other CV risk factors by acculturation level in elderly Latinos. (C) 2014 Elsevier Inc. All rights reserved. C1 [Lopez, Lenny] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Dept Gen Med, Boston, MA 02114 USA. [Lopez, Lenny] Brigham & Womens Hosp, Boston, MA 02115 USA. [Peralta, Carmen A.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, Div Nephrol, San Francisco, CA 94143 USA. [Lee, Anne; Al Hazzouri, Adina Zeki; Haan, Mary N.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA. RP Lopez, L (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Ninth Floor, Boston, MA 02114 USA. EM llopez1@partners.org FU NIH [AG12975, DK60753] FX The authors thank the SALSA participants and the following NIH grants: National Institute on Aging AG12975 and National Institute of Diabetes and Digestive and Kidney Diseases DK60753. Dr. Lopez thanks the Robert Wood Johnson Foundation Harold Amos Faculty Development Program and NIDDK 1K23DK098280-01. NR 41 TC 1 Z9 1 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 2014 VL 24 IS 10 BP 714 EP 719 DI 10.1016/j.annepidem.2014.07.011 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AP8KY UT WOS:000342329100002 PM 25172232 ER PT J AU Lengacher, CA Reich, RR Kip, KE Barta, M Ramesar, S Paterson, CL Moscoso, MS Carranza, I Budhrani, PH Kim, SJ Park, HY Jacobsen, PB Schell, MJ Jim, HSL Post-White, J Farias, JR Park, JY AF Lengacher, Cecile A. Reich, Richard R. Kip, Kevin E. Barta, Michelle Ramesar, Sophia Paterson, Carly L. Moscoso, Manolete S. Carranza, Irina Budhrani, Pinky H. Kim, Seung Joon Park, Hyun Y. Jacobsen, Paul B. Schell, Michael J. Jim, Heather S. L. Post-White, Janice Farias, Jerrica R. Park, Jong Y. TI Influence of Mindfulness-Based Stress Reduction (MBSR) on Telomerase Activity in Women With Breast Cancer (BC) SO BIOLOGICAL RESEARCH FOR NURSING LA English DT Article DE telomere length; telomerase activity; stress; breast cancer; mindfulness based stress reduction; MBSR(BC) ID CARDIOVASCULAR-DISEASE; ANXIETY DISORDERS; MEDITATION; INTERVENTION; LENGTH; LIFE; RECOGNITION; INSTABILITY; PREVENTION; PROGRAM AB Mindfulness-based stress reduction (MBSR) reduces symptoms of depression, anxiety, and fear of recurrence among breast cancer (BC) survivors. However, the effects of MBSR (BC) on telomere length (TL) and telomerase activity (TA), known markers of cellular aging, psychological stress, and disease risk, are not known. This randomized, wait-listed, controlled study, nested within a larger trial, investigated the effects of MBSR (BC) on TL and TA. BC patients (142) with Stages 0-III cancer who had completed adjuvant treatment with radiation and/or chemotherapy at least 2 weeks prior to enrollment and within 2 years of completion of treatment with lumpectomy and/or mastectomy were randomly assigned to either a 6-week MBSR for BC program or a usual care. Assessments of TA and TL were obtained along with psychological measurements at baseline, 6 weeks, and 12 weeks after completing the MBSR(BC) program. The mean age of 142 participants was 55.3 years; 72% were non-Hispanic White; 78% had Stage I or II cancer; and 36% received both chemotherapy and radiation. In analyses adjusted for baseline TA and psychological status, TA increased steadily over 12 weeks in the MBSR(BC) group (approximately 17%) compared to essentially no increase in the control group (approximately 3%, p < .01). In contrast, no between-group difference was observed for TL (p = .92). These results provide preliminary evidence that MBSR(BC) increases TA in peripheral blood mononuclear cells from BC patients and have implications for understanding how MBSR(BC) may extend cell longevity at the cellular level. C1 [Lengacher, Cecile A.; Kip, Kevin E.; Barta, Michelle; Ramesar, Sophia; Paterson, Carly L.; Moscoso, Manolete S.; Carranza, Irina; Post-White, Janice; Farias, Jerrica R.] Univ S Florida, Coll Nursing, Tampa, FL 33612 USA. [Reich, Richard R.; Park, Hyun Y.; Jacobsen, Paul B.; Schell, Michael J.; Jim, Heather S. L.; Park, Jong Y.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Reich, Richard R.] Univ South Florida Sarasota Manatee, Coll Arts & Sci, Manatee Cty, FL USA. [Budhrani, Pinky H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Budhrani, Pinky H.] Harvard Med Ctr, Boston, MA USA. [Kim, Seung Joon] Catholic Univ Korea, Div Pulmonol, Dept Internal Med, Seoul, South Korea. RP Lengacher, CA (reprint author), Univ S Florida, Coll Nursing, MDC22,12901 Bruce B Downs Blvd, Tampa, FL 33612 USA. EM clengach@health.usf.edu FU USF Established Researcher Grant Award; National Cancer Institute [R01-CA131080] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the USF Established Researcher Grant Award and, in part, by the National Cancer Institute (R01-CA131080). NR 52 TC 16 Z9 17 U1 4 U2 45 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1099-8004 EI 1552-4175 J9 BIOL RES NURS JI Biol. Res. Nurs. PD OCT PY 2014 VL 16 IS 4 BP 438 EP 447 DI 10.1177/1099800413519495 PG 10 WC Nursing SC Nursing GA AP9HQ UT WOS:000342390000009 PM 24486564 ER PT J AU Singer, SJ Tucker, AL AF Singer, Sara J. Tucker, Anita L. TI The evolving literature on safety WalkRounds: emerging themes and practical messages SO BMJ QUALITY & SAFETY LA English DT Editorial Material ID IMPROVING PATIENT SAFETY; INTENSIVE-CARE UNITS; LEADERSHIP WALKROUNDS; HEALTH-CARE; CLIMATE ATTITUDES; CULTURE; HOSPITALS; INTERVENTION; OUTCOMES; ERRORS C1 [Singer, Sara J.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Singer, Sara J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Mongan Inst Hlth Policy, Boston, MA 02115 USA. [Tucker, Anita L.] Brandeis Int Business Sch, Waltham, MA USA. RP Singer, SJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave,Kresge 3,Room 317, Boston, MA 02115 USA. EM ssinger@hsph.harvard.edu NR 72 TC 5 Z9 5 U1 0 U2 14 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD OCT PY 2014 VL 23 IS 10 BP 789 EP 800 DI 10.1136/bmjqs-2014-003416 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AP9CG UT WOS:000342375400001 PM 25228779 ER PT J AU Muniz, LD Moss, AK Setayeshi, NF Vicente, AC Fernandez-del Castillo, C AF de Gregorio Muniz, Lucia Moss, Angela K. Farhangmehr Setayeshi, Neda Colas Vicente, Antonio Fernandez-del Castillo, Carlos TI A young woman with a pancreatic head cystic neoplasm SO CIRUGIA ESPANOLA LA Spanish DT Editorial Material ID TUMOR C1 [de Gregorio Muniz, Lucia; Farhangmehr Setayeshi, Neda; Colas Vicente, Antonio] Hosp Univ Puerta Hierro Majadahonda, Serv Cirugia Gen & Digest, Madrid, Spain. [Moss, Angela K.; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Gen & Gastrointestinal Surg Dept, Boston, MA USA. RP Muniz, LD (reprint author), Hosp Univ Puerta Hierro Majadahonda, Serv Cirugia Gen & Digest, Madrid, Spain. EM ludegregoriomuniz@yahoo.es NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0009-739X EI 1578-147X J9 CIR ESPAN JI Cir. Espan. PD OCT PY 2014 VL 92 IS 8 BP 565 EP 567 DI 10.1016/j.ciresp.2013.02.014 PG 4 WC Surgery SC Surgery GA AP9GN UT WOS:000342387100015 ER PT J AU Nateras, OS Harrison, JM Muir, ER Zhang, Y Peng, Q Chalfin, S Gutierrez, JE Johnson, DA Kiel, JW Duong, TQ AF Nateras, Oscar San Emeterio Harrison, Joseph M. Muir, Eric R. Zhang, Yi Peng, Qi Chalfin, Steven Gutierrez, Juan E. Johnson, Daniel A. Kiel, Jeffrey W. Duong, Timothy Q. TI Choroidal Blood Flow Decreases with Age: An MRI Study SO CURRENT EYE RESEARCH LA English DT Article DE Choroidal basal blood flow; eye tracking; high-resolution MRI; visual fixation ID RETINITIS-PIGMENTOSA; MOUSE MODEL; FUNCTIONAL OPHTHALMODYNAMOMETRY; ANATOMICAL MRI; RISK-FACTORS; CIRCULATION; GLAUCOMA; RELAXATION; EFFICIENCY; MEMBRANE AB Purpose: To verify that a visual fixation protocol with cued eye blinks achieves sufficient stability for magnetic resonance imaging (MRI) blood-flow measurements and to determine if choroidal blood flow (ChBF) changes with age in humans. Methods: The visual fixation stability achievable during an MRI scan was measured in five normal subjects using an eye-tracking camera outside the MRI scanner. Subjects were instructed to blink immediately after recorded MRI sound cues but to otherwise maintain stable visual fixation on a small target. Using this fixation protocol, ChBF was measured with MRI using a 3 Tesla clinical scanner in 17 normal subjects (24-68 years old). Arterial and intraocular pressures (IOP) were measured to calculate perfusion pressure in the same subjects. Results: The mean temporal fluctuations (standard deviation) of the horizontal and vertical displacements were 29 +/- 9 mu m and 38 +/- 11 mu m within individual fixation periods, and 50 +/- 34 mu m and 48 +/- 19 mu m across different fixation periods. The absolute displacements were 67 +/- 31 mu m and 81 +/- 26 mu m. ChBF was negatively correlated with age (R = -0.7, p = 0.003), declining 2.7 ml/100 ml/min per year. There were no significant correlations between ChBF versus perfusion pressure, arterial pressure, or IOP. There were also no significant correlations between age versus perfusion pressure, arterial pressure, or IOP. Multiple regression analysis indicated that age was the only measured independent variable that was significantly correlated with ChBF (p = 0.03). Conclusions: The visual fixation protocol with cued eye blinks was effective in achieving sufficient stability for MRI measurements. ChBF had a significant negative correlation with age. C1 [Nateras, Oscar San Emeterio; Muir, Eric R.; Zhang, Yi; Peng, Qi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Nateras, Oscar San Emeterio; Zhang, Yi; Peng, Qi; Gutierrez, Juan E.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Harrison, Joseph M.; Muir, Eric R.; Chalfin, Steven; Johnson, Daniel A.; Kiel, Jeffrey W.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Peng, Qi] Albert Einstein Coll Med, Dept Radiol, Bronx, NY 10467 USA. [Peng, Qi] Montefiore Med Ctr, Bronx, NY 10467 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu FU Clinical Translational Science Award Pilot Grant [UL1RR025767]; NIH/NEI [R01 EY021179, EY014211, EY021173, EY018855, EY09702]; Department of Veterans Affairs MERIT awards FX This work was supported in part by a Clinical Translational Science Award Pilot Grant (parent grant UL1RR025767), NIH/NEI (R01 EY021179, EY014211, EY021173, EY018855, and EY09702), and Department of Veterans Affairs MERIT awards. The authors report no conflicts of interest. NR 55 TC 2 Z9 2 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0271-3683 EI 1460-2202 J9 CURR EYE RES JI Curr. Eye Res. PD OCT PY 2014 VL 39 IS 10 BP 1059 EP 1067 DI 10.3109/02713683.2014.892997 PG 9 WC Ophthalmology SC Ophthalmology GA AP6PM UT WOS:000342199700013 ER EF