FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Acharya, SS Fendler, W Watson, J Hamilton, A Pan, YF Gaudiano, E Moskwa, P Bhanja, P Saha, S Guha, C Parmar, K Chowdhury, D AF Acharya, Sanket S. Fendler, Wojciech Watson, Jacqueline Hamilton, Abigail Pan, Yunfeng Gaudiano, Emily Moskwa, Patryk Bhanja, Payel Saha, Subhrajit Guha, Chandan Parmar, Kalindi Chowdhury, Dipanjan TI Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID TOTAL-BODY IRRADIATION; CIRCULATING MICRORNAS; STEM-CELLS; MICE; MANAGEMENT; PLASMA; SENESCENCE; QUALITY; STRESS; MARROW AB Accidental radiation exposure is a threat to human health that necessitates effective clinical planning and diagnosis. Minimally invasive biomarkers that can predict long-term radiation injury are urgently needed for optimal management after a radiation accident. We have identified serum microRNA (miRNA) signatures that indicate long-term impact of total body irradiation (TBI) in mice when measured within 24 hours of exposure. Impact of TBI on the hematopoietic system was systematically assessed to determine a correlation of residual hematopoietic stem cells (HSCs) with increasing doses of radiation. Serum miRNA signatures distinguished untreated mice from animals exposed to radiation and correlated with the impact of radiation on HSCs. Mice exposed to sublethal (6.5 Gy) and lethal (8 Gy) doses of radiation were indistinguishable for 3 to 4 weeks after exposure. A serum miRNA signature detectable 24 hours after radiation exposure consistently segregated these two cohorts. Furthermore, using either a radioprotective agent before, or radiation mitigation after, lethal radiation, we determined that the serum miRNA signature correlated with the impact of radiation on animal health rather than the radiation dose. Last, using humanized mice that had been engrafted with human CD34(+) HSCs, we determined that the serum miRNA signature indicated radiation-induced injury to the human bone marrow cells. Our data suggest that serum miRNAs can serve as functional dosimeters of radiation, representing a potential breakthrough in early assessment of radiation-induced hematopoietic damage and timely use of medical countermeasures to mitigate the long-term impact of radiation. C1 [Acharya, Sanket S.; Watson, Jacqueline; Hamilton, Abigail; Pan, Yunfeng; Gaudiano, Emily; Parmar, Kalindi; Chowdhury, Dipanjan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Fendler, Wojciech] Med Univ Lodz, Dept Pediat Oncol Hematol & Diabetol, PL-91738 Lodz, Poland. [Moskwa, Patryk] Med Univ Greifswald, Dept Internal Med A, D-17475 Greifswald, Germany. [Bhanja, Payel; Saha, Subhrajit; Guha, Chandan] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Radiat Oncol, Bronx, NY 10461 USA. [Guha, Chandan] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Pathol, Bronx, NY 10461 USA. RP Chowdhury, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. EM dipanjan_chowdhury@dfci.harvard.edu RI Fendler, Wojciech/S-9592-2016 OI Fendler, Wojciech/0000-0002-5083-9168 FU National Institute of Allergy and Infectious Diseases [R01 AI101897-01]; Basic Scholar Grant (American Cancer Society); Ann-Fuller Foundation; Mary Kay Foundation; National Science Center of Poland [2012/05/E/NZ5/02130]; INTER program of the Foundation for Polish Science; Leukemia & Lymphoma Society Scholar Grant; [1U19AI091175-05] FX D.C. is supported by R01 AI101897-01 (National Institute of Allergy and Infectious Diseases), Basic Scholar Grant (American Cancer Society), Leukemia & Lymphoma Society Scholar Grant, Ann-Fuller Foundation, and Mary Kay Foundation. C.G. is supported by 1U19AI091175-05. W.F. is funded by the National Science Center of Poland (grant number 2012/05/E/NZ5/02130) and the INTER program of the Foundation for Polish Science. NR 37 TC 6 Z9 8 U1 0 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAY 13 PY 2015 VL 7 IS 287 AR 287ra69 DI 10.1126/scitranslmed.aaa6593 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CI0NM UT WOS:000354433900003 PM 25972001 ER PT J AU Vassy, JL Korf, BR Green, RC AF Vassy, Jason L. Korf, Bruce R. Green, Robert C. TI How to know when physicians are ready for genomic medicine SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material ID COMPETENCES; EDUCATION C1 [Vassy, Jason L.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA 02130 USA. [Vassy, Jason L.] Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Vassy, Jason L.; Green, Robert C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Korf, Bruce R.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35233 USA. [Green, Robert C.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. RP Vassy, JL (reprint author), VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA 02130 USA. EM jvassy@partners.org FU NCATS NIH HHS [KL2 TR001100]; NHGRI NIH HHS [R01 HG005092, U01 HG006500]; NICHD NIH HHS [U19 HD077671]; NIDDK NIH HHS [L30 DK089597] NR 10 TC 8 Z9 8 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAY 13 PY 2015 VL 7 IS 287 AR 287fs19 DI 10.1126/scitranslmed.aaa2401 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CI0NM UT WOS:000354433900012 PM 25971999 ER PT J AU Gori, F Lerner, U Ohlsson, C Baron, R AF Gori, Francesca Lerner, Ulf Ohlsson, Claes Baron, Roland TI A new WNT on the bone: WNT16, cortical bone thickness, porosity and fractures SO BONEKEY REPORTS LA English DT Review ID GENOME-WIDE ASSOCIATION; RECEPTOR-RELATED PROTEIN-5; HEMATOPOIETIC STEM-CELLS; MINERAL DENSITY; OSTEOPOROTIC FRACTURES; POSTMENOPAUSAL WOMEN; CATENIN; GENE; PATHWAY; DISEASE AB The last decade has provided abundant data implicating the WNT pathway in bone development and in the regulation of skeletal homeostasis. Rare human mutations together with gain-and loss-of-function approaches in mice have clearly demonstrated that disrupted regulation of this pathway leads to altered bone mass. In addition to these rare human and mice mutations, large population-based genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms in similar to 60 loci strongly associated with variations in bone mineral density (BMD) at different skeletal sites. Among the loci/genes identified by BMD GWAS, components of the WNT signaling pathway are numerous and have been shown to contribute to skeletal development and homeostasis. Within the components of WNT signaling, the gene coding for WNT16, one of the 19 WNT ligands of the human genome, has been found strongly associated with specific bone traits such as cortical bone thickness, cortical porosity and fracture risk. Recently, the first functional characterization of Wnt16 has confirmed the critical role of Wnt16 in the regulation of cortical bone mass and bone strength in mice. These reports have extended our understanding of Wnt16 function in bone homeostasis and have not only confirmed the unique association of Wnt16 with cortical bone and fracture susceptibility, as suggested by GWAS in human populations, but have also provided novel insights into the biology of this WNT ligand and the mechanism(s) by which it regulates cortical but not trabecular bone homeostasis. Most interestingly, Wnt16 appears to be a strong anti-resorptive soluble factor acting on both osteoblasts and osteoclast precursors. C1 [Gori, Francesca; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. [Lerner, Ulf; Ohlsson, Claes] Univ Gothenburg, Inst Med, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Gothenburg, Sweden. [Lerner, Ulf] Umea Univ, Mol Periodontol, Umea, Sweden. [Baron, Roland] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA USA. RP Gori, F (reprint author), Harvard Univ, Sch Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. EM francesca_gori@hsdm.harvard.edu FU NIAMS NIH HHS [R01 AR064724] NR 50 TC 2 Z9 2 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2047-6396 J9 BONEKEY REP JI BoneKEy Rep. PD MAY 13 PY 2015 VL 4 AR 669 DI 10.1038/bonekey.2015.36 PG 6 WC Orthopedics SC Orthopedics GA DL5PR UT WOS:000375689700001 PM 25987984 ER PT J AU Vinegoni, C Lee, S Aguirre, AD Weissleder, R AF Vinegoni, Claudio Lee, Sungon Aguirre, Aaron D. Weissleder, Ralph TI New techniques for motion-artifact-free in vivo cardiac microscopy SO FRONTIERS IN PHYSIOLOGY LA English DT Review DE cardiac imaging; motion artifacts; laser scanning microscopy; motion compensation; image stabilization ID INTRAVITAL MICROSCOPY; IMAGING WINDOW; BEATING HEART; RESOLUTION; MONOCYTES; CHAMBER AB Intravital imaging microscopy (i.e., imaging in live animals at microscopic resolution) has become an indispensable tool for studying the cellular micro-dynamics in cancer, immunology and neurobiology. High spatial and temporal resolution, combined with large penetration depth and multi-reporter visualization capability make fluorescence intravital microscopy compelling for heart imaging. However, tissue motion caused by cardiac contraction and respiration critically limits its use. As a result, in vitro cell preparations or non-contracting explanted heart models are more commonly employed. Unfortunately, these approaches fall short of understanding the more complex host physiology that may be dynamic and occur over longer periods of time. In this review, we report on novel technologies, which have been recently developed by our group and others, aimed at overcoming motion-induced artifacts and capable of providing in vivo subcellular resolution imaging in the beating mouse heart. The methods are based on mechanical stabilization, image processing algorithms, gated/triggered acquisition schemes or a combination of both. We expect that in the immediate future all these methodologies will have considerable applications in expanding our understanding of the cardiac biology, elucidating cardiomyocyte function and interactions within the organism in vivo, and ultimately improving the treatment of cardiac diseases. C1 [Vinegoni, Claudio; Lee, Sungon; Aguirre, Aaron D.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Vinegoni, Claudio; Lee, Sungon; Aguirre, Aaron D.; Weissleder, Ralph] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Sungon] Hanyang Univ, Sch Elect Engn, Ansan, South Korea. RP Vinegoni, C (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM cvinegoni@mgh.harvard.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services [HHSN268201000044C]; Institute of Biomedical Engineering [R0 1EB006432, R01 HL122208]; American Heart Association [14FTF20380185]; National Research Foundation of Korea - Korean Government (MSIP) [2012M3A6A3055694] FX This project was funded in part by Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (under Contract No. HHSN268201000044C), and from the Institute of Biomedical Engineering (under R0 1EB006432 and under Contract No. R01 HL122208). This work was also supported in part by the American Heart Association (14FTF20380185) and by the National Research Foundation of Korea funded by the Korean Government (MSIP) 2012M3A6A3055694. NR 29 TC 4 Z9 4 U1 3 U2 7 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PD MAY 12 PY 2015 VL 6 AR 147 DI 10.3389/fphys.2015.00147 PG 12 WC Physiology SC Physiology GA CM3NE UT WOS:000357588300002 PM 26029116 ER PT J AU Wang, HZ Sang, NL Zhang, C Raghupathi, R Tanzi, RE Saunders, A AF Wang, Haizhi Sang, Nianli Zhang, Can Raghupathi, Ramesh Tanzi, Rudolph E. Saunders, Aleister TI Cathepsin L Mediates the Degradation of Novel APP C-Terminal Fragments SO BIOCHEMISTRY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; GAMMA-SECRETASE; PROTEASOME INHIBITION; TRANSMEMBRANE DOMAIN; BONE-RESORPTION; IN-VIVO; BETA; CALPAIN; CLEAVAGE AB Alzheimer's disease (AD) is characterized by the deposition of amyloid beta (A beta), a peptide generated from proteolytic processing of its precursor, amyloid precursor protein (APP). Canonical APP proteolysis occurs via alpha-, beta-, and gamma-secretases. APP is also actively degraded by protein degradation systems. By pharmacologically inhibiting protein degradation with ALLN, we observed an accumulation of several novel APP C-terminal fragments (CTFs). The two major novel CTFs migrated around 15 and 25 kDa and can be observed across multiple cell types. The process was independent of cytotoxicity or protein synthesis. We further determine that the accumulation of the novel CTFs is not mediated by proteasome or calpain inhibition, but by cathepsin L inhibition. Moreover, these novel CTFs are not generated by an increased amount of BACE. Here, we name the CTF of 25 kDa as eta-CTF (eta-CTF). Our data suggest that under physiological conditions, a subset of APP undergoes alternative processing and the intermediate products, the 15 kDa CTFs, and the eta-CTFs aret rapidly degraded and/or processed via the protein degradation machinery, specifically, cathepsin L. C1 [Wang, Haizhi; Sang, Nianli; Saunders, Aleister] Drexel Univ, Coll Art & Sci, Dept Biol, Philadelphia, PA 19104 USA. [Wang, Haizhi; Raghupathi, Ramesh; Saunders, Aleister] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA. [Zhang, Can; Tanzi, Rudolph E.] Harvard Univ, Boston, MA 02114 USA. [Zhang, Can; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Saunders, Aleister] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19104 USA. RP Saunders, A (reprint author), 424 PISB 3245 Chestnut St, Philadelphia, PA 19104 USA. EM aleister.saunders@drexel.edu FU National Institutes of Health [R01 NS057295]; Drexel University; Commonwealth of Pennsylvania FX This study is supported by National Institutes of Health Grant R01 NS057295, Drexel University, and the Commonwealth of Pennsylvania. NR 53 TC 7 Z9 7 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 12 PY 2015 VL 54 IS 18 BP 2806 EP 2816 DI 10.1021/acs.biochem.5b00329 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI2LJ UT WOS:000354578800003 PM 25910068 ER PT J AU Lubitz, SA Yin, XY Rienstra, M Schnabel, RB Walkey, AJ Magnani, JW Rahman, F McManus, DD Tadros, TM Levy, D Vasan, RS Larson, MG Ellinor, PT Benjamin, EJ AF Lubitz, Steven A. Yin, Xiaoyan Rienstra, Michiel Schnabel, Renate B. Walkey, Allan J. Magnani, Jared W. Rahman, Faisal McManus, David D. Tadros, Thomas M. Levy, Daniel Vasan, Ramachandran S. Larson, Martin G. Ellinor, Patrick T. Benjamin, Emelia J. TI Long-Term Outcomes of Secondary Atrial Fibrillation in the Community The Framingham Heart Study SO CIRCULATION LA English DT Article DE atrial fibrillation; atrial flutter; epidemiology; heart failure; risk factors; stroke ID FOLLOW-UP; CARDIAC-SURGERY; MYOCARDIAL-INFARCTION; RISK SCORE; ONSET; POPULATION; FAILURE; STROKE; RECURRENCE; MANAGEMENT AB Background-Guidelines have proposed that atrial fibrillation (AF) can occur as an isolated event, particularly when precipitated by a secondary, or reversible, condition. However, knowledge of long-term AF outcomes after diagnosis during a secondary precipitant is limited. Methods and Results-In 1409 Framingham Heart Study participants with new-onset AF, we examined associations between first-detected AF episodes occurring with and without a secondary precipitant and both long-term AF recurrence and morbidity. We selected secondary precipitants based on guidelines (surgery, infection, acute myocardial infarction, thyrotoxicosis, acute alcohol consumption, acute pericardial disease, pulmonary embolism, or other acute pulmonary disease). Among 439 patients (31%) with AF diagnosed during a secondary precipitant, cardiothoracic surgery (n=131 [30%]), infection (n=102 [23%]), noncardiothoracic surgery (n=87 [20%]), and acute myocardial infarction (n=78 [18%]) were most common. AF recurred in 544 of 846 eligible individuals without permanent AF (5-, 10-, and 15-year recurrences of 42%, 56%, and 62% with versus 59%, 69%, and 71% without secondary precipitants; multivariable-adjusted hazard ratio, 0.65 [95% confidence interval, 0.54-0.78]). Stroke risk (n=209/1262 at risk; hazard ratio, 1.13 [95% confidence interval, 0.82-1.57]) and mortality (n=1098/1409 at risk; hazard ratio, 1.00 [95% confidence interval, 0.87-1.15]) were similar between those with and without secondary precipitants, although heart failure risk was reduced (n=294/1107 at risk; hazard ratio, 0.74 [95% confidence interval, 0.56-0.97]). Conclusions-AF recurs in most individuals, including those diagnosed with secondary precipitants. Long-term AF-related stroke and mortality risks were similar between individuals with and without secondary AF precipitants. Future studies may determine whether increased arrhythmia surveillance or adherence to general AF management principles in patients with reversible AF precipitants will reduce morbidity. C1 [Lubitz, Steven A.; Ellinor, Patrick T.] 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. [Yin, Xiaoyan; Magnani, Jared W.; Levy, Daniel; Vasan, Ramachandran S.; Larson, Martin G.; Benjamin, Emelia J.] Boston Univ, Framingham, MA USA. [Yin, Xiaoyan; Magnani, Jared W.; Levy, Daniel; Vasan, Ramachandran S.; Larson, Martin G.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 AB Groningen, Netherlands. [Schnabel, Renate B.] Univ Med Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, Hamburg, Germany. [Walkey, Allan J.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Framingham, MA USA. [Walkey, Allan J.] Boston Univ, Sch Med, Dept Med, Sect Pulm & Crit Care Med, Framingham, MA USA. [Magnani, Jared W.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Framingham, MA USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Framingham, MA USA. [Rahman, Faisal] Boston Univ, Med Ctr, Dept Med, Framingham, MA USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Tadros, Thomas M.] Sutter Med Grp, Sacramento, CA USA. [Levy, Daniel] NHLBI, Populat Sci Branch, Bethesda, MD 20892 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Framingham, MA USA. [Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Framingham, MA USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Framingham, MA USA. RP Lubitz, SA (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM slubitz@mgh.harvard.edu OI Walkey, Allan/0000-0003-4685-6894; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X FU National Institutes of Health [K23HL114724, N01-HC-25195, 6R01-NS17950, 2R01HL092577, 1R01 HL102214, R01HL104156, K24HL105780, 1U01HL105268-01, KL2RR031981, K01HL116768]; Doris Duke Charitable Foundation Clinical Scientist Development Award [2014105]; American Heart Association Established Investigator Award [13EIA14220013]; Netherlands Organization for Scientific Research (Veni grant) [016.136.055]; Department of Defense [W81XWH-12-FEST-IIA] FX This work was supported by National Institutes of Health grants K23HL114724 (to Dr Lubitz); N01-HC-25195, 6R01-NS17950, and 2R01HL092577 (to Drs Ellinor and Benjamin); 1R01 HL102214 (to Dr Benjamin), and R01HL104156 and K24HL105780 (to Dr Ellinor); a Doris Duke Charitable Foundation Clinical Scientist Development Award 2014105 (to Dr Lubitz); and an American Heart Association Established Investigator Award 13EIA14220013 (to Dr Ellinor). Dr Rienstra is supported by a grant from the Netherlands Organization for Scientific Research (Veni grant 016.136.055). Partial salary support is additionally provided by National Institutes of Health grants 1U01HL105268-01 and KL2RR031981 and Department of Defense grant W81XWH-12-FEST-IIA (to Dr McManus), as well as National Institutes of Health grant K01HL116768 (to Dr Walkey). NR 52 TC 8 Z9 9 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAY 12 PY 2015 VL 131 IS 19 BP 1648 EP U82 DI 10.1161/CIRCULATIONAHA.114.014058 PG 16 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CH7JT UT WOS:000354213000010 PM 25769640 ER PT J AU Sico, JJ Chang, CCH So-Armah, K Justice, AC Hylek, E Skanderson, M McGinnis, K Kuller, LH Kraemer, KL Rimland, D Goetz, MB Butt, AA Rodriguez-Barradas, MC Gibert, C Leaf, D Brown, ST Samet, J Kazis, L Bryant, K Freiberg, MS AF Sico, Jason J. Chang, Chung-Chou H. So-Armah, Kaku Justice, Amy C. Hylek, Elaine Skanderson, Melissa McGinnis, Kathleen Kuller, Lewis H. Kraemer, Kevin L. Rimland, David Goetz, Matthew Bidwell Butt, Adeel A. Rodriguez-Barradas, Maria C. Gibert, Cynthia Leaf, David Brown, Sheldon T. Samet, Jeffrey Kazis, Lewis Bryant, Kendall Freiberg, Matthew S. CA Vet Aging Cohort Study TI HIV status and the risk of ischemic stroke among men SO NEUROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; CEREBROVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; ADMINISTRATIVE DATA; INFECTED PATIENTS; HEPATITIS-C; CARE; VETERANS; AIDS; PREVENTION AB Objective:Given conflicting data regarding the association of HIV infection and ischemic stroke risk, we sought to determine whether HIV infection conferred an increased ischemic stroke risk among male veterans.Methods:The Veterans Aging Cohort Study-Virtual Cohort consists of HIV-infected and uninfected veterans in care matched (1:2) for age, sex, race/ethnicity, and clinical site. We analyzed data on 76,835 male participants in the Veterans Aging Cohort Study-Virtual Cohort who were free of baseline cardiovascular disease. We assessed demographics, ischemic stroke risk factors, comorbid diseases, substance use, HIV biomarkers, and incidence of ischemic stroke from October 1, 2003, to December 31, 2009.Results:During a median follow-up period of 5.9 (interquartile range 3.5-6.6) years, there were 910 stroke events (37.4% HIV-infected). Ischemic stroke rates per 1,000 person-years were higher for HIV-infected (2.79, 95% confidence interval 2.51-3.10) than for uninfected veterans (2.24 [2.06-2.43]) (incidence rate ratio 1.25 [1.09-1.43]; p < 0.01). After adjusting for demographics, ischemic stroke risk factors, comorbid diseases, and substance use, the risk of ischemic stroke was higher among male veterans with HIV infection compared with uninfected veterans (hazard ratio 1.17 [1.01-1.36]; p = 0.04).Conclusions:HIV infection is associated with an increased ischemic stroke risk among HIV-infected compared with demographically and behaviorally similar uninfected male veterans. C1 [Sico, Jason J.; Justice, Amy C.; Skanderson, Melissa; McGinnis, Kathleen] West Haven Vet Adm Med Ctr, VA Connecticut Hlth Care Syst, West Haven, CT 06516 USA. [Sico, Jason J.; So-Armah, Kaku; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. [Chang, Chung-Chou H.; Kraemer, Kevin L.; Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Chang, Chung-Chou H.; Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Hylek, Elaine] Boston Med Ctr, Boston, MA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Rimland, David] Atlanta Vet Adm Med Ctr, Atlanta, GA USA. [Goetz, Matthew Bidwell; Leaf, David] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Goetz, Matthew Bidwell; Leaf, David] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Butt, Adeel A.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Houston, TX 77030 USA. [Gibert, Cynthia] Washington DC Vet Adm Med Ctr, Washington, DC USA. [Gibert, Cynthia] George Washington Univ, Sch Med, Washington, DC USA. [Brown, Sheldon T.] James J Peters VA, Bronx, NY USA. [Brown, Sheldon T.] Mt Sinai Sch Med, New York, NY USA. [Samet, Jeffrey] Boston Univ, Sch Med, Boston, MA 02215 USA. [Kazis, Lewis] Boston Univ, Ctr Assessment Pharmaceut Practices, Dept Hlth Policy & Management, Sch Publ Hlth, Boston, MA 02215 USA. [Kazis, Lewis] Vet Adm Med Ctr, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Bryant, Kendall] NIAAA, Bethesda, MD USA. [Freiberg, Matthew S.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Freiberg, Matthew S.] Nashville Vet Affairs Med Ctr, Nashville, TN USA. RP Sico, JJ (reprint author), West Haven Vet Adm Med Ctr, VA Connecticut Hlth Care Syst, West Haven, CT 06516 USA. EM jason.sico@va.gov OI Butt, Adeel/0000-0002-1118-1826; Goetz, Matthew/0000-0003-4542-992X; Justice, Amy/0000-0003-0139-5502 FU NIH, National Institute on Alcohol Abuse and Alcoholism [5U10AA013566-10]; NIH, National Heart Lung and Blood Institute [R01 HL095136-05]; Department of Veteran Affairs Health Services Research and Development [11-262] FX Research funding was made possible by the NIH, National Institute on Alcohol Abuse and Alcoholism (grant 5U10AA013566-10); NIH, National Heart Lung and Blood Institute (grant R01 HL095136-05); and Department of Veteran Affairs Health Services Research and Development (grant 11-262). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veteran Affairs. No conflicts of interest are reported. NR 34 TC 24 Z9 24 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAY 12 PY 2015 VL 84 IS 19 BP 1933 EP 1940 DI 10.1212/WNL.0000000000001560 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CI2BY UT WOS:000354550900009 PM 25862803 ER PT J AU Rasool, N Prasad, S AF Rasool, Nailyn Prasad, Sashank TI Teaching NeuroImages: Upright-supine test to evaluate vertical diplopia SO NEUROLOGY LA English DT Editorial Material AB A 36-year-old woman presented with vertical diplopia, nausea, and disequilibrium. Maddox rod testing was performed in the upright and supine positions (figures 1 and 2). C1 [Rasool, Nailyn] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02163 USA. [Rasool, Nailyn; Prasad, Sashank] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Rasool, N (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02163 USA. EM nailyn.rasool@gmail.com NR 2 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAY 12 PY 2015 VL 84 IS 19 BP E153 EP E154 DI 10.1212/WNL.0000000000001569 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CI2BY UT WOS:000354550900003 PM 25964485 ER PT J AU March, MI Geahchan, C Wenger, J Raghuraman, N Berg, A Haddow, H Mckeon, BA Narcisse, R David, JL Scott, J Thadhani, R Karumanchi, SA Rana, S AF March, Melissa I. Geahchan, Carl Wenger, Julia Raghuraman, Nandini Berg, Anders Haddow, Hamish Mckeon, Bri Ann Narcisse, Rulx David, Jean Louis Scott, Jennifer Thadhani, Ravi Karumanchi, S. Ananth Rana, Sarosh TI Circulating Angiogenic Factors and the Risk of Adverse Outcomes among Haitian Women with Preeclampsia SO PLOS ONE LA English DT Article ID MATERNAL PLASMA-CONCENTRATIONS; PLACENTAL GROWTH-FACTOR; SUSPECTED PREECLAMPSIA; DEVELOP PREECLAMPSIA; SOLUBLE ENDOGLIN; HYPERTENSION; PREGNANCY; COUNTRIES AB Objective Angiogenic factors are strongly associated with adverse maternal and fetal outcomes among women with preterm preeclampsia (PE) in developed countries. We evaluated the role of angiogenic factors and their relationship to adverse outcomes among Haitian women with PE. Material and Methods We measured plasma antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) levels in women with PE (n=35) compared to controls with no hypertensive disorders (NHD) (n=43) among subjects with singleton pregnancies that delivered at Hospital Albert Schweitzer (HAS) in Haiti. We divided the preeclamptic women into two groups, early onset (similar to 34 weeks) and late onset (>34 weeks) and examined relationships between sFlt1/PlGF ratios on admission and adverse outcomes (abruption, respiratory complications, stroke, renal insufficiency, eclampsia, maternal death, birth weight <2500 grams, or fetal/neonatal death) in women with PE subgroups as compared to NHD groups separated by week of admission. Data are presented as median (25th-75th centile), n (%), and proportions. Results Among patients with PE, most (24/35) were admitted at term. Adverse outcome rates in PE were much higher among the early onset group compared to the late onset group (100.0% vs. 54.2%, P=0.007). Plasma angiogenic factors were dramatically altered in both subtypes of PE. Angiogenic factors also correlated with adverse outcomes in both subtypes of PE. The median sFlt1/PlGF ratios for subjects with early onset PE with any adverse outcome vs. NHD <=34 weeks with no adverse outcome were 703.1 (146.6, 1614.9) and 9.6 (3.5, 58.6); P<0.001). Among late onset group the median sFlt1/PlGF ratio for women with any adverse outcome was 130.7 (56.1, 242.6) versus 22.4 (10.2, 58.7; P=0.005) in NHD >34 weeks with no adverse outcome. Conclusion PE-related adverse outcomes are common in women in Haiti and are associated with profound angiogenic imbalance regardless of gestational age at presentation. C1 [March, Melissa I.; Raghuraman, Nandini; Mckeon, Bri Ann; Scott, Jennifer; Karumanchi, S. Ananth; Rana, Sarosh] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [March, Melissa I.; Karumanchi, S. Ananth; Rana, Sarosh] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02215 USA. [March, Melissa I.; Wenger, Julia; Berg, Anders; Thadhani, Ravi; Karumanchi, S. Ananth; Rana, Sarosh] Harvard Univ, Sch Med, Boston, MA USA. [Geahchan, Carl; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol & Res, Boston, MA 02215 USA. [Wenger, Julia; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Berg, Anders] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Haddow, Hamish] Savjani Inst Hlth Res, Windham, ME USA. [Narcisse, Rulx; David, Jean Louis] Hosp Albert Schweitzer, Dept Obstet & Gynecol, Deshapelles, Haiti. [Scott, Jennifer] Brigham & Womens Hosp, Dept Med, Div Womens Hlth, Boston, MA 02115 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. [Rana, Sarosh] Univ Chicago, Dept Obstet & Gynecol, Maternal Fetal Med, Chicago, IL 60637 USA. RP Rana, S (reprint author), Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. EM srana2@bsd.uchicago.edu FU Aggamin Therapeutics FX S.A.K. is a co-inventor on patents related to preeclampsia biomarkers and is a consultant to Siemens and has financial interest in Aggamin Therapeutics. R.T. has patents in preeclampsia prediction markers, is a consultant to Roche and has a financial interest in Aggamin Therapeutics. All other authors report no conflicts. S.A.K. is co-inventor on multiple patents (USPTO #7,740,849, #7,407,658, #7,335,362, #7,344,892) related to the use of angiogenic markers for the diagnosis, prediction and therapy of preeclampsia. R.T. is a co-inventor on a patent (USPTO #7,344,892) related to the use of angiogenic proteins for the prediction of preeclampsia. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. NR 25 TC 4 Z9 4 U1 2 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 12 PY 2015 VL 10 IS 5 AR e0126815 DI 10.1371/journal.pone.0126815 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CI1ZI UT WOS:000354543500080 PM 25965397 ER PT J AU Rashidian, M Keliher, EJ Bilate, AM Duarte, JN Wojtkiewicz, GR Jacobsen, JT Cragnolini, J Swee, LK Victora, GD Weissleder, R Ploegh, HL AF Rashidian, Mohammad Keliher, Edmund J. Bilate, Angelina M. Duarte, Joao N. Wojtkiewicz, Gregory R. Jacobsen, Johanne Tracey Cragnolini, Juanjo Swee, Lee Kim Victora, Gabriel D. Weissleder, Ralph Ploegh, Hidde L. TI Noninvasive imaging of immune responses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PET imaging; non-invasive imaging; inflammation; cancer; camelid single domain antibodies ID SORTASE-MEDIATED REACTIONS; ANTIBODY FRAGMENTS; MAGIC BULLET; F-18-FDG PET; T-CELLS; IN-VIVO; TUMOR; INFLAMMATION; CONJUGATION; COMPLEXES AB At their margins, tumors often contain neutrophils, dendritic cells, and activated macrophages, which express class II MHC and CD11b products. The interplay between stromal cells, tumor cells, and migratory cells such as lymphocytes creates opportunities for noninvasive imaging of immune responses. We developed alpaca-derived antibody fragments specific for mouse class II MHC and CD11b products, expressed on the surface of a variety of myeloid cells. We validated these reagents by flow cytometry and two-photon microscopy to obtain images at cellular resolution. To enable noninvasive imaging of the targeted cell populations, we developed a method to site-specifically label VHHs [the variable domain (V-H) of a camelid heavy-chain only antibody] with F-18 or Cu-64. Radiolabeled VHHs rapidly cleared the circulation (t(1/2) approximate to 20 min) and clearly visualized lymphoid organs. We used VHHs to explore the possibility of imaging inflammation in both xenogeneic and syngeneic tumor models, which resulted in detection of tumors with remarkable specificity. We also imaged the infiltration of myeloid cells upon injection of complete Freund's adjuvant. Both anti-class II MHC and anti-CD11b VHHs detected inflammation with excellent specificity. Given the ease of manufacture and labeling of VHHs, we believe that this method could transform the manner in which antitumor responses and/or infectious events may be tracked. C1 [Rashidian, Mohammad; Bilate, Angelina M.; Duarte, Joao N.; Jacobsen, Johanne Tracey; Cragnolini, Juanjo; Swee, Lee Kim; Victora, Gabriel D.; Ploegh, Hidde L.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Rashidian, Mohammad; Ploegh, Hidde L.] MIT, Dept Biol, Cambridge, MA 02142 USA. [Keliher, Edmund J.; Wojtkiewicz, Gregory R.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Keliher, Edmund J.; Weissleder, Ralph] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Jacobsen, Johanne Tracey] Univ Oslo, Oslo Univ Hosp, Ctr Immune Regulat, N-0372 Oslo, Norway. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Ploegh, HL (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM ploegh@wi.mit.edu FU Cancer Research Institute; Calouste Gulbenkian Foundation; Champalimaud Foundation; Portuguese Science and Technology Foundation; Portuguese Ministry of Health; NIH [R01-AI087879-06, DP1-GM106409-03, R01-GM100518-04]; Lustgarten Foundation FX M.R. is a Cancer Research Institute Irvington Fellow supported by the Cancer Research Institute, and J.N.D. is a Calouste Gulbenkian Scholar funded by the Calouste Gulbenkian Foundation, Champalimaud Foundation, Portuguese Science and Technology Foundation, and Portuguese Ministry of Health. This work was funded by NIH R01-AI087879-06 (to H.L.P.), DP1-GM106409-03 (an NIH Pioneer Award to H.L.P.), R01-GM100518-04 (to H.L.P.), and by the Lustgarten Foundation (H.L.P.). NR 36 TC 31 Z9 32 U1 4 U2 31 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 12 PY 2015 VL 112 IS 19 BP 6146 EP 6151 DI 10.1073/pnas.1502609112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH9XS UT WOS:000354390600077 PM 25902531 ER PT J AU Keskin, DB Reinhold, BR Zhang, GL Ivanov, AR Karger, BL Reinherz, EL AF Keskin, Derin B. Reinhold, Bruce R. Zhang, Guang Lan Ivanov, Alexander R. Karger, Barry L. Reinherz, Ellis L. TI Reply to van de Sandt and Rimmelzwaan: Matching epitope display with functional avidity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID INFLUENZA-A VIRUS; RESPONSES C1 [Keskin, Derin B.; Reinhold, Bruce R.; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med Oncol, Immunobiol Lab, Boston, MA 02115 USA. [Keskin, Derin B.; Reinhold, Bruce R.; Zhang, Guang Lan; Reinherz, Ellis L.] Harvard Univ, Sch Med, Canc Vaccine Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. [Keskin, Derin B.; Reinhold, Bruce R.; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Zhang, Guang Lan] Boston Univ, Dept Comp Sci, Metropolitan Coll, Boston, MA 02115 USA. [Ivanov, Alexander R.; Karger, Barry L.] Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Immunobiol Lab, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu NR 6 TC 3 Z9 3 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 12 PY 2015 VL 112 IS 19 BP E2418 EP E2418 DI 10.1073/pnas.1503931112 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH9XS UT WOS:000354390600006 PM 25848066 ER PT J AU Harkins, K Sankar, P Sperling, R Grill, JD Green, RC Johnson, KA Healy, M Karlawish, J AF Harkins, Kristin Sankar, Pamela Sperling, Reisa Grill, Joshua D. Green, Robert C. Johnson, Keith A. Healy, Megan Karlawish, Jason TI Development of a process to disclose amyloid imaging results to cognitively normal older adult research participants SO ALZHEIMERS RESEARCH & THERAPY LA English DT Article ID ALZHEIMERS-DISEASE; APOE GENOTYPE; RISK; SCALE; MODEL AB Introduction: The objective of this study was to develop a process to maximize the safety and effectiveness of disclosing Positron Emission Tomography (PET) amyloid imaging results to cognitively normal older adults participating in Alzheimer's disease secondary prevention studies such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Study. Methods: Using a modified Delphi Method to develop consensus on best practices, we gathered and analyzed data over three rounds from experts in two relevant fields: informed consent for genetic testing or human amyloid imaging. Results: Experts reached consensus on (1) text for a brochure that describes amyloid imaging to a person who is considering whether to undergo such imaging in the context of a clinical trial, and (2) a process for amyloid PET result disclosure within such trials. Recommendations included: During consent, potential participants should complete an educational session, where they receive verbal and written information covering what is known and unknown about amyloid imaging, including possible results and their meaning, implications of results for risk of future cognitive decline, and information about Alzheimer's and risk factors. Participants should be screened for anxiety and depression to determine suitability to receive amyloid imaging information. The person conducting the sessions should check comprehension and be skilled in communication and recognizing distress. Imaging should occur on a separate day from consent, and disclosure on a separate day from imaging. Disclosure should occur in person, with time for questions. At disclosure, investigators should assess mood and willingness to receive results, and provide a written results report. Telephone follow-up within a few days should assess the impact of disclosure, and periodic scheduled assessments of depression and anxiety, with additional monitoring and follow-up for participants showing distress, should be performed. Conclusions: We developed a document for use with potential study participants to describe the process of amyloid imaging and the implications of amyloid imaging results; and a disclosure process with attention to ongoing monitoring of both mood and safety to receive this information. This document and process will be used in the A4 Study and can be adapted for other research settings. C1 [Harkins, Kristin; Healy, Megan] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Sankar, Pamela] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Sperling, Reisa] Harvard Univ, Massachusetts Gen Hosp, Brigham & Womens Hosp Massachusetts ADRC, Dept Neurol,Ctr Alzheimer Res & Treatment,Sch Med, Boston, MA USA. [Grill, Joshua D.] Univ Calif Los Angeles, Mary S Easton Ctr Alzheimers Dis Res, Los Angeles, CA USA. [Green, Robert C.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Green, Robert C.] Harvard Univ, Sch Med, Boston, MA USA. [Johnson, Keith A.] Harvard Univ, Brigham & Womens Hosp Massachusetts ADRC, Massachusetts Gen Hosp, Dept Neurol,Ctr Alzheimer Res & Treatment,Sch Med, Boston, MA USA. [Johnson, Keith A.] Harvard Univ, Brigham & Womens Hosp Massachusetts ADRC, Massachusetts Gen Hosp, Dept Radiol,Ctr Alzheimer Res & Treatment,Sch Med, Boston, MA USA. [Karlawish, Jason] Univ Penn, Penn Neurodegenerat Dis Eth & Policy Program, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Karlawish, Jason] Univ Penn, Penn Neurodegenerat Dis Eth & Policy Program, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. RP Karlawish, J (reprint author), Univ Penn, Penn Neurodegenerat Dis Eth & Policy Program, Perelman Sch Med, Dept Med, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM jason.karlawish@uphs.upenn.edu FU Alzheimer's Disease Cooperative Studies (ADCS); Penn Neurodegenerative Disease Ethics and Policy Program; NIA [P30-AG-10124] FX The authors thank Jeffrey Burns, MD, MS, Professor of Neurology at the University of Kansas Medical Center for review of the study guide and sharing language for describing amyloid imaging to cognitively normal older adults. Funding was provided by Alzheimer's Disease Cooperative Studies (ADCS), Penn Neurodegenerative Disease Ethics and Policy Program, and NIA P30-AG-10124. NR 26 TC 5 Z9 5 U1 2 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PD MAY 12 PY 2015 VL 7 AR 26 DI 10.1186/s13195-015-0112-7 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CH7UK UT WOS:000354241900001 PM 25969699 ER PT J AU Singh, JA Akhras, KS Shiozawa, A AF Singh, Jasvinder A. Akhras, Kasem S. Shiozawa, Aki TI Comparative effectiveness of urate lowering with febuxostat versus allopurinol in gout: analyses from large US managed care cohort SO ARTHRITIS RESEARCH & THERAPY LA English DT Article DE Gout; Comparative effectiveness; Serum urate; Febuxostat; Allopurinol ID QUALITY-OF-LIFE; SERUM URATE; HEALTH; COMORBIDITIES; HYPERURICEMIA; RISK; POPULATION; PREVALENCE; ARTHRITIS; DISEASE AB Introduction: To assess the comparative effectiveness of febuxostat and allopurinol in reducing serum urate (sUA) levels in a real-world U.S. managed care setting. Methods: This retrospective study utilized 2009 to 2012 medical and pharmacy claims and laboratory data from a large U.S. commercial and Medicare Advantage health plan. Study patients had at least one medical claim with a diagnosis of gout, at least one filled prescription for febuxostat or allopurinol and at least one sUA measurement post-index prescription. Reduction in sUA was examined using propensity score-matched cohorts, matched on patient demographics (gender, age), baseline sUA, comorbidities, geographic region and insurance type. Results: The study sample included 2,015 patients taking febuxostat and 14,025 taking allopurinol. At baseline, febuxostat users had a higher Quan-Charlson comorbidity score (0.78 vs. 0.53; P < 0.001), but similar age and gender distribution. Mean (standard deviation (SD)) sUA level following propensity score matching among treatment-naive febuxostat vs. allopurinol users (n = 873 each) were: pre-index sUA, 8.86 (SD, 1.79) vs. 8.72 (SD, 1.63; P = 0.20); and post-index sUA, 6.53 (SD, 2.01) vs. 6.71 (SD, 1.70; P = 0.04), respectively. A higher proportion of febuxostat users attained sUA goals of < 6.0 mg/dl (56.9% vs. 44.8%; P < 0.001) and < 5.0 mg/dl (35.5% vs. 19.2%; P < 0.001), respectively. Time to achieve sUA goals of < 6.0 mg/dl (346 vs. 397 days; P < 0.001) and < 5.0 mg/dl was shorter in febuxostat vs. allopurinol users (431 vs. 478 days; P < 0.001), respectively. Similar observations were made for overall propensity score-matched cohorts that included both treatment-naive and current users (n = 1,932 each). Conclusions: Febuxostat was more effective than allopurinol at the currently used doses (40 mg/day for febuxostat in 83% users and 300 mg/day or lower for allopurinol in 97% users) in lowering sUA in gout patients as demonstrated by post-index mean sUA level, the likelihood of and the time to achieving sUA goals. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN 55905 USA. [Akhras, Kasem S.; Shiozawa, Aki] Takeda Pharmaceut Int Inc, Deerfield, IL 60015 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, 700 South 19th St, Birmingham, AL 35233 USA. EM jassingh@uab.edu RI Shiozawa, Aki/O-2443-2014 OI Shiozawa, Aki/0000-0001-9757-6337 FU Takeda Pharmaceuticals International Inc.; 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]; VA Medical Center at Birmingham, Alabama, USA FX This study was funded by Takeda Pharmaceuticals International Inc. 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, and National Cancer Institute (NCI) U10 CA149950, and research contract CE-1304-6631 from Patient-Centered Outcomes Research Institute (PCORI). JAS is also supported by the resources and the use of facilities at the VA Medical Center at Birmingham, Alabama, USA. The views expressed in this manuscript 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 37 TC 10 Z9 10 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PD MAY 12 PY 2015 VL 17 AR 120 DI 10.1186/s13075-015-0624-3 PG 12 WC Rheumatology SC Rheumatology GA CH6QV UT WOS:000354162000001 PM 25963969 ER PT J AU Damschroder, LJ Moin, T Datta, SK Reardon, CM Steinle, N Weinreb, J Billington, CJ Maciejewski, ML Yancy, WS Hughes, M Makki, F Richardson, CR AF Damschroder, Laura J. Moin, Tannaz Datta, Santanu K. Reardon, Caitlin M. Steinle, Nanette Weinreb, Jane Billington, Charles J. Maciejewski, Matt L. Yancy, William S., Jr. Hughes, Maria Makki, Fatima Richardson, Caroline R. TI Implementation and evaluation of the VA DPP clinical demonstration: protocol for a multi-site non-randomized hybrid effectiveness-implementation type III trial SO IMPLEMENTATION SCIENCE LA English DT Article DE Diabetes prevention; Implementation; Veterans; Pragmatic study design ID DIABETES PREVENTION PROGRAM; IMPAIRED GLUCOSE-TOLERANCE; CONSENSUAL QUALITATIVE RESEARCH; LIFE-STYLE INTERVENTION; BUDGET IMPACT ANALYSIS; FOLLOW-UP; WEIGHT-LOSS; VETERANS; OBESITY; COMMUNITY AB Background: The Diabetes Prevention Program (DPP) study showed that lifestyle intervention resulted in a 58% reduction in incidence of type 2 diabetes among individuals with prediabetes. Additional large randomized controlled trials have confirmed these results, and long-term follow-up has shown sustained benefit 10-20 years after the interventions ended. Diabetes is a common and costly disease, especially among Veterans, and despite strong evidence supporting the feasibility of type 2 diabetes prevention, the DPP has not been widely implemented. The first aim of this study will evaluate implementation of the Veterans Affairs (VA) DPP in three VA medical centers. The second aim will assess weight and hemoglobin A1c (A1c) outcomes, and the third aim will determine the cost-effectiveness and budget impact of implementation of the VA DPP from a health system perspective. Methods/Design: This partnered multi-site non-randomized systematic assignment study will use a highly pragmatic hybrid effectiveness-implementation type III mixed methods study design. The implementation and administration of the VA DPP will be funded by clinical operations while the evaluation of the VA DPP will be funded by research grants. Seven hundred twenty eligible Veterans will be systematically assigned to the VA DPP clinical demonstration or the usual care VA MOVE!(R) weight management program. A multi-phase formative evaluation of the VA DPP implementation will be conducted. A theoretical program change model will be used to guide the implementation process and assess applicability and feasibility of the DPP for VA. The Consolidated Framework for Implementation Research (CFIR) will be used to guide qualitative data collection, analysis, and interpretation of barriers and facilitators to implementation. The RE-AIM framework will be used to assess Reach, Effectiveness, Adoption, Implementation, and Maintenance of the VA DPP. Twelve-month weight and A1c change will be evaluated for the VA DPP compared to the VA MOVE! program. Mediation analyses will be conducted to identify whether program design differences impact outcomes. Discussion: Findings from this pragmatic evaluation will be highly applicable to practitioners who are tasked with implementing the DPP in clinical settings. In addition, findings will determine the effectiveness and cost-effectiveness of the VA DPP in the Veteran population. C1 [Damschroder, Laura J.; Reardon, Caitlin M.; Hughes, Maria; Makki, Fatima; Richardson, Caroline R.] Ann Arbor VA Ctr Clin Management Res, Ann Arbor, MI 48113 USA. [Damschroder, Laura J.; Richardson, Caroline R.] VA Diabet QUERI, Ann Arbor, MI USA. [Moin, Tannaz; Weinreb, Jane] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Moin, Tannaz; Weinreb, Jane] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Moin, Tannaz] Greater Los Angeles VA Hlth Serv Res & Dev HSR &, Ctr Healthcare Innovat Implementat & Policy, Los Angeles, CA USA. [Datta, Santanu K.; Maciejewski, Matt L.; Yancy, William S., Jr.] Durham VA Med Ctr, Durham, NC USA. [Datta, Santanu K.; Maciejewski, Matt L.; Yancy, William S., Jr.] Duke Univ, Sch Med, Durham, NC USA. [Steinle, Nanette] Baltimore VA Med Ctr, Baltimore, MD USA. [Steinle, Nanette] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Billington, Charles J.] Minneapolis VA Healthcare Syst, Minneapolis, MN USA. [Billington, Charles J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Richardson, Caroline R.] Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA. RP Damschroder, LJ (reprint author), Ann Arbor VA Ctr Clin Management Res, POB 130170, Ann Arbor, MI 48113 USA. EM laura.damschroder@va.gov OI Damschroder, Laura/0000-0002-3657-8459 FU Veteran Affairs (VA) Quality Enhancement Research Initiative (QUERI) program [RRP 12-440, SDP 12-549, XVA 41-048]; VA Office of Academic Affiliations through the VA Health Services Research and Development Advanced Fellowship Program [TPM65-010]; VA Greater Los Angeles FX This work was funded by the Veteran Affairs (VA) Quality Enhancement Research Initiative (QUERI) program through two research grants (RRP 12-440 and SDP 12-549) and clinical quality improvement funding (XVA 41-048). Dr. Moin received support from the VA Office of Academic Affiliations through the VA Health Services Research and Development Advanced Fellowship Program (TPM65-010), VA Greater Los Angeles, from 2011-2014. We want to thank our partners at NCP, led by Dr. Linda Kinsinger, without whom this complex multi-component study could not have happened. NR 46 TC 4 Z9 4 U1 2 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD MAY 12 PY 2015 VL 10 AR UNSP 68 DI 10.1186/s13012-015-0250-0 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CH7RF UT WOS:000354233600001 PM 25962598 ER PT J AU Fisichella, PM AF Fisichella, P. Marco TI Hoarseness and Laryngopharyngeal Reflux SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID GASTROESOPHAGEAL-REFLUX AB IMPORTANCE Current approaches to the diagnosis and subsequent management of specific voice disorders vary widely among primary care physicians (PCPs). In addition, sparse literature describes current primary care practice patterns concerning empirical treatment for vocal disorders. OBJECTIVE To examine how PCPs manage patients with dysphonia, especially with regard to laryngopharyngeal reflux. DESIGN, SETTING, AND PARTICIPANTS Prospective, questionnaire-based study by an academic laryngology practice among academic PCPs from all major US geographic regions. MAIN OUTCOMES AND MEASURES A 16-question web-based survey, distributed via e-mail, concerning management and possible empirical treatment options for patients with dysphonia. RESULTS Of 2441 physicians who received the e-mail broadcast, 314 (12.9%) completed the survey. Among those who completed the survey, 46.3% were family practitioners, 46.5% were trained in internal medicine, and 7.2% identified as specialists. Among all respondents, 64.0% preferred to treat rather than immediately refer a patient with chronic hoarseness (symptoms persisting for > 6 weeks) of unclear origin. Reflux medication (85.8%) and antihistamines (54.2%) were the most commonly selected choices for empirical treatment. Most physician respondents (79.2%) reported that they would treat chronic hoarseness with reflux medication in a patient without evidence of gastroesophageal reflux disease. CONCLUSIONS AND RELEVANCE Most PCPs who responded to our survey report empirically treating patients with chronic hoarseness of unknown origin. Many physician respondents were willing to empirically prescribe reflux medication as primary therapy, even when symptoms of gastroesophageal reflux disease were not present. These data suggest that PCPs strongly consider reflux a common cause of dysphonia and may empirically treat patients having dysphonia with reflux medication before referral. C1 [Fisichella, P. Marco] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston VA Healthcare Syst, Boston, MA 02115 USA. RP Fisichella, PM (reprint author), Harvard Univ, Sch Med, Boston VA Healthcare Syst, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM piero.fisichella@va.gov NR 8 TC 2 Z9 3 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 12 PY 2015 VL 313 IS 18 BP 1853 EP 1854 DI 10.1001/jamaoto.2013.6533 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CH9XW UT WOS:000354391000029 PM 25965234 ER PT J AU Patel, MS Asch, DA Volpp, KG AF Patel, Mitesh S. Asch, David A. Volpp, Kevin G. TI Use of Wearable Monitoring Devices to Change Health Behavior Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID INCENTIVES; TRIAL C1 [Patel, Mitesh S.; Asch, David A.; Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Patel, MS (reprint author), Univ Penn, 423 Guardian Dr, Philadelphia, PA 19104 USA. EM mpatel@upenn.edu NR 4 TC 1 Z9 1 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 12 PY 2015 VL 313 IS 18 BP 1865 EP 1866 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CH9XW UT WOS:000354391000038 PM 25965243 ER PT J AU Joynt, KE Bhatt, DL Schwamm, LH Xian, Y Heidenreich, PA Fonarow, GC Smith, EE Neely, ML Grau-Sepulveda, MV Hernandez, AF AF Joynt, Karen E. Bhatt, Deepak L. Schwamm, Lee H. Xian, Ying Heidenreich, Paul A. Fonarow, Gregg C. Smith, Eric E. Neely, Megan L. Grau-Sepulveda, Maria V. Hernandez, Adrian F. TI Lack of Impact of Electronic Health Records on Quality of Care and Outcomes for Ischemic Stroke SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE hospital mortality; length of stay; medical order entry systems; outcome assessment (health care); registries ID GUIDELINES-STROKE; ORDER ENTRY; COMPUTERIZED REMINDERS; MORTALITY; ASSOCIATION; HOSPITALS; PROVIDERS; COMMON AB BACKGROUND Electronic health records (EHRs) may be key tools for improving the quality of health care, particularly for conditions for which guidelines are rapidly evolving and timely care is critical, such as ischemic stroke. OBJECTIVES The goal of this study was to determine whether hospitals with EHRs differed on quality or outcome measures for ischemic stroke from those without EHRs. METHODS We studied 626,473 patients from 1,236 U.S. hospitals in Get With the Guidelines-Stroke (GWTG-Stroke) from 2007 through 2010, linked with the American Hospital Association annual survey to determine the presence of EHRs. We conducted patient-level logistic regression analyses for each of the outcomes of interest. RESULTS A total of 511 hospitals had EHRs by the end of the study period. Hospitals with EHRs were larger and were more often teaching hospitals and stroke centers. After controlling for patient and hospital characteristics, patients admitted to hospitals with EHRs had similar odds of receiving "all-or-none" care (odds ratio [OR]: 1.03; 95% CI: 0.99 to 1.06; p = 0.12), of discharge home (OR: 1.02; 95% CI: 0.99 to 1.04; p = 0.15), and of in-hospital mortality (OR: 1.01; 95% CI: 0.96 to 1.05; p = 0.82). The odds of having a length of stay >4 days was slightly lower at hospitals with EHRs (OR: 0.97; 95% CI: 0.95 to 0.99; p = 0.01). CONCLUSIONS In our sample of GWTG-Stroke hospitals, EHRs were not associated with higher-quality care or better clinical outcomes for stroke care. Although EHRs may be necessary for an increasingly high-tech, transparent healthcare system, as currently implemented, they do not appear to be sufficient to improve outcomes for this important disease. (C) 2015 by the American College of Cardiology Foundation. C1 [Joynt, Karen E.; Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Joynt, Karen E.; Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Joynt, Karen E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Xian, Ying; Neely, Megan L.; Grau-Sepulveda, Maria V.; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA. [Heidenreich, Paul A.] Palo Alto Vet Affairs Hosp, Palo Alto, CA USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. RP Joynt, KE (reprint author), Brigham & Womens Hosp, Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM kjoynt@partners.org RI 刘, 李陆/H-8469-2015; Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU Boehringer Ingelheim; Merck; Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership; Janssen Pharmaceuticals; American Heart Association Pharmaceutical Roundtable; Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Forest Laboratories; Ischemix; Medtronic; Pfizer; Roche; Sanofi; Medicines Company; Portola Pharmaceuticals; Novartis FX The Get With the Guidelines-Stroke (GWTG-Stroke) program is provided by the American Heart Association/American Stroke Association. GWTG-Stroke was previously funded through support from Boehringer Ingelheim, Merck, Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership, Janssen Pharmaceuticals, and the American Heart Association Pharmaceutical Roundtable. The funders and former funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Dr. Bhatt has served on advisory boards for Cardax and Regado Biosciences; and has received research funding from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company. Dr. Hernandez has received grant funding from Bristol-Myers Squibb, Janssen Pharmaceuticals, Portola Pharmaceuticals, Medtronic, Novartis, and The Medicines Company; and has received honoraria from AstraZeneca, Bristol-Myers Squibb, Janssen Pharmaceuticals, Novartis, and Gilead. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. William Weintraub, MD, served as Guest Editor for this paper. NR 21 TC 3 Z9 3 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 12 PY 2015 VL 65 IS 18 BP 1964 EP 1972 DI 10.1016/j.jacc.2015.02.059 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CH4GD UT WOS:000353991000009 PM 25953748 ER PT J AU Golberg, A Khan, S Belov, V Quinn, KP Albadawi, H Broelsch, GF Watkins, MT Georgakoudi, I Papisov, M Mihm, MC Austen, WG Yarmush, ML AF Golberg, Alexander Khan, Saiqa Belov, Vasily Quinn, Kyle P. Albadawi, Hassan Broelsch, G. Felix Watkins, Michael T. Georgakoudi, Irene Papisov, Mikhail Mihm, Martin C., Jr. Austen, William G., Jr. Yarmush, Martin L. TI Skin Rejuvenation with Non-Invasive Pulsed Electric Fields SO SCIENTIFIC REPORTS LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HEALTHY-ADULTS; STEM-CELLS; I COLLAGEN; ELECTROPORATION; ANGIOGENESIS; DELIVERY; VASOCONSTRICTION; PROLIFERATION; KERATINOCYTES AB Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases. C1 [Golberg, Alexander; Yarmush, Martin L.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Ctr Engn Med, Boston, MA 02114 USA. [Golberg, Alexander; Belov, Vasily; Papisov, Mikhail; Yarmush, Martin L.] Shriners Burns Hosp, Boston, MA 02114 USA. [Golberg, Alexander] Tel Aviv Univ, Porter Sch Environm Studies, IL-69978 Tel Aviv, Israel. [Khan, Saiqa; Broelsch, G. Felix; Austen, William G., Jr.] Harvard Univ, Sch Med, Div Plast & Reconstruct Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Belov, Vasily; Papisov, Mikhail] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Quinn, Kyle P.; Georgakoudi, Irene] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. [Albadawi, Hassan; Watkins, Michael T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Mihm, Martin C., Jr.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Ctr Engn Med, Boston, MA 02114 USA. EM ireis@sbi.org OI Papisov, Mikhail/0000-0003-4716-2122 FU Shriners Grant [85120-BOS]; NCI Cancer Center Support Grant [NIH 5 P30 CA06516]; NIH [R01EB007542, K99EB017723] FX We acknowledge Shriners Grant # 85120-BOS for the support of this study. We thank Dana-Farber/ Harvard Cancer Center in Boston, MA, for the use of the Rodent Histopathology Core, which provided histological services for this project. Dana-Farber/Harvard Cancer Center is supported in part by an NCI Cancer Center Support Grant # NIH 5 P30 CA06516. The authors acknowledge Dr. Martin Villiger for the assistance with digital processing of the histology slides. KPQ and IG acknowledge support from NIH R01EB007542. K.P.Q. was supported by NIH K99EB017723. NR 50 TC 5 Z9 5 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD MAY 12 PY 2015 VL 5 AR 10187 DI 10.1038/srep10187 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH8UR UT WOS:000354312100001 PM 25965851 ER PT J AU Hempstead, J Jones, DP Ziouche, A Cramer, GM Rizvi, I Arnason, S Hasan, T Celli, JP AF Hempstead, Joshua Jones, Dustin P. Ziouche, Abdelali Cramer, Gwendolyn M. Rizvi, Imran Arnason, Stephen Hasan, Tayyaba Celli, Jonathan P. TI Low-cost photodynamic therapy devices for global health settings: Characterization of battery-powered LED performance and smartphone imaging in 3D tumor models SO SCIENTIFIC REPORTS LA English DT Article ID LIGHT-EMITTING DIODE; TOPICAL 5-AMINOLEVULINIC ACID; OVARIAN-CANCER; ENDOGENOUS PROTOPORPHYRIN; 3-DIMENSIONAL MODEL; ORAL LEUKOPLAKIA; LASER-LIGHT; QUANTIFICATION; FRACTIONATION; FLUORESCENCE AB A lack of access to effective cancer therapeutics in resource-limited settings is implicated in global cancer health disparities between developed and developing countries. Photodynamic therapy (PDT) is a light-based treatment modality that has exhibited safety and efficacy in the clinic using wavelengths and irradiances achievable with light-emitting diodes (LEDs) operated on battery power. Here we assess low-cost enabling technology to extend the clinical benefit of PDT to regions with little or no access to electricity or medical infrastructure. We demonstrate the efficacy of a device based on a 635 nm high-output LED powered by three AA disposable alkaline batteries, to achieve strong cytotoxic response in monolayer and 3D cultures of A431 squamous carcinoma cells following photosensitization by administering aminolevulinic acid (ALA) to induce the accumulation of protoporphyrin IX (PpIX). Here we characterize challenges of battery-operated device performance, including battery drain and voltage stability specifically over relevant PDT dose parameters. Further motivated by the well-established capacity of PDT photosensitizers to serve as tumour-selective fluorescence contrast agents, we demonstrate the capability of a consumer smartphone with lowcost add-ons to measure concentration-dependent PpIX fluorescence. This study lays the groundwork for the on-going development of image-guided ALA-PDT treatment technologies for global health applications. C1 [Hempstead, Joshua; Jones, Dustin P.; Cramer, Gwendolyn M.; Arnason, Stephen; Celli, Jonathan P.] Univ Massachusetts, Dept Phys, Boston, MA 02125 USA. [Ziouche, Abdelali] Univ Paris 13, Lab Phys Lasers, F-93430 Villetaneuse, France. [Rizvi, Imran; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Celli, JP (reprint author), Univ Massachusetts, Dept Phys, Boston, MA 02125 USA. EM jonathan.celli@umb.edu FU National Cancer Institute, of the US National Institutes of Health [R00CA155045, P01CA084203, UH2CA189901] FX We would like to thank Dr. Jonathan Rochford and Stephanie Bellinger-Buckley for providing solubilized protoporphyrin IX for imaging studies and Jeffrey La for assistance with LED characterization. We gratefully acknowledge productive conversations with Drs. Stephen Bown and Colin Hopper regarding clinical PDT for oral cancer, and discussions with Dr. Brett Bouma about LED-based devices. This work was funded by the National Cancer Institute, of the US National Institutes of Health: R00CA155045 (to JPC) and P01CA084203 (to TH) and UH2CA189901 (to TH and JPC). NR 40 TC 4 Z9 4 U1 8 U2 35 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD MAY 12 PY 2015 VL 5 AR 10093 DI 10.1038/srep10093 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH8UH UT WOS:000354311100001 PM 25965295 ER PT J AU Haney, CH Samuel, BS Bush, J Ausubel, FM AF Haney, Cara H. Samuel, Buck S. Bush, Jenifer Ausubel, Frederick M. TI Associations with rhizosphere bacteria can confer an adaptive advantage to plants SO NATURE PLANTS LA English DT Article ID INDUCED SYSTEMIC RESISTANCE; BRASSICA-NAPUS L.; GROWTH-PROMOTING RHIZOBACTERIA; PSEUDOMONAS-FLUORESCENS; ARABIDOPSIS-THALIANA; TRIGGERED IMMUNITY; TOMATO; ROOTS; DIVERSITY; COLONIZATION AB Host-associated microbiomes influence host health. However, it is unclear whether genotypic variations in host organisms influence the microbiome in ways that have adaptive consequences for the host. Here, we show that wild accessions of Arabidopsis thaliana differ in their ability to associate with the root-associated bacterium Pseudomonas fluorescens, with consequences for plant fitness. In a screen of 196 naturally occurring Arabidopsis accessions we identified lines that actively suppress Pseudomonas growth under gnotobiotic conditions. We planted accessions that support disparate levels of fluorescent Pseudomonads in natural soils; 16S ribosomal RNA sequencing revealed that accession-specific differences in the microbial communities were largely limited to a subset of Pseudomonadaceae species. These accession-specific differences in Pseudomonas growth resulted in enhanced or impaired fitness that depended on the host's ability to support Pseudomonas growth, the specific Pseudomonas strains present in the soil and the nature of the stress. We suggest that small host-mediated changes in a microbiome can have large effects on host health. C1 [Haney, Cara H.; Samuel, Buck S.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Haney, Cara H.; Samuel, Buck S.; Bush, Jenifer; 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 02114 USA. EM ausubel@molbio.mgh.harvard.edu OI Haney, Cara/0000-0002-6099-6677; Samuel, Buck/0000-0002-4347-3997 FU MGH Toteston and Fund for Medical Discovery Fellowship [2014A051303]; Gordon and Betty Moore Foundation [GBMF 2550.01]; Charles King Trust Sr. Postdoctoral Fellowship; NIH R37 grant [GM48707]; NSF [MCB-0519898, IOS-0929226] FX C.H.H. is funded by MGH Toteston and Fund for Medical Discovery Fellowship grant 2014A051303 and previously by the Gordon and Betty Moore Foundation through Grant GBMF 2550.01 to the Life Sciences Research Foundation. B.S.S. was funded by a Charles King Trust Sr. Postdoctoral Fellowship. This work was supported by NIH R37 grant GM48707 and NSF grants MCB-0519898 and IOS-0929226 awarded to F.M.A. We thank J. Meyer, D. McEwan, J. Griffitts and L. Shapiro for critical reading of the manuscript and A. Diener and members of the Ausubel Lab for helpful comments and discussion. NR 48 TC 21 Z9 21 U1 18 U2 66 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2055-026X EI 2055-0278 J9 NAT PLANTS JI Nat. Plants PD MAY 11 PY 2015 VL 1 IS 6 BP 1 EP 9 DI 10.1038/NPLANTS.2015.51 PG 9 WC Plant Sciences SC Plant Sciences GA CV6SL UT WOS:000364400600001 ER PT J AU Obeng, EA Ebert, BL AF Obeng, Esther A. Ebert, Benjamin L. TI Charting the "Splice'' Routes to MDS SO CANCER CELL LA English DT Editorial Material ID MUTATIONS; MYELODYSPLASIA C1 [Obeng, Esther A.; Ebert, Benjamin L.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Obeng, Esther A.; Ebert, Benjamin L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Obeng, Esther A.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Ebert, BL (reprint author), Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. EM bebert@partners.org NR 10 TC 1 Z9 1 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD MAY 11 PY 2015 VL 27 IS 5 BP 607 EP 609 DI 10.1016/j.ccell.2015.04.016 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CH8LG UT WOS:000354287300001 PM 25965565 ER PT J AU Shirai, CL Ley, JN White, BS Kim, S Tibbitts, J Shao, J Ndonwi, M Wadugu, B Duncavage, EJ Okeyo-Owuor, T Liu, TE Griffith, M McGrath, S Magrini, V Fulton, RS Fronick, C O'Laughlin, M Graubert, TA Walter, MJ AF Shirai, Cara Lunn Ley, James N. White, Brian S. Kim, Sanghyun Tibbitts, Justin Shao, Jin Ndonwi, Matthew Wadugu, Brian Duncavage, Eric J. Okeyo-Owuor, Theresa Liu, Tuoen Griffith, Malachi McGrath, Sean Magrini, Vincent Fulton, Robert S. Fronick, Catrina O'Laughlin, Michelle Graubert, Timothy A. Walter, Matthew J. TI Mutant U2AF1 Expression Alters Hematopoiesis and Pre-mRNA Splicing In Vivo SO CANCER CELL LA English DT Article ID ACUTE MYELOID-LEUKEMIA; MYELODYSPLASTIC SYNDROMES; PROGNOSTIC IMPACT; DRIVER MUTATIONS; GENETIC LESIONS; STEM-CELLS; APOPTOSIS; TRANSCRIPTOMES; 5Q-SYNDROME; MECHANISMS AB Heterozygous somatic mutations in the spliceosome gene U2AF1 occur in similar to 11% of patients with myelodysplastic syndromes (MDS), the most common adult myeloid malignancy. It is unclear how these mutations contribute to disease. We examined in vivo hematopoietic consequences of the most common U2AF1 mutation using a doxycycline-inducible transgenic mouse model. Mice expressing mutant U2AF1(S34F) display altered hematopoiesis and changes in pre-mRNA splicing in hematopoietic progenitor cells by whole transcriptome analysis (RNA-seq). Integration with human RNA-seq datasets determined that common mutant U2AF1-induced splicing alterations are enriched in RNA processing genes, ribosomal genes, and recurrently mutated MDS and acute myeloid leukemia-associated genes. These findings support the hypothesis that mutant U2AF1 alters downstream gene isoform expression, thereby contributing to abnormal hematopoiesis in patients with MDS. C1 [Shirai, Cara Lunn; Ley, James N.; White, Brian S.; Kim, Sanghyun; Tibbitts, Justin; Shao, Jin; Ndonwi, Matthew; Wadugu, Brian; Okeyo-Owuor, Theresa; Liu, Tuoen; Walter, Matthew J.] Washington Univ, Dept Med, Div Oncol, St Louis, MO 63110 USA. [White, Brian S.; Griffith, Malachi; McGrath, Sean; Magrini, Vincent; Fulton, Robert S.; Fronick, Catrina; O'Laughlin, Michelle] Washington Univ, Genome Inst, St Louis, MO 63110 USA. [Duncavage, Eric J.] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Graubert, Timothy A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Walter, MJ (reprint author), Washington Univ, Dept Med, Div Oncol, St Louis, MO 63110 USA. EM mjwalter@dom.wustl.edu OI Griffith, Malachi/0000-0002-6388-446X; Graubert, Timothy/0000-0002-7710-1171 FU NIH/NHLBI [T32HL007088]; Barnes-Jewish Hospital Foundation; NIH/NCI SPORE in Leukemia [P50CA171963]; NIH/NCI [K12CA167540]; Edward P. Evans Foundation; Clinical and Translational Award from the NIH National Center for Advancing Translational Sciences [UL1 TR000448]; Howard Hughes Medical Institute Physician-Scientist Early Career Award, Leukemia and Lymphoma Society Scholar Award, Department of Defense [BM120018]; Aplastic Anemia and MDS International Foundation; NCI Cancer Center [P30CA91842]; Genome Institute FX Support was provided by NIH/NHLBI (T32HL007088 to C.L.S.), Barnes-Jewish Hospital Foundation (to B.S.W., T.A.G., and M.J.W.); an NIH/NCI SPORE in Leukemia (P50CA171963 to B.S.W., T.A.G., and M.J.W.); an NIH/NCI grant (K12CA167540 to B.S.W); the Edward P. Evans Foundation (to T.A.G. and M.J.W.); a Clinical and Translational Award from the NIH National Center for Advancing Translational Sciences (UL1 TR000448 to B.S.W.); and a Howard Hughes Medical Institute Physician-Scientist Early Career Award, Leukemia and Lymphoma Society Scholar Award, Department of Defense (BM120018), and Aplastic Anemia and MDS International Foundation (to M.J.W.). Technical assistance was provided by the Alvin J. Siteman Cancer Center High Speed Cell Sorting Core and the Tissue Procurement Core supported by an NCI Cancer Center Support Grant (P30CA91842) and the Genome Institute. The authors thank Tianjiao Wang for technical assistance and Drs. Tim Ley and Dan Link for helpful scientific discussions. NR 50 TC 42 Z9 46 U1 2 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD MAY 11 PY 2015 VL 27 IS 5 BP 631 EP 643 DI 10.1016/j.ccell.2015.04.008 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CH8LG UT WOS:000354287300006 PM 25965570 ER PT J AU Chase, HW Fournier, JC Greenberg, T Almeida, JR Stiffler, R Zevallos, CR Aslam, H Cooper, C Deckersbach, T Weyandt, S Adams, P Toups, M Carmody, T Oquendo, MA Peltier, S Fava, M McGrath, PJ Weissman, M Parsey, R McInnis, MG Kurian, B Trivedi, MH Phillips, ML AF Chase, Henry W. Fournier, Jay C. Greenberg, Tsafrir Almeida, Jorge R. Stiffler, Richelle Zevallos, Carlos R. Aslam, Haris Cooper, Crystal Deckersbach, Thilo Weyandt, Sarah Adams, Phillip Toups, Marisa Carmody, Tom Oquendo, Maria A. Peltier, Scott Fava, Maurizio McGrath, Patrick J. Weissman, Myrna Parsey, Ramin McInnis, Melvin G. Kurian, Benji Trivedi, Madhukar H. Phillips, Mary L. TI Accounting for Dynamic Fluctuations across Time when Examining fMRI Test-Retest Reliability: Analysis of a Reward Paradigm in the EMBARC Study SO PLOS ONE LA English DT Article ID MAJOR DEPRESSIVE DISORDER; AMYGDALA RESPONSE; BOLD SIGNALS; PREDICTION; STRIATUM; ATTENTION; EMOTION; ANTICIPATION; ACTIVATION; STIMULI AB Longitudinal investigation of the neural correlates of reward processing in depression may represent an important step in defining effective biomarkers for antidepressant treatment outcome prediction, but the reliability of reward-related activation is not well understood. Thirty-seven healthy control participants were scanned using fMRI while performing a reward-related guessing task on two occasions, approximately one week apart. Two main contrasts were examined: right ventral striatum (VS) activation fMRI BOLD signal related to signed prediction errors (PE) and reward expectancy (RE). We also examined bilateral visual cortex activation coupled to outcome anticipation. Significant VS PE-related activity was observed at the first testing session, but at the second testing session, VS PE-related activation was significantly reduced. Conversely, significant VS RE-related activity was observed at time 2 but not time 1. Increases in VS RE-related activity from time 1 to time 2 were significantly associated with decreases in VS PE-related activity from time 1 to time 2 across participants. Intraclass correlations (ICCs) in VS were very low. By contrast, visual cortex activation had much larger ICCs, particularly in individuals with high quality data. Dynamic changes in brain activation are widely predicted, and failure to account for these changes could lead to inaccurate evaluations of the reliability of functional MRI signals. Conventional measures of reliability cannot distinguish between changes specified by algorithmic models of neural function and noisy signal. Here, we provide evidence for the former possibility: reward-related VS activations follow the pattern predicted by temporal difference models of reward learning but have low ICCs. C1 [Chase, Henry W.; Fournier, Jay C.; Greenberg, Tsafrir; Almeida, Jorge R.; Stiffler, Richelle; Zevallos, Carlos R.; Aslam, Haris; Phillips, Mary L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Cooper, Crystal; Weyandt, Sarah; Toups, Marisa; Carmody, Tom; Kurian, Benji; Trivedi, Madhukar H.] UT Southwestern Med Ctr, Dept Psychiat, Dallas, TX USA. [Adams, Phillip; Parsey, Ramin] SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. [Deckersbach, Thilo; Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Oquendo, Maria A.; McGrath, Patrick J.; Weissman, Myrna] NY State Psychiat Inst, Therapeut Depress Evaluat Serv, New York, NY USA. [Oquendo, Maria A.; McGrath, Patrick J.; Weissman, Myrna] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Peltier, Scott] Univ Michigan, Funct MRI Lab, Ann Arbor, MI 48109 USA. [Parsey, Ramin] SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA. [McInnis, Melvin G.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. RP Chase, HW (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. EM chaseh@upmc.edu RI Parsey, Ramin/J-8254-2014; Greenberg, Tsafrir /Q-7831-2016 FU National Institute of Mental Health of the National Institutes of Health [U01MH092221, U01MH092250]; EMBARC National Coordinating Center at UT Southwestern Medical Center; Data Center at Columbia University FX Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under award numbers U01MH092221 (Trivedi, M.H.) and U01MH092250 (Weissman, M.M., McGrath, P.J., Parsey, R.V.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Valeant Pharmaceuticals donated the Wellbutrin XL used in the study. This work was supported by the EMBARC National Coordinating Center at UT Southwestern Medical Center, Madhukar H. Trivedi, M.D., Coordinating PI, and the Data Center at Columbia University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 2 Z9 2 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 11 PY 2015 VL 10 IS 5 AR e0126326 DI 10.1371/journal.pone.0126326 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CI1YY UT WOS:000354542500089 PM 25961712 ER PT J AU Gilman, JM Treadway, MT Curran, MT Calderon, V Evins, AE AF Gilman, Jodi M. Treadway, Michael T. Curran, Max T. Calderon, Vanessa Evins, A. Eden TI Effect of Social Influence on Effort-Allocation for Monetary Rewards SO PLOS ONE LA English DT Article ID DECISION-MAKING; PEER INFLUENCE; RISK-TAKING; CONFORMITY; ANHEDONIA; SCHIZOPHRENIA; MOTIVATION; UNCERTAINTY; BEHAVIOR; TASK AB Though decades of research have shown that people are highly influenced by peers, few studies have directly assessed how the value of social conformity is weighed against other types of costs and benefits. Using an effort-based decision-making paradigm with a novel social influence manipulation, we measured how social influence affected individuals' decisions to allocate effort for monetary rewards during trials with either high or low probability of receiving a reward. We found that information about the effort-allocation of peers modulated participant choices, specifically during conditions of low probability of obtaining a reward. This suggests that peer influence affects effort-based choices to obtain rewards especially under conditions of risk. This study provides evidence that people value social conformity in addition to other costs and benefits when allocating effort, and suggests that neuroeconomic studies that assess trade-offs between effort and reward should consider social environment as a factor that can influence decision-making. C1 [Gilman, Jodi M.; Curran, Max T.; Calderon, Vanessa; Evins, A. Eden] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. [Gilman, Jodi M.; Evins, A. Eden] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Treadway, Michael T.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. RP Gilman, JM (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. EM jgilman1@partners.org FU Harvard Medical School Norman E. Zinberg Fellowship in Addiction Psychiatry Research; NIDA [K01 DA034093, K24 DA030443]; NIMH [K99 MH102355] FX This work was supported by the Harvard Medical School Norman E. Zinberg Fellowship in Addiction Psychiatry Research (JMG), NIDA K01 DA034093 (JMG), NIMH K99 MH102355 (MTT), and NIDA K24 DA030443 (AEE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 3 Z9 3 U1 5 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 11 PY 2015 VL 10 IS 5 AR UNSP e0126656 DI 10.1371/journal.pone.0126656 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CI1YY UT WOS:000354542500131 PM 25961725 ER PT J AU Feng, Y Shen, J Gao, Y Liao, YF Cote, G Choy, E Chebib, I Mankin, H Hornicek, F Duan, ZF AF Feng, Yong Shen, Jacson Gao, Yan Liao, Yunfei Cote, Gregory Choy, Edwin Chebib, Ivan Mankin, Henry Hornicek, Francis Duan, Zhenfeng TI Expression of programmed cell death ligand 1 (PD-L1) and prevalence of tumor-infiltrating lymphocytes (TILs) in chordoma SO ONCOTARGET LA English DT Article DE PD-L1; TILs; chordoma; immunotherapy ID CLINICAL-SIGNIFICANCE; BREAST-CANCER; CARCINOMA PATIENTS; PROGNOSTIC-FACTORS; B7-H1 EXPRESSION; IMMUNE EVASION; POOR-PROGNOSIS; T-CELLS; SAFETY; MICROENVIRONMENT AB Chordomas are primary malignant tumors of the notochord that are resistant to conventional chemotherapy. Expression of programmed cell death ligand 1 (PD-L1), prevalence of tumor-infiltrating lymphocytes (TILs), and their clinical relevance in chordoma remain unknown. We evaluated PD-L1 expression in three chordoma cell lines and nine chordoma tissue samples by western blot. Immunohistochemical staining was performed on a chordoma tissue microarray (TMA) that contained 78 tissue specimens. We also correlated the expression of PD-L1 and TILs with clinical outcomes. PD-L1 protein expression was demonstrated to be induced by IFN-. in both UCH1 and UCH2 cell lines. Across nine human chordoma tissue samples, PD-L1 protein was differentially expressed. 94.9% of chordoma samples showed positive PD-L1 expression in the TMA. The expression score of PD-L1 for metastatic chordoma tumors was significant higher as compared with non-metastatic chordoma tumors. Expression of PD-L1 protein significantly correlates with the presence of elevated TILs, which correlates with metastasis. In summary, our study showed high levels of PD-L1 are expressed in chordoma, which is correlated with the prevalence of TILs. The current study suggests targeting PD-L1 may be a novel immunotherapeutic strategy for chordoma clinical trials. C1 [Feng, Yong; Shen, Jacson; Gao, Yan; Liao, Yunfei; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Sarcoma Biol Lab, Boston, MA 02114 USA. [Feng, Yong; Shen, Jacson; Gao, Yan; Liao, Yunfei; Cote, Gregory; Choy, Edwin; Chebib, Ivan; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng] Harvard Univ, Sch Med, Boston, MA USA. [Feng, Yong] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Orthopaed Surg, Wuhan 430074, Peoples R China. [Liao, Yunfei] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Endocrine, Wuhan 430074, Peoples R China. [Cote, Gregory; Choy, Edwin] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Chebib, Ivan] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Sarcoma Biol Lab, Boston, MA 02114 USA. EM zduan@mgh.harvard.edu FU Stephan L. Harris Fund; Gattegno and Wechsler funds; Jennifer Hunter Yates Foundation; Chordoma Foundation; Sarcoma Foundation of America (SFA); National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1 [CA151452-01]; Sarcoma SPORE/NIH; Academic Enrichment Fund of MGH Orthopedic Surgery; National Natural Science Foundation of China (NSFC) [81101375] FX This work was supported in part by grants from the Stephan L. Harris Fund, the Gattegno and Wechsler funds, by the Jennifer Hunter Yates Foundation. Support has also been provided by the Chordoma Foundation. Dr. Duan is supported, in part, through a grant from Sarcoma Foundation of America (SFA), a grant from National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1, CA151452-01, a grant from Sarcoma SPORE/NIH, and a grant from an Academic Enrichment Fund of MGH Orthopedic Surgery. Dr. Feng is supported by the National Natural Science Foundation of China (NSFC), 81101375. NR 53 TC 11 Z9 11 U1 2 U2 8 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD MAY 10 PY 2015 VL 6 IS 13 BP 11139 EP 11149 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CO2SH UT WOS:000359006400037 PM 25871477 ER PT J AU Kawabata, S Hollander, MC Munasinghe, JP Brinster, LR Mercado-Matos, JR Li, J Regales, L Pao, W Janne, PA Wong, KK Butman, JA Lonser, RR Hansen, MR Gurgel, RK Vortmeyer, AO Dennis, PA AF Kawabata, Shigeru Hollander, M. Christine Munasinghe, Jeeva P. Brinster, Lauren R. Mercado-Matos, Jose R. Li, Jie Regales, Lucia Pao, William Jaenne, Pasi A. Wong, Kwok-Kin Butman, John A. Lonser, Russell R. Hansen, Marlan R. Gurgel, Richard K. Vortmeyer, Alexander O. Dennis, Phillip A. TI Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone SO ONCOTARGET LA English DT Article DE mouse model of adenomatous ear tumor; ear tumorigenesis; EGFR; EGFR-targeted therapy ID ENDOLYMPHATIC SAC TUMORS; HIPPEL-LINDAU-DISEASE; CELL LUNG-CANCER; CONDITIONAL EXPRESSION; ACQUIRED-RESISTANCE; KINASE INHIBITORS; GENE-EXPRESSION; EGFR T790M; GEFITINIB; MUTATION AB Adenomatous tumors in the middle ear and temporal bone are rare but highly morbid because they are difficult to detect prior to the development of audiovestibular dysfunction. Complete resection is often disfiguring and difficult because of location and the late stage at diagnosis, so identification of molecular targets and effective therapies is needed. Here, we describe a new mouse model of aggressive papillary ear tumor that was serendipitously discovered during the generation of a mouse model for mutant EGFR-driven lung cancer. Although these mice did not develop lung tumors, 43% developed head tilt and circling behavior. Magnetic resonance imaging (MRI) scans showed bilateral ear tumors located in the tympanic cavity. These tumors expressed mutant EGFR as well as active downstream targets such as Akt, mTOR and ERK1/2. EGFR-directed therapies were highly effective in eradicating the tumors and correcting the vestibular defects, suggesting these tumors are addicted to EGFR. EGFR activation was also observed in human ear neoplasms, which provides clinical relevance for this mouse model and rationale to test EGFR-targeted therapies in these rare neoplasms. C1 [Kawabata, Shigeru; Dennis, Phillip A.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Hollander, M. Christine; Mercado-Matos, Jose R.] NCI, Med Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. [Munasinghe, Jeeva P.] NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA. [Brinster, Lauren R.] NIH, Div Vet Resources, Bethesda, MD 20892 USA. [Li, Jie; Vortmeyer, Alexander O.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Regales, Lucia] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Pao, William] Vanderbilt Univ, Sch Med, Div Hematol Oncol, Dept Med,Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. [Jaenne, Pasi A.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Butman, John A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Hansen, Marlan R.] Univ Iowa Hosp & Clin, Dept Otolaryngol Head & Neck Surg, Iowa City, IA 52242 USA. [Gurgel, Richard K.] Univ Utah, Div Otolaryngol Head & Neck Surg, Salt Lake City, UT USA. RP Kawabata, S (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. EM skawaba1@jhmi.edu; pdennis@jhmi.edu RI Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 FU Intramural Research Program of the NIH, NCI, CCR; NIH Bench-to-Bedside Award; NIH/NCI [R01CA121210, P01CA129243, R01CA135257] FX The authors would like to thank Maiga Emmanuel (Office of the Director, NCI) for assistance with genotyping; Morales-Contreras Juan, Dumas Tarra, and Dr. John U. Dennis (Laboratory Animal Medicine, NCI) for veterinary services; Vivian Diaz and Danielle Donahue (Mouse Imaging Facility, NINDS) for assistance with mouse MRI scan and micro-CT scan, respectively; Dr. Liqiang Xi and Dr. Mark Raffeld (Laboratory of Pathology, NCI) for molecular diagnostic services; Dr. Hiroshi Furuta (Furuta clinic of Otolaryngology, Yodogawa-ku, Osaka, Japan) for advice on the analysis of mouse endolymphatic duct/sac system; and Dr. Nathanael S. Gray (Harvard Medical School, Boston, MA, USA) for providing WZ4002 compound. This research was supported by the Intramural Research Program of the NIH, NCI, CCR (PAD), the NIH Bench-to-Bedside Award (FY2010, PAD, AOV, and SK), and NIH/NCI grants R01CA121210 (WP), P01CA129243 (WP), and R01CA135257 (PAJ). NR 32 TC 1 Z9 1 U1 1 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD MAY 10 PY 2015 VL 6 IS 13 BP 11357 EP 11368 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CO2SH UT WOS:000359006400053 PM 26027747 ER PT J AU Yun, HY Xie, JP Olumi, AF Ghosh, R Kumar, AP AF Yun, Huiyoung Xie, Jianping Olumi, Aria F. Ghosh, Rita Kumar, Addanki P. TI Activation of AKR1C1/ER beta induces apoptosis by downregulation of c-FLIP in prostate cancer cells: A prospective therapeutic opportunity SO ONCOTARGET LA English DT Article DE androgen receptor; estrogen receptor beta; c-FLIP; 2-methoxyestradiol; transcription factor ID ENDOTHELIAL GROWTH-FACTOR; TRANSCRIPTION FACTOR SP1; ANDROGEN-RECEPTOR; BETULINIC ACID; TRANSGENIC ADENOCARCINOMA; PANCREATIC-CANCER; MOUSE PROSTATE; 2-METHOXYESTRADIOL; INVOLVEMENT; EXPRESSION AB We provide first-time evidence for ER beta-mediated transcriptional upregulation of c-FLIP as an underlying mechanism in the development of castrate-resistant cancer. While androgens inhibit apoptosis partly through transcriptional upregulation of the anti-apoptotic protein, c-FLIP in androgen-responsive cells, they downregulate c-FLIP in androgen-independent cells. We found that although Sp1 and p65 transactivate c-FLIP, the combination of Sp1 and p65 has differential effects in a cellular context-dependent manner. We show that activation of the androgen metabolism enzyme, aldo-keto reductase, AKR1C1, relieves androgen independence through activation of 3 beta-Adiol-mediated upregulation of ER beta. ER beta competes with Sp1 and Sp3 to transcriptionally downregulate c-FLIP in the absence of consensus estrogen-response element in androgen-independent cells. Forced expression of AR in androgen-independent cells show that ER beta-mediated growth inhibition occurs under conditions of androgen independence. Reactivation of ER beta with the estrogenic metabolite, 2-methoxyestradiol, decreased enrichment ratio of Sp1/Sp3 at the c-FLIP promoter with concomitant effects on cell growth and death. Expression of Sp1 and c-FLIP are elevated while AKR1C1, ER beta and Sp3 are significantly low in human prostate tumor samples. ER beta is epigenetically silenced in prostate cancer patients, therefore our results suggest that combination of ER beta agonists with ADT would benefit men stratified on the basis of high estrogen levels. C1 [Yun, Huiyoung; Xie, Jianping; Ghosh, Rita; Kumar, Addanki P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Yun, Huiyoung; Ghosh, Rita; Kumar, Addanki P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Olumi, Aria F.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ghosh, Rita; Kumar, Addanki P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Ghosh, Rita; Kumar, Addanki P.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Kumar, Addanki P.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Xie, Jianping] Shanxi Acad Med Sci, Dept Urol, Shanxi Dayi Hosp, Taiyuan, Peoples R China. RP Kumar, AP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. EM kumara3@uthscsa.edu FU National Cancer Institute [R01 CA 135451]; National Center for Complementary and Alternative Medicine [AT 005513-01A1, AT 007448-01]; Veterans Affairs-Merit Award [1 I01 BX 000766-01, 1 R01 CA 149516]; Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio through the National Cancer Institute [2P30 CA 054174-17] FX This work was supported in part by funds from National Cancer Institute R01 CA 135451; National Center for Complementary and Alternative Medicine AT 005513-01A1, AT 007448-01; Veterans Affairs-Merit Award 1 I01 BX 000766-01(APK) and 1 R01 CA 149516 (RG). We sincerely thank Dr Rong Li, Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio for providing the ER beta expression plasmid used in this work. We acknowledge support provided by Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio through the National Cancer Institute support grant #2P30 CA 054174-17 (APK and RG). NR 45 TC 5 Z9 5 U1 0 U2 5 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD MAY 10 PY 2015 VL 6 IS 13 BP 11600 EP 11613 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CO2SH UT WOS:000359006400071 PM 25816367 ER PT J AU Lin, NU AF Lin, Nancy U. TI Weighing the Options for Human Epidermal Growth Factor Receptor 2-Directed Therapy in Metastatic Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID LAPATINIB PLUS CAPECITABINE; NERVOUS-SYSTEM METASTASES; CLINICAL-PRACTICE GUIDELINE; BRAIN METASTASES; TRASTUZUMAB EMTANSINE; AMERICAN SOCIETY; PHASE-III; DOCETAXEL; PERTUZUMAB; OUTCOMES C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lin, NU (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM nlin@partners.org NR 20 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2015 VL 33 IS 14 BP 1530 EP + DI 10.1200/JCO.2014.60.1427 PG 5 WC Oncology SC Oncology GA CK2RR UT WOS:000356059900005 PM 25847924 ER PT J AU Kulke, MH AF Kulke, Matthew H. TI Sequencing and Combining Systemic Therapies for Pancreatic Neuroendocrine Tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADIOLABELED SOMATOSTATIN ANALOG; LIVER METASTASES; ENDOCRINE CARCINOMAS; MTOR PATHWAY; TEMOZOLOMIDE; SURVIVAL; EXPRESSION; OCTREOTIDE; EVEROLIMUS; SUNITINIB AB A 51-year-old man was referred for management of metastatic neuroendocrine tumor (NET). He had experienced several years of intermittent diarrhea. After developing an episode of severe, watery diarrhea for more than 48 hours, he was hospitalized for management of dehydration and hypokalemia. Computed tomography (CT) scans at that time showed a pancreatic mass and multiple hepatic lesions. A serum vasoactive intestinal peptide was markedly increased (815 pg/mL; normal range, 0 to 74 pg/mL). A biopsy of one of the hepatic lesions revealed grade 2 well-differentiated NETs, with a mitotic rate of 1:10 high-power fields (hpf) and a Ki-67 proliferative index of 5%. Somatostatin scintigraphy showed uptake in the region of the pancreatic mass and in the liver lesions. The patient initiated treatment with a somatostatin analog while he was still in the hospital, and the diarrhea was quickly resolved. A follow-up CT scan 3 months later showed stable disease. Over the course of the subsequent 3 years, he received additional sequential treatment with everolimus and sunitinib and experienced periods of stable disease on each treatment. His most recent CT scan showed evidence of new growth in both the liver metastases and the pancreatic lesion. His vasoactive intestinal peptide (VIP) level also increased from a nadir of 85 pg/mL to 220 pg/mL. He was again having intermittent episodes of diarrhea. C1 Dana Farber Canc Inst, Program Neuroendocrine & Carcinoid Tumors, Boston, MA 02115 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Program Neuroendocrine & Carcinoid Tumors, Boston, MA 02115 USA. EM matthew_kulke@dfci.harvard.edu NR 35 TC 4 Z9 4 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 MAY 10 PY 2015 VL 33 IS 14 BP 1534 EP + DI 10.1200/JCO.2014.59.0927 PG 6 WC Oncology SC Oncology GA CK2RR UT WOS:000356059900006 PM 25870092 ER PT J AU Dunn, EC Masyn, KE Johnston, WR Subramanian, SV AF Dunn, Erin C. Masyn, Katherine E. Johnston, William R. Subramanian, S. V. TI Modeling contextual effects using individual-level data and without aggregation: an illustration of multilevel factor analysis (MLFA) with collective efficacy SO POPULATION HEALTH METRICS LA English DT Article DE Multilevel; Factor analysis; Environment; Ecological; Context; Latent variable; Collective efficacy; Neighborhood ID CONFIRMATORY FACTOR-ANALYSIS; SOCIAL DETERMINANTS; HEALTH; NEIGHBORHOODS; POPULATIONS; ECOMETRICS; CHILDREN AB Population health scientists increasingly study how contextual-level attributes affect individual health. A major challenge in this domain relates to measurement, i.e., how best to measure and create variables that capture characteristics of individuals and their embedded contexts. This paper presents an illustration of multilevel factor analysis (MLFA), an analytic method that enables researchers to model contextual effects using individual-level data without using derived variables. MLFA uses the shared variance in sets of observed items among individuals within the same context to estimate a measurement model for latent constructs; it does this by decomposing the total sample variance-covariance matrix into within-group (e.g., individual-level) and between-group (e.g., contextual-level) matrices and simultaneously modeling distinct latent factor structures at each level. We illustrate the MLFA method using items capturing collective efficacy, which were self-reported by 2,599 adults in 65 census tracts from the Los Angeles Family and Neighborhood Survey (LAFANS). MLFA identified two latent factors at the individual level and one factor at the neighborhood level. Indicators of collective efficacy performed differently at each level. The ability of MLFA to identify different latent factor structures at each level underscores the utility of this analytic tool to model and identify attributes of contexts relevant to health. C1 [Dunn, Erin C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Masyn, Katherine E.] Georgia State Univ, Sch Publ Hlth, Div Epidemiol & Biostat, Atlanta, GA 30302 USA. [Johnston, William R.] Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. [Subramanian, S. V.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. RP Dunn, EC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, 185 Cambridge St,Room 6-252, Boston, MA 02114 USA. EM erindunn@pngu.mgh.harvard.edu NR 51 TC 0 Z9 0 U1 3 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-7954 J9 POPUL HEALTH METR JI Popul. Health Metr. PD MAY 10 PY 2015 VL 13 AR 12 DI 10.1186/s12963-015-0045-1 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CI9FJ UT WOS:000355075500001 PM 26019691 ER PT J AU Gu, GS Ren, JA Liu, S Li, GW Yuan, YJ Chen, J Han, G Ren, HJ Hong, ZW Yan, DS Wu, XW Li, N Li, JS AF Gu, Guosheng Ren, Jianan Liu, Song Li, Guanwei Yuan, Yujie Chen, Jun Han, Gang Ren, Huajian Hong, Zhiwu Yan, Dongsheng Wu, Xiuwen Li, Ning Li, Jieshou TI Comparative evaluation of sump drainage by trocar puncture, percutaneous catheter drainage versus operative drainage in the treatment of Intra-abdominal abscesses: a retrospective controlled study SO BMC SURGERY LA English DT Article DE Percutaneous catheter drainage; Operative drainage; Sump drainage; Trocar puncture; Intra-abdominal abscesses ID CROHNS-DISEASE; MANAGEMENT; STRATEGY AB Background: Intra-abdominal and pelvic abscesses are common and result from various illnesses. Percutaneous drainage applies limitedly to well-localized abscesses with appropriate density while surgical drainage usually causes significant physiological disturbance. We herein illustrated an innovative choice "sump drainage with trocar puncture" for the management of intra-abdominal abscesses and compare it with conventional percutaneous and surgical drainage in terms of clinical outcomes and prognosis. Methods: Medical records of a total of 75 patients with abscesses were retrospectively retrieved and scrutinized. Data consisted of demographics, abscesses characteristics and treatment outcomes including postoperative complication, duration of hospitalization, postoperative recurrence of abscesses, subsequent surgery, ultimate stoma creation and survival rate. All enrolled patients were divided into trocar group (n = 30), percutaneous group (n = 20) and surgical group (n = 25) according to the therapeutic modalities. One-way ANOVA and t-test with Welch's correction were used in continuous variables, and Chi-squared test as well as Fisher's exact test for categorical variables. The cumulative incidence of subsequent surgery and ultimate stoma creation was also indicated by the Kaplan-Meier method and compared by log-rank test. Results: The risk of ultimate stoma creation (p = 0.0069) and duration of postoperative hospitalization (p = 0.0077) were significantly decreased in trocar group compared with the surgical group. Patients receiving trocar puncture also tended to be less likely to have subsequent surgery (p = 0.097). Patients in trocar group displayed a lower rate of postoperative complication than the percutaneous (p = 0.0317) and surgical groups (p = 0.0175). As for Kaplan-Meier analysis, the cumulative incidence of ultimate stoma creation of the patients using sump drainage was also significantly different among three groups during follow-up period (p = 0.011). Conclusion: This novel technique "sump drainage by trocar puncture" could produce better clinical outcomes and prognosis than conventional percutaneous drainage and surgical intervention. It might become an optimal choice in the management of intra-abdominal abscesses in the future. C1 [Gu, Guosheng; Ren, Jianan; Liu, Song; Li, Guanwei; Chen, Jun; Han, Gang; Ren, Huajian; Hong, Zhiwu; Yan, Dongsheng; Wu, Xiuwen; Li, Ning; Li, Jieshou] Nanjing Univ, Jinling Hosp, Sch Med, Dept Surg, Nanjing 210002, Jiangsu, Peoples R China. [Liu, Song] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. [Yuan, Yujie] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gastrointestinal Pancreat Surg, Guangzhou 510275, Guangdong, Peoples R China. [Han, Gang] Jilin Univ, Affiliated Hosp 2, Ctr Jilin Univ, Dept Gen Surg,Gen Surg, Changchun 130023, Peoples R China. RP Ren, JA (reprint author), Nanjing Univ, Jinling Hosp, Sch Med, Dept Surg, 305 East Zhongshan Rd, Nanjing 210002, Jiangsu, Peoples R China. EM JiananR@gmail.com FU Research Talents of Jiangsu Province, China [BRA2011232]; National Natural Science Foundation of China [81270478] FX This study was supported by grants from Research Talents of Jiangsu Province, China (BRA2011232) and National Natural Science Foundation of China (81270478). NR 15 TC 0 Z9 1 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2482 J9 BMC SURG JI BMC Surg. PD MAY 9 PY 2015 VL 15 AR 59 DI 10.1186/s12893-015-0049-6 PG 7 WC Surgery SC Surgery GA CI0LC UT WOS:000354427600001 PM 25956593 ER PT J AU Charidimou, A Nicoll, JAR McCarron, MO AF Charidimou, Andreas Nicoll, James A. R. McCarron, Mark O. TI Thrombolysis-related intracerebral hemorrhage and cerebral amyloid angiopathy: accumulating evidence SO FRONTIERS IN NEUROLOGY LA English DT Editorial Material DE cerebral amyloid angiopathy; intracerebral hemorrhage; thrombolysis ID MICROBLEEDS; RISK; METAANALYSIS C1 [Charidimou, Andreas] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Nicoll, James A. R.] Univ Southampton, Dept Neuropathol, Southampton, Hants, England. EM markmccarron@doctors.org.uk NR 14 TC 4 Z9 4 U1 0 U2 0 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-2295 J9 FRONT NEUROL JI Front. Neurol. PD MAY 8 PY 2015 VL 6 AR UNSP 99 DI 10.3389/fneur.2015.00099 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CU9CA UT WOS:000363839200001 PM 26005432 ER PT J AU Braga, RM Roze, E Ball, G Merchant, N Tusor, N Arichi, T Edwards, D Rueckert, D Counsell, SJ AF Braga, Rodrigo M. Roze, Elise Ball, Gareth Merchant, Nazakat Tusor, Nora Arichi, Tomoki Edwards, David Rueckert, Daniel Counsell, Serena J. TI Development of the Corticospinal and Callosal Tracts from Extremely Premature Birth up to 2 Years of Age SO PLOS ONE LA English DT Article ID CEREBRAL WHITE-MATTER; WEIGHT PRETERM INFANTS; DIFFUSION-TENSOR MRI; TERM-EQUIVALENT AGE; SPATIAL STATISTICS; NEURODEVELOPMENTAL OUTCOMES; MICROSTRUCTURAL DEVELOPMENT; FIBER TRACTOGRAPHY; CORPUS-CALLOSUM; BRAIN AB White matter tracts mature asymmetrically during development, and this development can be studied using diffusion magnetic resonance imaging. The aims of this study were i. to generate dynamic population-averaged white matter registration templates covering in detail the period from 25 weeks gestational age to term, and extending to 2 years of age based on DTI and fractional anisotropy, ii. to produce tract-specific probability maps of the corticospinal tracts, forceps major and forceps minor using probabilistic tractography, and iii. to assess the development of these tracts throughout this critical period of neurodevelopment. We found evidence for asymmetric development across the fiber bundles studied, with the corticospinal tracts showing earlier maturation (as measured by fractional anisotropy) but slower volumetric growth compared to the callosal fibers. We also found evidence for an anterior to posterior gradient in white matter microstructure development (as measured by mean diffusivity) in the callosal fibers, with the posterior forceps major developing at a faster rate than the anterior forceps minor in this age range. Finally, we report a protocol for delineating callosal and corticospinal fibers in extremely premature cohorts, and make available population-averaged registration templates and a probabilistic tract atlas which we hope will be useful for future neonatal and infant white-matter imaging studies. C1 Univ London Imperial Coll Sci Technol & Med, Div Brain Sci, Computat Cognit & Clin Neuroimaging Lab, London, England. Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Braga, Rodrigo M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Braga, Rodrigo M.] Harvard Univ, Sch Med, Charlestown, MA USA. [Roze, Elise] Univ Utrecht, Wilhelmina Childrens Hosp, Univ Med Ctr Utrecht, NL-3508 TC Utrecht, Netherlands. [Ball, Gareth; Merchant, Nazakat; Tusor, Nora; Arichi, Tomoki; Edwards, David; Counsell, Serena J.] Kings Coll London, Ctr Developing Brain, Div Imaging Sci & Biomed Engn, London SE1 7EH, England. [Rueckert, Daniel] Univ London Imperial Coll Sci Technol & Med, Dept Comp, London, England. RP Counsell, SJ (reprint author), Kings Coll London, Ctr Developing Brain, Div Imaging Sci & Biomed Engn, London SE1 7EH, England. EM serena.counsell@kcl.ac.uk OI Tusor, Nora/0000-0002-3664-7397; Arichi, Tomoki/0000-0002-3550-1644; Ball, Gareth/0000-0003-3509-1435 FU National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London; Imperial College London; EPSRC; Garfield Weston Foundation; MRC FX This research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, and at Imperial College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Funding for the research was supplied by MRC, EPSRC, and the Garfield Weston Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 3 Z9 4 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 8 PY 2015 VL 10 IS 5 AR e0125681 DI 10.1371/journal.pone.0125681 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CL2IX UT WOS:000356768100065 PM 25955638 ER PT J AU Jensen, JB Lysaght, AC Liberman, MC Qvortrup, K Stankovic, KM AF Jensen, Jane Bjerg Lysaght, Andrew C. Liberman, M. Charles Qvortrup, Klaus Stankovic, Konstantina M. TI Immediate and Delayed Cochlear Neuropathy after Noise Exposure in Pubescent Mice SO PLOS ONE LA English DT Article ID GUINEA-PIG COCHLEA; INDUCED HEARING-LOSS; CELL RIBBON SYNAPSE; INNER HAIR-CELLS; PRODUCT OTOACOUSTIC EMISSIONS; SPIRAL GANGLION; TRANSMITTER RELEASE; EVOKED POTENTIALS; AUDITORY NEURONS; NORMAL AUDIOGRAM AB Moderate acoustic overexposure in adult rodents is known to cause acute loss of synapses on sensory inner hair cells (IHCs) and delayed degeneration of the auditory nerve, despite the completely reversible temporary threshold shift (TTS) and morphologically intact hair cells. Our objective was to determine whether a cochlear synaptopathy followed by neuropathy occurs after noise exposure in pubescence, and to define neuropathic versus non-neuropathic noise levels for pubescent mice. While exposing 6 week old CBA/CaJ mice to 8-16 kHz bandpass noise for 2 hrs, we defined 97 dB sound pressure level (SPL) as the threshold for this particular type of neuropathic exposure associated with TTS, and 94 dB SPL as the highest non-neuropathic noise level associated with TTS. Exposure to 100 dB SPL caused permanent threshold shift although exposure of 16 week old mice to the same noise is reported to cause only TTS. Amplitude of wave I of the auditory brainstem response, which reflects the summed activity of the cochlear nerve, was complemented by synaptic ribbon counts in IHCs using confocal microscopy, and by stereological counts of peripheral axons and cell bodies of the cochlear nerve from 24 hours to 16 months post exposure. Mice exposed to neuropathic noise demonstrated immediate cochlear synaptopathy by 24 hours post exposure, and delayed neurodegeneration characterized by axonal retraction at 8 months, and spiral ganglion cell loss at 8-16 months post exposure. Although the damage was initially limited to the cochlear base, it progressed to also involve the cochlear apex by 8 months post exposure. Our data demonstrate a fine line between neuropathic and non-neuropathic noise levels associated with TTS in the pubescent cochlea. C1 [Jensen, Jane Bjerg; Lysaght, Andrew C.; Liberman, M. Charles; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Jensen, Jane Bjerg; Lysaght, Andrew C.; Liberman, M. Charles; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Jensen, Jane Bjerg; Lysaght, Andrew C.; Liberman, M. Charles; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Lysaght, Andrew C.; Liberman, M. Charles; Stankovic, Konstantina M.] Harvard & Massachusetts Inst Technol, Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Boston, MA 02139 USA. [Jensen, Jane Bjerg; Qvortrup, Klaus] Univ Copenhagen, CFIM, Dept Biomed Sci, DK-2200 Copenhagen N, Denmark. RP Stankovic, KM (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. EM konstantina_stankovic@meei.harvard.edu FU National Institute on Deafness and Other Communicative Disorders [K08DC010419, R01 DC00188, P30 05209, T32 DC00038]; Bertarelli Foundation; Aase and Ejnar Danielsens Foundation FX This study was supported by grants from the National Institute on Deafness and Other Communicative Disorders: K08DC010419 (KMS), R01 DC00188 (MCL), P30 05209 (MCL) and T32 DC00038 (ACL, KMS); The Bertarelli Foundation (KMS); and The Aase and Ejnar Danielsens Foundation (JBJ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 8 Z9 8 U1 2 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 8 PY 2015 VL 10 IS 5 AR UNSP e0125160 DI 10.1371/journal.pone.0125160 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CL2IX UT WOS:000356768100045 PM 25955832 ER PT J AU Sutherasan, Y Penuelas, O Muriel, A Vargas, M Frutos-Vivar, F Brunetti, I Raymondos, K D'Antini, D Nielsen, N Ferguson, ND Bottiger, BW Thille, AW Davies, AR Hurtado, J Rios, F Apezteguia, C Violi, DA Cakar, N Gonzalez, M Du, B Kuiper, MA Soares, MA Koh, Y Moreno, RP Amin, P Tomicic, V Soto, L Bulow, HH Anzueto, A Esteban, A Pelosi, P AF Sutherasan, Yuda Penuelas, Oscar Muriel, Alfonso Vargas, Maria Frutos-Vivar, Fernando Brunetti, Iole Raymondos, Konstantinos D'Antini, Davide Nielsen, Niklas Ferguson, Niall D. Boettiger, Bernd W. Thille, Arnaud W. Davies, Andrew R. Hurtado, Javier Rios, Fernando Apezteguia, Carlos Violi, Damian A. Cakar, Nahit Gonzalez, Marco Du, Bin Kuiper, Michael A. Soares, Marco Antonio Koh, Younsuck Moreno, Rui P. Amin, Pravin Tomicic, Vinko Soto, Luis Buelow, Hans-Henrik Anzueto, Antonio Esteban, Andres Pelosi, Paolo CA VENTILA Grp TI Management and outcome of mechanically ventilated patients after cardiac arrest SO CRITICAL CARE LA English DT Article ID INTENSIVE-CARE-UNIT; AMERICAN-HEART-ASSOCIATION; TIDAL-VOLUME VENTILATION; EXPERIMENTAL LUNG INJURY; ARTERIAL CARBON-DIOXIDE; IN-HOSPITAL MORTALITY; CARDIOPULMONARY-RESUSCITATION; THERAPEUTIC HYPOTHERMIA; ABDOMINAL-SURGERY; PRESSURE AB Introduction: The aim of this study was to describe and compare the changes in ventilator management and complications over time, as well as variables associated with 28-day hospital mortality in patients receiving mechanical ventilation (MV) after cardiac arrest. Methods: We performed a secondary analysis of three prospective, observational multicenter studies conducted in 1998, 2004 and 2010 in 927 ICUs from 40 countries. We screened 18,302 patients receiving MV for more than 12 hours during a one-month-period. We included 812 patients receiving MV after cardiac arrest. We collected data on demographics, daily ventilator settings, complications during ventilation and outcomes. Multivariate logistic regression analysis was performed to calculate odds ratios, determining which variables within 24 hours of hospital admission were associated with 28-day hospital mortality and occurrence of acute respiratory distress syndrome (ARDS) and pneumonia acquired during ICU stay at 48 hours after admission. Results: Among 812 patients, 100 were included from 1998, 239 from 2004 and 473 from 2010. Ventilatory management changed over time, with decreased tidal volumes (VT) (1998: mean 8.9 (standard deviation (SD) 2) ml/kg actual body weight (ABW), 2010: 6.7 (SD 2) ml/kg ABW; 2004: 9 (SD 2.3) ml/kg predicted body weight (PBW), 2010: 7.95 (SD 1.7) ml/kg PBW) and increased positive end-expiratory pressure (PEEP) (1998: mean 3.5 (SD 3), 2010: 6.5 (SD 3); P < 0.001). Patients included from 2010 had more sepsis, cardiovascular dysfunction and neurological failure, but 28-day hospital mortality was similar over time (52% in 1998, 57% in 2004 and 52% in 2010). Variables independently associated with 28-day hospital mortality were: older age, PaO2 < 60 mmHg, cardiovascular dysfunction and less use of sedative agents. Higher VT, and plateau pressure with lower PEEP were associated with occurrence of ARDS and pneumonia acquired during ICU stay. Conclusions: Protective mechanical ventilation with lower VT and higher PEEP is more commonly used after cardiac arrest. The incidence of pulmonary complications decreased, while other non-respiratory organ failures increased with time. The application of protective mechanical ventilation and the prevention of single and multiple organ failure may be considered to improve outcome in patients after cardiac arrest. C1 [Sutherasan, Yuda] Mahidol Univ, Ramathibodi Hosp, Dept Med, Bangkok 10400, Thailand. [Sutherasan, Yuda; Brunetti, Iole; Pelosi, Paolo] IRCCS AOU San Martino, IST, Dept Surg Sci & Integrated Diagnost, I-16131 Genoa, Italy. [Penuelas, Oscar] Hosp Univ Infanta Cristina, Madrid 28981, Spain. [Penuelas, Oscar] CIBER Enfermedades Resp, Madrid 28981, Spain. [Muriel, Alfonso] Hosp Ramon y Cajal Ctra, CIBERESP, IRYCIS, Ramon Cajal Inst & Res Hlth,Biostat Unit, Madrid 28034, Spain. [Vargas, Maria] Univ Naples Federico II, Dept Neurosci Odonthostomatol & Reprod Sci, I-80100 Naples, Italy. [Frutos-Vivar, Fernando; Esteban, Andres] Hosp Univ Getafe, Madrid 28905, Spain. [Frutos-Vivar, Fernando; Esteban, Andres] CIBER Enfermedades Resp, Madrid 28905, Spain. [Raymondos, Konstantinos] Med Sch Hanover, Anaesthesiol & Intens Care Med, D-30625 Hannover, Germany. [D'Antini, Davide] Univ Foggia, Dipartimento Anestesia Rianimaz & Terapia Intens, I-71100 Foggia, Italy. [Nielsen, Niklas] Helsingborg Hosp, Dept Anesthesia & Intens Care, Intens Care Unit, S-25187 Helsingborg, Sweden. [Ferguson, Niall D.] Univ Toronto, Univ Hlth Network, Dept Med, Interdept Div Crit Care Med, Toronto, ON M5G 2N2, Canada. [Ferguson, Niall D.] Mt Sinai Hosp, Toronto, ON M5G 2N2, Canada. [Boettiger, Bernd W.] Univ Hosp Cologne, Dept Anaesthesiol & Intens Care Med, D-50937 Cologne, Germany. [Thille, Arnaud W.] Univ Poitiers, Ctr Hosp, INSERM, CIC 1402,Reanimat Med, F-86000 Poitiers, France. [Davies, Andrew R.] Monash Univ, ANZIC RC, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Hurtado, Javier] Univ Republica, Hosp Clin, Dept Pathophysiol, Montevideo 11600, Uruguay. [Rios, Fernando; Apezteguia, Carlos] Hosp Nacl Prof Alejandro Posadas El Palomar, Dept Intens Care, RA-1684 Buenos Aires, DF, Argentina. [Violi, Damian A.] Hosp Prof Dr Luis Guemes, Med Staff Crit Care, Buenos Aires, DF, Argentina. [Cakar, Nahit] Istanbul Univ, Istanbul Fac Med, Anesthesiol & Intens Care, TR-34093 Istanbul, Turkey. [Gonzalez, Marco] Clin Medellin, Medellin, Colombia. [Gonzalez, Marco] Univ Pontificia Bolivariana, Medellin, Colombia. [Du, Bin] Beijing Union Med Coll Hosp, Med ICU, Beijing 100730, Peoples R China. [Kuiper, Michael A.] Med Ctr Leeuwarden, Dept Intens Care, NL-8934 AD Leeuwarden, Netherlands. [Soares, Marco Antonio] Hosp Univ Sao Jose, Belo Horizonte, MG, Brazil. [Koh, Younsuck] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pulm & Crit Care Med, Seoul 138736, South Korea. [Moreno, Rui P.] Sao Jose Ctr Hosp Lisboa Cent, Unidade Cuidados Intensivos Neurocrit Hosp, P-1150199 Lisbon, Portugal. [Amin, Pravin] Bombay Hosp Inst Med Sci, Mumbai 400020, Maharashtra, India. [Tomicic, Vinko] Clin Lilas Santiago, Santiago, Chile. [Soto, Luis] Inst Nacl Torax Santiago, Santiago, Chile. [Buelow, Hans-Henrik] Reg Zealand Univ Copenhagen, Holbaek Hosp, Anaesthesiol & Intens Care, DK-4300 Holbaek, Denmark. [Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Pelosi, P (reprint author), IRCCS AOU San Martino, IST, Dept Surg Sci & Integrated Diagnost, Largo Rosanna Benzi 8, I-16131 Genoa, Italy. EM ppelosi@hotmail.com RI koca, ugur/F-1265-2016; Vargas, Maria/H-6876-2014; OI Ferguson, Niall/0000-0002-6213-5264; Muriel, Alfonso /0000-0002-4805-4011; koca, ugur/0000-0002-2949-4265; Vargas, Maria/0000-0001-7652-970X; D'Antini, Davide/0000-0002-2346-9720; Frutos-Vivar, Fernando/0000-0002-4648-9636 FU Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES); Instituto de Salud Carlos III, Madrid, Spain; Canadian Institutes of Health Research New Investigator Award (Ottawa, Canada) FX We are grateful to all investigators of the VENTILA study group for collecting data for this article (see Additional file 1). The VENTILA study was supported by Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. Dr Ferguson is supported by a Canadian Institutes of Health Research New Investigator Award (Ottawa, Canada). The funding organizations had no role in the design or conduct of the study, collection, management, analysis, or interpretation of the data, or preparation, review, or approval of the manuscript. NR 48 TC 11 Z9 12 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PD MAY 8 PY 2015 VL 19 AR 215 DI 10.1186/s13054-015-0922-9 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA CK4ZE UT WOS:000356231100001 PM 25953483 ER PT J AU Lin, H Bukovskaya, Y De Moya, M Lee, J Schmidt, U AF Lin, Hsin Bukovskaya, Yana De Moya, Marc Lee, Jarone Schmidt, Ulrich TI Vancomycin continuous infusion versus intermittent infusion during continuous venovenous hemofiltration: slow and steady may win the race SO ANNALS OF INTENSIVE CARE LA English DT Article DE Vancomycin; Continuous infusion; Continuous venovenous hemofiltration ID RENAL-REPLACEMENT THERAPY; CRITICALLY-ILL PATIENTS; STAPHYLOCOCCUS-AUREUS BACTEREMIA; MULTICENTER; INFECTIONS; PHARMACODYNAMICS; GUIDELINES; MORTALITY; OUTCOMES; FAILURE AB Background: Vancomycin during continuous venovenous hemofiltration (CVVH) is either administered by intermittent infusion (II) or continuous infusion (CI). In this patient population, the best method to rapidly achieve target serum concentrations of 15 mcg/ml to 25 mcg/ml remains to be elucidated. We hypothesized that CI would achieve a target serum level of 15 mcg/ml to 25 mcg/ml within 24 h of the initiation of therapy more consistently than II. Methods: A retrospective cohort study of adult patients admitted to the intensive care unit (ICU) between 2011 and 2014 receiving intravenous vancomycin with 24-hour serum level while on CVVH was included. Patients were excluded from this review if they had residual renal function during CVVH, were concomitantly on extracorporeal membrane oxygenation, or if the first dose of vancomycin was received six or more hours prior to the initiation of CVVH. The primary outcome was the achievement of a therapeutic level of 15mcg/ml to 25 mcg/ml by 24 hours. Results: Fifty-nine patients met the inclusion criteria and 14 received CI and 45 in II. Therapeutic 24-hour levels were achieved in 14/14 versus 2/45 in CI and II, respectively (p < 0.001). Mean 24-hour vancomycin levels were 20.35 +/- 2.78 mcg/ml for CI compared to 9.7 +/- 3.52 mcg/ml for II (p < 0.001). Mean loading dose was 26.65 +/- 3.06 mg/kg for CI compared to 17.58 +/- 5.72 mg/kg for II (p < 0.001). Daily maintenance doses were 15.66 +/- 6.26 mg/kg for CI compared to 17.28 +/- 4.96 mg/kg for II (p = 0.339). In the subgroup of 27 patients who received vancomycin-loading dose >20 mg/kg, mean 24-hour levels were 20.35 +/- 2.78 mcg/ml for CI versus 11.8 +/- 2.7 mcg/ml for II (p < 0.001). No significant differences were found between patients in the two groups with respect to CVVH rate and length of CVVH prior to vancomycin administration. Conclusions: The results of our study suggest that critically ill patients on CVVH treated with CI achieved the target level faster than II and consistently keep the vancomycin level within target range. C1 [Lin, Hsin] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Bukovskaya, Yana] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pharm, Los Angeles, CA USA. [De Moya, Marc] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Lee, Jarone] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lee, Jarone] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Schmidt, Ulrich] Univ Calif San Diego, Dept Anesthesiol, San Diego, CA 92103 USA. RP Lin, H (reprint author), Massachusetts Gen Hosp, Dept Pharm, 55 Fruit St, Boston, MA 02114 USA. EM Hlin13@partners.org FU Harvard Catalyst: The Harvard Clinical and Translational Science Center (National Center for Research Resources; Harvard Catalyst: The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health [UL1 TR001102]; Harvard University and its affiliated academic health care centers FX We acknowledge Dr. Hang Lee, Ph. D, (assistant professor of medicine at Harvard Medical School, Harvard Catalyst Consultations Services) for assistance and expertise in statistical analyses. This work was conducted with support from Harvard Catalyst: The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102, and financial contributions from Harvard University and its affiliated academic health care centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. NR 20 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 2110-5820 J9 ANN INTENSIVE CARE JI Ann. Intensive Care PD MAY 8 PY 2015 VL 5 AR 10 DI 10.1186/s13613-015-0048-x PG 8 WC Critical Care Medicine SC General & Internal Medicine GA CK0TF UT WOS:000355917200001 PM 25995967 ER PT J AU Nansel, TR Laffel, LMB Haynie, DL Mehta, SN Lipsky, LM Volkening, LK Butler, DA Higgins, LA Liu, AY AF Nansel, Tonja R. Laffel, Lori M. B. Haynie, Denise L. Mehta, Sanjeev N. Lipsky, Leah M. Volkening, Lisa K. Butler, Deborah A. Higgins, Laurie A. Liu, Aiyi TI Improving dietary quality in youth with type 1 diabetes: randomized clinical trial of a family-based behavioral intervention SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY LA English DT Article DE Behavioral intervention; Nutrition; Diet; Type 1 diabetes; Children; Adolescents ID NUTRITION EXAMINATION SURVEY; CARDIOVASCULAR-DISEASE RISK; WHOLE-GRAIN INTAKE; GLYCEMIC CONTROL; NATIONAL-HEALTH; NUTRIENT INTAKE; WEIGHT-GAIN; DASH DIET; CHILDREN; ADOLESCENTS AB Background: Diets of children with type 1 diabetes are low in fruits, vegetables, and whole grains, and high in foods of minimal nutritional value, increasing risk for future adverse health outcomes. This 18-month randomized clinical trial tested the effect of a family-based behavioral intervention integrating motivational interviewing, active learning, and applied problem-solving on the primary outcomes of dietary intake and glycemic control among youth with type 1 diabetes. Methods: A parallel-group study with equal randomization was conducted at an outpatient, free-standing, multidisciplinary tertiary diabetes center in the United States. Eligible youth were those age 8-16 years with type 1 diabetes diagnosis >= 1 year and hemoglobin A1c (HbA1c) >= 6.5% and <= 10.0%. Participants were 136 parent-youth dyads (treatment n = 66, control n = 70). The intervention consisted of 9 in-clinic sessions delivered to the child and parent; control condition comprised equivalent assessments and number of contacts without dietary advice. Dietary intake was assessed using 3-day diet records at 6 time points across the 18-month study. Dietary outcomes included the Healthy Eating Index-2005 (HEI2005; index measuring conformance to the 2005 United States Dietary Guidelines for Americans) and Whole Plant Food Density (WPFD; number of cup or ounce equivalents per 1000 kcal of whole grains, whole fruit, vegetables, legumes, nuts, and seeds consumed). HbA1c was obtained every 3 months. Overall comparison of outcome variables between intervention and usual care groups was conducted using permutation tests. Results: There was a positive intervention effect across the study duration for HEI2005 (p = .015) and WPFD (p = .004). At 18 months, HEI2005 was 7.2 greater (mean +/- SE 64.6 +/- 2.0 versus 57.4 +/- 1.6), and WPFD was 0.5 greater (2.2 +/- 0.1 versus 1.7 +/- 0.1) in the intervention group versus control. There was no difference between groups in HbA1c across the study duration. Conclusions: This behavioral nutrition intervention improved dietary quality among youth with type 1 diabetes, but did not impact glycemic control. Findings indicate the potential utility of incorporating such strategies into clinical care, and suggest that improvement in diet quality can be achieved in families living with this burdensome disease. C1 [Nansel, Tonja R.; Haynie, Denise L.; Lipsky, Leah M.; Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Hlth Behav Branch, Bethesda, MD 20892 USA. [Laffel, Lori M. B.; Mehta, Sanjeev N.; Volkening, Lisa K.; Butler, Deborah A.; Higgins, Laurie A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect,Genet & Epid, Boston, MA 02115 USA. RP Nansel, TR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Hlth Behav Branch, 6100 Execut Blvd Rm 7B13R,MSC 7510, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595; Liu, Aiyi/0000-0002-6618-5082; Haynie, Denise/0000-0002-8270-6079 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural Research Program [HHSN267200703434C, HHSN2752008000031/HHSN275002]; National Institute of Diabetes and Digestive and Kidney Diseases Diabetes Research Center [P30DK036836] FX This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural Research Program (contract #HHSN267200703434C and #HHSN2752008000031/HHSN275002). Support for the research infrastructure for study performance at the clinical site was provided to the Joslin Diabetes Center by the National Institute of Diabetes and Digestive and Kidney Diseases Diabetes Research Center grant P30DK036836. NR 52 TC 8 Z9 8 U1 2 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5868 J9 INT J BEHAV NUTR PHY JI Int. J. Behav. Nutr. Phys. Act. PD MAY 8 PY 2015 VL 12 AR 58 DI 10.1186/s12966-015-0214-4 PG 11 WC Nutrition & Dietetics; Physiology SC Nutrition & Dietetics; Physiology GA CI5ZR UT WOS:000354838900001 PM 25952160 ER PT J AU Liu, Y Lear, T Iannone, O Shiva, S Corey, C Rajbhandari, S Jerome, J Chen, BB Mallampalli, RK AF Liu, Yuan Lear, Travis Iannone, Olivia Shiva, Sruti Corey, Catherine Rajbhandari, Shristi Jerome, Jacob Chen, Bill B. Mallampalli, Rama K. TI The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial Function by Mediating the Ubiquitylation and Proteasomal Degradation of Survivin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cell Biology; E3 Ubiquitin Ligase; Lung Injury; Mitochondria; Protein Degradation; Oxygen ID SCF UBIQUITIN LIGASE; RECOGNIZES SUGAR CHAINS; X-LINKED INHIBITOR; IAP PROTEINS; CANCER; APOPTOSIS; COMPLEX; FAMILY; PHOSPHORYLATION; LOCALIZATION AB Background: The SCF ubiquitin E3 ligase component Fbxl7 possesses proapoptotic activity. Results: Fbxl7 targets the antiapoptotic protein survivin for polyubiquitylation and proteasomal degradation. Conclusion: Survivin protects mitochondria from damage induced by Fbxl7. Significance: Understanding how F-box proteins regulate survivin might impact therapies to preserve cellular bioenergetics. Fbxl7, a component of the Skp1Cul1F-box protein type ubiquitin E3 ligase, regulates mitotic cell cycle progression. Here we demonstrate that overexpression of Fbxl7 in lung epithelia decreases the protein abundance of survivin, a member of the inhibitor of apoptosis family. Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin by interacting with Glu-126 within its carboxyl-terminal helix. Furthermore, both Lys-90 and Lys-91 within survivin serve as ubiquitin acceptor sites. Ectopically expressed Fbxl7 impairs mitochondrial function, whereas depletion of Fbxl7 protects mitochondria from actions of carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of oxidative phosphorylation. Compared with wild-type survivin, cellular expression of a survivin mutant protein deficient in its ability to interact with Fbxl7 (E126A) and a ubiquitylation-resistant double point mutant (KK90RR/KK91RR) rescued mitochondria to a larger extent from damage induced by overexpression of Fbxl7. Therefore, these data suggest that the Skp1Cul1F-box protein complex subunit Fbxl7 modulates mitochondrial function by controlling the cellular abundance of survivin. The results raise opportunities for F-box protein targeting to preserve mitochondrial function. C1 [Liu, Yuan; Lear, Travis; Iannone, Olivia; Rajbhandari, Shristi; Jerome, Jacob; Chen, Bill B.; Mallampalli, Rama K.] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Shiva, Sruti; Corey, Catherine] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. RP Chen, BB (reprint author), Univ Pittsburgh, Dept Med, Pulm Allergy & Crit Care Med, Biomed Sci Tower 1,W1254, Pittsburgh, PA 15213 USA. EM chenb@upmc.edu; mallampallirk@upmc.edu RI Regan, Clinton/E-6250-2012; OI Lear, Travis/0000-0001-9156-0844 FU National Institutes of Health [HL096376, HL097376, HL098174, HL081784, 1UH2HL123502, P01 HL114453, HL116472]; Department of Veterans Affairs; Flight Attendants Medical Research Institute FX This work was supported, in whole or in part, by National Institutes of Health R01 Grants HL096376, HL097376, HL098174, HL081784, 1UH2HL123502, and P01 HL114453 (to R. K. M.) and HL116472 (to B. B. C.). This work was also supported by a merit review award from the Department of Veterans Affairs and the Flight Attendants Medical Research Institute. NR 41 TC 6 Z9 6 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 8 PY 2015 VL 290 IS 19 BP 11843 EP 11852 DI 10.1074/jbc.M114.629931 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CH9XA UT WOS:000354388600004 PM 25778398 ER PT J AU Ardlie, KG DeLuca, DS Segre, AV Sullivan, TJ Young, TR Gelfand, ET Trowbridge, CA Maller, JB Tukiainen, T Lek, M Ward, LD Kheradpour, P Iriarte, B Meng, Y Palmer, CD Esko, T Winckler, W Hirschhorn, JN Kellis, M MacArthur, DG Getz, G Shabalin, AA Li, G Zhou, YH Nobel, AB Rusyn, I Wright, FA Lappalainen, T Ferreira, PG Ongen, H Rivas, MA Battle, A Mostafavi, S Monlong, J Sammeth, M Mele, M Reverter, F Goldmann, JM Koller, D Guigo, R McCarthy, MI Dermitzakis, ET Gamazon, ER Im, HK Konkashbaev, A Nicolae, DL Cox, NJ Flutre, T Wen, XQ Stephens, M Pritchard, JK Tu, ZD Zhang, B Huang, T Long, Q Lin, L Yang, JL Zhu, J Liu, J Brown, A Mestichelli, B Tidwell, D Lo, E Salvatore, M Shad, S Thomas, JA Lonsdale, JT Moser, MT Gillard, BM Karasik, E Ramsey, K Choi, C Foster, BA Syron, J Fleming, J Magazine, H Hasz, R Walters, GD Bridge, JP Miklos, M Sullivan, S Barker, LK Traino, HM Mosavel, M Siminoff, LA Valley, DR Rohrer, DC Jewell, SD Branton, PA Sobin, LH Barcus, M Qi, LQ McLean, J Hariharan, P Um, KS Wu, SP Tabor, D Shive, C Smith, AM Buia, SA Undale, AH Robinson, KL Roche, N Valentino, KM Britton, A Burges, R Bradbury, D Hambright, KW Seleski, J Korzeniewski, GE Erickson, K Marcus, Y Tejada, J Taherian, M Lu, CR Basile, M Mash, DC Volpi, S Struewing, JP Temple, GF Boyer, J Colantuoni, D Little, R Koester, S Carithers, LJ Moore, HM Guan, P Compton, C Sawyer, SJ Demchok, JP Vaught, JB Rabiner, CA Lockhart, NC Ardlie, KG Getz, G Wright, FA Kellis, M Volpi, S Dermitzakis, ET AF Ardlie, Kristin G. DeLuca, David S. Segre, Ayellet V. Sullivan, Timothy J. Young, Taylor R. Gelfand, Ellen T. Trowbridge, Casandra A. Maller, Julian B. Tukiainen, Taru Lek, Monkol Ward, Lucas D. Kheradpour, Pouya Iriarte, Benjamin Meng, Yan Palmer, Cameron D. Esko, Tonu Winckler, Wendy Hirschhorn, Joel N. Kellis, Manolis MacArthur, Daniel G. Getz, Gad Shabalin, Andrey A. Li, Gen Zhou, Yi-Hui Nobel, Andrew B. Rusyn, Ivan Wright, Fred A. Lappalainen, Tuuli Ferreira, Pedro G. Ongen, Halit Rivas, Manuel A. Battle, Alexis Mostafavi, Sara Monlong, Jean Sammeth, Michael Mele, Marta Reverter, Ferran Goldmann, Jakob M. Koller, Daphne Guigo, Roderic McCarthy, Mark I. Dermitzakis, Emmanouil T. Gamazon, Eric R. Im, Hae Kyung Konkashbaev, Anuar Nicolae, Dan L. Cox, Nancy J. Flutre, Timothee Wen, Xiaoquan Stephens, Matthew Pritchard, Jonathan K. Tu, Zhidong Zhang, Bin Huang, Tao Long, Quan Lin, Luan Yang, Jialiang Zhu, Jun Liu, Jun Brown, Amanda Mestichelli, Bernadette Tidwell, Denee Lo, Edmund Salvatore, Michael Shad, Saboor Thomas, Jeffrey A. Lonsdale, John T. Moser, Michael T. Gillard, Bryan M. Karasik, Ellen Ramsey, Kimberly Choi, Christopher Foster, Barbara A. Syron, John Fleming, Johnell Magazine, Harold Hasz, Rick Walters, Gary D. Bridge, Jason P. Miklos, Mark Sullivan, Susan Barker, Laura K. Traino, Heather M. Mosavel, Maghboeba Siminoff, Laura A. Valley, Dana R. Rohrer, Daniel C. Jewell, Scott D. Branton, Philip A. Sobin, Leslie H. Barcus, Mary Qi, Liqun McLean, Jeffrey Hariharan, Pushpa Um, Ki Sung Wu, Shenpei Tabor, David Shive, Charles Smith, Anna M. Buia, Stephen A. Undale, Anita H. Robinson, Karna L. Roche, Nancy Valentino, Kimberly M. Britton, Angela Burges, Robin Bradbury, Debra Hambright, Kenneth W. Seleski, John Korzeniewski, Greg E. Erickson, Kenyon Marcus, Yvonne Tejada, Jorge Taherian, Mehran Lu, Chunrong Basile, Margaret Mash, Deborah C. Volpi, Simona Struewing, Jeffery P. Temple, Gary F. Boyer, Joy Colantuoni, Deborah Little, Roger Koester, Susan Carithers, Latarsha J. Moore, Helen M. Guan, Ping Compton, Carolyn Sawyer, Sherilyn J. Demchok, Joanne P. Vaught, Jimmie B. Rabiner, Chana A. Lockhart, Nicole C. Ardlie, Kristin G. Getz, Gad Wright, Fred A. Kellis, Manolis Volpi, Simona Dermitzakis, Emmanouil T. CA GTEx Consortium TI The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans SO SCIENCE LA English DT Article ID GENOME-WIDE ASSOCIATION; HUMAN TRANSCRIPTOME; VARIANTS; DISEASE; IDENTIFICATION; LOCI; ARCHITECTURE; INDIVIDUALS; RESOURCE; SYSTEMS AB Understanding the functional consequences of genetic variation, and how it affects complex human disease and quantitative traits, remains a critical challenge for biomedicine. We present an analysis of RNA sequencing data from 1641 samples across 43 tissues from 175 individuals, generated as part of the pilot phase of the Genotype-Tissue Expression (GTEx) project. We describe the landscape of gene expression across tissues, catalog thousands of tissue-specific and shared regulatory expression quantitative trait loci (eQTL) variants, describe complex network relationships, and identify signals from genome-wide association studies explained by eQTLs. These findings provide a systematic understanding of the cellular and biological consequences of human genetic variation and of the heterogeneity of such effects among a diverse set of human tissues. C1 [DeLuca, David S.; Segre, Ayellet V.; Sullivan, Timothy J.; Young, Taylor R.; Gelfand, Ellen T.; Trowbridge, Casandra A.; Maller, Julian B.; Tukiainen, Taru; Lek, Monkol; Ward, Lucas D.; Kheradpour, Pouya; Meng, Yan; Palmer, Cameron D.; Esko, Tonu; Winckler, Wendy; Hirschhorn, Joel N.; MacArthur, Daniel G.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Maller, Julian B.; Tukiainen, Taru; Lek, Monkol; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ward, Lucas D.; Kheradpour, Pouya; Iriarte, Benjamin] MIT, MIT Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Palmer, Cameron D.; Esko, Tonu; Hirschhorn, Joel N.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. [Palmer, Cameron D.; Esko, Tonu; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Esko, Tonu] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Shabalin, Andrey A.] Virginia Commonwealth Univ, Ctr Biomarker Res & Personalized Med, Richmond, VA 23298 USA. [Li, Gen; Nobel, Andrew B.] Univ N Carolina, Dept Stat & Operat Res, Chapel Hill, NC 27599 USA. [Li, Gen; Nobel, Andrew B.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Zhou, Yi-Hui] N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA. [Zhou, Yi-Hui] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. [Zhou, Yi-Hui] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA. [Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Rusyn, Ivan] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. [Lappalainen, Tuuli; Ferreira, Pedro G.; Ongen, Halit] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Lappalainen, Tuuli; Ferreira, Pedro G.; Ongen, Halit] Univ Geneva, Inst Genet & Genom Geneva iG3, CH-1211 Geneva, Switzerland. [Lappalainen, Tuuli; Ferreira, Pedro G.; Ongen, Halit] Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland. [Lappalainen, Tuuli] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Lappalainen, Tuuli] New York Genome Ctr, New York, NY 10011 USA. [Lappalainen, Tuuli] Columbia Univ, Med Ctr, Dept Syst Biol, New York, NY 10032 USA. [Rivas, Manuel A.; McCarthy, Mark I.] Univ Oxford, Nuffield Dept Clin Med, Wellcome Trust Ctr Human Genet Res, Oxford OX3 7BN, England. [Battle, Alexis; Mostafavi, Sara; Koller, Daphne] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA. [Battle, Alexis] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA. [Monlong, Jean; Sammeth, Michael; Mele, Marta; Reverter, Ferran; Goldmann, Jakob M.; Guigo, Roderic] CRG, Barcelona 08003, Catalonia, Spain. [Monlong, Jean; Sammeth, Michael; Mele, Marta; Guigo, Roderic] Univ Pompeu Fabra, Barcelona 08003, Catalonia, Spain. [Monlong, Jean] McGill Univ, Human Genet Dept, Montreal, PQ H3A 0G1, Canada. [Sammeth, Michael] Natl Inst Sci Comp, BR-25651075 Rio De Janeiro, Brazil. [Mele, Marta] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Reverter, Ferran] Univ Barcelona, E-08028 Barcelona, Spain. [Goldmann, Jakob M.] Radboud Univ Nijmegen, NL-6525 ED Nijmegen, Netherlands. [Guigo, Roderic] Inst Hosp Mar Invest Med IMIM, Barcelona 08003, Spain. [McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Gamazon, Eric R.; Im, Hae Kyung; Konkashbaev, Anuar; Nicolae, Dan L.; Cox, Nancy J.] Univ Chicago, Dept Med, Sect Genet Med, Chicago, IL 60637 USA. [Gamazon, Eric R.; Im, Hae Kyung; Konkashbaev, Anuar; Nicolae, Dan L.; Cox, Nancy J.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Gamazon, Eric R.; Konkashbaev, Anuar; Cox, Nancy J.] Vanderbilt Univ, Dept Med, Div Genet Med, Nashville, TN 37232 USA. [Flutre, Timothee; Stephens, Matthew; Pritchard, Jonathan K.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Flutre, Timothee] INRA, Dept Plant Biol & Breeding, UMR 1334, AGAP, F-34060 Montpellier, France. [Wen, Xiaoquan] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Stephens, Matthew] Univ Chicago, Dept Stat, Chicago, IL 60637 USA. [Pritchard, Jonathan K.] Stanford Univ, Dept Genet & Biol, Stanford, CA 94305 USA. [Pritchard, Jonathan K.] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA. [Tu, Zhidong; Zhang, Bin; Huang, Tao; Long, Quan; Lin, Luan; Yang, Jialiang; Zhu, Jun] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Tu, Zhidong; Zhang, Bin; Huang, Tao; Long, Quan; Lin, Luan; Yang, Jialiang; Zhu, Jun] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Liu, Jun] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. [Brown, Amanda; Mestichelli, Bernadette; Tidwell, Denee; Lo, Edmund; Salvatore, Michael; Shad, Saboor; Thomas, Jeffrey A.; Lonsdale, John T.] Natl Dis Res Interchange, Philadelphia, PA 19103 USA. [Moser, Michael T.; Gillard, Bryan M.; Karasik, Ellen; Ramsey, Kimberly; Choi, Christopher; Foster, Barbara A.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Syron, John; Fleming, Johnell; Magazine, Harold] Sci Care Inc, Phoenix, AZ USA. [Hasz, Rick] Gift Life Donor Program, Philadelphia, PA 19103 USA. [Walters, Gary D.] LifeNet Hlth, Virginia Beach, VA 23453 USA. [Bridge, Jason P.; Miklos, Mark; Sullivan, Susan] UNYTS, Buffalo, NY 14203 USA. [Barker, Laura K.; Traino, Heather M.; Mosavel, Maghboeba; Siminoff, Laura A.] Virginia Commonwealth Univ, Richmond, VA 23298 USA. [Traino, Heather M.; Siminoff, Laura A.] Temple Univ, Dept Publ Hlth, Philadelphia, PA 19122 USA. [Valley, Dana R.; Rohrer, Daniel C.; Jewell, Scott D.] Van Andel Res Inst, Grand Rapids, MI 49503 USA. [Branton, Philip A.; Carithers, Latarsha J.; Moore, Helen M.; Guan, Ping; Compton, Carolyn; Sawyer, Sherilyn J.; Vaught, Jimmie B.; Rabiner, Chana A.; Lockhart, Nicole C.] NCI, Biorepositories & Biospecimen Res Branch, Bethesda, MD 20892 USA. [Sobin, Leslie H.; Barcus, Mary; Qi, Liqun; McLean, Jeffrey; Hariharan, Pushpa; Um, Ki Sung; Wu, Shenpei; Tabor, David; Shive, Charles; Smith, Anna M.; Buia, Stephen A.; Undale, Anita H.; Robinson, Karna L.; Roche, Nancy; Valentino, Kimberly M.; Britton, Angela; Burges, Robin; Bradbury, Debra; Hambright, Kenneth W.; Korzeniewski, Greg E.] Leidos Biomed Res Inc, Clin Res Directorate, Biospecimen Res Grp, Rockville, MD 20852 USA. [Seleski, John] iDoxSolutions Inc, Bethesda, MD 20814 USA. [Erickson, Kenyon] Sapient Govt Serv, Arlington, VA 22201 USA. [Marcus, Yvonne; Tejada, Jorge; Taherian, Mehran; Lu, Chunrong; Basile, Margaret; Mash, Deborah C.] Univ Miami, Miller Sch Med, Dept Neurol, Brain Endowment Bank, Miami, FL 33136 USA. [Struewing, Jeffery P.; Temple, Gary F.; Colantuoni, Deborah] NHGRI, Div Genom Med, Bethesda, MD 20892 USA. [Boyer, Joy; Lockhart, Nicole C.] NHGRI, Div Genom & Soc, Bethesda, MD 20892 USA. [Little, Roger] NIMH, Off Sci Policy Planning & Commun, Bethesda, MD 20892 USA. [Koester, Susan] NIMH, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA. [Demchok, Joanne P.] NCI, Canc Diag Program, Bethesda, MD 20892 USA. RP Ardlie, KG (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM kardlie@broadinstitute.org; emmanouil.dermitzakis@unige.ch RI Guigo, Roderic/D-1303-2010; reverter, ferran/I-1547-2015; Sammeth, Michael/C-1157-2014; Rusyn, Ivan/S-2426-2016; OI Guigo, Roderic/0000-0002-5738-4477; reverter, ferran/0000-0002-9489-3350; Sammeth, Michael/0000-0002-6528-9883; Monlong, Jean/0000-0002-9737-5516; Wen, Xiaoquan/0000-0001-8990-2737 FU Common Fund of the Office of the Director, U.S. National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NIA; NIAID; NINDS through NIH [HHSN261200800001E, 10XS170, 10XS171, 12ST1039, 10ST1035, HHSN268201000029C]; European Research Council; Swiss National Science Foundation; Louis-Jeantet Foundation; Wellcome Trust [098381]; Clarendon Scholarship; NDM Studentship; Univ. of Oxford Green Templeton College Award; NIH [R01 DA006227-17, R01 MH090941, R01 MH090951, R01 MH090937, R01 MH090936, R01 MH090948, R01 GM104371, R01AG046170, R01CA163772, U01AI111598-01] FX We thank the donors and their families for their generous gifts of organ donation for transplantation and tissue donations for the GTEx research study; the Genomics Platform at the Broad Institute for data generation; J. Nedzel, K. Huang, and K. Hadley for work on the GTEx Portal; L. Gaffney for help with figures; and members of the Analysis Working Group for scientific editing and feedback. The primary and processed data used to generate the analyses presented here are available in the following locations: all primary sequence and clinical data files, and any other protected data, are deposited in and available from dbGaP (www.ncbi.nlm.nih.gov/gap) (phs000424.v3.p1, except for whole-exome sequencing data, which are part of phs000424.v5.p1); derived analysis files are available on the GTEx Portal (www.gtexportal.org). Biospecimens remaining from the study may be requested for research studies. The sample request form, biospecimen access policy, and material transfer agreement (MTA) are available on the GTEx Portal (www.gtexportal.org/home/samplesPage). Supported by the Common Fund of the Office of the Director, U.S. National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, NIA, NIAID, and NINDS through NIH contracts HHSN261200800001E (Leidos Prime contract with NCI), 10XS170 (NDRI), 10XS171 (Roswell Park Cancer Institute), 10X172 (Science Care Inc.), 12ST1039 (IDOX), 10ST1035 (Van Andel Institute), and HHSN268201000029C (Broad Institute) and through NIH grants R01 DA006227-17 (Univ. of Miami Brain Bank), R01 MH090941 (Univ. of Geneva), R01 MH090951 and R01 MH090937 (Univ. of Chicago), R01 MH090936 (Univ. of North Carolina-Chapel Hill), R01 MH090948 (Harvard Univ.), R01 GM104371 (Massachusetts General Hospital), and R01AG046170, R01CA163772, and U01AI111598-01 (Icahn School of Medicine, Mount Sinai). Additional support: European Research Council, Swiss National Science Foundation, and Louis-Jeantet Foundation (E.T.D.); Wellcome Trust grant 098381 (M.I.M.); Clarendon Scholarship, a NDM Studentship, and a Univ. of Oxford Green Templeton College Award (M.A.R.). J.K.P. is compensated for his work on the scientific advisory board for 23andMe and computational advisory board for DNANexus; W.W. is an employee and shareholder of Novartis Inc.; A. Battle is a shareholder of Google, Inc.; J. Fleming is executive director of the American Medical and Research Association; and J.B.V. and R. Little serve on the board of NDRI. Author contributions: The GTEx Consortium contributed collectively to this study. Biospecimens were provided by the Biospecimen source sites and the brain bank operations, and processed by the LDACC and comprehensive biospecimen resource. Pathological review of specimens was conducted by the pathology resource center, and all donor data entry and review by the comprehensive data resource. Data generation was undertaken by the Laboratory, Data Analysis and Coordinating Center (LDACC), and analyses were performed by all members of the Analysis Working Group. Project activities were coordinated by caHUB operations and overseen by the NHGRI, NIMH, and NCI project teams. We acknowledge the following investigators of the Analysis Working Group who contributed substantially to analyses presented here. Transcriptome variation: D.S.D., P.G.F. Single-tissue eQTL analysis: A.A.S., D.S.D., A.V.S. Multitissue eQTL analysis: T.F., X.W., A.A.S., G.L. Allele-specific expression: T.L. Splice QTLs: J.M., H.O. Functional annotation: L.D.W., P.K. Network Analyses: A. Battle, S.M., Z.T., T.H., B.I. Protein-truncating analyses: M.A.R., M.; L. GWAS analysis: E.R.G., A.V.S., L.D.W. NR 45 TC 309 Z9 311 U1 16 U2 73 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAY 8 PY 2015 VL 348 IS 6235 BP 648 EP 660 DI 10.1126/science.1262110 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH5AI UT WOS:000354045700036 ER PT J AU Mele, M Ferreira, PG Reverter, F DeLuca, DS Monlong, J Sammeth, M Young, TR Goldmann, JM Pervouchine, DD Sullivan, TJ Johnson, R Segre, AV Djebali, S Niarchou, A Wright, FA Lappalainen, T Calvo, M Getz, G Dermitzakis, ET Ardlie, KG Guigo, R AF Mele, Marta Ferreira, Pedro G. Reverter, Ferran DeLuca, David S. Monlong, Jean Sammeth, Michael Young, Taylor R. Goldmann, Jakob M. Pervouchine, Dmitri D. Sullivan, Timothy J. Johnson, Rory Segre, Ayellet V. Djebali, Sarah Niarchou, Anastasia Wright, Fred A. Lappalainen, Tuuli Calvo, Miquel Getz, Gad Dermitzakis, Emmanouil T. Ardlie, Kristin G. Guigo, Roderic CA GTEx Consortium TI The human transcriptome across tissues and individuals SO SCIENCE LA English DT Article ID GENE-EXPRESSION; HUMAN GENOME; REVEALS; DISCOVERY; ELEMENTS AB Transcriptional regulation and posttranscriptional processing underlie many cellular and organismal phenotypes. We used RNA sequence data generated by Genotype-Tissue Expression (GTEx) project to investigate the patterns of transcriptome variation across individuals and tissues. Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples. These signatures are dominated by a relatively small number of genes-which is most clearly seen in blood-though few are exclusive to a particular tissue and vary more across tissues than individuals. Genes exhibiting high interindividual expression variation include disease candidates associated with sex, ethnicity, and age. Primary transcription is the major driver of cellular specificity, with splicing playing mostly a complementary role; except for the brain, which exhibits a more divergent splicing program. Variation in splicing, despite its stochasticity, may play in contrast a comparatively greater role in defining individual phenotypes. C1 [Mele, Marta; Ferreira, Pedro G.; Reverter, Ferran; Monlong, Jean; Sammeth, Michael; Goldmann, Jakob M.; Pervouchine, Dmitri D.; Johnson, Rory; Djebali, Sarah; Guigo, Roderic] CRG, Barcelona, Catalonia, Spain. [Mele, Marta] Harvard Univ, Harvard Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Ferreira, Pedro G.; Niarchou, Anastasia; Lappalainen, Tuuli; Dermitzakis, Emmanouil T.] Univ Geneva, Dept Genet Med & Dev, Geneva, Switzerland. [Ferreira, Pedro G.; Niarchou, Anastasia; Lappalainen, Tuuli; Dermitzakis, Emmanouil T.] Univ Geneva, Inst Genet, Geneva, Switzerland. [Ferreira, Pedro G.; Niarchou, Anastasia; Lappalainen, Tuuli; Dermitzakis, Emmanouil T.] Univ Geneva, Genom Geneva iGE3, Geneva, Switzerland. [Ferreira, Pedro G.; Niarchou, Anastasia; Lappalainen, Tuuli; Dermitzakis, Emmanouil T.] Swiss Inst Bioinformat, Geneva, Switzerland. [Reverter, Ferran; Calvo, Miquel] UB, Fac Biol, Barcelona, Catalonia, Spain. [Reverter, Ferran; Monlong, Jean; Sammeth, Michael; Goldmann, Jakob M.; Pervouchine, Dmitri D.; Johnson, Rory; Djebali, Sarah; Guigo, Roderic] UPF, Barcelona, Catalonia, Spain. [DeLuca, David S.; Young, Taylor R.; Sullivan, Timothy J.; Segre, Ayellet V.; Getz, Gad; Ardlie, Kristin G.] Broad Inst & Harvard, Cambridge, MA USA. [Monlong, Jean] McGill Univ, Montreal, PQ, Canada. [Sammeth, Michael] Natl Inst Sci Comp LNCC, Rio De Janeiro, Brazil. [Goldmann, Jakob M.] Radboud Univ Nijmegen, NL-6525 ED Nijmegen, Netherlands. [Pervouchine, Dmitri D.] Moscow MV Lomonosov State Univ, Fac Bioengn & Bioinformat, Moscow 119992, Russia. [Wright, Fred A.] N Carolina State Univ, Raleigh, NC 27695 USA. [Lappalainen, Tuuli] New York Genome Ctr, New York, NY USA. [Lappalainen, Tuuli] Columbia Univ, Dept Syst Biol, New York, NY USA. [Getz, Gad] Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02114 USA. [Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Guigo, Roderic] Inst Hosp Mar Invest Med IMIM, Barcelona, Catalonia, Spain. [Guigo, Roderic] IRB, Joint CRG Barcelona Super Comp Ctr BSC, Program Computat Biol, Barcelona, Catalonia, Spain. RP Ardlie, KG (reprint author), CRG, Barcelona, Catalonia, Spain. EM kardlie@broadinstitute.org; roderic.guigo@crg.cat RI Djebali, Sarah/O-9817-2014; Goldmann, Jakob/K-5948-2013; Pervouchine, Dmitri/H-5252-2015; Guigo, Roderic/D-1303-2010; reverter, ferran/I-1547-2015; Sammeth, Michael/C-1157-2014; OI Monlong, Jean/0000-0002-9737-5516; Djebali, Sarah/0000-0002-0599-1267; Goldmann, Jakob/0000-0002-8514-573X; Pervouchine, Dmitri/0000-0003-0543-9760; Guigo, Roderic/0000-0002-5738-4477; reverter, ferran/0000-0002-9489-3350; Sammeth, Michael/0000-0002-6528-9883; Calvo LLorca, Miguel/0000-0002-4016-3336 FU Common Fund of the Office of the Director of the National Institutes of Health; National Cancer Institute (NCI); National Human Genome Research Institute; National Heart, Lung, and Blood Institute; National Institute on Drug Abuse; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; United States National Institutes of Health [HHSN261200800001E, 10XS170, 10XS171, 10X172, 12ST1039, 10ST1035, HHSN268201000029C, R01 DA006227-17, R01 MH090941]; European Research Council; Swiss National Science Foundation; Louis-Jeantet Foundation [R01 MH090936]; Spanish Ministerio de Ciencia e Innovacion (MICINN) [BIO2011-26205]; Generalitat de Catalunya [2014 SGR 464, 2014 SGR 1319]; European Research Council-European Commission [294653] FX We acknowledge and thank the donors and their families for their generous gifts of organ donation for transplantation and tissue donations for the GTEx research study. We thank the Genomics Platform at the Broad Institute for data generation; L. Gaffney for help with figures; E. Gelfand and C. Trowbridge for project support and members of the Analysis Working Group for feedback; and D. MacArthur, J. Maller, and B. Neale for critical reading of the manuscript. The primary and processed data used to generate the analyses presented here are available in the following locations: All primary sequence files are deposited in and available from dbGaP (phs000424.v3.p1); gene and transcript quantifications are available on the GTEx Portal (www.gtexportal.org). The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health (http://commonfund.nih.gov/GTEx). Additional funds were provided by the National Cancer Institute (NCI); National Human Genome Research Institute; National Heart, Lung, and Blood Institute; National Institute on Drug Abuse; National Institute of Mental Health; and National Institute of Neurological Disorders and Stroke. This work was supported by the following grants and contracts from the United States National Institutes of Health: contract HHSN261200800001E (Leidos Prime contract with NCI); contracts 10XS170 [National Disease Research Interchange (NDRI)], 10XS171 (Roswell Park Cancer Institute), 10X172 (Science Care Inc.), and 12ST1039 (IDOX); contract 10ST1035 (Van Andel Institute); contract HHSN268201000029C (Broad Institute); R01 DA006227-17 (University of Miami Brain Bank); R01 MH090941 (University of Geneva), European Research Council, Swiss National Science Foundation, and Louis-Jeantet Foundation to E.T.D.; R01 MH090936 (University of North Carolina-Chapel Hill); and grants BIO2011-26205 from the Spanish Ministerio de Ciencia e Innovacion (MICINN), 2014 SGR 464 and 2014 SGR 1319 from the Generalitat de Catalunya, and 294653 from the European Research Council-European Commission. NR 22 TC 138 Z9 140 U1 6 U2 56 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAY 8 PY 2015 VL 348 IS 6235 BP 660 EP 665 DI 10.1126/science.aaa0355 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH5AI UT WOS:000354045700037 PM 25954002 ER PT J AU Rivas, MA Pirinen, M Conrad, DF Lek, M Tsang, EK Karczewski, KJ Maller, JB Kukurba, KR DeLuca, DS Fromer, M Ferreira, PG Smith, KS Zhang, R Zhao, FM Banks, E Poplin, R Ruderfer, DM Purcell, SM Tukiainen, T Minikel, EV Stenson, PD Cooper, DN Huang, KH Sullivan, TJ Nedzel, J Bustamante, CD Li, JB Daly, MJ Guigo, R Donnelly, P Ardlie, K Sammeth, M Dermitzakis, ET McCarthy, MI Montgomery, SB Lappalainen, T MacArthur, DG AF Rivas, Manuel A. Pirinen, Matti Conrad, Donald F. Lek, Monkol Tsang, Emily K. Karczewski, Konrad J. Maller, Julian B. Kukurba, Kimberly R. DeLuca, David S. Fromer, Menachem Ferreira, Pedro G. Smith, Kevin S. Zhang, Rui Zhao, Fengmei Banks, Eric Poplin, Ryan Ruderfer, Douglas M. Purcell, Shaun M. Tukiainen, Taru Minikel, Eric V. Stenson, Peter D. Cooper, David N. Huang, Katharine H. Sullivan, Timothy J. Nedzel, Jared Bustamante, Carlos D. Li, Jin Billy Daly, Mark J. Guigo, Roderic Donnelly, Peter Ardlie, Kristin Sammeth, Michael Dermitzakis, Emmanouil T. McCarthy, Mark I. Montgomery, Stephen B. Lappalainen, Tuuli MacArthur, Daniel G. CA GTEx Consortium Geuvadis Consortium TI Effect of predicted protein-truncating genetic variants on the human transcriptome SO SCIENCE LA English DT Article ID RNA-SEQ DATA; HUMAN GENOMES; EXPRESSION; DISEASE; DOSAGE AB Accurate prediction of the functional effect of genetic variation is critical for clinical genome interpretation. We systematically characterized the transcriptome effects of protein-truncating variants, a class of variants expected to have profound effects on gene function, using data from the Genotype-Tissue Expression (GTEx) and Geuvadis projects. We quantitated tissue-specific and positional effects on nonsense-mediated transcript decay and present an improved predictive model for this decay. We directly measured the effect of variants both proximal and distal to splice junctions. Furthermore, we found that robustness to heterozygous gene inactivation is not due to dosage compensation. Our results illustrate the value of transcriptome data in the functional interpretation of genetic variants. C1 [Rivas, Manuel A.; Donnelly, Peter; McCarthy, Mark I.] Univ Oxford, Nuffield Dept Clin Med, Wellcome Trust Ctr Human Genet, Oxford, England. [Pirinen, Matti] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Conrad, Donald F.] Washington Univ, St Louis, MO USA. [Lek, Monkol; Karczewski, Konrad J.; Maller, Julian B.; DeLuca, David S.; Fromer, Menachem; Zhao, Fengmei; Banks, Eric; Poplin, Ryan; Purcell, Shaun M.; Tukiainen, Taru; Minikel, Eric V.; Huang, Katharine H.; Sullivan, Timothy J.; Nedzel, Jared; Daly, Mark J.; Ardlie, Kristin; MacArthur, Daniel G.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Lek, Monkol; Karczewski, Konrad J.; Maller, Julian B.; Fromer, Menachem; Zhao, Fengmei; Purcell, Shaun M.; Tukiainen, Taru; Minikel, Eric V.; Daly, Mark J.; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Tsang, Emily K.; Kukurba, Kimberly R.; Smith, Kevin S.; Zhang, Rui; Bustamante, Carlos D.; Li, Jin Billy; Montgomery, Stephen B.; Lappalainen, Tuuli] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Tsang, Emily K.; Kukurba, Kimberly R.; Smith, Kevin S.; Montgomery, Stephen B.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. [Tsang, Emily K.] Stanford Univ, Biomed Informat Program, Stanford, CA 94305 USA. [Fromer, Menachem; Ruderfer, Douglas M.; Purcell, Shaun M.] Mt Sinai Hosp, Dept Psychiat, New York, NY USA. [Ferreira, Pedro G.; Dermitzakis, Emmanouil T.; Lappalainen, Tuuli] Univ Geneva, Dept Genet Med & Dev, Geneva, Switzerland. [Ferreira, Pedro G.; Dermitzakis, Emmanouil T.; Lappalainen, Tuuli] Univ Geneva, Inst Genet & Genom Geneva iGE3, Geneva, Switzerland. [Ferreira, Pedro G.; Dermitzakis, Emmanouil T.; Lappalainen, Tuuli] Swiss Inst Bioinformat, Geneva, Switzerland. [Ruderfer, Douglas M.; Purcell, Shaun M.] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY 10029 USA. [Stenson, Peter D.; Cooper, David N.] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff CF10 3AX, S Glam, Wales. [Guigo, Roderic; Sammeth, Michael] UPF, CRG, Barcelona, Catalonia, Spain. [Donnelly, Peter] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Sammeth, Michael] Natl Inst Sci Comp LNCC, Rio De Janeiro, Brazil. [McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Lappalainen, Tuuli] New York Genome Ctr, New York, NY USA. [Lappalainen, Tuuli] Columbia Univ, Dept Syst Biol, New York, NY USA. [MacArthur, Daniel G.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Rivas, MA (reprint author), Univ Oxford, Nuffield Dept Clin Med, Wellcome Trust Ctr Human Genet, Oxford, England. EM rivas@well.ox.ac.uk; tlappalainen@nygenome.org; macarthur@atgu.mgh.harvard.edu RI Guigo, Roderic/D-1303-2010; Sammeth, Michael/C-1157-2014; Beltran, Sergi/I-3408-2015; Meitinger, Thomas/O-1318-2015; Ruderfer, Douglas/M-5795-2016; Hasler, Robert/A-4908-2009; OI Guigo, Roderic/0000-0002-5738-4477; Sammeth, Michael/0000-0002-6528-9883; Beltran, Sergi/0000-0002-2810-3445; Pirinen, Matti/0000-0002-1664-1350; Ruderfer, Douglas/0000-0002-2365-386X; Cooper, David N./0000-0002-8943-8484; Karczewski, Konrad/0000-0003-2878-4671 FU National Institutes of Health [NIGMS R01GM104371, NIMH R01MH101814, R01MH090941, U01HG007593, R01MH101810]; Academy of Finland [257654]; Hewlett-Packard Stanford Graduate Fellowship; Natural Science and Engineering Research Council of Canada; National Defense Science and Engineering Graduate Fellowship (NDSEG) from the United States Department of Defense (DoD); European Research Council; Swiss National Science Foundation; Louis-Jeantet Foundation; Wellcome Trust [095552/Z/11/Z, 090532/Z/09/Z, 098381]; University of Oxford; Common Fund of the Office of the Director of NIH; NCI/SAIC-Frederick, Inc. (SAIC-F) [X10S172]; University of Geneva [MH090941]; University of Chicago [MH090951, MH090937]; University of North Carolina-Chapel Hill [MH090936]; Harvard University [MH090948]; [HHSN268201000029C]; [10ST1035]; [DA006227] FX We thank all the members of the GTEx and Geuvadis consortia and L. Solomon for assistance with the figures. This work was supported by the National Institutes of Health (NIGMS R01GM104371 to D.G.M.; NIMH R01MH101814 to E.T.D, C.D.B., S.B.M., R.G., T.L., and M.I.M.; R01MH090941 to E.T.D. and M.I.M.; U01HG007593 to J.B.L. and S.B.M.; and R01MH101810 to D.F.C.); Academy of Finland (257654 to M.P.); a Hewlett-Packard Stanford Graduate Fellowship and a doctoral fellowship from the Natural Science and Engineering Research Council of Canada to E.K.T.; a National Defense Science and Engineering Graduate Fellowship (NDSEG) from the United States Department of Defense (DoD) to K.R.K.; European Research Council, Swiss National Science Foundation, and Louis-Jeantet Foundation to E.T.D.; Wellcome Trust (095552/Z/11/Z and 090532/Z/09/Z to P.D. and 098381 to M.I.M.); and a Clarendon Scholarship, NDM Studentship, and Green Templeton College Award from University of Oxford to M.A.R. The Genotype-Tissue Expression (GTEx) project was supported by the Common Fund of the Office of the Director of NIH. Additional funds were enrolled at Biospecimen Source sites funded by NCI/SAIC-Frederick, Inc. (SAIC-F) subcontracts to the National Disease Research Interchange (10XS170), Roswell Park Cancer Institute (10XS171), and Science Care, Inc. (X10S172). The Laboratory, Data Analysis, and Coordinating Center (LDACC) was funded through a contract (HHSN268201000029C) to the Broad Institute, Inc. Biorepository operations were funded through an SAIC-F subcontract to Van Andel Institute (10ST1035). Additional data repository and project management were provided by SAIC-F (HHSN261200800001E). The Brain Bank was supported by a supplement to University of Miami grant DA006227. Statistical methods development grants were made to the University of Geneva (MH090941), the University of Chicago (MH090951 and MH090937), the University of North Carolina-Chapel Hill (MH090936), and Harvard University (MH090948). The primary and processed data used to generate the analyses presented here are available in the following locations: All primary sequence and clinical data files, and any other protected data, are deposited in and available from the database of Genotypes and Phenotypes (www.ncbi.nlm.nih.gov/gap) (phs000424.v3.p1, except for whole-exome sequencing data in phs000424.v5.p1 and mmPCR-seq data and processed ASE data in phs000424.v6.p1); derived analysis files are available on the GTEx Portal (www.gtexportal.org). Biospecimens remaining from the study may be requested for research studies. The sample request form, biospecimen access policy, and material transfer agreement are available on the GTEx Portal (www.gtexportal.org/home/samplesPage). The Geuvadis data are available in ArrayExpress accession E-GEUV-1. Further details and links to data and software are available in www.well.ox.ac.uk/similar to rivas/ptv2015. C.D.B. is a paid member of the Scientific Advisory Boards of Personalis, InVitae, and Ancestry.com; he is founder and chair of the SAB of Identify Genomics, LLC; he also owns stock options in Personalis, Invitae, and Identify Genomics, LLC. NR 27 TC 33 Z9 35 U1 3 U2 30 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAY 8 PY 2015 VL 348 IS 6235 BP 666 EP 669 DI 10.1126/science.1261877 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH5AI UT WOS:000354045700038 PM 25954003 ER PT J AU Egan, ES Jiang, RHY Moechtar, MA Barteneva, NS Weekes, MP Nobre, LV Gygi, SP Paulo, JA Frantzreb, C Tani, Y Takahashi, J Watanabe, S Goldberg, J Paul, AS Brugnara, C Root, DE Wiegand, RC Doench, JG Duraisingh, MT AF Egan, Elizabeth S. Jiang, Rays H. Y. Moechtar, Mischka A. Barteneva, Natasha S. Weekes, Michael P. Nobre, Luis V. Gygi, Steven P. Paulo, Joao A. Frantzreb, Charles Tani, Yoshihiko Takahashi, Junko Watanabe, Seishi Goldberg, Jonathan Paul, Aditya S. Brugnara, Carlo Root, David E. Wiegand, Roger C. Doench, John G. Duraisingh, Manoj T. TI A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion SO SCIENCE LA English DT Article ID RED-BLOOD-CELLS; DECAY-ACCELERATING FACTOR; GROUP-A STREPTOCOCCUS; RESISTANCE LOCI; INAB PHENOTYPE; GENOME-WIDE; MALARIA; INFECTION; RECEPTOR; ASSOCIATION AB Efforts to identify host determinants for malaria have been hindered by the absence of a nucleus in erythrocytes, which precludes genetic manipulation in the cell in which the parasite replicates. We used cultured red blood cells derived from hematopoietic stem cells to carry out a forward genetic screen for Plasmodium falciparum host determinants. We found that CD55 is an essential host factor for P. falciparum invasion. CD55-null erythrocytes were refractory to invasion by all isolates of P. falciparum because parasites failed to attach properly to the erythrocyte surface. Thus, CD55 is an attractive target for the development of malaria therapeutics. Hematopoietic stem cell-based forward genetic screens may be valuable for the identification of additional host determinants of malaria pathogenesis. C1 [Egan, Elizabeth S.; Jiang, Rays H. Y.; Moechtar, Mischka A.; Frantzreb, Charles; Goldberg, Jonathan; Paul, Aditya S.; Duraisingh, Manoj T.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Egan, Elizabeth S.] Boston Childrens Hosp, Div Infect Dis, Boston, MA USA. [Jiang, Rays H. Y.] Univ S Florida, Dept Global Hlth, Tampa, FL USA. [Jiang, Rays H. Y.] Univ S Florida, Ctr Drug Discovery & Innovat, Tampa, FL USA. [Barteneva, Natasha S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Barteneva, Natasha S.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Weekes, Michael P.; Nobre, Luis V.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. [Gygi, Steven P.; Paulo, Joao A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Tani, Yoshihiko; Takahashi, Junko] Japanese Red Cross Kinki Block Blood Ctr, Osaka, Japan. [Watanabe, Seishi] Japanese Red Cross Kyushu Block Blood Ctr, Fukuoka, Japan. [Brugnara, Carlo] Boston Childrens Hosp, Dept Lab Med, Boston, MA USA. [Brugnara, Carlo] Harvard Univ, Sch Med, Boston, MA USA. [Root, David E.; Wiegand, Roger C.; Doench, John G.; Duraisingh, Manoj T.] Broad Inst Harvard & Massachussetts Insititute Te, Cambridge, MA 02142 USA. RP Duraisingh, MT (reprint author), Broad Inst Harvard & Massachussetts Insititute Te, Cambridge, MA 02142 USA. EM mduraisi@hsph.harvard.edu OI Doench, John/0000-0002-3707-9889 FU Foundation Grand Challenges Exploration Award [OPP1035276]; NIH [R01AI091787, K08 1K08AI103034-01A1, K01DK098285]; Pediatric Scientist Development Program Fellowship from the Eunice Kennedy Shriver National Institute of Child Health and Human Development [K12-HD000850]; Boston Children's Hospital Faculty Development Award; Cambridge Biomedical Research Center, UK FX We thank D. Wirth, M. Ganter, A. Nicholson-Weller, M. Waldor, S. Lux, R. Husson, B. Burleigh, and members of the Duraisingh Laboratory for helpful discussions and reading of the manuscript. We thank C. Westhoff and C. Lomas-Francis of the New York Blood Center for gift of the second Inab sample. We thank U. Kanjee for technical assistance and D. Ndiaye, S. Mboup, and S. Volkman for P. falciparum clinical isolates from Senegal. This work was supported by a Gates Foundation Grand Challenges Exploration Award OPP1035276 (M.T.D.), NIH grant R01AI091787 (M.T.D.), a Pediatric Scientist Development Program Fellowship from the Eunice Kennedy Shriver National Institute of Child Health and Human Development K12-HD000850 (E.S.E), NIH grant K08 1K08AI103034-01A1 (E.S.E.), Boston Children's Hospital Faculty Development Award (E.S.E.), NIH grant K01DK098285 (J.A.P.), and the Cambridge Biomedical Research Center, UK (M.P.W. and L.V.N.). Additional data can be found in the supplementary materials. NR 35 TC 20 Z9 20 U1 1 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAY 8 PY 2015 VL 348 IS 6235 BP 711 EP 714 DI 10.1126/science.aaa3526 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH5AI UT WOS:000354045700050 PM 25954012 ER PT J AU SanGiovanni, JP Chen, J Gupta, AS Smith, LEH Sapieha, P Lee, PH AF SanGiovanni, John Paul Chen, Jing Gupta, Ankur S. Smith, Lois E. H. Sapieha, Przemyslaw Lee, Phil H. TI Netrin-1-DCC Signaling Systems and Age-Related Macular Degeneration SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; ANGIOGENESIS; HYPOXIA; DISEASE; GROWTH AB We conducted a nested candidate gene study and pathway-based enrichment analysis on data from a multi-national 77,000-person project on the molecular genetics of age-related macular degeneration (AMD) to identify AMD-associated DNA-sequence variants in genes encoding constituents of a netrin-1 (NTN1)-based signaling pathway that converges on DNA-binding transcription complexes through a 3'-5'-cyclic adenosine monophosphate-calcineurin (cAMP-CN)-dependent axis. AMD-associated single nucleotide polymorphisms (SNPs) existed in 9 linkage disequilibrium-independent genomic regions; these included loci overlapping NTN1 (rs9899630, P <= 9.48 x 10(-5)), DCC (Deleted in Colorectal Cancer)-the gene encoding a primary NTN1 receptor (rs8097127, P <= 3.03 x 10(-5)), and 6 other netrin-related genes. Analysis of the NTN1-DCC pathway with exact methods demonstrated robust enrichment with AMD-associated SNPs (corrected P-value = 0.038), supporting the idea that processes driven by NTN1-DCC signaling systems operate in advanced AMD. The NTN1-DCC pathway contains targets of FDA-approved drugs and may offer promise for guiding applied clinical research on preventive and therapeutic interventions for AMD. C1 [SanGiovanni, John Paul] NIAAA, Sect Nutr Neurosci, NIH, Bethesda, MD 20892 USA. [Chen, Jing; Smith, Lois E. H.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston Childrens Hosp, Boston, MA USA. [Gupta, Ankur S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Sapieha, Przemyslaw] Univ Montreal, Dept Ophthalmol, Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ, Canada. [Lee, Phil H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Analyt & Translat Genet Unit,Ctr Human Genet Res, Boston, MA USA. RP SanGiovanni, JP (reprint author), NIAAA, Sect Nutr Neurosci, NIH, Bethesda, MD 20892 USA. EM jpsangio@post.harvard.edu FU Canadian Institutes of Health Research [221478]; Foundation Fighting Blindness; U.S. National Institute of Mental Health (NIMH) grant [K99MH101367]; U.S. National Eye Institute [NEI EY022274, EY017017, PO1 HD18655, R01 EY024963]; Lowey Medical Research Institute; European Commission FP7 Project [305485]; NIH Intramural Research Program; Bright Focus Foundation FX PS holds a Canada Research Chair in Retinal Cell Biology and is supported by operating grants from the Canadian Institutes of Health Research (221478) and the Foundation Fighting Blindness. PHL is supported by U.S. National Institute of Mental Health (NIMH) grant K99MH101367. LEHS was supported by grants from the U.S. National Eye Institute (NEI EY022274, EY017017, PO1 HD18655), The Lowey Medical Research Institute, European Commission FP7 Project 305485 PREVENT-ROP. JPSG was supported by the NIH Intramural Research Program. JC was supported by the Bright Focus Foundation and a grant from the U.S. National Eye Institute (R01 EY024963). None of these funders had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Extant GWA study findings were published by Fritsche et al.[12] The data used for the original genetic analyses were obtained from the NEI Study of Age-Related Macular Degeneration (NEI-AMD) Database found at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id = phs000182.v2.p1 (dbGaP Study Accession: phs000182.v2.p1). We thank NEI-AMD and AGC participants and the NEI-AMD and AGC Research Groups for their valuable contributions to this research project. JPSG was supported by the NIH Intramural Research Program. PS holds a Canada Research Chair in Retinal Cell Biology and is supported by operating grants from the Canadian Institutes of Health Research (221478) and the Foundation Fighting Blindness. NR 24 TC 1 Z9 1 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 7 PY 2015 VL 10 IS 5 AR e0125548 DI 10.1371/journal.pone.0125548 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA4RU UT WOS:000367788800006 PM 25950802 ER PT J AU Brown, JR Barrientos, JC Barr, PM Flinn, IW Burger, JA Tran, A Clow, F James, DF Graef, T Friedberg, JW Rai, K O'Brien, S AF Brown, Jennifer R. Barrientos, Jacqueline C. Barr, Paul M. Flinn, Ian W. Burger, Jan A. Anh Tran Clow, Fong James, Danelle F. Graef, Thorsten Friedberg, Jonathan W. Rai, Kanti O'Brien, Susan TI The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia SO BLOOD LA English DT Article ID FLUDARABINE PLUS CYCLOPHOSPHAMIDE; ANTIGEN RECEPTOR; KAPPA-B; INITIAL THERAPY; OPEN-LABEL; ACTIVATION; RITUXIMAB; TRIAL; PCI-32765; SURVIVAL AB The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naive previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either CIT or single-agent ibrutinib. The overall response rate (ORR) with BR-ibrutinib was 93.3%, including 16.7% complete responses (CRs) initially, which increased to 40% with the extension period. Including 1 patient with partial response with lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and 70.3% remained progression-free, respectively. All 3 patients treated with ibrutinib-FCR achieved CR. Ibrutinib may enhance CIT efficacy without additive toxicities, providing the rationale for studying this combination in an ongoing phase 3 trial. C1 [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Barrientos, Jacqueline C.; Rai, Kanti] Hofstra Univ, Hofstra North Shore Long Isl Jewish Med Ctr, Sch Med, Hempstead, NY 11550 USA. [Barr, Paul M.; Friedberg, Jonathan W.] Univ Rochester, James P Wilmot Canc Ctr, Div Hematol Oncol, Rochester, NY USA. [Flinn, Ian W.] Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN USA. [Burger, Jan A.; O'Brien, Susan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Anh Tran; Clow, Fong; James, Danelle F.; Graef, Thorsten] Pharmacyclics, Sunnyvale, CA USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jennifer_brown@dfci.harvard.edu OI Barr, Paul/0000-0002-9733-401X FU Pharmacyclics; Pharmacyclics (Sunnyvale, CA) FX The authors thank Zeena Salman for trial management and Ying Luan for statistical support. Medical writing assistance was provided by Karen Pemberton and funded by Pharmacyclics.; This study was supported by research funding from Pharmacyclics (Sunnyvale, CA), which provided each site with the pharmaceuticals and funding for the research costs of the study. NR 42 TC 44 Z9 46 U1 1 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 7 PY 2015 VL 125 IS 19 BP 2915 EP 2922 DI 10.1182/blood-2014-09-585869 PG 8 WC Hematology SC Hematology GA CJ7OX UT WOS:000355687500011 PM 25755291 ER PT J AU Kim, SH Wu, SY Baek, JI Choi, SY Su, Y Flynn, CR Gamse, JT Ess, KC Hardiman, G Lipschutz, JH Abumrad, NN Rockey, DC AF Kim, Seok-Hyung Wu, Shu-Yu Baek, Jeong-In Choi, Soo Young Su, Yanhui Flynn, Charles R. Gamse, Joshua T. Ess, Kevin C. Hardiman, Gary Lipschutz, Joshua H. Abumrad, Naji N. Rockey, Don C. TI A Post-Developmental Genetic Screen for Zebrafish Models of Inherited Liver Disease SO PLOS ONE LA English DT Article ID CHEDIAK-HIGASHI-SYNDROME; ANIMAL-MODELS; HEPATIC STEATOSIS; LEADS; IDENTIFICATION; INHIBITION; STRESS AB Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease such as simple steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis and fibrosis. However, the molecular pathogenesis and genetic variations causing NAFLD are poorly understood. The high prevalence and incidence of NAFLD suggests that genetic variations on a large number of genes might be involved in NAFLD. To identify genetic variants causing inherited liver disease, we used zebrafish as a model system for a large-scale mutant screen, and adopted a whole genome sequencing approach for rapid identification of mutated genes found in our screen. Here, we report on a forward genetic screen of ENU mutagenized zebrafish. From 250 F2 lines of ENU mutagenized zebrafish during post-developmental stages (5 to 8 days post fertilization), we identified 19 unique mutant zebrafish lines displaying visual evidence of hepatomegaly and/or steatosis with no developmental defects. Histological analysis of mutants revealed several specific phenotypes, including common steatosis, micro/macrovesicular steatosis, hepatomegaly, ballooning, and acute hepatocellular necrosis. This work has identified multiple post-developmental mutants and establishes zebrafish as a novel animal model for post-developmental inherited liver disease. C1 [Kim, Seok-Hyung; Baek, Jeong-In; Choi, Soo Young; Su, Yanhui; Hardiman, Gary; Lipschutz, Joshua H.; Rockey, Don C.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Wu, Shu-Yu; Gamse, Joshua T.] Vanderbilt Univ, Dept Biol, Nashville, TN 37232 USA. [Flynn, Charles R.; Abumrad, Naji N.] Vanderbilt Univ, Dept Surg, Nashville, TN 37232 USA. [Ess, Kevin C.] Vanderbilt Univ, Dept Pediat, Nashville, TN 37232 USA. [Lipschutz, Joshua H.] Ralph H Johnson Vet Affairs Med Ctr, Dept Med, Charleston, SC 29401 USA. RP Kim, SH (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. EM kims@musc.edu RI Flynn, Charles/M-3895-2015 OI Flynn, Charles/0000-0002-3749-0598 FU Norman S. Coplon Extramural Research Grant; Metabolic Technologies, Inc.; [W81XWH-10-1-0854]; [DK069909]; [DK070980]; [DK057830]; [DK098819]; [DK091748]; [DK096527]; [P30 DK020593]; [P30 DK058404] FX This study was supported by the following grants: W81XWH-10-1-0854 (to KCE) (http://www.defense.gov/); Merit Award (to JHL) (http://www.va.gov/); Norman S. Coplon Extramural Research Grant (to JHL) (http://www.satellitehealth.com/); DK069909 and DK070980 (to JHL), DK057830 and DK098819 (to DCR), DK091748 and DK096527 (to NNA), P30 DK020593 and P30 DK058404 (to CRF) (http://www.nih.gov/); Metabolic Technologies, Inc. (to NNA) (http://www.mettechinc.com/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 1 Z9 1 U1 2 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 7 PY 2015 VL 10 IS 5 AR e0125980 DI 10.1371/journal.pone.0125980 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH7KF UT WOS:000354214400058 PM 25950913 ER PT J AU Dutta, P Sager, HB Stengel, KR Naxerova, K Courties, G Saez, B Silberstein, L Heidt, T Sebas, M Sun, Y Wojtkiewicz, G Feruglio, PF King, K Baker, JN van der Laan, AM Borodovsky, A Fitzgerald, K Hulsmans, M Hoyer, F Iwamoto, Y Vinegoni, C Brown, D Di Carli, M Libby, P Hiebert, SW Scadden, DT Swirski, FK Weissleder, R Nahrendorf, M AF Dutta, Partha Sager, Hendrik B. Stengel, Kristy R. Naxerova, Kamila Courties, Gabriel Saez, Borja Silberstein, Lev Heidt, Timo Sebas, Matthew Sun, Yuan Wojtkiewicz, Gregory Feruglio, Paolo Fumene King, Kevin Baker, Joshua N. van der Laan, Anja M. Borodovsky, Anna Fitzgerald, Kevin Hulsmans, Maarten Hoyer, Friedrich Iwamoto, Yoshiko Vinegoni, Claudio Brown, Dennis Di Carli, Marcelo Libby, Peter Hiebert, Scott W. Scadden, David T. Swirski, Filip K. Weissleder, Ralph Nahrendorf, Matthias TI Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells SO CELL STEM CELL LA English DT Article ID BONE-MARROW; MONOCYTE EMIGRATION; SELF-RENEWAL; IN-VIVO; ATHEROSCLEROSIS; IDENTIFICATION; PROLIFERATION; INFLAMMATION; MACROPHAGES; MECHANISMS AB Following myocardial infarction (MI), myeloid cells derived from the hematopoietic system drive a sharp increase in systemic leukocyte levels that correlates closely with mortality. The origin of these myeloid cells, and the response of hematopoietic stem and progenitor cells (HSPCs) to MI, however, is unclear. Here, we identify a CCR2(+)CD150(+)CD48(-) LSK hematopoietic subset as the most upstream contributor to emergency myelopoiesis after ischemic organ injury. This subset has 4-fold higher proliferation rates than CCR2(-)CD150(+)CD48(-) LSK cells, displays a myeloid differentiation bias, and dominates the migratory HSPC population. We further demonstrate that the myeloid translocation gene 16 (Mtg16) regulates CCR2(+) HSPC emergence. Mtg16(-/-) mice have decreased levels of systemic monocytes and infarct-associated macrophages and display compromised tissue healing and post-MI heart failure. Together, these data provide insights into regulation of emergency hematopoiesis after ischemic injury and identify potential therapeutic targets to modulate leukocyte output after MI. C1 [Dutta, Partha; Sager, Hendrik B.; Courties, Gabriel; Heidt, Timo; Sebas, Matthew; Sun, Yuan; Wojtkiewicz, Gregory; Feruglio, Paolo Fumene; King, Kevin; Hulsmans, Maarten; Hoyer, Friedrich; Iwamoto, Yoshiko; Vinegoni, Claudio; Brown, Dennis; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Dutta, Partha; Sager, Hendrik B.; Courties, Gabriel; Heidt, Timo; Sebas, Matthew; Sun, Yuan; Wojtkiewicz, Gregory; Feruglio, Paolo Fumene; King, Kevin; Hulsmans, Maarten; Hoyer, Friedrich; Iwamoto, Yoshiko; Vinegoni, Claudio; Brown, Dennis; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Stengel, Kristy R.; Hiebert, Scott W.] Vanderbilt Univ Sch Med, Dept Biochem, Nashville, TN 37235 USA. [Naxerova, Kamila] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02144 USA. [Saez, Borja; Silberstein, Lev; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Baker, Joshua N.] Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02144 USA. [van der Laan, Anja M.] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands. [Borodovsky, Anna; Fitzgerald, Kevin] Alnylam Pharmaceut, Cambridge, MA 02142 USA. [Di Carli, Marcelo] Brigham & Womens Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA. [Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Dutta, P (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM dutta.partha@mgh.harvard.edu; mnahrendorf@mgh.harvard.edu OI Naxerova, Kamila/0000-0001-7744-5110 FU NIH [R01-HL096576, R01-HL117829, R01-NS084863, HHSN268201000044C, K99-HL121076]; Deutsche Forschungsgemeinschaft [SA1668/2-1, HE-6382/1-1]; Boston Area Diabetes and Endocrinology Research Center [DK57521]; MGH Center for the Study of Inflammatory Bowel Disease [DK43351]; [U24 DK059637] FX We thank Michael Waring and Adam Chicoine from Ragon Institute (of MGH, MIT, and Harvard) and Laura Prickett-Rice, Kat Folz-Donahue, and Meredith Weglarz from the Flow Cytometry Core Facility (Massachusetts General Hospital, Center for Regenerative Medicine andHarvard Stem Cell Institute) for assistance with cell sorting. We also acknowledge Dr. Chee Lim, Vanderbilt Medical Center MMPC (supported by U24 DK059637) for help with infarct surgery. We thank Mary McKee (Program in Membrane Biology Microscopy) for help with electron microscopy. This work was funded in part by grants from the NIH: R01-HL096576, R01-HL117829, and R01-NS084863 (M.N.); HHSN268201000044C (R.W.); and K99-HL121076 (P.D.). Hendrik B. Sager and Timo Heidt were funded by Deutsche Forschungsgemeinschaft (SA1668/2-1 to H.B.S and HE-6382/1-1 to T.H.). Support for the Program in Membrane Biology Microscopy Core comes from the Boston Area Diabetes and Endocrinology Research Center (DK57521) and the MGH Center for the Study of Inflammatory Bowel Disease (DK43351). A.B. and K.F. are Alnylam Pharmaceuticals employees. NR 50 TC 24 Z9 24 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD MAY 7 PY 2015 VL 16 IS 5 BP 477 EP 487 DI 10.1016/j.stem.2015.04.008 PG 11 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA CH7AS UT WOS:000354188600009 PM 25957903 ER PT J AU Yin, YF Yan, PX Lu, JL Song, G Zhu, YY Li, ZH Zhao, Y Shen, B Huang, XX Zhu, H Orkin, SH Shen, XH AF Yin, Yafei Yan, Pixi Lu, Jinlong Song, Guang Zhu, Yangyang Li, Zhaohui Zhao, Yi Shen, Bin Huang, Xingxu Zhu, Heng Orkin, Stuart H. Shen, Xiaohua TI Opposing Roles for the lncRNA Haunt and Its Genomic Locus in Regulating HOXA Gene Activation during Embryonic Stem Cell Differentiation SO CELL STEM CELL LA English DT Article ID LONG NONCODING RNAS; CHROMATIN INTERACTOME; IDENTITY GENES; SELF-RENEWAL; TRANSCRIPTION; EXPRESSION; PLURIPOTENCY; ENHANCERS; EVOLUTION; LINCRNAS AB Long noncoding RNAs (lncRNAs) have been implicated in controlling various aspects of embryonic stem cell (ESC) biology, although the functions of specific lncRNAs, and the molecular mechanisms through which they act, remain unclear. Here, we demonstrate discrete and opposing roles for the lncRNA transcript Haunt and its genomic locus in regulating the HOXA gene cluster during ESC differentiation. Reducing or enhancing Haunt expression, with minimal disruption of the Haunt locus, led to upregulation or downregulation of HOXA genes, respectively. In contrast, increasingly large genomic deletions within the Haunt locus attenuated HOXA activation. The Haunt DNA locus contains potential enhancers of HOXA activation, whereas Haunt RNA acts to prevent aberrant HOXA expression. This work reveals a multifaceted model of lncRNA-mediated transcriptional regulation of the HOXA cluster, with distinct roles for a lncRNA transcript and its genomic locus, while illustrating the power of rapid CRISPR/Cas9-based genome editing for assigning lncRNA functions. C1 [Yin, Yafei; Yan, Pixi; Lu, Jinlong; Zhu, Yangyang; Li, Zhaohui; Zhao, Yi; Shen, Xiaohua] Tsinghua Univ, Sch Med, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China. [Yin, Yafei] Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China. [Song, Guang; Zhu, Heng] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Song, Guang; Zhu, Heng] Johns Hopkins Univ, Sch Med, HiT Ctr, Baltimore, MD 21205 USA. [Zhao, Yi] Chinese Acad Sci, Inst Comp Technol, Bioinformat Res Grp, Beijing 100190, Peoples R China. [Shen, Bin; Huang, Xingxu] Nanjing Univ, Model Anim Res Ctr, MOE Key Lab Model Anim Dis Study, Natl Resource Ctr Mutant Mice, Nanjing 210061, Jiangsu, Peoples R China. [Orkin, Stuart H.] Boston Childrens Hosp, Howard Hughes Med Inst, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shen, XH (reprint author), Tsinghua Univ, Sch Med, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China. EM xshen@tsinghua.edu.cn RI Zhao, Yi/A-2962-2011 OI Zhao, Yi/0000-0001-6046-8420 FU National Basic Research Program of China [2012CB966703]; National Natural Science Foundation of China [81171906, 31471219]; Center of Life Sciences (CLS) at Tsinghua University FX We thank L. Yu, Y. Chen, Y. Wang, F. Tang, T. Xie, J. Wang, Q. Xi, P. Das, Y. Huang, and X.S. laboratory members for critical reading of the manuscript and insightful discussions. Grant support was provided by the National Basic Research Program of China (2012CB966703), the National Natural Science Foundation of China (81171906, 31471219), and the Center of Life Sciences (CLS) at Tsinghua University. NR 52 TC 32 Z9 35 U1 4 U2 33 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD MAY 7 PY 2015 VL 16 IS 5 BP 504 EP 516 DI 10.1016/j.stem.2015.03.007 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA CH7AS UT WOS:000354188600011 PM 25891907 ER PT J AU Yao, H Dittmann, M Peisley, A Hoffmann, HH Gilmore, RH Schmidt, T Schmid-Burgk, JL Hornung, V Rice, CM Hur, S AF Yao, Hui Dittmann, Meike Peisley, Alys Hoffmann, Hans-Heinrich Gilmore, Rachel H. Schmidt, Tobias Schmid-Burgk, Jonathan L. Hornung, Veit Rice, Charles M. Hur, Sun TI ATP-Dependent Effector-like Functions of RIG-I-like Receptors SO MOLECULAR CELL LA English DT Article ID DOUBLE-STRANDED-RNA; PROTEIN-KINASE; MDA5 FILAMENTS; GENE-PRODUCTS; NS1 PROTEIN; ACTIVATION; VIRUS; INTERFERON; MECHANISM; BINDING AB The vertebrate antiviral innate immune system is often considered to consist of two distinct groups of proteins: pattern recognition receptors (PRRs) that detect viral infection and induce the interferon (IFN) signaling, and effectors that directly act against viral replication. Accordingly, previous studies on PRRs, such as RIG-I and MDA5, have primarily focused on their functions in viral double-stranded RNA (dsRNA) detection and consequent antiviral signaling. We report here that both RIG-I and MDA5 efficiently displace viral proteins pre-bound to dsRNA in a manner dependent on their ATP hydrolysis, and that this activity assists a dsRNA-dependent antiviral effector protein, PKR, and allows RIG-I to promote MDA5 signaling. Furthermore, truncated RIG-I/MDA5 lacking the signaling domain, and hence the IFN stimulatory activity, displaces viral proteins and suppresses replication of certain viruses in an ATP-dependent manner. Thus, this study reveals novel "effector-like'' functions of RIG-I and MDA5 that challenge the conventional view of PRRs. C1 [Yao, Hui; Peisley, Alys; Hur, Sun] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Yao, Hui] Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China. [Dittmann, Meike; Hoffmann, Hans-Heinrich; Gilmore, Rachel H.; Rice, Charles M.] Rockefeller Univ, Ctr Study Hepatitis C, Lab Virol & Infect Dis, New York, NY 10065 USA. [Peisley, Alys; Hur, Sun] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Schmidt, Tobias; Schmid-Burgk, Jonathan L.; Hornung, Veit] Univ Klinikum Bonn, Inst Mol Med, D-53127 Bonn, Germany. RP Hur, S (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. EM sun.hur@childrens.harvard.edu RI Hornung, Veit/C-3565-2012; OI Hornung, Veit/0000-0002-4150-194X; Dittmann, Meike/0000-0002-1741-7916; Schmid-Burgk, Jonathan/0000-0003-0988-2487 FU Chinese Scholarship Council; Deutsche Forschungsgemeinschaft; [AI106912]; [AI111784]; [AI091707] FX This work was supported by the Chinese Scholarship Council joint PhD program (H.Y.), a fellowship from the Deutsche Forschungsgemeinschaft (M.D.), anonymous donors, and R01 grants AI106912 (S.H.), AI111784 (S.H.), and AI091707 (C.M.R.). We thank Jihong Han for supporting the graduate program of H.Y.; Yoandris del Toro Duany for helping with protein purification; and Melody Li, Hachung Chung, and Kierstin Bell for generously providing virus stocks. NR 20 TC 15 Z9 15 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD MAY 7 PY 2015 VL 58 IS 3 BP 541 EP 548 DI 10.1016/j.molcel.2015.03.014 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CH6XD UT WOS:000354178800015 PM 25891073 ER PT J AU Nakayama, T Al-Maawali, A El-Quessny, M Rajab, A Khalil, S Stoler, JM Tan, WH Nasir, R Schmitz-Abe, K Hill, RS Partlow, JN Al-Saffar, M Servattalab, S LaCoursiere, CM Tambunan, DE Coulter, ME Elhosary, PC Gorski, G Barkovich, AJ Markianos, K Poduri, A Mochida, GH AF Nakayama, Tojo Al-Maawali, Almundher El-Quessny, Malak Rajab, Anna Khalil, Samir Stoler, Joan M. Tan, Wen-Hann Nasir, Ramzi Schmitz-Abe, Klaus Hill, R. Sean Partlow, Jennifer N. Al-Saffar, Muna Servattalab, Sarah LaCoursiere, Christopher M. Tambunan, Dimira E. Coulter, Michael E. Elhosary, Princess C. Gorski, Grzegorz Barkovich, A. James Markianos, Kyriacos Poduri, Annapurna Mochida, Ganeshwaran H. TI Mutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause Microcephaly and Hypomyelination SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID 3-PHOSPHOGLYCERATE DEHYDROGENASE-DEFICIENCY; RECESSIVE CUTIS LAXA; PROTEOLIPID PROTEIN; GENE; MITOCHONDRIA; METABOLISM; APOPTOSIS; DISORDER AB Despite recent advances in understanding the genetic bases of microcephaly, a large number of cases of microcephaly remain unexplained, suggesting that many microcephaly syndromes and associated genes have yet to be identified. Here, we report mutations in PYCR2, which encodes an enzyme in the proline biosynthesis pathway, as the cause of a unique syndrome characterized by postnatal microcephaly, hypomyelination, and reduced cerebral whitematter volume. Linkage mapping and wholeexome sequencing identified homozygous mutations (c.355C>T [p.Arg119Cys] and c.751C>T [p.Arg251Cys]) in PYCR2 in the affected individuals of two consanguineous families. A lymphoblastoid cell line from one affected individual showed a strong reduction in the amount of PYCR2. When mutant cDNAs were transfected into HEK293FT cells, both variant proteins retained normal mitochondrial localization but had lower amounts than the wildtype protein, suggesting that the variant proteins were less stable. A PYCR2deficient HEK293FT cell line generated by genome editing with the clustered regularly interspaced short palindromic repeat (CRISPR)Cas9 system showed that PYCR2 loss of function led to decreased mitochondrial membrane potential and increased susceptibility to apoptosis under oxidative stress. Morpholinobased knockdown of a zebrafish PYCR2 ortholog, pycr1b, recapitulated the human microcephaly phenotype, which was rescued by wildtype human PYCR2 mRNA, but not by mutant mRNAs, further supporting the pathogenicity of the identified variants. Hypomyelination and the absence of lax, wrinkly skin distinguishes this condition from that caused by previously reported mutations in the gene encoding PYCR2's isozyme, PYCR1, suggesting a unique and indispensable role for PYCR2 in the human CNS during development. C1 [Nakayama, Tojo; Al-Maawali, Almundher; El-Quessny, Malak; Stoler, Joan M.; Tan, Wen-Hann; Schmitz-Abe, Klaus; Hill, R. Sean; Partlow, Jennifer N.; Al-Saffar, Muna; Servattalab, Sarah; Coulter, Michael E.; Elhosary, Princess C.; Markianos, Kyriacos; Mochida, Ganeshwaran H.] Boston Childrens Hosp, Div Genet & Genom, Dept Med, Boston, MA 02115 USA. [Nakayama, Tojo; Al-Maawali, Almundher; El-Quessny, Malak; Schmitz-Abe, Klaus; Hill, R. Sean; Partlow, Jennifer N.; Al-Saffar, Muna; Servattalab, Sarah; Coulter, Michael E.; Elhosary, Princess C.; Markianos, Kyriacos; Mochida, Ganeshwaran H.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Nakayama, Tojo; Stoler, Joan M.; Tan, Wen-Hann; Nasir, Ramzi; Schmitz-Abe, Klaus; Markianos, Kyriacos; Mochida, Ganeshwaran H.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Al-Maawali, Almundher] Sultan Qaboos Univ, Coll Med & Hlth Sci, Dept Genet, Muscat 123, Oman. [Rajab, Anna] Minist Hlth, Natl Genet Ctr, Directorate Gen Hlth Affairs, Muscat 113, Oman. [Khalil, Samir] Al Makassed Islamic Charitable Soc Hosp, Dept Pediat, IL-91220 Jerusalem, Israel. [Khalil, Samir] Al Quds Univ, Fac Med, IL-90612 Jerusalem, Israel. [Nasir, Ramzi] Boston Childrens Hosp, Div Dev Med, Dept Med, Boston, MA 02115 USA. [Schmitz-Abe, Klaus; Markianos, Kyriacos] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Hill, R. Sean; Partlow, Jennifer N.; Al-Saffar, Muna; Servattalab, Sarah; Coulter, Michael E.; Elhosary, Princess C.] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Al-Saffar, Muna] United Arab Emirates Univ, Coll Med & Hlth Sci, Dept Paediat, Al Ain, U Arab Emirates. [LaCoursiere, Christopher M.; Tambunan, Dimira E.; Elhosary, Princess C.; Poduri, Annapurna] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Coulter, Michael E.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Gorski, Grzegorz] Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Cellular Neurosci Core, Boston, MA 02115 USA. [Barkovich, A. James] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Poduri, Annapurna] Boston Childrens Hosp, Epilepsy Genet Program, Boston, MA 02115 USA. [Poduri, Annapurna] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Mochida, Ganeshwaran H.] Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. RP Mochida, GH (reprint author), Boston Childrens Hosp, Div Genet & Genom, Dept Med, Boston, MA 02115 USA. EM ganesh.mochida@childrens.harvard.edu FU Manton Center for Orphan Disease Research; National Institute of Neurological Disorders and Stroke (NINDS) [R01NS035129]; NIH Fogarty International Center [R21TW008223]; Dubai Harvard Foundation for Medical Research; Japan Foundation for Pediatric Research; Japan Epilepsy Research Foundation; NINDS [1K23 NS069784]; Boston Children's Hospital Translational Research Program; F. Hoffmann-La Roche; Qatar National Research Fund; Boston Children's Hospital Faculty Career Development Award; Medical Research Council [099175/Z/12/Z]; Wellcome Trust [099175/Z/12/Z] FX The study was supported by grants from the Manton Center for Orphan Disease Research, National Institute of Neurological Disorders and Stroke (NINDS, R01NS035129), NIH Fogarty International Center (R21TW008223), and the Dubai Harvard Foundation for Medical Research. T.N. was supported by fellowship grants from the Japan Foundation for Pediatric Research and the Japan Epilepsy Research Foundation. A.P. was supported by the NINDS (1K23 NS069784) and the Boston Children's Hospital Translational Research Program. G.H.M. was also supported by grants from F. Hoffmann-La Roche, the Qatar National Research Fund, and the Boston Children's Hospital Faculty Career Development Award. Human embryonic material was provided by the joint Medical Research Council and Wellcome Trust (grant 099175/Z/12/Z) Human Developmental Biology Resource (www.HDBR.org). We thank the families for their participation in this research, Dr. Gilad D. Evrony for help with RNA sequencing, Dr. Xiaochang Zhang, Dr. Aldo Rozzo, Dr. Byoung-Il Bae, Ms. Rachel E. Reiff, and Dr. Anthony D. Hill for technical assistance, and Dr. Christopher A. Walsh and Dr. Gerard T. Berry for helpful discussions and critical comments on the manuscript. NR 34 TC 8 Z9 9 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY 7 PY 2015 VL 96 IS 5 BP 709 EP 719 DI 10.1016/j.ajhg.2015.03.003 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA CH7AZ UT WOS:000354189300002 PM 25865492 ER PT J AU Mlynarski, EE Sheridan, MB Xie, M Guo, TW Racedo, SE McDonald-McGinn, DM Gai, XW Chow, EWC Vorstman, J Swillen, A Devriendt, K Breckpot, J Digilio, MC Marino, B Dallapiccola, B Philip, N Simon, TJ Roberts, AE Piotrowicz, M Bearden, CE Eliez, S Gothelf, D Coleman, K Kates, WR Devoto, M Zackai, E Heine-Suner, D Shaikh, TH Bassett, AS Goldmuntz, E Morrow, BE Emanuel, BS AF Mlynarski, Elisabeth E. Sheridan, Molly B. Xie, Michael Guo, Tingwei Racedo, Silvia E. McDonald-McGinn, Donna M. Gai, Xiaowu Chow, Eva W. C. Vorstman, Jacob Swillen, Ann Devriendt, Koen Breckpot, Jeroen Digilio, Maria Cristina Marino, Bruno Dallapiccola, Bruno Philip, Nicole Simon, Tony J. Roberts, Amy E. Piotrowicz, Malgorzata Bearden, Carrie E. Eliez, Stephan Gothelf, Doron Coleman, Karlene Kates, Wendy R. Devoto, Marcella Zackai, Elaine Heine-Suner, Damian Shaikh, Tamim H. Bassett, Anne S. Goldmuntz, Elizabeth Morrow, Bernice E. Emanuel, Beverly S. CA Int Chromosome 22q11 2 Consortium TI Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and Congenital Heart Defects in the 22q11.2 Deletion Syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID INTRAUTERINE GROWTH RESTRICTION; CARDIOVASCULAR-DISEASE; SCIENTIFIC STATEMENT; STRUCTURAL VARIATION; DEVELOPMENTAL DELAY; CHROMOSOME 22Q11.2; CURRENT KNOWLEDGE; CARDIAC DEFECTS; 3 GLUT3; GENOME AB The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS) is the most common microdeletion syndrome and the phenotypic presentation is highly variable. Approximately 65% of individuals with 22q11DS have a congenital heart defect (CHD), mostly of the conotruncal type, and/or an aortic arch defect. The etiology of this phenotypic variability is not currently known. We hypothesized that copy-number variants (CNVs) outside the 22q11.2 deleted region might increase the risk of being born with a CHD in this sensitized population. Genotyping with Affymetrix SNP Array 6.0 was performed on two groups of subjects with 22q11DS separated by time of ascertainment and processing. CNV analysis was completed on a total of 949 subjects (cohort 1, n = 562; cohort 2, n = 387), 603 with CHDs (cohort 1, n = 363; cohort 2, n = 240) and 346 with normal cardiac anatomy (cohort 1, n = 199; cohort 2, n = 147). Our analysis revealed that a duplication of SLC2A3 was the most frequent CNV identified in the first cohort. It was present in 18 subjects with CHDs and 1 subject without (p = 3.12 x 10(-3), two-tailed Fisher's exact test). In the second cohort, the SLC2A3 duplication was also significantly enriched in subjects with CHDs (p = 3.30 x 10(-2), two-tailed Fisher's exact test). The SLC2A3 duplication was the most frequent CNV detected and the only significant finding in our combined analysis (p = 2.68 x 10(-4), two-tailed Fisher's exact test), indicating that the SLC2A3 duplication might serve as a genetic modifier of CHDs and/or aortic arch anomalies in individuals with 22q11DS. C1 [Mlynarski, Elisabeth E.; Sheridan, Molly B.; McDonald-McGinn, Donna M.; Devoto, Marcella; Zackai, Elaine; Emanuel, Beverly S.] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. [Xie, Michael] Childrens Hosp Philadelphia, Ctr Biomed Informat, Philadelphia, PA 19104 USA. [Guo, Tingwei; Racedo, Silvia E.; Morrow, Bernice E.] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA. [McDonald-McGinn, Donna M.; Devoto, Marcella; Zackai, Elaine; Goldmuntz, Elizabeth; Emanuel, Beverly S.] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Gai, Xiaowu] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ocular Genom Inst, Boston, MA 02114 USA. [Gai, Xiaowu] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chow, Eva W. C.; Bassett, Anne S.] Univ Toronto, Clin Genet Res Program, Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada. [Chow, Eva W. C.; Bassett, Anne S.] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada. [Vorstman, Jacob] Univ Med Ctr Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, NL-3584 Utrecht, Netherlands. [Swillen, Ann; Devriendt, Koen; Breckpot, Jeroen] Univ Leuven, Ctr Human Genet, B-3000 Leuven, Belgium. [Digilio, Maria Cristina; Dallapiccola, Bruno] Bambino Gesu Pediat Hosp, Med Genet, I-00165 Rome, Italy. [Marino, Bruno] Univ Roma La Sapienza, Lorillard Spencer Cenci Fdn, I-00165 Rome, Italy. [Marino, Bruno] Univ Roma La Sapienza, Dept Pediat, I-00165 Rome, Italy. [Philip, Nicole] AP HM, Dept Med Genet, F-13005 Marseille, France. [Philip, Nicole] Univ Aix Marseille 2, Timone Childrens Hosp, F-13005 Marseille, France. [Simon, Tony J.] Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA. [Simon, Tony J.] Univ Calif Davis, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. [Roberts, Amy E.] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Roberts, Amy E.] Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Piotrowicz, Malgorzata] Polish Mothers Mem Hosp, Res Inst, Dept Genet, PL-93338 Lodz, Poland. [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Eliez, Stephan] Univ Geneva, Sch Med, Dept Psychiat, Off Medicopedag Res Unit, CH-1211 Geneva 8, Switzerland. [Gothelf, Doron] Edmond & Lily Safra Childrens Hosp, Sheba Med Ctr, Tel Hashomer, Israel. [Gothelf, Doron] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Coleman, Karlene] Childrens Healthcare Atlanta, Atlanta, GA 30322 USA. [Coleman, Karlene] Emory Univ, Sch Nursing, Atlanta, GA 30322 USA. [Kates, Wendy R.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. [Kates, Wendy R.] SUNY Upstate Med Univ, Program Neurosci, Syracuse, NY 13210 USA. [Devoto, Marcella] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Devoto, Marcella] Univ Roma La Sapienza, Dept Mol Med, I-00185 Rome, Italy. [Heine-Suner, Damian] Hosp Univ Son Espases, Dept Genet, Palma De Mallorca 07020, Spain. [Shaikh, Tamim H.] Univ Colorado, Dept Pediat, Denver, CO 80202 USA. [Goldmuntz, Elizabeth] Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA. RP Emanuel, BS (reprint author), Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. EM beverly@mail.med.upenn.edu RI Philip, Nicole/I-2881-2016; Dallapiccola, Bruno/K-8692-2016; OI Dallapiccola, Bruno/0000-0002-5031-1013; Heine Suner, Damian/0000-0001-9374-1219 FU NIH [MH87636, HL84410, HD070454, HD026979]; NIH/NCATS (National Center for Advancing Translational Sciences) [UL1TR000003] FX Thanks to Colleen Franconi, Meghan McNamara, April Hacker, Tracy Busse, Mark Bowser, Anne Marie Higgins, Chad Haldeman-Englert, Petra Warner, Jenna Walck, and Danica Kuncio for technical assistance. Special thanks go to the subjects and their families for their willing participation. We also thank the Molecular Cytogenetics and Genomics Cores at Einstein for preparing DNA and genotyping with Affymetrix 6.0 arrays. This work was funded by NIH (MH87636, HL84410, HD070454, and HD026979) and in part by NIH/NCATS (National Center for Advancing Translational Sciences), Grant UL1TR000003. NR 53 TC 15 Z9 15 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY 7 PY 2015 VL 96 IS 5 BP 753 EP 764 DI 10.1016/j.ajhg.2015.03.007 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA CH7AZ UT WOS:000354189300006 PM 25892112 ER PT J AU Migliavacca, E Golzio, C Mannik, K Blumenthal, I Oh, EC Harewood, L Kosmicki, JA Loviglio, MN Giannuzzi, G Hippolyte, L Maillard, AM Alfaiz, AA van Haelst, MM Andrieux, J Gusella, JF Daly, MJ Beckmann, JS Jacquemont, S Talkowski, ME Katsanis, N Reymond, A AF Migliavacca, Eugenia Golzio, Christelle Maennik, Katrin Blumenthal, Ian Oh, Edwin C. Harewood, Louise Kosmicki, Jack A. Loviglio, Maria Nicla Giannuzzi, Giuliana Hippolyte, Loyse Maillard, Anne M. Alfaiz, Ali Abdullah van Haelst, Mieke M. Andrieux, Joris Gusella, James F. Daly, Mark J. Beckmann, Jacques S. Jacquemont, Sebastien Talkowski, Michael E. Katsanis, Nicholas Reymond, Alexandre CA 16p11 2 European Consortium TI A Potential Contributory Role for Ciliary Dysfunction in the 16p11.2 600 kb BP4-BP5 Pathology SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID COPY NUMBER VARIATION; DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDER; SPINAL MUSCULAR-ATROPHY; SPATIAL WORKING-MEMORY; JOUBERT-SYNDROME; CHROMOSOME 16P11.2; PRIMARY CILIUM; CENTROSOMAL PROTEIN; SCHIZOPHRENIA AB The 16p11.2 600 kb copy-number variants (CNVs) are associated with mirror phenotypes on BMI, head circumference, and brain volume and represent frequent genetic lesions in autism spectrum disorders (ASDs) and schizophrenia. Here we interrogated the transcriptome of individuals carrying reciprocal 16p11.2 CNVs. Transcript perturbations correlated with clinical endophenotypes and were enriched for genes associated with ASDs, abnormalities of head size, and ciliopathies. Ciliary gene expression was also perturbed in orthologous mouse models, raising the possibility that ciliary dysfunction contributes to 16p11.2 pathologies. In support of this hypothesis, we found structural ciliary defects in the CA1 hippocampal region of 16p11.2 duplication mice. Moreover, by using an established zebrafish model, we show genetic interaction between KCTD13, a key driver of the mirrored neuroanatomical phenotypes of the 16p11.2 CNV, and ciliopathy-associated genes. Overexpression of BBS7 rescues head size and neuroanatomical defects of kctd13 morphants, whereas suppression or overexpression of CEP290 rescues phenotypes induced by KCTD13 under-or overexpression, respectively. Our data suggest that dysregulation of ciliopathy genes contributes to the clinical phenotypes of these CNVs. C1 [Migliavacca, Eugenia; Maennik, Katrin; Harewood, Louise; Loviglio, Maria Nicla; Giannuzzi, Giuliana; Alfaiz, Ali Abdullah; Reymond, Alexandre] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland. [Migliavacca, Eugenia; Alfaiz, Ali Abdullah; Beckmann, Jacques S.] SIB, CH-1015 Lausanne, Switzerland. [Golzio, Christelle; Oh, Edwin C.; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA. [Golzio, Christelle; Oh, Edwin C.; Katsanis, Nicholas] Duke Univ, Dept Cell Biol, Durham, NC 27710 USA. [Maennik, Katrin] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia. [Blumenthal, Ian; Gusella, James F.; Talkowski, Michael E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kosmicki, Jack A.; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Kosmicki, Jack A.; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kosmicki, Jack A.; Daly, Mark J.] Broad Inst Harvard & MIT, Cambridge Ctr 7, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Kosmicki, Jack A.; Daly, Mark J.] Broad Inst Harvard & MIT, Cambridge Ctr 7, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Hippolyte, Loyse; Maillard, Anne M.; Beckmann, Jacques S.; Jacquemont, Sebastien] Lausanne Univ Hosp CHUV, Serv Med Genet, CH-1011 Lausanne, Switzerland. [van Haelst, Mieke M.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3508 AB Utrecht, Netherlands. [Andrieux, Joris] CHRU Lille, Inst Genet Med, Hop Jeanne de Flandre, F-59037 Lille, France. [Gusella, James F.; Talkowski, Michael E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Gusella, James F.; Talkowski, Michael E.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Beckmann, Jacques S.] Univ Lausanne, Dept Med Genet, CH-1011 Lausanne, Switzerland. RP Katsanis, N (reprint author), Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA. EM katsanis@cellbio.duke.edu; alexandre.reymond@unil.ch RI Rauch, Anita/C-5568-2014; Le Caignec, Cedric/K-8467-2015; Isidor, Bertrand/L-2435-2015; Vulto-van Silfhout, Anneke/H-4199-2015; Nordgren, Ann/N-4057-2013; Kooy, Frank/F-5276-2014; Ounap, Katrin/Q-1103-2016; Beckmann, Jacques S /A-9772-2008; OI Rauch, Anita/0000-0003-2930-3163; Le Caignec, Cedric/0000-0002-0598-653X; Isidor, Bertrand/0000-0001-6480-126X; Nordgren, Ann/0000-0003-3285-4281; Kooy, Frank/0000-0003-2024-0485; Beckmann, Jacques S /0000-0002-9741-1900; Harewood, Louise/0000-0002-6398-6714 FU Swiss Scientific Exchange NMS Program; Swiss National Science Foundation (SNSF); Brain and Behavior Research Foundation; Saudi Arabian National Guard Health Affairs; Simons Foundation [SFARI274424, SFARI239983, SFARI238504, SFARI240021]; Swiss National Science Foundation [31003A_160203]; SNSF [CRIS FN CRSII33-133044]; Leenaards Foundation Prize; NIH [P50MH094260, MH095867]; Nancy Lurie Marks Family Foundation FX We thank the members of the Lausanne Genomic Technologies Facility, Patrick Meylan, and Alexandre Thiery for technical help. We are grateful to all the families participating to the Simons Variation in Individuals Project (Simons VIP), as well as to the Simons VIP working group. K.M. was awarded a scholarship from the Swiss Scientific Exchange NMS Program, S.J. is recipient of a Bursary Professor fellowship of the Swiss National Science Foundation (SNSF), and C.G., E.C.O., and M.E.T. are grantees of NARSAD Young Investigator Grants from the Brain and Behavior Research Foundation. A. A. A. was awarded a scholarship from the Saudi Arabian National Guard Health Affairs. This work is supported by the Simons Foundation (grants SFARI274424 to A.R., SFARI239983 to N.K., SFARI238504 to M.E.T., and SFARI240021 to J.F.G.), the Swiss National Science Foundation (grant 31003A_160203 to A.R.), a specific SNSF Sinergia grant (CRIS FN CRSII33-133044 to A.R.), the Leenaards Foundation Prize (S.J. and A.R.), by NIH P50MH094260 (N.K.) and MH095867 (M.E.T.), and the Nancy Lurie Marks Family Foundation (J.F.G. and M.E.T.). N.K. is a Distinguished Brumley Professor. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 86 TC 7 Z9 7 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY 7 PY 2015 VL 96 IS 5 BP 784 EP 796 DI 10.1016/j.ajhg.2015.04.002 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA CH7AZ UT WOS:000354189300009 PM 25937446 ER PT J AU Pefanis, E Wang, JG Rothschild, G Lim, J Kazadi, D Sun, JB Federation, A Chao, J Elliott, O Liu, ZP Economides, AN Bradner, JE Rabadan, R Basu, U AF Pefanis, Evangelos Wang, Jiguang Rothschild, Gerson Lim, Junghyun Kazadi, David Sun, Jianbo Federation, Alexander Chao, Jaime Elliott, Oliver Liu, Zhi-Ping Economides, Aris N. Bradner, James E. Rabadan, Raul Basu, Uttiya TI RNA Exosome-Regulated Long Non-Coding RNA Transcription Controls Super-Enhancer Activity SO CELL LA English DT Article ID POLYMERASE-II; DIVERGENT TRANSCRIPTION; SEQUENCING REVEALS; HUMAN PROMOTERS; CELL IDENTITY; FISSION YEAST; TARGETS AID; B-CELLS; TERMINATION; CHROMATIN AB We have ablated the cellular RNA degradation machinery in differentiated B cells and pluripotent embryonic stem cells (ESCs) by conditional mutagenesis of core (Exosc3) and nuclear RNase (Exosc10) components of RNA exosome and identified a vast number of long non-coding RNAs (lncRNAs) and enhancer RNAs (eRNAs) with emergent functionality. Unexpectedly, eRNA-expressing regions accumulate R-loop structures upon RNA exosome ablation, thus demonstrating the role of RNA exosome in resolving deleterious DNA/RNA hybrids arising from active enhancers. We have uncovered a distal divergent eRNA-expressing element (lncRNA-CSR) engaged in long-range DNA interactions and regulating IgH 30 regulatory region super-enhancer function. CRISPR-Cas9-mediated ablation of lncRNA-CSR transcription decreases its chromosomal looping-mediated association with the IgH 30 regulatory region super-enhancer and leads to decreased class switch recombination efficiency. We propose that the RNA exosome protects divergently transcribed lncRNA expressing enhancers by resolving deleterious transcription-coupled secondary DNA structures, while also regulating long-range super-enhancer chromosomal interactions important for cellular function. C1 [Pefanis, Evangelos; Rothschild, Gerson; Lim, Junghyun; Kazadi, David; Sun, Jianbo; Chao, Jaime; Basu, Uttiya] Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA. [Wang, Jiguang; Elliott, Oliver; Rabadan, Raul] Columbia Univ, Coll Phys & Surg, Dept Biomed Informat, New York, NY 10032 USA. [Wang, Jiguang; Elliott, Oliver; Rabadan, Raul] Columbia Univ, Coll Phys & Surg, Dept Syst Biol, New York, NY 10032 USA. [Liu, Zhi-Ping] Shandong Univ, Sch Control Sci & Engn, Dept Biomed Engn, Jinan 250061, Shandong, Peoples R China. [Pefanis, Evangelos; Economides, Aris N.] Regeneron Pharmaceut & Regeneron Genet Ctr, Tarrytown, NY 10591 USA. [Federation, Alexander; Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Federation, Alexander; Bradner, James E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rabadan, R (reprint author), Columbia Univ, Coll Phys & Surg, Dept Biomed Informat, New York, NY 10032 USA. EM rr2579@cumc.columbia.edu; ub2121@cumc.columbia.edu RI Wang, Jiguang/B-2717-2012; Sun, Jianbo/E-2316-2013; Liu, Zhi-Ping/C-9846-2010; OI Sun, Jianbo/0000-0001-8153-1847; Liu, Zhi-Ping/0000-0001-7742-9161; Economides, Aris/0000-0002-6508-8942 FU NIH [1DP2OD008651-01, 1R01CA185486-01, 1R01CA179044-01A1, 1U54CA121852-05, F31AI098411-01A1]; NIAID [1R01AI099195-01A1] FX We thank Christopher Lima (MSKCC, New York), Frederic Chedin (University of California, Davis), Saul Silverstein, Stephen Goff, Sankar Ghosh, Lorraine Symington, and members of the Basu lab for critical input and reagents. We thank Olivier Courrone of Columbia University genome center for RNA sequencing and Victor Lin of Herbert Irving Cancer Center Transgenic facility for targeting and generation of Exosc3COIN and Exosc10COIN allele ESCs and mouse models. This work was supported by grants from NIH (1DP2OD008651-01) and NIAID (1R01AI099195-01A1) to U.B.; NIH (1R01CA185486-01; 1R01CA179044-01A1; 1U54CA121852-05) to R.R.; and F31AI098411-01A1 to D.K. U.B. is a scholar of the Irma Hirschl Charitable Trust and the Leukemia and Lymphoma Society. NR 58 TC 50 Z9 52 U1 18 U2 128 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD MAY 7 PY 2015 VL 161 IS 4 BP 774 EP 789 DI 10.1016/j.cell.2015.04.034 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CH6VT UT WOS:000354175200012 PM 25957685 ER PT J AU Kardon, JR Yien, YY Huston, NC Branco, DS Hildick-Smith, GJ Rhee, KY Paw, BH Baker, TA AF Kardon, Julia R. Yien, Yvette Y. Huston, Nicholas C. Branco, Diana S. Hildick-Smith, Gordon J. Rhee, Kyu Y. Paw, Barry H. Baker, Tania A. TI Mitochondrial ClpX Activates a Key Enzyme for Heme Biosynthesis and Erythropoiesis SO CELL LA English DT Article ID CONGENITAL SIDEROBLASTIC ANEMIA; 5-AMINOLEVULINATE SYNTHASE; ASPARTATE-AMINOTRANSFERASE; SACCHAROMYCES-CEREVISIAE; PYRIDOXAL KINASE; PORE LOOPS; PROTEIN; DEGRADATION; CHAPERONE; MACHINE AB The mitochondrion maintains and regulates its proteome with chaperones primarily inherited from its bacterial endosymbiont ancestor. Among these chaperones is the AAA+ unfoldase ClpX, an important regulator of prokaryotic physiology with poorly defined function in the eukaryotic mitochondrion. We observed phenotypic similarity in S. cerevisiae genetic interaction data between mitochondrial ClpX (mtClpX) and genes contributing to heme biosynthesis, an essential mitochondrial function. Metabolomic analysis revealed that 5-aminolevulinic acid (ALA), the first heme precursor, is 5-fold reduced in yeast lacking mtClpX activity and that total heme is reduced by half. mtClpX directly stimulates ALA synthase in vitro by catalyzing incorporation of its cofactor, pyridoxal phosphate. This activity is conserved in mammalian homologs; additionally, mtClpX depletion impairs vertebrate erythropoiesis, which requires massive upregulation of heme biosynthesis to supply hemoglobin. mtClpX, therefore, is a widely conserved stimulator of an essential biosynthetic pathway and uses a previously unrecognized mechanism for AAA+ unfoldases. C1 [Kardon, Julia R.; Baker, Tania A.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Yien, Yvette Y.; Huston, Nicholas C.; Branco, Diana S.; Hildick-Smith, Gordon J.; Paw, Barry H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol,Dept Med, Boston, MA 02115 USA. [Rhee, Kyu Y.] Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA. [Rhee, Kyu Y.] Weill Cornell Med Coll, Dept Med, Div Infect Dis, New York, NY 10065 USA. [Paw, Barry H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematology Oncol,Dept Med, Boston, MA 02115 USA. [Paw, Barry H.] Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Kardon, Julia R.; Baker, Tania A.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Baker, TA (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM tabaker@mit.edu FU NIH [RO1 GM049224, F32DK095726, T32HL007574, F32DK098866, R01DK070838, P01HL032262]; March of Dimes Foundation [6-FY09-289]; Brazilian CAPES Foundation; Brazilian FAPESP Foundation; Burroughs Wellcome Career Award in the Biomedical Sciences; William Randolph Hearst Foundation FX We thank S. Bell, J. Weissman, R. Vale, J. Nunnari, and N. Bradshaw for critical reading of the manuscript; L. Zon for the Tg(globin-LCR:eGFP) transgenic line; K. Hoffmeister for fluorescence-activated cell sorting (FACS) machine use; and C. Lawrence and his team for zebrafish husbandry. This work was supported by grants from the NIH (RO1 GM049224 to T.A.B., F32DK095726 to J. R. K., T32HL007574 and F32DK098866 to Y.Y.Y., and R01DK070838 and P01HL032262 to B.H.P.), the March of Dimes Foundation (6-FY09-289 to B.H.P.), and the Brazilian CAPES and FAPESP Foundations (to D.S.B.). K.Y.R. is the recipient of a Burroughs Wellcome Career Award in the Biomedical Sciences and of support from the William Randolph Hearst Foundation. T.A.B. is an employee of the Howard Hughes Medical Institute. NR 57 TC 10 Z9 14 U1 3 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD MAY 7 PY 2015 VL 161 IS 4 BP 858 EP 867 DI 10.1016/j.cell.2015.04.017 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CH6VT UT WOS:000354175200018 PM 25957689 ER PT J AU van de Wetering, M Francies, HE Francis, JM Bounova, G Iorio, F Pronk, A van Houdt, W van Gorp, J Taylor-Weiner, A Kester, L McLaren-Douglas, A Blokker, J Jaksani, S Bartfeld, S Volckman, R van Sluis, P Li, VSW Seepo, S Pedamallu, CS Cibulskis, K Carter, SL McKenna, A Lawrence, MS Lichtenstein, L Stewart, C Koster, J Versteeg, R van Oudenaarden, A Saez-Rodriguez, J Vries, RGJ Getz, G Wessels, L Stratton, MR McDermott, U Meyerson, M Garnett, MJ Clevers, H AF van de Wetering, Marc Francies, Hayley E. Francis, Joshua M. Bounova, Gergana Iorio, Francesco Pronk, Apollo van Houdt, Winan van Gorp, Joost Taylor-Weiner, Amaro Kester, Lennart McLaren-Douglas, Anne Blokker, Joyce Jaksani, Sridevi Bartfeld, Sina Volckman, Richard van Sluis, Peter Li, Vivian S. W. Seepo, Sara Pedamallu, Chandra Sekhar Cibulskis, Kristian Carter, Scott L. McKenna, Aaron Lawrence, Michael S. Lichtenstein, Lee Stewart, Chip Koster, Jan Versteeg, Rogier van Oudenaarden, Alexander Saez-Rodriguez, Julio Vries, Robert G. J. Getz, Gad Wessels, Lodewyk Stratton, Michael R. McDermott, Ultan Meyerson, Matthew Garnett, Mathew J. Clevers, Hans TI Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients SO CELL LA English DT Article ID SMALL-INTESTINE; DRUG-SENSITIVITY; WNT RECEPTORS; COLON-CANCER; STEM-CELLS; GENE; LGR5; EPITHELIUM; MUTATIONS; GENOME AB In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. For most, organoids were also generated from adjacent normal tissue. Organoids closely recapitulate several properties of the original tumor. The spectrum of genetic changes within the "living biobank'' agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43, rather than in APC. Organoid technology may fill the gap between cancer genetics and patient trials, complement cell-line- and xenograft-based drug studies, and allow personalized therapy design. C1 [van de Wetering, Marc; Kester, Lennart; Blokker, Joyce; Jaksani, Sridevi; Bartfeld, Sina; van Oudenaarden, Alexander; Vries, Robert G. J.; Clevers, Hans] Canc Genom & Univ Med Ctr, Royal Netherlands Acad Arts & Sci KNAW, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands. [van de Wetering, Marc; Blokker, Joyce; Jaksani, Sridevi; Vries, Robert G. J.; Clevers, Hans] Fdn Hubrecht Organoid Technol HUB, NL-3584 CT Utrecht, Netherlands. [Francies, Hayley E.; McLaren-Douglas, Anne; Stratton, Michael R.; McDermott, Ultan; Garnett, Mathew J.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England. [Francis, Joshua M.; Taylor-Weiner, Amaro; Seepo, Sara; Pedamallu, Chandra Sekhar; Cibulskis, Kristian; Carter, Scott L.; McKenna, Aaron; Lawrence, Michael S.; Lichtenstein, Lee; Getz, Gad; Meyerson, Matthew] MIT, Broad Inst, Cambridge, MA 02142 USA. [Francis, Joshua M.; Taylor-Weiner, Amaro; Seepo, Sara; Pedamallu, Chandra Sekhar; Cibulskis, Kristian; Carter, Scott L.; McKenna, Aaron; Lawrence, Michael S.; Lichtenstein, Lee; Stewart, Chip; Getz, Gad; Meyerson, Matthew] Harvard Univ, Cambridge, MA 02142 USA. [Francis, Joshua M.; Pedamallu, Chandra Sekhar; Carter, Scott L.; Getz, Gad; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bounova, Gergana; Wessels, Lodewyk] Netherlands Canc Inst, Computat Canc Biol, NL-1066 CX Amsterdam, Netherlands. [Iorio, Francesco; Saez-Rodriguez, Julio] European Bioinformat Inst, European Mol Biol, Cambridge CB10 1SA, England. [Pronk, Apollo; van Houdt, Winan] Diakonessen Hosp, Dept Surg, NL-3582 KE Utrecht, Netherlands. [van Gorp, Joost] Diakonessen Hosp, Dept Pathol, NL-3582 KE Utrecht, Netherlands. [Volckman, Richard; van Sluis, Peter; Koster, Jan; Versteeg, Rogier] Univ Amsterdam, Acad Med Ctr, Dept Oncogenom, NL-1105 AZ Amsterdam, Netherlands. [Li, Vivian S. W.] MRC Natl Inst Med Res, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England. RP Garnett, MJ (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, Cambs, England. EM mg12@sanger.ac.uk; h.clevers@hubrecht.eu OI Iorio, Francesco/0000-0001-7063-8913; McDermott, Ultan/0000-0001-9032-4700; Li, Vivian/0000-0003-2041-0085; Saez-Rodriguez, Julio/0000-0002-8552-8976 FU Stichting Virtutis Opus; Alpe dHuzes/KWF; Dutch Cancer Society [H1/2014-6919]; Stichting Vrienden van het Hubrecht FX Thanks to the Broad Institute Genomics Platform for processing and generating the sequence data, the cell line screening, and analysis team at the Sanger Institute, Liliane Wijnaendts and Joost Oudejans for help with tumor dissections, Harry Begthel and Jeroen Korving for histology, Sepideh Darakhshan for help with organoids, and the members of the M.M., M.J.G., and H.C. laboratories for support. M.v.d.W. is supported by Stichting Virtutis Opus and Stichting Vrienden van het Hubrecht. R.G.J.V., S.J., and J.B. are supported by a Grant from Alpe dHuzes/KWF. This work was supported with a grant from the Dutch Cancer Society to M.S. (H1/2014-6919). The organoids are available for academic research upon evaluation of a research proposal by the Medical Ethical Comity. M.M. received a commercial research grant from Bayer and has ownership interest (including patents) in and is a consultant/advisory board member for Foundation Medicine. NR 54 TC 130 Z9 132 U1 15 U2 68 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD MAY 7 PY 2015 VL 161 IS 4 BP 933 EP 945 DI 10.1016/j.cell.2015.03.053 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CH6VT UT WOS:000354175200024 PM 25957691 ER PT J AU Schoenthaler, R AF Schoenthaler, Robin TI Lessons in Medicine, Mortality, and Reflexive Verbs SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Schoenthaler, R (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 7 PY 2015 VL 372 IS 19 BP 1787 EP 1789 DI 10.1056/NEJMp1413815 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CH4BB UT WOS:000353974700003 PM 25946278 ER PT J AU Bonaca, MP Bhatt, DL Cohen, M Steg, PG Storey, RF Jensen, EC Magnani, G Bansilal, S Fish, MP Im, K Bengtsson, O Ophuis, TO Budaj, A Theroux, P Ruda, M Hamm, C Goto, S Spinar, J Nicolau, JC Kiss, RG Murphy, SA Wiviott, SD Held, P Braunwald, E Sabatine, MS AF Bonaca, Marc P. Bhatt, Deepak L. Cohen, Marc Steg, Philippe Gabriel Storey, Robert F. Jensen, Eva C. Magnani, Giulia Bansilal, Sameer Fish, M. Polly Im, Kyungah Bengtsson, Olof Ophuis, Ton Oude Budaj, Andrzej Theroux, Pierre Ruda, Mikhail Hamm, Christian Goto, Shinya Spinar, Jindrich Nicolau, Jose Carlos Kiss, Robert G. Murphy, Sabina A. Wiviott, Stephen D. Held, Peter Braunwald, Eugene Sabatine, Marc S. CA PEGASUS-TIMI 54 Steering Comm TI Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE CORONARY SYNDROMES; ASSOCIATION TASK-FORCE; ST-SEGMENT ELEVATION; HEART-ASSOCIATION; PRACTICE GUIDELINES; AMERICAN-COLLEGE; CLOPIDOGREL; MANAGEMENT; ASPIRIN; TRIAL AB BACKGROUND The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infarction has not been established. We investigated the efficacy and safety of ticagrelor, a P2Y(12) receptor antagonist with established efficacy after an acute coronary syndrome, in this context. METHODS We randomly assigned, in a double-blind 1: 1: 1 fashion, 21,162 patients who had had a myocardial infarction 1 to 3 years earlier to ticagrelor at a dose of 90 mg twice daily, ticagrelor at a dose of 60 mg twice daily, or placebo. All the patients were to receive low-dose aspirin and were followed for a median of 33 months. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. RESULTS The two ticagrelor doses each reduced, as compared with placebo, the rate of the primary efficacy end point, with Kaplan-Meier rates at 3 years of 7.85% in the group that received 90 mg of ticagrelor twice daily, 7.77% in the group that received 60 mg of ticagrelor twice daily, and 9.04% in the placebo group (hazard ratio for 90 mg of ticagrelor vs. placebo, 0.85; 95% confidence interval [CI], 0.75 to 0.96; P = 0.008; hazard ratio for 60 mg of ticagrelor vs. placebo, 0.84; 95% CI, 0.74 to 0.95; P = 0.004). Rates of TIMI major bleeding were higher with ticagrelor (2.60% with 90 mg and 2.30% with 60 mg) than with placebo (1.06%) (P < 0.001 for each dose vs. placebo); the rates of intracranial hemorrhage or fatal bleeding in the three groups were 0.63%, 0.71%, and 0.60%, respectively. CONCLUSIONS In patients with a myocardial infarction more than 1 year previously, treatment with ticagrelor significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke and increased the risk of major bleeding. (Funded by AstraZeneca; PEGASUS-TIMI 54 ClinicalTrials.gov number, NCT01225562.) C1 [Bonaca, Marc P.; Bhatt, Deepak L.; Magnani, Giulia; Fish, M. Polly; Im, Kyungah; Murphy, Sabina A.; Wiviott, Stephen D.; Braunwald, Eugene; Sabatine, Marc S.] Brigham & Womens Hosp, Thrombolysis Myocardial Infarct TIMI Study Grp, Cardiovasc Div, Dept Med, Boston, MA 02115 USA. [Bonaca, Marc P.; Bhatt, Deepak L.; Magnani, Giulia; Fish, M. Polly; Im, Kyungah; Murphy, Sabina A.; Wiviott, Stephen D.; Braunwald, Eugene; Sabatine, Marc S.] Harvard Univ, Sch Med, Boston, MA USA. [Cohen, Marc] Rutgers New Jersey Med Sch, Newark Beth Israel Med Ctr, Dept Med, Cardiovasc Div, Newark, NJ USA. [Steg, Philippe Gabriel] Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ Fibrosis,INSERM,U1148, French Alliance Cardiovasc Trials,Inflammat,Remod, F-75877 Paris, France. [Steg, Philippe Gabriel] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. [Steg, Philippe Gabriel] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, Natl Heart & Lung Inst, London, England. [Storey, Robert F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. [Jensen, Eva C.; Bengtsson, Olof; Held, Peter] AstraZeneca, Molndal, Sweden. [Bansilal, Sameer] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Ophuis, Ton Oude] Canisius Wilhelmina Hosp, Nijmegen, Netherlands. [Budaj, Andrzej] Grochowski Hosp, Postgrad Med Sch, Warsaw, Poland. [Theroux, Pierre] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Ruda, Mikhail] Cardiol Res Ctr, Moscow, Russia. [Hamm, Christian] Kerckhoff Heart Ctr, Bad Nauheim, Germany. [Hamm, Christian] Univ Giessen, D-35390 Giessen, Germany. [Goto, Shinya] Tokai Univ, Sch Med, Dept Med Cardiol, Isehara, Kanagawa 25911, Japan. [Spinar, Jindrich] Univ Hosp, Brno, Czech Republic. [Nicolau, Jose Carlos] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil. [Kiss, Robert G.] Mil Hosp, Dept Cardiol, Budapest, Hungary. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org RI Frey, Norbert/A-9695-2010; Rizzotti, Diego/H-5610-2015; Urina, Miguel/H-2605-2016; Prunier, Fabrice/A-5210-2011; Henrion, Daniel/J-8141-2015; Rubino, Mara/K-1537-2016; Nicolau, Jose/E-1487-2012; MacKenzie, M.A./L-4499-2015; Arkhipov, Mikhail/Q-2316-2015; Statsenko, Mikhail/N-7573-2015; CIOCA, GABRIELA/B-5504-2012; Benedek, Theodora/F-6353-2016; Ponikowski, Piotr/O-6454-2015; Derevyanchenko, Maria/A-1859-2016; Ferrari, Emile/R-2917-2016; Marin-Neto, Jose Antonio/F-6099-2012; Benedek, Imre/E-7052-2017; Derevyanchenko, Mariya/C-1673-2016; OI Safarova, Maya/0000-0003-3069-3752; Aboyans, Victor/0000-0002-0322-9818; Rizzotti, Diego/0000-0003-0641-8857; Urina, Miguel/0000-0001-6003-4622; Henrion, Daniel/0000-0003-1094-0285; Rubino, Mara/0000-0001-7820-9814; Statsenko, Mikhail/0000-0002-3306-0312; CIOCA, GABRIELA/0000-0003-1165-1389; Benedek, Theodora/0000-0001-8326-1537; Ponikowski, Piotr/0000-0002-3391-7064; Derevyanchenko, Maria/0000-0002-6232-4583; Benedek, Imre/0000-0003-0051-4047; Derevyanchenko, Mariya/0000-0001-7742-3085; Abdel-Latif, Ahmed/0000-0002-8178-7102; Patti, Giuseppe/0000-0002-5404-3968 FU AstraZeneca; PEGASUS-TIMI [54] FX Funded by AstraZeneca; PEGASUS-TIMI 54 ClinicalTrials.gov number, NCT01225562. NR 25 TC 263 Z9 280 U1 14 U2 70 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 7 PY 2015 VL 372 IS 19 BP 1791 EP 1800 DI 10.1056/NEJMoa1500857 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CH4BB UT WOS:000353974700004 PM 25773268 ER PT J AU Hoo, GWS Klaustermeyer, WB AF Hoo, Guy W. Soo Klaustermeyer, William B. TI Icatibant in ACE-Inhibitor-Induced Angioedema SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID UNITED-STATES C1 [Hoo, Guy W. Soo; Klaustermeyer, William B.] VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. RP Hoo, GWS (reprint author), VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. EM guy.soohoo@va.gov NR 3 TC 0 Z9 0 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 7 PY 2015 VL 372 IS 19 BP 1866 EP 1866 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CH4BB UT WOS:000353974700021 ER PT J AU Schlumberger, M Tahara, M Wirth, LJ AF Schlumberger, Martin Tahara, Makoto Wirth, Lori J. TI Lenvatinib in Radioiodine-Refractory Thyroid Cancer REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Schlumberger, Martin] Inst Gustave Roussy, Villejuif, France. [Tahara, Makoto] Natl Canc Ctr Hosp East, Kashiwa, Chiba, Japan. [Wirth, Lori J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schlumberger, M (reprint author), Inst Gustave Roussy, Villejuif, France. EM martin.schlumberger@gustaveroussy.fr NR 0 TC 5 Z9 5 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 7 PY 2015 VL 372 IS 19 BP 1868 EP 1868 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CH4BB UT WOS:000353974700025 PM 25946295 ER PT J AU Fernando, ATP Andrabi, S Cizmecioglu, O Zhu, C Livingston, DM Higgins, JMG Schaffhausen, BS Roberts, TM AF Fernando, A. T. Pores Andrabi, S. Cizmecioglu, O. Zhu, C. Livingston, D. M. Higgins, J. M. G. Schaffhausen, B. S. Roberts, T. M. TI Polyoma small T antigen triggers cell death via mitotic catastrophe SO ONCOGENE LA English DT Article ID PROTEIN PHOSPHATASE 2A; MIDDLE-T; KINETOCHORE LOCALIZATION; SV40-TRANSFORMED CELLS; CHROMOSOME COHESION; SPINDLE ORIENTATION; CARCINOMA-CELLS; KINASE-ACTIVITY; SIMIAN-VIRUS-40; PP2A AB Polyoma small T antigen (PyST), an early gene product of the polyoma virus, has been shown to cause cell death in a number of mammalian cells in a protein phosphatase 2A (PP2A)-dependent manner. In the current study, using a cell line featuring regulated expression of PyST, we found that PyST arrests cells in mitosis. Live-cell and immunofluorescence studies showed that the majority of the PyST expressing cells were arrested in prometaphase with almost no cells progressing beyond metaphase. These cells exhibited defects in chromosomal congression, sister chromatid cohesion and spindle positioning, thereby resulting in the activation of the spindle assembly checkpoint. Prolonged mitotic arrest then led to cell death via mitotic catastrophe. Cell cycle inhibitors that block cells in G1/S prevented PyST-induced death. PyST-induced cell death that occurs during M is not dependent on p53 status. These data suggested, and our results confirmed, that PP2A inhibition could be used to preferentially kill cancer cells with p53 mutations that proliferate normally in the presence of cell cycle inhibitors. C1 [Fernando, A. T. Pores; Andrabi, S.; Cizmecioglu, O.; Livingston, D. M.; Roberts, T. M.] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Fernando, A. T. Pores; Cizmecioglu, O.; Roberts, T. M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhu, C.; Higgins, J. M. G.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Higgins, J. M. G.] Newcastle Univ, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Schaffhausen, B. S.] Tufts Univ, Sch Med, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. RP Roberts, TM (reprint author), Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM shaida.andrabi@kashmiruniversity.ac.in; thomas_roberts@dfci.harvard.edu FU National Institutes of Health PO1 grant [CA50661]; National Institutes of Health RO1 grant [CA30002, CA34722]; Ramalingaswami fellowship; CREST fellowship; Association for International Cancer Research FX This work was supported by an National Institutes of Health PO1 grant CA50661 to TMR, BSS and DML; and an RO1 grant to TMR (CA30002) and BSS (CA34722); and a Ramalingaswami fellowship and a CREST fellowship to SA. JMGH is supported by the Association for International Cancer Research, and is a Scholar of the Leukemia and Lymphoma Society. We thank Drs Jennifer Spangle and Meera Bhanu for their helpful comments on this manuscript. NR 52 TC 3 Z9 3 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD MAY 7 PY 2015 VL 34 IS 19 BP 2483 EP 2492 DI 10.1038/onc.2014.192 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CH7BK UT WOS:000354190400007 ER PT J AU Dhou, S Hurwitz, M Mishra, P Cai, W Rottmann, J Li, R Williams, C Wagar, M Berbeco, R Ionascu, D Lewis, JH AF Dhou, S. Hurwitz, M. Mishra, P. Cai, W. Rottmann, J. Li, R. Williams, C. Wagar, M. Berbeco, R. Ionascu, D. Lewis, J. H. TI 3D fluoroscopic image estimation using patient-specific 4DCBCT-based motion models SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE cone-beam CT; motion model; 3D fluoroscopic images ID CONE-BEAM CT; TOTAL-VARIATION MINIMIZATION; LUNG-CANCER RADIOTHERAPY; COMPUTED-TOMOGRAPHY; RESPIRATORY MOTION; TUMOR-LOCALIZATION; XCAT PHANTOM; RECONSTRUCTION; REGISTRATION; PROJECTIONS AB 3D fluoroscopic images represent volumetric patient anatomy during treatment with high spatial and temporal resolution. 3D fluoroscopic images estimated using motion models built using 4DCT images, taken days or weeks prior to treatment, do not reliably represent patient anatomy during treatment. In this study we developed and performed initial evaluation of techniques to develop patient-specific motion models from 4D cone-beam CT (4DCBCT) images, taken immediately before treatment, and used these models to estimate 3D fluoroscopic images based on 2D kV projections captured during treatment. We evaluate the accuracy of 3D fluoroscopic images by comparison to ground truth digital and physical phantom images. The performance of 4DCBCT-based and 4DCT-based motion models are compared in simulated clinical situations representing tumor baseline shift or initial patient positioning errors. The results of this study demonstrate the ability for 4DCBCT imaging to generate motion models that can account for changes that cannot be accounted for with 4DCT-based motion models. When simulating tumor baseline shift and patient positioning errors of up to 5 mm, the average tumor localization error and the 95th percentile error in six datasets were 1.20 and 2.2 mm, respectively, for 4DCBCT-based motion models. 4DCT-based motion models applied to the same six datasets resulted in average tumor localization error and the 95th percentile error of 4.18 and 5.4 mm, respectively. Analysis of voxel-wise intensity differences was also conducted for all experiments. In summary, this study demonstrates the feasibility of 4DCBCT-based 3D fluoroscopic image generation in digital and physical phantoms and shows the potential advantage of 4DCBCT-based 3D fluoroscopic image estimation when there are changes in anatomy between the time of 4DCT imaging and the time of treatment delivery. C1 [Dhou, S.; Hurwitz, M.; Cai, W.; Rottmann, J.; Williams, C.; Wagar, M.; Berbeco, R.; Lewis, J. H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Dhou, S.; Hurwitz, M.; Cai, W.; Rottmann, J.; Williams, C.; Wagar, M.; Berbeco, R.; Lewis, J. H.] Harvard Univ, Sch Med, Boston, MA USA. [Mishra, P.] Varian Med Syst, Palo Alto, CA USA. [Li, R.] Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA. [Ionascu, D.] William Beaumont Hosp, Dept Radiat Oncol, Royal Oak, MI USA. RP Dhou, S (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM sdhou@lroc.harvard.edu; jhlewis@lroc.harvard.edu FU Varian Medical Systems, Inc, Palo Alto, CA; National Cancer Institute [R21CA156068] FX The authors thank Dr Seiko Nishioka of the Department of Radiology, NTT Hospital, Sapporo, Japan, and Dr Hiroki Shirato of the Department of Radiation Medicine, Hokkaido University School of Medicine, Sapporo, Japan, for sharing the patient tumor motion dataset with us. This project was supported, in part, through a Master Research Agreement with Varian Medical Systems, Inc, Palo Alto, CA. The project was also supported, in part, by Award Number R21CA156068 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 49 TC 3 Z9 3 U1 0 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 7 PY 2015 VL 60 IS 9 BP 3807 EP 3824 DI 10.1088/0031-9155/60/9/3807 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CH5VX UT WOS:000354104700027 PM 25905722 ER PT J AU Banks, HT Flores, KB Hu, SH Rosenberg, E Buzon, M Yu, X Lichterfeld, M AF Banks, H. T. Flores, Kevin B. Hu, Shuhua Rosenberg, Eric Buzon, Maria Yu, Xu Lichterfeld, Matthias TI Immuno-modulatory strategies for reduction of HIV reservoir cells SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE Immune response; Mathematical model; Inverse problem; Stability analysis ID ACTIVE ANTIRETROVIRAL THERAPY; INTERMITTENT VIRAL BLIPS; CD4(+) T-CELLS; LATENT RESERVOIR; VIRUS REACTIVATION; PERIPHERAL-BLOOD; PERSISTENCE; LYMPHOCYTES; PROLIFERATION; REPLICATION AB Antiretroviral therapy is able to suppress the viral load to below the detection limit, but it is not able to eradicate HIV reservoirs. Thus, there is a critical need for a novel treatment to eradicate (or reduce) the reservoir in order to eliminate the need for a lifelong adherence to antiretroviral therapy, which is expensive and potentially toxic. In this paper, we investigate the possible pharmacological strategies or combinations of strategies that may be beneficial to reduce or possibly eradicate the latent reservoir. We do this via studies with a validated mathematical model, where the parameter values are obtained with newly acquired clinical data for HIV patients. Our findings indicate that the strategy of reactivating the reservoir combined with enhancement of the killing rate of HIV-specific CD8+ T cells is able to eradicate the reservoir. In addition, our analysis shows that a targeted suppression of the immune system is also a possible strategy to eradicate the reservoir. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Banks, H. T.; Flores, Kevin B.; Hu, Shuhua] N Carolina State Univ, Ctr Res Sci Computat, Raleigh, NC 27695 USA. [Rosenberg, Eric; Buzon, Maria; Yu, Xu; Lichterfeld, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Rosenberg, Eric; Buzon, Maria; Yu, Xu; Lichterfeld, Matthias] Mass Gen Hosp, Ragon Inst, Boston, MA USA. RP Banks, HT (reprint author), N Carolina State Univ, Ctr Res Sci Computat, Raleigh, NC 27695 USA. EM htbanks@ncsu.edu RI Buzon, Maria J/G-8286-2015 OI Buzon, Maria J/0000-0003-4427-9413 FU National Institute of Allergy and Infectious Diseases [NIAID R01AI071915-10]; Air Force Office of Scientific Research [AFOSR FA9550-12-1-0188] FX This research was supported in part by Grant number NIAID R01AI071915-10 from the National Institute of Allergy and Infectious Diseases, and in part by the Air Force Office of Scientific Research under Grant number AFOSR FA9550-12-1-0188. In addition, the authors are grateful to anonymous referees for their careful reading and helpful comments which led to an improved version of this paper. NR 34 TC 2 Z9 2 U1 0 U2 7 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 EI 1095-8541 J9 J THEOR BIOL JI J. Theor. Biol. PD MAY 7 PY 2015 VL 372 BP 146 EP 158 DI 10.1016/j.jtbi.2015.02.006 PG 13 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA CG5DQ UT WOS:000353311700016 PM 25701451 ER PT J AU Meyers, EM Borzello, M Freiwald, WA Tsao, D AF Meyers, Ethan M. Borzello, Mia Freiwald, Winrich A. Tsao, Doris TI Intelligent Information Loss: The Coding of Facial Identity, Head Pose, and Non-Face Information in the Macaque Face Patch System SO JOURNAL OF NEUROSCIENCE LA English DT Article DE face processing; face recognition; macaque; neural decoding; population coding ID TEMPORAL CORTEX; HUMAN BRAIN; PROCESSING FACES; NEURONS; LOBE; REPRESENTATIONS; RECOGNITION; ACTIVATION; REGION; FMRI AB Faces are a behaviorally important class of visual stimuli for primates. Recent work in macaque monkeys has identified six discrete face areas where most neurons have higher firing rates to images of faces compared with other objects (Tsao et al., 2006). While neurons in these areas appear to have different tuning (Freiwald and Tsao, 2010; Issa and DiCarlo, 2012), exactly what types of information and, consequently, which visual behaviors neural populations within each face area can support, is unknown. Here we use population decoding to better characterize three of these face patches (ML/MF, AL, and AM). We show that neural activity in all patches contains information that discriminates between the broad categories of face and nonface objects, individual faces, and nonface stimuli. Information is present in both high and lower firing rate regimes. However, there were significant differences between the patches, with the most anterior patch showing relatively weaker representation of nonface stimuli. Additionally, we find that pose-invariant face identity information increases as one moves to more anterior patches, while information about the orientation of the head decreases. Finally, we show that all the information we can extract from the population is present in patterns of activity across neurons, and there is relatively little information in the total activity of the population. These findings give new insight into the representations constructed by the face patch system and how they are successively transformed. C1 [Meyers, Ethan M.] Hampshire Coll, Sch Cognit Sci, Amherst, MA 01002 USA. [Meyers, Ethan M.; Borzello, Mia; Freiwald, Winrich A.] MIT, Ctr Brains Minds & Machines, Cambridge, MA 02139 USA. [Borzello, Mia] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Freiwald, Winrich A.] Rockefeller Univ, Lab Neural Syst, New York, NY 10065 USA. [Tsao, Doris] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91126 USA. RP Meyers, EM (reprint author), Hampshire Coll, Adele Simmons Hall 133,893 West St, Amherst, MA 01002 USA. EM emeyers@hampshire.edu FU Center for Brains, Minds and Machines - National Science Foundation (NSF) STC award [CCF-1231216]; National Institutes of Health (NIH) [R01-EY019702]; NIH grant [R01-EY021594]; Pew Scholarship in Biomedical Sciences; Defense Advanced Research Planning Agency grant (Information Processing Techniques Office); NSF [NSF-0640097, NSF-0827427]; Honda Research Institute USA; King Abdullah University Science and Technology; Defense Advanced Research Planning Agency grant (Defense Sciences Office); Adobe; Klingenstein Fellowship FX This work was supported by the Center for Brains, Minds and Machines, funded by National Science Foundation (NSF) STC award CCF-1231216. Additional support comes from National Institutes of Health (NIH) Grant R01-EY019702 and Klingenstein Fellowship to D.T.; NIH grant R01-EY021594 and Pew Scholarship in the Biomedical Sciences for W.A.F.; and the Defense Advanced Research Planning Agency grants (Information Processing Techniques Office and Defense Sciences Office), NSF grants NSF-0640097 and NSF-0827427, and from Adobe, Honda Research Institute USA, and a King Abdullah University Science and Technology grant to B. DeVore. We would also like to thank Tomaso Poggio for his continual support and Jim Mutch for his help creating the S1 and C2 HMAX features. NR 32 TC 14 Z9 14 U1 1 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 6 PY 2015 VL 35 IS 18 BP 7069 EP 7081 DI 10.1523/JNEUROSCI.3086-14.2015 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CL0YG UT WOS:000356668400009 PM 25948258 ER PT J AU Fernandez-Bustamante, A Hashimoto, S Neto, AS Moine, P Melo, MFV Repine, JE AF Fernandez-Bustamante, Ana Hashimoto, Soshi Neto, Ary Serpa Moine, Pierre Melo, Marcos F. Vidal Repine, John E. TI Perioperative lung protective ventilation in obese patients SO BMC ANESTHESIOLOGY LA English DT Review DE Lung protective ventilation; Obese surgical patients; Mechanical ventilation; Perioperative ventilation; Obesity ID END-EXPIRATORY PRESSURE; RESPIRATORY-DISTRESS-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; OBSTRUCTIVE SLEEP-APNEA; BODY-MASS INDEX; LOWER TIDAL VOLUMES; POSTOPERATIVE PULMONARY COMPLICATIONS; LAPAROSCOPIC BARIATRIC SURGERY; ALVEOLAR RECRUITMENT MANEUVER; NECROSIS-FACTOR-ALPHA AB The perioperative use and relevance of protective ventilation in surgical patients is being increasingly recognized. Obesity poses particular challenges to adequate mechanical ventilation in addition to surgical constraints, primarily by restricted lung mechanics due to excessive adiposity, frequent respiratory comorbidities (i.e. sleep apnea, asthma), and concerns of postoperative respiratory depression and other pulmonary complications. The number of surgical patients with obesity is increasing, and facing these challenges is common in the operating rooms and critical care units worldwide. In this review we summarize the existing literature which supports the following recommendations for the perioperative ventilation in obese patients: (1) the use of protective ventilation with low tidal volumes (approximately 8 mL/kg, calculated based on predicted -not actual-body weight) to avoid volutrauma; (2) a focus on lung recruitment by utilizing PEEP (8-15 cmH(2)O) in addition to recruitment maneuvers during the intraoperative period, as well as incentivized deep breathing and noninvasive ventilation early in the postoperative period, to avoid atelectasis, hypoxemia and atelectrauma; and (3) a judicious oxygen use (ideally less than 0.8) to avoid hypoxemia but also possible reabsorption atelectasis. Obesity poses an additional challenge for achieving adequate protective ventilation during one-lung ventilation, but different lung isolation techniques have been adequately performed in obese patients by experienced providers. Postoperative efforts should be directed to avoid hypoventilation, atelectasis and hypoxemia. Further studies are needed to better define optimum protective ventilation strategies and analyze their impact on the perioperative outcomes of surgical patients with obesity. C1 [Fernandez-Bustamante, Ana; Moine, Pierre; Repine, John E.] Univ Colorado SOM, Dept Anesthesiol, Aurora, CO 80045 USA. [Fernandez-Bustamante, Ana; Repine, John E.] Univ Colorado SOM, Webb Waring Ctr, Aurora, CO USA. [Hashimoto, Soshi; Melo, Marcos F. Vidal] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Neto, Ary Serpa] Hosp Israelita Albert Einstein, Dept Crit Care Med, Sao Paulo, Brazil. [Neto, Ary Serpa] Univ Amsterdam, Acad Med Ctr, Dept Intens Care, NL-1105 AZ Amsterdam, Netherlands. [Repine, John E.] Univ Colorado SOM, Dept Med, Aurora, CO USA. RP Fernandez-Bustamante, A (reprint author), Univ Colorado SOM, Dept Anesthesiol, Aurora, CO 80045 USA. EM Ana.Fernandez-Bustamante@ucdenver.edu RI Serpa Neto, Ary/D-1927-2012; OI Serpa Neto, Ary/0000-0003-1520-9387; Fernandez-Bustamante, Ana/0000-0002-2996-7704 NR 130 TC 11 Z9 11 U1 1 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2253 J9 BMC ANESTHESIOL JI BMC Anesthesiol. PD MAY 6 PY 2015 VL 15 AR 56 DI 10.1186/s12871-015-0032-x PG 13 WC Anesthesiology SC Anesthesiology GA CK1LC UT WOS:000355967800001 PM 25907273 ER PT J AU Wasfy, JH Armstrong, K Milford, CE Sundt, TM AF Wasfy, Jason H. Armstrong, Katrina Milford, Creagh E. Sundt, Thoralf M., III TI Doctors should share their uncertainty with patients and make decisions together SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Clinical decision making; Aortic aneurysm; Aortic valvular disease C1 [Wasfy, Jason H.; Milford, Creagh E.] Harvard Univ, Sch Med, Massachusetts Gen Phys Org, Boston, MA USA. [Wasfy, Jason H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Boston, MA USA. [Armstrong, Katrina; Milford, Creagh E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Sundt, Thoralf M., III] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Cardiac Surg Div, Boston, MA 02115 USA. RP Wasfy, JH (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Phys Org, BUL 205,55 Fruit St, Boston, MA 02114 USA. EM jwasfy@mgh.harvard.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD MAY 6 PY 2015 VL 187 BP 109 EP 110 DI 10.1016/j.ijcard.2015.03.312 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CI6WT UT WOS:000354905600031 PM 25828326 ER PT J AU Cunningham, KF Beeson, GC Beeson, CC Baicu, CF Zile, MR McDermott, PJ AF Cunningham, Kathryn F. Beeson, Gyda C. Beeson, Craig C. Baicu, Catalin F. Zile, Michael R. McDermott, Paul J. TI Estrogen-Related Receptor a (ERRa) is required for adaptive increases in PGC-1 isoform expression during electrically stimulated contraction of adult cardiomyocytes in sustained hypoxic conditions SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Contraction; Cardiomyocyte; Hypoxia; Estrogen-Related Receptor; Peroxisome Proliferator-Activated Receptor; gamma Coactivator-1 ID PROLIFERATOR-ACTIVATED RECEPTOR; HEART-FAILURE; ENERGY-METABOLISM; INVERSE AGONIST; TRANSCRIPTIONAL CONTROL; FELINE CARDIOCYTES; BROWN-ADIPOCYTES; ALPHA EXPRESSION; SKELETAL-MUSCLE; GENE-EXPRESSION AB Background and objectives: In adultmyocardium, Estrogen-Related Receptora(ERR alpha) programs energetic capacity of cardiomyocytes by regulating expression of target genes required for mitochondrial biogenesis, fatty acid metabolism and oxidative phosphorylation. Transcriptional activation by ERRa is dependent on the alpha or beta isoform of Peroxisome Proliferator-Activated Receptor gamma Coactivator-1 (PGC-1). This study utilized a model of continuously contracting adult cardiomyocytes to determine the effects of sustained oxygen reduction (hypoxia) on ERRa target gene expression. Methods and results: Adult feline cardiomyocytes in primary culture were electrically stimulated to contract at 1 Hz in either normoxia (21% O-2) or hypoxia (0.5% O-2). Compared to normoxia, hypoxia increased PGC-1 alpha mRNA and PGC-1 beta mRNA levels by 16-fold and 14-fold after 24 h. ERRa mRNA levels were increased 3-fold by hypoxia over the same time period. Treatment of cardiomyocytes with XCT-790, an ERRa inverse agonist, caused knockdown of ERR alpha protein expression. The increases in PGC-1 mRNA levels in response to hypoxia were blocked by XCT-790 treatment, which indicates that expression of PGC-1 isoforms is dependent on ERRa activity. The products of two ERRa target genes required for energy metabolism, Cox6c mRNA and Fabp3 mRNA, increased by 4.5-fold and 3.5 fold after 24 h of hypoxia as compared to normoxic controls. These increases were blocked by XCT-790 treatment of hypoxic cardiomyocytes with a concomitant decrease in ERRa expression. Conclusions: ERRa activity is required to increase expression of PGC-1 isoforms and downstream target genes as part of the adaptive response of contracting adult cardiomyocytes to sustained hypoxia. Published by Elsevier Ireland Ltd. C1 [Cunningham, Kathryn F.; Baicu, Catalin F.; Zile, Michael R.; McDermott, Paul J.] Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Charleston, SC 29425 USA. [Beeson, Gyda C.; Beeson, Craig C.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Zile, Michael R.; McDermott, Paul J.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP McDermott, PJ (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, 114 Doughty St,Room 303,MSC 773, Charleston, SC 29425 USA. EM mcdermp@musc.edu FU Merit Review Award of the Department of Veterans Affairs; NIH Predoctoral Fellowship Training Grant to Improve Cardiovascular Therapies; American Heart Association Predoctoral Fellowship [12PRE1205007] FX We wish to thank Daisy Dominick, Dr. Harinath Kasiganesan and Shaun R. Wahl for their excellent technical assistance. This research was supported by a Merit Review Award of the Department of Veterans Affairs (to P.J.M.); NIH Predoctoral Fellowship Training Grant to Improve Cardiovascular Therapies (to K.F.C.); and American Heart Association Predoctoral Fellowship (K.F.C., 12PRE1205007). NR 50 TC 2 Z9 4 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD MAY 6 PY 2015 VL 187 BP 393 EP 400 DI 10.1016/j.ijcard.2015.03.353 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CI6WT UT WOS:000354905600111 PM 25841134 ER PT J AU Vestman, NR Chen, T Holgerson, PL Ohman, C Johansson, I AF Vestman, Nelly Romani Chen, Tsute Holgerson, Pernilla Lif Ohman, Carina Johansson, Ingegerd TI Oral Microbiota Shift after 12-Week Supplementation with Lactobacillus reuteri DSM 17938 and PTA 5289; A Randomized Control Trial SO PLOS ONE LA English DT Article ID SALIVARY MUTANS STREPTOCOCCI; FULL-MOUTH DISINFECTION; LACTIC-ACID BACTERIA; IN-VITRO; PROBIOTIC BACTERIA; HEALTHY-ADULTS; GUT MICROBIOME; RHAMNOSUS GG; FED INFANTS; CARIES AB Background Lactobacillus spp. potentially contribute to health by modulating bacterial biofilm formation, but their effects on the overall oral microbiota remain unclear. Methods and Findings Oral microbiota was characterized via 454-pyrosequencing of the 16S rDNA hypervariable region V3-V4 after 12 weeks of daily Lactobacillus reuteri DSM 17938 and PTA 5289 consumption. Forty-four adults were assigned to a test group (n = 22) that received lactobacilli lozenges (108 CFU of each strain/lozenge) or a control group that received placebo (n = 22). Presence of L. reuteri was confirmed by cultivation and species specific PCR. Tooth biofilm samples from 16 adults before, during, and after exposure were analyzed by pyrosequencing. A total of 1,310,292 sequences were quality filtered. After removing single reads, 257 species or phylotypes were identified at 98.5% identity in the Human Oral Microbiome Database. Firmicutes, Bacteroidetes, Fusobacteria, Proteobacteria, and Actinobacteriawere the most abundant phyla. Streptococcus was the most common genus and the S. oralis/S. mitis/S. mitis bv2/S. infantis group comprised the dominant species. The number of observed species was unaffected by L. reuteri exposure. However, subjects who had consumed L. reuteri were clustered in a principal coordinates analysis relative to scattering at baseline, and multivariate modeling of pyrosequencing microbiota, and culture and PCR detected L. reuteri separated baseline from 12-week samples in test subjects. L. reuteri intake correlated with increased S. oralis/S. mitis/S. mitis bv2/S. infantis group and Campylobacter concisus, Granulicatella adiacens, Bergeyella sp. HOT322, Neisseria subflava, and SR1 [G1] sp. HOT874 detection and reduced S. mutans, S. anginosus, N. mucosa, Fusobacterium periodicum, F. nucleatum ss vincentii, and Prevotella maculosadetection. This effect had disappeared 1 month after exposure was terminated. Conclusions L. reuteri consumption did not affect species richness but induced a shift in the oral microbiota composition. The biological relevance of this remains to be elucidated. C1 [Vestman, Nelly Romani; Ohman, Carina; Johansson, Ingegerd] Umea Univ, Dept Odontol, Cardiol Sect, Umea, Sweden. [Chen, Tsute] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Holgerson, Pernilla Lif] Umea Univ, Dept Odontol, Sect Pedodont, Umea, Sweden. RP Johansson, I (reprint author), Umea Univ, Dept Odontol, Cardiol Sect, Umea, Sweden. EM ingegerd.johansson@odont.umu.se FU Vasterbotten County Council (TUA); Swedish Research Council FX This work was supported by the Vasterbotten County Council (TUA). The Swedish Research Council funded the National School of Odontological Sciences, The Swedish Nutrition Foundation, and The Swedish Dental Society. Test and placebo lozenges were obtained from the manufacturer BioGaia AB (Lund, Sweden). The supplier had no role in the study design or implementation, data analysis, decision to publish, or manuscript preparation. The authors declare no conflicts of interest. NR 67 TC 3 Z9 4 U1 2 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 6 PY 2015 VL 10 IS 5 AR e0125812 DI 10.1371/journal.pone.0125812 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH5BQ UT WOS:000354049700089 ER PT J AU Hickey, AJ Gounder, L Moosa, MYS Drain, PK AF Hickey, Andrew J. Gounder, Lilishia Moosa, Mahomed-Yunus S. Drain, Paul K. TI A systematic review of hepatic tuberculosis with considerations in human immunodeficiency virus co-infection SO BMC INFECTIOUS DISEASES LA English DT Review DE Tuberculosis; Liver; Extrapulmonary tuberculosis; HIV/AIDS ID POLYMERASE-CHAIN-REACTION; HEPATOBILIARY TUBERCULOSIS; EXTRAPULMONARY TUBERCULOSIS; NODULAR FORM; PATHOLOGICAL CORRELATION; ULTRASOUND FINDINGS; HIV-INFECTION; SINGLE-CENTER; LIVER; GRANULOMAS AB Background: Mycobacterium tuberculosis (TB) infection of the liver, known as hepatic TB, is an extrapulmonary manifestation of TB. Hepatic TB has become more prevalent, likely as a result of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic. We sought to review case series to characterize the epidemiology, pathophysiology, clinical features, diagnosis, and treatment of hepatic TB and to comment on the impact of HIV co-infection on these characteristics. Methods: We conducted a systematic literature search in PubMed and ScienceDirect for articles pertaining to hepatic TB with human subjects from 1960 to July 2013. Results: We obtained data on 618 hepatic TB patients from 14 case series. The most common reported signs and symptoms were hepatomegaly (median: 80%, range: 10-100%), fever (median: 67%, range: 30-100), respiratory symptoms (median: 66%, range: 32-78%), abdominal pain (median: 59.5%, range: 40-83%), and weight loss (median: 57.5%, range: 20-100%). Common laboratory abnormalities were elevated alkaline phosphatase and gamma-glutamyl transferase. Ultrasound and computerized tomography (CT) were sensitive but non-specific. On liver biopsy, smear microscopy for acid-fast bacilli had a median sensitivity of 25% (range: 0-59%), histology of caseating granulomas had a median sensitivity of 68% (range: 14-100%), and polymerase chain reaction for TB had a median sensitivity of 86% (range: 30-100%). Standard anti-tuberculous chemotherapy for 6 to 12 months achieved positive outcomes for nearly all patients with drug-susceptible TB. Conclusions: Clinicians in TB-endemic regions should maintain a high index of suspicion for hepatic TB in patients presenting with hepatomegaly, fever, respiratory symptoms, and elevated liver enzymes. The most sensitive imaging modality is a CT scan, while the most specific diagnostic modality is a liver biopsy with nucleic acid testing of liver tissue samples. Upon diagnosis, 4-drug anti-TB therapy should promptly be initiated. HIV co-infected patients may have more complex cases and should be closely monitored for complications. C1 [Hickey, Andrew J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Gounder, Lilishia; Moosa, Mahomed-Yunus S.] Univ KwaZulu Natal, Nelson Mandela Sch Med, Dept Infect Dis, Durban, South Africa. [Gounder, Lilishia] Inkosi Albert Luthuli Cent Hosp, Natl Hlth Lab Serv, Dept Virol, Durban, South Africa. [Drain, Paul K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. [Drain, Paul K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practice Evaluat Ctr,Dept Med, Boston, MA USA. RP Hickey, AJ (reprint author), Univ Maryland, Sch Med, 655 W Baltimore St, Baltimore, MD 21201 USA. EM andrew.hickey@som.umaryland.edu FU Duke University Dean's Summer Research Fellowship; Harvard Global Health Institute; Infectious Disease Society of America Education & Research Foundation (IDSA ERF); National Foundation for Infectious Diseases (NFID); Massachusetts General Hospital Executive Committee on Research; National Institute of Allergy and Infectious Diseases [K23 AI108293]; Harvard University Center for AIDS Research [P30 AI060354] FX This research was supported by the Duke University Dean's Summer Research Fellowship. PKD is supported by the Harvard Global Health Institute, the Infectious Disease Society of America Education & Research Foundation (IDSA ERF) and National Foundation for Infectious Diseases (NFID), Massachusetts General Hospital Executive Committee on Research, the National Institute of Allergy and Infectious Diseases K23 AI108293, and the Harvard University Center for AIDS Research P30 AI060354. We thank our research staff and nurses who carried out the study. NR 76 TC 3 Z9 3 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD MAY 6 PY 2015 VL 15 AR 209 DI 10.1186/s12879-015-0944-6 PG 11 WC Infectious Diseases SC Infectious Diseases GA CH5LX UT WOS:000354078300001 PM 25943103 ER PT J AU Liu, CC DeRoo, EP Stecyk, C Wolsey, M Szuchnicki, M Hagos, EG AF Liu, Changchang DeRoo, Elise P. Stecyk, Catherine Wolsey, Margaret Szuchnicki, Mateusz Hagos, Engda G. TI Impaired autophagy in mouse embryonic fibroblasts null for Kruppel-like Factor 4 promotes DNA damage and increases apoptosis upon serum starvation SO MOLECULAR CANCER LA English DT Article DE Kruppel-like Factor 4; Autophagy; Apoptosis; Mammalian target of rapamycin; DNA damage; Mouse embryonic fibroblasts; Autophagy related genes ID TRANSCRIPTION FACTOR KLF4; TUMOR-SUPPRESSOR GENE; COLORECTAL-CANCER; DOWN-REGULATION; CELL-DEATH; MTOR; TUMORIGENESIS; MACROAUTOPHAGY; INHIBITION; KRUPPEL-LIKE-FACTOR-4 AB Background: Autophagy is a major cellular process by which cytoplasmic components such as damaged organelles and misfolded proteins are recycled. Although low levels of autophagy occur in cells under basal conditions, certain cellular stresses including nutrient depletion, DNA damage, and oxidative stress are known to robustly induce autophagy. Kruppel-like factor 4 (KLF4) is a zinc-finger transcription factor activated during oxidative stress to maintain genomic stability. Both autophagy and KLF4 play important roles in response to stress and function in tumor suppression. Methods: To explore the role of KLF4 on autophagy in mouse embryonic fibroblasts (MEFs), we compared wild-type with Klf4 deficient cells. To determine the levels of autophagy, we starved MEFs for different times with Earle's balanced salts solution (EBSS). Rapamycin was used to manipulate mTOR activity and autophagy. The percentage of cells with gamma-H2AX foci, a marker for DNA damage, and punctate pattern of GFP-LC3 were counted by confocal microscopy. The effects of the drug treatments, Klf4 overexpression, or Klf4 transient silencing on autophagy were analyzed using Western blot. Trypan Blue assay and flow cytometry were used to study cell viability and apoptosis, respectively. qPCR was also used to assay basal and the effects of Klf4 overexpression on Atg7 expression levels. Results: Here our data suggested that Klf4(-/-) MEFs exhibited impaired autophagy, which sensitized them to cell death under nutrient deprivation. Secondly, DNA damage in Klf4-null MEFs increased after treatment with EBSS and was correlated with increased apoptosis. Thirdly, we found that Klf4(-/-) MEFs showed hyperactive mTOR activity. Furthermore, we demonstrated that rapamycin reduced the increased level of mTOR in Klf4-/-MEFs, but did not restore the level of autophagy. Finally, re-expression of Klf4 in Klf4 deficient MEFs resulted in increased levels of LC3II, a marker for autophagy, and Atg7 expression level when compared to GFP-control transfected Klf4(-/-) MEFs. Conclusion: Taken together, our results strongly suggest that KLF4 plays a critical role in the regulation of autophagy and suppression of mTOR activity. In addition, we showed that rapamycin decreased the level of mTOR in Klf4(-/-) MEFs, but did not restore autophagy. This suggests that KLF4 regulates autophagy through both mTOR-dependent and independent mechanisms. Furthermore, for the first time, our findings provide novel insights into the mechanism by which KLF4 perhaps prevents DNA damage and apoptosis through activation of autophagy. C1 [Liu, Changchang; DeRoo, Elise P.; Stecyk, Catherine; Wolsey, Margaret; Szuchnicki, Mateusz; Hagos, Engda G.] Colgate Univ, Dept Biol, Hamilton, NY 13346 USA. [DeRoo, Elise P.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [DeRoo, Elise P.] Harvard Univ, Sch Med Sch, Boston, MA 02115 USA. [Stecyk, Catherine] Tufts Univ, Cummings Sch Vet Med, North Grafton, MA 01536 USA. RP Hagos, EG (reprint author), Colgate Univ, Dept Biol, 13 Oak Dr,Olin Hall 205A, Hamilton, NY 13346 USA. EM ehagos@colgate.edu FU Colgate University Research Council FX This work was supported in part by Picker Research Fellowship and Major Grant from Colgate University Research Council. We acknowledge the lab of Dr. Vincent W. Yang (Stony Brook Medical School, NY) for providing KLF4-GFP and GFP constructs. The authors would also like to thank Dr. Kenneth Belanger for critically reviewing the manuscript. NR 48 TC 3 Z9 4 U1 1 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD MAY 6 PY 2015 VL 14 AR 101 DI 10.1186/s12943-015-0373-6 PG 13 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA CH3NZ UT WOS:000353938700001 PM 25944097 ER PT J AU Rego, GG Lapenta, OM Marques, LM Costa, TL Leite, J Carvalho, S Goncalves, OF Brunoni, AR Fregni, F Boggio, PS AF Rego, Gabriel G. Lapenta, Olivia M. Marques, Lucas M. Costa, Thiago L. Leite, Jorge Carvalho, Sandra Goncalves, Oscar F. Brunoni, Andre R. Fregni, Felipe Boggio, Paulo S. TI Hemispheric dorsolateral prefrontal cortex lateralization in the regulation of empathy for pain SO NEUROSCIENCE LETTERS LA English DT Article DE Physical pain; Pain empathy; Emotion regulation; Dorsolateral prefrontal cortex; Transcranial direct current stimulation; Pupil dilation ID DIRECT-CURRENT STIMULATION; MODULATION AB The dorsolateral prefrontal cortex (DLPFC) is involved in the cognitive appraisal and modulation of the pain experience. In this sham-controlled study, with healthy volunteers, we used bi-hemispheric transcranial direct current stimulation (tDCS) over the DLPFC to assess emotional reactions elicited by pain observation. Left-cathodal/right-anodal tDCS decreased valence and arousal evaluations compared to other tDCS conditions. Compared to sham condition, both left-cathodal/right-anodal and left-anodal/right-cathodal tDCS decreased hostility, sadness and self-pain perception. These decreased sensations after both active tDCS suggest a common role for left and right DLPFC in personal distress modulation. However, the differences in arousal and valence evaluations point to distinct roles of lateralized DLPFC in cognitive empathy, probably through distinct emotion regulation mechanisms. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Rego, Gabriel G.; Lapenta, Olivia M.; Marques, Lucas M.; Costa, Thiago L.; Boggio, Paulo S.] Univ Prebiteriana Mackenzie, Ctr Hlth & Biol Sci, Social & Cognit Neurosci Lab, BR-01241001 Sao Paulo, Brazil. [Rego, Gabriel G.; Lapenta, Olivia M.; Marques, Lucas M.; Costa, Thiago L.; Boggio, Paulo S.] Univ Prebiteriana Mackenzie, Ctr Hlth & Biol Sci, Dev Disorders Program, BR-01241001 Sao Paulo, Brazil. [Leite, Jorge; Carvalho, Sandra; Goncalves, Oscar F.] Northeastern Univ, Bouve Coll Hlth Sci, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. [Brunoni, Andre R.] Univ Sao Paulo, Dept & Inst Psychiat, SIN, Sao Paulo, Brazil. [Brunoni, Andre R.] Univ Sao Paulo, Univ Hosp, Sao Paulo, Brazil. [Leite, Jorge; Carvalho, Sandra; Goncalves, Oscar F.] Univ Minho, CIPsi Sch Psychol, Neuropsychophysiol Lab, Braga, Portugal. [Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Spaulding Neuromodulat Ctr, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Boggio, PS (reprint author), Univ Prebiteriana Mackenzie, Ctr Hlth & Biol Sci, Social & Cognit Neurosci Lab, BR-01241001 Sao Paulo, Brazil. EM boggio@mackenzie.br RI Leite, Jorge/E-4404-2013; Boggio, Paulo/K-6272-2012; Goncalves, Oscar/G-5278-2010; Marques, Lucas/F-5583-2016; OI Leite, Jorge/0000-0002-0323-9012; Boggio, Paulo/0000-0002-6109-0447; Goncalves, Oscar/0000-0003-2735-9155; Carvalho, Sandra/0000-0003-1759-5146; Russowsky Brunoni, Andre/0000-0002-6310-3571 FU National Council for Scientific and Technological Development [CNPq-480891/2012-5]; scientific initiation grant (CNPq) [160553/2013-0]; FAPESP PhD grant (FAPESP) [2012/24696-1] FX This experiment was supported by the National Council for Scientific and Technological Development (CNPq-480891/2012-5). LMM is supported by a scientific initiation grant (CNPq - 160553/2013-0). OML is supported by a FAPESP PhD grant (FAPESP - 2012/24696-1). PSB is a CNPq research fellow (304164/2012-7). NR 19 TC 10 Z9 10 U1 2 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 6 PY 2015 VL 594 BP 12 EP 16 DI 10.1016/j.neulet.2015.03.042 PG 5 WC Neurosciences SC Neurosciences & Neurology GA CH0ZF UT WOS:000353750200003 PM 25805457 ER PT J AU Clark, TK Newman, MC Oman, CM Merfeld, DM Young, LR AF Clark, Torin K. Newman, Michael C. Oman, Charles M. Merfeld, Daniel M. Young, Laurence R. TI Modeling human perception of orientation in altered gravity SO FRONTIERS IN SYSTEMS NEUROSCIENCE LA English DT Article DE orientation perception; hyper-gravity; vestibular; mathematical model; observer ID INNERVATING OTOLITH ORGANS; SPATIAL ORIENTATION; SQUIRREL-MONKEY; SEMICIRCULAR CANALS; MOTION SICKNESS; ROLL-TILT; SENSORY CONFLICT; INTERNAL-MODELS; EYE-MOVEMENTS; PHYSIOLOGY AB Altered gravity environments, such as those experienced by astronauts, impact spatial orientation perception, and can lead to spatial disorientation and sensorimotor impairment. To more fully understand and quantify the impact of altered gravity on orientation perception, several mathematical models have been proposed. The utricular shear, tangent, and the idiotropic vector models aim to predict static perception of tilt in hyper-gravity. Predictions from these prior models are compared to the available data, but are found to systematically err from the perceptions experimentally observed. Alternatively, we propose a modified utricular shear model for static tilt perception in hyper-gravity. Previous dynamic models of vestibular function and orientation perception are limited to 1 G. Specifically, they fail to predict the characteristic overestimation of roll tilt observed in hyper-gravity environments. To address this, we have proposed a modification to a previous observer-type canal-otolith interaction model based upon the hypothesis that the central nervous system (CNS) treats otolith stimulation in the utricular plane differently than stimulation out of the utricular plane. Here we evaluate our modified utricular shear and modified observer models in four altered gravity motion paradigms: (a) static roll tilt in hyper gravity, (b) static pitch tilt in hyper gravity, (c) static roll tilt in hypo-gravity, and (d) static pitch tilt in hypo-gravity. The modified models match available data in each of the conditions considered. Our static modified utricular shear model and dynamic modified observer model may be used to help quantitatively predict astronaut perception of orientation in altered gravity environments. C1 [Clark, Torin K.; Oman, Charles M.; Young, Laurence R.] MIT, Dept Aeronaut & Astronaut, Man Vehicle Lab, Cambridge, MA 02139 USA. [Clark, Torin K.; Merfeld, Daniel M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Jenks Vestibular Psychol Lab, Boston, MA USA. [Newman, Michael C.] Natl Aerosp Training & Res Ctr, Southampton, PA USA. RP Clark, TK (reprint author), MIT, Dept Aeronaut & Astronaut, Man Vehicle Lab, 70 Vassar St,Rm 37-219, Cambridge, MA 02139 USA. EM tkc@mit.edu FU NIDCD NIH HHS [R01 DC004158] NR 62 TC 2 Z9 2 U1 3 U2 9 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5137 J9 FRONT SYST NEUROSCI JI Front. Syst. Neurosci. PD MAY 5 PY 2015 VL 9 AR 68 DI 10.3389/fnsys.2015.00068 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CU8PZ UT WOS:000363806700001 PM 25999822 ER PT J AU Im, H Castro, CM Shao, HL Liong, M Song, J Pathania, D Fexon, L Min, C Avila-Wallace, M Zurkiya, O Rho, J Magaoay, B Tambouret, RH Pivovarov, M Weissleder, R Lee, H AF Im, Hyungsoon Castro, Cesar M. Shao, Huilin Liong, Monty Song, Jun Pathania, Divya Fexon, Lioubov Min, Changwook Avila-Wallace, Maria Zurkiya, Omar Rho, Junsung Magaoay, Brady Tambouret, Rosemary H. Pivovarov, Misha Weissleder, Ralph Lee, Hakho TI Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer diagnostics; smartphone; molecular sensing; point-of-care diagnostics; cervical cancer ID NONCOMMUNICABLE DISEASES; HOLOGRAPHIC MICROSCOPY; CERVICAL-CANCER; PROTEIN EXPRESSION; WIDE-FIELD; CHIP; CELL; AIDS; SUPERRESOLUTION; RECONSTRUCTION AB The widespread distribution of smartphones, with their integrated sensors and communication capabilities, makes them an ideal platform for point-of-care (POC) diagnosis, especially in resource-limited settings. Molecular diagnostics, however, have been difficult to implement in smartphones. We herein report a diffraction-based approach that enables molecular and cellular diagnostics. The D3 (digital diffraction diagnosis) system uses microbeads to generate unique diffraction patterns which can be acquired by smartphones and processed by a remote server. We applied the D3 platform to screen for precancerous or cancerous cells in cervical specimens and to detect human papillomavirus (HPV) DNA. The D3 assay generated readouts within 45 min and showed excellent agreement with gold-standard pathology or HPV testing, respectively. This approach could have favorable global health applications where medical access is limited or when pathology bottlenecks challenge prompt diagnostic readouts. C1 [Im, Hyungsoon; Castro, Cesar M.; Shao, Huilin; Liong, Monty; Song, Jun; Pathania, Divya; Fexon, Lioubov; Min, Changwook; Zurkiya, Omar; Rho, Junsung; Magaoay, Brady; Pivovarov, Misha; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Im, Hyungsoon; Pathania, Divya; Zurkiya, Omar; Pivovarov, Misha; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Castro, Cesar M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Song, Jun] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Avila-Wallace, Maria] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Tambouret, Rosemary H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; hlee@mgh.harvard.edu RI Im, Hyungsoon/A-3178-2009 OI Im, Hyungsoon/0000-0002-0626-1346 FU US NIH [R01-HL113156, R01-EB010011, R01-EB00462605A1, T32CA79443, K12CA087723-11A1]; Massachusetts General Hospital Physician Scientist Development Award; National Heart, Lung, and Blood Institute [HHSN268201000044C]; Department of Defense Ovarian Cancer Research Program Award [W81XWH-14-1-0279] FX The authors thank M. Birrer, D. Dizon, and M. Del Carmen for many helpful suggestions; Melina Pectasides for assistance with clinical sample collection; and K. Joyes for reviewing the manuscript. This work was supported in part by US NIH Grants R01-HL113156 (to H.L.), R01-EB010011 (to R.W.), R01-EB00462605A1 (to R.W.), T32CA79443 (to R.W.), K12CA087723-11A1 (to C.M.C.), Massachusetts General Hospital Physician Scientist Development Award (to C.M.C.), National Heart, Lung, and Blood Institute Contract HHSN268201000044C (to R.W.), and Department of Defense Ovarian Cancer Research Program Award W81XWH-14-1-0279 (to H.L.) NR 46 TC 13 Z9 13 U1 2 U2 40 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 5 PY 2015 VL 112 IS 18 BP 5613 EP 5618 DI 10.1073/pnas.1501815112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH3TS UT WOS:000353953800039 PM 25870273 ER PT J AU Rotem, A Janzer, A Izar, B Ji, Z Doench, JG Garraway, LA Struhl, K AF Rotem, Asaf Janzer, Andreas Izar, Benjamin Ji, Zhe Doench, John G. Garraway, Levi A. Struhl, Kevin TI Alternative to the soft-agar assay that permits high-throughput drug and genetic screens for cellular transformation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; transformation; drug screen; genetic screen; personalized medicine ID ANCHORAGE-INDEPENDENT GROWTH; CELLS; CULTURE; CANCER; ONCOLOGY; VIRUS; MICE AB Colony formation in soft agar is the gold-standard assay for cellular transformation in vitro, but it is unsuited for high-throughput screening. Here, we describe an assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the soft-agar assay. Using GILA, we describe high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. Such molecules are unlikely to be found through conventional drug screening, and they include kinase inhibitors and drugs for noncancer diseases. In addition to known oncogenes, the genetic screen identifies genes that contribute to cellular transformation. Lastly, we demonstrate the ability of Food and Drug Administration-approved noncancer drugs to selectively kill ovarian cancer cells derived from patients with chemotherapy-resistant disease, suggesting this approach may provide useful information for personalized cancer treatment. C1 [Rotem, Asaf; Janzer, Andreas; Ji, Zhe; Struhl, Kevin] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Izar, Benjamin; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Izar, Benjamin; Doench, John G.; Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA 02139 USA. RP Struhl, K (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM kevin@hms.harvard.edu OI Doench, John/0000-0002-3707-9889 FU German Academic Exchange Service; National Institutes of Health [CA 107486] FX We thank Harvard Medical School core facilities Image and Data Analysis Core (IDAC), The Nikon Imaging Center (microscopy), and The Institute of Chemistry and Cell Biology (ICCB); Nathanael Gray for the kinase inhibitor focused library; Roy Kishony for imaging of soft-agar plates; Robert Weinberg for early passage fibroblast lines; Marcia Haigis for prostate cell lines; Joan Brugge and Suha Naffar abu Amara for ovarian cancer cells; and Joseph Geisberg for critical reading of the manuscript. This work was supported by a Postdoctoral Fellowship (to A.J.) from the German Academic Exchange Service and National Institutes of Health Research Grant CA 107486 (to K.S.). NR 22 TC 6 Z9 6 U1 5 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 5 PY 2015 VL 112 IS 18 BP 5708 EP 5713 DI 10.1073/pnas.1505979112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH3TS UT WOS:000353953800055 PM 25902495 ER PT J AU Linas, BP Barter, DM Morgan, JR Pho, MT Leff, JA Schackman, BR Horsburgh, CR Assoumou, SA Salomon, JA Weinstein, MC Freedberg, KA Kim, AY AF Linas, Benjamin P. Barter, Devra M. Morgan, Jake R. Pho, Mai T. Leff, Jared A. Schackman, Bruce R. Horsburgh, C. Robert Assoumou, Sabrina A. Salomon, Joshua A. Weinstein, Milton C. Freedberg, Kenneth A. Kim, Arthur Y. TI The Cost-Effectiveness of Sofosbuvir-Based Regimens for Treatment of Hepatitis C Virus Genotype 2 or 3 Infection SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID QUALITY-OF-LIFE; SUSTAINED VIROLOGICAL RESPONSE; FIBROSIS PROGRESSION; NATURAL-HISTORY; UNITED-STATES; ALL-CAUSE; RIBAVIRIN; CIRRHOSIS; THERAPY; PEGINTERFERON AB Background: Chronic infection with hepatitis C virus (HCV) genotype 2 or 3 can be treated with sofosbuvir without interferon. Because sofosbuvir is costly, its benefits should be compared with the additional resources used. Objective: To estimate the cost-effectiveness of sofosbuvir-based treatments for HCV genotype 2 or 3 infection in the United States. Design: Monte Carlo simulation, including deterministic and probabilistic sensitivity analyses. Data Sources: Randomized trials, observational cohorts, and national health care spending surveys. Target Population: 8 patient types defined by HCV genotype (2 vs. 3), treatment history (naive vs. experienced), and cirrhosis status (noncirrhotic vs. cirrhotic). Time Horizon: Lifetime. Perspective: Payer. Intervention: Sofosbuvir-based therapies, pegylated interferon-ribavirin, and no therapy. Outcome Measures: Discounted quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Results of Base-Case Analysis: The ICER of sofosbuvir-based treatment was less than $100 000 per QALY in cirrhotic patients (genotype 2 or 3 and treatment-naive or treatment-experienced) and in treatment-experienced noncirrhotic patients but was greater than $200 000 per QALY in treatment-naive noncirrhotic patients. Results of Sensitivity Analysis: The ICER of sofosbuvir-based therapy for treatment-naive noncirrhotic patients with genotype 2 or 3 infection was less than $100 000 per QALY when the cost of sofosbuvir was reduced by approximately 40% and 60%, respectively. In probabilistic sensitivity analyses, cost-effectiveness conclusions were robust to uncertainty in treatment efficacy. Limitation: The analysis did not consider possible benefits of preventing HCV transmission. Conclusion: Sofosbuvir provides good value for money for treatment-experienced patients with HCV genotype 2 or 3 infection and those with cirrhosis. At their current cost, sofosbuvir-based regimens for treatment-naive noncirrhotic patients exceed willingness-to-pay thresholds commonly cited in the United States. C1 Boston Univ, Harvard Univ, Sch Publ Hlth, Boston Med Ctr, Boston, MA 02118 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Chicago, Chicago, IL 60637 USA. Weill Cornell Med Coll, New York, NY USA. RP Linas, BP (reprint author), Boston Med Ctr, HIV Epidemiol & Outcomes Res Unit, 850 Harrison Ave,Dowling 3N,Room 3205, Boston, MA 02118 USA. EM Benjamin.Linas@BMC.org RI Salomon, Joshua/D-3898-2009; OI Salomon, Joshua/0000-0003-3929-5515; Leff, Jared/0000-0001-6995-6009; Morgan, Jake/0000-0002-1559-3983 FU National Institute on Drug Abuse; National Institute of Allergy and Infectious Diseases FX National Institute on Drug Abuse and National Institute of Allergy and Infectious Diseases. NR 55 TC 31 Z9 31 U1 2 U2 10 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 5 PY 2015 VL 162 IS 9 BP 619 EP U220 DI 10.7326/M14-1313 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CH6AZ UT WOS:000354119100006 PM 25820703 ER PT J AU Zhang, BC Calado, DP Wang, Z Frohler, S Kochert, K Qian, Y Koralov, SB Schmidt-Supprian, M Sasaki, Y Unitt, C Rodig, S Chen, W Dalla-Favera, R Alt, FW Pasqualucci, L Rajewsky, K AF Zhang, Baochun Calado, Dinis Pedro Wang, Zhe Froehler, Sebastian Koechert, Karl Qian, Yu Koralov, Sergei B. Schmidt-Supprian, Marc Sasaki, Yoshiteru Unitt, Christine Rodig, Scott Chen, Wei Dalla-Favera, Riccardo Alt, Frederick W. Pasqualucci, Laura Rajewsky, Klaus TI An Oncogenic Role for Alternative NF-kappa B Signaling in DLBCL Revealed upon Deregulated BCL6 Expression SO CELL REPORTS LA English DT Article ID PLASMA-CELL DIFFERENTIATION; MULTIPLE-MYELOMA; GENE-EXPRESSION; ALPHA PROTEOLYSIS; SURVIVAL SIGNALS; BAFF-RECEPTOR; LYMPHOMA; DIFFUSE; ACTIVATION; PATHWAY AB Diffuse large B cell lymphoma (DLBCL) is a complex disease comprising diverse subtypes and genetic profiles. Possibly because of the prevalence of genetic alterations activating canonical NF-kappa B activity, a role for oncogenic lesions that activate the alternative NF-kappa B pathway in DLBCL has remained elusive. Here, we show that deletion/mutation of TRAF3, a negative regulator of the alternative NF-kappa B pathway, occurs in similar to 15% of DLBCLs and that it often coexists with BCL6 translocation, which prevents terminal B cell differentiation. Accordingly, in a mouse model constitutive activation of the alternative NF-kappa B pathway cooperates with BCL6 deregulation in DLBCL development. This work demonstrates a key oncogenic role for the alternative NF-kappa B pathway in DLBCL development. C1 [Zhang, Baochun; Calado, Dinis Pedro; Wang, Zhe; Koralov, Sergei B.; Schmidt-Supprian, Marc; Sasaki, Yoshiteru; Rajewsky, Klaus] Harvard Univ, Sch Med, Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Zhang, Baochun; Calado, Dinis Pedro; Wang, Zhe; Koralov, Sergei B.; Schmidt-Supprian, Marc; Sasaki, Yoshiteru; Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Zhang, Baochun; Wang, Zhe; Qian, Yu] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02215 USA. [Calado, Dinis Pedro; Froehler, Sebastian; Koechert, Karl; Chen, Wei; Rajewsky, Klaus] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. [Calado, Dinis Pedro] Canc Res UK London Res Inst, London WC2A 3LY, England. [Calado, Dinis Pedro] Kings Coll London, Peter Gorer Dept Immunobiol, London SE1 9RT, England. [Koralov, Sergei B.] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Schmidt-Supprian, Marc] Tech Univ Munich, Dept Hematol & Oncol, Klinikum Rechts Isar, D-81675 Munich, Germany. [Sasaki, Yoshiteru] Kyoto Univ, Grad Sch Med, Dept Mol & Cellular Physiol, Kyoto 6068501, Japan. [Unitt, Christine; Rodig, Scott] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Dalla-Favera, Riccardo; Pasqualucci, Laura] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. [Dalla-Favera, Riccardo; Pasqualucci, Laura] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. [Dalla-Favera, Riccardo; Pasqualucci, Laura] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Alt, Frederick W.] Harvard Univ, Sch Med, Boston Childrens Hosp, Howard Hughes Med Inst,Program Cellular & Mol Med, Boston, MA 02115 USA. [Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Zhang, BC (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. EM baochun_zhang@dfci.harvard.edu; dinis.calado@cancer.org.uk; klaus.rajewsky@mdc-berlin.de RI Frohler, Sebastian/D-7555-2013; Schmidt-Supprian, Marc/F-5893-2011; OI Frohler, Sebastian/0000-0001-8000-2927; Schmidt-Supprian, Marc/0000-0002-8543-6166; Zhang, Baochun/0000-0003-1759-1161 FU National Cancer Institute [P01 CA092625, R01 CA098285, CA172492]; Leukemia & Lymphoma Society SCOR grant; European Research Council, ERC Advanced Grant [ERC-AG-LS6]; Leukemia & Lymphoma Society fellowships; Dana-Farber Cancer Institute Faculty Startup Funds; Cancer Research UK; MRC career development award [MR/J008060/1] FX We thank J. Xia, X. Chen, D. Ghitza, A. Pellerin, J. Grundy, and C. Langnick for technical assistance; M. Bamberg, M. Ottaviano, H.-L. Cheng, J. Needham, and L. Lynch for administrative assistance; and K.R. laboratory members and M. Janz for critical comments and suggestions. This work was supported by the National Cancer Institute grants P01 CA092625 and R01 CA098285, a Leukemia & Lymphoma Society SCOR grant, and the European Research Council, ERC Advanced Grant ERC-AG-LS6 to K.R.; the National Cancer Institute grant CA172492 to L. P.; the Leukemia & Lymphoma Society fellowships to B.Z. and D.P.C.; the Dana-Farber Cancer Institute Faculty Startup Funds to B.Z.; and core funding from Cancer Research UK, and a MRC career development award MR/J008060/1 to D. C. NR 46 TC 14 Z9 14 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAY 5 PY 2015 VL 11 IS 5 BP 715 EP 726 DI 10.1016/j.celrep.2015.03.059 PG 12 WC Cell Biology SC Cell Biology GA CH3CB UT WOS:000353902900006 PM 25921526 ER PT J AU Wahlster, S Wijdicks, EFM Patel, PV Greer, DM Hemphill, JC Carone, M Mateen, FJ AF Wahlster, Sarah Wijdicks, Eelco F. M. Patel, Pratik V. Greer, David M. Hemphill, J. Claude, III Carone, Marco Mateen, Farrah J. TI Brain death declaration Practices and perceptions worldwide SO NEUROLOGY LA English DT Article ID ORGAN DONATION; CASE-FATALITY; TRANSPLANTATION; EPIDEMIOLOGY; ATTITUDES; ADULTS; CARE AB Objective:To assess the practices and perceptions of brain death determination worldwide and analyze the extent and nature of variations among countries.Methods:An electronic survey was distributed globally to physicians with expertise in neurocritical care, neurology, or related disciplines who would encounter patients at risk of brain death.Results:Most countries (n = 91, response rate 76%) reported a legal provision (n = 63, 70%) and an institutional protocol (n = 70, 77%) for brain death. Institutional protocols were less common in lower-income countries (2/9 of low [22%], 9/18 lower-middle [50%], 22/26 upper-middle [85%], and 37/38 high-income countries [97%], p < 0.001). Countries with an organized transplant network were more likely to have a brain death provision compared with countries without one (53/64 [83%] vs 6/25 [24%], p < 0.001). Among institutions with a formalized brain death protocol, marked variability occurred in requisite examination findings (n = 37, 53% of respondents deviated from the American Academy of Neurology criteria), apnea testing, necessity and type of ancillary testing (most commonly required test: EEG [n = 37, 53%]), time to declaration, number and qualifications of physicians present, and criteria in children (distinct pediatric criteria: n = 38, 56%).Conclusions:Substantial differences in perceptions and practices of brain death exist worldwide. The identification of discrepancies, improvement of gaps in medical education, and formalization of protocols in lower-income countries provide first pragmatic steps to reconciling these variations. Whether a harmonized, uniform standard for brain death worldwide can be achieved remains questionable. C1 [Wahlster, Sarah; Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Wahlster, Sarah] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Wahlster, Sarah; Mateen, Farrah J.] Harvard Univ, Sch Med, Boston, MA USA. [Wijdicks, Eelco F. M.] Mayo Clin, Div Neurocrit Care, Rochester, MN USA. [Patel, Pratik V.] Univ Washington, Harborview Med Ctr, Dept Anesthesiol & Pain Med, Seattle, WA 98104 USA. [Greer, David M.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Hemphill, J. Claude, III] San Francisco Gen Hosp, Dept Neurol, San Francisco, CA USA. [Carone, Marco] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM fmateen@partners.org NR 22 TC 13 Z9 14 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAY 5 PY 2015 VL 84 IS 18 BP 1870 EP 1879 DI 10.1212/WNL.0000000000001540 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA CH5VR UT WOS:000354104100013 PM 25854866 ER PT J AU Sawyer, KS Poey, A Ruiz, SM Marinkovic, K Oscar-Berman, M AF Sawyer, Kayle S. Poey, Alan Ruiz, Susan Mosher Marinkovic, Ksenija Oscar-Berman, Marlene TI Measures of skin conductance and heart rate in alcoholic men and women during memory performance SO PEERJ LA English DT Article DE Alcoholism; Heart rate; Skin conductance; Psychophysiology; Emotion; Memory ID CUE-REACTIVITY; PREFRONTAL CORTEX; NERVOUS-SYSTEM; ELECTRODERMAL ACTIVITY; DECISION-MAKING; SOCIAL DRINKERS; BRAIN; ACTIVATION; GENDER; RESPONSES AB We examined abnormalities in physiological responses to emotional stimuli associated with long-term chronic alcoholism. Skin conductance responses (SCR) and heart rate (HR) responses were measured in 32 abstinent alcoholic (ALC) and 30 healthy nonalcoholic (NC) men and women undergoing an emotional memory task in an MRI scanner. The task required participants to remember the identity of two emotionally-valenced faces presented at the onset of each trial during functional magnetic resonance imaging (fMRI) scanning. After viewing the faces, participants saw a distractor image (an alcoholic beverage, nonalcoholic beverage, or scrambled image) followed by a single probe face. The task was to decide whether the probe face matched one of the two encoded faces. Skin conductance measurements (before and after the encoded faces, distractor, and probe) were obtained from electrodes on the index and middle fingers on the left hand. HR measurements (beats per minute before and after the encoded faces, distractor, and probe) were obtained by a pulse oximeter placed on the little finger on the left hand. We expected that, relative to NC participants, the ALC participants would show reduced SCR and HR responses to the face stimuli, and that we would identify greater reactivity to the alcoholic beverage stimuli than to the distractor stimuli unrelated to alcohol. While the beverage type did not differentiate the groups, the ALC group did have reduced skin conductance and HR responses to elements of the task, as compared to the NC group. C1 [Sawyer, Kayle S.; Poey, Alan; Ruiz, Susan Mosher; Oscar-Berman, Marlene] Boston Univ, Sch Med, Boston, MA 02118 USA. [Sawyer, Kayle S.; Poey, Alan; Ruiz, Susan Mosher; Oscar-Berman, Marlene] VA Boston Healthcare Syst, Boston, MA USA. [Sawyer, Kayle S.; Poey, Alan; Ruiz, Susan Mosher; Oscar-Berman, Marlene] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Marinkovic, Ksenija] Univ Calif San Diego, La Jolla, CA 92093 USA. [Marinkovic, Ksenija] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. RP Sawyer, KS (reprint author), Boston Univ, Sch Med, Boston, MA 02118 USA. EM kslays@bu.edu OI Sawyer, Kayle/0000-0001-7767-5688 FU US Department of Health and Human Services, National Institute on Alcohol Abuse and Alcoholism [R01AA07112, K05AA00219, K01AA13402, R01AA016624]; National Center for Research Resources (Harvard Clinical and Translational Science Center) [1 UL1 RR025758-04]; Medical Research Service of the US Department of Veterans Affairs FX This research was supported by funds from the US Department of Health and Human Services, National Institute on Alcohol Abuse and Alcoholism (R01AA07112, K05AA00219, K01AA13402, R01AA016624) and National Center for Research Resources (1 UL1 RR025758-04, Harvard Clinical and Translational Science Center), and the Medical Research Service of the US Department of Veterans Affairs. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 1 Z9 1 U1 7 U2 18 PU PEERJ INC PI LONDON PA 341-345 OLD ST, THIRD FLR, LONDON, EC1V 9LL, ENGLAND SN 2167-8359 J9 PEERJ JI PeerJ PD MAY 5 PY 2015 VL 3 AR e941 DI 10.7717/peerj.941 PG 25 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH7CE UT WOS:000354192400006 PM 26020002 ER PT J AU Sierra-Mercado, D McAllister, LM Lee, CCH Milad, MR Eskandar, EN Whalen, MJ AF Sierra-Mercado, Demetrio McAllister, Lauren M. Lee, Christopher C. H. Milad, Mohammed R. Eskandar, Emad N. Whalen, Michael J. TI Controlled cortical impact before or after fear conditioning does not affect fear extinction in mice SO BRAIN RESEARCH LA English DT Article DE Traumatic brain injury; Fear learning; Extinction; Anxiety disorder; Dorsal hippocampus; Learning and memory; Rodent ID TRAUMATIC BRAIN-INJURY; VENTROMEDIAL PREFRONTAL CORTEX; POSTTRAUMATIC-STRESS-DISORDER; VENTRAL HIPPOCAMPUS; DORSAL HIPPOCAMPUS; AMYGDALA; LESIONS; MILD; EXPRESSION; ANXIETY AB Post-traumatic stress disorder (PTSD) is characterized in part by impaired extinction of conditioned fear. Traumatic brain injury (TBI) is thought to be a risk factor for development of PTSD. We tested the hypothesis that controlled cortical impact (CCI) would impair extinction of fear learned by Pavlovian conditioning, in mice. To mimic the scenarios in which TBI occurs prior to or after exposure to an aversive event, severe CCI was delivered to the left parietal cortex at one of two time points: (1) Prior to fear conditioning, or (2) after conditioning. Delay auditory conditioning was achieved by pairing a tone with a foot shock in "context A". Extinction training involved the presentation of tones in a different context (context B) in the absence of foot shock. Test for extinction memory was achieved by presentation of additional tones alone in context B over the following two days. In pre- or post-injury paradigms, CCI did not influence fear learning and extinction. Furthermore, CCI did not affect locomotor activity or elevated plus maze testing. Our results demonstrate that, within the time frame studied, CCI does not impair the acquisition and expression of conditioned fear or extinction memory. (C) 2015 Elsevier B.V. All rights reserved. C1 [Sierra-Mercado, Demetrio; McAllister, Lauren M.; Lee, Christopher C. H.; Whalen, Michael J.] Massachusetts Gen Hosp, Neurosci Ctr, Boston, MA 02114 USA. [Sierra-Mercado, Demetrio; McAllister, Lauren M.; Lee, Christopher C. H.; Whalen, Michael J.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Sierra-Mercado, Demetrio; McAllister, Lauren M.; Lee, Christopher C. H.; Milad, Mohammed R.; Eskandar, Emad N.; Whalen, Michael J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sierra-Mercado, Demetrio; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Milad, Mohammed R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sierra-Mercado, Demetrio] Univ Puerto Rico, Sch Med, Dept Anat & Neurobiol, San Juan, PR 00936 USA. RP Sierra-Mercado, D (reprint author), Univ Puerto Rico, Sch Med, Dept Anat & Neurobiol, San Juan, PR 00936 USA. EM demetrio.sierra@upr.edu; LMCALLISTER1@mgh.harvard.edu; lee.chris.ch@gmail.com; milad@nmr.mgh.harvard.edu; eeskandar@mgh.harvard.edu; mwhalen@partners.org FU RCMI [8G12MD007600]; Brain & Behavior Research Foundation (NARSAD) [MH097964, MH097880, MH086400, NS086422]; DOD/CIMIT [W81XWH-07-2-0011]; Behavioral Core Facility [P01NS5510406]; [DA026297] FX We thank Jimmy Zhang for technical assistance. This study was supported in part by RCMI 8G12MD007600, a supplement from DA026297 and a Young Investigator Grant from the Brain & Behavior Research Foundation (NARSAD) to DS-M, MH097964 and MH097880 to MRM, MH086400 and NS086422 to ENE, DOD/CIMIT W81XWH-07-2-0011 to MJW, and Behavioral Core Facility (P01NS5510406). NR 55 TC 5 Z9 5 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD MAY 5 PY 2015 VL 1606 BP 133 EP 141 DI 10.1016/j.brainres.2015.02.031 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CH0XR UT WOS:000353746200014 PM 25721797 ER PT J AU Benzon, HT Huntoon, MA Rathmell, JP AF Benzon, Honorio T. Huntoon, Marc A. Rathmell, James P. TI Improving the Safety of Epidural Steroid Injections SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Benzon, Honorio T.] Northwestern Univ, Dept Anesthesiol, Feinberg Sch Med, Chicago, IL 60611 USA. [Huntoon, Marc A.] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37212 USA. [Rathmell, James P.] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Rathmell, James P.] Harvard Univ, Sch Med, Boston, MA USA. RP Benzon, HT (reprint author), Northwestern Univ, Dept Anesthesiol, Feinberg Sch Med, 251 E Huron St,Feinberg Pavil,Ste 5-704, Chicago, IL 60611 USA. EM h-benzon@northwestern.edu NR 9 TC 9 Z9 10 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 5 PY 2015 VL 313 IS 17 BP 1713 EP 1714 DI 10.1001/jama.2015.2912 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CH3HQ UT WOS:000353921000014 PM 25822848 ER PT J AU Gerding, DN Meyer, T Lee, C Cohen, SH Murthy, UK Poirier, A Van Schooneveld, TC Pardi, DS Ramos, A Barron, MA Chen, HZ Villano, S AF Gerding, Dale N. Meyer, Thomas Lee, Christine Cohen, Stuart H. Murthy, Uma K. Poirier, Andre Van Schooneveld, Trevor C. Pardi, Darrell S. Ramos, Antonio Barron, Michelle A. Chen, Hongzi Villano, Stephen TI Administration of Spores of Nontoxigenic Clostridium difficile Strain M3 for Prevention of Recurrent C difficile Infection A Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DIARRHEA; DISEASE; METRONIDAZOLE; COLONIZATION; VANCOMYCIN; HAMSTERS AB IMPORTANCE Clostridium difficile is the most common cause of health care-associated infection in US hospitals. Recurrence occurs in 25% to 30% of patients. OBJECTIVE To determine the safety, fecal colonization, recurrence rate, and optimal dosing schedule of nontoxigenic C difficile strain M3 (VP20621; NTCD-M3) for prevention of recurrent C difficile infection (CDI). DESIGN, SETTING, AND PARTICIPANTS Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from June 2011 to June 2013 among 173 patients aged 18 years or older who were diagnosed as having CDI (first episode or first recurrence) and had successfully completed treatment with metronidazole, oral vancomycin, or both at 44 study centers in the United States, Canada, and Europe. INTERVENTIONS Patients were randomly assigned to receive 1 of 4 treatments: oral liquid formulation of NTCD-M3, 104 spores/d for 7 days (n = 43), 107 spores/d for 7 days (n = 44), or 107 spores/d for 14 days (n = 42), or placebo for 14 days (n = 44). MAIN OUTCOMES AND MEASURES The primary outcomewas safety and tolerability of NTCD-M3 within 7 days of treatment. Exploratory secondary outcomes included fecal colonization with NTCD-M3 from end of study drug through week 6 and CDI recurrence from day 1 through week 6. RESULTS Among 168 patients who started treatment, 157 completed treatment. One or more treatment-emergent adverse events were reported in 78% of patients receiving NTCD-M3 and 86% of patients receiving placebo. Diarrhea and abdominal pain were reported in 46% and 17% of patients receiving NTCD-M3 and 60% and 33% of placebo patients, respectively. Serious treatment-emergent adverse events were reported in 7% of patients receiving placebo and 3% of all patients who received NTCD-M3. Headache was reported in 10% of patients receiving NTCD-M3 and 2% of placebo patients. Fecal colonization occurred in 69% of NTCD-M3 patients: 71% with 10(7) spores/d and 63% with 10(4) spores/d. Recurrence of CDI occurred in 13 (30%) of 43 placebo patients and 14 (11%) of 125 NTCD-M3 patients (odds ratio [OR], 0.28; 95% CI, 0.11-0.69; P = .006); the lowest recurrence was in 2 (5%) of 43 patients receiving 10(7) spores/d for 7 days (OR, 0.1; 95% CI, 0.0-0.6; P = .01 vs placebo]). Recurrence occurred in 2 (2%) of 86 patients who were colonized vs 12 (31%) of 39 patients who received NTCD-M3 and were not colonized (OR, 0.01; 95% CI, 0.00-0.05; P < .001). CONCLUSIONS AND RELEVANCE Among patients with CDI who clinically recovered following treatment with metronidazole or vancomycin, oral administration of spores of NTCD-M3 was well tolerated and appeared to be safe. Nontoxigenic C difficile strain M3 colonized the gastrointestinal tract and significantly reduced CDI recurrence. Copyright 2015 American Medical Association. All rights reserved. C1 [Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Gerding, Dale N.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. [Meyer, Thomas] Indiana Univ, Hlth Arnett Hosp, Lafayette, IN USA. [Lee, Christine] McMaster Univ, St Josephs Healthcare Hamilton, Hamilton, ON, Canada. [Cohen, Stuart H.] Univ Calif Davis, Med Ctr, Div Infect Dis, Sacramento, CA 95817 USA. [Murthy, Uma K.] VA Med Ctr, Syracuse, NY USA. [Murthy, Uma K.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Poirier, Andre] Ctr Sante & Serv Sociaux Trois Rivieres, Trois Rivieres, PQ, Canada. [Van Schooneveld, Trevor C.] Univ Nebraska Med Ctr, Div Infect Dis, Omaha, NE USA. [Pardi, Darrell S.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Ramos, Antonio] Hosp Univ Puerta Hierro, Madrid, Spain. [Barron, Michelle A.] Univ Colorado Denver, Internal Med & Infect Dis, Aurora, CO USA. [Chen, Hongzi; Villano, Stephen] Shire, Wayne, PA USA. RP Gerding, DN (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res & Dev, Fifth Ave & Roosevelt Rd,Bldg 1,Room B347, Hines, IL 60141 USA. EM dale.gerding2@va.gov RI Ramos, Antonio/G-5535-2016 OI Ramos, Antonio/0000-0002-4840-9425 FU ViroPharma Incorporated, which is now part of the Shire group of companies FX This study was sponsored by ViroPharma Incorporated, which is now part of the Shire group of companies. NR 20 TC 59 Z9 59 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 5 PY 2015 VL 313 IS 17 BP 1719 EP 1727 DI 10.1001/jama.2015.3725 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CH3HQ UT WOS:000353921000017 PM 25942722 ER PT J AU Poordad, F Sievert, W Mollison, L Bennett, M Tse, E Brau, N Levin, J Sepe, T Lee, SS Angus, P Conway, B Pol, S Boyer, N Bronowicki, JP Jacobson, I Muir, AJ Reddy, KR Tam, E Ortiz-Lasanta, G de Ledinghen, V Sulkowski, M Boparai, N McPhee, F Hughes, E Swenson, ES Yin, PD AF Poordad, Fred Sievert, William Mollison, Lindsay Bennett, Michael Tse, Edmund Braeu, Norbert Levin, James Sepe, Thomas Lee, Samuel S. Angus, Peter Conway, Brian Pol, Stanislas Boyer, Nathalie Bronowicki, Jean-Pierre Jacobson, Ira Muir, Andrew J. Reddy, K. Rajender Tam, Edward Ortiz-Lasanta, Grisell de Ledinghen, Victor Sulkowski, Mark Boparai, Navdeep McPhee, Fiona Hughes, Eric Swenson, E. Scott Yin, Philip D. CA UNITY-1 Study Grp TI Fixed-Dose Combination Therapy With Daclatasvir, Asunaprevir, and Beclabuvir for Noncirrhotic Patients With HCV Genotype 1 Infection SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEPATITIS-C VIRUS; TREATMENT-NAIVE PATIENTS; PLUS ASUNAPREVIR; RIBAVIRIN; ABT-450/R-OMBITASVIR; SOFOSBUVIR; LEDIPASVIR; DASABUVIR; BMS-791325 AB IMPORTANCE The antiviral activity of all-oral, ribavirin-free, direct-acting antiviral regimens requires evaluation in patients with chronic hepatitis C virus (HCV) infection. OBJECTIVE To determine the rates of sustained virologic response (SVR) in patients receiving the 3-drug combination of daclatasvir (a pan-genotypic NS5A inhibitor), asunaprevir (an NS3 protease inhibitor), and beclabuvir (a nonnucleoside NS5B inhibitor). DESIGN, SETTING, AND PARTICIPANTS Thiswas an open-label, single-group, uncontrolled international study (UNITY-1) conducted at 66 sites in the United States, Canada, France, and Australia between December 2013 and August 2014. Patients without cirrhosis who were either treatment-naive (n = 312) or treatment-experienced (n = 103) and had chronic HCV genotype 1 infection were included. INTERVENTIONS Patients received a twice-daily fixed-dose combination of daclatasvir, 30mg; asunaprevir, 200mg; and beclabuvir, 75 mg. MAIN OUTCOMES AND MEASURES The primary study outcome was SVR12 (HCV-RNA <25 IU/mL at posttreatment week 12) in patients naive to treatment. A key secondary outcome was SVR12 in the treatment-experienced cohort. RESULTS Baseline characteristics were comparable between the treatment-naive and treatment-experienced cohorts. Patients were 58% male, 26% had IL28B (rs12979860) CC genotype, 73% were infected with genotype 1a, and 27% were infected with genotype 1b. Overall, SVR12 was observed in 379 of 415 patients (91.3%; 95% CI, 88.6%-94.0%): 287 of 312 treatment-naive patients (92.0%; 95% CI, 89.0%-95.0%) and 92 of 103 treatment-experienced patients (89.3%; 95% CI, 83.4%-95.3%). Virologic failure occurred in 34 patients (8%) overall. One patient died at posttreatment week 3; this was not considered related to study medication. There were 7 serious adverse events, all considered unrelated to study treatment, and 3 adverse events (<1%) leading to treatment discontinuation, including 2 grade 4 alanine aminotransferase elevations. The most common adverse events (in >= 10% of patients) were headache, fatigue, diarrhea, and nausea. CONCLUSIONS AND RELEVANCE In this open-label, nonrandomized, uncontrolled study, a high rate of SVR12 was achieved in treatment-naive and treatment-experienced noncirrhotic patients with chronic HCV genotype 1 infection who received 12 weeks of treatment with the oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir. Copyright 2015 American Medical Association. All rights reserved. C1 [Poordad, Fred] Univ Texas Hlth Sci Ctr San Antonio, Texas Liver Inst, San Antonio, TX 78215 USA. [Sievert, William] Monash Hlth, Melbourne, Vic, Australia. [Sievert, William] Monash Univ, Melbourne, Vic 3004, Australia. [Mollison, Lindsay] Univ Western Australia, Sch Med & Pharmacol, Fremantle Hepatitis Serv, Fremantle, WA, Australia. [Bennett, Michael] Med Associates Res Grp, San Diego, CA USA. [Tse, Edmund] Royal Adelaide Hosp, Adelaide, SA 5000, Australia. [Braeu, Norbert] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Braeu, Norbert] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Levin, James] Dean Fdn, Madison, WI USA. [Sepe, Thomas] Univ Gastroenterol, Providence, RI USA. [Lee, Samuel S.] Univ Calgary, Calgary, AB, Canada. [Angus, Peter] Austin Hosp, Heidelberg, Vic, Australia. [Conway, Brian] Vancouver Infect Dis Ctr, Vancouver, BC, Canada. [Pol, Stanislas] Univ Paris 05, Hop Cochin, AP HP, Unite Hepatol,INSERM,UMS 20,Inst Pasteur, Paris, France. [Boyer, Nathalie] Hop Beaujon, Serv Hepatol, Clichy, France. [Bronowicki, Jean-Pierre] Univ Lorraine, Ctr Hosp Univ Nancy, INSERM, U954, Vandoeuvre Les Nancy, France. [Jacobson, Ira] Weill Cornell Med Coll, New York, NY USA. [Muir, Andrew J.] Duke Univ, Med Ctr, Durham, NC USA. [Reddy, K. Rajender] Univ Penn, Philadelphia, PA 19104 USA. [Tam, Edward] LAIR Ctr, Vancouver, BC, Canada. [Ortiz-Lasanta, Grisell] Fdn Invest, San Juan, PR USA. [de Ledinghen, Victor] Hop Du Haut Leveque, Pessac, France. [Sulkowski, Mark] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Boparai, Navdeep; Hughes, Eric] Bristol Myers Squibb Co, Princeton, NJ USA. [McPhee, Fiona; Swenson, E. Scott; Yin, Philip D.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. RP Poordad, F (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Texas Liver Inst, 607 Camden St,Ste 101, San Antonio, TX 78215 USA. EM poordad@uthscsa.edu OI TAM, EDWARD/0000-0002-8306-3968 FU Bristol-Myers Squibb FX This study was funded by Bristol-Myers Squibb. Editorial support was provided by Andrew Street, PhD, of Articulate Science and was funded by Bristol-Myers Squibb. NR 20 TC 42 Z9 44 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 5 PY 2015 VL 313 IS 17 BP 1728 EP 1735 DI 10.1001/jama.2015.3860 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CH3HQ UT WOS:000353921000018 PM 25942723 ER PT J AU Warnes, CA Bhatt, AB Daniels, CJ Gillam, LD Stout, KK AF Warnes, Carole A. Bhatt, Ami B. Daniels, Curtis J. Gillam, Linda D. Stout, Karen K. TI COCATS 4 Task Force 14: Training in the Care of Adult Patients With Congenital Heart Disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE ACC Training Statement; clinical competence; COCATS; congenital heart disease; fellowship training C1 [Warnes, Carole A.] Mayo Clin, Congenital Heart Dis Clin, Rochester, MN 55905 USA. [Bhatt, Ami B.] Massachusetts Gen Hosp, Div Cardiol, Congenital Heart Dis Program, Boston, MA 02114 USA. [Daniels, Curtis J.] Ohio State Univ, Internal Med & Pediat, Columbus, OH 43210 USA. [Gillam, Linda D.] Morristown Med Ctr Chair, Dept CV Med, Morristown, NJ USA. [Stout, Karen K.] Univ Washington, Seattle, WA 98195 USA. RP Warnes, CA (reprint author), Mayo Clin, Congenital Heart Dis Clin, Rochester, MN 55905 USA. NR 9 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 5 PY 2015 VL 65 IS 17 BP 1887 EP 1898 DI 10.1016/j.jacc.2015.03.030 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG9OA UT WOS:000353644200016 PM 25777639 ER PT J AU Truchan, NA Brar, HK Gallagher, SJ Neuman, JC Kimple, ME AF Truchan, Nathan A. Brar, Harpreet K. Gallagher, Shannon J. Neuman, Joshua C. Kimple, Michelle E. TI A single-islet microplate assay to measure mouse and human islet insulin secretion SO ISLETS LA English DT Article DE assay development; islet culture; insulin secretion; microplate assay; beta-cell function ID PANCREATIC-ISLETS; TISSUE-CULTURE; CELL-SURVIVAL; RECEPTOR; GLUCOSE; MICE AB One complication to comparing -cell function among islet preparations, whether from genetically identical or diverse animals or human organ donors, is the number of islets required per assay. Islet numbers can be limiting, meaning that fewer conditions can be tested; other islet measurements must be excluded; or islets must be pooled from multiple animals/donors for each experiment. Furthermore, pooling islets negates the possibility of performing single-islet comparisons. Our aim was to validate a 96-well plate-based single islet insulin secretion assay that would be as robust as previously published methods to quantify glucose-stimulated insulin secretion from mouse and human islets. First, we tested our new assay using mouse islets, showing robust stimulation of insulin secretion 24 or 48h after islet isolation. Next, we utilized the assay to quantify mouse islet function on an individual islet basis, measurements that would not be possible with the standard pooled islet assay methods. Next, we validated our new assay using human islets obtained from the Integrated Islet Distribution Program (IIDP). Human islets are known to have widely varying insulin secretion capacity, and using our new assay we reveal biologically relevant factors that are significantly correlated with human islet function, whether displayed as maximal insulin secretion response or fold-stimulation of insulin secretion. Overall, our results suggest this new microplate assay will be a useful tool for many laboratories, expert or not in islet techniques, to be able to precisely quantify islet insulin secretion from their models of interest. C1 [Truchan, Nathan A.; Brar, Harpreet K.; Gallagher, Shannon J.; Kimple, Michelle E.] Univ Wisconsin, Dept Med, Div Endocrinol Diabet & Metab, Madison, WI 53706 USA. [Neuman, Joshua C.; Kimple, Michelle E.] Univ Wisconsin, Interdisciplinary Grad Program Nutr Sci, Madison, WI USA. [Truchan, Nathan A.; Brar, Harpreet K.; Gallagher, Shannon J.; Neuman, Joshua C.; Kimple, Michelle E.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Kimple, ME (reprint author), Univ Wisconsin, Dept Med, Div Endocrinol Diabet & Metab, Madison, WI 53706 USA. EM mkimple@medicine.wisc.edu FU University of Wisconsin Institute for Clinical and Translational Research (UW-ICTR) pilot grant [ICTR-UWHC-20120919]; Pharmaceutical Researchers and Manufacturers of America (PhRMA) Foundation; American Diabetes Association [1-14-BS-115]; NIH [R01 DK102598]; University of Wisconsin Institute of Aging [5T32 AG000213]; Hilldale Under-graduate/Faculty Research Award from the University of Wisconsin-Madison FX This work was funded primarily by University of Wisconsin Institute for Clinical and Translational Research (UW-ICTR) pilot grant ICTR-UWHC-20120919 (to M.E.K.) and a starter grant from the Pharmaceutical Researchers and Manufacturers of America (PhRMA) Foundation (to M.E.K.). Additional support was provided by American Diabetes Association grant 1-14-BS-115 (to M.E.K.) and NIH grant R01 DK102598 (to M.E.K.). Joshua Neuman is supported by a training fellowship from the University of Wisconsin Institute of Aging (5T32 AG000213). Harpreet K. Brar was funded in part through a Hilldale Under-graduate/Faculty Research Award from the University of Wisconsin-Madison. This material is the result of work supported in part with the resources and use of facilities at the William S. Middleton Memorial Veterans Hospital, Madison, WI. NR 16 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1938-2014 EI 1938-2022 J9 ISLETS JI Islets PD MAY 4 PY 2015 VL 7 IS 3 DI 10.1080/19382014.2015.1076607 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CZ8LO UT WOS:000367351400001 ER PT J AU Friedrich, P Steinfield, E Kim, F Hays, MM Lehmann, L Sprinz, P AF Friedrich, Paola Steinfield, Elizabeth Kim, Francis Hays, Mary Margaret Lehmann, Leslie Sprinz, Philippa TI Lessons Learned From Talking With Parents About the Role of Hematopoietic Stem Cell Transplantation in the Treatment of Children With Sickle Cell Disease SO AMERICAN JOURNAL OF HEALTH EDUCATION LA English DT Article ID BONE-MARROW-TRANSPLANTATION; ANTI-THYMOCYTE GLOBULIN; SIBLING DONORS; ADULT PATIENTS; GENE-THERAPY; RISK-FACTORS; ANEMIA; MORTALITY; THALASSEMIA; HEMOGLOBINOPATHIES AB Background: Hematopoietic stem cell transplantation (HSCT) is currently the only cure for sickle cell disease (SCD), but only a fraction of eligible children proceed to transplantation. We aimed to understand parental awareness and perceptions as a contributor. Purpose: To discuss HSCT with parents of children with SCD and assess their awareness and perceptions. Methods: A standardized educational session and pre-post surveys were used. Results: Fifty-seven parents completed the educational session. Parental awareness of HSCT and independent search for information were poor; only 40% of parents were previously aware of HSCT as a treatment option in SCD. However, 91% reported that the information was valuable, and 67% that they would consider HSCT as a treatment option for their child. Parents' main concerns were death, isolation, and infertility. Discussion: Our results support the use of structured educational materials during routine SCD health visits to provide information to parents about HSCT and begin discussing complex treatment options. Translation to Health Education Practice: Our results are relevant to clinicians, health educators, and patient advocates responsible for counseling parents of children with chronic conditions about high-risk curative options. A patient education sheet was generated from this experience and will be used to standardize ongoing parental education at our institutions. C1 [Friedrich, Paola; Lehmann, Leslie] Dana Farber Canc Inst, Boston, MA 02115 USA. [Steinfield, Elizabeth; Kim, Francis; Hays, Mary Margaret] Boston Univ, Sch Med, Boston, MA 02215 USA. [Sprinz, Philippa] Boston Med Ctr, Boston, MA USA. RP Friedrich, P (reprint author), Dana Farber Canc Inst, Pediat Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM paola_friedrich@dfci.harvard.edu NR 57 TC 0 Z9 0 U1 2 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1932-5037 EI 2168-3751 J9 AM J HEALTH EDUC JI Am. J. Health Educ. PD MAY 4 PY 2015 VL 46 IS 3 BP 144 EP 156 DI 10.1080/19325037.2015.1021059 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CH8EC UT WOS:000354268000004 ER PT J AU Berrett-Abebe, J Cadet, T Pirl, W Lennes, I AF Berrett-Abebe, Julie Cadet, Tamara Pirl, William Lennes, Inga TI Exploring the Relationship Between Fear of Cancer Recurrence and Sleep Quality in Cancer Survivors SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE cancer survivorship; oncology social work; mixed cancer diagnoses; sleep quality; fear of cancer recurrence ID OF-LIFE; BREAST; PROGRESSION; SYMPTOMS; INSOMNIA; SUPPORT AB Fear of cancer recurrence (FCR) and sleep disturbance are identified as top psychosocial concerns in cancer survivorship, yet few studies have explored the association between these two factors. Using data from a study of 67 cancer survivors, hierarchical logistic regression models examined the relationships between socio-demographic characteristics, FCR, and sleep disturbance. More than half of survivors reported poor sleep quality; those with some college education and those with higher levels of FCR were at greater risk for poor sleep. These findings provide formative data for oncology social workers to implement interventions that target FCR as a strategy for improving sleep. C1 [Berrett-Abebe, Julie; Cadet, Tamara] Simmons Coll, Sch Social Work, Boston, MA 02115 USA. [Berrett-Abebe, Julie; Lennes, Inga] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Pirl, William] Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Boston, MA USA. RP Berrett-Abebe, J (reprint author), Simmons Coll, Sch Social Work, 300 Fenway, Boston, MA 02115 USA. EM berrett@simmons.edu NR 27 TC 1 Z9 1 U1 3 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 EI 1540-7586 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PD MAY 4 PY 2015 VL 33 IS 3 BP 297 EP 309 DI 10.1080/07347332.2015.1020586 PG 13 WC Psychology, Social SC Psychology GA CI6NP UT WOS:000354877000006 PM 25751193 ER PT J AU Kim, PG Nakano, H Das, PP Chen, MJ Rowe, RG Chou, SS Ross, SJ Sakamoto, KM Zon, LI Schlaeger, TM Orkin, SH Nakano, A Daley, GQ AF Kim, Peter Geon Nakano, Haruko Das, Partha P. Chen, Michael J. Rowe, R. Grant Chou, Stephanie S. Ross, Samantha J. Sakamoto, Kathleen M. Zon, Leonard I. Schlaeger, Thorsten M. Orkin, Stuart H. Nakano, Atsushi Daley, George Q. TI Flow-induced protein kinase A-CREB pathway acts via BMP signaling to promote HSC emergence SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HEMATOPOIETIC STEM-CELLS; MOUSE EMBRYO; HUMAN GENOME; CYCLIC-AMP; YOLK-SAC; DEFINITIVE HEMATOPOIESIS; AORTIC ENDOTHELIUM; AGM REGION; BLOOD-FLOW; IN-VITRO AB Fluid shear stress promotes the emergence of hematopoietic stem cells (HSCs) in the aortagonad- mesonephros (AGM) of the developing mouse embryo. We determined that the AGM is enriched for expression of targets of protein kinase A (PKA)-cAMP response element-binding protein (CREB), a pathway activated by fluid shear stress. By analyzing CREB genomic occupancy from chromatin-immunoprecipitation sequencing (ChIP-seq) data, we identified the bone morphogenetic protein (BMP) pathway as a potential regulator of CREB. By chemical modulation of the PKA-CREB and BMP pathways in isolated AGM VE-cadherin(+) cells from mid-gestation embryos, we demonstrate that PKA-CREB regulates hematopoietic engraftment and clonogenicity of hematopoietic progenitors, and is dependent on secreted BMP ligands through the type I BMP receptor. Finally, we observed blunting of this signaling axis using Ncx1-null embryos, which lack a heartbeat and intravascular flow. Collectively, we have identified a novel PKA-CREB-BMP signaling pathway downstream of shear stress that regulates HSC emergence in the AGM via the endothelial-tohematopoietic transition. C1 [Kim, Peter Geon; Das, Partha P.; Chen, Michael J.; Rowe, R. Grant; Chou, Stephanie S.; Ross, Samantha J.; Zon, Leonard I.; Schlaeger, Thorsten M.; Orkin, Stuart H.; Daley, George Q.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Kim, Peter Geon; Das, Partha P.; Chen, Michael J.; Rowe, R. Grant; Chou, Stephanie S.; Ross, Samantha J.; Zon, Leonard I.; Schlaeger, Thorsten M.; Orkin, Stuart H.; Daley, George Q.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Peter Geon; Das, Partha P.; Chen, Michael J.; Rowe, R. Grant; Chou, Stephanie S.; Ross, Samantha J.; Zon, Leonard I.; Schlaeger, Thorsten M.; Orkin, Stuart H.; Daley, George Q.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Kim, Peter Geon; Chen, Michael J.; Rowe, R. Grant; Chou, Stephanie S.; Ross, Samantha J.; Zon, Leonard I.; Schlaeger, Thorsten M.; Daley, George Q.] Harvard Univ, Stem Cell Transplantat Program, Boston Childrens Hosp, Div Pediat Hematol Oncol,Med Sch, Boston, MA 02115 USA. [Kim, Peter Geon; Chen, Michael J.; Rowe, R. Grant; Chou, Stephanie S.; Ross, Samantha J.; Zon, Leonard I.; Schlaeger, Thorsten M.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Nakano, Haruko; Nakano, Atsushi] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Dept Mol Cell & Dev Biol, Jonsson Comprehens Canc Ctr,Mol Biol Inst, Los Angeles, CA 90095 USA. [Sakamoto, Kathleen M.] Stanford Univ, Sch Med, Lucile Packard Childrens Hosp, Div Pediat Hematol Oncol, Stanford, CA 94305 USA. RP Daley, GQ (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu FU US National Institute of Diabetes and Digestive and Kidney Diseases [R24-DK092760]; National Heart, Lung, Blood Institute Progenitor Cell Biology Consortium [U01-HL100001]; Alex's Lemonade Stand; Doris Duke Medical Foundation; American Heart Association; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA; True North Therapeutics, Inc.; Solasia; KK; Epizyme, Inc.; Verastem, Inc.; Ocata Therapeutics; Raze, Inc.; MPM Capital; LLP FX Q. Daley is supported by grants from the US National Institute of Diabetes and Digestive and Kidney Diseases (R24-DK092760) and the National Heart, Lung, Blood Institute Progenitor Cell Biology Consortium (U01-HL100001), Alex's Lemonade Stand, and the Doris Duke Medical Foundation. G.Q. Daley is an associate member of the Broad Institute and an investigator of the Howard Hughes Medical Institute (HHMI) and the Manton Center for Orphan Disease Research. PGK is a HHMI Medical Student Research Fellow. Informatics analysis was performed on the Harvard Medical School Orchestra High Computing Cluster. A. Nakano is supported by the American Heart Association and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.; L.I. Zon is a founder and stockholder of Fate Therapeutics, Inc. and Scholar Rock and is a scientific advisor for Stemgent. G.Q. Daley is a member of the Scientific Advisory Boards of the following companies, and receives consulting fees and/or holds equity in True North Therapeutics, Inc., Solasia, KK, Epizyme, Inc., Verastem, Inc., Ocata Therapeutics, Raze, Inc., and MPM Capital, LLP. The authors have no additional conflicts of interests to declare. NR 70 TC 11 Z9 11 U1 0 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD MAY 4 PY 2015 VL 212 IS 5 BP 633 EP 648 DI 10.1084/jem.20141514 PG 16 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CH3AO UT WOS:000353898100008 PM 25870201 ER PT J AU Jing, L Tamplin, OJ Chen, MJ Deng, Q Patterson, S Kim, PG Durand, EM McNeil, A Green, JM Matsuura, S Ablain, J Brandt, MK Schlaeger, TM Huttenlocher, A Daley, GQ Ravid, K Zon, LI AF Jing, Lili Tamplin, Owen J. Chen, Michael J. Deng, Qing Patterson, Shenia Kim, Peter G. Durand, Ellen M. McNeil, Ashley Green, Julie M. Matsuura, Shinobu Ablain, Julien Brandt, Margot K. Schlaeger, Thorsten M. Huttenlocher, Anna Daley, George Q. Ravid, Katya Zon, Leonard I. TI Adenosine signaling promotes hematopoietic stem and progenitor cell emergence SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IN-VIVO; AORTIC ENDOTHELIUM; A(2B) RECEPTORS; INTERLEUKIN-8; TRANSITION; BLOOD; ZEBRAFISH; DRUGS; MICE; IDENTIFICATION AB Hematopoietic stem cells (HSCs) emerge from aortic endothelium via the endothelial-to-hematopoietic transition (EHT). The molecular mechanisms that initiate and regulate EHT remain poorly understood. Here, we show that adenosine signaling regulates hematopoietic stem and progenitor cell (HSPC) development in zebrafish embryos. The adenosine receptor A(2)b is expressed in the vascular endothelium before HSPC emergence. Elevated adenosine levels increased runx1(+)/cmyb(+) HSPCs in the dorsal aorta, whereas blocking the adenosine pathway decreased HSPCs. Knockdown of A(2b) adenosine receptor disrupted scl(+) hemogenic vascular endothelium and the subsequent EHT process. A(2b) adenosine receptor activation induced CXCL8 via cAMP-protein kinase A (PKA) and mediated hematopoiesis. We further show that adenosine increased multipotent progenitors in a mouse embryonic stem cell colony-forming assay and in embryonic day 10.5 aorta-gonad-mesonephros explants. Our results demonstrate that adenosine signaling plays an evolutionary conserved role in the first steps of HSPC formation in vertebrates. C1 [Jing, Lili; Tamplin, Owen J.; Chen, Michael J.; Kim, Peter G.; Durand, Ellen M.; McNeil, Ashley; Ablain, Julien; Brandt, Margot K.; Schlaeger, Thorsten M.; Daley, George Q.; Zon, Leonard I.] Boston Childrens Hosp, Stem Cell Program, Div Hematol Oncol, Boston, MA 02115 USA. [Jing, Lili; Tamplin, Owen J.; Chen, Michael J.; Kim, Peter G.; Durand, Ellen M.; McNeil, Ashley; Ablain, Julien; Brandt, Margot K.; Schlaeger, Thorsten M.; Daley, George Q.; Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jing, Lili; Tamplin, Owen J.; Chen, Michael J.; Kim, Peter G.; Durand, Ellen M.; McNeil, Ashley; Ablain, Julien; Brandt, Margot K.; Schlaeger, Thorsten M.; Daley, George Q.; Zon, Leonard I.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Kim, Peter G.; Daley, George Q.; Zon, Leonard I.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Zon, Leonard I.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Deng, Qing; Green, Julie M.; Huttenlocher, Anna] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. [Deng, Qing; Green, Julie M.; Huttenlocher, Anna] Univ Wisconsin, Dept Pediat, Madison, WI 53706 USA. [Patterson, Shenia; Matsuura, Shinobu; Ravid, Katya] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Patterson, Shenia; Matsuura, Shinobu; Ravid, Katya] Evans Ctr Interdisciplinary Biomed Res, Boston, MA 02118 USA. RP Zon, LI (reprint author), Boston Childrens Hosp, Stem Cell Program, Div Hematol Oncol, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu OI Deng, Qing/0000-0002-9254-9951 FU National Heart, Lung, and Blood Institute (NHLBI) [R01 HL04880-21, P015P01HL32262-32, 5U01 HL10001-05, HL93149]; National Institute of Diabetes and Digestive and Kidney Diseases [5P30 DK49216, R24 DK092760, 5R01 DK53298]; Howard Hughes Medical Institute; NHLBI [HL007969] FX This work was supported by grants from the National Heart, Lung, and Blood Institute (NHLBI; R01 HL04880-21 to L.I. Zon, P015P01HL32262-32, and 5U01 HL10001-05; and HL93149 to K. Ravid), National Institute of Diabetes and Digestive and Kidney Diseases (5P30 DK49216, R24 DK092760, and 5R01 DK53298), and Howard Hughes Medical Institute to L.I. Zon. S. Patterson was supported by a Cardiovascular Training Grant from the NHLBI (HL007969). NR 51 TC 12 Z9 12 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD MAY 4 PY 2015 VL 212 IS 5 BP 649 EP 663 DI 10.1084/jem.20141528 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CH3AO UT WOS:000353898100009 PM 25870200 ER PT J AU Diaz, MF Li, N Lee, HJ Adamo, L Evans, SM Willey, HE Arora, N Torisawa, Y Vickers, DA Morris, SA Naveiras, O Murthy, SK Ingber, DE Daley, GQ Garcia-Cardena, G Wenzel, PL AF Diaz, Miguel F. Li, Nan Lee, Hyun Jung Adamo, Luigi Evans, Siobahn M. Willey, Hannah E. Arora, Natasha Torisawa, Yu-suke Vickers, Dwayne A. Morris, Samantha A. Naveiras, Olaia Murthy, Shashi K. Ingber, Donald E. Daley, George Q. Garcia-Cardena, Guillermo Wenzel, Pamela L. TI Biomechanical forces promote blood development through prostaglandin E-2 and the cAMP-PKA signaling axis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HEMATOPOIETIC STEM-CELLS; LAMINAR SHEAR-STRESS; SMOOTH-MUSCLE-CELLS; ENDOTHELIAL-CELLS; YOLK-SAC; HAEMOGENIC ENDOTHELIUM; NITRIC-OXIDE; FLOW; WNT; CYCLOOXYGENASE-2 AB Blood flow promotes emergence of definitive hematopoietic stem cells (HSCs) in the developing embryo, yet the signals generated by hemodynamic forces that influence hematopoietic potential remain poorly defined. Here we show that fluid shear stress endows long-term multilineage engraftment potential upon early hematopoietic tissues at embryonic day 9.5, an embryonic stage not previously described to harbor HSCs. Effects on hematopoiesis are mediated in part by a cascade downstream of wall shear stress that involves calcium efflux and stimulation of the prostaglandin E-2 (PGE(2))-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling axis. Blockade of the PGE(2)-cAMP- PKA pathway in the aorta-gonad-mesonephros (AGM) abolished enhancement in hematopoietic activity. Furthermore, Ncx1 heartbeat mutants, as well as static cultures of AGM, exhibit lower levels of expression of prostaglandin synthases and reduced phosphorylation of the cAMP response element-binding protein (CREB). Similar to flow-exposed cultures, transient treatment of AGM with the synthetic analogue 16,16-dimethyl-PGE(2) stimulates more robust engraftment of adult recipients and greater lymphoid reconstitution. These data provide one mechanism by which biomechanical forces induced by blood flow modulate hematopoietic potential. C1 [Diaz, Miguel F.; Li, Nan; Lee, Hyun Jung; Evans, Siobahn M.; Wenzel, Pamela L.] Univ Texas Hlth Sci Ctr Houston, Dept Pediat Surg, Program Childrens Regenerat Med, Houston, TX 77030 USA. [Diaz, Miguel F.; Li, Nan; Lee, Hyun Jung; Evans, Siobahn M.; Wenzel, Pamela L.] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Ctr Stem Cell & Regenerat Med, Houston, TX 77030 USA. [Diaz, Miguel F.; Li, Nan; Lee, Hyun Jung; Evans, Siobahn M.; Wenzel, Pamela L.] Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Program Immunol, Houston, TX 77030 USA. [Adamo, Luigi; Garcia-Cardena, Guillermo] Brigham & Womens Hosp, Dept Pathol, Ctr Excellence Vasc Biol, Boston, MA 02115 USA. [Adamo, Luigi; Torisawa, Yu-suke; Ingber, Donald E.; Garcia-Cardena, Guillermo] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Willey, Hannah E.] Rice Univ, Dept Bioengn, Houston, TX 77030 USA. [Arora, Natasha; Morris, Samantha A.; Naveiras, Olaia; Daley, George Q.] Childrens Hosp Boston, Stem Cell Transplantat Program, Boston, MA 02115 USA. [Arora, Natasha; Morris, Samantha A.; Naveiras, Olaia; Daley, George Q.] Childrens Hosp Boston, Div Pediat Hematol & Oncol, Boston, MA 02115 USA. [Arora, Natasha; Morris, Samantha A.; Naveiras, Olaia; Daley, George Q.] Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Arora, Natasha; Morris, Samantha A.; Naveiras, Olaia; Daley, George Q.] Childrens Hosp Boston, Howard Hughes Med Inst, Boston, MA 02115 USA. [Arora, Natasha; Morris, Samantha A.; Naveiras, Olaia; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Arora, Natasha; Morris, Samantha A.; Naveiras, Olaia; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Arora, Natasha; Morris, Samantha A.; Naveiras, Olaia; Daley, George Q.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Torisawa, Yu-suke; Ingber, Donald E.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Torisawa, Yu-suke; Ingber, Donald E.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Torisawa, Yu-suke; Ingber, Donald E.] Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Vickers, Dwayne A.; Murthy, Shashi K.] Northeastern Univ, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA. RP Garcia-Cardena, G (reprint author), Brigham & Womens Hosp, Dept Pathol, Ctr Excellence Vasc Biol, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu; guillermo_garcia-cardena@hms.harvard.edu; pamela.l.wenzel@uth.tmc.edu FU American Society of Hematology; State of Texas Emerging Technology Fund; National Institutes of Health; Giovanni Armenise-Harvard Foundation FX This work was funded by grants from the American Society of Hematology (to P.L. Wenzel), State of Texas Emerging Technology Fund (to P.L. Wenzel), and National Institutes of Health (to P.L. Wenzel, G.Q. Daley, and G. Garcia-Cardena). L. Adamo was partially funded by the Giovanni Armenise-Harvard Foundation. G.Q. Daley is an Investigator of the Howard Hughes Medical Institute. NR 52 TC 10 Z9 10 U1 1 U2 12 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD MAY 4 PY 2015 VL 212 IS 5 BP 665 EP 680 DI 10.1084/jem.20142235 PG 16 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CH3AO UT WOS:000353898100010 PM 25870199 ER PT J AU Yu, VWC Saez, B Cook, C Lotinun, S Pardo-Saganta, A Wang, YH Lymperi, S Ferraro, F Raaijmakers, MHGP Wu, JY Zhou, L Rajagopal, J Kronenberg, HM Baron, R Scadden, DT AF Yu, Vionnie W. C. Saez, Borja Cook, Colleen Lotinun, Sutada Pardo-Saganta, Ana Wang, Ying-Hua Lymperi, Stefania Ferraro, Francesca Raaijmakers, Marc H. G. P. Wu, Joy Y. Zhou, Lan Rajagopal, Jayaraj Kronenberg, Henry M. Baron, Roland Scadden, David T. TI Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID COMMON LYMPHOID PROGENITOR; HEMATOPOIETIC STEM-CELLS; DELTA-LIKE 4; IN-VIVO; LINEAGE COMMITMENT; SIGNALING PATHWAYS; ADOPTIVE TRANSFER; T-LYMPHOPOIESIS; NOTCH; DIFFERENTIATION AB Production of the cells that ultimately populate the thymus to generate alpha/beta T cells has been controversial, and their molecular drivers remain undefined. Here, we report that specific deletion of bone-producing osteocalcin (Ocn)-expressing cells in vivo markedly reduces T-competent progenitors and thymus-homing receptor expression among bone marrow hematopoietic cells. Decreased intrathymic T cell precursors and decreased generation of mature T cells occurred despite normal thymic function. The Notch ligand DLL4 is abundantly expressed on bone marrow Ocn(+) cells, and selective depletion of DLL4 from these cells recapitulated the thymopoietic abnormality. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell-based adaptive immunity. C1 [Yu, Vionnie W. C.; Saez, Borja; Cook, Colleen; Pardo-Saganta, Ana; Wang, Ying-Hua; Lymperi, Stefania; Ferraro, Francesca; Rajagopal, Jayaraj; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02215 USA. [Yu, Vionnie W. C.; Saez, Borja; Cook, Colleen; Pardo-Saganta, Ana; Wang, Ying-Hua; Lymperi, Stefania; Ferraro, Francesca; Rajagopal, Jayaraj; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02215 USA. [Yu, Vionnie W. C.; Saez, Borja; Cook, Colleen; Wang, Ying-Hua; Lymperi, Stefania; Ferraro, Francesca; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02215 USA. [Lotinun, Sutada; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Lotinun, Sutada] Chulalongkorn Univ, Dept Physiol & STAR Craniofacial & Skeletal Disor, Bangkok 10330, Thailand. [Raaijmakers, Marc H. G. P.] Erasmus Univ, Med Ctr, Inst Canc, Dept Hematol, NL-3015 CE Rotterdam, Netherlands. [Raaijmakers, Marc H. G. P.] Erasmus Univ, Med Ctr, Inst Canc, Erasmus Stem Cell Inst, NL-3015 CE Rotterdam, Netherlands. [Wu, Joy Y.; Kronenberg, Henry M.; Baron, Roland] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02215 USA. [Wu, Joy Y.; Kronenberg, Henry M.; Baron, Roland] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Zhou, Lan] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Pardo-Saganta, Ana; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Internal Med, Boston, MA 02215 USA. [Pardo-Saganta, Ana; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Pediat, Boston, MA 02215 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02215 USA. EM david_scadden@harvard.edu OI Yu, Vionnie W. C./0000-0002-6658-0285 FU MGH Federal Share of the Program Income [C06 CA059267]; Proton Therapy Research and Treatment Center; BD Biosciences Stem Cell Grant; Bullock-Wellman Fellowship Award; Tosteson & Fund for Medical Discovery Fellowship; NHLBI [HL097794, HL044851, HL100402] FX This work was supported by MGH Federal Share of the Program Income under C06 CA059267, Proton Therapy Research and Treatment Center (V.W.C. Yu), BD Biosciences Stem Cell Grant (V.W.C. Yu), Bullock-Wellman Fellowship Award (V.W.C. Yu), Tosteson & Fund for Medical Discovery Fellowship (V.W.C. Yu), NHLBI grants HL097794 (D.T. Scadden), HL044851 (D.T. Scadden), and HL100402 (D.T. Scadden). NR 45 TC 15 Z9 15 U1 2 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD MAY 4 PY 2015 VL 212 IS 5 BP 759 EP 774 DI 10.1084/jem.20141843 PG 16 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CH3AO UT WOS:000353898100016 PM 25918341 ER PT J AU Waldo, SW Brenner, DA McCabe, JM Dela Cruz, M Long, B Narla, VA Park, J Kulkarni, A Sinclair, E Chan, SY Schick, SF Malik, N Ganz, P Hsue, PY AF Waldo, Stephen W. Brenner, Daniel A. McCabe, James M. Dela Cruz, Mark Long, Brian Narla, Venkata A. Park, Joseph Kulkarni, Ameya Sinclair, Elizabeth Chan, Stephen Y. Schick, Suzaynn F. Malik, Namita Ganz, Peter Hsue, Priscilla Y. TI A novel minimally-invasive method to sample human endothelial cells for molecular profiling (vol 10, e0118081, 2015) SO PLOS ONE LA English DT Correction C1 [Dela Cruz, Mark; Narla, Venkata A.; Ganz, Peter; Hsue, Priscilla Y.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Cardiol, San Francisco, CA USA. [Dela Cruz, Mark; Narla, Venkata A.; Ganz, Peter; Hsue, Priscilla Y.] Univ Calif San Francisco, San Francisco Gen Hosp, Ctr Excellence Vasc Res, San Francisco, CA USA. [Long, Brian; Sinclair, Elizabeth] Univ Calif San Francisco, Div Expt Med, San Francisco, CA 94143 USA. [Park, Joseph; Chan, Stephen Y.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Schick, Suzaynn F.; Malik, Namita] Univ Calif San Francisco, Div Occupat & Environm Med, San Francisco, CA 94143 USA. RP Waldo, SW (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 4 PY 2015 VL 10 IS 5 AR e0126062 DI 10.1371/journal.pone.0126062 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH3PP UT WOS:000353943000134 PM 26859004 ER PT J AU Hughes, JM Martin, JL AF Hughes, Jaime M. Martin, Jennifer L. TI Sleep Characteristics of Veterans Affairs Adult Day Health Care Participants SO BEHAVIORAL SLEEP MEDICINE LA English DT Article ID INSOMNIA; DISORDERS; INDEX AB Addressing sleep disturbance can help to slow functional decline, delay nursing home admission, and improve overall health among older adults; however, sleep is not widely studied in high-risk older adults such as Adult Day Health Care (ADHC) participants. Sixty-eight ADHC participants were interviewed for sleep disturbance using a 28-item screening questionnaire. More than two thirds (n = 48, 70.6%) reported one or more characteristics of poor sleep, and 38% of participants met basic criteria for insomnia. Individuals with insomnia attended ADHC less frequently, reported worse sleep quality and shorter sleep duration, and were more likely to endorse trouble falling asleep, staying asleep, and waking up too early (ps < 0.001). Research is needed to better understand perceptions, predictors, and outcomes of sleep disturbance within ADHC participants. C1 [Hughes, Jaime M.] Univ N Carolina, Sch Social Work, Chapel Hill, NC USA. [Martin, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Martin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Martin, JL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Geriatr Res Educ & Clin Ctr, VA Greater Los Angeles Healthcare Syst, 16111 Plummer St,11E, North Hills, CA 91343 USA. EM jennifer.martin@va.gov FU National Institute on Aging [K23 AG028452, L30 AG032916]; VA Rehabilitation Research and Development [1RX000135-01]; VA Greater Los Angeles Healthcare System Geriatric Research, Education, and Clinical Center FX This work was supported by the National Institute on Aging [K23 AG028452 and L30 AG032916 to Martin]; VA Rehabilitation Research and Development [1RX000135-01 to Martin]; and VA Greater Los Angeles Healthcare System Geriatric Research, Education, and Clinical Center. NR 22 TC 2 Z9 2 U1 1 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1540-2002 EI 1540-2010 J9 BEHAV SLEEP MED JI Behav. Sleep Med. PD MAY 4 PY 2015 VL 13 IS 3 BP 197 EP 207 DI 10.1080/15402002.2013.855212 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CH0QR UT WOS:000353727800003 PM 24654988 ER PT J AU Gehrman, PR Harb, GC Cook, JM Barilla, H Ross, RJ AF Gehrman, Philip R. Harb, Gerlinde C. Cook, Joan M. Barilla, Holly Ross, Richard J. TI Sleep Diaries of Vietnam War Veterans With Chronic PTSD: The Relationships Among Insomnia Symptoms, Psychosocial Stress, and Nightmares SO BEHAVIORAL SLEEP MEDICINE LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; POSTTRAUMATIC-STRESS; IMAGERY REHEARSAL; DISORDER AB Impaired sleep and nightmares are known symptoms of posttraumatic stress disorder (PTSD) in the veteran population. In order to assess prospectively the sleep disturbances in this population, sleep diaries are an effective way to obtain information over an extended period of time. In this investigation, a sample of veterans (N = 105) completed daily sleep diaries for a 6-week period. Greater PTSD severity and nightmare-related distress were correlated with more awakenings, shorter duration of sleep, longer sleep latency, and greater frequency of nightmares. Perceived frequency of daytime stressors was associated with an increased number of nightmares, nightmare-related distress, and longer sleep latency. The use of sleep diaries in future investigations may allow targeted treatments for veteran populations with PTSD and sleep disturbances. C1 [Gehrman, Philip R.; Harb, Gerlinde C.; Ross, Richard J.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Gehrman, Philip R.; Ross, Richard J.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Cook, Joan M.] Yale Univ, New Haven, CT 06520 USA. [Cook, Joan M.] Natl Ctr PTSD, Boston, MA USA. [Barilla, Holly] Univ Penn, Philadelphia, PA 19104 USA. RP Gehrman, PR (reprint author), Univ Penn, Dept Psychiat, 3535 Market St,Suite 670, Philadelphia, PA 19104 USA. EM gehrman@exchange.upenn.edu FU Office of Research and Development, Department of Veterans Affairs FX This project was supported by the Office of Research and Development, Department of Veterans Affairs. The content of this article does not represent the views of the Department of Veterans Affairs or of the U.S. Government. NR 20 TC 2 Z9 2 U1 7 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1540-2002 EI 1540-2010 J9 BEHAV SLEEP MED JI Behav. Sleep Med. PD MAY 4 PY 2015 VL 13 IS 3 BP 255 EP 264 DI 10.1080/15402002.2014.880344 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CH0QR UT WOS:000353727800008 PM 24617942 ER PT J AU Bekalu, MA Eggermont, S AF Bekalu, Mesfin Awoke Eggermont, Steven TI Aligning HIV/AIDS Communication With the Oral Tradition of Africans: A Theory-Based Content Analysis of Songs' Potential in Prevention Efforts SO HEALTH COMMUNICATION LA English DT Article ID PARALLEL PROCESS MODEL; ENTERTAINMENT-EDUCATION; MASS-COMMUNICATION; FEAR APPEALS; CAMPAIGNS; MUSIC; BEHAVIOR; MEDIA; PROGRAMS; TANZANIA AB Despite a growing recognition of songs as a useful HIV/AIDS campaign strategy, little research has investigated their potential and/or actual impact. In this study, through a theory-based content analysis, we have assessed the prevention domains covered and the health-relevant constructs promoted by 23 AIDS songs widely used to aid prevention efforts in Ethiopia. To identify the health-relevant constructs and reveal their potential to facilitate or inhibit positive changes, the Extended Parallel Process Model (EPPM) has been used. The findings revealed that the songs cover most of the prevention domains that constitute the current agenda of behavior change communication in Sub-Saharan Africa. However, although all the EPPM variables have been found in almost every song, there were significantly more efficacy messages than threat messages. This suggests that although the songs may lead to positive changes in HIV/AIDS-related outcomes among audiences who have already perceived the threat posed by HIV/AIDS, they are less likely to motivate and thereby generate responses from audiences who have less or no threat perceptions. It is argued that given their potential as a culturally appropriate strategy in Sub-Saharan Africa where oral channels of communication play significant roles, songs could be harnessed for better outcomes through a theory-based design. C1 [Bekalu, Mesfin Awoke; Eggermont, Steven] Katholieke Univ Leuven, Leuven Sch Mass Commun Res, B-3000 Leuven, Belgium. [Bekalu, Mesfin Awoke] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Bekalu, Mesfin Awoke] Dana Farber Canc Inst, Boston, MA USA. RP Bekalu, MA (reprint author), Katholieke Univ Leuven, Leuven Sch Mass Commun Res, Brusselsestr 165, B-3000 Leuven, Belgium. EM mesfinawoke.bekalu@soc.kuleuven.be RI Eggermont, Steven/G-5670-2010 OI Eggermont, Steven/0000-0003-0428-092X NR 56 TC 1 Z9 2 U1 4 U2 22 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1041-0236 EI 1532-7027 J9 HEALTH COMMUN JI Health Commun. PD MAY 4 PY 2015 VL 30 IS 5 BP 441 EP 450 DI 10.1080/10410236.2013.867004 PG 10 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA CB5LC UT WOS:000349667500003 PM 24945716 ER PT J AU Seano, G Primo, L AF Seano, Giorgio Primo, Luca TI Podosomes and invadopodia: tools to breach vascular basement membrane SO CELL CYCLE LA English DT Article DE tumor angiogenesis; podosome; rosette; tumor dissemination; invadopodia; vascular basement membrane; vascular sprouting; endothelial cell ID AORTIC ENDOTHELIAL-CELLS; METASTASIS; EXPRESSION; INTEGRIN AB The vascular basement membrane (BM) is a thin and dense cross-linked extracellular matrix layer that covers and protects blood vessels. Understanding how cells cross the physical barrier of the vascular BM will provide greater insight into the potentially critical role of vascular BM breaching in cancer extravasation, leukocyte trafficking and angiogenic sprouting. In the last year, new evidence has mechanistically linked the breaching of vascular BM with the formation of specific cellular micro-domains known as podosomes and invadopodia. These structures are specialized cell-matrix contacts with an inherent ability to degrade the extracellular matrix. Specifically, the formation of podosomes or invadopodia was shown as an important step in vascular sprouting and tumor cell extravasation, respectively. Here, we review and comment on these recent findings and explore the functions of podosomes and invadopodia within the context of pathological processes such as tumor dissemination and tumor angiogenesis. C1 [Seano, Giorgio; Primo, Luca] IRCCS, Candiolo Canc Inst FPO, Lab Cell Migrat, Turin, Italy. [Seano, Giorgio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab Tumor Biol,Dept Radiat Oncol, Boston, MA USA. [Primo, Luca] Univ Turin, Dept Oncol, Turin, Italy. RP Primo, L (reprint author), IRCCS, Candiolo Canc Inst FPO, Lab Cell Migrat, Turin, Italy. EM luca.primo@ircc.it RI Seano, Giorgio/R-6611-2016 OI Seano, Giorgio/0000-0002-7294-302X FU Associazione Italiana per la Ricerca sul Cancro [IG 14635]; MIUR-Fondo Investimenti per la Ricerca di Base [RBAP11-BYNP]; Susan G. Komen Breast Cancer Foundation [PDF14301739] FX This work was supported by Associazione Italiana per la Ricerca sul Cancro (IG 14635) and MIUR-Fondo Investimenti per la Ricerca di Base (RBAP11-BYNP Newton) to LP, and The Susan G. Komen Breast Cancer Foundation (grant PDF14301739) to GS. NR 25 TC 6 Z9 6 U1 2 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD MAY 3 PY 2015 VL 14 IS 9 BP 1370 EP 1374 DI 10.1080/15384101.2015.1026523 PG 5 WC Cell Biology SC Cell Biology GA CH0KP UT WOS:000353708900011 PM 25789660 ER PT J AU Adler, J Hyder, J Markmann, J Yeh, H AF Adler, J. Hyder, J. Markmann, J. Yeh, H. TI Socioeconomic Status of Local Vs Exported Liver Recipients and Their Donors SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Adler, J.; Markmann, J.; Yeh, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hyder, J.] Mayo Clin, Rochester, MN 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1903 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200267 ER PT J AU Adler, J Yeh, H Markmann, J Nguyen, L Axelrod, D AF Adler, J. Yeh, H. Markmann, J. Nguyen, L. Axelrod, D. TI Does DSA Market Competition Influence OPO Performance? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Adler, J.; Yeh, H.; Markmann, J.] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. [Nguyen, L.] Brigham & Womens Hosp, Surg, Boston, MA 02115 USA. [Axelrod, D.] Dartmouth Hitchcock Med Ctr, Surg, Lebanon, NH 03766 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 413 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200085 ER PT J AU Batal, I De Serres, S Safa, K Waaga, A Onozato, M Najafian, N Chandraker, A AF Batal, I. De Serres, S. Safa, K. Waaga, A. Onozato, M. Najafian, N. Chandraker, A. TI Dendritic Cells in Kidney Transplant Biopsies Are Associated With Poor Allograft Survival SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Batal, I.; De Serres, S.; Safa, K.; Waaga, A.; Najafian, N.; Chandraker, A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Onozato, M.] Harvard Univ, Massachusetts Gen Hosp, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 862 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200037 ER PT J AU Baum, C Khattar, M Schroder, P Chen, W Stepkowski, S AF Baum, C. Khattar, M. Schroder, P. Chen, W. Stepkowski, S. TI IL-21 Regulates Creation of Tertiary Lymphoid Organs in Chronic Allograft Rejection SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Baum, C.; Schroder, P.; Stepkowski, S.] Univ Toledo, Coll Med, Med Microbiol & Immunol, Toledo, OH 43606 USA. [Khattar, M.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Chen, W.] Houston Methodist Res Inst, Transplant Immunol Res Program, Houston, TX 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1580 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200327 ER PT J AU Boneschansker, L Nakayama, H Eisenga, M Klagsbrun, M Irimia, D Briscoe, D AF Boneschansker, L. Nakayama, H. Eisenga, M. Klagsbrun, M. Irimia, D. Briscoe, D. TI Neogenin Functions as a Chemokinetic Receptor on Activated CD4+T Lymphocytes SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Boneschansker, L.; Nakayama, H.; Eisenga, M.; Klagsbrun, M.; Briscoe, D.] Boston Childrens Hosp, Boston, MA USA. [Irimia, D.] 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 550 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124202224 ER PT J AU Carrico, R Fridell, J Odorico, J Yeh, H Tyler, K Niederhaus, S AF Carrico, R. Fridell, J. Odorico, J. Yeh, H. Tyler, K. Niederhaus, S. TI Why Are Pancreas Transplant Volumes Declining? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Carrico, R.; Tyler, K.] UNOS, Richmond, VA USA. [Fridell, J.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Odorico, J.] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Yeh, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Niederhaus, S.] Univ Maryland Med Syst, Baltimore, MD 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 111 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200008 ER PT J AU Cosimi, A Dehnadi, A Smith, R Ko, D Li, X Arnaout, M AF Cosimi, A. Dehnadi, A. Smith, R. Ko, D. Li, X. Arnaout, M. TI Targeting Leukocyte Integrin CD11b/CD18 With a Novel mAb Salvages Renal Function Following an Otherwise Irreversible Ischemic Insult in Cynomolgus Monkeys SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Cosimi, A.; Dehnadi, A.; Ko, D.] Massachusetts Gen Hosp, Transplant Surg, Boston, MA 02114 USA. [Dehnadi, A.; Smith, R.] MGH, Pathol, Boston, MA USA. [Li, X.; Arnaout, M.] MGH, Nephrol, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 339 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200507 ER PT J AU Elias, N Shao, S Gift, T Patel, B Cosimi, A Kawai, T AF Elias, N. Shao, S. Gift, T. Patel, B. Cosimi, A. Kawai, T. TI Economic Analysis of Kidney Transplant Tolerance: The Holy Grail Is Less Costly SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Elias, N.; Shao, S.; Gift, T.; Patel, B.; Cosimi, A.; Kawai, T.] Massachusetts Gen Hosp, Transplant Surg, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1312 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200239 ER PT J AU Fischer, K Ohori, S Meral, F Giannini, S Hoffmeister, K Athar, H Ichimura, T Smith, R Giverts, M Jolesz, F Abdi, R AF Fischer, K. Ohori, S. Meral, F. Giannini, S. Hoffmeister, K. Athar, H. Ichimura, T. Smith, R. Giverts, M. Jolesz, F. Abdi, R. TI High-Resolution Perfusion Mapping to Detect Heart Transplant Rejection Using Contrast Enhance Ultrasound SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Fischer, K.; Meral, F.; Jolesz, F.] Brigham & Womens Hosp, Radiol, Boston, MA 02115 USA. [Fischer, K.; Ohori, S.; Giannini, S.; Hoffmeister, K.; Athar, H.; Ichimura, T.; Giverts, M.; Abdi, R.] Brigham & Womens Hosp, Med, Boston, MA 02115 USA. [Smith, R.] Massachusetts Gen Hosp, Pathol, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1647 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200525 ER PT J AU Hotta, K Aoyama, A Putheti, P Yamada, Y Ohura, T Colvin, R Cosimi, B Benichou, G Strom, T Kawai, T AF Hotta, K. Aoyama, A. Putheti, P. Yamada, Y. Ohura, T. Colvin, R. Cosimi, B. Benichou, G. Strom, T. Kawai, T. TI Activation of Th17 and Chronic Renal Allograft Rejection in Nonhuman Primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Hotta, K.; Aoyama, A.; Putheti, P.; Yamada, Y.; Ohura, T.; Colvin, R.; Cosimi, B.; Benichou, G.; Strom, T.; Kawai, T.] Massachusetts Gen Hosp, Transplant Ctr, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 686 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124202137 ER PT J AU Hotta, K Aoyama, A Ohura, T Tonsho, M Yamada, Y Allan, J Madsen, J Cosimi, B Benichou, G Kawai, T AF Hotta, K. Aoyama, A. Ohura, T. Tonsho, M. Yamada, Y. Allan, J. Madsen, J. Cosimi, B. Benichou, G. Kawai, T. TI Donor Specific Expansion of Regulatory T-Cells Was Associated With Allograft Tolerance Induced By Transient Mixed Chimerism in Nonhuman Primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Hotta, K.; Aoyama, A.; Ohura, T.; Tonsho, M.; Yamada, Y.; Allan, J.; Madsen, J.; Cosimi, B.; Benichou, G.; Kawai, T.] Massachusetts Gen Hosp, Transplant Ctr, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 595 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200245 ER PT J AU Kershaw, C Rogers, C Pavlakis, M Tang, H Alonso, C Khwaja, K Evenson, A Raven, K Wong, M AF Kershaw, C. Rogers, C. Pavlakis, M. Tang, H. Alonso, C. Khwaja, K. Evenson, A. Raven, K. Wong, M. TI Impact of Induction Therapy on Outcomes in HIV plus Renal Transplant Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Kershaw, C.; Pavlakis, M.; Tang, H.; Wong, M.] BIDMC, Med, Boston, MA USA. [Rogers, C.; Pavlakis, M.; Tang, H.; Alonso, C.; Khwaja, K.; Evenson, A.; Raven, K.; Wong, M.] BIDMC, Transplant Inst, Boston, MA USA. [Khwaja, K.; Evenson, A.; Raven, K.] BIDMC, Surg, Boston, MA USA. [Rogers, C.] BIDMC, Pharm, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 538 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200285 ER PT J AU Kim, J Liu, W Liu, L Lee, K Stott, R Yeh, H Markmann, J AF Kim, J. Liu, W. Liu, L. Lee, K. Stott, R. Yeh, H. Markmann, J. TI TGF beta Production By B Cells Is Critical for Transplant Tolerance Induction SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Kim, J.; Liu, W.; Liu, L.; Lee, K.; Stott, R.; Yeh, H.; Markmann, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg, Boston, MA USA. [Liu, W.; Liu, L.] Chengdu Mil Gen Hosp, Surg, Chengdu, Sichuan, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1618 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200250 ER PT J AU Kumar, D Humar, A Crossman, H Kotton, C Levi, M AF Kumar, D. Humar, A. Crossman, H. Kotton, C. Levi, M. TI Infections After Transplant Tourism in Organ Transplant Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Kumar, D.; Humar, A.] Univ Hlth Network, Toronto, ON, Canada. [Crossman, H.; Levi, M.] Univ Colorado, Denver, CO 80202 USA. [Kotton, C.] Massachussetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 942 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200024 ER PT J AU Leonard, D Shanmugarajah, K Powell, H Albritton, A Mallard, C Sachs, D Cetrulo, C Kurtz, J AF Leonard, D. Shanmugarajah, K. Powell, H. Albritton, A. Mallard, C. Sachs, D. Cetrulo, C., Jr. Kurtz, J. TI The Role of Skin-Specific Immunobiology and Major Histocompatibility Complex Sharing in Vascularized Composite Allograft Tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Leonard, D.; Shanmugarajah, K.; Powell, H.; Albritton, A.; Mallard, C.; Sachs, D.; Cetrulo, C., Jr.; Kurtz, J.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 420 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124201433 ER PT J AU Madariaga, M Shanmugarajah, K Michel, S Villani, V La Muraglia, G Torabi, R Leonard, D Randolph, M Colvin, R Yamada, K Madsen, J Cetrulo, C Sachs, D AF Madariaga, M. Shanmugarajah, K. Michel, S. Villani, V. La Muraglia, G., II Torabi, R. Leonard, D. Randolph, M. Colvin, R. Yamada, K. Madsen, J. Cetrulo, C., Jr. Sachs, D. TI Immunomodulatory Strategies Directed Towards Tolerance of Vascularized Composite Allografts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 411 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124201449 ER PT J AU Madariaga, M Spencer, P Michel, S La Muraglia, G O'Neil, M Mannon, E Leblang, C Rosales, I Colvin, R Sachs, D Allan, J Madsen, J AF Madariaga, M. Spencer, P. Michel, S. La Muraglia, G., II O'Neil, M. Mannon, E. Leblang, C. Rosales, I. Colvin, R. Sachs, D. Allan, J. Madsen, J. TI Effects of Heart and Lung Co-Transplantation Across a Full MHC Barrier in Miniature Swine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 450 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124201114 ER PT J AU Madariaga, M Michel, S La Muraglia, G O'Neil, M Orent, W Villani, V Sekijima, M Farkash, E Colvin, R Allan, J Yamada, K Madsen, J Sachs, D AF Madariaga, M. Michel, S. La Muraglia, G., II O'Neil, M. Orent, W. Villani, V. Sekijima, M. Farkash, E. Colvin, R. Allan, J. Yamada, K. Madsen, J. Sachs, D. TI Regulatory Tolerance Across a Full MHC Barrier Is More Robust Than Tolerance Across a Class I MHC Disparity Alone SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 407 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200247 ER PT J AU Marino, J Bertorini, PC Uehara, M Paster, J Mordecai, S Liu, WH Liu, L Abdi, R Tocco, G Kim, J Markmann, J Benichou, G AF Marino, J. Bertorini, P. Crosby Uehara, M. Paster, J. Mordecai, S. Liu, W. -H. Liu, L. Abdi, R. Tocco, G. Kim, J. Markmann, J. Benichou, G. TI Presence of Donor Leukocytes and Donor MHC-Cross-Dressed Recipient Cells and Its Relationship to Direct T Cell Alloresponses After Allotransplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Marino, J.; Bertorini, P. Crosby; Paster, J.; Liu, W. -H.; Liu, L.; Tocco, G.; Kim, J.; Markmann, J.; Benichou, G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Dept,Ctr Transplantat Sci, Boston, MA USA. [Uehara, M.; Abdi, R.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. [Mordecai, S.] Massachusetts Gen Hosp, Dept Pathol, Flow & Imaging Cytometry Core, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1632 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124201467 ER PT J AU Marino, J Bertorini, PC Paster, J Trowell, A Briggs, K Maxwell, L Benichou, G AF Marino, J. Bertorini, P. Crosby Paster, J. Trowell, A. Briggs, K. Maxwell, L. Benichou, G. TI B Cell Depletion With an Anti-CD20 Antibody Enhances Alloreactive Memory T Cell Response After Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Marino, J.; Bertorini, P. Crosby; Paster, J.; Trowell, A.; Briggs, K.; Maxwell, L.; Benichou, G.] Harvard Univ, Sch Med, Dept Surg, Ctr Transplantat Sci,Massachusetts Gen 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1414 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200255 ER PT J AU Oh, N Tonsho, M Ndishabandi, D Colvin, R Madsen, J Alessandrini, A AF Oh, N. Tonsho, M. Ndishabandi, D. Colvin, R. Madsen, J. Alessandrini, A. TI Kidney Plasmacytoid Dendritic Cells Display Distinct Cell Surface Markers and May Explain the Induction of Tolerance by Kidney Allografts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Oh, N.; Tonsho, M.; Ndishabandi, D.; Colvin, R.; Madsen, J.; Alessandrini, A.] 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 635 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200424 ER PT J AU Okamoto, T Yasuda, A Mathisen, D Ott, H AF Okamoto, T. Yasuda, A. Mathisen, D. Ott, H. TI Lifor Organ Preservation Solution Protects Pulmonary Microvasculature in a Rat Model of Ex Vivo Lung Perfusion and Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Okamoto, T.; Yasuda, A.; Mathisen, D.; Ott, H.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Yasuda, A.] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Okamoto, T.; Mathisen, D.; Ott, H.] Massachusetts Gen Hosp, Dept Surg, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 449 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124201205 ER PT J AU Oura, T Ko, D O'Neil, J Boskovic, S Nadazdin, O Hotta, K Kawai, K Cosimi, B Kawai, T AF Oura, T. Ko, D. O'Neil, J. Boskovic, S. Nadazdin, O. Hotta, K. Kawai, K. Cosimi, B. Kawai, T. TI Kidney Versus Islet Allograft Survival After Induction of Mixed Chimerism in Nonhuman Primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Oura, T.; Ko, D.; O'Neil, J.; Boskovic, S.; Nadazdin, O.; Hotta, K.; Kawai, K.; Cosimi, B.; Kawai, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 632 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124201194 ER PT J AU Oura, T Hotta, K Lei, J Markmann, J Dehnadi, A Benichou, G Cosimi, B Kawai, T AF Oura, T. Hotta, K. Lei, J. Markmann, J. Dehnadi, A. Benichou, G. Cosimi, B. Kawai, T. TI Immunosuppression With Anti-CD40 mAb and Rapamycin for Islet and Kidney Co-Transplantation in Nonhuman Primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Oura, T.; Hotta, K.; Lei, J.; Markmann, J.; Dehnadi, A.; Benichou, G.; Cosimi, B.; Kawai, T.] Massachusetts Gen Hosp, Transplant Ctr, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 567 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200496 ER PT J AU Patil, A Climov, M Matar, A Musa, A Harrington, E Sachs, D Duran-Struuck, R Huang, C AF Patil, A. Climov, M. Matar, A. Musa, A. Harrington, E. Sachs, D. Duran-Struuck, R. Huang, C. TI B-Cell Tolerance to Donor Alloantigens SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Patil, A.; Climov, M.; Matar, A.; Musa, A.; Harrington, E.; Sachs, D.; Duran-Struuck, R.; Huang, C.] Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 3006 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200517 ER PT J AU Salama, A Conchon, S Perota, A Martinet, B Judor, JP Evanno, G Bernardet, SL Le Berre, L Hervouet, J Minault, D Concordet, JP Dugast, E Vanhove, B Abadie, J Gaide, N Lagutina, I Duchi, R Lazzari, G Sachs, D Gauthier, O Brouard, S Cozzi, E Blancho, G Perreault, H Bach, JM Galli, C Soulillou, JP AF Salama, A. Conchon, S. Perota, A. Martinet, B. Judor, J. -P. Evanno, G. Bernardet, S. Le-Bas Le Berre, L. Hervouet, J. Minault, D. Concordet, J. -P. Dugast, E. Vanhove, B. Abadie, J. Gaide, N. Lagutina, I. Duchi, R. Lazzari, G. Sachs, D. Gauthier, O. Brouard, S. Cozzi, E. Blancho, G. Perreault, H. Bach, J. -M. Galli, C. Soulillou, J. -P. TI Characteristics of IgGs Produced in Neu5Gc and alpha 1-3 Gal Double Knock-Out Pigs SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Salama, A.; Conchon, S.; Martinet, B.; Judor, J. -P.; Evanno, G.; Bernardet, S. Le-Bas; Le Berre, L.; Hervouet, J.; Minault, D.; Dugast, E.; Vanhove, B.; Brouard, S.; Blancho, G.; Soulillou, J. -P.] Univ Nantes, CHU Nantes, INSERM, ITUN,UMR 1064, Nantes, France. [Salama, A.] Soc Accelerat Transfert Technol Ouest Valorisat, Rennes, France. [Perota, A.; Lagutina, I.; Lazzari, G.; Galli, C.] Avantea, Lab Reprod Technol, Cremona, Italy. [Concordet, J. -P.] CNRS, UMR7196, INSERM, U565,MNHN,USM503, Paris, France. [Abadie, J.; Gaide, N.] ONIRIS, AMaROC, Nantes, France. [Sachs, D.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Gauthier, O.] ONIRIS, Ctr Rech & Invest Preclin, Nantes, France. [Cozzi, E.] Padua Hosp, Padua, Italy. [Cozzi, E.] Consortium Res Organ Transplantat, Padua, Italy. [Perreault, H.] Univ Manitoba, Dept Chem, Winnipeg, MB R3T 2N2, Canada. [Bach, J. -M.] Univ Nantes, ONIRIS, INRA, IECM,EA644,USC1383, Nantes, France. [Galli, C.] Univ Bologna, Dept Vet Med Sci, Bologna, Italy. NR 0 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 562 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124201444 ER PT J AU Shah, J Navarro-Alvarez, N Yeh, H Elias, N Ligocka, J Markmann, J Hertl, M Sachs, D Vagefi, P AF Shah, J. Navarro-Alvarez, N. Yeh, H. Elias, N. Ligocka, J. Markmann, J. Hertl, M. Sachs, D. Vagefi, P. TI Infusion of Human Factor 7a Restores Circulating Platelets and Prevents TMA in Pig-to-Baboon Liver Xenotransplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Shah, J.; Navarro-Alvarez, N.; Yeh, H.; Elias, N.; Ligocka, J.; Markmann, J.; Hertl, M.; Sachs, D.; Vagefi, P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 70 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124201446 ER PT J AU Shinoda, K Chase, C Russell, P Madsen, J Colvin, R Alessandrini, A AF Shinoda, K. Chase, C. Russell, P. Madsen, J. Colvin, R. Alessandrini, A. TI Rejection of an Allograft Through Non-MHC Antigens Does Not Translate to the Rejection of a Different Allograft from the Same Donor in Mixed Chimeras SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Shinoda, K.; Chase, C.; Russell, P.; Madsen, J.; Alessandrini, A.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Colvin, R.] Massachusetts Gen Hosp, Pathol, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1606 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200151 ER PT J AU Thamer, A Elias, N Varughese, C Gift, T Fishman, J Shao, S AF Thamer, A. Elias, N. Varughese, C. Gift, T. Fishman, J. Shao, S. TI Assessment of Renal Function in Kidney Transplant Recipients Through Therapeutic Drug Monitoring of Vancomycin SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Thamer, A.; Elias, N.; Varughese, C.; Gift, T.; Fishman, J.; Shao, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1421 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124201180 ER PT J AU Tonsho, M Spencer, P Millington, T Muniappan, A Tena, A Smith, R Colvin, R Allan, J Madsen, J AF Tonsho, M. Spencer, P. Millington, T. Muniappan, A. Tena, A. Smith, R. Colvin, R. Allan, J. Madsen, J. TI Heart En Bloc Thymus Transplantation Permits Long-Term, Acute Rejection-Free Cardiac Allograft Survival in Nonhuman Primates (NHPs) SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Tonsho, M.; Spencer, P.; Millington, T.; Muniappan, A.; Allan, J.; Madsen, J.] Massachusetts Gen Hosp, MGH Transplant Ctr, Boston, MA 02114 USA. [Tonsho, M.; Spencer, P.; Millington, T.; Muniappan, A.; Tena, A.; Smith, R.; Colvin, R.; Allan, J.; Madsen, J.] Harvard Univ, Sch Med, Boston, MA USA. [Tena, A.; Allan, J.; Madsen, J.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Smith, R.; Colvin, R.] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [Madsen, J.] Massachusetts Gen Hosp, Cardiac Surg, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 600 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124201111 ER PT J AU Tonsho, M Benichou, G Smith, R Colvin, R Madsen, J AF Tonsho, M. Benichou, G. Smith, R. Colvin, R. Madsen, J. TI Effects of Late Kidney Graftectomy in Nonhuman Primates (NHPs) Tolerant of Co-Transplanted Heart and Kidney Allografts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Tonsho, M.; Benichou, G.; Madsen, J.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Smith, R.; Colvin, R.] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [Madsen, J.] Massachusetts Gen Hosp, Cardiac Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1937 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200493 ER PT J AU Ueno, T Yeung, M McGrath, M Iwamoto, H Nakamura, Y Konnno, O Kihara, Y Yokoyama, T Ono, S Ikeda, T Kawachi, S Ibrahim, B Chandraker, A AF Ueno, T. Yeung, M. McGrath, M. Iwamoto, H. Nakamura, Y. Konnno, O. Kihara, Y. Yokoyama, T. Ono, S. Ikeda, T. Kawachi, S. Ibrahim, B. Chandraker, A. TI < i > Donor Dendritic Cells - Potential New Therapeutic Target in Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Ueno, T.; Yeung, M.; McGrath, M.; Ibrahim, B.; Chandraker, A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Renal, Boston, MA 02115 USA. [Ueno, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Ueno, T.; Iwamoto, H.; Nakamura, Y.; Konnno, O.; Kihara, Y.; Yokoyama, T.; Ono, S.; Ikeda, T.; Kawachi, S.] Tokyo Med Univ, Transplant Surg, Hachioji, Tokyo, Japan. 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 156 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124201480 ER PT J AU Viehman, J Clarke, L Shields, R Clancy, C Nguyen, M AF Viehman, J. Clarke, L. Shields, R. Clancy, C. Nguyen, M. TI Deep Surgical Site Infections (dSSI) After Liver Transplantation (LTx): Emergence of Multiple-Drug Resistant (MDR) Pathogens SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Viehman, J.; Clarke, L.; Nguyen, M.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Shields, R.; Clancy, C.; Nguyen, M.] Univ Pittsburgh, Pittsburgh, PA USA. [Clancy, C.] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 330 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200173 ER PT J AU Yamada, K Tasaki, M Sekijima, M Kawai, A Villani, V Tanabe, T Hanekamp, I Shimizu, A Sachs, D AF Yamada, K. Tasaki, M. Sekijima, M. Kawai, A. Villani, V. Tanabe, T. Hanekamp, I. Shimizu, A. Sachs, D. TI Thymic Transplantation to Determine Mechanisms of Thymic Involution: Insulin-Like Growth Factor 1 Receptor and Forkhead Box Protein N1 in the Thymus Play a Role in Maintaining the Juvenile Thymus SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Yamada, K.; Tasaki, M.; Sekijima, M.; Kawai, A.; Villani, V.; Tanabe, T.; Hanekamp, I.; Shimizu, A.; Sachs, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boton, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1033 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124201123 ER PT J AU Yamada, K Sekijima, M Kawai, A Tanabe, T Tasaki, M Villani, V Hanekamp, I Shimizu, A Sachs, D AF Yamada, K. Sekijima, M. Kawai, A. Tanabe, T. Tasaki, M. Villani, V. Hanekamp, I. Shimizu, A. Sachs, D. TI Chimeric Thymus Versus Antigen Presenting Thymus for the Induction of Tolerance: Donor DCs in Vascularized Thymus Grafts Play an Essential Role in the Induction of Tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Yamada, K.; Sekijima, M.; Kawai, A.; Tanabe, T.; Tasaki, M.; Villani, V.; Hanekamp, I.; Shimizu, A.; Sachs, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1026 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200422 ER PT J AU Zhang, W Yi, Z Li, Z Menon, M Li, L Xi, C Greene, I Wei, C Gallon, L Samaniego, M Djamali, A Alexander, S Schroppel, B Nankivell, B Chapman, J Rosales, I Smith, RN Colvin, R O'Connell, P Heeger, P Murphy, B AF Zhang, W. Yi, Z. Li, Z. Menon, M. Li, L. Xi, C. Greene, I. Wei, C. Gallon, L. Samaniego, M. Djamali, A. Alexander, S. Schroppel, B. Nankivell, B. Chapman, J. Rosales, I. Smith, R. Neal Colvin, R. O'Connell, P. Heeger, P. Murphy, B. TI Distinct Blood and Biopsy Meta-Signatures for Acute Rejection Post Kidney Transplant SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Zhang, W.; Yi, Z.; Li, Z.; Menon, M.; Li, L.; Xi, C.; Greene, I.; Wei, C.; Schroppel, B.; Heeger, P.; Murphy, B.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Gallon, L.] North Western Univ, Chicago, IL USA. [Samaniego, M.] Univ Michigan, Ann Arbor, MI 48109 USA. [Djamali, A.] Univ Wisconsin, Madison, WI 53706 USA. [Alexander, S.; Nankivell, B.; Chapman, J.; O'Connell, P.] Univ Sydney, Sydney, NSW 2006, Australia. [Rosales, I.; Smith, R. Neal; Colvin, R.] 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1851 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200181 ER PT J AU Zhong, Z Ye, S Xiong, Y Fan, X Huang, W Ko, D Wang, Y Ye, Q AF Zhong, Z. Ye, S. Xiong, Y. Fan, X. Huang, W. Ko, D. Wang, Y. Ye, Q. TI Decreased Expression of Mitochondrial Aldehyde Dehydrogenase 2 Induces Liver Injury Via Activation of the MAPK Pathway in Grafts from Brain-Dead Donors SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Zhong, Z.; Ye, S.; Xiong, Y.; Fan, X.; Huang, W.; Wang, Y.; Ye, Q.] Wuhan Univ, Hubei Key Lab Med Technol Transplantat, Zhongnan Hosp, Inst Hepatobiliary Dis,Transplant Ctr, Wuhan 430072, Hubei, Peoples R China. [Ye, Q.] Cent S Univ, Xiangya Hosp 3, Res Ctr, Natl Hlth Minist Transplantat Med Engn & Technol, Changsha, Hunan, Peoples R China. [Ko, D.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 184 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124202119 ER PT J AU Zhong, Z Liu, Z Wang, R Fu, Z Zhang, Y Hu, Q Jin, K Ko, D Wang, Y Ye, Q AF Zhong, Z. Liu, Z. Wang, R. Fu, Z. Zhang, Y. Hu, Q. Jin, K. Ko, D. Wang, Y. Ye, Q. TI Establishment of a Novel Model for Hypothermic Machine Perfusion In Vivo in Rabbits SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Zhong, Z.; Liu, Z.; Wang, R.; Hu, Q.; Jin, K.; Wang, Y.; Ye, Q.] Wuhan Univ, Hubei Key Lab Med Technol Transplantat, Zhongnan Hosp, Inst Hepatobiliary Dis,Transplant Ctr, Wuhan 430072, Hubei, Peoples R China. [Fu, Z.; Zhang, Y.; Ye, Q.] Cent S Univ, Xiangya Hosp 3, Res Ctr, Natl Hlth Minist Transplantat Med Engn & Technol, Changsha, Hunan, Peoples R China. [Ko, D.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1905 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124201247 ER PT J AU Zhong, Z Liu, Z Fu, Z Zhang, Y Ko, D Wang, Y Ye, Q AF Zhong, Z. Liu, Z. Fu, Z. Zhang, Y. Ko, D. Wang, Y. Ye, Q. TI Hypothermic Machine Perfusion Improves Kidney Viability through Amelioration of Vasospasm and Edema of Podocytes and Renal Tubular Epithelial Cells SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 02-06, 2015 CL Philadelphia, PA C1 [Zhong, Z.; Liu, Z.; Wang, Y.; Ye, Q.] Wuhan Univ, Transplant Ctr, Inst Hepatobiliary Dis, Zhongnan Hosp,Hubei Key Lab Med Technol Transplan, Wuhan 430072, Peoples R China. [Fu, Z.; Zhang, Y.; Ye, Q.] Cent S Univ, Xiangya Hosp 3, Res Ctr, Natl Hlth Minist Transplantat Med Engn & Technol, Changsha, Hunan, Peoples R China. [Ko, D.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 SU 3 SI SI MA 1859 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DD7SK UT WOS:000370124200470 ER PT J AU Pyne, JM Fortney, JC Mouden, S Lu, LY Hudson, TJ Mittal, D AF Pyne, Jeffrey M. Fortney, John C. Mouden, Sip Lu, Liya Hudson, Teresa J. Mittal, Dinesh TI Cost-Effectiveness of On-Site Versus Off-Site Collaborative Care for Depression in Rural FQHCs SO PSYCHIATRIC SERVICES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; LATE-LIFE DEPRESSION; QUALITY IMPROVEMENT; MAJOR DEPRESSION; DECISION-SUPPORT; HEALTH CENTERS; MENTAL-HEALTH; MANAGEMENT; INTERVENTION; TELEPHONE AB Objective: Collaborative care for depression in primary care settings is effective and cost-effective. However, there is minimal evidence to support the choice of on-site versus off-site models. This study examined the cost-effectiveness of on-site practice-based collaborative care (PBCC) versus off-site telemedicine-based collaborative care (TBCC) for depression in federally qualified health centers (FQHCs). Methods: In a multisite, randomized, pragmatic comparative cost-effectiveness trial, 19,285 patients were screened for depression, 2,863 (14.8%) screened positive, and 364 were enrolled. Telephone interview data were collected at baseline and at six, 12, and 18 months. Base case analysis used Arkansas FQHC health care costs, and secondary analysis used national cost estimates. Effectiveness measures were depression-free days and quality-adjusted life years (QALYs) derived from depression-free days, the 12-Item Short-Form Survey, and the Quality of Well-Being (QWB) Scale. Nonparametric bootstrap with replacement methods were used to generate an empirical joint distribution of incremental costs and QALYs and acceptability curves. Results: The TBCC intervention resulted in more depression-free days and QALYs but at a greater cost than the PBCC intervention. The disease-specific (depression-free day) and generic (QALY) incremental cost-effectiveness ratios (ICERs) were below their respective ICER thresholds for implementation, suggesting that the TBCC intervention was more cost effective than the PBCC intervention. Conclusions: These results support the cost-effectiveness of TBCC in medically underserved primary care settings. Information about whether to insource (make) or outsource (buy) depression care management is important, given the current interest in patient-centered medical homes, value-based purchasing, and bundled payments for depression care. C1 [Pyne, Jeffrey M.; Lu, Liya; Hudson, Teresa J.] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. [Pyne, Jeffrey M.; Hudson, Teresa J.] Cent Arkansas Vet Healthcare Syst, Dept Psychiat, North Little Rock, AR USA. [Fortney, John C.; Mittal, Dinesh] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Fortney, John C.; Mittal, Dinesh] VA Puget Sound Hlth Care Syst, Ctr Innovat Vet Ctr & Value Driven, Hlth Serv Res & Dev, Seattle, WA USA. [Mouden, Sip] Community Hlth Ctr Arkansas Inc, North Little Rock, AR USA. RP Pyne, JM (reprint author), Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. EM jmpyne@uams.edu FU National Institute of Mental Health [R01 MH076908, MH076908-04S1]; National Institutes of Health [UL1TR000039, KL2TR000063]; National Institute of General Medical Science [P30 GM110702] FX This research was supported by grants from the National Institute of Mental Health (R01 MH076908 and MH076908-04S1), National Institutes of Health (UL1TR000039 and KL2TR000063), and National Institute of General Medical Science (P30 GM110702). This study is registered at www.clinicaltrials.gov (NCT00439452). NR 37 TC 3 Z9 3 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAY PY 2015 VL 66 IS 5 BP 491 EP 499 DI 10.1176/appi.ps.201400186 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE5RH UT WOS:000370688500011 PM 25686811 ER PT J AU Koo, KH Madden, E Maguen, S AF Koo, Kelly H. Madden, Erin Maguen, Shira TI Race-Ethnicity and Gender Differences in VA Health Care Service Utilization Among US Veterans of Recent Conflicts SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; AFGHANISTAN VETERANS; UNITED-STATES; AMERICANS; IRAQ; PREVALENCE; DIAGNOSES; QUALITY; CLINICS; MEMBERS AB Objective: The purpose of this study was to compare health care utilization patterns by race-ethnicity and gender among veterans returning from Iraq and Afghanistan. Methods: A retrospective analysis was conducted with records from U.S. service members and veterans returning from Iraq and Afghanistan who enrolled in health care through the Veterans Health Administration, who received a psychiatric diagnosis, and who had used primary or mental health outpatient care between October 7, 2001, and December 31, 2012 (N=309,050). Racial-ethnic minority groups were first collapsed together and compared with whites and then separated by racial-ethnic group. Gender was also tested as a moderator of utilization. Results: Although rates of mental health outpatient care, primary care, and emergency service utilization were relatively similar for racial-ethnic minority groups and whites, minority groups were admitted to psychiatric inpatient care at lower rates than whites. When veterans were separately categorized by specific racial-ethnic groups, some differences in utilization rates emerged; most notably, only black and Hispanic men were admitted less frequently to psychiatric inpatient care, and male and female Asian/Pacific Islander veterans used emergency services less, than their white counterparts. Gender moderated the association between race-ethnicity and mental health outpatient use, such that American Indian and Hispanic women used mental health outpatient services less than white women, but American Indian and Hispanic men showed the opposite pattern. Furthermore, black men were more likely than white men to use mental health outpatient services, but there was no difference between these women. Conclusions: Although service utilization rates between minority groups and whites were similar when minority groups were combined, examination of utilization by racial-ethnic groups and by men and women separately yielded more robust findings. C1 [Koo, Kelly H.; Madden, Erin; Maguen, Shira] San Francisco VA Med Ctr, Dept Mental Hlth, San Francisco, CA USA. [Koo, Kelly H.; Maguen, Shira] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Koo, KH (reprint author), San Francisco VA Med Ctr, Dept Mental Hlth, San Francisco, CA USA. EM kelly.koo@va.gov FU Department of Defense [W81XWH-11-2-0189]; VA Advanced Fellowship in Women's Health FX This research was supported by Department of Defense Award Grant W81XWH-11-2-0189 and the VA Advanced Fellowship in Women's Health. NR 32 TC 4 Z9 4 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAY PY 2015 VL 66 IS 5 BP 507 EP 513 DI 10.1176/appi.ps.201300498 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE5RH UT WOS:000370688500013 PM 25588415 ER PT J AU Manini, AF Yiannoulos, G Bergamaschi, MM Hernandez, S Olmedo, R Barnes, AJ Winkel, G Sinha, R Jutras-Aswad, D Huestis, MA Hurd, YL AF Manini, Alex F. Yiannoulos, Georgia Bergamaschi, Mateus M. Hernandez, Stephanie Olmedo, Ruben Barnes, Allan J. Winkel, Gary Sinha, Rajita Jutras-Aswad, Didier Huestis, Marilyn A. Hurd, Yasmin L. TI Safety and Pharmacokinetics of Oral Cannabidiol When Administered Concomitantly With Intravenous Fentanyl in Humans SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE cannabidiol; cannabis; opioid dependence; pharmacokinetics ID CANNABINOID RECEPTOR; OPIOID RECEPTORS; NEURAL BASIS; NUCLEUS; PLASMA; CB1; DELTA-9-TETRAHYDROCANNABINOL; SCHIZOPHRENIA; INHIBITION; HYDROLYSIS AB Objectives: Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects. Methods: This double-blind, placebo-controlled cross-over study of CBD, coadministered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center in New York City. Participants were healthy volunteers aged 21 to 65 years with prior opioid exposure, regardless of the route. Blood samples were obtained before and after 400 or 800 mg of CBD pretreatment, followed by a single 0.5 (session 1) or 1.0 mu g/kg (session 2) of intravenous fentanyl dose. The primary outcome was the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (t(max)), and area under the curve (AUC) were measured. Results: SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. After low-dose CBD, t(max) occurred at 3 and 1.5 hours in sessions 1 and 2, respectively. After high-dose CBD, tmax occurred at 3 and 4 hours in sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC P = NS) between sessions. Conclusions: Cannabidiol does not exacerbate adverse effects associated with intravenous fentanyl administration. Coadministration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse. C1 [Manini, Alex F.; Hernandez, Stephanie; Olmedo, Ruben] Icahn Sch Med Mt Sinai, Div Med Toxicol, Dept Emergency Med, New York, NY 10029 USA. [Yiannoulos, Georgia; Hurd, Yasmin L.] Icahn Sch Med Mt Sinai, Dept Psychiat, Bronx, NY USA. [Yiannoulos, Georgia; Hurd, Yasmin L.] Icahn Sch Med Mt Sinai, Dept Neurosci, Bronx, NY USA. [Yiannoulos, Georgia; Hurd, Yasmin L.] James J Peters VA Med Ctr, Bronx, NY USA. [Bergamaschi, Mateus M.] Univ Sao Paulo, Dept Clin Toxicol & Food Sci Anal, Sch Pharmaceut Sci Ribeirao Preto, BR-05508 Sao Paulo, Brazil. [Barnes, Allan J.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, Baltimore, MD USA. [Winkel, Gary] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA. [Sinha, Rajita] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Jutras-Aswad, Didier] Univ Montreal, Ctr Hosp Univ Montreal, Res Ctr, Montreal, PQ, Canada. [Jutras-Aswad, Didier] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. RP Hurd, YL (reprint author), Icahn Sch Med Mt Sinai, New York, NY 10029 USA. EM yasmin.hurd@mssm.edu FU National Institutes of Health [DA027781]; CTSA [UL1RR029887] FX Supported by a research grant from the National Institutes of Health grant DA027781 (YLH) and CTSA (UL1RR029887). NR 39 TC 2 Z9 2 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1932-0620 EI 1935-3227 J9 J ADDICT MED JI J. Addict. Med. PD MAY-JUN PY 2015 VL 9 IS 3 BP 204 EP 210 DI 10.1097/ADM.0000000000000118 PG 7 WC Substance Abuse SC Substance Abuse GA DD1VH UT WOS:000369710200006 PM 25748562 ER PT J AU Nedelec, B Carter, A Forbes, L Hsu, SCC McMahon, M Parry, I Ryan, CM Serghiou, MA Schneider, JC Sharp, PA de Oliveira, A Boruff, J AF Nedelec, Bernadette Carter, Alissa Forbes, Lisa Hsu, Shu-Chuan Chen McMahon, Margaret Parry, Ingrid Ryan, Colleen M. Serghiou, Michael A. Schneider, Jeffrey C. Sharp, Patricia A. de Oliveira, Ana Boruff, Jill TI Practice Guidelines for the Application of Nonsilicone or Silicone Gels and Gel Sheets After Burn Injury SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HYPERTROPHIC SCARS; KELOID SCARS; CLINICAL-TRIAL; QUANTITATIVE MEASUREMENT; MEDIAN STERNOTOMY; SURGICAL SCARS; CICA-CARE; SIL-K; PREVENTION AB The objective of this review was to systematically evaluate available clinical evidence for the application of nonsilicone or silicone gels and gel sheets on hypertrophic scars and keloids after a burn injury so that practice guidelines could be proposed. This review provides evidence based recommendations, specifically for the rehabilitation interventions required for the treatment of aberrant wound healing after burn injury with gels or gel sheets. These guidelines are designed to assist all healthcare providers who are responsible for initiating and supporting scar management interventions prescribed for burn survivors. Summary recommendations were made after the literature, retrieved by systematic review, was critically appraised and the level of evidence determined according to Oxford Centre for Evidence-based Medicine criteria.(1) C1 [Nedelec, Bernadette] McGill Univ, Sch Phys & Occupat Therapy, Montreal, PQ H3G 1Y5, Canada. [Nedelec, Bernadette; de Oliveira, Ana] Ctr Hosp Univ Montreal, Ctr Rech, Montreal, PQ, Canada. [Nedelec, Bernadette; Carter, Alissa] Hop Readaptat Villa Med, Montreal, PQ, Canada. [Forbes, Lisa] Hlth Sci Ctr, Winnipeg, MB, Canada. [Hsu, Shu-Chuan Chen] Univ Calif Irvine, Med Ctr, Orange, CA USA. [McMahon, Margaret] Our Ladys Hosp & Care Serv, Dublin, Ireland. [Parry, Ingrid] Shriners Hosp Children, Sacramento, CA USA. [Ryan, Colleen M.; Schneider, Jeffrey C.] Harvard Univ, Shriners Hosp Children, Massachusetts Gen Hosp, Surg Serv,Spaulding Rehabil Hosp,Med Sch, Boston, MA USA. [Serghiou, Michael A.] Shriners Hosp Children, Galveston, TX 77550 USA. [Schneider, Jeffrey C.] Harvard Univ, Massachusetts Gen Hosp, Shriners Hosp Children,Sch Med, Spaulding Rehabil Hosp,Dept Phys Med & Rehabil, Boston, MA USA. [Sharp, Patricia A.] Cincinnati Childrens Med Ctr, Cincinnati, OH USA. [Boruff, Jill] McGill Univ, Montreal, PQ H3G 1Y5, Canada. RP Nedelec, B (reprint author), McGill Univ, Fac Med, 3654 Promenade Sir William Osler, Montreal, PQ H3G 1Y5, Canada. RI Boruff, Jill/K-4940-2015 OI Boruff, Jill/0000-0002-0338-7322 FU Fondation des pompiers du Quebec pour les Grands Brules FX This work was supported by the Fondation des pompiers du Quebec pour les Grands Brules. The editorial assistance of Kathe Lieber, Research Support Office, Research Centre, CHUM, is gratefully acknowledged. NR 81 TC 4 Z9 4 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD MAY-JUN PY 2015 VL 36 IS 3 BP 345 EP 374 DI 10.1097/BCR.0000000000000124 PG 30 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA DD1UI UT WOS:000369707000017 PM 25094007 ER PT J AU Dias-Santos, D Ferrone, CR Zheng, H Lillemoe, KD Fernandez-del Castillo, C AF Dias-Santos, Daniela Ferrone, Cristina R. Zheng, Hui Lillemoe, Keith D. Fernandez-del Castillo, Carlos TI The Charlson age comorbidity index predicts early mortality after surgery for pancreatic cancer SO SURGERY LA English DT Article ID TRIAL; ADENOCARCINOMA; GEMCITABINE; MORBIDITY; SURVIVAL; OUTCOMES; THERAPY AB Background. Although operative resection represents the only hope for cure in pancreatic cancer, it is associated with significant morbidity and mortality. Furthermore, in some patients disease occurs very early postoperatively and no tangible benefit is seen from the operation. Identification of preoperative predictors of death within the first year of surgery could help in the counseling of diagnosed with pancreatic cancer. Methods. We studied retrospectively patients who underwent resection for pancreatic adenocarcinoma from 2002 to 2012. We calculated the age-adjusted Charlson Age Comorbidity Index (CACI) and logistic regression models to determine predictors of mortality within 1 year of surgery. Kaplan-Meier curves and Cox proportional hazards models were developed to determine hazard ratios on survival. Results. Surgery with curative intent was performed in 497 patients; 136 (27%) died within the year. A CACI score of >4 was predictive of increased duration of stay (P < .001), postoperative complications (P = .042), and mortality within 1 year of pancreatic resection (P < .001). A CACI score of >= 6 increased 3-fold the odds of death within the first year. Conclusion. CACI is useful to predict outcome after pancreatectomy for pancreatic cancer. Patients a high CACI score have a <50% likelihood of being alive 1 year postoperatively. This information should be used when considering the appropriateness of pancreatic resection in patients with multiple comorbidities. C1 [Dias-Santos, Daniela; Ferrone, Cristina R.; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Pancreas & Biliary Surg Program, Boston, MA 02114 USA. [Dias-Santos, Daniela] Univ Nova Lisboa, Fac Ciencias Med, Chron Dis Res Ctr, P-1200 Lisbon, Portugal. [Zheng, Hui] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, 15 Parkman St, Boston, MA 02114 USA. EM CFERNANDEZ@mgh.harvard.edu RI Faculdade de Ciencias Medicas, Nova Medical School/K-6209-2013 FU EMC Laboratories; Quantum Enterprises; RA Inc FX Dr. Einstein reports having received lecture fees from EMC Laboratories, and research funding from Quantum Enterprises. Dr. Curie disclosed consulting fees from RA Inc. Dr. Newton reported his patent on "Newtonian physics". Dr. Archimedes reported no biomedical financial interests or potential conflicts of interest. NR 21 TC 14 Z9 14 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 2015 VL 157 IS 5 BP 881 EP 887 DI 10.1016/j.surg.2014.12.006 PG 7 WC Surgery SC Surgery GA DB5MB UT WOS:000368557100008 PM 25704415 ER PT J AU Yan, K Pogoda, TK AF Yan, Kun Pogoda, Terri K. TI Diabetes Management and Its Association with Transtibial Amputation SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Article ID MICROVASCULAR COMPLICATIONS; RISK-FACTORS AB Background: Transtibial (TTA) and transfemoral (TFA) amputations are rarely considered as distinct events when examining major lower-limb amputation outcomes. The objective of this study was to investigate the relationships among type 2 diabetes, diabetes management strategies, hemoglobin A(1c) levels, and other health factors related to TTA and TFA. Methods: The retrospective medical record review included abstracting demographic and health-related data from the electronic medical records of 92 patients who received amputation-related services in a Department of Veterans Affairs hospital. Results: Patients who controlled their diabetes with insulin (with or without other oral agents) were significantly more likely to undergo TTA (adjusted odds ratio [aOR] = 7.63; 95% confidence interval [CI], 1.17-49.97; P = .03) compared with patients who controlled their diabetes through noninsulin medications or by diet. Patients who underwent no previous surgery (aOR = 6.66; 95% CI, 0.89-49.72; P = .06) or partial amputation only (aOR = 15.44; 95% CI, 1.04-228.29; P = .05) compared with a combination of partial amputation and bypass, thrombolectomy, or stent procedures were marginally to statistically significantly more likely to undergo TTA than TFA. Conclusions: The preferential association between TTA with insulin-dependent diabetes and higher hemoglobin A1c levels versus TFA with previous lower-limb bypasses, stent placement, and thrombolytic interventions distinguishes TTA and TFA as two distinct entities, and awareness of this difference may help clinicians design preventive strategies accordingly. C1 [Yan, Kun] Tufts Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02111 USA. [Pogoda, Terri K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. RP Pogoda, TK (reprint author), VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, 150 S Huntington Ave 152M, Boston, MA 02130 USA. EM terri.pogoda@va.gov NR 14 TC 0 Z9 0 U1 0 U2 1 PU AMER PODIATRIC MED ASSOC PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA SN 8750-7315 EI 1930-8264 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD MAY-JUN PY 2015 VL 105 IS 3 BP 238 EP 243 PG 6 WC Orthopedics SC Orthopedics GA DA3CZ UT WOS:000367674900006 PM 26146970 ER PT J AU Sato, N Lam, CS Teerlink, JR Greenberg, BH Tsutsui, H Oh, BH Zhang, J Hua, TA Wang, XL Ge, J AF Sato, N. Lam, C. S. Teerlink, J. R. Greenberg, B. H. Tsutsui, H. Oh, B. H. Zhang, J. Hua, T. A. Wang, X. L. Ge, J. CA Novartis Pharmaceuticals TI Evaluating the efficacy, safety and tolerability of serelaxin when added to standard therapy in asian patients with acute heart failure: The RELAX-AHF-ASIA trial SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [Sato, N.] Musashi Kosugi Hosp, Nippon Med Sch, Cardiol & Intens Care Unit, Kanagawa, Japan. [Lam, C. S.] Natl Heart Ctr Singapore, Duke NUS, Singapore, Singapore. [Teerlink, J. R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Greenberg, B. H.] Univ Calif San Diego, Cardiol, San Diego, CA 92103 USA. [Tsutsui, H.] Hokkaido Univ, Grad Sch Med, Cardiovasc Med, Sapporo, Hokkaido, Japan. [Oh, B. H.] Seoul Natl Univ, Coll Med, Internal Med, Seoul, South Korea. [Zhang, J.] Chinese Acad Med Sci, Fuwai Hosp, Beijing 100730, Peoples R China. [Zhang, J.] Peking Union Med Coll, Natl Ctr Cardiovasc Dis, Beijing 100021, Peoples R China. [Hua, T. A.; Wang, X. L.] Nova Pharmaceut Corp, E Hanover, NJ USA. [Ge, J.] Fudan Univ, Zhongshan Hosp, Cardiol, Shanghai 200433, Peoples R China. 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 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2015 VL 17 SU 1 SI SI MA P210 BP 41 EP 41 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY1XB UT WOS:000366200401099 ER PT J AU Corvera-Tindel, T Doering, LVD AF Corvera-Tindel, Teresita Doering, L. V. D. TI Comparative validity of depression assessment scales for screening depression in heart failure SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [Corvera-Tindel, Teresita] VA Greater Los Angeles Hlth Care Syst, Nursing Educ & Res, Los Angeles, CA USA. [Doering, L. V. D.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 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 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2015 VL 17 SU 1 SI SI MA 624 BP 139 EP 140 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY1XB UT WOS:000366200402012 ER PT J AU Mark, A Luis, G Robert, L Igor, P AF Mark, Arokiaraj Luis, Guerrero Robert, Levine Igor, Palacios TI Contact analysis and device leaflet interaction of a nitinol based goretex patch device in the treatment of mitral regurgitation by finite element analysis SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [Mark, Arokiaraj] Pondicherry Inst Med Sci, Pondicherry, India. [Luis, Guerrero; Robert, Levine; Igor, Palacios] Massachusetts Gen Hosp, Div Cardiol, 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 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2015 VL 17 SU 1 SI SI MA P928 BP 199 EP 200 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY1XB UT WOS:000366200402221 ER PT J AU Sanders-Van Wijk, S Lupon, J Januzzi, JL De Antonio, M Brunner-La Rocca, HP Gaggin, H Galan, A Shah, R Pfisterer, M Bayes-Genis, A AF Sanders-Van Wijk, S. Lupon, J. Januzzi, J. L. De Antonio, M. Brunner-La Rocca, H. P. Gaggin, H. Galan, A. Shah, R. Pfisterer, M. Bayes-Genis, A. TI Reverse remodelling and 4-year survival using the ST2-R2 score in patients with heart failure. A multicenter study SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [Sanders-Van Wijk, S.; Brunner-La Rocca, H. P.] MUMC, Maastricht, Netherlands. [Lupon, J.; De Antonio, M.; Galan, A.; Bayes-Genis, A.] Germans Trias & Pujol Univ Hosp, Badalona, Spain. [Januzzi, J. L.; Gaggin, H.; Shah, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pfisterer, M.] Univ Basel Hosp, CH-4031 Basel, Switzerland. NR 0 TC 10 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2015 VL 17 SU 1 SI SI MA P1003 BP 220 EP 220 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY1XB UT WOS:000366200402296 ER PT J AU Earle, CC Jacobson, JO Blayney, DW AF Earle, Craig C. Jacobson, Joseph O. Blayney, Douglas W. TI American Society of Clinical Oncology Third Quality Care Symposium SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material C1 Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Univ, Stanford, CA 94305 USA. RP Earle, CC (reprint author), Inst Clin Evaluat Sci, 2075 Bayview Ave,G Wing,Room 106, Toronto, ON M4N 3M5, Canada. EM craig.earle@ices.on.ca NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD MAY PY 2015 VL 11 IS 3 BP 167 EP + DI 10.1200/JOP.2015.004119 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY1PL UT WOS:000366179600025 PM 25804987 ER PT J AU Shulman, LN McCabe, R Gay, G Palis, B McKellar, D AF Shulman, Lawrence N. McCabe, Ryan Gay, Greer Palis, Bryan McKellar, Daniel TI Building Data Infrastructure to Evaluate and Improve Quality: The National Cancer Data Base and the Commission on Cancer's Quality Improvement Programs SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material ID RECTAL-CANCER; SURVIVAL; SURGERY; VOLUME C1 Commiss Canc, Chicago, IL USA. [Shulman, Lawrence N.] Dana Farber Canc Inst, Boston, MA 02215 USA. Wright State Univ, Dayton, OH 45435 USA. RP Shulman, LN (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM law-rence_shulman@dfci.harvard.edu NR 9 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD MAY PY 2015 VL 11 IS 3 BP 209 EP + DI 10.1200/JOP.2015.003863 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY1PL UT WOS:000366179600042 PM 25901051 ER PT J AU Kehl, KL Landrum, MB Kahn, KL Gray, SW Chen, AB Keating, NL AF Kehl, Kenneth L. Landrum, Mary Beth Kahn, Katherine L. Gray, Stacy W. Chen, Aileen B. Keating, Nancy L. TI Tumor Board Participation Among Physicians Caring for Patients With Lung or Colorectal Cancer SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID CARE OUTCOMES RESEARCH; SURVEILLANCE CONSORTIUM; COMORBIDITY; MANAGEMENT AB Purpose: Multidisciplinary tumor board meetings are common in cancer care, but limited evidence is available about their benefits. We assessed the associations of tumor board participation and structure with care delivery and patient outcomes. Methods: As part of the CanCORS study, we surveyed 1,601 oncologists and surgeons about participation in tumor boards and specific tumor board features. Among 4,620 patients with lung or colorectal cancer diagnosed from 2003 to 2005 and seen by 1,198 of these physicians, we assessed associations of tumor board participation with patient survival, clinical trial enrollment, guideline-recommended care, and patient-reported quality, adjusting for patient and physician characteristics. Results: Weekly physician tumor board participation (v participation less often or never) was not associated with patient survival, although in exploratory subgroup analyses, weekly participation was associated with lower mortality for extensive-stage small-cell lung cancer and stage IV colorectal cancer. Patients treated by the 54% of physicians participating in tumor boards weekly (v less often or never) were more likely to enroll onto clinical trials (odds ratio [OR], 1.6; 95% CI, 1.1 to 2.2). Patients with stage I to II non-small-cell lung cancer (NSCLC) whose physicians participated in tumor boards weekly were more likely to undergo curative-intent surgery (OR, 2.9; 95% CI, 1.3 to 6.8), although those with stage I to II NSCLC whose physicians' meetings reviewed > one cancer site were less likely to undergo curative-intent surgery (OR, 0.1; 95% CI, 0.03 to 0.4). Conclusion: Among patients with lung or colorectal cancer, frequent physician tumor board engagement was associated with patient clinical trial participation and higher rates of curativeintent surgery for stage I to II NSCLC but not with overall survival. C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, Los Angeles, CA 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 NCI NIH HHS [U01CA093324, U01 CA093344, U01CA093348, U01 CA093332, U01 CA093329, U01 CA093326, R01 CA164021, 1R01CA164021-01A1, U01CA093339, U01CA093329, U01CA093326, U01CA093344, U01CA093332, K24 CA181510, U01 CA093324, U01 CA093339, U01 CA093348] NR 25 TC 4 Z9 4 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD MAY PY 2015 VL 11 IS 3 BP E267 EP E278 DI 10.1200/JOP.2015.003673 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY1PL UT WOS:000366179600001 PM 25922221 ER PT J AU Pirl, WF Greer, JA Irwin, K Lennes, IT Jackson, VA Park, ER Fujisawa, D Wright, AA Temel, JS AF Pirl, William F. Greer, Joseph A. Irwin, Kelly Lennes, Inga T. Jackson, Vicki A. Park, Elyse R. Fujisawa, Daisuke Wright, Alexi A. Temel, Jennifer S. TI Processes of Discontinuing Chemotherapy for Metastatic Non-Small-Cell Lung Cancer at the End of Life SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID EARLY PALLIATIVE CARE; OF-LIFE; PROSPECTIVE COHORT; OVARIAN-CANCER; QUALITY INDICATORS; AGGRESSIVENESS; ASSOCIATIONS; DEATH AB Purpose: Administration of chemotherapy close to death is widely recognized as poor-quality care. Prior research has focused on predictors and outcomes of chemotherapy administration at the end of life. This study describes processes of chemotherapy discontinuation and examines their relationships with timing before death, hospice referral, and hospital death. Patients and Methods: We reviewed health records of a prospective cohort of 151 patients with newly diagnosed metastatic non-small-cell lung cancer who participated in a trial of early palliative care. Chemotherapy treatments during final regimen were qualitatively analyzed to identify categories of discontinuation processes. We then quantitatively compared predictors and outcomes of the process categories. Results: A total of 144 patients died, with 81 and 48 receiving intravenous (IV) and oral chemotherapies as their final regimen, respectively. Five processes were identified for IV chemotherapy: definitive decisions (19.7%), deferred decisions or breaks (22.2%), disruptions for radiation therapy (22.2%), disruptions resulting from hospitalization (27.2%), and no decisions (8.6%). The five processes occurred at significantly different times before death and, except for definitive decisions, ultimate decisions for no further chemotherapy and referral to hospice were often made months later. Among patients receiving oral chemotherapy, 83.3% (40 of 48) were switched from IV to oral delivery as their final regimen, sometimes concurrent with or even after hospice referral. Conclusion: Date of last chemotherapy is not a proxy for when a decision to stop treatment is made. Patients with metastatic non-small-cell lung cancer stop their final chemotherapy regimen via different processes, which significantly vary in time before death and subsequent end-of-life care. C1 [Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Cambridge, MA 02138 USA. Keio Univ, Sch Med, Tokyo, Japan. RP Pirl, WF (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 10B,55 Fruit St, Boston, MA 02114 USA. EM wpirl@partners.org FU NCI NIH HHS [K07 CA166210] NR 26 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD MAY PY 2015 VL 11 IS 3 BP E405 EP E412 DI 10.1200/JOP.2014.002428 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY1PL UT WOS:000366179600017 PM 25829525 ER PT J AU Stover, DG Zerillo, JA AF Stover, Daniel G. Zerillo, Jessica A. TI Morbidity and Mortality Revisited: Applying a New Quality Improvement Paradigm in Oncology SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material ID ADVERSE EVENTS; PATIENT SAFETY; CONFERENCES; COMPETENCES C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Zerillo, JA (reprint author), Beth Israel Deaconess Med Ctr, Div Med Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM jzerillo@bidmc.harvard.edu OI Stover, Daniel/0000-0001-9003-8165 FU NCI NIH HHS [T32 CA009172] NR 25 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD MAY PY 2015 VL 11 IS 3 BP E428 EP E433 DI 10.1200/JOP.2014.003566 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY1PL UT WOS:000366179600020 PM 25901054 ER PT J AU Suneja, G Boyer, M Yehia, BR Shiels, MS Engels, EA Bekelman, JE Long, JA AF Suneja, Gita Boyer, Matthew Yehia, Baligh R. Shiels, Meredith S. Engels, Eric A. Bekelman, Justin E. Long, Judith A. TI Cancer Treatment in Patients With HIV Infection and Non-AIDS-Defining Cancers: A Survey of US Oncologists SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; UNITED-STATES; LUNG-CANCER; IMMUNODEFICIENCY; INDIVIDUALS; POPULATION; CARE; CHEMOTHERAPY; ASSOCIATION; GUIDELINES AB Purpose: HIV-infected individuals with non-AIDS-defining cancers are less likely to receive cancer treatment compared with uninfected individuals. We sought to identify provider-level factors influencing the delivery of oncology care to HIV-infected patients. Methods: A survey was mailed to 500 randomly selected US medical and radiation oncologists. The primary outcome was delivery of standard treatment, assessed by responses to three specialty-specific management questions. We used the chi(2) test to evaluate associations between delivery of standard treatment, provider demographics, and perceptions of HIV-infected individuals. Multivariable logistic regression identified associations using factor analysis to combine several correlated survey questions. Results: Our response rate was 60%; 69% of respondents felt that available cancer management guidelines were insufficient for the care of HIV-infected patients with cancer; 45% never or rarely discussed their cancer management plan with an HIV specialist; 20% and 15% of providers were not comfortable discussing cancer treatment adverse effects and prognosis with their HIV-infected patients with cancer, respectively; 79% indicated that they would provide standard cancer treatment to HIV-infected patients. In multivariable analysis, physicians comfortable discussing adverse effects and prognosis were more likely to provide standard cancer treatment (adjusted odds ratio, 1.52; 95% CI, 1.12 to 2.07). Physicians with concerns about toxicity and efficacy of treatment were significantly less likely to provide standard cancer treatment (adjusted odds ratio, 0.67; 95% CI, 0.53 to 0.85). Conclusion: Provider-level factors are associated with delivery of nonstandard cancer treatment to HIV-infected patients. Policy change, provider education, and multidisciplinary collaboration are needed to improve access to cancer treatment. C1 Univ Utah, Salt Lake City, UT USA. Marshall Univ, Huntington, WV USA. Univ Penn, Philadelphia, PA 19104 USA. Vet Affairs Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. NCI, Bethesda, MD 20892 USA. RP Suneja, G (reprint author), Huntsman Canc Hosp, 1950 Cir Hope,Room 1570, Salt Lake City, UT 84112 USA. EM gita.suneja@icloud.com NR 27 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD MAY PY 2015 VL 11 IS 3 BP E380 EP E387 DI 10.1200/JOP.2014.002709 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY1PL UT WOS:000366179600014 PM 25873060 ER PT J AU Veenstra, CM Epstein, AJ Liao, KJ Griggs, JJ Pollack, CE Armstrong, K AF Veenstra, Christine M. Epstein, Andrew J. Liao, Kaijun Griggs, Jennifer J. Pollack, Craig E. Armstrong, Katrina TI Hospital Academic Status and Value of Care for Nonmetastatic Colon Cancer SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID FLUOROURACIL PLUS LEVAMISOLE; COLORECTAL-CANCER; TEACHING HOSPITALS; ADJUVANT THERAPY; STAGE-II; HEALTH-CARE; QUALITY; CHEMOTHERAPY; PERFORMANCE; INTERGROUP AB Purpose: The relationship between oncologic hospital academic status and the value of care for stage II and III colon cancer is unknown. Methods: Retrospective SEER-Medicare analysis of patients age >= 66 years with stage II or III colon cancer and seen by medical oncology. Eligible patients were diagnosed 2000 to 2009 and followed through December 31, 2010. Hospitals reporting a major medical school affiliation in the NCI Hospital File were classified as academic medical centers. The association between hospital academic status and survival was assessed using Kaplan-Meier curves and Cox proportional hazards models. The association with mean cost of care was estimated using generalized linear models with log link and gamma family and with cost of care at various quantiles using quantile regression models. Results: Of 24,563 eligible patients, 5,707 (23%) received care from academic hospitals. There were no significant differences in unadjusted disease-specific median survival or adjusted risk of colon cancer death by hospital academic status (stage II hazard ratio = 1.12; 95% CI, 0.98 to 1.28; P = .103; stage III hazard ratio = 0.99; 95% CI, 0.90 to 1.08; P = .763). Excepting patients at the upper limits of the cost distribution, there was no significant difference in adjusted cost by hospital academic status. Conclusion: We found no survival differences for elderly patients with stage II or III colon cancer, treated by a medical oncologist, between academic and nonacademic hospitals. Furthermore, cost of care was similar across virtually the full range of the cost distribution. C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Med, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Veenstra, CM (reprint author), North Ingalls Bldg,3A22,300 North Ingalls, Ann Arbor, MI 48109 USA. EM cveenstr@med.umich.edu NR 31 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD MAY PY 2015 VL 11 IS 3 BP E304 EP E312 DI 10.1200/JOP.2014.003137 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY1PL UT WOS:000366179600005 PM 25901052 ER PT J AU Warner, JL Cowan, AJ Hall, AC Yang, PC AF Warner, Jeremy L. Cowan, Andrew J. Hall, Aric C. Yang, Peter C. TI HemOnc.org: A Collaborative Online Knowledge Platform for Oncology Professionals SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article AB Purpose: Cancer care involves extensive knowledge about numerous chemotherapy drugs and chemotherapy regimens. This information is constantly evolving, and there has been no freely available, comprehensive, centralized repository of chemotherapy information to date. Methods: We created an online, freely accessible, ad-free, collaborative wiki of chemotherapy information entitled HemOnc.org to address the unmet need for a central repository of this information. This Web site was developed with wiki development software and is hosted on a cloud platform. Chemotherapy drug and regimen information (including regimen variants), as well as other information of interest to hematology/oncology professionals, is housed on the site in a fully referenced and standardized format. Accredited users are allowed to freely contribute information to the site. Results: From its inception in November 2011, HemOnc.org has grown rapidly and most recently has detailed information on 383 drugs and 1,298 distinct chemotherapy regimens (not counting variants) in 92 disease subtypes. There are regularly more than 2,000 visitors per week from the United States and international locations. A user evaluation demonstrated that users find the site useful, usable, and recommendable. Conclusion: HemOnc.org is now the largest free source of chemotherapy drug and regimen information and is widely used. Future enhancements, including more metadata about drugs and increasingly detailed efficacy and toxicity information, will continue to improve the value of the resource. C1 Vanderbilt Univ, Nashville, TN 37232 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Sch Med, Seattle, WA USA. Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Warner, JL (reprint author), Vanderbilt Univ, Hematol Oncol, Internal Med & Biomed Informat, 2220 Pierce Ave,PRB 777, Nashville, TN 37232 USA. EM Jeremy.warner@vanderbilt.edu FU NCI NIH HHS [T32 CA009515] NR 17 TC 3 Z9 3 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD MAY PY 2015 VL 11 IS 3 BP E336 EP E350 DI 10.1200/JOP.2014.001511 PG 15 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY1PL UT WOS:000366179600009 PM 25736385 ER PT J AU Davison, BA Metra, M Cotter, G Massie, BM Cleland, JGF Dittrich, HC Edwards, C Filippatos, G Givertz, MM Greenberg, B Ponikowski, P Voors, AA O'Connor, CM Teerlink, JR AF Davison, Beth A. Metra, Marco Cotter, Gad Massie, Barry M. Cleland, John G. F. Dittrich, Howard C. Edwards, Christopher Filippatos, Gerasimos Givertz, Michael M. Greenberg, Barry Ponikowski, Piotr Voors, Adriaan A. O'Connor, Christopher M. Teerlink, John R. CA PROTECT & RELAX-AHF Executive Comm TI Worsening Heart Failure Following Admission for Acute Heart Failure A Pooled Analysis of the PROTECT and RELAX-AHF Studies SO JACC-HEART FAILURE LA English DT Article DE acute heart failure; heart failure readmission; mortality; prognosis; renal function; worsening heart failure ID RECEPTOR ANTAGONIST ROLOFYLLINE; 60-DAY OUTCOMES; ASSOCIATION; DYSPNEA; TEZOSENTAN; SERELAXIN; SYMPTOMS; VERITAS; TRIALS; DESIGN AB OBJECTIVES These studies conducted analyses to examine patient characteristics and outcomes associated with worsening heart failure (WHF). BACKGROUND WHF during an admission for acute heart failure (AHF) represents treatment failure and is a potential therapeutic target for clinical trials of AHF. METHODS Individual patient data from the PROTECT (Placebo-Controlled Randomized Study of the Selective A(1) Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function) and RELAX-AHF (Relaxin in Acute Heart Failure) phase II and III studies were pooled for analysis. RESULTS Of 3,691 patients, death or WHF through day 5 occurred in 12.4%, ranging from 9.5% to 14.5% among studies. A multivariable model provided modest discrimination between patients who did or did not develop WHF (C-index = 0.68). After multivariable adjustment, WHF was associated with a mean increase in length of stay of 5.2 days (95% confidence interval [CI]: 4.6 to 5.8 days) and increased risks of 60-day HF or renal failure readmission or cardiovascular death (hazard ratio [HR]: 1.64, 95% CI: 1.34 to 2.01) and 180-day mortality (HR: 1.93, 95% CI: 1.55 to 2.41) (all p < 0.001). The risk of mortality was higher in patients whose WHF required intravenous inotropes or mechanical therapy (HR: 3.03, 95% CI: 2.11 to 4.36) compared with patients whose WHF was treated with intravenous loop diuretic alone (HR: 1.80, 95% CI: 1.36 to 2.36) (both p < 0.001). WHF was associated with larger increases in markers of renal and hepatic dysfunction during the first days of admission, but remained significantly associated with adverse outcomes after adjustment for these changes. CONCLUSIONS WHF during the first 5 days of admission for AHF occurred in approximately 10% to 15% of patients and was associated with longer length of stay and higher risk for readmission and death. (C) 2015 by the American College of Cardiology Foundation. C1 [Davison, Beth A.; Cotter, Gad; Edwards, Christopher] Momentum Res Inc, Durham, NC 27707 USA. [Metra, Marco] Univ Brescia, Dept Med & Surg Specialties Radiol Sci & Publ Hlt, Cardiol, Brescia, Italy. [Massie, Barry M.; Teerlink, John R.] Univ Calif San Francisco, Sch Med, Div Cardiol, San Francisco, CA USA. [Cleland, John G. F.] Univ Hull, Dept Cardiol, Kingston Upon Hull, Yorks, England. [Cleland, John G. F.] Univ London Imperial Coll Sci Technol & Med, Royal Brompton & Harefield Hosp Natl Hlth Serv Tr, Natl Heart & Lung Inst, London, England. [Dittrich, Howard C.] NovaCardia, San Diego, CA USA. [Filippatos, Gerasimos] Athens Univ Hosp, Dept Cardiol, Athens, Greece. [Givertz, Michael M.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Greenberg, Barry] Univ Calif San Diego, Div Cardiol, San Diego, CA 92103 USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Dept Cardiol, Wroclaw, Poland. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. [Teerlink, John R.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA USA. RP Edwards, C (reprint author), Momentum Res Inc, 3100 Tower Blvd,Suite 802, Durham, NC 27707 USA. EM bethdavison@momentum-research.com RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Cleland, John/0000-0002-1471-7016 FU Corthera, a Novartis affiliate company; Novartis; Corthera; Novacardia; Trevena; Merck; Amgen; ChanRx Corp.; Cardio3 Biosciences; Sorbent Therapeutics; Singulex; Bayer; Servier; Merck/Novacardia; Corthera/Novartis; MSD; Cardiorentis; Johnson Johnson; Coridea; Bayer Health Care; Cardio3Biosciences; Celladon; GlaxoSmithKline; Nephera Ltd.; Servuier; Vifor; Resmed; Stealth Peptides; Otsuka; Amgen/Cytokinetics FX The RELAX-AHF studies were sponsored by Corthera, a Novartis affiliate company. No external support was provided for these analyses. Drs. Davison, Cotter, and Edwards are employees of Momentum Research Inc., which has received research grants from Novartis, Corthera, Novacardia, Trevena, Merck, Amgen, ChanRx Corp., Cardio3 Biosciences, Sorbent Therapeutics, and Singulex. Dr. Metra has received consulting fees from Bayer, Novartis, Servier, and Trevena. Dr. Massie has received consulting fees and research funding from Merck/Novacardia and Corthera/Novartis. Dr. Cleland has received honoraria and research funding from MSD, Novartis, and Amgen. Dr. Dittrich is a former employee of NovaCardia and Sorbent; and is a consultant to Corthera. Dr. Filippatos is a member of the steering committees of trials sponsored by Novartis, Cardiorentis, and Bayer. Dr. Givertz is an employee of Brigham and Women's Hospital. Dr. Greenberg has received consulting fees from Novartis. Dr. Ponikowski has received consulting and lecture fees from Novartis, Johnson & Johnson, Bayer, Coridea, and Cardiorentis. Dr. Voors serves on the steering committee of RELAX-AHF, and has received speaker, consultancy, or research fees from Amgen, Bayer Health Care, Cardio3Biosciences, Celladon, GlaxoSmithKline, Merck, Nephera Ltd., Novartis, Servuier, Singulex, Trevena, and Vifor. Dr. O'Connor has received consulting fees from Cardiorentis, Resmed, and Stealth Peptides; and research funding from Otsuka and Resmed. Dr. Teerlink has received consulting fees and research funding from Merck/NovaCardia, Corthera, Novartis, and Amgen/Cytokinetics. Anthony DeMaria, MD, served as Guest Editor for this paper. NR 22 TC 18 Z9 18 U1 2 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD MAY PY 2015 VL 3 IS 5 BP 395 EP 403 DI 10.1016/j.jchf.2015.01.007 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4EK UT WOS:000365651400009 PM 25951761 ER PT J AU Murphy, C Huang, S Peletier, C Harrington, A Clarridge, JE AF Murphy, Colin Huang, Sze Peletier, Chelsea Harrington, Amanda Clarridge, Jill E., III TI Ribotypes of Clostridium difficile Isolates Correlate With Whole Genome Mapping and Reveal Long-Term Presence of Both Toxigenic and Nontoxigenic Strains SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of Academy-of-Clinical-Laboratory-Physicians-and-Scientists (ACLPS) CY MAY 28-30, 2015 CL Minneapolis, MN SP Acad Clin Lab Phys & Scientists C1 Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAY PY 2015 VL 143 SU 1 MA 68 BP A40 EP A40 PG 1 WC Pathology SC Pathology GA CV9DD UT WOS:000364586600041 ER PT J AU Katz, IT Tsai, AC AF Katz, Ingrid T. Tsai, Alexander C. TI Psychological therapy to improve HIV care and reduce stigma SO LANCET HIV LA English DT Editorial Material ID SOUTH-AFRICA; DISORDERS; METAANALYSIS; DEPRESSION; HEALTH C1 [Katz, Ingrid T.] Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02115 USA. [Katz, Ingrid T.; Tsai, Alexander C.] Harvard Univ, Sch Med, Boston, MA USA. [Katz, Ingrid T.; Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. RP Katz, IT (reprint author), Brigham & Womens Hosp, Div Womens Hlth, 75 Francis St, Boston, MA 02115 USA. EM ikatz2@partners.org FU NIMH NIH HHS [K23 MH097667] NR 16 TC 1 Z9 1 U1 2 U2 5 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 2352-3018 J9 LANCET HIV JI Lancet HIV PD MAY PY 2015 VL 2 IS 5 BP E172 EP E173 DI 10.1016/S2352-3018(15)00044-2 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CU8KY UT WOS:000363792500004 PM 26422997 ER PT J AU Karimian, N Matton, APM Westerkamp, AC Burlage, LC Op den Dries, S Leuvenink, HGD Lisman, T Uygun, K Markmann, JF Porte, RJ AF Karimian, Negin Matton, Alix P. M. Westerkamp, Andrie C. Burlage, Laura C. Op den Dries, Sanna Leuvenink, Henri G. D. Lisman, Ton Uygun, Korkut Markmann, James F. Porte, Robert J. TI Ex Situ Normothermic Machine Perfusion of Donor Livers SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Medicine; Issue 99; Machine perfusion; liver transplantation; preservation; normothermic; hypothermic; human donor liver ID BILIARY COMPLICATIONS; RISK-FACTORS; TRANSPLANTATION; PRESERVATION; GRAFTS; REPERFUSION; STRICTURES; INJURY AB In contrast to conventional static cold preservation (0-4 degrees C), ex situ machine perfusion may provide better preservation of donor livers. Continuous perfusion of organs provides the opportunity to improve organ quality and allows ex situ viability assessment of donor livers prior to transplantation. This video article provides a step by step protocol for ex situ normothermic machine perfusion (37 degrees C) of human donor livers using a device that provides a pressure and temperature controlled pulsatile perfusion of the hepatic artery and continuous perfusion of the portal vein. The perfusion fluid is oxygenated by two hollow fiber membrane oxygenators and the temperature can be regulated between 10 degrees C and 37 degrees C. During perfusion, the metabolic activity of the liver as well as the degree of injury can be assessed by biochemical analysis of samples taken from the perfusion fluid. Machine perfusion is a very promising tool to increase the number of livers that are suitable for transplantation. C1 [Karimian, Negin; Matton, Alix P. M.; Westerkamp, Andrie C.; Burlage, Laura C.; Op den Dries, Sanna; Lisman, Ton; Porte, Robert J.] Univ Groningen, Univ Med Ctr Groningen, Sect Hepatopancreatobiliary Surg & Liver Transpla, NL-9700 AB Groningen, Netherlands. [Karimian, Negin; Matton, Alix P. M.; Westerkamp, Andrie C.; Burlage, Laura C.; Op den Dries, Sanna; Leuvenink, Henri G. D.; Lisman, Ton; Porte, Robert J.] Univ Groningen, Univ Med Ctr Groningen, Dept Surg, Surg Res Lab, NL-9700 AB Groningen, Netherlands. [Uygun, Korkut] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Surg Serv, Cambridge, MA 02138 USA. [Uygun, Korkut] Shriners Burns Hosp, Galveston, TX USA. [Markmann, James F.] Harvard Univ, Massachusetts Gen Hosp, Div Transplantat, Dept Surg,Sch Med, Cambridge, MA 02138 USA. RP Porte, RJ (reprint author), Univ Groningen, Univ Med Ctr Groningen, Sect Hepatopancreatobiliary Surg & Liver Transpla, NL-9700 AB Groningen, Netherlands. EM r.j.porte@umcg.nl FU Innovatief Actieprogramma Groningen, the Netherlands [IAG-3]; Jan Kornelis de Cock Stichting, the Netherlands; Tekke Huizingafonds, the Netherlands FX This research work was financially supported by grants provided by Innovatief Actieprogramma Groningen (IAG-3), Jan Kornelis de Cock Stichting and Tekke Huizingafonds, all in the Netherlands. We are appreciative to all the Dutch transplantation coordinators for identifying the potential discarded livers and obtaining informed consent. NR 23 TC 1 Z9 1 U1 0 U2 2 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD MAY PY 2015 IS 99 AR e52688 DI 10.3791/52688 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CR7MV UT WOS:000361535300038 PM 26067131 ER PT J AU Wong, SM Freedman, RA Stamell, E Golshan, M AF Wong, Stephanie M. Freedman, Rachel A. Stamell, Emily Golshan, Mehra TI Modern Trends in the Surgical Management of Paget's Disease SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 29-MAY 03, 2015 CL Orlando, FL SP Amer Soc Breast Surg C1 [Wong, Stephanie M.; Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Wong, Stephanie M.; Golshan, Mehra] Dana Farber Canc Inst, Boston, MA 02115 USA. [Freedman, Rachel A.; Stamell, Emily] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2015 VL 22 SU 2 BP 20 EP 20 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA CQ9NH UT WOS:000360941400022 ER PT J AU Mallory, AM Losk, K Lin, UN Sagara, Y Birdwell, R Cutone, L Camuso, K Bunnell, C Aydogan, F Golshan, M AF Mallory, Melissa A. Losk, Katya Lin, Nancy U. Sagara, Yasuaki Birdwell, Robyn Cutone, Linda Camuso, Kristen Bunnell, Craig Aydogan, Fatih Golshan, Mehra TI The Influence of Radiology Image Consultation in the Surgical Management of Breast Cancer Patients SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 29-MAY 03, 2015 CL Orlando, FL SP Amer Soc Breast Surg C1 [Mallory, Melissa A.; Sagara, Yasuaki; Cutone, Linda; Aydogan, Fatih; Golshan, Mehra] Brigham & Womens Hosp, Surg, Boston, MA 02115 USA. [Losk, Katya; Camuso, Kristen] Dana Farber Canc Inst, Qual & Patient Safety, Boston, MA 02115 USA. [Lin, Nancy U.; Bunnell, Craig] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Birdwell, Robyn] Brigham & Womens Hosp, Radiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2015 VL 22 SU 2 BP 76 EP 77 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA CQ9NH UT WOS:000360941400090 ER PT J AU McEvoy, M Coopey, S Mazzola, E Merrill, LA Specht, M Gadd, M Smith, B Hughes, K AF McEvoy, Maureen Coopey, Suzanne Mazzola, Emanuele Merrill, Andrea L. Specht, Michelle Gadd, Michele Smith, Barbara Hughes, Kevin TI Breast Cancer Risk and Follow-Up Recommendations for Young Women Diagnosed With Atypical Hyperplasia and Lobular Carcinoma In Situ SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 29-MAY 03, 2015 CL Orlando, FL SP Amer Soc Breast Surg C1 [McEvoy, Maureen; Coopey, Suzanne; Mazzola, Emanuele; Merrill, Andrea L.; Specht, Michelle; Gadd, Michele; Smith, Barbara; Hughes, Kevin] Massachusetts Gen Hosp, Breast Surg Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2015 VL 22 SU 2 BP 80 EP 80 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA CQ9NH UT WOS:000360941400095 ER PT J AU Merrill, LA Tang, R Rai, U Coopey, BS McEvoy, M Hughes, K Specht, M Gadd, M Smith, B AF Merrill, Andrea L. Tang, Rong Rai, Upahvan Coopey, Suzanne B. McEvoy, Maureen Hughes, Kevin Specht, Michelle Gadd, Michele Smith, Barbara TI Should New "No Tumor on Ink" Lumpectomy Margin Guidelines Be Applied to Ductal Carcinoma In Situ (DCIS)? A Retrospective Review Using Shaved Cavity Margins SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 29-MAY 03, 2015 CL Orlando, FL SP Amer Soc Breast Surg C1 [Merrill, Andrea L.; Tang, Rong; Rai, Upahvan; Coopey, Suzanne B.; McEvoy, Maureen; Hughes, Kevin; Specht, Michelle; Gadd, Michele; Smith, Barbara] Massachusetts Gen Hosp, Surg Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2015 VL 22 SU 2 BP 81 EP 82 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA CQ9NH UT WOS:000360941400097 ER PT J AU Tang, R Coopey, S Colwell, A Specht, M Gadd, M McEvoy, M Merrill, AL Rai, U Taghian Alphonse, A William, SB AF Tang, Rong Coopey, Suzanne Colwell, Amy Specht, Michelle Gadd, Michele McEvoy, Maureen Merrill, Andrea L. Rai, Upahvan Taghian Alphonse, Austen William, Smith Barbara TI Prior Breast Irradiation and Post-Mastectomy Irradiation Are Not Contraindications to Nipple-Sparing Mastectomy With Immediate Reconstruction SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 29-MAY 03, 2015 CL Orlando, FL SP Amer Soc Breast Surg C1 [Tang, Rong; Coopey, Suzanne; Colwell, Amy; Specht, Michelle; Gadd, Michele; McEvoy, Maureen; Merrill, Andrea L.; Rai, Upahvan; Taghian; Alphonse, Austen; William, Smith Barbara] Massachusetts Gen Hosp, Surg Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2015 VL 22 SU 2 BP 109 EP 109 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA CQ9NH UT WOS:000360941400131 ER PT J AU Chen, A Ho, V Wu, P AF Chen, Amy Ho, Vincent Wu, Peggy TI Analysis of secondary skin cancers in allogeneic hematopoietic stem cell transplant patients SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract C1 [Chen, Amy] Harvard Univ, Sch Med, Boston, MA USA. [Ho, Vincent] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wu, Peggy] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2015 VL 72 IS 5 SU 1 MA 1005 BP AB40 EP AB40 PG 1 WC Dermatology SC Dermatology GA CQ9NW UT WOS:000360942900157 ER PT J AU Donigan, J Snowden, C Carter, J Kimball, A AF Donigan, Jessica Snowden, Caroline Carter, Joi Kimball, Alexa TI The temporal association between cutaneous T-cell lymphoma and psoriasis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract C1 [Donigan, Jessica; Snowden, Caroline; Carter, Joi; Kimball, Alexa] Massachusetts Gen Hosp, Boston, MA 02114 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2015 VL 72 IS 5 SU 1 MA 592 BP AB255 EP AB255 PG 1 WC Dermatology SC Dermatology GA CQ9NW UT WOS:000360942902142 ER PT J AU Kimball, A Rice, KC Harrison, DJ Kricorian, G Gelfand, JM AF Kimball, Alexa Rice, Kara Creamer Harrison, David J. Kricorian, Greg Gelfand, Joel M. TI Discontinuation from etanercept in OBSERVE-5, a 5-year surveillance registry of patients with moderate to severe plaque psoriasis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract C1 [Kimball, Alexa] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rice, Kara Creamer; Harrison, David J.; Kricorian, Greg] Amgen Inc, Thousand Oaks, CA 91320 USA. [Gelfand, Joel M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2015 VL 72 IS 5 SU 1 MA 1074 BP AB231 EP AB231 PG 1 WC Dermatology SC Dermatology GA CQ9NW UT WOS:000360942902057 ER PT J AU Kuye, IO Adisa, M Nazarian, RM Arvikar, SL Smith, GP AF Kuye, Ifedayo O. Adisa, Morayo Nazarian, Rosalynn M. Arvikar, Sheila L. Smith, Gideon P. TI Granulomatous skin involvement in a patient with an unusual NOD2 mutation SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract C1 [Kuye, Ifedayo O.] Harvard Univ, Sch Med, Boston, MA USA. [Adisa, Morayo; Nazarian, Rosalynn M.; Arvikar, Sheila L.; Smith, Gideon P.] Massachusetts Gen Hosp, Boston, MA 02114 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2015 VL 72 IS 5 SU 1 MA 1408 BP AB106 EP AB106 PG 1 WC Dermatology SC Dermatology GA CQ9NW UT WOS:000360942901156 ER PT J AU Pascoe, V Kimball, A AF Pascoe, Vanessa Kimball, Alexandra TI Seasonal variation in acne and psoriasis: A three-year study utilizing the Physician's Global Assessment psoriasis severity scale SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract C1 [Pascoe, Vanessa; Kimball, Alexandra] Massachusetts Gen Hosp, Boston, MA 02114 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2015 VL 72 IS 5 SU 1 MA 887 BP AB248 EP AB248 PG 1 WC Dermatology SC Dermatology GA CQ9NW UT WOS:000360942902116 ER PT J AU Pascoe, V Kimball, A AF Pascoe, Vanessa Kimball, Alexandra TI iPLEDGE and the changing provider landscape: Nondermatologists represent a decreasing percentage of isotretinoin providers SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract C1 [Pascoe, Vanessa; Kimball, Alexandra] Massachusetts Gen Hosp, Boston, MA 02114 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2015 VL 72 IS 5 SU 1 MA 817 BP AB98 EP AB98 PG 1 WC Dermatology SC Dermatology GA CQ9NW UT WOS:000360942901125 ER PT J AU Paul, S Rabito, C Vedak, P Nigwekar, S Kroshinsky, D AF Paul, Suchismita Rabito, Carlos Vedak, Priyanka Nigwekar, Sagar Kroshinsky, Daniela TI The role of bone scintigraphy for the diagnosis of calciphylaxis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract C1 [Paul, Suchismita] Harvard Univ, Sch Med, Boston, MA USA. [Rabito, Carlos; Vedak, Priyanka; Nigwekar, Sagar; Kroshinsky, Daniela] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2015 VL 72 IS 5 SU 1 MA 1923 BP AB153 EP AB153 PG 1 WC Dermatology SC Dermatology GA CQ9NW UT WOS:000360942901337 ER PT J AU Paul, S Song, P Ogbechie, O Sugai, D Morley, K Schalock, P Kroshinsky, D AF Paul, Suchismita Song, Philip Ogbechie, Oluwatobi Sugai, Daniel Morley, Keith Schalock, Peter Kroshinsky, Daniela TI Vesiculobullous and hemorrhagic erythema migrans SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract C1 [Paul, Suchismita; Ogbechie, Oluwatobi] Harvard Univ, Sch Med, Boston, MA USA. [Song, Philip; Sugai, Daniel; Morley, Keith; Schalock, Peter; Kroshinsky, Daniela] Massachusetts Gen Hosp, Boston, MA 02114 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2015 VL 72 IS 5 SU 1 MA 1918 BP AB131 EP AB131 PG 1 WC Dermatology SC Dermatology GA CQ9NW UT WOS:000360942901254 ER PT J AU Tran, TN Zhu, A Horn, T Lagana, F Sinclair, N AF Tran, Thanh-Nga Zhu, Alec Horn, Tom Lagana, Frances Sinclair, Natalie TI "Acne on the breast": A case report and examination of the culture of denial in dermatology SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract C1 [Tran, Thanh-Nga] Harvard Univ, Sch Med, Dermatol, Boston, MA USA. [Zhu, Alec] Kuchnir Dermatol, Milford, MA USA. [Horn, Tom] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lagana, Frances] Univ Massachusetts, Worcester, MA 01605 USA. [Sinclair, Natalie] Dana Farber Canc Insitute, Milford, MA 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2015 VL 72 IS 5 SU 1 MA 1995 BP AB142 EP AB142 PG 1 WC Dermatology SC Dermatology GA CQ9NW UT WOS:000360942901298 ER PT J AU Williams, RF Hoang, M Kroshinsky, D Smith, G AF Williams, Ramone Faith Hoang, Mai Kroshinsky, Daniela Smith, Gideon TI Follicular mucinosis of the face as a sign of infliximab-induced lupus SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract C1 [Williams, Ramone Faith] Harvard Univ, Sch Med, Boston, MA USA. [Hoang, Mai; Kroshinsky, Daniela; Smith, Gideon] Massachusetts Gen Hosp, Boston, MA 02114 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2015 VL 72 IS 5 SU 1 MA 1048 BP AB148 EP AB148 PG 1 WC Dermatology SC Dermatology GA CQ9NW UT WOS:000360942901317 ER PT J AU Marquard, AM Eklund, AC Joshi, T Krzystanek, M Favero, F Wang, ZGC Richardson, AL Silver, DP Szallasi, Z Birkbak, NJ AF Marquard, Andrea M. Eklund, Aron C. Joshi, Tejal Krzystanek, Marcin Favero, Francesco Wang, Zhigang C. Richardson, Andrea L. Silver, Daniel P. Szallasi, Zoltan Birkbak, Nicolai J. TI Pan-cancer analysis of genomic scar signatures associated with homologous recombination deficiency suggests novel indications for existing cancer drugs SO BIOMARKER RESEARCH LA English DT Article DE Cancer; Homologous recombination deficiency; Genomic scars ID BREAST-CANCER; DNA-REPAIR; OVARIAN-CANCER; COPY NUMBERS; INSTABILITY; CELLS; CHEMOTHERAPY; SENSITIVITY; CISPLATIN; DEFECTS AB Background: Ovarian and triple-negative breast cancers with BRCA1 or BRCA2 loss are highly sensitive to treatment with PARP inhibitors and platinum-based cytotoxic agents and show an accumulation of genomic scars in the form of gross DNA copy number aberrations. Cancers without BRCA1 or BRCA2 loss but with accumulation of similar genomic scars also show increased sensitivity to platinum-based chemotherapy. Therefore, reliable biomarkers to identify DNA repair-deficient cancers prior to treatment may be useful for directing patients to platinum chemotherapy and possibly PARP inhibitors. Recently, three SNP array-based signatures of chromosomal instability were published that each quantitate a distinct type of genomic scar considered likely to be caused by improper DNA repair. They measure telomeric allelic imbalance (named NtAI), large scale transition (named LST), and loss of heterozygosity (named HRD-LOH), and it is suggested that these signatures may act as biomarkers for the state of DNA repair deficiency in a given cancer. Results: We explored the pan-cancer distribution of scores of the three signatures utilizing a panel of 5371 tumors representing 15 cancer types from The Cancer Genome Atlas, and found a good correlation between scores of the three signatures (Spearman's. 0.73-0.87). In addition we found that cancer types ordinarily receiving platinum as standard of care have higher median scores of all three signatures. Interestingly, we also found that smaller subpopulations of high-scoring tumors exist in most cancer types, including those for which platinum chemotherapy is not standard therapy. Conclusions: Within several cancer types that are not ordinarily treated with platinum chemotherapy, we identified tumors with high levels of the three genomic biomarkers. These tumors represent identifiable subtypes of patients which may be strong candidates for clinical trials with PARP inhibitors or platinum-based chemotherapeutic regimens. C1 [Marquard, Andrea M.; Eklund, Aron C.; Joshi, Tejal; Krzystanek, Marcin; Favero, Francesco; Szallasi, Zoltan; Birkbak, Nicolai J.] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Wang, Zhigang C.; Silver, Daniel P.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Wang, Zhigang C.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Silver, Daniel P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Szallasi, Zoltan] Harvard Univ, Sch Med, Childrens Hosp, Informat Program,Harvard Massachusetts Inst Techn, Boston, MA USA. RP Birkbak, NJ (reprint author), Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, Kemitorvet 8, DK-2800 Lyngby, Denmark. EM njuul@cbs.dtu.dk OI Krzystanek, Marcin/0000-0002-5920-2147; Szallasi, Zoltan/0000-0001-5395-7509; Eklund, Aron Charles/0000-0003-0861-1001; Marquard, Andrea/0000-0003-2928-6017 NR 30 TC 9 Z9 9 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2050-7771 J9 BIOMARK RES JI Biomark. Res. PD MAY 1 PY 2015 VL 3 AR 9 DI 10.1186/s40364-015-0033-4 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CR1TY UT WOS:000361109200001 PM 26015868 ER PT J AU Lessard, CJ Sajuthi, S Zhao, J Kim, K Harley, JB Vyse, TJ Sivils, KL Langefeld, CD Bae, S Tsao, BP AF Lessard, C. J. Sajuthi, S. Zhao, J. Kim, K. Harley, J. B. Vyse, T. J. Sivils, K. L. Langefeld, C. D. Bae, S. Tsao, B. P. TI Identification of a systemic lupus erythematosus risk locus spanning the genes ATG16L2, FCHSD2, and p2RY2 in Koreans SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article; Proceedings Paper CT 11th International Congress on Systemic Lupus Erythematosus CY SEP 02-06, 2015 CL Vienna, AUSTRIA C1 [Lessard, C. J.; Sivils, K. L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Sajuthi, S.; Langefeld, C. D.] Wake Forest Univ Hlth Sci, Ctr Publ Hlth Genom, Winston Salem, NC USA. [Sajuthi, S.; Langefeld, C. D.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Zhao, J.; Tsao, B. P.] Univ Calif Los Angeles, Dept Med, Div Rheumatol, Los Angeles, CA 90024 USA. [Kim, K.; Bae, S.] Hanyang Univ, Hosp Rheumat Dis, Dept Rheumatol, Seoul 133791, South Korea. [Harley, J. B.] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA. [Harley, J. B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Vyse, T. J.] Kings Coll London, Div Genet & Mol Med, London WC2R 2LS, England. [Vyse, T. J.] Kings Coll London, Div Immunol Infect & Inflammatory Dis, London WC2R 2LS, England. [Vyse, T. J.] System Lupus Erythematosus Genet SLEGEN Consort, London, England. [Bae, S.] Korean Rheumat Dis Grp, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X EI 1593-098X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAY-JUN PY 2015 VL 33 IS 3 SU 90 MA P8.01 BP S74 EP S74 PG 1 WC Rheumatology SC Rheumatology GA CQ2HY UT WOS:000360421900265 ER PT J AU Tiao, J Feng, R Carr, K Werth, VP AF Tiao, J. Feng, R. Carr, K. Werth, V. P. TI Using the American College of Rheumatology and Systemic Lupus International Collaborating Clinics Criteria to Determine Diagnosis of Systemic Lupus Erythematosus in Subacute Cutaneous Lupus Erythematosus SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article; Proceedings Paper CT 11th International Congress on Systemic Lupus Erythematosus CY SEP 02-06, 2015 CL Vienna, AUSTRIA C1 [Tiao, J.; Carr, K.; Werth, V. P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Tiao, J.; Werth, V. P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Feng, R.] Hosp Univ Penn, Biostat & Epidemiol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X EI 1593-098X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAY-JUN PY 2015 VL 33 IS 3 SU 90 MA P5.88 BP S62 EP S62 PG 1 WC Rheumatology SC Rheumatology GA CQ2HY UT WOS:000360421900224 ER PT J AU Krumholz, A Wiebe, S Gronseth, GS Gloss, DS Sanchez, AM Kabir, AA Liferidge, AT Martello, JP Kanner, AM Shinnar, S Hopp, JL French, JA AF Krumholz, A. Wiebe, S. Gronseth, G. S. Gloss, D. S. Sanchez, A. M. Kabir, A. A. Liferidge, A. T. Martello, J. P. Kanner, A. M. Shinnar, S. Hopp, J. L. French, J. A. TI Evidence-Based Guideline: Management of an Unprovoked First Seizure in Adults Report of the Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society SO EPILEPSY CURRENTS LA English DT Article ID TONIC-CLONIC SEIZURE; QUALITY STANDARDS SUBCOMMITTEE; RANDOMIZED CLINICAL-TRIAL; NEW-ONSET EPILEPSY; ANTIEPILEPTIC DRUGS; PRACTICE PARAMETER; SINGLE SEIZURES; FOLLOW-UP; RECURRENCE; RISK AB OBJECTIVE: To provide evidence-based recommendations for treatment of adults with an unprovoked first seizure. METHODS: We defined relevant questions and systematically reviewed published studies according to the American Academy of Neurology's classification of evidence criteria; we based recommendations on evidence level. RESULTS AND RECOMMENDATIONS: Adults with an unprovoked first seizure should be informed that their seizure recurrence risk is greatest early within the first 2 years (21%-45%) (Level A), and clinical variables associated with increased risk may include a prior brain insult (Level A), an EEG with epileptiform abnormalities (Level A), a significant brain-imaging abnormality (Level B), and a nocturnal seizure (Level B). Immediate antiepileptic drug (AED) therapy, as compared with delay of treatment pending a second seizure, is likely to reduce recurrence risk within the first 2 years (Level B) but may not improve quality of life (Level C). Over a longer term (> 3 years), immediate AED treatment is unlikely to improve prognosis as measured by sustained seizure remission (Level B). Patients should be advised that risk for AED adverse events (AEs) may range from 7%-31% (Level B) and that these AEs are likely predominantly mild and reversible. Clinicians' recommendations whether to initiate immediate AED treatment after a first seizure should be based on individualized assessments that weigh the risk of recurrence against the AEs of AED therapy, consider educated patient preferences, and advise that immediate treatment will not improve the long-term prognosis for seizure remission but will reduce seizure risk over the subsequent 2 years. C1 [Krumholz, A.; Sanchez, A. M.; Kabir, A. A.; Martello, J. P.; Hopp, J. L.] Univ Maryland, Sch Med, Dept Neurol, Maryland Epilepsy Ctr, Baltimore, MD 21201 USA. [Krumholz, A.] US Dept Vet Affairs, Maryland Healthcare Syst, Epilepsy Ctr Excellence, Baltimore, MD USA. [Wiebe, S.] Univ Calgary, Dept Clin Neurosci, Fac Med, Calgary, AB T2N 1N4, Canada. [Gronseth, G. S.] Univ Kansas, Dept Neurol, Sch Med, Kansas City, KS USA. [Gloss, D. S.] Geisinger Hlth Syst, Dept Neurol, Danville, PA USA. [Liferidge, A. T.] George Washington Univ, Sch Med, Dept Emergency Med, Washington, DC USA. [Kanner, A. M.] Univ Miami, Dept Neurol, Int Ctr Epilepsy, Miller Sch Med, Coral Gables, FL 33124 USA. [Shinnar, S.] Yeshiva Univ, Dept Neurol, Albert Einstein Coll Med, Bronx, NY USA. [Shinnar, S.] Yeshiva Univ, Dept Pediat, Albert Einstein Coll Med, Bronx, NY USA. [Shinnar, S.] Yeshiva Univ, Dept Epidemiol & Populat Hlth, Albert Einstein Coll Med, Bronx, NY USA. [French, J. A.] NYU, Comprehens Epilepsy Ctr, New York, NY USA. RP Krumholz, A (reprint author), Univ Maryland, Sch Med, Dept Neurol, Maryland Epilepsy Ctr, Baltimore, MD 21201 USA. RI French, Jacqueline/G-6795-2013 OI French, Jacqueline/0000-0003-2242-8027 FU American Academy of Neurology FX This guideline was developed with financial support from the American Academy of Neurology. NR 36 TC 1 Z9 1 U1 1 U2 7 PU AMER EPILEPSY SOCIETY PI WEST HARTFORD PA 342 NORTH MAIN STREET, WEST HARTFORD, CT 06117-2507 USA SN 1535-7597 EI 1535-7511 J9 EPILEPSY CURR JI Epilepsy Curr. PD MAY-JUN PY 2015 VL 15 IS 3 BP 144 EP 152 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CQ6IL UT WOS:000360707900014 PM 26316856 ER PT J AU Van Stan, JH Roy, N Awan, S Stemple, J Hillman, RE AF Van Stan, Jarrad H. Roy, Nelson Awan, Shaheen Stemple, Joseph Hillman, Robert E. TI A Taxonomy of Voice Therapy SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article ID INTENSIVE SPEECH TREATMENT; RANDOMIZED CLINICAL-TRIAL; LARYNGEAL MANUAL THERAPY; MUSCLE TENSION DYSPHONIA; VOCAL FUNCTION EXERCISES; SCIREHAB PROJECT SERIES; PARKINSONS-DISEASE; ACCENT METHOD; REHABILITATION TREATMENTS; INPATIENT REHABILITATION AB Purpose: Voice therapy practice and research, as in most types of rehabilitation, is currently limited by the lack of a taxonomy describing what occurs during a therapy session (with enough precision) to determine which techniques/components contribute most to treatment outcomes. To address this limitation, a classification system of voice therapy is proposed that integrates descriptions of therapeutic approaches from the clinical literature into a framework that includes relevant theoretical constructs. Method: Literature searches identified existing rehabilitation taxonomies/therapy classification schemes to frame an initial taxonomic structure. An additional literature search and review of clinical documentation provided a comprehensive list of therapy tasks. The taxonomy's structure underwent several iterations to maximize accuracy, intuitive function, and theoretical underpinnings while minimizing redundancy. The taxonomy was then used to classify established voice therapy programs. Results: The taxonomy divided voice therapy into direct and indirect interventions delivered using extrinsic and/or intrinsic methods, and Venn diagrams depicted their overlapping nature. A dictionary was developed of the taxonomy's terms, and 7 established voice therapy programs were successfully classified. Conclusion: The proposed taxonomy represents an important initial step toward a standardized voice therapy classification system expected to facilitate outcomes research and communication among clinical stakeholders. C1 [Van Stan, Jarrad H.; Hillman, Robert E.] MGH Inst Hlth Profess, Boston, MA 02129 USA. [Van Stan, Jarrad H.; Hillman, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Roy, Nelson] Univ Utah, Salt Lake City, UT USA. [Awan, Shaheen] Bloomsburg Univ Penn, Bloomsburg, PA 17815 USA. [Stemple, Joseph] Univ Kentucky, Lexington, KY 40506 USA. [Hillman, Robert E.] Harvard Univ, Sch Med, Boston, MA USA. RP Van Stan, JH (reprint author), MGH Inst Hlth Profess, Boston, MA 02129 USA. EM jvanstan@mghihp.edu FU NIDCD NIH HHS [R01-DC012519, R01-DC010367] NR 98 TC 3 Z9 4 U1 2 U2 7 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1058-0360 EI 1558-9110 J9 AM J SPEECH-LANG PAT JI Am. J. Speech-Lang. Pathol. PD MAY PY 2015 VL 24 IS 2 BP 101 EP 125 DI 10.1044/2015_AJSLP-14-0030 PG 25 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA CQ0II UT WOS:000360278300003 PM 25763678 ER PT J AU Ahmed, SG Hadaegh, F Sena-Esteves, M Maguire, CA Fulci, G Breakefield, XO Brenner, GJ AF Ahmed, Sherif G. Hadaegh, Farnaz Sena-Esteves, Miguel Maguire, C. A. Fulci, Giulia Breakefield, Xandra O. Brenner, Gary J. TI Mechanisms of Caspase-1 Mediated Schwannoma Regression SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 18th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 13-16, 2015 CL New Orleans, LA SP Amer Soc Gene & Cell Therapy C1 [Ahmed, Sherif G.; Hadaegh, Farnaz; Brenner, Gary J.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Maguire, C. A.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Fulci, Giulia] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Sena-Esteves, Miguel] Univ Massachusetts, Gene Therapy Ctr, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2015 VL 23 SU 1 MA 635 BP S252 EP S252 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CP5UY UT WOS:000359951700637 ER PT J AU Carvalho, LS Xiao, R Comander, JI Kim, LA Lim, L Khaychuck, V Plovie, E Zinn, E Vandenberghe, LH AF Carvalho, Livia S. Xiao, Ru Comander, Jason I. Kim, Leo A. Lim, Laurence Khaychuck, Vadim Plovie, Eva Zinn, Eric Vandenberghe, Luk H. TI Ancestral AAV Demonstrates Unique Transduction Properties in Mouse and Primate SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 18th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 13-16, 2015 CL New Orleans, LA SP Amer Soc Gene & Cell Therapy C1 [Carvalho, Livia S.; Xiao, Ru; Kim, Leo A.; Khaychuck, Vadim; Plovie, Eva; Zinn, Eric; Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA 02114 USA. [Comander, Jason I.; Kim, Leo A.; Lim, Laurence] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2015 VL 23 SU 1 MA 383 BP S152 EP S153 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CP5UY UT WOS:000359951700387 ER PT J AU Carvalho, LS Gyorgy, B Mu, D Shah, S Vandenberghe, LH Maguire, CA AF Carvalho, Livia S. Gyoergy, Bence Mu, Dakai Shah, Samiksha Vandenberghe, Luk H. Maguire, Casey A. TI Retinal Tropism of Exosome-Associated AAV Vector Via Intravitreal Delivery SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 18th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 13-16, 2015 CL New Orleans, LA SP Amer Soc Gene & Cell Therapy C1 [Carvalho, Livia S.; Shah, Samiksha; Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Dept Ophthalmol,Med Sch, Boston, MA 02114 USA. [Gyoergy, Bence] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02115 USA. [Gyoergy, Bence; Mu, Dakai; Maguire, Casey A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2015 VL 23 SU 1 MA 152 BP S61 EP S61 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CP5UY UT WOS:000359951700154 ER PT J AU Fitzpatrick, Z Maus, A Gyorgy, B Mu, D Csomos, K Walter, JE Maguire, CA AF Fitzpatrick, Zachary Maus, Andreas Gyorgy, Bence Mu, Dakai Csomos, Krisztian Walter, Jolan E. Maguire, Casey A. TI G-Force Loading of Virus Vectors into Vesicles for Enhanced Gene Therapy Vehicles SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 18th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 13-16, 2015 CL New Orleans, LA SP Amer Soc Gene & Cell Therapy C1 [Fitzpatrick, Zachary] Louisiana State Univ, Baton Rouge, LA 70803 USA. [Maus, Andreas; Gyorgy, Bence; Mu, Dakai; Csomos, Krisztian; Walter, Jolan E.; Maguire, Casey A.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2015 VL 23 SU 1 MA 266 BP S106 EP S106 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CP5UY UT WOS:000359951700271 ER PT J AU Hudry, EM Martin, C Mu, DK Mingozzi, F Hyman, BT Maguire, CA AF Hudry, Eloise M. Martin, Courtney Mu, Dakai Mingozzi, Federico Hyman, Bradley T. Maguire, Casey A. TI Highly-Efficient CNS Transduction With Vesicle-Associated AAV Vector SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 18th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 13-16, 2015 CL New Orleans, LA SP Amer Soc Gene & Cell Therapy C1 [Hudry, Eloise M.; Martin, Courtney; Hyman, Bradley T.] Massachusetts Gen Hosp, Alzheimer Res Unit, Inst Neurodegenerat Dis, Charlestown, MA USA. [Hudry, Eloise M.; Martin, Courtney; Mu, Dakai; Hyman, Bradley T.; Maguire, Casey A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hudry, Eloise M.; Martin, Courtney; Mu, Dakai; Hyman, Bradley T.; Maguire, Casey A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Mingozzi, Federico] Univ Paris 06, Evry, France. [Mingozzi, Federico] Genethon, Evry, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2015 VL 23 SU 1 MA 312 BP S126 EP S126 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CP5UY UT WOS:000359951700317 ER PT J AU Kleinstiver, BP Prew, MS Topkar, VV Tsai, SQ Joung, JK AF Kleinstiver, Benjamin P. Prew, Michelle S. Topkar, Ved V. Tsai, Shengdar Q. Joung, Jae K. TI Engineered Cas9 Variants with Novel PAM Specificities Expand the Targeting Range of CRISPR/Cas Nucleases SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 18th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 13-16, 2015 CL New Orleans, LA SP Amer Soc Gene & Cell Therapy C1 [Kleinstiver, Benjamin P.; Prew, Michelle S.; Topkar, Ved V.; Tsai, Shengdar Q.; Joung, Jae K.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Kleinstiver, Benjamin P.; Prew, Michelle S.; Topkar, Ved V.; Tsai, Shengdar Q.; Joung, Jae K.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Kleinstiver, Benjamin P.; Tsai, Shengdar Q.; Joung, Jae K.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2015 VL 23 SU 1 MA 58 BP S26 EP S26 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CP5UY UT WOS:000359951700060 ER PT J AU Pacouret, S Turunen, H Plovie-Buys, E Xiao, R Shelke, R Lin, Y Zinn, E Vandenberghe, LH AF Pacouret, Simon Turunen, Heikki Plovie-Buys, Eva Xiao, Ru Shelke, Rajani Lin, Yang Zinn, Eric Vandenberghe, Luk H. TI Structural Studies Into the Stability of Novel In Silico Reconstructed Ancestral AAV Vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 18th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 13-16, 2015 CL New Orleans, LA SP Amer Soc Gene & Cell Therapy C1 [Pacouret, Simon; Turunen, Heikki; Plovie-Buys, Eva; Xiao, Ru; Shelke, Rajani; Lin, Yang; Zinn, Eric; Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2015 VL 23 SU 1 MA 88 BP S38 EP S38 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CP5UY UT WOS:000359951700090 ER PT J AU Parekkadan, B AF Parekkadan, Biju TI Pharmacokinetics of Natural and Engineered Secreted Factors Delivered by a Cell Therapeutic SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 18th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 13-16, 2015 CL New Orleans, LA SP Amer Soc Gene & Cell Therapy C1 [Parekkadan, Biju] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2015 VL 23 SU 1 MA 256 BP S100 EP S101 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CP5UY UT WOS:000359951700257 ER PT J AU Saha, D Martuza, RL Rabkin, SD AF Saha, Dipongkor Martuza, Robert L. Rabkin, Samuel D. TI Immunovirotherapy Combined with Immune Checkpoint Inhibitors for Treating Glioblastoma SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 18th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 13-16, 2015 CL New Orleans, LA SP Amer Soc Gene & Cell Therapy C1 [Saha, Dipongkor; Martuza, Robert L.; Rabkin, Samuel D.] Massachusetts Gen Hosp, Neurosurg, Boston, MA 02114 USA. [Saha, Dipongkor; Martuza, Robert L.; Rabkin, Samuel D.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2015 VL 23 SU 1 MA 624 BP S248 EP S248 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CP5UY UT WOS:000359951700626 ER PT J AU Tsai, SQ Zheng, ZL Nguyen, NT Liebers, M Topkar, VV Thapar, V Wyvekens, N Khayter, C AF Tsai, Shengdar Q. Zheng, Zongli Nguyen, Nhu T. Liebers, Matthew Topkar, Ved V. Thapar, Vishal Wyvekens, Nicolas Khayter, Cyd TI Defining Genome-Wide Off-Target Cleavage Profiles of CRISPR-Cas RNA-Guided Nucleases Using GUIDE-Seq SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 18th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 13-16, 2015 CL New Orleans, LA SP Amer Soc Gene & Cell Therapy C1 [Tsai, Shengdar Q.; Zheng, Zongli; Nguyen, Nhu T.; Liebers, Matthew; Topkar, Ved V.; Thapar, Vishal; Wyvekens, Nicolas; Khayter, Cyd] Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. [Tsai, Shengdar Q.; Zheng, Zongli; Liebers, Matthew; Wyvekens, Nicolas] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Zheng, Zongli] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2015 VL 23 SU 1 MA 689 BP S274 EP S274 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CP5UY UT WOS:000359951700691 ER PT J AU Zinn, EM Khaychuk, V Turunen, H Vandenberghe, LH AF Zinn, Eric M. Khaychuk, Vadim Turunen, Heikki Vandenberghe, Luk H. TI In Silico Reconstruction of AAV Evolutionary Intermediates To Identify Genetic Determinants of Capsid Function SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 18th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 13-16, 2015 CL New Orleans, LA SP Amer Soc Gene & Cell Therapy C1 [Zinn, Eric M.; Khaychuk, Vadim; Turunen, Heikki; Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Opthamol,Schepens Eye Res Inst,Dept Opthamol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2015 VL 23 SU 1 MA 89 BP S38 EP S38 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CP5UY UT WOS:000359951700091 ER PT J AU Rao, TN Marks-Bluth, J Sullivan, J Gupta, MK Chandrakanthan, V Fitch, SR Ottersbach, K Jang, YC Piao, XH Kulkarni, RN Serwold, T Pimanda, JE Wagers, AJ AF Rao, Tata Nageswara Marks-Bluth, Jonathan Sullivan, Jessica Gupta, Manoj K. Chandrakanthan, Vashe Fitch, Simon R. Ottersbach, Katrin Jang, Young C. Piao, Xianhua Kulkarni, Rohit N. Serwold, Thomas Pimanda, John E. Wagers, Amy J. TI High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice SO STEM CELL RESEARCH LA English DT Article ID COUPLED RECEPTOR 56; GENOME-WIDE ANALYSIS; TRANSCRIPTIONAL REGULATORS; MOLECULAR SIGNATURES; GENE-EXPRESSION; MARROW; BLOOD; NICHES; LAMINATION; MIGRATION AB Blood formation by hematopoietic stem cells (HSCs) is regulated by a still incompletely defined network of general and HSC-specific regulators. In this study, we analyzed the role of G-protein coupled receptor 56 (Gpr56) as a candidate HSC regulator based on its differential expression in quiescent relative to proliferating HSCs and its common targeting by core HSC regulators. Detailed expression analysis revealed that Gpr56 is abundantly expressed by HSPCs during definitive hematopoiesis in the embryo and in the adult bone marrow, but its levels are reduced substantially as HSPCs differentiate. However, despite enriched expression in HSPCs, Gpr56-deficiency did not impair HSPC maintenance or function during steady-state or myeloablative stress-induced hematopoiesis. Gpr56-deficient HSCs also responded normally to physiological and pharmacological mobilization signals, despite the reported role of this GPCR as a regulator of cell adhesion and migration in neuronal cells. Moreover, Gpr56-deficient bone marrow engrafted with equivalent efficiency as wild-type HSCs in primary recipients; however, their reconstituting ability was reduced when subjected to serial transplantation. These data indicate that although GPR56 is abundantly and selectively expressed by primitive HSPCs, its high level expression is largely dispensable for steady-state and regenerative hematopoiesis. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Rao, Tata Nageswara; Sullivan, Jessica; Jang, Young C.; Wagers, Amy J.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Rao, Tata Nageswara; Sullivan, Jessica; Jang, Young C.; Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Rao, Tata Nageswara; Sullivan, Jessica; Gupta, Manoj K.; Jang, Young C.; Kulkarni, Rohit N.; Serwold, Thomas; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Rao, Tata Nageswara; Sullivan, Jessica; Gupta, Manoj K.; Jang, Young C.; Kulkarni, Rohit N.; Serwold, Thomas; Wagers, Amy J.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Marks-Bluth, Jonathan; Chandrakanthan, Vashe; Pimanda, John E.] Univ New S Wales, Lowy Canc Res Ctr, Sydney, NSW 2052, Australia. [Marks-Bluth, Jonathan; Chandrakanthan, Vashe; Pimanda, John E.] Univ New S Wales, Prince Wales Clin Sch, Sydney, NSW 2052, Australia. [Fitch, Simon R.; Ottersbach, Katrin] Univ Cambridge, Cambridge Inst Med Res, Dept Haematol, Cambridge CB2 0XY, England. [Fitch, Simon R.; Ottersbach, Katrin] Univ Cambridge, Stem Cell Inst, MRC, Wellcome Trust, Cambridge CB2 0XY, England. [Piao, Xianhua] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Newborn Med, Boston, MA 02215 USA. RP Wagers, AJ (reprint author), Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM amy_wagers@harvard.edu OI Ottersbach, Katrin/0000-0002-6880-4895 FU NIH [P30 DK036836]; National Institutes of Health (NIH) [OD004345, HL088582, DK67536, DK103215]; National Health and Medical Research Council of Australia [1042934, 1024364, 1008515]; Leukaemia and Lymphoma Research (LLR) grant [10015]; NCRR-NIH; [B6N.129S5-Gpr56tm1Lex/Mmcd] FX We thank all the members of Wagers laboratory and E. Gussoni and E. Dzierzak for helpful discussions. We also thank A. Wakabayashi, G. Buruzula and J. LaVecchio at Joslin/HSCI Flow Cytometry Core for excellent flow cytometry support, funded in part by NIH P30 DK036836. This work was supported in part by grants from the National Institutes of Health (NIH, OD004345 and HL088582 to AJW and DK67536 and DK103215 to RNK), from the National Health and Medical Research Council of Australia 1042934, 1024364 and 1008515 to JEP), and from Leukaemia and Lymphoma Research (LLR) grant 10015 to KO. Content is solely the responsibility of the authors and does not necessarily reflect the official views of the NIH or other funding agencies. The mouse strain used for this research project, B6N.129S5-Gpr56tm1Lex/Mmcd, identification number 032342-UCD, was obtained from the Mutant Mouse Regional Resource Center, a NCRR-NIH funded strain repository, and was donated to the MMRRC by Genentech, Inc. NR 41 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-5061 EI 1876-7753 J9 STEM CELL RES JI Stem Cell Res. PD MAY PY 2015 VL 14 IS 3 BP 307 EP 322 DI 10.1016/j.scr.2015.02.001 PG 16 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP6JR UT WOS:000359993400006 PM 25840412 ER PT J AU Littman, AJ Jacobson, IG Boyko, EJ Smith, TC AF Littman, Alyson J. Jacobson, Isabel G. Boyko, Edward J. Smith, Tyler C. TI Changes in Meeting Physical Activity Guidelines After Discharge From the Military SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE exercise; military personnel; Veterans ID MILLENNIUM COHORT; RELIABILITY; VETERANS; VALIDITY; SERVICE; HEALTH; VACCINATION; BEHAVIORS; PERSONNEL; TRENDS AB Background: Understanding physical activity (PA) after discharge from the military can inform theory on the role of habit and reinforcement in behavior maintenance and has implications for this population's future health. Methods: Using data from 28,866 Millennium Cohort Study participants (n = 3782 of whom were discharged during the years between assessments), we 1) investigated changes in meeting federal PA guidelines for moderate-to-vigorous activity (MVPA) following military discharge and 2) determined predictors of meeting these guidelines after discharge. Results: MVPA declined more in those who were discharged than in those who were not (-17.8 percentage points vs. 2.7 percentage points), with greater declines in former active-duty personnel, those who had deployed with combat exposures, had 14 to 25 years of service, and had been discharged more recently (>2 years prior). In those who were discharged, being normal or overweight (vs. obese), and a nonsmoker or former smoker (vs. current smoker) were positively associated with meeting MVPA Guidelines at follow-up, while meeting MVPA Guidelines at baseline and depression were inversely associated. Conclusions: Reductions in MVPA were substantial and unexpected. Increased understanding of transitional periods that may benefit from interventions to mitigate declines in PA will help prevent excess weight gain and physical inactivity-associated health consequences. C1 [Littman, Alyson J.; Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. [Jacobson, Isabel G.] Naval Hlth Res Ctr, Deployment Hlth Res Dept, San Diego, CA USA. [Smith, Tyler C.] Natl Univ, Dept Community Hlth, Sch Hlth & Human Serv, San Diego, CA USA. RP Littman, AJ (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. EM Alyson.littman@va.gov FU Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD; VA Rehabilitation Research and Development Career Development Award [6982] FX We are indebted to the Millennium Cohort Study participants, without whom these analyses would not be possible, the other the Millennium Cohort Study Team members, includes Melissa Bagnell, MPH; James Davies; Raechel Del Rosario, MPH; Gia Gumbs, MPH; Nisara Granado, MPH, PhD; Jaime Horton, MPH; Andrea Ippolito; Lauren Kipp, MPH; Kelly Jones, MPH; Cynthia LeardMann, MPH; William Lee; Michelle Linfesty; Gordon Lynch; Hope McMaster, PhD; Sheila Medina-Torne, MPH; Teresa Powell, MS; Toni Rush, MPH; Emma Schaller; Amber Seelig, MPH; Beverly Sheppard; Donald Slymen, PhD; Katherine Snell; Steven Speigle; Karl Sausedo, MA; Jennifer Walstrom; John Wesner; Martin White, MPH; James Whitmer; and Charlene Wong, MPH; from the Deployment Health Research Department, Naval Health Research Center, San Diego, CA. We thank Scott L. Seggerman and Greg D. Boyd from the Management Information Division, Defense Manpower Data Center, Monterey, CA. In addition, we thank Michelle LeWark from the Naval Health Research Center. We also thank all the professionals from the US Army Medical Research and Materiel Command, especially those from the Military Operational Medicine Research Program, Fort Detrick, MD, We appreciate the support of the Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD. This material is the result of work partly supported with resources and the use of facilities from the Cooperative Studies Program, Department of Veterans Affairs, and the Puget Sound VA Medical Center. Dr. Littman was supported by a VA Rehabilitation Research and Development Career Development Award (#6982). This work represents report 12-XX, supported by the Department of Defense, under work unit no. 60002. The views expressed in this article are those of the authors and do not reflect the official policy or position or constitute endorsement of the Department of the Navy, Department of the Army, Department of the Air Force, Department of Defense, Department of Veterans Affairs, the US Government, or the American College of Sports Medicine. This research has been conducted in compliance with all applicable federal regulations governing the protection of human subjects in research (protocol NHRC.2000.0007). NR 23 TC 3 Z9 3 U1 0 U2 0 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 EI 1543-5474 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD MAY PY 2015 VL 12 IS 5 BP 666 EP 674 DI 10.1123/jpah.2013-0260 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CO5DD UT WOS:000359178900011 PM 26237780 ER PT J AU Butryn, ML Arigo, D Raggio, GA Kaufman, AI Kerrigan, SG Forman, EM AF Butryn, Meghan L. Arigo, Danielle Raggio, Greer A. Kaufman, Alison Infield Kerrigan, Stephanie G. Forman, Evan M. TI Measuring the Ability to Tolerate Activity-Related Discomfort: Initial Validation of the Physical Activity Acceptance Questionnaire (PAAQ) SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE Acceptance and Commitment Therapy (ACT); exercise; assessment; adherence ID TEST-RETEST RELIABILITY; QUALITY-OF-LIFE; ACTIVITY PARTICIPATION; ACTIVITY INTERVENTIONS; EXERCISE INTENSITY; COMMITMENT THERAPY; CONSTRUCT-VALIDITY; ENERGY-EXPENDITURE; UNITED-STATES; SELF-EFFICACY AB Background: Physical activity (PA) is essential for health, but many adults find PA adherence challenging. Acceptance of discomfort related to PA may influence an individual's ability to begin and sustain a program of exercise. The aim of this study was to evaluate the psychometric properties of the Physical Activity Acceptance Questionnaire (PAAQ). Methods: The PAAQ was administered to 3 distinct samples (N = 418). Each sample completed additional self-report measures; 1 sample also wore accelerometers for 7 days (at baseline and 6 months later). Results: The PAAQ demonstrated high internal validity for its total score (alpha = .89) and 2 subscales (Cognitive Acceptance alpha = .86, Behavioral Commitment alpha = .85). The PAAQ also showed convergent validity with measures of mindfulness, self-reported physical activity levels, and accelerometer-verified levels of moderate-to-vigorous PA (MVPA; P-values < .05). The Cognitive Acceptance subscale showed predictive validity for objectively-verified PA levels among individuals attempting to increase PA over 6 months (P = .05). Test-retest reliability for a subset of participants (n = 46) demonstrated high consistency over 1 week (P < .0001). Conclusions: The PAAQ demonstrates sound psychometric properties, and shows promise for improving the current understanding of PA facilitators and barriers among adults. C1 [Butryn, Meghan L.; Kerrigan, Stephanie G.; Forman, Evan M.] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. [Arigo, Danielle] Univ Scranton, Dept Psychol, Scranton, PA 18510 USA. [Raggio, Greer A.] VA Boston Healthcare Syst, Behav Med Program, Boston, MA USA. [Kaufman, Alison Infield] Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat & Behav Sci, Philadelphia, PA USA. RP Butryn, ML (reprint author), Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. EM mlb34@drexel.edu FU National Institute for Diabetes and Digestive and Kidney Diseases, National Institutes of Health [DK092374, DK095069] FX This work was supported by 2 grants from the National Institute for Diabetes and Digestive and Kidney Diseases, National Institutes of Health (DK092374, DK095069). These studies are registered at www.clinicaltrials. gov (numbers NCT01858714 and NCT01854320, respectively). NR 87 TC 2 Z9 2 U1 3 U2 7 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 EI 1543-5474 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD MAY PY 2015 VL 12 IS 5 BP 717 EP 726 DI 10.1123/jpah.2013-0338 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CO5DD UT WOS:000359178900018 PM 25106049 ER PT J AU Abbott, A Kuzuhara, Y Syrkin, L Nguyen, QD McCall, K Qin, L Jacene, H Van den Abbeele, A AF Abbott, Amanda Kuzuhara, Yuji Syrkin, Leonid Quang-De Nguyen McCall, Keisha Qin, Lei Jacene, Heather Van den Abbeele, Annick TI Bridging the gaps to build the future of clinical and pre-clinical imaging research. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Abbott, Amanda; Kuzuhara, Yuji; Syrkin, Leonid; Quang-De Nguyen; McCall, Keisha; Qin, Lei; Jacene, Heather; Van den Abbeele, Annick] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging,Ctr Biomed Imaging Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 2508 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738804052 ER PT J AU Al Tamimi, A Zaheer, S Osmany, S AF Al Tamimi, Ammad Zaheer, Sumbul Osmany, Saabry TI FDG PET/CT imaging of bone metastases in nasopharyngeal carcinoma (NPC) SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Al Tamimi, Ammad] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Radiol,Div Nucl Med & Mol Imaging, Boston, MA USA. [Osmany, Saabry] RadLink Cardiac & PET Imaging, Nucl Med, Singapore, Singapore. [Zaheer, Sumbul] Singapore Gen Hosp, Nucl Med & PET, Singapore, Singapore. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 21 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738800022 ER PT J AU Albrecht, D Loggia, M Borra, R Hooker, J Opalacz, A Mao, JR Zhang, Y AF Albrecht, Daniel Loggia, Marco Borra, Ronald Hooker, Jacob Opalacz, Arissa Mao, Jianren Zhang, Yi TI Activation of spinal glia in sciatica; a pilot [C-11]PBR28 study SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Albrecht, Daniel; Loggia, Marco; Borra, Ronald; Hooker, Jacob] MGH, Martinos Ctr, Radiol, Charlestown, MA USA. [Opalacz, Arissa; Mao, Jianren; Zhang, Yi] Massachusetts Gen Hosp, Anesthesia, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 1557 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738803177 ER PT J AU Alpert, N Guehl, N Ptaszek, L Takahashi, K Josephson, L Shoup, T El Fakhri, G Normandin, M AF Alpert, Nathaniel Guehl, Nicolas Ptaszek, Leon Takahashi, Kazue Josephson, Lee Shoup, Timothy El Fakhri, Georges Normandin, Marc TI Quantitative mapping of cardiac membrane potential: A feasibility study SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Alpert, Nathaniel; Guehl, Nicolas; Ptaszek, Leon; Takahashi, Kazue; Josephson, Lee; Shoup, Timothy; El Fakhri, Georges; Normandin, Marc] Massachusetts Gen Hosp, White, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 522 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738801173 ER PT J AU Belov, V Mushti, C Levine, D Papisov, M Fischman, A AF Belov, Vasily Mushti, Chandra Levine, Dylan Papisov, Mikhail Fischman, Alan TI Monitoring cholesterol transport in vivo by PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Belov, Vasily; Mushti, Chandra; Papisov, Mikhail] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children, Boston, MA USA. [Levine, Dylan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fischman, Alan] Shriners Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 466 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738801117 ER PT J AU Bernskoetter, N Rold, T Szczodroski, A Hoffman, T AF Bernskoetter, Nicole Rold, Tammy Szczodroski, Ashley Hoffman, Timothy TI Enhancement of tumor directed radiopharmaceutical delivery: Assessing NEP inhibition effects in prostate and breast cancer models. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Bernskoetter, Nicole; Szczodroski, Ashley; Hoffman, Timothy] US Dept Vet Affairs, Columbia, MO USA. [Rold, Tammy] Univ Missouri, Med, Columbia, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 1201 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738802171 ER PT J AU Blasi, F Oliveira, B Rietz, T Rotile, N Caravan, P AF Blasi, Francesco Oliveira, Bruno Rietz, Tyson Rotile, Nicholas Caravan, Peter TI Molecular imaging of thrombosis using FBP8-PET allows whole-body thrombus detection and fibrin content estimation SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Blasi, Francesco; Oliveira, Bruno; Rietz, Tyson; Rotile, Nicholas; Caravan, Peter] Massachusetts Gen Hosp, Radiol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 78 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738800079 ER PT J AU Boros, E Holland, J Caravan, P AF Boros, Eszter Holland, Jason Caravan, Peter TI Macrocycle based hydroxamate chelators for stable complexation of Zr-89 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Boros, Eszter; Holland, Jason; Caravan, Peter] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 276 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738800276 ER PT J AU Catafau, A Bullich, S Seibyl, J Barthel, H Ghetti, B Leverenz, J Ironside, J Walter, SS Hoffmann, A Sabri, O AF Catafau, Ana Bullich, Santiago Seibyl, John Barthel, Henryk Ghetti, Bernardino Leverenz, James Ironside, James Walter, Schulz-Schaefer Hoffmann, Anja Sabri, Osama TI Cerebellar senile plaques: How frequent are they, and do they influence 18F-Florbetaben SUVR? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Catafau, Ana; Bullich, Santiago] Piramal Imaging GmbH, Berlin, Germany. [Seibyl, John] Mol Neuroimaging, New Haven, CT USA. [Barthel, Henryk; Sabri, Osama] Univ Leipzig, D-04109 Leipzig, Germany. [Ghetti, Bernardino] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Leverenz, James] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Leverenz, James] Univ Washington, Seattle, WA 98195 USA. [Ironside, James] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Walter, Schulz-Schaefer] Univ Gottingen, D-37073 Gottingen, Germany. [Hoffmann, Anja] Bayer Pharma AG, Berlin, Germany. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 194 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738800195 ER PT J AU Cross, D Hysa, L Pagulayan, K Mayer, C Cook, D Petrie, E Raskind, M Minoshima, S Peskind, E AF Cross, Donna Hysa, Lisa Pagulayan, Kathleen Mayer, Cynthia Cook, David Petrie, Eric Raskind, Murray Minoshima, Satoshi Peskind, Elaine TI Longitudinal assessment of repetitive blast mild traumatic brain injury in veterans using FDG-PET imaging SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Cross, Donna; Hysa, Lisa] U Wash, Seattle, WA USA. [Pagulayan, Kathleen; Mayer, Cynthia; Cook, David; Petrie, Eric; Raskind, Murray; Peskind, Elaine] VA Puget Sound, Seattle, WA USA. [Minoshima, Satoshi] U Utah, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 1609 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738803229 ER PT J AU Dearling, J Tupper, T Modiste, R Dai, GP Nguyen, QD Kung, A Packard, A O'Neill, A AF Dearling, Jason Tupper, Tanya Modiste, Rebecca Dai, Guangping Quang-De Nguyen Kung, Andrew Packard, Alan O'Neill, Allison TI Multimodal imaging of Ewing sarcoma in a preclinical model demonstrates the advantage of immunoPET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [O'Neill, Allison] DFCI, Dept Pediat Oncol, Boston, MA USA. [O'Neill, Allison] Boston Childrens Hosp, Boston, MA USA. [Kung, Andrew] Columbia Univ, Med Ctr, New York, NY USA. [Dearling, Jason; Packard, Alan] Harvard Univ, Sch Med, Nucl Med Radiol, Boston Childrens Hosp, Boston, MA USA. [Tupper, Tanya; Modiste, Rebecca; Dai, Guangping; Quang-De Nguyen] DFCI, Lurie Family Imaging Ctr, Ctr Biomed Imaging Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 1131 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738802101 ER PT J AU Dutta, J El Fakhri, G Li, QZ AF Dutta, Joyita El Fakhri, Georges Li, Quanzheng TI Dynamic PET image denoising using higher-order singular value decomposition SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Dutta, Joyita; El Fakhri, Georges; Li, Quanzheng] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 426 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738801077 ER PT J AU Groll, A Kim, K Dutta, J Li, QZ Meng, LJ AF Groll, Andrew Kim, Kyungsang Dutta, Joyita Li, Quanzheng Meng, Ling-Jian TI Evaluation of Hybrid Pixel-Waveform (HPWF) CdTe and CZT Detectors for Sub-500 mu m Resolution PET Imaging for Mouse Brain Studies SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Groll, Andrew; Meng, Ling-Jian] Univ Illinois, Urbana, IL 61801 USA. [Kim, Kyungsang; Dutta, Joyita; Li, Quanzheng] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 101 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738800102 ER PT J AU Guehl, N Normandin, M Wooten, D Rozen, G Sitek, A Mansour, M Shoup, T Ptaszek, L El Fakhri, G Alpert, N AF Guehl, Nicolas Normandin, Marc Wooten, Dustin Rozen, Guy Sitek, Arkadiusz Mansour, Moussa Shoup, Timothy Ptaszek, Leon El Fakhri, Georges Alpert, Nathaniel TI Single-scan rest/stress imaging with [F-18]flurpiridaz: demonstration in a porcine model SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Guehl, Nicolas; Normandin, Marc; Wooten, Dustin; Rozen, Guy; Sitek, Arkadiusz; Mansour, Moussa; Shoup, Timothy; Ptaszek, Leon; El Fakhri, Georges; Alpert, Nathaniel] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 516 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738801167 ER PT J AU Guehl, N Wooten, D El Fakhri, G Alpert, N Normandin, M AF Guehl, Nicolas Wooten, Dustin El Fakhri, Georges Alpert, Nathaniel Normandin, Marc TI A combined PET-fMRI model for mapping neurotransmission: simulation and initial demonstration SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Guehl, Nicolas; Wooten, Dustin; El Fakhri, Georges; Alpert, Nathaniel; Normandin, Marc] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 97 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738800098 ER PT J AU Guo, N Zheng, K Wang, MD El Fakhri, G Li, F Chen, XY Zhu, ZH Li, QZ AF Guo, Ning Zheng, Kun Wang, Mengdie El Fakhri, Georges Li, Fang Chen, Xiaoyuan Zhu, Zhaohui Li, Quanzheng TI Whole-body Parametric Imaging of Lung Cancer Patients with Ga-68-PRGD2 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Guo, Ning; Wang, Mengdie; El Fakhri, Georges; Li, Quanzheng] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Adv Med Imaging Sci,Radiol, Boston, MA USA. [Zheng, Kun; Li, Fang; Zhu, Zhaohui] Beijing Union Med Coll Hosp, Dept Nucl Med, Beijing, Peoples R China. [Chen, Xiaoyuan] NIBIB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 122 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738800123 ER PT J AU Guo, N Yen, RF Wang, MD El Fakhri, G Li, QZ AF Guo, Ning Yen, Ruoh-Fang Wang, Mengdie El Fakhri, Georges Li, Quanzheng TI F-18-FDG dynamic PET/CT is Effective on Early Assessment of Therapy Response in Patients with Head and Neck Cancer SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Guo, Ning; Wang, Mengdie; El Fakhri, Georges; Li, Quanzheng] Mass Gen Hosp, CAMIS, Boston, MA USA. [Yen, Ruoh-Fang] Natl Taiwan Univ Hosp, Taipei, Taiwan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 17 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738800018 ER PT J AU Horn, K Yap, J Agarwal, N Morton, K Kadrmas, D Beardmore, B Butterfield, R Boucher, K Hoffman, J AF Horn, Kevin Yap, Jeffrey Agarwal, Neeraj Morton, Kathryn Kadrmas, Dan Beardmore, Britney Butterfield, Regan Boucher, Ken Hoffman, John TI FDG- and FLT-PET for early measurement of response to 37.5 mg per day of sunitinib in metastatic renal cell carcinoma SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Horn, Kevin; Yap, Jeffrey; Morton, Kathryn; Kadrmas, Dan; Beardmore, Britney; Hoffman, John] Huntsman Canc Inst, Ctr Quantitat Canc Imaging, Salt Lake City, UT USA. [Butterfield, Regan] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Boucher, Ken] Univ Utah, Internal Med, Salt Lake City, UT USA. [Agarwal, Neeraj] Univ Utah, Med, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 1213 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738802183 ER PT J AU Huang, C Ouyang, JS Reese, T Wu, YT El Fakhri, G Ackerman, J AF Huang, Chuan Ouyang, Jinsong Reese, Timothy Wu, Yaotang El Fakhri, Georges Ackerman, Jerome TI Accurate measurement of bone attenuation in PET-MR SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Huang, Chuan] Stony Brook Med, Psychiat, Radiol, Stony Brook, NY USA. [Ouyang, Jinsong; Reese, Timothy; El Fakhri, Georges; Ackerman, Jerome] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wu, Yaotang] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 258 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738800258 ER PT J AU Papisov, M Belov, V Fischman, A Bonab, A Levine, D Shi, RN AF Papisov, Mikhail Belov, Vasily Fischman, Alan Bonab, Ali Levine, Dylan Shi, Rena TI The dynamics of intrathecal bolus and cerebrospinal solute transport SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Papisov, Mikhail; Belov, Vasily; Bonab, Ali; Levine, Dylan; Shi, Rena] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Papisov, Mikhail; Belov, Vasily; Bonab, Ali] Harvard Univ, Sch Med, Boston, MA USA. [Fischman, Alan] Shriners Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 1555 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738803175 ER PT J AU Rotstein, B Wang, L Stephenson, N Patteson, J Liang, S Vasdev, N AF Rotstein, Benjamin Wang, Lu Stephenson, Nickeisha Patteson, Jonathan Liang, Steven Vasdev, Neil TI F-18-Labeling of iodonium ylides: Translation from labeled compounds to radiopharmaceuticals SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Rotstein, Benjamin; Wang, Lu; Stephenson, Nickeisha; Patteson, Jonathan; Liang, Steven; Vasdev, Neil] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Adv Mol Imaging Sci Nucl Med & Mol Imaging, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 3 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738800004 ER PT J AU Sabet, H Christensen, M El Fakhri, G AF Sabet, Hamid Christensen, Matthew El Fakhri, Georges TI Development of high spatial resolution detector with DOI for PET using laser induced optical barriers SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Sabet, Hamid; Christensen, Matthew; El Fakhri, Georges] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Radiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 1843 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738804024 ER PT J AU Salavati, A Khiewvan, B Houshmand, S Cheng, G Akers, S Werner, T AF Salavati, Ali Khiewvan, Benjapa Houshmand, Sina Cheng, Gang Akers, Scott Werner, Thomas TI The impact of partial volume effect correction on the diagnostic performance of quantitative FDG-PET/CT parameters: A lesion based analysis of suspected lung malignancy. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Salavati, Ali; Khiewvan, Benjapa; Houshmand, Sina; Werner, Thomas] Univ Penn, Philadelphia, PA 19104 USA. [Cheng, Gang; Akers, Scott] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 1387 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738803007 ER PT J AU Serapio, P Hope, M Yee, J Aparici, CM Hope, T AF Serapio, Paulo Hope, Michael Yee, Judy Aparici, Carina Mari Hope, Thomas TI 18F-Sodium Fluoride Uptake in the Abdominal Aorta SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Serapio, Paulo] New York Med Coll, Valhalla, NY 10595 USA. [Serapio, Paulo; Hope, Michael; Yee, Judy; Hope, Thomas] Univ Calif San Francisco, Radiol, San Francisco, CA 94143 USA. [Aparici, Carina Mari] San Francisco VA Med Ctr, Dept Radiol, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 350 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738801001 ER PT J AU Sitek, A Kadrmas, D AF Sitek, Arkadiusz Kadrmas, Dan TI Bayesian Analysis of Multi-Compartment Kinetic Models SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Kadrmas, Dan] Univ Utah, Salt Lake City, UT USA. [Sitek, Arkadiusz] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 623 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738801274 ER PT J AU Sitek, A Normandin, M Wooten, D Alpert, N El Fakhri, G AF Sitek, Arkadiusz Normandin, Marc Wooten, Dustin Alpert, Nathaniel El Fakhri, Georges TI Nonstationary compartmental modeling: application to receptor binding in PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Sitek, Arkadiusz; Normandin, Marc; Wooten, Dustin; Alpert, Nathaniel; El Fakhri, Georges] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Adv Med Imaging Sci, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 626 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738801277 ER PT J AU Wang, MD Guo, N Schaefferkoetter, J Yan, JH Hu, GS Zhang, H El Fakhri, G Li, QZ AF Wang, Mengdie Guo, Ning Schaefferkoetter, Joshua Yan, Jianhua Hu, Guangshu Zhang, Hui El Fakhri, Georges Li, Quanzheng TI Automatic respiratory gating of TOF-PET data using time-of-flight information SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Wang, Mengdie; Hu, Guangshu; Zhang, Hui] Tsinghua Univ, Dept Biomed Engn, Beijing 100084, Peoples R China. [Guo, Ning; El Fakhri, Georges; Li, Quanzheng] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 USA. [Schaefferkoetter, Joshua; Yan, Jianhua] A STAR NUS, Singapore, Singapore. NR 0 TC 0 Z9 0 U1 1 U2 5 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 427 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738801078 ER PT J AU Wang, YB Ulaner, G Manning, HC Bardia, A Mayer, I Dickler, M Maneval, EC Lewis, J Baselga, J Mahmood, U AF Wang, Yingbing Ulaner, Gary Manning, H. Charles Bardia, Aditya Mayer, Ingrid Dickler, Maura Maneval, Edna Chow Lewis, Jason Baselga, Jose Mahmood, Umar TI Validation of target engagement using 18F-fluoroestradiol PET in patients undergoing therapy with selective estrogen receptor degrader, ARN-810 (GDC-0810) SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Wang, Yingbing; Bardia, Aditya; Mahmood, Umar] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ulaner, Gary; Dickler, Maura; Lewis, Jason; Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Manning, H. Charles; Mayer, Ingrid] Vanderbilt Univ, Nashville, TN 37235 USA. [Maneval, Edna Chow] Seragon Pharmaceut, San Diego, CA USA. NR 0 TC 3 Z9 3 U1 0 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 565 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738801216 ER PT J AU Wilks, M Normandin, M Yuan, HS El Fakhri, G Josephson, L AF Wilks, Moses Normandin, Marc Yuan, Hushan El Fakhri, Georges Josephson, Lee TI A Deferoxamine-PEG-like Nanoprobe for Imaging Tumor Fluid Pinocytosis by PET and Fluorescence SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Wilks, Moses; Normandin, Marc; Yuan, Hushan; El Fakhri, Georges; Josephson, Lee] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 1140 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738802110 ER PT J AU Zhang, XM Petibon, Y Sitek, A Takahashi, K Alpert, N El Fakhri, G Guehl, N Kolnick, A Hosseini, SM Ouyang, JS AF Zhang, Xiaomeng Petibon, Yoann Sitek, Arkadiusz Takahashi, Kazue Alpert, Nathaniel El Fakhri, Georges Guehl, Nicolas Kolnick, Aleksandra Hosseini, Seyed Mohammadreza Ouyang, Jinsong TI In-vivo Simultaneous DCE-MRI/O-15-water-PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging CY JUN 06-10, 2015 CL Baltimore, MD SP Soc Nucl Med & Mol Imaging C1 [Zhang, Xiaomeng; Petibon, Yoann; Sitek, Arkadiusz; Takahashi, Kazue; Alpert, Nathaniel; El Fakhri, Georges; Guehl, Nicolas; Kolnick, Aleksandra; Hosseini, Seyed Mohammadreza; Ouyang, Jinsong] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Ctr Adv Radiol Sci, Boston, MA 02114 USA. [Zhang, Xiaomeng; Petibon, Yoann; Sitek, Arkadiusz; Takahashi, Kazue; Alpert, Nathaniel; El Fakhri, Georges; Guehl, Nicolas; Kolnick, Aleksandra; Hosseini, Seyed Mohammadreza; Ouyang, Jinsong] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 3 SU 3 MA 644 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN9AU UT WOS:000358738801295 ER PT J AU Fikry, K Blute, ML Sundt, TM McKeen, M AF Fikry, Karim Blute, Michael L. Sundt, Thoralf M., III McKeen, Mark TI Emergency Cardiopulmonary Bypass for Massive Pulmonary Embolism Occurring During Nephrectomy SO A & A CASE REPORTS LA English DT Article ID RENAL-CELL CARCINOMA; VENOUS TUMOR THROMBUS; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; PROGNOSTIC-SIGNIFICANCE; SURGICAL-MANAGEMENT; EXTENSION; COMPLICATIONS; VEIN AB We report a case of cardiac arrest secondary to pulmonary tumor embolization occurring in a patient undergoing nephrectomy for renal cell carcinoma with a tumor thrombus invading the inferior vena cava infrahepatically. Tumor embolization in such cases is very rare (1.5%), but if it occurs, mortality is 75%. In our case, resources were rapidly mobilized, and cardiopulmonary bypass was initiated for pulmonary embolectomy within 34 minutes of the cardiac arrest. The patient's trachea was extubated on postoperative day 1, and he was discharged home 9 days later neurologically intact. Excellent preoperative and intraoperative communication among all involved health care providers, as well as rapid mobilization of the available resources, played important roles in the patient's positive outcome. C1 [Fikry, Karim; McKeen, Mark] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Blute, Michael L.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Sundt, Thoralf M., III] Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. RP Fikry, K (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM kfikry@mgh.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2325-7237 J9 A A CASE REP JI A A Case Rep. PD MAY 1 PY 2015 VL 4 IS 9 BP 117 EP 119 DI 10.1213/XAA.0000000000000142 PG 3 WC Anesthesiology SC Anesthesiology GA CM3HC UT WOS:000357571700003 PM 25909776 ER PT J AU Black, H Gonzalez, R Priolo, C Schapira, MM Sonnad, SS Hanson, CW Langlotz, CP Howell, JT Apter, AJ AF Black, Heather Gonzalez, Rodalyn Priolo, Chantel Schapira, Marilyn M. Sonnad, Seema S. Hanson, C. William, III Langlotz, Curtis P. Howell, John T. Apter, Andrea J. TI True "Meaningful Use": Technology Meets Both Patient and Provider Needs SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID ELECTRONIC MEDICAL-RECORDS; HEALTH-CARE; ATTITUDES; ADOPTION; OUTCOMES; IMPLEMENTATION; PHYSICIANS; PORTALS; ACCESS; ASTHMA AB Objectives: Voluntary patient uptake and use of electronic health record (EHR) features have been low. It is unknown whether EHRs fully meet needs of providers or patients with chronic diseases. Study Design: To explore in-depth user experiences, we conducted 6 focus groups: 3 of patients followed by 3 of providers discussing 2 key EHR components: the after-visit summary (AVS) and the patient portal (PP). Focus groups were audio-recorded, transcribed, and analyzed by 3 independent coders. Methods: Participants with moderate-to-severe asthma and prevalent comorbidities were recruited from 4 primary care and 2 asthma clinics serving low-income urban neighborhoods. Participants discussed their expectations and experience using the AVS and PP, and responded to prototype formats of these features. Additionally, one-on-one interviews were conducted with 10 patients without PP experience to assess their ability to use the system. Results: The 21 patient and 13 provider perspectives differed regarding AVS features and use. Patients wanted a unified view of their medical issues and health management tools, while providers wanted to focus on recommendations from 1 visit at a time. Both groups advocated improving the AVS format and content. Lack of awareness and knowledge about the PP was patients' largest barrier, and was traced back to providers' lack of PP training. Conclusions: Our results underscore the importance of user-centered design when constructing the content and features of the EHR. As technology evolves, an ongoing understanding of patient and provider experiences will be critical to improve uptake, increase use, and ensure engagement, optimizing the potential of EHRs. C1 [Black, Heather; Gonzalez, Rodalyn; Priolo, Chantel; Apter, Andrea J.] Div Pulm Allergy & Crit Care Med, Sect Allergy & Immunol, Philadelphia, PA USA. [Black, Heather; Gonzalez, Rodalyn; Priolo, Chantel; Schapira, Marilyn M.; Apter, Andrea J.] Dept Med, Philadelphia, PA USA. [Langlotz, Curtis P.] Dept Radiol, Philadelphia, PA USA. [Black, Heather; Gonzalez, Rodalyn; Priolo, Chantel; Schapira, Marilyn M.; Hanson, C. William, III; Langlotz, Curtis P.; Howell, John T.; Apter, Andrea J.] Univ Penn, Philadelphia, PA 19104 USA. [Schapira, Marilyn M.] Dept Vet Affairs Med Ctr, Ctr Hlth Equ Res Program, Philadelphia, PA 19104 USA. [Sonnad, Seema S.] Christiana Care Hlth Syst, Value Inst, Wilmington, DE USA. RP Apter, AJ (reprint author), Hosp Univ Penn, 829 Gates Bldg,3600 Spruce St, Philadelphia, PA 19104 USA. EM apter@mail.med.upenn.edu FU University of Pennsylvania Research Foundation; University of Pennsylvania Health System FX This study was funded by the University of Pennsylvania Research Foundation and Bach Fund Grant of the University of Pennsylvania Health System. These foundations had no role in study design; in data collection; analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 25 TC 1 Z9 1 U1 6 U2 15 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD MAY PY 2015 VL 21 IS 5 BP E329 EP E337 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN8BI UT WOS:000358661300006 PM 26167781 ER PT J AU Ogbechie, OA Hsu, J AF Ogbechie, Oluwatobi Awele Hsu, John TI Systematic Review of Benefit Designs With Differential Cost Sharing for Prescription Drugs SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Review ID CONVERTING-ENZYME-INHIBITORS; INCENTIVE-BASED FORMULARIES; INSURANCE DESIGN; 3-TIER FORMULARY; ANTIDEPRESSANT UTILIZATION; MEDICAL UTILIZATION; PHARMACY BENEFIT; IMPACT; COPAYMENTS; CARE AB Objectives: To evaluate the effects of health insurance benefit designs that introduced or increased the price difference between prescription drugs representing potential clinical substitutes. Study Design: Systematic review of peer-reviewed articles. Methods: Using English-language articles listed in PubMed between 1980 and 2012, we identified articles meeting our inclusion criteria and minimum methodological standards. We compared findings regarding the immediate patient response, total spending, and health outcomes after implementing the price change. Results: Among the 31 articles identified, the mechanisms varied for creating the price differential between prescription drug substitutes, though they most frequently involved tiered formularies (19) or reference pricing (10). While nearly all studies (29 of 31) reported on patient responses to price changes, only 5 articles comprehensively assessed patient price responses, total spending, and health outcomes. Several studies found that some patients switched to cheaper drugs, but out-of-pocket spending increased on average, suggesting that other patients continued using the more expensive drug (ie, cost shifting to patients). Few studies examined the degree of heterogeneity in behavior responses, especially between patient cohorts for whom the substitute drugs had varying value. Some studies observed long-term effects, but most had limited post intervention observation periods. Conclusions: Differential cost-sharing designs influence drug use behavior, but there is limited evidence on how these designs affect the overall value of received care. The existing literature provides limited guidance for policy makers or organizational leaders to design benefits. We offer suggestions for future studies to inform policy and practice. C1 [Hsu, John] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Ogbechie, Oluwatobi Awele; Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02114 USA. RP Hsu, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Rm 901B, Boston, MA 02114 USA. EM jhsu7@partners.org FU NIH [R01AG029316, R01CA164023] FX NIH R01AG029316 and R01CA164023. NR 51 TC 0 Z9 0 U1 2 U2 3 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD MAY PY 2015 VL 21 IS 5 BP E338 EP + PG 12 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN8BI UT WOS:000358661300007 PM 26167782 ER PT J AU Oldenburg, CE Perez-Brumer, AG Biello, KB Landers, SJ Rosenberger, JG Novak, DS Mayer, KH Mimiaga, MJ AF Oldenburg, Catherine E. Perez-Brumer, Amaya G. Biello, Katie B. Landers, Stewart J. Rosenberger, Joshua G. Novak, David S. Mayer, Kenneth H. Mimiaga, Matthew J. TI Transactional Sex Among Men Who Have Sex With Men in Latin America: Economic, Sociodemographic, and Psychosocial Factors SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SEXUALLY-TRANSMITTED INFECTIONS; MIDDLE-INCOME COUNTRIES; HIV RISK BEHAVIOR; SYPHILIS PREVALENCE; WORKERS; BRAZIL; SEEKING; HEALTH; ABUSE; WOMEN AB Objectives. We assessed factors associated with engagement in transactional sex among men who have sex with men recruited from one of the largest Internet sites for men seeking social or sexual interactions with other men in Latin America. Methods. We constructed multilevel logistic regression models to analyze factors associated with engagement in transactional sex in 17 Latin American countries in 2012. Results. Of 24 051 respondents, 1732 (7.2%) reported being paid for sexual intercourse in the past 12 months. In a multivariable model, higher country-level unemployment was associated with increased odds of transactional sex (adjusted odds ratio [AOR] = 1.07 per 1% increase in unemployment; 95% confidence interval [CI] = 1.00, 1.13). Individual or interpersonal factors associated with increased odds of engagement in transactional sex included self-reported HIV (AOR= 1.33; 95% CI = 1.04, 1.69) or sexually transmitted infection (AOR = 1.33; 95% CI = 1.11, 1.59), childhood sexual abuse history (AOR = 1.75; 95% CI = 1.48, 2.06), intimate partner violence (past 5 years, AOR= 1.68; 95% CI = 1.45, 1.95), and sexual compulsivity (AOR= 1.77; 95% CI = 1.49, 2.11). Conclusions. Structural-level economic interventions and those that address individual and interpersonal factors may improve HIV prevention efforts among men who have sex with men who engage in transactional sex. C1 [Oldenburg, Catherine E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Perez-Brumer, Amaya G.] Columbia Univ, Dept Sociomed Sci, New York, NY USA. [Biello, Katie B.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Landers, Stewart J.] John Snow Inc, Boston, MA USA. [Rosenberger, Joshua G.] George Mason Univ, Dept Global & Community Hlth, Fairfax, VA 22030 USA. [Novak, David S.] Online Buddies Inc, OLB Res Inst, Cambridge, MA USA. [Mimiaga, Matthew J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Oldenburg, CE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM ceo242@mail.harvard.edu FU National Institute of Allergy and Infectious Disease (National Research Service Award [NRSA]) [T32 AI007535]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NRSA) [T32 HD049339]; National Institute on Drug Abuse, National Institutes of Health [R21DA035113, R21DA033720] FX This work was supported by the National Institute of Allergy and Infectious Disease (National Research Service Award [NRSA] grant T32 AI007535 to C. E. O.); the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NRSA grant T32 HD049339 to A. P. B.); and the National Institute on Drug Abuse, National Institutes of Health (awards R21DA035113 and R21DA033720 to M. J. M., K. B. B., and K. H. M.). NR 43 TC 5 Z9 5 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2015 VL 105 IS 5 BP E95 EP E102 DI 10.2105/AJPH.2014.302402 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CN3AN UT WOS:000358295600021 PM 25790381 ER PT J AU Agranat, MB Ashitkov, SI Ovchinnikov, AV Sitnikov, DS Yurkevich, AA Chefonov, OV Perel'man, LT Anisimov, SI Fortov, VE AF Agranat, M. B. Ashitkov, S. I. Ovchinnikov, A. V. Sitnikov, D. S. Yurkevich, A. A. Chefonov, O. V. Perel'man, L. T. Anisimov, S. I. Fortov, V. E. TI Thermal emission of hot electrons in a metal SO JETP LETTERS LA English DT Article ID NONEQUILIBRIUM ELECTRON; LATTICE TEMPERATURES; NOBLE-METALS; DYNAMICS; PHOTOLUMINESCENCE; SPECTROSCOPY; TRANSPORT; SURFACES; PULSES AB The first reliable observation of emission from a hot gas of free electrons in a metal with a cold lattice is reported. The emission is observed upon the irradiation of the metal with femtosecond laser pulses. The distinctive feature of this emission as compared to the case of equilibrium heating is the dependence of the emission quantum yield on the parameters of the electron-phonon interaction. C1 [Agranat, M. B.; Ashitkov, S. I.; Ovchinnikov, A. V.; Sitnikov, D. S.; Yurkevich, A. A.; Chefonov, O. V.; Fortov, V. E.] Russian Acad Sci, Joint Inst High Temp, Moscow 125412, Russia. [Perel'man, L. T.] Harvard Univ, Ctr Adv Biomed Imaging & Photon, BIDMC, Boston, MA 02215 USA. [Anisimov, S. I.] Russian Acad Sci, Landau Inst Theoret Phys, Chernogolovka 142432, Moscow Region, Russia. RP Agranat, MB (reprint author), Russian Acad Sci, Joint Inst High Temp, Moscow 125412, Russia. EM sitnik.ds@gmail.com FU Russian Science Foundation [14-50-00124] FX This study was supported by the Russian Science Foundation (project no. 14-50-00124). NR 27 TC 1 Z9 1 U1 4 U2 12 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0021-3640 EI 1090-6487 J9 JETP LETT+ JI Jetp Lett. PD MAY PY 2015 VL 101 IS 9 BP 598 EP 602 DI 10.1134/S0021364015090039 PG 5 WC Physics, Multidisciplinary SC Physics GA CN6WX UT WOS:000358576200003 ER PT J AU Beloiartsev, A Rodrigues-Machado, MD Zhou, GL Tan, TC Zazzeron, L Tainsh, RE Leyton, P Jones, RC Scherrer-Crosbie, M Zapol, WM AF Beloiartsev, Arkadi Rodrigues-Machado, Maria da Gloria Zhou, Guo Ling Tan, Timothy C. Zazzeron, Luca Tainsh, Robert E. Leyton, Patricio Jones, Rosemary C. Scherrer-Crosbie, Marielle Zapol, Warren M. TI Pulmonary Hypertension after Prolonged Hypoxic Exposure in Mice with a Congenital Deficiency of Cyp2j SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE hypoxia; cytochrome P450 epoxygenases; pulmonary vascular remodeling; right ventricular hypertrophy ID SOLUBLE EPOXIDE HYDROLASE; ARACHIDONIC-ACID METABOLITES; SMOOTH-MUSCLE-CELLS; EPOXYEICOSATRIENOIC ACIDS; NITRIC-OXIDE; ERYTHROPOIETIN PRODUCTION; CYTOCHROME-P450; VASOCONSTRICTION; EXPRESSION; RATS AB Cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids contribute to the regulation of pulmonary vascular tone and hypoxic pulmonary vasoconstriction. We investigated whether the attenuated acute vasoconstrictor response to hypoxic exposure of Cyp2j(-/-) mice would protect these mice against the pulmonary vascular remodeling and hypertension associated with prolonged exposure to hypoxia. Cyp2j(-/-) and Cyp2j(+/+) male and female mice continuously breathed an inspired oxygen fraction of 0.21 (normoxia) or 0.10 (hypoxia) in a normobaric chamber for 6 weeks. We assessed hemoglobin (Hb) concentrations, right ventricular (RV) systolic pressure (RVSP), and transthoracic echocardiographic parameters (pulmonary acceleration time [PAT] and RV wall thickness). Pulmonary Cyp2c29, Cyp2c38, and sEH mRNA levels were measured in Cyp2j(-/-) and Cyp2j(-/-) male mice. At baseline, Cyp2j(-/-) and Cyp2j(+/+) mice had similar Hb levels and RVSP while breathing air. After 6 weeks of hypoxia, circulating Hb concentrations increased but did not differ between Cyp2j(-/-) and Cyp2j(+/+) mice. Chronic hypoxia increased RVSP in Cyp2j(-/-) and Cyp2j(+/+) mice of either gender. Exposure to chronic hypoxia decreased PAT and increased RV wall thickness in both genotypes and genders to a similar extent. Prolonged exposure to hypoxia produced similar levels of RV hypertrophy in both genotypes of either gender. Pulmonary Cyp2c29, Cyp2c38, and sEH mRNA levels did not differ between Cyp2j(-/-) and Cyp2j(+/+) male mice after breathing at normoxia or hypoxia for 6 weeks. These results suggest that murine Cyp2j deficiency does not attenuate the development of murine pulmonary vascular remodeling and hypertension associated with prolonged exposure to hypoxia in mice of both genders. C1 [Beloiartsev, Arkadi; Rodrigues-Machado, Maria da Gloria; Zazzeron, Luca; Tainsh, Robert E.; Leyton, Patricio; Jones, Rosemary C.; Zapol, Warren M.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Zhou, Guo Ling] Anesthesia Ctr Crit Care Res, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Tan, Timothy C.; Scherrer-Crosbie, Marielle] Anesthesia Ctr Crit Care Res, Div Cardiol, Dept Med, Boston, MA 02114 USA. [Tan, Timothy C.; Scherrer-Crosbie, Marielle] Harvard Univ, Sch Med, Boston, MA USA. RP Zapol, WM (reprint author), Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Anesthesia, 55 Fruit St,Thier 503, Boston, MA 02114 USA. EM wzapol@mgh.harvard.edu FU CAPES/National Institute of Science and Technology in Nanobiopharmaceutics-UFMG, Minas Gerais, Brazil; National Institutes of Health/National Heart, Lung, and Blood Institute Shared Equipment Grant [1S10RR022586-01A1] FX This work was supported by a postdoctoral fellowship from CAPES/National Institute of Science and Technology in Nanobiopharmaceutics-UFMG, Minas Gerais, Brazil (M.d.G.R.-M.). The use of the 30-MHz transducer Vevo 770 was supported by National Institutes of Health/National Heart, Lung, and Blood Institute Shared Equipment Grant 1S10RR022586-01A1. NR 42 TC 2 Z9 2 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAY PY 2015 VL 52 IS 5 BP 563 EP 570 DI 10.1165/rcmb.2013-0482OC PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA CN2DH UT WOS:000358230200005 PM 25233285 ER PT J AU David, LA Weil, A Ryan, ET Calderwood, SB Harris, JB Chowdhury, F Begum, Y Qadri, F LaRocque, RC Turnbaugh, PJ AF David, Lawrence A. Weil, Ana Ryan, Edward T. Calderwood, Stephen B. Harris, Jason B. Chowdhury, Fahima Begum, Yasmin Qadri, Firdausi LaRocque, Regina C. Turnbaugh, Peter J. TI Gut Microbial Succession Follows Acute Secretory Diarrhea in Humans SO MBIO LA English DT Article ID EARLY-CHILDHOOD DIARRHEA; ENTEROTOXIGENIC ESCHERICHIA-COLI; VIBRIO-CHOLERAE INFECTION; RICE-WATER STOOL; INTESTINAL MICROFLORA; COLONIZATION FACTORS; ASIATIC CHOLERA; YOUNG-CHILDREN; COG DATABASE; IN-VIVO AB Disability after childhood diarrhea is an important burden on global productivity. Recent studies suggest that gut bacterial communities influence how humans recover from infectious diarrhea, but we still lack extensive data and mechanistic hypotheses for how these bacterial communities respond to diarrheal disease and its treatment. Here, we report that after Vibrio cholerae infection, the human gut microbiota undergoes an orderly and reproducible succession that features transient reversals in relative levels of enteric Bacteroides and Prevotella. Elements of this succession may be a common feature in microbiota recovery from acute secretory diarrhea, as we observed similar successional dynamics after enterotoxigenic Escherichia coli (ETEC) infection. Our metagenomic analyses suggest that multiple mechanisms drive microbial succession after cholera, including bacterial dispersal properties, changing enteric oxygen and carbohydrate levels, and phage dynamics. Thus, gut microbiota recovery after cholera may be predictable at the level of community structure but is driven by a complex set of temporally varying ecological processes. Our findings suggest opportunities for diagnostics and therapies targeting the gut microbiota in humans recovering from infectious diarrhea. IMPORTANCE Disability after diarrhea is a major burden on public health in the developing world. Gut bacteria may affect this recovery, but it remains incompletely understood how resident microbes in the digestive tract respond to diarrheal illness. Here, we observed an orderly and reproducible succession of gut bacterial groups after cholera in humans. Genomic analyses associated the succession with bacterial dispersal in food, an altered microbial environment, and changing phage levels. Our findings suggest that it may one day be feasible to manage resident bacterial populations in the gut after infectious diarrhea. C1 [David, Lawrence A.] Harvard Univ, Soc Fellows, Cambridge, MA 02138 USA. [David, Lawrence A.; Turnbaugh, Peter J.] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. [Weil, Ana; Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.; LaRocque, Regina C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Weil, Ana; Ryan, Edward T.; Calderwood, Stephen B.; LaRocque, Regina C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Chowdhury, Fahima; Begum, Yasmin; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, Dhaka 1000, Bangladesh. RP LaRocque, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM rclarocque@partners.org; Peter.Turnbaugh@ucsf.edu OI Turnbaugh, Peter/0000-0002-0888-2875 FU ICDDR,B; National Institutes of Health, National Institute of Allergy and Infectious Diseases [U01 AI058935, U01 AI106878, R01 AI03055, P50 GM068763, T32 AI070611976]; Harvard University's William F. Milton Fund; Duke University's Whitehead Scholars Program; Alfred P. Sloan Research Fellowship; Physician-Scientist Early Career Award from the Howard Hughes Medical Institute; Harvard Bauer Fellows program FX This work was supported by the ICDDR,B and its donors, which provide unrestricted support to ICDDR,B for its operations and research. This study was also supported by grants from the National Institutes of Health, including the following National Institute of Allergy and Infectious Diseases grants: U01 AI058935 (S.B.C. and E.T.R.), U01 AI106878 (E.T.R. and F.Q.), R01 AI03055 (J.B.H.), P50 GM068763 (P.J.T.), and T32 AI070611976 (A.W.). Support for L.D. was provided by Harvard University's William F. Milton Fund, Duke University's Whitehead Scholars Program, and an Alfred P. Sloan Research Fellowship. R.C.L. was supported by a Physician-Scientist Early Career Award from the Howard Hughes Medical Institute. P.J.T. was supported by the Harvard Bauer Fellows program. NR 84 TC 15 Z9 15 U1 6 U2 19 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAY-JUN PY 2015 VL 6 IS 3 AR e00381-15 DI 10.1128/mBio.00381-15 PG 14 WC Microbiology SC Microbiology GA CM7JH UT WOS:000357867400025 PM 25991682 ER PT J AU Nikolajski, C Miller, E McCauley, HL Akers, A Schwarz, EB Freedman, L Steinberg, J Ibrahim, S Borrero, S AF Nikolajski, Cara Miller, Elizabeth McCauley, Heather L. Akers, Aletha Schwarz, Eleanor Bimla Freedman, Lori Steinberg, Julia Ibrahim, Said Borrero, Sonya TI Race and Reproductive Coercion: A Qualitative Assessment SO WOMENS HEALTH ISSUES LA English DT Article ID INTIMATE PARTNER VIOLENCE; UNINTENDED PREGNANCY; CONTRACEPTIVE USE; FEMALE ADOLESCENTS; UNITED-STATES; EXPERIENCES; WOMEN; DISCONTINUATION; DISPARITIES; ATTITUDES AB Background: Unintended pregnancy is common and disproportionately occurs among low-income and African-American (AA) women. Male partners may influence women's risk of unintended pregnancy through reproductive coercion, although studies have not assessed whether racial differences in reproductive coercion impact AA women's disparate risk for unintended pregnancy. We sought to describe women's experiences with pregnancy-promoting behaviors by male partners and explore differences in such experiences by race. Methods: Semistructured interviews were conducted with low-income, AA and White women aged 18 to 45 years recruited from reproductive health clinics in Western Pennsylvania to explore contextual factors that shape women's contraceptive behaviors. Narratives were analyzed using content analysis and the constant comparison method. Findings: Among the 66 participants (36 AA and 30 White), 25 (38%) described experiences with male partner reproductive coercion. Narratives provided accounts of contraceptive sabotage, verbal pressure to promote pregnancy and specific pregnancy outcomes, and potential motives behind these behaviors. AA women in the sample reported experiences of reproductive coercion more often than White women (53% and 20%, respectively). AA women were also more likely than White women to attribute a current or prior pregnancy to reproductive coercion. AA women identified relationship transiency and impending incarceration as potential motivations for men to secure a connection with a female partner via pregnancy. Conclusions: Our findings suggest that reproductive coercion may be a factor contributing to disparities in unintended pregnancy. More research, including population-level studies, is needed to determine the impact of reproductive coercion on unintended pregnancy and to understand the social and structural factors associated with pregnancy-promoting behaviors. Published by Elsevier Inc. C1 [Nikolajski, Cara; Schwarz, Eleanor Bimla; Borrero, Sonya] Univ Pittsburgh, Ctr Res Hlth Care, Dept Med, Pittsburgh, PA 15213 USA. [Miller, Elizabeth; McCauley, Heather L.] Childrens Hosp Pittsburgh, Dept Pediat, Div Adolescent Med, Pittsburgh, PA 15213 USA. [Miller, Elizabeth] Univ Pittsburgh, Sch Med, Pediat, Pittsburgh, PA 15213 USA. [Akers, Aletha; Schwarz, Eleanor Bimla] Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Freedman, Lori] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Oakland, CA USA. [Steinberg, Julia] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Ibrahim, Said] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ibrahim, Said] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [McCauley, Heather L.] Univ Pittsburgh, Pediat, Pittsburgh, PA 15213 USA. [Akers, Aletha] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. [Schwarz, Eleanor Bimla] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. RP Borrero, S (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM borrerosp@upmc.edu OI Freedman, Lori/0000-0002-7919-9520 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), a component of the National Institutes of Health (NIH) [1 R21 HD068736-01]; NICHD [K01 D075834] FX This study was made possible by Dr. Borrero's grant (1 R21 HD068736-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), a component of the National Institutes of Health (NIH). Dr. Steinberg's effort on this project was funded by her K01 grant from NICHD (K01 D075834). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of NICHD or NIH. NR 42 TC 4 Z9 4 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD MAY-JUN PY 2015 VL 25 IS 3 BP 216 EP 223 DI 10.1016/j.whi.2014.12.004 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA CN7HG UT WOS:000358604400005 PM 25748823 ER PT J AU Horner-Johnson, W Dobbertin, K Iezzoni, LI AF Horner-Johnson, Willi Dobbertin, Konrad Iezzoni, Lisa I. TI Disparities in Receipt of Breast and Cervical Cancer Screening for Rural Women Age 18 to 64 with Disabilities SO WOMENS HEALTH ISSUES LA English DT Article ID HEALTH-CARE ACCESS; UNITED-STATES; MOBILITY IMPAIRMENTS; PREVENTIVE SERVICES; MAMMOGRAPHY; BARRIERS; METAANALYSIS; LIMITATIONS; CARCINOMA AB Background: Previous research has found breast and cervical cancer screening disparities between women with and without disabilities, and between women living in rural versus urban areas. Living in a rural area may add to the barriers women with disabilities experience when attempting to obtain screening for breast and cervical cancer. The purpose of this study was to examine the combination of disability status and rurality in association with receipt of breast and cervical cancer screening among women age 18 to 64 in the United States. Methods: We conducted cross-sectional analyses of data from the Medical Expenditure Panel Survey, using pooled annual data files from 2002 through 2008. We compared recent receipt of breast and cervical cancer screening among four groups: 1) urban women without disabilities, 2) urban women with disabilities, 3) rural women without disabilities, and 4) rural women with disabilities. Findings: Overall, women with disabilities were less likely to be up to date with mammograms and Pap tests compared with women with no disabilities. Similarly, women in rural areas were less likely to have received breast or cervical cancer screening within recommended timeframes. Women who both had a disability and lived in a rural area were the least likely to be current with screening. Conclusions: Our findings suggest that living in rural regions compounds disparities in receipt of cancer screening among women with disabilities. Increased attention is needed to improve receipt of cancer screening among rural women with disabilities. Copyright (C) 2015 by the Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Horner-Johnson, Willi; Dobbertin, Konrad] Oregon Hlth & Sci Univ, Inst Dev & Disabil, Portland, OR 97239 USA. [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Horner-Johnson, W (reprint author), Oregon Hlth & Sci Univ, Inst Dev & Disabil, 707 SW Gaines St, Portland, OR 97239 USA. EM hornerjo@ohsu.edu FU National Center on Birth Defects and Developmental Disabilities (NCBDDD), Centers for Disease Control and Prevention (CDC) [U59DD00942]; Administration on Intellectual and Developmental Disabilities [90DD0684]; Institute on Development & Disability at Oregon Health & Science University; National Institute on Disability and Rehabilitation Research (NIDRR), U.S. Department of Education [H133A080031]; Agency for Healthcare Research and Quality (AHRQ) [K12HS022981] FX This research was supported in part by cooperative agreement #U59DD00942 from the National Center on Birth Defects and Developmental Disabilities (NCBDDD), Centers for Disease Control and Prevention (CDC); grant #90DD0684 from the Administration on Intellectual and Developmental Disabilities; and by the Institute on Development & Disability at Oregon Health & Science University. Development of the analytic dataset used in this study was supported in part by grant #H133A080031 from the National Institute on Disability and Rehabilitation Research (NIDRR), U.S. Department of Education. Additional support for Dr. Horner-Johnson's time was provided by grant #K12HS022981 from the Agency for Healthcare Research and Quality (AHRQ). The content of this material does not necessarily reflect the views and policies of CDC, NCBDDD, NIDRR, or AHRQ. NR 33 TC 3 Z9 3 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD MAY-JUN PY 2015 VL 25 IS 3 BP 246 EP 253 DI 10.1016/j.whi.2015.02.004 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA CN7HG UT WOS:000358604400009 PM 25864023 ER PT J AU Martinez, EA Beaulieu, N Gibbons, R Pronovost, P Wang, T AF Martinez, Elizabeth A. Beaulieu, Nancy Gibbons, Robert Pronovost, Peter Wang, Thomas TI Organizational Culture and Performance SO AMERICAN ECONOMIC REVIEW LA English DT Article; Proceedings Paper CT 127th Annual Meeting of the American-Economic-Association CY JAN 03-05, 2015 CL Boston, MA SP Amer Econ Assoc ID BLOOD-STREAM INFECTIONS C1 [Martinez, Elizabeth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Beaulieu, Nancy] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gibbons, Robert; Wang, Thomas] MIT, Cambridge, MA 02142 USA. [Pronovost, Peter] Johns Hopkins Univ, Sch Med, Armstrong Inst Patient Safety & Qual, Baltimore, MD 21202 USA. EM beaulieu@hsph.harvard.edu; rgib-bons@mit.edu; ppronovo@jhmi.edu; td_wang@mit.edu3 FU MIT Sloan School's Program on Innovation in Markets and Organizations FX Martinez: Formerly of Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114; Beaulieu: Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115 (e-mail: beaulieu@hsph.harvard.edu); Gibbons: MIT, 100 Main Street, Cambridge, MA 02142 (e-mail: rgibbons@mit.edu); Pronovost: Armstrong Institute for Patient Safety and Quality, Johns Hopkins University School of Medicine, 750 E Pratt Street, 15th Floor, Baltimore, MD 21202 (e-mail: ppronovo@jhmi.edu); Wang: MIT, 100 Main Street, Cambridge, MA 02142 (e-mail: td_wang@mit.edu3). We are very grateful for comments from David Cutler, Joe Doyle, Ann Orloff, Edgar Schein, and Doug Staiger, and financial support from the MIT Sloan School's Program on Innovation in Markets and Organizations. We dedicate this paper to our late colleague and co-author Dr. Elizabeth Martinez. In her quiet and inspiring way, Elizabeth brought us together, showed us the goal, launched us toward achieving it, and insisted that we could finish. The remaining authors are ordered alphabetically, as conventional in economics if not in medicine. NR 23 TC 0 Z9 0 U1 5 U2 20 PU AMER ECONOMIC ASSOC PI NASHVILLE PA 2014 BROADWAY, STE 305, NASHVILLE, TN 37203 USA SN 0002-8282 EI 1944-7981 J9 AM ECON REV JI Am. Econ. Rev. PD MAY PY 2015 VL 105 IS 5 BP 331 EP 335 DI 10.1257/aer.p20151001 PG 5 WC Economics SC Business & Economics GA CM8EF UT WOS:000357929400061 ER PT J AU Tripathy, D Cobb, JE Gall, W Adam, KP George, T Schwenke, DC Banerji, M Bray, GA Buchanan, TA Clement, SC Henry, RR Kitabchi, AE Mudaliar, S Ratner, RE Stentz, FB Reaven, PD Musi, N Ferrannini, E DeFronzo, RA AF Tripathy, Devjit Cobb, Jeff E. Gall, Walter Adam, Klaus-Peter George, Tabitha Schwenke, Dawn C. Banerji, MaryAnn Bray, George A. Buchanan, Thomas A. Clement, Stephen C. Henry, Robert R. Kitabchi, Abbas E. Mudaliar, Sunder Ratner, Robert E. Stentz, Frankie B. Reaven, Peter D. Musi, Nicolas Ferrannini, Ele DeFronzo, Ralph A. TI A Novel Insulin Resistance Index to Monitor Changes in Insulin Sensitivity and Glucose Tolerance: the ACT NOW Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TYPE-2 DIABETES-MELLITUS; IMPAIRED FASTING GLUCOSE; HEPATIC FAT-CONTENT; BETA-CELL FUNCTION; LIFE-STYLE; PIOGLITAZONE; PREVENTION; METABOLISM; ROSIGLITAZONE; METABONOMICS AB Objective: The objective was to test the clinical utility of Quantose M-Q to monitor changes in insulin sensitivity after pioglitazone therapy in prediabetic subjects. Quantose M-Q is derived from fasting measurements of insulin, alpha-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal. Research Design and Methods: Participants were 428 of the total of 602 ACT NOW impaired glucose tolerance (IGT) subjects randomized to pioglitazone (45 mg/d) or placebo and followed for 2.4 years. At baseline and study end, fasting plasma metabolites required for determination of Quantose, glycated hemoglobin, and oral glucose tolerance test with frequent plasma insulin and glucose measurements to calculate the Matsuda index of insulin sensitivity were obtained. Results: Pioglitazone treatment lowered IGT conversion to diabetes (hazard ratio = 0.25; 95% confidence interval = 0.13-0.50; P < .0001). Although glycated hemoglobin did not track with insulin sensitivity, Quantose M-Q increased in pioglitazone-treated subjects (by 1.45 [3.45] mg.min(-1).kg(wbm)(-1)) (median [interquartile range]) (P < .001 vs placebo), as did the Matsuda index (by 3.05 [4.77] units; P < .0001). Quantose M-Q correlated with the Matsuda index at baseline and change in the Matsuda index from baseline (rho, 0.85 and 0.79, respectively; P < .0001) and was progressively higher across closeout glucose tolerance status (diabetes, IGT, normal glucose tolerance). In logistic models including only anthropometric and fasting measurements, Quantose M-Q outperformed both Matsuda and fasting insulin in predicting incident diabetes. Conclusions: In IGT subjects, Quantose M-Q parallels changes in insulin sensitivity and glucose tolerance with pioglitazone therapy. Due to its strong correlation with improved insulin sensitivity and its ease of use, Quantose M-Q may serve as a useful clinical test to identify and monitor therapy in insulin-resistant patients. C1 [Tripathy, Devjit; Musi, Nicolas; DeFronzo, Ralph A.] Univ Texas Hlth Sci Ctr San Antonio, Texas Diabet Inst, San Antonio, TX 78229 USA. [Tripathy, Devjit; Musi, Nicolas; DeFronzo, Ralph A.] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78228 USA. [Cobb, Jeff E.; Gall, Walter; Adam, Klaus-Peter; George, Tabitha] Metabolon Inc, Durham, NC 27713 USA. [Schwenke, Dawn C.; Reaven, Peter D.] Phoenix VA Hlth Care Syst, Phoenix, AZ 85012 USA. [Schwenke, Dawn C.] Arizona State Univ, Coll Nursing & Hlth Care Innovat, Phoenix, AZ 85004 USA. [Banerji, MaryAnn] SUNY Hlth Sci Ctr Brooklyn, Brooklyn, NY 11203 USA. [Bray, George A.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Henry, Robert R.; Mudaliar, Sunder] VA San Diego Healthcare Syst, San Diego, CA 92161 USA. [Henry, Robert R.; Mudaliar, Sunder] Univ Calif San Diego, San Diego, CA 92161 USA. [Kitabchi, Abbas E.; Stentz, Frankie B.] Univ Tennessee, Div Endocrinol Diabet & Metab, Memphis, TN 38163 USA. [Clement, Stephen C.] Inova Fairfax Hosp, Falls Church, VA 22042 USA. [Ratner, Robert E.] Medstar Res Inst, Hyattsville, MD 20782 USA. [Ferrannini, Ele] CNR, Inst Clin Physiol, Dept Clin & Expt Med, I-56126 Pisa, Italy. RP DeFronzo, RA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Diabet, 7703 Floyd Curl Dr,MSC 7886, San Antonio, TX 78229 USA. EM albarado@uthscsa.edu FU National Institutes of Health Grant (CTSA) [UL1TR000130]; HDL Diagnostics Inc.; Phoenix Data Coordinating Center from a Takeda grant; Sanofi Aventis; Merck; Roche; Boehringer-Ingelheim; Takeda; Novartis; BMS; Allergan; AstraZeneca; Eli Lilly; Sanofi-Aventis; Medtronics; Astra-Zeneca; Janssen; Novo Nordisk; Lilly Co; Amylin; Bristol Myers Squibb FX This work was supported by National Institutes of Health Grant (CTSA) UL1TR000130. This trial is registered at Clinical Trials.gov, no. NCT00220961.; D.T. reports receiving consultant fees from HDL Diagnostics Inc. J.E.C., W.G., K.-P. A., and T.G. report working at Metabolon, Inc. D.C.S. reports receiving funding of the Phoenix Data Coordinating Center from a Takeda grant. MA.B. reports receiving consulting fees from Sanofi Aventis, Merck, Roche, and Boehringer-Ingelheim; grants from Takeda and Merck; and fees for participation in review activities from Novartis and BMS. T.A.B. reports receiving grant support from Allergan and Takeda, being on advisory panel and speakers bureau for Takeda, and receiving stock options from Tethys Bioscience. S.C.C. reports that he is a full-time employee of Merck and Co. R.R.H. reports receiving grant support from AstraZeneca, BMS, Eli Lilly, Sanofi-Aventis, and Medtronics; is a consultant to Boehringer-Ingelheim, Gilead, Intarcia, Isis, Eli Lilly, Novo Nordisk, Roche, and Medtronics; and is on the advisory board to Amgen, AstraZeneca, BMS, Gilead, Intarcia, Johnson & Johnson/Janssen, Eli Lilly, Merck, Novo Nordisk, Roche, Sanofi-Aventis, Daiichi Sankyo, and Elcelyx. S.M. reports being a speaker to Takeda ans Astra-Zeneca; a consultant to AstraZeneca and has received research support from Astra-Zeneca and Janssen. R.E.R. reports receiving research support from Takeda. P.D.R. reports receiving research grants from BMS and Novo Nordisk, speaker support through Amylin, and is a consultant of BMS. E.F. reports receiving grants from Boehringer-Ingelheim and Lilly & Co and serves on the advisory board of Boehringer-Ingelheim, GSK, Lilly & Co, Sanofi, Astra Zeneca, and Johnson & Johnson/Janssen. R.A.D. reports receiving grants from Amylin, Bristol Myers Squibb, Boehringer-Ingelheim, and Takeda; serves on the advisory board for Amylin, Takeda, Bristol Myers Squibb, Astra Zeneca, Novo Nordisk, Janssen, Lexicon, and Boehringer-Ingelheim; and is on the Speakers Bureau for Novo Nordisk, Bristol Myers Squibb, Astra Zeneca, and Janssen. A.E.K., F.B.S., N.M., and G.A.B. report no conflict of interest. NR 36 TC 3 Z9 3 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 MAY PY 2015 VL 100 IS 5 BP 1855 EP 1862 DI 10.1210/jc.2014-3824 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CM4QG UT WOS:000357669000037 PM 25603459 ER PT J AU Cauley, JA Greendale, GA Ruppert, K Lian, YJ Randolph, JF Lo, JC Burnett-Bowie, SA Finkelstein, JS AF Cauley, Jane A. Greendale, Gail A. Ruppert, Kristine Lian, Yinjuan Randolph, John F., Jr. Lo, Joan C. Burnett-Bowie, Sherri-Ann Finkelstein, Joel S. TI Serum 25 Hydroxyvitamin D, Bone Mineral Density and Fracture Risk Across the Menopause SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID VITAMIN-D STATUS; 25-HYDROXYVITAMIN D LEVELS; FINAL MENSTRUAL PERIOD; MULTIETHNIC COHORT; WOMENS HEALTH; OSTEOPOROTIC FRACTURES; POSTMENOPAUSAL WOMEN; VERTEBRAL FRACTURES; NONSPINE FRACTURES; PHYSICAL-ACTIVITY AB Context: Low levels of serum 25 Hydroxyvitamin D [25(OH)D] have been linked to greater fracture risk in older women. Objective: This study aimed to determine whether higher 25(OH)D is associated with slower loss of bone mineral density (BMD) and lower fracture risk during the menopausal transition. Design, Setting, and Participants: This was a prospective cohort study at five clinical centers in the United States. Mean age was 48.5 +/- 2.7 years. The fracture analysis included 124 women with an incident traumatic fracture, 88 with incident nontraumatic fracture, and 1532 women without incident fractures; average followup was 9.5 years. BMD analysis included 922 women with a documented final menstrual period. Main Outcome Measures: Serum 25(OH)D was measured by liquid chromatography tandem mass spectrometry at the third annual clinic visit. BMD was measured and incident fractures ascertained at each annual visit. Results: The mean 25(OH)D was 21.8 ng/mL; seven-hundred two (43%) of the women had 25(OH)D values <20 ng/mL. There was no significant association between 25(OH)D and traumatic fractures. In multivariate adjusted hazards models, the hazard ratio (HR) for nontraumatic fractures (95% confidence interval [CI]) was 0.72 (0.54-0.96) for each 10-ng/mL increase in 25(OH)D. Comparing women whose 25(OH)D was >= 20 vs <20 ng/mL, the HR (95% CI) for fracture was 0.54 (0.32-0.89). Changes in lumbar spine and femoral neck bone mineral density across menopause were not significantly associated with serum 25(OH)D level. Conclusion: Serum 25(OH)D levels are inversely associated with nontraumatic fracture in mid-life women. Vitamin D supplementation is warranted in midlife women with 25(OH) D levels <20 ng/mL. C1 [Cauley, Jane A.; Ruppert, Kristine; Lian, Yinjuan] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Greendale, Gail A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. [Randolph, John F., Jr.] Univ Michigan, Sch Med, Div Reprod Endocrinol & Infertil, Ann Arbor, MI 48109 USA. [Lo, Joan C.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Burnett-Bowie, Sherri-Ann; Finkelstein, Joel S.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. RP Cauley, JA (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 Desoto St,Crabtree A510, Pittsburgh, PA 15261 USA. EM jcauley@edc.pitt.edu RI Cauley, Jane/N-4836-2015; Ruppert, Kristine/C-2555-2016 OI Cauley, Jane/0000-0003-0752-4408; Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X; Ruppert, Kristine/0000-0002-3008-6584 FU National Institutes of Health (NIH), Department of Health and Human Services (DHHS), through the National Institute on Aging; National Institute of Nursing Research; NIH Office of Research on Women's Health [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495] FX The Study of Women's Health Across the Nation has grant support from the National Institutes of Health (NIH), Department of Health and Human Services (DHHS), through the National Institute on Aging, the National Institute of Nursing Research, and the NIH Office of Research on Women's Health (Grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, and AG012495). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH or the NIH. NR 30 TC 8 Z9 8 U1 2 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 MAY PY 2015 VL 100 IS 5 BP 2046 EP 2054 DI 10.1210/jc.2014-4367 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CM4QG UT WOS:000357669000061 PM 25719933 ER PT J AU Todd, JN Poon, W Lyssenko, V Groop, L Nichols, B Wilmot, M Robson, S Enjyoji, K Herman, MA Hu, C Zhang, R Jia, WP Ma, R Florez, JC Friedman, DJ AF Todd, Jennifer N. Poon, Wenny Lyssenko, Valeriya Groop, Leif Nichols, Brendan Wilmot, Michael Robson, Simon Enjyoji, Keiichi Herman, Mark A. Hu, Cheng Zhang, Rong Jia, Weiping Ma, Ronald Florez, Jose C. Friedman, David J. TI Variation in Glucose Homeostasis Traits Associated With P2RX7 Polymorphisms in Mice and Humans SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GENOME-WIDE ASSOCIATION; PANCREATIC BETA-CELL; INSULIN-RESISTANCE; LINKAGE DISEQUILIBRIUM; P2X(7) RECEPTOR; COMMON VARIANTS; P2X7 RECEPTOR; ATP; PATHOPHYSIOLOGY; ENPP1 AB Context: Extracellular nucleotide receptors are expressed in pancreatic B-cells. Purinergic signaling via these receptors may regulate pancreatic B-cell function. Objective: We hypothesized that purinergic signaling might influence glucose regulation and sought evidence in human studies of glycemic variation and a mouse model of purinergic signaling dysfunction. Design: In humans, we mined genome-wide meta-analysis data sets to examine purinergic signaling genes for association with glycemic traits and type 2 diabetes. We performed additional testing in two genomic regions (P2RX4/P2RX7 and P2RY1) in a cohort from the Prevalence, Prediction, and Prevention of Diabetes in Botnia (n = 3504), which includes more refined measures of glucose homeostasis. In mice, we generated a congenic model of purinergic signaling dysfunction by crossing the naturally hypomorphic C57BL6 P2rx7 allele onto the 129SvJ background. Results: Variants in five genes were associated with glycemic traits and in three genes with diabetes risk. In the Prevalence, Prediction, and Prevention of Diabetes in Botnia study, the minor allele in the missense functional variant rs1718119 (A348T) in P2RX7 was associated with increased insulin sensitivity and secretion, consistent with its known effect on increased pore function. Both male and female P2x7-C57 mice demonstrated impaired glucose tolerance compared with matched P2x7-129 mice. Insulin tolerance testing showed that P2x7-C57 mice were also less responsive to insulin than P2x7-129 mice. Conclusions: We show association of the purinergic signaling pathway in general and hypofunctioning P2X7 variants in particular with impaired glucose homeostasis in both mice and humans. C1 [Todd, Jennifer N.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Todd, Jennifer N.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Robson, Simon; Enjyoji, Keiichi; Herman, Mark A.; Florez, Jose C.; Friedman, David J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Nichols, Brendan; Wilmot, Michael; Robson, Simon; Enjyoji, Keiichi; Herman, Mark A.; Friedman, David J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. [Nichols, Brendan; Wilmot, Michael; Friedman, David J.] Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Boston, MA 02115 USA. [Todd, Jennifer N.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Poon, Wenny; Lyssenko, Valeriya; Groop, Leif] Lund Univ, Skane Univ Hosp, Dept Clin Sci Diabet & Endocrinol, SE-20502 Malmo, Sweden. [Lyssenko, Valeriya] Steno Diabet Ctr AS, Dept Translat Pathophysiol, DK-2820 Gentofte, Denmark. [Groop, Leif] Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland. [Hu, Cheng; Zhang, Rong; Jia, Weiping] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai 200233, Peoples R China. [Ma, Ronald] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China. RP Friedman, DJ (reprint author), 330 Brookline Ave, Boston, MA 02215 USA. EM jcflorez@partners.org; dfriedma@bidmc.harvard.edu RI Ma, Ronald/C-2788-2009 OI Ma, Ronald/0000-0002-1227-803X FU National Institutes of Health [F32 DK103486-01]; Doris Duke Clinical Scientist Development Award; Massachusetts General Hospital Research Scholars Award; Academy of Finland at the Finnish Institute for Molecular Medicine, Helsinki University; National Institute of Diabetes and Digestive and Kidney Diseases Grant [DK098091]; Sigrid Juselius Foundation; Finnish Diabetes Research Society; Signe and Ane Gyllenberg Foundation; Swedish Cultural Foundation in Finland; Ollqvist Foundation; Foundation for Life and Health in Finland; Jakobstad Hospital; Medical Society of Finland; Narpes Research Foundation; Vasa and Narpes Health centers; Natural Science Foundation of China [81322010]; National Young Top Talent Supporting Program FX J.N.T. is supported by National Institutes of Health Training Grant F32 DK103486-01. D.J.F. is a recipient of the Doris Duke Clinical Scientist Development Award. J.C.F. is a recipient of the Massachusetts General Hospital Research Scholars Award. L.G. is also a Finnish Distinguished Professor supported by the Academy of Finland at the Finnish Institute for Molecular Medicine, Helsinki University. Mouse studies were supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK098091 (to D.J.F.). The Prevalence, Prediction, and Prevention of Diabetes in Botnia study was supported by grants from the Sigrid Juselius Foundation, the Finnish Diabetes Research Society, the Signe and Ane Gyllenberg Foundation, the Swedish Cultural Foundation in Finland, the Ollqvist Foundation, the Foundation for Life and Health in Finland, Jakobstad Hospital, the Medical Society of Finland, the Narpes Research Foundation, and the Vasa and Narpes Health centers. Genotyping in Han Chinese was supported by Grant 81322010 from the Natural Science Foundation of China and by the National Young Top Talent Supporting Program. NR 40 TC 2 Z9 2 U1 2 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2015 VL 100 IS 5 BP E688 EP E696 DI 10.1210/jc.2014-4160 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CM4QG UT WOS:000357669000003 PM 25719930 ER PT J AU Moriarty, H Winter, L Robinson, K True, G Piersol, C Vause-Earland, T Iacovone, DB Holbert, L Newhart, B Fishman, D Short, TH AF Moriarty, Helene Winter, Laraine Robinson, Keith True, Gala Piersol, Catherine Vause-Earland, Tracey Iacovone, Dolores Blazer Holbert, Laura Newhart, Brian Fishman, Deborah Short, Thomas H. TI Exploration of Individual and Family Factors Related to Community Reintegration in Veterans With Traumatic Brain Injury SO JOURNAL OF THE AMERICAN PSYCHIATRIC NURSES ASSOCIATION LA English DT Article DE traumatic brain injury; veterans; community reintegration; depression; posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; PERSISTENT POSTCONCUSSIVE SYMPTOMS; MAJOR DEPRESSION; NEUROPSYCHIATRIC SEQUELAE; TEMPORAL RELATIONSHIP; LIFE SATISFACTION; COMBAT VETERANS; INTEGRATION; MILITARY; REHABILITATION AB BACKGROUND: Community reintegration (CR) poses a major problem for military veterans who have experienced a traumatic brain injury (TBI). Factors contributing to CR after TBI are poorly understood. OBJECTIVE: To address the gap in knowledge, an ecological framework was used to explore individual and family factors related to CR. DESIGN: Baseline data from an intervention study with 83 veterans with primarily mild to moderate TBI were analyzed. Instruments measured CR, depressive symptoms, physical health, quality of the relationship with the family member, and sociodemographics. Posttraumatic stress disorder and TBI characteristics were determined through record review. RESULTS: Five variables that exhibited significant bivariate relationships with CR (veteran rating of quality of relationship, physical functioning, bodily pain, posttraumatic stress disorder diagnosis, and depressive symptoms) were entered into hierarchical regression analysis. In the final analysis, the five variables together accounted for 35% of the variance, but only depression was a significant predictor of CR, with more depressed veterans exhibiting lower CR. CONCLUSIONS: Efforts to support CR of Veterans with TBI should carefully assess and target depression, a modifiable factor. C1 [Moriarty, Helene] Philadelphia Vet Affairs VA Med Ctr, Nursing Serv, Philadelphia, PA USA. [Moriarty, Helene] Villanova Univ, Coll Nursing, Villanova, PA 19085 USA. [Winter, Laraine; Fishman, Deborah] Philadelphia VA Med Ctr, Nursing Serv, Philadelphia, PA USA. [Winter, Laraine; Holbert, Laura] Philadelphia VA Med Ctr, Philadelphia Res & Educ Fdn, Philadelphia, PA USA. [Robinson, Keith; Iacovone, Dolores Blazer; Newhart, Brian] Philadelphia VA Med Ctr, Polytrauma Serv, Philadelphia, PA USA. [Robinson, Keith; True, Gala] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [True, Gala] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Piersol, Catherine; Vause-Earland, Tracey] Thomas Jefferson Univ, Sch Hlth Profess, Philadelphia, PA 19107 USA. [Short, Thomas H.] John Carroll Univ, Dept Math & Comp Sci, University Hts, OH USA. RP Moriarty, H (reprint author), Villanova Univ, Coll Nursing, Driscoll Hall,800 Lancaster Ave, Villanova, PA 19085 USA. EM helene.moriarty@villanova.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [R21 HD068857-01] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The project described was supported by Award No. R21 HD068857-01 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. This material is the result of work also supported with resources and the use of facilities at the Philadelphia VA Medical Center. NR 93 TC 3 Z9 3 U1 3 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1078-3903 EI 1532-5725 J9 J AM PSYCHIAT NURSES JI J. Am. Psych. Nurses Assoc. PD MAY-JUN PY 2015 VL 21 IS 3 BP 195 EP 211 DI 10.1177/1078390315591879 PG 17 WC Nursing; Psychiatry SC Nursing; Psychiatry GA CM5SN UT WOS:000357749000005 PM 26156059 ER PT J AU Javaid, S Zhang, JM Smolen, GA Yu, M Wittner, BS Singh, A Arora, KS Madden, MW Desai, R Zubrowski, MJ Schott, BJ Ting, DT Stott, SL Toner, M Maheswaran, S Shioda, T Ramaswamy, S Haber, DA AF Javaid, Sarah Zhang, Jianmin Smolen, Gromoslaw A. Yu, Min Wittner, Ben S. Singh, Anurag Arora, Kshitij S. Madden, Marissa W. Desai, Rushil Zubrowski, Matthew J. Schott, Benjamin J. Ting, David T. Stott, Shannon L. Toner, Mehmet Maheswaran, Shyamala Shioda, Toshi Ramaswamy, Sridhar Haber, Daniel A. TI MAPK7 Regulates EMT Features and Modulates the Generation of CTCs SO MOLECULAR CANCER RESEARCH LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITIONS; ACTIVATED PROTEIN-KINASE; BREAST-CANCER CELLS; TUMOR-CELLS; PHENOTYPE; METASTASIS; EXPRESSION; ERK5; RNAI; SCREEN AB Epithelial-to-mesenchymal transition (EMT) has been implicated inmodels of tumor cell migration, invasion, and metastasis. In a search for candidate therapeutic targets to reverse this process, nontumorigenic MCF10A breast epithelial cells were infected with an arrayed lentiviral kinome shRNA library and screened for either suppression or enhancement of a 26-gene EMT RNA signature. No individual kinase gene knock down was sufficient to induce EMT. In contrast, grouped epithelial markers were induced by knockdown of multiple kinases, including mitogen activated protein kinase 7 (MAPK7). In breast cancer cells, suppression of MAPK7 increased E-cadherin (CDH1) expression and inhibited cell migration. In an orthotopic mouse model, MAPK7 suppression reduced the generation of circulating tumor cells and the appearance of lung metastases. Together, these observations raise the possibility that targeting kinases that maintain mesenchymal cell properties in cancer cells, such as MAPK7, may lessen tumor invasiveness. (C)2015 AACR. C1 [Javaid, Sarah; Zhang, Jianmin; Smolen, Gromoslaw A.; Yu, Min; Wittner, Ben S.; Singh, Anurag; Arora, Kshitij S.; Madden, Marissa W.; Desai, Rushil; Zubrowski, Matthew J.; Schott, Benjamin J.; Ting, David T.; Stott, Shannon L.; Maheswaran, Shyamala; Shioda, Toshi; Ramaswamy, Sridhar; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Javaid, Sarah; Zhang, Jianmin; Smolen, Gromoslaw A.; Yu, Min; Wittner, Ben S.; Singh, Anurag; Arora, Kshitij S.; Madden, Marissa W.; Desai, Rushil; Zubrowski, Matthew J.; Schott, Benjamin J.; Ting, David T.; Stott, Shannon L.; Toner, Mehmet; Maheswaran, Shyamala; Shioda, Toshi; Ramaswamy, Sridhar] Harvard Univ, Sch Med, Charlestown, MA USA. [Javaid, Sarah; Wittner, Ben S.; Ting, David T.; Stott, Shannon L.; Shioda, Toshi; Ramaswamy, Sridhar; Haber, Daniel A.] Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. [Stott, Shannon L.; Toner, Mehmet] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Ctr Bioengn Med, Charlestown, MA 02129 USA. [Toner, Mehmet; Maheswaran, Shyamala] Massachusetts Gen Hosp, Dept Surg, Charlestown, MA 02129 USA. [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Bldg 149,13th St, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu OI Ting, David/0000-0002-3261-2322 FU Howard Hughes Medical Institute; NIH [CA-129933, NIBIB-EB008047]; National Foundation for Cancer Research (NFCR) FX This work was supported by the Howard Hughes Medical Institute (to D.A. Haber), the NIH (grant CA-129933 to D. A. Haber, NIBIB-EB008047), and the National Foundation for Cancer Research (NFCR). NR 48 TC 8 Z9 8 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAY PY 2015 VL 13 IS 5 BP 934 EP 943 DI 10.1158/1541-7786.MCR-14-0604 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CM9VN UT WOS:000358057500013 PM 25678598 ER PT J AU Huynh, H Hao, HX Chan, SL Chen, D Ong, R Soo, KC Pochanard, P Yang, D Ruddy, D Liu, M Derti, A Balak, MN Palmer, MR Wang, Y Lee, BH Sellami, D Zhu, AX Schlegel, R Huang, A AF Huynh, Hung Hao, Huai-Xiang Chan, Stephen L. Chen, David Ong, Richard Soo, Khee Chee Pochanard, Panisa Yang, David Ruddy, David Liu, Manway Derti, Adnan Balak, Marissa N. Palmer, Michael R. Wang, Yan Lee, Benjamin H. Sellami, Dalila Zhu, Andrew X. Schlegel, Robert Huang, Alan TI Loss of Tuberous Sclerosis Complex 2 (TSC2) Is Frequent in Hepatocellular Carcinoma and Predicts Response to mTORC1 Inhibitor Everolimus SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID SIGNALING PATHWAY; TUMOR-SUPPRESSOR; RECURRENT MUTATIONS; XENOGRAFT MODELS; CELL CARCINOMA; CANCER; GENOME; GROWTH; SENSITIVITY; ACTIVATION AB Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and hyperactivation of mTOR signaling plays a pivotal role in HCC tumorigenesis. Tuberous sclerosis complex (TSC), a heterodimer of TSC1 and TSC2, functions as a negative regulator of mTOR signaling. In the current study, we discovered that TSC2 loss-of-function is common in HCC. TSC2 loss was found in 4 of 8 HCC cell lines and 8 of 28 (28.6%) patient-derived HCC xenografts. TSC2 mutations and deletions are likely to be the underlying cause of TSC2 loss in HCC cell lines, xenografts, and primary tumors for most cases. We further demonstrated that TSC2-null HCC cell lines and xenografts had elevated mTOR signaling and, more importantly, were significantly more sensitive to RAD001/everolimus, an mTORC1 inhibitor. These preclinical findings led to the analysis of TSC2 status in HCC samples collected in the EVOLVE-1 clinical trial of everolimus using an optimized immunohistochemistry assay and identified 15 of 139 (10.8%) samples with low to undetectable levels of TSC2. Although the sample size is too small for formal statistical analysis, TSC2-null/low tumor patients who received everolimus tended to have longer overall survival than those who received placebo. Finally, we performed an epidemiology survey of more than 239 Asian HCC tumors and found the frequency of TSC2 loss to be approximately 20% in Asian HBV+ HCC. Taken together, our data strongly argue that TSC2 loss is a predictive biomarker for the response to everolimus in HCC patients. (C)2015 AACR. C1 [Huynh, Hung; Ong, Richard; Soo, Khee Chee] Natl Canc Ctr, Humphrey Oei Inst Canc Res, Div Cellular & Mol Res, Mol Endocrinol Lab, Singapore, Singapore. [Hao, Huai-Xiang; Pochanard, Panisa; Yang, David; Ruddy, David; Liu, Manway; Derti, Adnan; Balak, Marissa N.; Palmer, Michael R.; Wang, Yan; Lee, Benjamin H.; Schlegel, Robert; Huang, Alan] Novartis Inst Biomed Res, Oncol Translat Med, Cambridge, MA 02139 USA. [Chan, Stephen L.] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Clin Oncol, State Key Lab Oncol South China, Hong Kong, Hong Kong, Peoples R China. [Chen, David; Sellami, Dalila] Novartis Pharmaceut, Oncol Global Dev, E Hanover, NJ USA. [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. RP Huang, A (reprint author), Novartis Inst BioMed Res, 250 Mass Ave, Cambridge, MA 02139 USA. EM cmrhth@nccs.com.sg; alan.huang@novartis.com RI Chan, Stephen L./I-3197-2016 FU Novartis Pharmaceutical Company FX This work was supported by Novartis Pharmaceutical Company to both Novartis authors and authors from other institutions. NR 46 TC 19 Z9 19 U1 1 U2 2 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 MAY PY 2015 VL 14 IS 5 BP 1224 EP 1235 DI 10.1158/1535-7163.MCT-14-0768 PG 12 WC Oncology SC Oncology GA CM9TX UT WOS:000358053000014 PM 25724664 ER PT J AU Mitra, D Nout, R Catalano, PJ Creutzberg, C Cimbak, N Lee, L Viswanathan, AN AF Mitra, Devarati Nout, Remi Catalano, Paul J. Creutzberg, Carien Cimbak, Nicole Lee, Larissa Viswanathan, Akila N. TI Rectal bleeding after radiation therapy for endometrial cancer SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Rectal bleeding; Endometrial cancer; Vaginal brachytherapy ID QUALITY-OF-LIFE; EXTERNAL-BEAM RADIOTHERAPY; MULTICENTER RANDOMIZED-TRIAL; PROSTATE-CANCER; VAGINAL BRACHYTHERAPY; PELVIC RADIOTHERAPY; PORTEC-2 TRIAL; CARCINOMA; IRRADIATION; SURGERY AB Background and purpose: The goals of this study were to determine the rate and risk factors of rectal bleeding (RB) after external beam radiotherapy and vaginal brachytherapy (EBRT + VB), and to compare these data to previously unreported RB rates from PORTEC-2 patients receiving EBRT or VB alone. Materials and methods: Retrospective chart review identified 212 endometrial cancer patients receiving adjuvant EBRT + VB between 2006 and 2013. Patient-reported RB data were also obtained from PORTEC-2 patients randomized to EBRT (n = 166) or VB (n = 182). The two populations were compared using an RB scale of symptom severity. Results: After a median 35 months, 17.9% of EBRT + VB patients (n = 38) experienced any RB with 1.9% (n = 4) having bleeding requiring intervention. Age <= 70 years was the only predictor of RB (OR 2.8; 95% CI 1.1-8.7; p = 0.027). Rates of patient-reported RB after EBRT were similar with 15.0% (n = 25) having any RB and 0.6% (n = 1) having "very much" bleeding. On regression analysis, any EBRT (either EBRT alone or EBRT + VB) increased the risk of RB compared to those who received VB alone (OR 3.0; p = 0.0028; 95% CI 1.4-6.7). The rates of more severe RB were low and did not significantly differ between treatments. Conclusions: Significant RB is rare after radiation. EBRT has higher rates of rectal bleeding than VB. The addition of VB to EBRT does not significantly alter bleeding rates. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Mitra, Devarati; Cimbak, Nicole; Lee, Larissa; Viswanathan, Akila N.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Nout, Remi; Creutzberg, Carien] Leiden Univ, Med Ctr, Dept Radiat Oncol, NL-2300 RA Leiden, Netherlands. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Mitra, D (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM dmitral@partners.org FU National Institutes of Health [R21 167800]; Dutch Cancer Society [CKTO 2001-04] FX Dr. Viswanathan receives funding from National Institutes of Health R21 167800. PORTEC-2 was funded by the Dutch Cancer Society (CKTO 2001-04). NR 20 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD MAY PY 2015 VL 115 IS 2 BP 240 EP 245 DI 10.1016/j.radonc.2015.03.030 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CM5YN UT WOS:000357765000015 PM 26003340 ER PT J AU Homma, S Thompson, JLP Qian, M Ye, SQ Di Tullio, MR Lip, GYH Mann, DL Sacco, RL Levin, B Pullicino, PM Freudenberger, RS Teerlink, JR Graham, S Mohr, JP Labovitz, AJ Buchsbaum, R Estol, CJ Lok, DJ Ponikowski, P Anker, SD AF Homma, Shunichi Thompson, John L. P. Qian, Min Ye, Siqin Di Tullio, Marco R. Lip, Gregory Y. H. Mann, Douglas L. Sacco, Ralph L. Levin, Bruce Pullicino, Patrick M. Freudenberger, Ronald S. Teerlink, John R. Graham, Susan Mohr, J. P. Labovitz, Arthur J. Buchsbaum, Richard Estol, Conrado J. Lok, Dirk J. Ponikowski, Piotr Anker, Stefan D. TI Quality of Anticoagulation Control in Preventing Adverse Events in Patients With Heart Failure in Sinus Rhythm Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction Trial Substudy SO CIRCULATION-HEART FAILURE LA English DT Article DE anticoagulant; heart failure; hemorrhage; stroke ID NORMALIZED RATIO CONTROL; ATRIAL-FIBRILLATION INSIGHTS; NET CLINICAL BENEFIT; RE-LY TRIAL; ORAL ANTICOAGULANT; STROKE PREVENTION; MODELING ANALYSIS; DABIGATRAN; APIXABAN; EFFICACY AB Background The aim of this study is to examine the relationship between time in the therapeutic range (TTR) and clinical outcomes in heart failure patients in sinus rhythm treated with warfarin. Methods and Results We used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death), with death alone, ischemic stroke alone, major hemorrhage alone, and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin-treated patients, with TTR being treated as a time-dependent covariate. A total of 2217 patients were included in the analyses; among whom 1067 were randomized to warfarin and 1150 were randomized to aspirin. The median (interquartile range) follow-up duration was 3.6 (2.0-5.0) years. Mean (SD) age was 6111.3 years, with 80% being men. The mean (+/- SD) TTR was 57% (+/- 28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted P<0.001), death alone (adjusted P=0.001), and improved net clinical benefit (adjusted P<0.001). A similar trend was observed for the other 2 outcomes, but significance was not reached (adjusted P=0.082 for ischemic stroke and adjusted P=0.109 for major hemorrhage). Conclusions In patients with heart failure in sinus rhythm, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938. C1 [Homma, Shunichi; Ye, Siqin; Di Tullio, Marco R.] Columbia Univ, Med Ctr, Dept Med, Div Cardiol, New York, NY 10032 USA. [Mohr, J. P.] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA. [Thompson, John L. P.; Qian, Min; Levin, Bruce; Buchsbaum, Richard] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA. [Lip, Gregory Y. H.] Univ Birmingham, City Hosp, Ctr Cardiovasc Sci, Birmingham, W Midlands, England. [Mann, Douglas L.] Washington Univ, Dept Med, St Louis, MO USA. [Sacco, Ralph L.] Univ Miami, Sch Med, Dept Neurol, Coral Gables, FL 33124 USA. [Pullicino, Patrick M.] Univ Kent, Kent Inst Med & Hlth Sci, Canterbury, Kent, England. [Freudenberger, Ronald S.] Lehigh Valley Hosp, Dept Med, Div Cardiol, Allentown, PA USA. [Teerlink, John R.] San Francisco VA Med Ctr, Dept Med, Cardiol Sect, San Francisco, CA USA. [Teerlink, John R.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Graham, Susan] SUNY Upstate Med Univ, Dept Med, Div Cardiol, Buffalo, NY USA. [Labovitz, Arthur J.] Univ S Florida, Dept Cardiovasc Med, Tampa, FL USA. [Estol, Conrado J.] Ctr Neurol Tratamiento & Rehabil, Buenos Aires, DF, Argentina. [Lok, Dirk J.] Deventer Hosp, Dept Cardiol, Deventer, Netherlands. [Ponikowski, Piotr] Wroclaw Med Univ, Mil Hosp, Dept Heart Dis, Wroclaw, Poland. [Anker, Stefan D.] Univ Med Gottingen, Dept Cardiol, Div Innovat Clin Trials, Gottingen, Germany. RP Homma, S (reprint author), Columbia Univ, Med Ctr, PH 3-342,622 W 168th St, New York, NY 10032 USA. EM sh23@columbia.edu RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Beran, David/0000-0001-7229-3920; Kohsaka, Shun/0000-0003-3779-2972 FU [U01-NS-043975]; [U01-NS-039143] FX The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial was supported by grant numbers U01-NS-043975 to S. Homma and U01-NS-039143 to J.L.P. Thompson from the National Institute of Neurological Diseases and Stroke. Warfarin and warfarin placebo were provided by Taro Pharmaceuticals, United States and aspirin and aspirin placebo by Bayer HealthCare. NR 23 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2015 VL 8 IS 3 BP 504 EP 509 DI 10.1161/CIRCHEARTFAILURE.114.001725 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CL6LX UT WOS:000357079700014 PM 25850425 ER PT J AU Borlaug, BA Lewis, GD McNulty, SE Semigran, MJ LeWinter, M Chen, H Lin, G Deswal, A Margulies, KB Redfield, MM AF Borlaug, Barry A. Lewis, Gregory D. McNulty, Steven E. Semigran, Marc J. LeWinter, Martin Chen, Horng Lin, Grace Deswal, Anita Margulies, Kenneth B. Redfield, Margaret M. TI Effects of Sildenafil on Ventricular and Vascular Function in Heart Failure With Preserved Ejection Fraction SO CIRCULATION-HEART FAILURE LA English DT Article DE diastolic heart failure; heart failure; vascular function; ventricular function ID MEDIATED ARTERIAL DILATION; EXERCISE CAPACITY; PULMONARY-HYPERTENSION; CLINICAL STATUS; PHOSPHODIESTERASE-5 INHIBITION; NITRIC-OXIDE; PATHOPHYSIOLOGY; DYSFUNCTION; ECHOCARDIOGRAPHY; CONTRACTILITY AB Background Early studies showed beneficial effects of phosphodiesterase 5 inhibitors on cardiovascular function in heart failure (HF) patients, but the RELAX trial observed no improvement in exercise capacity with sildenafil treatment in subjects with HF and preserved ejection fraction. Methods and Results A subgroup of participants in the RELAX trial (n=48) underwent comprehensive noninvasive cardiovascular assessment before and after treatment with sildenafil or placebo in a prospective ancillary study. Left ventricular contractility was assessed by peak power index and stroke work index. Systemic arterial load was assessed by arterial elastance (Ea) and right ventricular afterload by pulmonary artery systolic pressure. Endothelial function was assessed by reactive hyperemia index after upper arm cuff occlusion. Compared with placebo (n=25), sildenafil (n=23) decreased Ea (-0.290.28 mm Hg/mL versus +0.020.29, P=0.008) and tended to improve reactive hyperemia index (+0.30 +/- 0.45 versus -0.17 +/- 0.30, P=0.054). In contrast, left ventricular contractility was reduced by 11% to 16% with sildenafil compared with placebo (PWR/EDV -52 +/- 70 versus +0 +/- 40 mm Hg/s, P=0.006; SW/EDV +0.3 +/- 5.8 versus -6.0 +/- 5.1 mm Hg, P=0.04). Sildenafil had no effect on pulmonary artery systolic pressure. Conclusions In subjects with HF and preserved ejection fraction, sildenafil displayed opposing effects on ventricular and vascular function. We speculate that beneficial effects of phosphodiesterase 5 inhibitors in the systemic vasculature and endothelium were insufficient to improve clinical status or that the deleterious effects on left ventricular function offset any salutary vascular effects, contributing to the absence of benefit observed with sildenafil in subjects with HF and preserved ejection fraction in the RELAX trial. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302. C1 [Borlaug, Barry A.; Chen, Horng; Lin, Grace; Redfield, Margaret M.] Mayo Clin, Dept Med, Div Cardiol, Rochester, MN USA. [Lewis, Gregory D.; Semigran, Marc J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [McNulty, Steven E.] Duke Clin Res Inst, Dept Med, Durham, NC USA. [LeWinter, Martin] Univ Vermont, Coll Med, Dept Med, Cardiol Unit, Burlington, VT 05405 USA. [Deswal, Anita] Michael E DeBakey VA Med Ctr, Dept Med, Houston, TX USA. [Deswal, Anita] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Margulies, Kenneth B.] Univ Penn, Dept Med, Translat Res Ctr, Philadelphia, PA 19104 USA. RP Borlaug, BA (reprint author), Mayo Clin & Mayo Fdn, 200 First St SW, Rochester, MN 55905 USA. EM borlaug.barry@mayo.edu FU National Heart Lung and Blood Institute Heart Failure Research Network [U10HL084904, U10HL084907, PO1HL 076611]; American Heart Association National Clinical Research Program Grant [10CRP2600071] FX This study was funded by the National Heart Lung and Blood Institute Heart Failure Research Network (U10HL084904, U10HL084907, and PO1HL 076611) and an American Heart Association National Clinical Research Program Grant (10CRP2600071). NR 34 TC 18 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2015 VL 8 IS 3 BP 533 EP 541 DI 10.1161/CIRCHEARTFAILURE.114.001915 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CL6LX UT WOS:000357079700018 PM 25782985 ER PT J AU Liu, EH Solorzano, CC Katznelson, L Vinik, AI Wong, R Randolph, G AF Liu, Eric H. Solorzano, Carmen C. Katznelson, Laurence Vinik, Aaron I. Wong, Richard Randolph, Gregory CA AACE Endocrine Surg Sci Committee Neuroendocrine Carcinoid Subgrp TI AACE/ACE DISEASE STATE CLINICAL REVIEW: DIAGNOSIS AND MANAGEMENT OF MIDGUT CARCINOIDS SO ENDOCRINE PRACTICE LA English DT Review ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS; CONSENSUS GUIDELINES; COMPUTED-TOMOGRAPHY; LIVER METASTASES; CHROMOGRANIN-A; 5-HYDROXYINDOLEACETIC ACID; OPERATIVE RESECTION; HEPATIC METASTASES; PASIREOTIDE SOM230 AB Objective: Neuroendocrine tumors (NETs) are a collection of complex tumors that arise from the diffuse endocrine system, primarily from the digestive tract. Carcinoid tumors most commonly originate from the small intestine. These tumors are either referred to as small intestinal neuroendocrine tumors or midgut carcinoids (MGCs). The purpose of this review article is to survey the diagnostic and therapeutic pathways for patients with MGC and provide an overview of the complex multidisciplinary care involved in improving their quality of life, treatment outcomes, and survival. Methods: The current literature regarding the diagnosis and management of MGCs was reviewed. Results: Dry flushing and secretory diarrhea are the hallmarks of the clinical syndrome of MGC. Managing MGC requires attention to the overall symptom complex, including the physical effects of the tumor and biomarker levels. The somatostatin analogs (SAs) octreotide and lanreotide are highly efficacious for symptomatic improvement. MGCs require resection to encompass the primary tumor and mesenteric lymph node metastases and should include cholecystectomy if the patient is likely to receive SA therapy. Debulking of liver metastasis by resection in combination with ablative therapies and other liver-directed modalities may help palliate symptoms and hormonal overproduction in carefully selected patients. Quality of life is an important measure of patients' perception of the burden of their disease and impact of treatment modalities and may be a useful guide in deciding changes in therapy to alter apparent health status. Conclusion: MGC is a challenging malignancy that requires the input of a multidisciplinary team to develop the best treatment plan. Consultation with expert centers that specialize in NETs may also be indicated for complex cases. With expert care, patients can be cured or live with the disease and enjoy good quality of life. C1 [Liu, Eric H.; Solorzano, Carmen C.] Vanderbilt Univ, Div Surg Oncol & Endocrine Surg, Nashville, TN 37235 USA. [Katznelson, Laurence] Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. [Vinik, Aaron I.] Eastern Virginia Med Sch, Dept Med, Norfolk, VA 23501 USA. [Wong, Richard] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Randolph, Gregory] Massachusetts Gen Hosp, Dept Otolaryngol, Boston, MA 02114 USA. RP Solorzano, CC (reprint author), 597 PRB,2220 Pierce Ave, Nashville, TN 37212 USA. EM Carmen.solorzano@vanderbilt.edu FU NCI NIH HHS [P30 CA008748] NR 53 TC 4 Z9 5 U1 0 U2 2 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD MAY PY 2015 VL 21 IS 5 BP 534 EP 545 DI 10.4158/EP14464.DSC PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CM5MJ UT WOS:000357731800010 PM 25962092 ER PT J AU Herrera, MF Akerstrom, G Angelos, P Grant, CS Hoff, AO Pantoja, JP Perez-Johnston, R Sahani, DV Wong, RJ Randolph, G AF Herrera, Miguel F. Akerstrom, Goran Angelos, Peter Grant, Clive S. Hoff, Ana O. Pantoja, Juan Pablo Perez-Johnston, Rocio Sahani, Dushyant V. Wong, Richard J. Randolph, Gregory TI AACE/ACE DISEASE STATE CLINICAL REVIEW: PANCREATIC NEUROENDOCRINE INCIDENTALOMAS SO ENDOCRINE PRACTICE LA English DT Review ID ENDOCRINE TUMORS; CONSENSUS GUIDELINES; GRADING SYSTEM; DIAGNOSIS; MANAGEMENT; NEOPLASMS; KI-67; CARCINOMAS; MALIGNANCY; EXPERIENCE AB Incidental detection of pancreatic neuroendocrine tumors (PNETs) has substantially increased over the last decade due to widespread use of advanced imaging studies. Reliable initial imaging-based characterization is crucial for the differential diagnosis from other exocrine neoplasms and to determine the appropriate management plan. Measurements of chromogranin A, pancreatic polypeptide, and calcitonin are recommended for the biochemical evaluation. A thorough medical history needs to be performed to rule out multiple endocrine neoplasia (MEN) type 1. The European Neuroendocrine Tumor Society (ENETS)/Tumor Node Metastasis (TNM) staging system together with a grading based on the Ki-67 proliferation index and mitotic counts has proven to give more appropriate prognostic information than the World Health Organization (WHO)/American Joint Committee on Cancer (AJCC) TNM staging but may still fail to safely differentiate benign from malignant lesions. Poorly differentiated PNETs generally present with metastases and are rarely amenable for resection. Well-or intermediately differentiated tumors >= 2 cm with imaging evidence of malignancy or with a Ki-67 > 2% should be resected. It has been suggested that non-MEN related, nonfunctioning, and asymptomatic PNETs < 2 cm with a Ki-67 index >= 2% carry a low risk of metastasis and may be observed in the absence of clinical or radiologic criteria of malignancy or progression, especially in older patients. However, because metastases may occur with long delay with smaller PNETS, physicians should consider patient age, lesion location, and the risks of operation, and patients not undergoing surgery need to be closely followed closely. C1 [Herrera, Miguel F.; Pantoja, Juan Pablo] Univ Nacl Autonoma Mexico, Inst Nacl Nutr Salvador Zubiran, Endocrine Surg, Mexico City, DF, Mexico. [Akerstrom, Goran] Uppsala Univ, Endocrine Surg, Uppsala, Sweden. [Angelos, Peter] Univ Chicago, Endocrine Surg, Chicago, IL 60637 USA. [Grant, Clive S.] Mayo Clin, Surg, Rochester, MN USA. [Hoff, Ana O.] Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Endocrinol, BR-05508 Sao Paulo, Brazil. [Perez-Johnston, Rocio] CT Scanner Lomas Altas, Ciudad Mexico, DF, Mexico. [Sahani, Dushyant V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent,Radiol, Cambridge, MA 02138 USA. [Wong, Richard J.] Mem Sloan Kettering Canc Ctr, Dept Surg, Head & Neck Serv, New York, NY USA. [Randolph, Gregory] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Thyroid & Parathyroid Endocrine Surg, Massachusetts Eye & Ear Infirm,Endocrine Surg Ser, Cambridge, MA 02138 USA. RP Herrera, MF (reprint author), Vasco Quiroga 15, Mexico City 14000, DF, Mexico. EM miguelfherrera@gmail.com FU NCI NIH HHS [P30 CA008748] NR 54 TC 3 Z9 3 U1 0 U2 9 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD MAY PY 2015 VL 21 IS 5 BP 546 EP 553 DI 10.4158/EP14465.DSC PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CM5MJ UT WOS:000357731800011 PM 25962093 ER PT J AU McNamara, RL Spatz, ES Kelley, TA Stowell, CJ Beltrame, J Heidenreich, P Tresserras, R Jernberg, T Chua, T Morgan, L Panigrahi, B Ruiz, AR Rumsfeld, JS Sadwin, L Schoeberl, M Shahian, D Weston, C Yeh, R Lewin, J AF McNamara, Robert L. Spatz, Erica S. Kelley, Thomas A. Stowell, Caleb J. Beltrame, John Heidenreich, Paul Tresserras, Ricard Jernberg, Tomas Chua, Terrance Morgan, Louise Panigrahi, Bishnu Rosas Ruiz, Alba Rumsfeld, John S. Sadwin, Lawrence Schoeberl, Mark Shahian, David Weston, Clive Yeh, Robert Lewin, Jack TI Standardized Outcome Measurement for Patients With Coronary Artery Disease: Consensus From the International Consortium for Health Outcomes Measurement (ICHOM) SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE coronary artery disease; outcomes; patient-centered ID ACUTE MYOCARDIAL-INFARCTION; AMERICAN-HEART-ASSOCIATION; TERM SURVIVAL; REGISTRY; RISK; CARE; MORTALITY; QUESTIONNAIRE; MANAGEMENT; ANGINA AB Background-Coronary artery disease (CAD) outcomes consistently improve when they are routinely measured and provided back to physicians and hospitals. However, few centers around the world systematically track outcomes, and no global standards exist. Furthermore, patient-centered outcomes and longitudinal outcomes are under-represented in current assessments. Methods and Results-The nonprofit International Consortium for Health Outcomes Measurement (ICHOM) convened an international Working Group to define a consensus standard set of outcome measures and risk factors for tracking, comparing, and improving the outcomes of CAD care. Members were drawn from 4 continents and 6 countries. Using a modified Delphi method, the ICHOM Working Group defined who should be tracked, what should be measured, and when such measurements should be performed. The ICHOM CAD consensus measures were designed to be relevant for all patients diagnosed with CAD, including those with acute myocardial infarction, angina, and asymptomatic CAD. Thirteen specific outcomes were chosen, including acute complications occurring within 30 days of acute myocardial infarction, coronary artery bypass grafting surgery, or percutaneous coronary intervention; and longitudinal outcomes for up to 5 years for patient-reported health status (Seattle Angina Questionnaire [SAQ-7], elements of Rose Dyspnea Score, and Patient Health Questionnaire [PHQ-2]), cardiovascular hospital admissions, cardiovascular procedures, renal failure, and mortality. Baseline demographic, cardiovascular disease, and comorbidity information is included to improve the interpretability of comparisons. Conclusions-ICHOM recommends that this set of outcomes and other patient information be measured for all patients with CAD. C1 [McNamara, Robert L.; Spatz, Erica S.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [McNamara, Robert L.; Morgan, Louise; Sadwin, Lawrence; Schoeberl, Mark] Amer Heart Assoc, Dallas, TX USA. [Spatz, Erica S.; Kelley, Thomas A.; Stowell, Caleb J.] Int Consortium Hlth Outcomes Measurement, Cambridge, MA USA. [Beltrame, John] Univ Adelaide, Adelaide, SA 5005, Australia. [Beltrame, John] Queen Elizabeth Hosp, Adelaide, SA, Australia. [Heidenreich, Paul] Stanford Univ, Stanford, CA 94305 USA. [Tresserras, Ricard; Rosas Ruiz, Alba] Autonomous Govt Catalonia, Dept Hlth, Catalonia, Spain. [Jernberg, Tomas] Karolinska Inst, Stockholm, Sweden. [Chua, Terrance] Natl Heart Ctr, Singapore, Singapore. [Panigrahi, Bishnu] Fortis Healthcare, Gurgaon, India. [Rumsfeld, John S.] Vet Hlth Adm, Washington, DC USA. [Shahian, David; Yeh, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shahian, David; Yeh, Robert] Harvard Univ, Sch Med, Boston, MA USA. [Weston, Clive] Swansea Univ, Swansea, W Glam, Wales. [Lewin, Jack] Cardiovasc Res Fdn, New York, NY USA. RP McNamara, RL (reprint author), Yale Univ, Sch Med, Cardiol, POB 208017,333 Cedar St, New Haven, CT 06520 USA. EM robert.mcnamara@yale.edu FU International Consortium for Health Outcomes Measurement (ICHOM) FX Costs to run the Working Group were covered by the International Consortium for Health Outcomes Measurement (ICHOM). NR 38 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD MAY PY 2015 VL 4 IS 5 AR e001767 DI 10.1161/JAHA.115.001767 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CK6OO UT WOS:000356347600011 ER PT J AU Wells, JM Gagger, A Blalock, JE AF Wells, J. Michael Gagger, Amit Blalock, J. Edwin TI MMP generated matrikines SO MATRIX BIOLOGY LA English DT Article DE Matrix metalloproteinase; Elastin; Proline-glycine-proline; COPD ID ELASTIN-BINDING-PROTEIN; PROLINE-GLYCINE-PROLINE; EXTRACELLULAR-MATRIX DEGRADATION; OBSTRUCTIVE PULMONARY-DISEASE; ARGININE-THREONINE-ARGININE; LEUKOTRIENE A(4) HYDROLASE; INJURED RABBIT CORNEA; PRO-GLY-PRO; NEUTROPHIL CHEMOATTRACTANT; CHEMOTACTIC PEPTIDE AB Matrikines originate from the fragmentation of extracellular matrix proteins and regulate cellular activities by interacting with specific receptors. Matrikines are implicated in inflammation, immune responses, organ development, wound repair, angiogenesis, atherosclerosis, tumor progression and metastasis due to their ability to alter cellular migration, chemotaxis, and mitogenesis. Matrix metalloproteinases (MMPs) degrade extracellular matrix components under normal circumstances and in disease processes. Of the 20 MMPs identified, MMP-1, MMP-2, MMP-8, MMP-9, and MMP-12 have been implicated in regulating the matrikines Val-Gly-Val-Ala-Pro-Gly (elastin peptide) and proline glycine proline (PGP). Elastin peptide fragments are generated by elastolytic enzymes and have implications in atherosclerosis, neovascularization, chronic obstructive pulmonary disease, skin disease, as well as tumor invasion and spread. PGP is produced through a multistep pathway that liberates the tripeptide fragment from extracellular collagen. PGP is best described for its role in neutrophil chemotaxis and is implicated in the pathogenesis of corneal ulcers and in chronic lung conditions. In chronic cigarette smoke related lung disease, the PGP pathway can become a self-propagating cycle of inflammation through cigarette-smoke mediated inhibition of leukotriene A4 hydrolase, the enzyme responsible for degrading PGP and halting acute inflammation. This review highlights the roles of MMPs in generating these important matrikines. (C) 2015 Published by Elsevier B.V. C1 [Wells, J. Michael; Gagger, Amit; Blalock, J. Edwin] Univ Alabama Birmingham (UAB, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA. [Wells, J. Michael; Gagger, Amit; Blalock, J. Edwin] UAB Lung Hlth Ctr, Birmingham, AL USA. [Wells, J. Michael; Gagger, Amit] Birmingham VA Med Ctr, Dept Med, Birmingham, AL USA. RP Wells, JM (reprint author), 1900 Univ Blvd,MCLM 894, Birmingham, AL 35294 USA. EM jmwells@uab.edu OI Blalock, J. Edwin/0000-0001-5303-8123 FU NHLBI; NIH; Family Smoking Prevention and Tobacco Control Act FX Research reported in this publication was supported by the NHLBI, NIH, and the Family Smoking Prevention and Tobacco Control Act. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration. NR 73 TC 24 Z9 25 U1 3 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X EI 1569-1802 J9 MATRIX BIOL JI Matrix Biol. PD MAY-JUL PY 2015 VL 44-46 SI SI BP 122 EP 129 DI 10.1016/j.matbio.2015.01.016 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CL8MT UT WOS:000357229500014 PM 25636538 ER PT J AU Manchikanti, L Atluri, S Hirsch, JA AF Manchikanti, Laxmaiah Atluri, Sairam Hirsch, Joshua A. TI The Effect of Abuse-Deterrent Extended-Release Oxycodone Leads to Inappropriate Conclusions with Over Estimation of Safety of Abuse-Deterrent Formulations SO PAIN PHYSICIAN LA English DT Letter C1 [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Atluri, Sairam] Tristate Spine Care Inst, Cincinnati, OH USA. [Hirsch, Joshua A.] Harvard Univ, Intervent Care Serv Line, Massachusetts Gen Hosp, Neuroendovasc Program,Dept Radiol,Sch Med, Cambridge, MA 02138 USA. [Hirsch, Joshua A.] Harvard Univ, Intervent Radiol, Massachusetts Gen Hosp, Neuroendovasc Program,Dept Radiol,Sch Med, Cambridge, MA 02138 USA. [Hirsch, Joshua A.] Harvard Univ, Endovasc & Intervent Neuroradiol, Massachusetts Gen Hosp, Neuroendovasc Program,Dept Radiol,Sch Med, Cambridge, MA 02138 USA. [Hirsch, Joshua A.] Harvard Univ, NeuroIntervent Spine Serv, Massachusetts Gen Hosp, Neuroendovasc Program,Dept Radiol,Sch Med, Cambridge, MA 02138 USA. [Hirsch, Joshua A.] Harvard Univ, Neuroendovasc Program, Dept Radiol, Massachusetts Gen Hosp,Sch Med, Cambridge, MA 02138 USA. RP Manchikanti, L (reprint author), Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. EM drlm@thepainmd.com; saiatluri@gmail.com; hirsch@snisonline.org NR 5 TC 0 Z9 0 U1 0 U2 1 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAY-JUN PY 2015 VL 18 IS 3 BP E445 EP E446 PG 2 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CM5QK UT WOS:000357743200025 PM 26000699 ER PT J AU Manchikanti, L Hirsch, JA AF Manchikanti, Laxmaiah Hirsch, Joshua A. TI A Case for Restraint of Explosive Growth of Health Information Technology: First, Do No Harm SO PAIN PHYSICIAN LA English DT Review ID UNITED-STATES; AMBULATORY-CARE; RECORDS; MEDICINE; METAMORPHOSIS; QUALITY; SAFETY; POLICY C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroIntervent Serv & Neuroendovasc Program, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 45 TC 5 Z9 5 U1 0 U2 1 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAY-JUN PY 2015 VL 18 IS 3 BP E293 EP E298 PG 6 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CM5QK UT WOS:000357743200002 PM 26000676 ER PT J AU Manchikanti, L Staats, PS Boswell, MV Hirsch, JA AF Manchikanti, Laxmaiah Staats, Peter S. Boswell, Mark V. Hirsch, Joshua A. TI Analysis of the Carrot and Stick Policy of Repeal of the Sustainable Growth Rate Formula: The Good, The Bad, and The Ugly SO PAIN PHYSICIAN LA English DT Review DE Balanced Budget Act; sustainable growth rate; alternative payment models; Medicare Access and CHIP Reauthorization Act of 2015; Merit-based Incentive Payment System; payment reform; payment modernization; health information technology ID INTERVENTIONAL PAIN MANAGEMENT; LOW-BACK-PAIN; UNITED-STATES; HEALTH-CARE; DOC FIX; TRENDS; EPIDEMIOLOGY; METAMORPHOSIS; MEDICINE; ADULTS AB The Balanced Budget Act which became law in 1997 was designed to help stem the increasing in costs of healthcare. The Sustainable Growth Rate (SGR) formula was incorporated into that law as a method of helping balance the budget through a complex formula tying reimbursement to the growth in the economy. Soon after its inception, the flawed nature of the formula, linking the balancing of the federal budget to physician professional fees was realized. Congress has provided multiple short-term fixes known as SGR patches over the years so as to avoid generally progressively larger negative corrections to professional reimbursement. The near annual SGR correction requirement has been compared to Groundhog Day in the legislative arena. Over the years, physician and other providers faced numerous looming, large cuts. Most recently, on April 1, 2015 physicians faced a 21.2% cut in provider payments. To the surprise of many, in April 2015 a bipartisan bicameral effort permanently repealed the Medicare SGR formula for controlling provider payment. The repeal of SGR means the temporary measures to override the growth rate formula will no longer dominate Medicare policy discussions and now the focus turns to continue payment reforms. The MACRA provides physicians and other health care professionals with stable fee update for 5 years and it follows with a new incentive program, termed the Merit-based Incentive Payment System (MIPS) replacing and consolidating preexisting incentive payment programs: meaningful use of electronic health records (EHR), physician quality reporting system, and the value-based payment modified. Thus, payments to clinicians will be subjected to adjustments based on participation in MIPS or other approved alternative payment mechanisms. This legislation also creates numerous other regulations. The MACRA has been criticized for providing insufficient statutory updates, enacting a flawed quality and performance improvement program associated with MIPS and inappropriate use of utilization and payment data. Thus, the MACRA offers physicians a predictable schedule for Medicare rates - a carrot, and controls the physician behaviors with payment reforms analogous to a stick. Thus, it could be said that this legislation embodies some good, bad, and ugly aspects. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Staats, Peter S.] Premier Pain Ctr, Shrewsbury, NJ USA. [Staats, Peter S.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Boswell, Mark V.] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroIntervent Serv & Neuroendovasc Program, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com FU Boston Scientific; St Jude; Spinal Modulation; Vertos FX Dr. Manchikanti has provided limited consulting services to Semnur Pharmaceuticals, Incorporated, which is developing nonparticulate steroids. Dr Staats Is a Consultant for Medtronic, Boston Scientific, St Jude, Electrocore Medical, Currently is involved in research funded by Boston Scientific, St Jude, Spinal Modulation, Vertos, Dr. Hirsch is a consultant for Medtronic. NR 56 TC 14 Z9 14 U1 3 U2 5 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAY-JUN PY 2015 VL 18 IS 3 BP E273 EP E292 PG 20 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CM5QK UT WOS:000357743200001 PM 26000675 ER PT J AU Ortiz, VE Vidal-Melo, MF Walsh, JL AF Ortiz, Vilma E. Vidal-Melo, Marcos F. Walsh, John L. TI Strategies for managing oxygenation in obese patients undergoing laparoscopic surgery SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Review DE Body mass index (BMI); Pneumoperitoneum; Obesity; Perioperative management; Airway management; Ventilation; Oxygenation; General anesthesia ID OBSTRUCTIVE SLEEP-APNEA; POSITIVE-PRESSURE VENTILATION; RANDOMIZED CLINICAL-TRIAL; END-EXPIRATORY PRESSURE; SURGICAL SITE INFECTION; NATIONAL AUDIT PROJECT; AIRWAY MANAGEMENT; DIFFICULT AIRWAY; RESPIRATORY-FUNCTION; GENERAL-ANESTHESIA AB The worldwide trend toward increasing body mass index (BMI) has caused the anesthetic management of overweight, obese, and severely obese patients to become common. The increase in oxygen demand coupled with the anatomic and physiologic changes associated with excess adipose tissue make maintenance of oxygenation a major challenge during induction, maintenance and recovery from general anesthesia. It is crucial for anesthesiologists, surgeons and perioperative healthcare providers alike to have a thorough understanding of the impact of airway management and mechanical ventilation on the respiratory care of the obese in the immediate perioperative setting. In this manuscript we aim to discuss the consequences of obesity, particularly abdominal obesity, on respiratory physiology and provide suggestions on intraoperative ventilatory strategies to maintain oxygenation in the severely obese patient undergoing pneumoperitoneum. (C) 2015 American Society for Metabolic and Bariatric Surgery. All rights reserved. C1 [Ortiz, Vilma E.; Vidal-Melo, Marcos F.; Walsh, John L.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Ortiz, VE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM vortiz@partners.org FU Merck Company FX Dr. Vilma E. Ortiz: None. Dr. Marcos F. Vidal-Melo: Investigator-initiated grant from Merck Company. Dr. John L. Walsh: None. Sources of funding: None. NR 72 TC 0 Z9 0 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 EI 1878-7533 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD MAY-JUN PY 2015 VL 11 IS 3 BP 721 EP 728 DI 10.1016/j.soard.2014.11.021 PG 8 WC Surgery SC Surgery GA CM0JH UT WOS:000357363700040 PM 25863532 ER PT J AU Anderson, KS Pepe, M Marks, J Engstrom, P Patriotis, C Zangar, R Skates, S Lampe, P LaBaer, J Li, CI AF Anderson, Karen S. Pepe, Margaret Marks, Jeffrey Engstrom, Paul Patriotis, Christos Zangar, Richard Skates, Steven Lampe, Paul LaBaer, Joshua Li, Christopher I. TI A blinded multicenter phase II study of a panel of plasma biomarkers for the detection of triple negative breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Anderson, Karen S.; LaBaer, Joshua] Arizona State Univ, Biodesign Inst, Tempe, AZ 85287 USA. [Pepe, Margaret; Lampe, Paul; Li, Christopher I.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Marks, Jeffrey] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Engstrom, Paul] Fox Chase Canc Ctr, Philadelphia, PA USA. [Patriotis, Christos] Natl Canc Inst, Bethesda, MD USA. [Zangar, Richard] Pacific NW Natl Lab, Richland, WA USA. [Skates, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P4-02-05 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730202156 ER PT J AU Balmna, J Cruz, C Garber, J Fidalgo, JAP Lluch, A Tung, N Antolin, S Fernandez, C Kahatt, C Szyldergemajn, S Matos, AS Extremera, S Baselga, J Isakoff, SJ AF Balmna, Judit Cruz, Cristina Garber, Judy Fidalgo, Jose A. Perez Lluch, Ana Tung, Nadine Antolin, Silvia Fernandez, Cristian Kahatt, Carmen Szyldergemajn, Sergio Matos, Arturo Soto Extremera, Sonia Baselga, Jose Isakoff, Steven J. TI Lurbinectedin (PM01183) activity in BRCA1/2-associated or unselected metastatic breast cancer. Interim results of an ongoing phase II trial SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Balmna, Judit; Cruz, Cristina] Hosp Valle De Hebron, Barcelona, Spain. [Garber, Judy] Dana Farber Canc Inst, Boston, MA USA. [Fidalgo, Jose A. Perez; Lluch, Ana] Hosp Clin Valencia, Valencia, Spain. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Antolin, Silvia] Complejo Hosp Univ Coruna, Coruna, Spain. [Fernandez, Cristian; Kahatt, Carmen; Szyldergemajn, Sergio; Matos, Arturo Soto; Extremera, Sonia] Pharma Mar SA Soc Unipersonal, Madrid, Spain. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Isakoff, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P3-13-01 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730202122 ER PT J AU Bardia, A Starodub, A Moroose, RL Mayer, IA Diamond, JR Chuang, E Govindan, SV Sharkey, RM Maliakal, P Wegener, WA Hamburger, SA Ocean, AJ Goldenberg, DM Vahdat, LT AF Bardia, Aditya Starodub, Alexander Moroose, Rebecca L. Mayer, Ingrid A. Diamond, Jennifer R. Chuang, Ellen Govindan, Serengulam V. Sharkey, Robert M. Maliakal, Pius Wegener, William A. Hamburger, Steven A. Ocean, Allyson J. Goldenberg, David M. Vahdat, Linda T. TI IMMU-132, a new antibody-drug conjugate (ADC) against Trop-2, as a novel therapeutic for patients with relapsed/refractory, metastatic, triple-negative breast cancer (TNBC): Results from Phase I/II clinical trial (NCT01631552) SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Bardia, Aditya] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Cambridge, MA 02138 USA. [Starodub, Alexander] Indiana Univ, Hlth Ctr Canc Care, Bloomington, IN 47405 USA. [Moroose, Rebecca L.] UF Hlth Canc Ctr, Orlando, FL USA. [Mayer, Ingrid A.] Vanderbilt Ingram Canc Ctr, Breast Canc Program, Nashville, TN USA. [Diamond, Jennifer R.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Chuang, Ellen] Weill Cornell Med Coll, New York, NY USA. [Govindan, Serengulam V.; Sharkey, Robert M.; Maliakal, Pius; Wegener, William A.; Hamburger, Steven A.; Ocean, Allyson J.; Goldenberg, David M.; Vahdat, Linda T.] Immunomedics Inc, Morris Plains, NJ USA. [Goldenberg, David M.] Ctr Mol Med & Immunol, Garden State Canc Ctr, Belleville, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P5-19-27 DI 10.1158/1538-7445.SABCS14-P5-19-27 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730203178 ER PT J AU Bardia, A Dickler, MN Mayer, IA Winer, EP Mahmood, U Ulaner, G Manning, HC Rix, P Hager, JH Roychowdhury, D Maneval, EC Arteaga, CL Baselga, J AF Bardia, Aditya Dickler, Maura N. Mayer, Ingrid A. Winer, Eric P. Mahmood, Umar Ulaner, Gary Manning, H. Charles Rix, Peter Hager, Jeffrey H. Roychowdhury, Debasish Maneval, Edna Chow Arteaga, Carlos L. Baselga, Jose TI Phase I study of ARN-810, a novel and potent oral selective estrogen receptor degrader, in postmenopausal women with metastatic estrogen receptor positive (ER+), HER2-breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Bardia, Aditya; Mahmood, Umar] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Dickler, Maura N.; Ulaner, Gary; Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Mayer, Ingrid A.; Manning, H. Charles; Arteaga, Carlos L.] Vanderbilt Ingram Canc Ctr, Springfield, TN USA. [Winer, Eric P.] Dana Farber Canc Inst, Boston, MA USA. [Rix, Peter; Hager, Jeffrey H.; Roychowdhury, Debasish; Maneval, Edna Chow] Seragon Pharmaceut, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P1-13-01 DI 10.1158/1538-7445.SABCS14-P1-13-01 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730201024 ER PT J AU Borges, VF Goddard, E Partridge, AH Schedin, P AF Borges, Virginia F. Goddard, Erica Partridge, Ann H. Schedin, Pepper TI Postpartum breast cancer demonstrates increased liver and brain metastasis with a proposed role for postpartum involution SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Borges, Virginia F.; Goddard, Erica; Schedin, Pepper] Univ Colorado, Boulder, CO 80309 USA. [Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P6-08-08 DI 10.1158/1538-7445.SABCS14-P6-08-08 PG 1 WC Oncology SC Oncology GA CL1UK UT WOS:000356730203255 ER PT J AU Borges, VF Hamilton, E Yardley, DA Chaves, J Aucoin, N Ferrario, C Walker, L Krop, I AF Borges, Virginia F. Hamilton, Erika Yardley, Denise A. Chaves, Jorge Aucoin, Nathalie Ferrario, Cristiano Walker, Luke Krop, Ian TI A phase 1b study of ONT-380, an oral HER2-specific inhibitor, combined with ado-trastuzumab emtansine (T-DM1), in HER2+metastatic breast cancer (MBC) SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Borges, Virginia F.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Hamilton, Erika; Yardley, Denise A.] Sarah Cannon Res Inst, Nashville, TN USA. [Hamilton, Erika; Yardley, Denise A.] Tennessee Oncol PLLC, Nashville, TN USA. [Chaves, Jorge] Northwest Med Specialties, Tacoma, WA USA. [Aucoin, Nathalie] Hop Cite de la Sante, Laval, PQ, Canada. [Ferrario, Cristiano] Jewish Gen Hosp, Montreal, PQ, Canada. [Walker, Luke] Oncothyreon Inc, Seattle, WA USA. [Krop, Ian] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P4-15-08 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730202296 ER PT J AU Cardoso, F Bartlett, J Slaets, L van Deurzen, C van Leewen-Stok, E Porter, P Linderholm, B Hedenfalk, I Schroder, C Martens, J Bayani, J van Asperen, C Murray, M Hudis, C Middleton, L Vermeij, J Peeters, S Fraser, J Nowaczyk, M Rubio, I Aebi, S Kelly, C Ruddy, K Winer, E Nilsson, C Dal Lago, L Korde, L Benstead, K Van Den Weyngaert, D Bogler, O Goulioti, T Dif, N Messina, C Tryfonidis, K Bogaerts, J Giordano, S AF Cardoso, Fatima Bartlett, John Slaets, Leen van Deurzen, Carolien van Leewen-Stok, Elise Porter, Peggy Linderholm, Barbro Hedenfalk, Ingrid Schroder, Carolien Martens, John Bayani, Jane van Asperen, Christi Murray, Melissa Hudis, Clifford Middleton, Lavinia Vermeij, Joanna Peeters, Stephanie Fraser, Judith Nowaczyk, Monica Rubio, Isabel Aebi, Stefan Kelly, Catherine Ruddy, Kathryn Winer, Eric Nilsson, Cecilia Dal Lago, Lissandra Korde, Larissa Benstead, Kim Van Den Weyngaert, Danielle Bogler, Oliver Goulioti, Theodora Dif, Nicolas Messina, Carlo Tryfonidis, Konstantinos Bogaerts, Jan Giordano, Sharon TI Characterization of male breast cancer: First results of the EORTC10085/TBCRC/BIG/NABCG International Male BC Program SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Cardoso, Fatima] Champalimaud Canc Ctr, Lisbon, Portugal. [Bartlett, John; Bayani, Jane] Ontario Inst Canc Res, Transformat Pathol, Toronto, ON, Canada. [Bartlett, John] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. [Slaets, Leen; Dif, Nicolas; Messina, Carlo; Tryfonidis, Konstantinos; Bogaerts, Jan] European Org Res Treatment Canc, Brussels, Belgium. [van Deurzen, Carolien] Erasmus MC, Rotterdam, Netherlands. [van Deurzen, Carolien; van Leewen-Stok, Elise; Schroder, Carolien; Martens, John; van Asperen, Christi] Dutch Breast Canc Res Grp BOOG, Amsterdam, Netherlands. [Porter, Peggy] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Porter, Peggy; Korde, Larissa] Univ Washington, Seattle, WA 98195 USA. [Linderholm, Barbro] Sahlgrens Univ Hosp, Gothenburg, Sweden. [Hedenfalk, Ingrid] Lund Univ, S-22100 Lund, Sweden. [Schroder, Carolien] Univ Med Ctr, Lebanon, NH USA. [Martens, John] Erasmus MC, Breast Canc Genom & Prote Lab, Rotterdam, Netherlands. [van Asperen, Christi] Leiden Univ, Med Ctr, NL-2300 RA Leiden, Netherlands. [Murray, Melissa] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Hudis, Clifford] Mem Sloan Kettering Canc Ctr, Breast Med Serv, New York, NY USA. [Hudis, Clifford] Weill Cornell Med Coll, New York, NY USA. [Middleton, Lavinia; Giordano, Sharon] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Vermeij, Joanna] ZNA Jan Palfijn, Merksem, Belgium. [Peeters, Stephanie] UZ Leuven, Leuven, Belgium. [Fraser, Judith] Beatson West Scotland Ctr, Glasgow, Lanark, Scotland. [Nowaczyk, Monica] Specialist Hosp St Wojciech, Gdansk, Poland. [Rubio, Isabel] Hosp Univ Vall dHebron, Breast Surg Unit, Barcelona, Spain. [Aebi, Stefan] Swiss Grp Clin Canc Res SAAK, Bern, Switzerland. [Kelly, Catherine] All Ireland Cooperat Oncol Res Grp ICORG, Dublin, Ireland. [Ruddy, Kathryn] Mayo Clin, Rochester, MN USA. [Winer, Eric] Dana Farber Canc Inst, Boston, MA USA. [Nilsson, Cecilia] Vastmanlands Hosp, Vasteras, Sweden. [Dal Lago, Lissandra] Inst Jules Bordet, Brussels, Belgium. [Benstead, Kim] Cheltenham Gen Hosp, Cheltenham, Glos, England. [Van Den Weyngaert, Danielle] ZNA, Antwerp, Belgium. [Bogler, Oliver] Univ Texas MD Anderson Canc Ctr, Global Acad Programs, Houston, TX USA. [Goulioti, Theodora] Breast Int Grp, Headquarters, Brussels, Belgium. RI Aebi, Stefan/F-2004-2010 OI Aebi, Stefan/0000-0002-3383-9449 NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA S6-05 DI 10.1158/1538-7445.SABCS14-S6-05 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200043 ER PT J AU Clark, AM Wheeler, SE Taylor, DP Young, CL Pillai, VC Stolz, DB Venkataramanan, R Lauffenburger, DA Griffith, LG Wells, A AF Clark, Amanda M. Wheeler, Sarah E. Taylor, Donald P. Young, Carissa L. Pillai, Venkateswaran C. Stolz, Donna B. Venkataramanan, Raman Lauffenburger, Douglas A. Griffith, Linda G. Wells, Alan TI Modeling breast cancer dormancy and re-emergence SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Clark, Amanda M.; Wheeler, Sarah E.; Taylor, Donald P.; Young, Carissa L.; Pillai, Venkateswaran C.; Stolz, Donna B.; Venkataramanan, Raman; Lauffenburger, Douglas A.; Griffith, Linda G.; Wells, Alan] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Stolz, Donna B.; Wells, Alan] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15260 USA. [Wells, Alan] VA Pittsburgh Healthcare Syst, Pittsburgh VA Med Ctr, Pittsburgh, PA USA. [Stolz, Donna B.] Univ Pittsburgh, Ctr Canc, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P1-07-01 DI 10.1158/1538-7445.SABCS14-P1-07-01 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200220 ER PT J AU Cortes, J Perez, J He, Y Metzger, O AF Cortes, Javier Perez, Jose He, Yi Metzger-Filho, Otto TI Efficacy of eribulin in patients with invasive lobular carcinoma of the breast: data from a pooled analysis SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Cortes, Javier; Perez, Jose] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, E-08193 Barcelona, Spain. [He, Yi] Eisai Inc, Tokyo, Japan. [Metzger-Filho, Otto] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P3-13-06 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730202126 ER PT J AU Couch, FJ Hart, SN Sharma, P Toland, AE Miron, P Olson, JE Godwin, A Pankratz, VS Olswold, C Slettedahl, S Guidugli, L Beckmann, MW Rack, B Ekici, AB Konstantopoulou, I Fostira, F Fountzilas, G Pelttari, LM Yao, S Garber, J Cox, A Brauch, H Ambrosone, C Nevanlinna, H Yannoukakos, D Slager, SL Vachon, CM Eccles, DM Fasching, PA AF Couch, Fergus J. Hart, Steven N. Sharma, Priyanka Toland, Amanda Ewart Miron, Penelope Olson, Janet E. Godwin, Andrew Pankratz, Vernon S. Olswold, Curtis Slettedahl, Seth Guidugli, Lucia Beckmann, Matthias W. Rack, Brigitte Ekici, Arif B. Konstantopoulou, Irene Fostira, Florentia Fountzilas, George Pelttari, Liisa M. Yao, Song Garber, Judy Cox, Angela Brauch, Hiltrud Ambrosone, Christine Nevanlinna, Heli Yannoukakos, Drakoulis Slager, Susan L. Vachon, Celine M. Eccles, Diana M. Fasching, Peter A. TI Triple-negative breast cancer: Frequency of inherited mutations in breast cancer susceptibility genes SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Couch, Fergus J.; Hart, Steven N.; Olson, Janet E.; Pankratz, Vernon S.; Olswold, Curtis; Slettedahl, Seth; Guidugli, Lucia; Slager, Susan L.; Vachon, Celine M.] Mayo Clin, Rochester, MN USA. [Sharma, Priyanka; Godwin, Andrew] Univ Kansas, Med Ctr, Lawrence, KS 66045 USA. [Toland, Amanda Ewart] Ohio State Univ, Columbus, OH 43210 USA. [Miron, Penelope; Garber, Judy] Dana Farber Canc Inst, Boston, MA USA. [Beckmann, Matthias W.; Fasching, Peter A.] Univ Hosp, Ghent, Belgium. [Rack, Brigitte] Univ Munich, D-81377 Munich, Germany. [Ekici, Arif B.] Univ Erlangen Nurnberg, Nurnberg, Germany. [Konstantopoulou, Irene; Fostira, Florentia] Demokritos Natl Ctr Sci Res, Bern, Switzerland. [Fountzilas, George; Yannoukakos, Drakoulis] Aristotle Univ Thessaloniki, Sch Med, Thessaloniki, Greece. [Pelttari, Liisa M.; Nevanlinna, Heli] Univ Helsinki, FIN-00014 Helsinki, Finland. [Yao, Song; Ambrosone, Christine] Roswell Pk Canc Inst, Buffalo, NY USA. [Cox, Angela] Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Eccles, Diana M.] Univ Southampton, Southampton SO9 5NH, Hants, England. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P4-12-03 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730202262 ER PT J AU Cuiffo, BG Campagne, A Bell, GW Lembo, A Orso, F Lien, E Bhasin, MK Raimo, M Hanson, SE Marusyk, A Hematti, P Polyak, K Mariani, O Volinia, S Vincent-Salomon, A Taverna, D Karnoub, AE AF Cuiffo, Benjamin G. Campagne, Antoine Bell, George W. Lembo, Antonio Orso, Francesca Lien, Evan Bhasin, Manoj K. Raimo, Monica Hanson, Summer E. Marusyk, Andriy Hematti, Peiman Polyak, Kornelia Mariani, Odette Volinia, Stefano Vincent-Salomon, Anne Taverna, Daniela Karnoub, Antoine E. TI Mesenchymal stem cell regulated microRNAs converge on the speech gene FOXP2 and regulate breast cancer metastasis SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Cuiffo, Benjamin G.; Campagne, Antoine; Lien, Evan; Bhasin, Manoj K.; Karnoub, Antoine E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA. [Campagne, Antoine; Mariani, Odette; Vincent-Salomon, Anne] Inst Curie, F-75231 Paris, France. [Bell, George W.] Whitehead Inst Biomed Res, Cambridge, MA USA. [Lembo, Antonio; Orso, Francesca; Raimo, Monica; Taverna, Daniela] Univ Turin, I-10124 Turin, Italy. [Lembo, Antonio; Orso, Francesca; Raimo, Monica; Taverna, Daniela] MBC, Turin, Italy. [Hanson, Summer E.; Hematti, Peiman] Univ Wisconsin Madison, Sch Med & Publ Hlth, Madison, WI USA. [Marusyk, Andriy; Polyak, Kornelia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Volinia, Stefano] Univ Ferrara, I-44100 Ferrara, Italy. [Karnoub, Antoine E.] Harvard Stem Cell Inst, Cambridge, MA USA. [Karnoub, Antoine E.] Broad Inst MIT & Harvard, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P1-07-02 DI 10.1158/1538-7445.SABCS14-P1-07-02 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200221 ER PT J AU Desmedt, C Gundem, G Zoppoli, G Pruneri, G Biganzoli, E Fornili, M Fumagalli, D Rothe, F Brown, D Van Loo, P Brohee, S Vincent, D Keddoumi, N Majjaj, S Rouas, G Van Brussel, T Lambrechts, D Metzger, O Galant, C Bertucci, F Piccart, M Larsimont, D Viale, G Campbell, PJ Sotiriou, C AF Desmedt, Christine Gundem, Gunes Zoppoli, Gabriele Pruneri, Giancarlo Biganzoli, Elia Fornili, Marco Fumagalli, Debora Rothe, Francoise Brown, David Van Loo, Peter Brohee, Sylvain Vincent, Delphine Keddoumi, Naima Majjaj, Samira Rouas, Ghizlane Van Brussel, Thomas Lambrechts, Diether Metzger, Otto Galant, Christine Bertucci, Franois Piccart, Martine Larsimont, Denis Viale, Giuseppe Campbell, Peter J. Sotiriou, Christos TI Characterization and clinical relevance of the genomic alterations defining lobular breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Desmedt, Christine; Zoppoli, Gabriele; Fumagalli, Debora; Rothe, Francoise; Brown, David; Brohee, Sylvain; Vincent, Delphine; Keddoumi, Naima; Majjaj, Samira; Rouas, Ghizlane; Piccart, Martine; Larsimont, Denis; Sotiriou, Christos] Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium. [Gundem, Gunes; Van Loo, Peter; Campbell, Peter J.] Wellcome Trust Sanger Inst Canc Genome Project, Hinxton, Cambs, England. [Pruneri, Giancarlo; Viale, Giuseppe] European Inst Oncol, Milan, Italy. [Biganzoli, Elia; Fornili, Marco] Univ Milan, Fdn IRCCS Ist Nazl Tumori, I-20122 Milan, Italy. [Van Brussel, Thomas; Lambrechts, Diether] Vesalius Res Ctr, VIB, Ghent, Belgium. [Metzger, Otto] Dana Farber Canc Inst, Boston, MA USA. [Galant, Christine] Catholic Univ Louvain, Louvain, Belgium. [Bertucci, Franois] Inst J Paoli I Calmettes, Marseille, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA S2-05 DI 10.1158/1538-7445.SABCS14-S2-05 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200015 ER PT J AU Ellisen, L Kurian, A Lincoln, S Desmond, A Mills, M Shannon, K Gabree, M Anderson, M Kobayashi, Y Monzon, F Ford, J AF Ellisen, Leif Kurian, Allison Lincoln, Stephen Desmond, Andrea Mills, Meredith Shannon, Kristen Gabree, Michelle Anderson, Michael Kobayashi, Yuya Monzon, Federico Ford, James TI Clinical evaluation of multigene testing for hereditary breast and ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Ellisen, Leif; Desmond, Andrea; Shannon, Kristen; Gabree, Michelle] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kurian, Allison; Mills, Meredith; Ford, James] Stanford Univ, Stanford, CA 94305 USA. [Lincoln, Stephen; Anderson, Michael; Kobayashi, Yuya; Monzon, Federico] Invitae, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P4-12-04 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730202263 ER PT J AU Ferguson, CM Miller, CL Horick, N Skolny, MN Swaroop, MN Jammallo, LS O'Toole, JA Specht, MC Taghian, AG AF Ferguson, Chantal M. Miller, Cynthia L. Horick, Nora Skolny, Melissa N. Swaroop, Meyha N. Jammallo, Lauren S. O'Toole, Jean A. Specht, Michelle C. Taghian, Alphonse G. TI Blood draws, injections, blood pressure readings in the at-risk arm, and flying might not be associated with increases in arm volume: A prospective study SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Ferguson, Chantal M.; Miller, Cynthia L.; Horick, Nora; Skolny, Melissa N.; Swaroop, Meyha N.; Jammallo, Lauren S.; O'Toole, Jean A.; Specht, Michelle C.; Taghian, Alphonse G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA PD4-5 DI 10.1158/1538-7445.SABCS14-PD4-5 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200162 ER PT J AU Fumagalli, D Gacquer, D Rothe, F Lefort, A Libert, F Brown, DN Kheddoumi, N Shlien, A Konopka, T Salgado, R Larsimont, D Polyak, K Willard-Gallo, K Desmedt, C Piccart, M Abramowicz, M Campbell, PJ Detours, V Sotiriou, C AF Fumagalli, Debora Gacquer, David Rothe, Franoise Lefort, Anne Libert, Frederick Brown, David N. Kheddoumi, Naima Shlien, Adam Konopka, Tomasz Salgado, Roberto Larsimont, Denis Polyak, Kornelia Willard-Gallo, Karen Desmedt, Christine Piccart, Martine Abramowicz, Marc Campbell, Peter J. Detours, Vincent Sotiriou, Christos TI Principles governing A-to-I RNA editing in breast cancer transcriptome SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Fumagalli, Debora; Rothe, Franoise; Brown, David N.; Kheddoumi, Naima; Salgado, Roberto; Larsimont, Denis; Willard-Gallo, Karen; Desmedt, Christine; Piccart, Martine; Sotiriou, Christos] Inst Jules Bordet, Brussels, Belgium. [Gacquer, David; Lefort, Anne; Libert, Frederick; Konopka, Tomasz; Detours, Vincent] ULB, Brussels, Belgium. [Shlien, Adam; Campbell, Peter J.] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. [Polyak, Kornelia] Dana Farber Canc Inst, Boston, MA USA. [Abramowicz, Marc] Erasme Univ Hosp, Brussels, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA S4-02 DI 10.1158/1538-7445.SABCS14-S4-02 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200028 ER PT J AU Goldenberg, DM Vahdat, LT Starodub, AN Bardia, A Chuang, E Moroose, RL Diamond, JR Sharkey, RM Maliakal, PP Hamburger, SA Ocean, AJ AF Goldenberg, David M. Vahdat, Linda T. Starodub, Alexander N. Bardia, Aditya Chuang, Ellen Moroose, Rebecca L. Diamond, Jennifer R. Sharkey, Robert M. Maliakal, Pius P. Hamburger, Steven A. Ocean, Allyson J. TI IMMU-132, a potential new antibody-drug conjugate (ADC) for the treatment of triple-negative breast cancer (TNBC): Preclinical and initial clinical results SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Goldenberg, David M.] Ctr Mol Med & Immunol, Garden State Canc Ctr, Belleville, NJ USA. [Goldenberg, David M.; Sharkey, Robert M.; Maliakal, Pius P.; Hamburger, Steven A.] Immunomedics Inc, New York, NY USA. [Vahdat, Linda T.; Chuang, Ellen; Ocean, Allyson J.] Weill Cornell Med Coll, New York, NY USA. [Starodub, Alexander N.] Indiana Univ, Hlth Ctr Canc Care, Bloomington, IN 47405 USA. [Bardia, Aditya; Moroose, Rebecca L.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Diamond, Jennifer R.] Univ Florida, Hlth Canc Ctr, Gainesville, FL 32611 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P5-19-08 DI 10.1158/1538-7445.SABCS14-P5-19-08 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730203160 ER PT J AU Greenup, RA Blitzblau, R Houck, K Horton, J Howie, L Palta, M Mackey, A Scheri, R Sosa, JA Taghian, AG Peppercorn, J Smith, BL Hwang, ES AF Greenup, Rachel A. Blitzblau, Rachel Houck, Kevin Horton, Janet Howie, Lynn Palta, Manisha Mackey, Aimee Scheri, Randy Sosa, Julie A. Taghian, Alphonse G. Peppercorn, Jeffrey Smith, Barbara L. Hwang, E. Shelley TI Adjuvant radiation after lumpectomy: A cost comparison of treatment patterns in 43,247 women from the National Cancer Data Base SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Greenup, Rachel A.; Blitzblau, Rachel; Houck, Kevin; Horton, Janet; Howie, Lynn; Palta, Manisha; Mackey, Aimee; Scheri, Randy; Sosa, Julie A.; Peppercorn, Jeffrey; Hwang, E. Shelley] Duke Canc Inst, Durham, NC USA. [Taghian, Alphonse G.; Smith, Barbara L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P1-10-02 DI 10.1158/1538-7445.SABCS14-P1-10-02 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200287 ER PT J AU Isakoff, SJ Bendell, JC Cervantes, A Soria, JC Molife, LR Sanabria-Bohorquez, SM Punnoose, EA Jia, SD Patel, P Saura, C AF Isakoff, Steven J. Bendell, Johanna C. Cervantes, Andres Soria, Jean-Charles Molife, L. R. Sanabria-Bohorquez, Sandra M. Punnoose, Elizabeth A. Jia, Shidong Patel, Premal Saura, Cristina TI Phase Ib dose-escalation study of an Akt inhibitor ipatasertib (Ipat) in combination with docetaxel (Doc) or paclitaxel (Pac) in patients (pts) with metastatic breast cancer (MBC) SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Isakoff, Steven J.] Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. [Bendell, Johanna C.] Sarah Cannon Res Inst, Nashville, TN USA. [Cervantes, Andres] Hosp Clin Univ Valencia, Valencia, Spain. [Soria, Jean-Charles] Inst Gustave Roussy, Villejuif, France. [Molife, L. R.] Royal Marsden Inst Canc Res, London, England. [Sanabria-Bohorquez, Sandra M.; Punnoose, Elizabeth A.; Jia, Shidong; Patel, Premal] Genentech Inc, San Francisco, CA USA. [Saura, Cristina] Vall DHebron Univ Hosp, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P6-12-02 DI 10.1158/1538-7445.SABCS14-P6-12-02 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730204029 ER PT J AU Isakoff, SJ Kim, SB Im, SA Dent, RA Traina, TA Valero, V Saura, C Yalamanchili, S Patel, P Oliveira, M AF Isakoff, Steven J. Kim, Sung-Bae Im, Seock-Ah Dent, Rebecca A. Traina, Tiffany A. Valero, Vicente Saura, Cristina Yalamanchili, Sreeni Patel, Premal Oliveira, Mafalda TI A randomized, multicenter, phase II study of ipatasertib (Ipat, GDC-0068), an inhibitor of Akt, in combination with paclitaxel (Pac) as front-line treatment for patients (pts) with metastatic triple-negative breast cancer (TNBC) SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Isakoff, Steven J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Kim, Sung-Bae] Univ Ulsan, Coll Med, Asan Med Ctr, Ulsan, South Korea. Seoul Natl Univ, Coll Med, Seoul 151, South Korea. [Dent, Rebecca A.] Duke NUS, Natl Canc Ctr Singapore, Singapore, Singapore. [Traina, Tiffany A.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Valero, Vicente] Univ Texas MD Anderson Canc Ctr, New York, NY USA. [Saura, Cristina; Oliveira, Mafalda] VHIO, Vall Hebron Univ Hosp, Barcelona, Spain. [Yalamanchili, Sreeni; Patel, Premal] Genentech Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA OT1-1-16 DI 10.1158/1538-7445.SABCS14-OT1-1-16 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200090 ER PT J AU Janku, F Juric, D Cortes, J Rugo, H Burris, HA Schuler, M Deschler-Baier, B Middleton, MR Gil-Martin, M Berlin, J Winer, E Bootle, D Blumenstein, L Demanse, D Coughlin, C Quadt, C Baselga, J AF Janku, Filip Juric, Dejan Cortes, Javier Rugo, Hope Burris, Howard A. Schuler, Martin Deschler-Baier, Barbara Middleton, Mark R. Gil-Martin, Marta Berlin, Jordan Winer, Eric Bootle, Douglas Blumenstein, Lars Demanse, David Coughlin, Christina Quadt, Cornelia Baselga, Jose TI Phase I study of the PI3K alpha inhibitor BYL719 plus fulvestrant in patients with PIK3CA-altered and wild type ER+/HER2-locally advanced or metastatic breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Janku, Filip] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Juric, Dejan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cortes, Javier] Vall dHebron Inst Oncol, Barcelona, Spain. [Burris, Howard A.] Sarah Cannon Res Inst, Nashville, TN USA. [Burris, Howard A.] Tennessee Oncol PLLC, Murfreesboro, TN USA. [Schuler, Martin] Univ Hosp, West German Canc Ctr, Essen, Germany. [Deschler-Baier, Barbara] Univ Klinikum Wurzburg, CCC MF, Wurzburg, Germany. [Middleton, Mark R.] Churchill Hosp, Oxford Natl Inst Hlth Res, Biomed Res Ctr, Oxford, England. [Gil-Martin, Marta] Catalan Inst Oncol IDIBELL, Catalonia, Spain. [Berlin, Jordan] Vanderbilt Canc Ctr, Nashville, TN USA. [Winer, Eric] Dana Farber Canc Inst, Boston, MA USA. [Bootle, Douglas; Blumenstein, Lars; Demanse, David] Novartis Pharma AG, Basel, Switzerland. [Coughlin, Christina; Quadt, Cornelia] Novartis Pharmaceut, E Hanover, NJ USA. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA PD5-5 DI 10.1158/1538-7445.SABCS14-PD5-5 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200168 ER PT J AU Juric, D Hamilton, E Estevez, LG De Boer, RH Mayer, I Campone, M Asano, S Bhansali, S Zhang, V Hewes, B Munster, P AF Juric, Dejan Hamilton, Erika Garcia Estevez, Laura De Boer, Richard H. Mayer, Ingrid Campone, Mario Asano, Shizuka Bhansali, Suraj Zhang, Vickie Hewes, Becker Munster, Pamela TI Phase Ib/II study of LEE011 and BYL719 and letrozole in ER+, HER2-breast cancer: Safety, preliminary efficacy and molecular analysis SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Juric, Dejan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hamilton, Erika] Sarah Cannon Res Inst, Nashville, TN USA. [Garcia Estevez, Laura] Hosp San Chinarro, Madrid, Spain. [De Boer, Richard H.] Royal Melbourne Hosp, Parkville, Vic, Australia. [Mayer, Ingrid] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Campone, Mario] Inst Cancerol Ouest Rene Gauducheau, St Herblain, France. [Asano, Shizuka; Zhang, Vickie; Hewes, Becker] Novartis Inst BioMed Res, Cambridge, MA USA. [Bhansali, Suraj] Novartis Pharmaceut, San Carlos, CA USA. [Munster, Pamela] Univ Calif, Oakland, CA USA. NR 0 TC 3 Z9 3 U1 4 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P5-19-24 DI 10.1158/1538-7445.SABCS14-P5-19-24 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730203175 ER PT J AU Keenan, TE Mroz, EA Rocco, JW Ellisen, LW Moy, B Bardia, A AF Keenan, Tanya E. Mroz, Edmund A. Rocco, James W. Ellisen, Leif W. Moy, Beverly Bardia, Aditya TI Whole exome sequencing reveals greater intratumor genetic heterogeneity in primary breast cancer arising in African American compared to Caucasian women SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Keenan, Tanya E.; Mroz, Edmund A.; Rocco, James W.; Ellisen, Leif W.; Moy, Beverly; Bardia, Aditya] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P4-14-01 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730202278 ER PT J AU Lincoln, S Kurian, A Desmond, A Nilsen, G Jacobs, K Yang, S Hart, R Monzon, F Ellisen, L Ford, J AF Lincoln, Stephen Kurian, Allison Desmond, Andrea Nilsen, Geoffrey Jacobs, Kevin Yang, Shan Hart, Reece Monzon, Federico Ellisen, Leif Ford, James TI Technical evaluation of multigene testing for hereditary breast and ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Lincoln, Stephen; Nilsen, Geoffrey; Jacobs, Kevin; Yang, Shan; Hart, Reece; Monzon, Federico] Invitae, San Francisco, CA USA. [Kurian, Allison; Ford, James] Stanford Univ, Stanford, CA 94305 USA. [Desmond, Andrea; Ellisen, Leif] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P4-12-07 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730202266 ER PT J AU Luis, IV Hughes, ME Cronin, A Rugo, HS Edge, SB Moy, B Theriault, R Hassett, MJ Winer, EP Lin, NU AF Luis, Ines Vaz Hughes, Melissa E. Cronin, Angel Rugo, Hope S. Edge, Stephen B. Moy, Beverly Theriault, Richard Hassett, Michael J. Winer, Eric P. Lin, Nancy U. TI Variation in the use of mastectomy (MAST) in women with small node negative breast cancer (BC) treated at US academic institutions SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Luis, Ines Vaz; Hughes, Melissa E.; Cronin, Angel; Hassett, Michael J.; Winer, Eric P.; Lin, Nancy U.] Dana Farber Canc Inst, Boston, MA USA. [Luis, Ines Vaz] Intituto Med Mol, Lisbon, Portugal. [Rugo, Hope S.] Univ Calif, Davis, CA USA. [Edge, Stephen B.] Baptist Canc Ctr, Jacksonville, FL USA. [Moy, Beverly] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Theriault, Richard] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P2-13-03 DI 10.1158/1538-7445.SABCS14-P2-13-03 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730201200 ER PT J AU Micalizzi, DS Juric, D Niemierko, A Reynolds, KL Borger, D Vora, SR Isakoff, SJ Moy, B Ellisen, LW Bardia, A AF Micalizzi, Douglas S. Juric, Dejan Niemierko, Andrzej Reynolds, Kerry L. Borger, Darrell Vora, Sadhna R. Isakoff, Steven J. Moy, Beverly Ellisen, Leif W. Bardia, Aditya TI Association of PIK3CA mutation with clinical response to specific endocrine therapies in metastatic hormone receptor positive (HR plus ) breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Micalizzi, Douglas S.; Juric, Dejan; Niemierko, Andrzej; Reynolds, Kerry L.; Borger, Darrell; Vora, Sadhna R.; Isakoff, Steven J.; Moy, Beverly; Ellisen, Leif W.; Bardia, Aditya] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P1-13-03 DI 10.1158/1538-7445.SABCS14-P1-13-03 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730201026 ER PT J AU Miller, K Cortes, J Hurvitz, SA Krop, IE Tripathy, D Verma, S Riahi, K Yardley, DA AF Miller, Kathy Cortes, Javier Hurvitz, Sara A. Krop, Ian E. Tripathy, Debu Verma, Sunil Riahi, Kaveh Yardley, Denise A. TI HERmione: A Phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with physician's choice of chemotherapy plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer, previously treated with pe SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Miller, Kathy] Indiana Univ, Melvin & Bren Simon Canc Ctr, Bloomington, IN 47405 USA. [Cortes, Javier] Vall dHebron Inst Oncol, Barcelona, Spain. [Hurvitz, Sara A.] Univ Calif, Davis, CA USA. [Krop, Ian E.] Dana Farber Canc Inst, Boston, MA USA. [Tripathy, Debu] MD Anderson Canc Ctr, Houston, TX USA. [Verma, Sunil] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Riahi, Kaveh] Merrimack Pharmaceut Inc, Cambridge, MA USA. [Yardley, Denise A.] Sarah Cannon Res Inst & Tennessee Oncol PLLC, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA OT3-1-10 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200126 ER PT J AU Parkes, A Shin, JA Knight, H El-Jawahri, A Traeger, L Temel, JS AF Parkes, Amanda Shin, Jennifer A. Knight, Helen El-Jawahri, Areej Traeger, Lara Temel, Jennifer S. TI End-of-life outcomes and hospice and palliative care utilization in hospitalized patients with metastatic breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Parkes, Amanda; Shin, Jennifer A.; Knight, Helen; El-Jawahri, Areej; Traeger, Lara; Temel, Jennifer S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P5-16-01 DI 10.1158/1538-7445.SABCS14-P5-16-01 PG 1 WC Oncology SC Oncology GA CL1UK UT WOS:000356730203141 ER PT J AU Parkes, A Shin, JA Knight, H Schleicher, SM El-Jawahri, A Traeger, L Temel, JS AF Parkes, Amanda Shin, Jennifer A. Knight, Helen Schleicher, Stephen M. El-Jawahri, Areej Traeger, Lara Temel, Jennifer S. TI Prognostic understanding and associations with mood and quality of life in patients with metastatic breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Parkes, Amanda; Shin, Jennifer A.; Knight, Helen; El-Jawahri, Areej; Traeger, Lara; Temel, Jennifer S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schleicher, Stephen M.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P5-15-04 DI 10.1158/1538-7445.SABCS14-P5-15-04 PG 1 WC Oncology SC Oncology GA CL1UK UT WOS:000356730203122 ER PT J AU Pathania, S Bade, S Le Guillou, M Burke, K Su, Y Ting, DT Polyak, K Richardson, AL Feunteun, J Garber, JE Livingston, DM AF Pathania, Shailja Bade, Sangeeta Le Guillou, Morwenna Burke, Karly Su, Ying Ting, David T. Polyak, Kornelia Richardson, Andrea L. Feunteun, Jean Garber, Judy E. Livingston, David M. TI Defective stalled replication fork repair and predisposition to hereditary breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Pathania, Shailja; Bade, Sangeeta; Su, Ying; Polyak, Kornelia; Richardson, Andrea L.; Garber, Judy E.; Livingston, David M.] Dana Farber Canc Inst, Boston, MA USA. [Pathania, Shailja; Burke, Karly; Polyak, Kornelia; Garber, Judy E.; Livingston, David M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Le Guillou, Morwenna; Feunteun, Jean] Univ Paris 11, Lab Stabilite Genet & Oncogenese, Orsay, France. [Ting, David T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Richardson, Andrea L.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA S5-05 DI 10.1158/1538-7445.SABCS14-S5-05 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200035 ER PT J AU Phillips, KA Feng, Y Ribi, K Bernhard, J Puglisi, F Bellet, M Spazzapan, S Karlsson, P Budman, DR Zaman, K Abdi, EA Domchek, SM Regan, MM Coates, AS Gelber, RD Maruff, P Boyle, F Forbes, JF Fleming, GF Francis, PA AF Phillips, Kelly-Anne Feng, Yang Ribi, Karin Bernhard, Juerg Puglisi, Fabio Bellet, Meritxell Spazzapan, Simon Karlsson, Per Budman, Daniel R. Zaman, Khalil Abdi, Ehtesham A. Domchek, Susan M. Regan, Meredith M. Coates, Alan S. Gelber, Richard D. Maruff, Paul Boyle, Frances Forbes, John F. Fleming, Gini F. Francis, Prudence A. TI Co-SOFT: The cognitive function substudy of the suppression of ovarian function trial (SOFT) SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Phillips, Kelly-Anne; Francis, Prudence A.] ANZBCTG, Peter MacCallum Canc Ctr, Cooks Hill, NSW, Australia. [Phillips, Kelly-Anne; Puglisi, Fabio; Spazzapan, Simon; Karlsson, Per; Zaman, Khalil; Abdi, Ehtesham A.; Boyle, Frances; Forbes, John F.; Francis, Prudence A.] IBCSG, Bern, Switzerland. [Feng, Yang; Regan, Meredith M.; Gelber, Richard D.] Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA USA. [Ribi, Karin; Bernhard, Juerg] IBCSG Coordinating Ctr, Bern, Switzerland. [Puglisi, Fabio] Univ Hosp Udine, Udine, Italy. [Bellet, Meritxell] Hosp Valle De Hebron, Barcelona, Spain. [Bellet, Meritxell] SOLTI, Barcelona, Spain. [Spazzapan, Simon] Ctr Riferimento Oncol, Aviano, Italy. [Karlsson, Per] Sahlgrens Univ Hosp, Gothenburg, Sweden. [Budman, Daniel R.] Hofstra North Shore LIJ Sch Med, Hempstead, NY USA. [Budman, Daniel R.] NRG Oncol, Denver, CO USA. [Zaman, Khalil] Ctr Pluridisciplinaire Oncol CHUV, Lausanne, Switzerland. [Abdi, Ehtesham A.] Tweed Heads Hosp, Tweed Heads, Australia. [Abdi, Ehtesham A.] Griffith Univ, ANZBCTG, Nathan, Qld 4111, Australia. [Domchek, Susan M.] Abramson Canc Ctr, Philadelphia, PA USA. [Domchek, Susan M.] ECOG ACRIN, Chicago, IL USA. [Coates, Alan S.] Int Breast Canc Study Grp, Bern, Switzerland. [Coates, Alan S.] ANZBCTG, Cooks Hill, NSW, Australia. [Maruff, Paul] Cogstate Ltd, Melbourne, Vic, Australia. [Boyle, Frances] Mater Hosp, ANZBCTG, Dublin, Ireland. [Forbes, John F.] ANZBCTG, Calgary Mater Newcastle, Cooks Hill, NSW, Australia. [Fleming, Gini F.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Fleming, Gini F.] Alliance Clin Trials Oncol, Sydney, NSW, Australia. OI Phillips, Kelly-Anne/0000-0002-0475-1771 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P1-12-06 DI 10.1158/1538-7445.SABCS14-P1-12-06 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730201012 ER PT J AU Richardson, AL Silver, DP Szallasi, Z Birkbak, NJ Wang, ZGC Iglehart, JD Mayer, EL Winer, EP Tung, NM Ryan, PD Isakoff, SJ Barry, WT Greene-Collozi, A Gutin, A Reid, J Neff, C Jones, J Timms, K Hartman, AR Garber, JE AF Richardson, Andrea L. Silver, Daniel P. Szallasi, Zoltan Birkbak, Nicolai J. Wang, Zhigang C. Iglehart, J. Dirk Mayer, Erica L. Winer, Eric P. Tung, Nadine M. Ryan, Paula D. Isakoff, Steven J. Barry, William T. Greene-Collozi, April Gutin, Alexander Reid, Julia Neff, Chris Jones, Joshua Timms, Kirsten Hartman, Anne-Renee Garber, Judy E. TI Homologous recombination deficiency (HRD) assay predicts response to cisplatin neoadjuvant chemotherapy in patients with triple negative breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Richardson, Andrea L.; Silver, Daniel P.; Wang, Zhigang C.; Iglehart, J. Dirk; Mayer, Erica L.; Winer, Eric P.; Barry, William T.; Greene-Collozi, April; Neff, Chris; Garber, Judy E.] Dana Farber Canc Inst, Boston, MA USA. [Szallasi, Zoltan; Birkbak, Nicolai J.] Tech Univ Denmark, Lyngby, Denmark. [Szallasi, Zoltan] Childrens Hosp Boston, Boston, MA USA. [Tung, Nadine M.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Isakoff, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gutin, Alexander; Reid, Julia; Jones, Joshua; Timms, Kirsten; Hartman, Anne-Renee] Myriad Genet Labs Inc, Salt Lake City, UT USA. [Ryan, Paula D.] Fox Chase Canc Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P3-06-11 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730202004 ER PT J AU Robson, M Tutt, A Balmana, J Kaufman, B Garber, J Geyer, C Ford, J Sharma, P Stuart, M Mann, H Fasching, PA AF Robson, Mark Tutt, Andrew Balmana, Judith Kaufman, Bella Garber, Judy Geyer, Charles Ford, James Sharma, Priyanka Stuart, Mary Mann, Helen Fasching, Peter A. TI OlympiA, Neo-Olympia and OlympiAD: Randomized phase III trials of olaparib in patients (pts) with breast cancer (BC) and a germline BRCA1/2 mutation (gBRCAm) SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Robson, Mark] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Tutt, Andrew] Kings Coll London, Sch Med, London WC2R 2LS, England. [Tutt, Andrew] Kings Coll London, Inst Canc Reseach, London WC2R 2LS, England. [Balmana, Judith] Univ Hosp Vall dHebron, Barcelona, Spain. [Kaufman, Bella] Sheba Med Ctr, Tel Hashomer, Israel. [Garber, Judy] Dana Farber Canc Inst, Boston, MA USA. [Geyer, Charles] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23284 USA. [Ford, James] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Sharma, Priyanka] Univ Kansas, Med Ctr, Lawrence, KS 66045 USA. [Stuart, Mary; Mann, Helen] AstraZeneca, Bengaluru, Karnataka, India. [Fasching, Peter A.] Univ Hosp, Newark, NJ USA. [Fasching, Peter A.] German Breast Grp, Neu Isenburg, Germany. [Balmana, Judith] SOLTI Breast Canc Res Grp, Barcelona, Spain. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA OT1-1-04 DI 10.1158/1538-7445.SABCS14-OT1-1-04 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200079 ER PT J AU Rosenberg, SM Sepucha, K Ruddy, KJ Schapira, L Come, S Borges, V Morgan, E Lin, NU Gelber, S Tamimi, RM Partridge, AH AF Rosenberg, Shoshana M. Sepucha, Karen Ruddy, Kathryn J. Schapira, Lidia Come, Steven Borges, Virginia Morgan, Evan Lin, Nancy U. Gelber, Shari Tamimi, Rulla M. Partridge, Ann H. TI Decision-making surrounding adjuvant chemotherapy in young women with early stage breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Rosenberg, Shoshana M.; Morgan, Evan; Lin, Nancy U.; Gelber, Shari; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA USA. [Sepucha, Karen; Schapira, Lidia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ruddy, Kathryn J.] Mayo Clin, Rochester, MN USA. [Come, Steven] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Borges, Virginia] Univ Colorado, Boulder, CO 80309 USA. [Tamimi, Rulla M.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P2-10-03 DI 10.1158/1538-7445.SABCS14-P2-10-03 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730201173 ER PT J AU Saura, C Sachdev, J Patel, MR Cervantes, A Juric, D Infante, JR Richards, D Sanabria, S Lu, XY Ware, J Wilson, TR Parmar, H Hsu, JY Oliveira, M Winer, EP Von Hoff, DD Baselga, J Krop, IE AF Saura, Cristina Sachdev, Jasgit Patel, Manish R. Cervantes, Andres Juric, Dejan Infante, Jeffrey R. Richards, Donald Sanabria, Sandra Lu, Xuyang Ware, Joseph Wilson, Timothy R. Parmar, Hema Hsu, Jerry Y. Oliveira, Mafalda Winer, Eric P. Von Hoff, Daniel D. Baselga, Jose Krop, Ian E. TI Ph1b study of the PI3K inhibitor taselisib (GDC-0032) in combination with letrozole in patients with hormone receptor-positive advanced breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Saura, Cristina; Oliveira, Mafalda] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol Barcelona, Barcelona, Spain. [Sachdev, Jasgit; Von Hoff, Daniel D.] Virginia G Piper Canc Ctr TGen, Scottsdale, AZ USA. [Patel, Manish R.] Florida Canc Specialists, Sarah Cannon Res Inst, Ft Myers, FL USA. [Cervantes, Andres] Univ Valencia, Inst Hlth Res INCLIVA, E-46003 Valencia, Spain. [Juric, Dejan] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Infante, Jeffrey R.] Sarah Cannon Res Inst & Tennessee Oncol PLLC, Nashville, TN USA. [Richards, Donald] Texas Oncol, Dallas, TX USA. [Winer, Eric P.; Krop, Ian E.] Dana Farber Canc Inst, Boston, MA USA. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Sanabria, Sandra; Lu, Xuyang; Ware, Joseph; Wilson, Timothy R.; Parmar, Hema; Hsu, Jerry Y.] Genentech Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA PD5-2 DI 10.1158/1538-7445.SABCS14-PD5-2 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200166 ER PT J AU Schoffski, P Cresta, S Mayer, IA Wildiers, H Rooney, I Apt, D Gendreau, S Morrissey, K Lackner, M Spoerke, J Winer, E AF Schoffski, Patrick Cresta, Sara Mayer, Ingrid A. Wildiers, Hans Rooney, Isabelle Apt, Doris Gendreau, Steve Morrissey, Kari Lackner, Mark Spoerke, Jill Winer, Eric TI Tolerability and anti-tumor activity of the oral PI3K inhibitor GDC-0941 in combination with paclitaxel, with and without bevacizumab or trastuzumab in patients with locally recurrent or metastatic breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Schoffski, Patrick; Wildiers, Hans] Univ Hosp Leuven, Expt Oncol Lab, Louvain, Belgium. [Cresta, Sara] Fdn IRCCS Inst Nazl Tumori, Milan, Italy. [Mayer, Ingrid A.] Vanderbilt Ingram Canc Ctr, Springfield, TN USA. [Rooney, Isabelle; Apt, Doris; Gendreau, Steve; Spoerke, Jill] Genentech Inc, Exploratory Clin Dev, San Francisco, CA USA. [Morrissey, Kari] Genentech Inc, Small Mol Clin Pharmacol, San Francisco, CA USA. [Lackner, Mark] Genentech Inc, Oncol Biomarker Dev, San Francisco, CA USA. [Winer, Eric] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P5-19-10 DI 10.1158/1538-7445.SABCS14-P5-19-10 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730203162 ER PT J AU Sestak, I Zhang, Y Schroeder, BE Goss, PE Dowsett, M Sgroi, DC Schnabel, CA Cuzick, J AF Sestak, Ivana Zhang, Yi Schroeder, Brock E. Goss, Paul E. Dowsett, Mitch Sgroi, Dennis C. Schnabel, Catherine A. Cuzick, Jack TI Integration of breast cancer index (BCI) with clinicopathological factors for prediction of distant recurrence in ER plus breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Sestak, Ivana; Cuzick, Jack] Queen Mary Univ, Ctr Canc Prevent, London, England. [Zhang, Yi; Schroeder, Brock E.; Schnabel, Catherine A.] BioTheranost Inc, San Diego, CA USA. [Goss, Paul E.; Sgroi, Dennis C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dowsett, Mitch] Royal Marsden Hosp, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P4-11-19 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730202242 ER PT J AU Sgroi, D Goss, P Chapman, JA Richardson, E Binns, S Zhang, Y Schnabel, C Erlander, M Pritchard, K Han, L Sheperd, L Pollack, M AF Sgroi, Dennis Goss, Paul Chapman, Judy-Anne Richardson, Elizabeth Binns, Shemeica Zhang, Yi Schnabel, Cathy Erlander, Mark Pritchard, Kathy Han, Lei Sheperd, Lois Pollack, Michael TI Prognostic significance of breast cancer index (BCI) in node-positive hormone receptor positive early breast cancer: NCIC CTG MA. 14 SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Sgroi, Dennis; Goss, Paul; Richardson, Elizabeth; Binns, Shemeica] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chapman, Judy-Anne; Han, Lei; Sheperd, Lois] Queens Univ, Kingston, ON K7L 3N6, Canada. [Zhang, Yi; Schnabel, Cathy; Erlander, Mark] BioTheranostics Inc, San Diego, CA USA. [Pritchard, Kathy] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON M5S 1A1, Canada. [Pollack, Michael] McGill Univ, Montreal, PQ H3A 2T5, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P6-01-10 DI 10.1158/1538-7445.SABCS14-P6-01-10 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730203200 ER PT J AU Sparano, JA Zhao, FM Martino, S Ligibel, J Saphner, T Wolff, AC Sledge, GW Perez, EA Wood, WC Davidson, NE AF Sparano, Joseph A. Zhao, Fengmin Martino, Silvana Ligibel, Jennifer Saphner, Thomas Wolff, Antonio C. Sledge, George W., Jr. Perez, Edith A. Wood, William C. Davidson, Nancy E. TI Ten year update of E1199: Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in patients with axillary node-positive or high-risk node-negative breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Sparano, Joseph A.] Montefiore Med Ctr, Albert Einstein Coll Med, New York, NY USA. [Zhao, Fengmin; Ligibel, Jennifer] Dana Farber Canc Inst, Boston, MA USA. [Martino, Silvana] Angeles Clin, Los Angeles, CA USA. [Saphner, Thomas] Aurora Hlth, Milwaukee, WI USA. [Wolff, Antonio C.] Johns Hopkins, Baltimore, MD USA. [Sledge, George W., Jr.] Stanford Univ, Stanford, CA 94305 USA. [Perez, Edith A.] Mayo Clin, Rochester, MN USA. [Wood, William C.] Emory Univ, Atlanta, GA 30322 USA. [Davidson, Nancy E.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA S3-03 DI 10.1158/1538-7445.SABCS14-S3-03 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200020 ER PT J AU Swaroop, MN Miller, CL Horick, N Ferguson, CM Skolny, MN O'Toole, J Jammallo, LS Specht, MC Taghian, AG AF Swaroop, Meyha N. Miller, Cynthia L. Horick, Nora Ferguson, Chantal M. Skolny, Melissa N. O'Toole, Jean Jammallo, Lauren S. Specht, Michelle C. Taghian, Alphonse G. TI Risk of breast cancer related lymphedema after treatment with taxane-based chemotherapy: A prospective cohort study SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Swaroop, Meyha N.; Miller, Cynthia L.; Horick, Nora; Ferguson, Chantal M.; Skolny, Melissa N.; O'Toole, Jean; Jammallo, Lauren S.; Specht, Michelle C.; Taghian, Alphonse G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P1-09-13 DI 10.1158/1538-7445.SABCS14-P1-09-13 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200266 ER PT J AU Tolaney, SM Rosen, LS Beeram, M Goldman, JW Gandhi, L Tolcher, AW Papadopoulos, KP Rasco, DW Myrand, SP Kulanthaivel, P Andrews, JM Frenzel, M Cronier, DM Chan, EM Flaherty, KT Wen, PY Shapiro, GI Patnaik, A AF Tolaney, Sara M. Rosen, Lee S. Beeram, Muralidhar Goldman, Jonathan W. Gandhi, Leena Tolcher, Anthony W. Papadopoulos, Kyriakos P. Rasco, Drew W. Myrand, Scott P. Kulanthaivel, Palaniappan Andrews, Joan M. Frenzel, Martin Cronier, Damien M. Chan, Edward M. Flaherty, Keith T. Wen, Patrick Y. Shapiro, Geoffrey I. Patnaik, Amita TI Clinical activity of abemaciclib, an oral cell cycle inhibitor, in metastatic breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Tolaney, Sara M.; Gandhi, Leena; Wen, Patrick Y.; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA USA. [Rosen, Lee S.; Goldman, Jonathan W.] Univ Calif, Davis, CA USA. [Beeram, Muralidhar; Tolcher, Anthony W.; Papadopoulos, Kyriakos P.; Rasco, Drew W.; Patnaik, Amita] South Texas Accelerated Res Therapeut, Seoul, South Korea. [Myrand, Scott P.; Kulanthaivel, Palaniappan; Andrews, Joan M.; Frenzel, Martin; Cronier, Damien M.; Chan, Edward M.] Eli Lilly & Co, Indianapolis, IN USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 4 U2 6 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 MAY 1 PY 2015 VL 75 SU 9 MA P5-19-13 DI 10.1158/1538-7445.SABCS14-P5-19-13 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730203165 ER PT J AU Tromberg, BJ Zhang, Z Leproux, A O'Sullivan, TD Cerussi, AE Carpenter, P Mehta, R Roblyer, D Yang, W Paulsen, KD Pogue, BW Jiang, SD Kaufman, P Yodh, AG Chung, SH Schnall, M Snyder, B Hylton, N Boas, DA Carp, SA Isakoff, SJ Mankoff, D AF Tromberg, Bruce J. Zhang, Zheng Leproux, Anais O'Sullivan, Thomas D. Cerussi, Albert E. Carpenter, Philip Mehta, Rita Roblyer, Darren Yang, Wei Paulsen, Keith D. Pogue, Brian W. Jiang, Shudong Kaufman, Peter Yodh, Arjun G. Chung, So-Hyun Schnall, Mitchell Snyder, Brad Hylton, Nola Boas, David A. Carp, Stefan A. Isakoff, Steven J. Mankoff, David TI Predicting pre-surgical neoadjuvant chemotherapy response in breast cancer using diffuse optical spectroscopic imaging (DOSI): Results from the ACRIN 6691 study SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Zhang, Zheng; Snyder, Brad] Brown Univ, Providence, RI 02912 USA. [Paulsen, Keith D.; Pogue, Brian W.; Jiang, Shudong; Kaufman, Peter] Dartmouth Coll, Hanover, NH 03755 USA. [Roblyer, Darren] Boston Univ, Boston, MA 02215 USA. [Yang, Wei] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Yodh, Arjun G.; Chung, So-Hyun; Schnall, Mitchell; Mankoff, David] Univ Penn, Philadelphia, PA 19104 USA. [Boas, David A.; Carp, Stefan A.; Isakoff, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA S4-04 DI 10.1158/1538-7445.SABCS14-S4-04 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730200030 ER PT J AU Zhang, Y Schroeder, BE Jannok, PLJ Fornander, T Stal, O Schnabel, CA Sgroi, DC AF Zhang, Yi Schroeder, Brock E. Jannok, Piiha-Lotta Jerevall Fornander, Tommy Stal, Olle Schnabel, Catherine A. Sgroi, Dennis C. TI Prediction of benefit from endocrine therapy in ER plus early stage breast cancer: Correlative studies of the breast cancer index HoxB13/IL17BR (H/I) ratio, ER, PR, and HER2 expression in the randomized Stockholm trial SO CANCER RESEARCH LA English DT Meeting Abstract CT 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium CY DEC 09-13, 2014 CL San Antonio, TX SP Canc Therapy Res Ctr, Amer Assoc Canc Res C1 [Zhang, Yi; Schroeder, Brock E.; Schnabel, Catherine A.] BioTheranostics Inc, San Diego, CA USA. [Jannok, Piiha-Lotta Jerevall; Sgroi, Dennis C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fornander, Tommy] Karolinska Univ Hosp, Solna, Sweden. [Stal, Olle] Linkoping Univ, S-58183 Linkoping, Sweden. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2015 VL 75 SU 9 MA P3-06-06 DI 10.1158/1538-7445.SABCS14-P3-06-06 PG 2 WC Oncology SC Oncology GA CL1UK UT WOS:000356730201299 ER PT J AU Ji, JS Power, MC Sparrow, D Spiro, A Hu, H Louis, ED Weisskopf, MG AF Ji, John S. Power, Melinda C. Sparrow, David Spiro, Avron, III Hu, Howard Louis, Elan D. Weisskopf, Marc G. TI Lead Exposure and Tremor among Older Men: The VA Normative Aging Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID ACID-DEHYDRATASE POLYMORPHISM; AMYOTROPHIC-LATERAL-SCLEROSIS; BONE LEAD; ALZHEIMERS-DISEASE; BMAA; BURDEN; GUAM; ALS AB BACKGROUND: Tremor is one of the most common neurological signs, yet its etiology is poorly understood. Case-control studies suggest an association between blood lead and essential tremor, and that this association is modified by polymorphisms in the -aminolevulinic acid dehydrogenase (ALAD) gene. OBJECTIVE: We aimed to examine the relationship between lead and tremor, including modification by ALAD, in a prospective cohort study, using both blood lead and bone lead-a biomarker of cumulative lead exposure. METHODS: We measured tibia (n = 670) and patella (n = 672) bone lead and blood lead (n = 807) among older men (age range, 50-98 years) in the VA Normative Aging Study cohort. A tremor score was created based on an approach using hand-drawing samples. ALAD genotype was dichotomized as ALAD-2 carriers or not. We used linear regression adjusted for age, education, smoking, and alcohol intake to estimate the associations between lead biomarkers and tremor score. RESULTS: In unadjusted analyses, there was a marginal association between quintiles of all lead biomarkers and tremor scores (p-values < 0.13), which did not persist in adjusted models. Age was the strongest predictor of tremor. Among those younger than the median age (68.9 years), tremor increased significantly with blood lead (p = 0.03), but this pattern was not apparent for bone lead. We did not see modification by ALAD or an association between bone lead and change in tremor score over time. CONCLUSION: Our results do not strongly support an association between lead exposure and tremor, and suggest no association with cumulative lead biomarkers, although there is some suggestion that blood lead may be associated with tremor among the younger men in our cohort. C1 [Ji, John S.; Power, Melinda C.; Weisskopf, Marc G.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. [Power, Melinda C.; Weisskopf, Marc G.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Sparrow, David; Spiro, Avron, III] VA Boston Healthcare Syst, Boston, MA USA. [Sparrow, David; Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Sparrow, David; Spiro, Avron, III] Boston Univ, Sch Med, Boston, MA 02118 USA. [Hu, Howard] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Louis, Elan D.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. RP Ji, JS (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, 401 Pk Dr,3 East, Boston, MA 02215 USA. EM joj518@mail.harvard.edu OI Hu, Howard/0000-0002-3676-2707 FU National Institutes of Health (NIH) [R01-ES05257, ES-00002]; Education and Research Center for Occupational Safety and Health Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health [T42/OH008416]; VA Clinical Science Research & Development Merit Review and Research Career Scientist awards; Clinical Science Research and Development Service of the U.S. Department of Veterans Affairs (VA); NIH [R01-ES05257, R01-AA08941, R01-AG13006, R01-AG14345, R01-AG18436, 5-P42-ES05947]; U.S. Department of Agriculture, Agricultural Research Service [53-K06-510]; VA Cooperative Studies Program/ERIC FX This work was supported by grants R01-ES05257 and ES-00002 from the National Institutes of Health (NIH). J.S.J. was supported by the Education and Research Center for Occupational Safety and Health Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health grant award T42/OH008416 at the Harvard School of Public Health. D.S. and A.S. were both supported by VA Clinical Science Research & Development Merit Review and Research Career Scientist awards.; The Cognition and Health in Aging Men Project (CHAMP) is supported by the Clinical Science Research and Development Service of the U.S. Department of Veterans Affairs (VA), the NIH (grants R01-AA08941, R01-AG13006, R01-AG14345, R01-AG18436, 5-P42-ES05947, and R01-ES05257), and the U.S. Department of Agriculture, Agricultural Research Service (contract 53-K06-510). The VA Normative Aging Study is supported by the VA Cooperative Studies Program/ERIC, and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). NR 23 TC 0 Z9 0 U1 0 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2015 VL 123 IS 5 BP 445 EP 450 DI 10.1289/ehp.1408535 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA CL9JK UT WOS:000357294000023 PM 25633720 ER PT J AU Kang, W Sha, L Berlin, RB Goldman, JM AF Kang, Woochul Sha, Lui Berlin, Richard B., Jr. Goldman, Julian M. TI The Design of Safe Networked Supervisory Medical Systems Using Organ-Centric Hierarchical Control Architecture SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS LA English DT Article DE Device interoperability; medical device; networking; organ-centric; plug-and-play; safety; supervisory control ID INTEGRATION; MODEL AB There are growing demands to leverage network connectivity and interoperability of medical devices in order to improve patient safety and the effectiveness of medical services. However, if not properly designed, the integration of medical devices through networking could significantly increase the complexity of the system and make the system more vulnerable to potential errors, jeopardizing patient safety. The system must be designed and verified to guarantee the safety of patients and the effectiveness of medical services in the face of potential problems such as network failures. In this paper, we propose organ-centric hierarchical control architecture as a viable solution that reduces the complexity in system design and verification. In our approach, medical devices are grouped into clusters according to organ-specific human physiology. Each cluster captures common patterns arising out of medical device interactions and becomes a survivable semiautonomous unit during network failures. Further, safety verification and runtime enforcement can be modularized along organ-centric hierarchical control structure. We show the feasibility of the proposed approach under Simulink's model-based development framework. A simplified scenario for airway laser surgery is used as a case study. C1 [Kang, Woochul] Incheon Natl Univ, Embedded Syst Engn Dept, Inchon, South Korea. [Sha, Lui] Univ Illinois, Dept Comp Sci, Champaign, IL 61820 USA. [Berlin, Richard B., Jr.] Carle Fdn Hosp, Urbana, IL 61801 USA. [Goldman, Julian M.] Massachusetts Gen Hosp, CIMIT, Boston, MA 02114 USA. RP Kang, W (reprint author), Incheon Natl Univ, Embedded Syst Engn Dept, Inchon, South Korea. EM wchkang@incheon.ac.kr; lrs@illinois.edu; richard.berlin@carle.com; jmgoldman@partners.org FU NIBIB NIH HHS [1U01EB012470] NR 29 TC 1 Z9 1 U1 3 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2168-2194 J9 IEEE J BIOMED HEALTH JI IEEE J. Biomed. Health Inform. PD MAY PY 2015 VL 19 IS 3 BP 1077 EP 1086 DI 10.1109/JBHI.2014.2333778 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA CK8TR UT WOS:000356511900035 PM 24988597 ER PT J AU Storzbach, D O'Neil, ME Roost, SM Kowalski, H Iverson, GL Binder, LM Fann, JR Huckans, M AF Storzbach, Daniel O'Neil, Maya Elin Roost, Saw-Myo Kowalski, Halina Iverson, Grant L. Binder, Laurence M. Fann, Jesse R. Huckans, Marilyn TI Comparing the Neuropsychological Test Performance of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans with and without Blast Exposure, Mild Traumatic Brain Injury, and Posttraumatic Stress Symptoms SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Brain injuries; Blast injuries; Explosions; Military personnel; Combat disorders; Stress disorders; Post-traumatic; Cognitive symptoms ID MILITARY; OUTCOMES; PERSONNEL; SOLDIERS; HEALTH; WAR AB To compare neuropsychological test performance of Veterans with and without mild traumatic brain injury (MTBI), blast exposure, and posttraumatic stress disorder (PTSD) symptoms. We compared the neuropsychological test performance of 49 Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans diagnosed with MTBI resulting from combat blast-exposure to that of 20 blast-exposed OEF/OIF Veterans without history of MTBI, 23 OEF/OIF Veterans with no blast exposure or MTBI history, and 40 matched civilian controls. Comparison of neuropsychological test performance across all four participant groups showed a complex pattern of mixed significant and mostly nonsignificant results, with omnibus tests significant for measures of attention, spatial abilities, and executive function. The most consistent pattern was the absence of significant differences between blast-exposed Veterans with MTBI history and blast-exposed Veterans without MTBI history. When blast-exposed Veteran groups with and without MTBI history were aggregated and compared to non-blast-exposed Veterans, there were significant differences for some measures of learning and memory, spatial abilities, and executive function. However, covariation for severity of PTSD symptoms eliminated all significant omnibus neuropsychological differences between Veteran groups. Our results suggest that, although some mild neurocognitive effects were associated with blast exposure, these neurocognitive effects might be better explained by PTSD symptom severity rather than blast exposure or MTBI history alone. C1 [Storzbach, Daniel; O'Neil, Maya Elin; Roost, Saw-Myo; Kowalski, Halina; Huckans, Marilyn] Portland VA Med Ctr, Portland, OR USA. [Storzbach, Daniel; O'Neil, Maya Elin; Binder, Laurence M.; Huckans, Marilyn] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Storzbach, Daniel; Binder, Laurence M.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [O'Neil, Maya Elin] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Iverson, Grant L.] Def & Vet Brain Injury Ctr, Bethesda, MD USA. [Fann, Jesse R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Fann, Jesse R.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP O'Neil, ME (reprint author), Portland VA Med Ctr R&D 66, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM maya.oneil@va.gov FU VA Merit Review Award from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development [B5060R]; Veterans Affairs Health Services Research and Development Center of Innovation grant; Center to Improve Veteran Involvement in Care [CIN 13-404]; Agency for Healthcare Research Quality [1 K12 HS019456 01] FX This work was supported by VA Merit Review Award #B5060R to D.S. from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development, a Veterans Affairs Health Services Research and Development Center of Innovation grant, Center to Improve Veteran Involvement in Care, Award #CIN 13-404, and an Agency for Healthcare Research & Quality-funded PCOR K12 award to MEO (#1 K12 HS019456 01). This material is the result of work supported with resources and the use of facilities at the Portland Veterans Affairs Medical Center, Portland, Oregon. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. All authors declare no conflicts of interests involved in the research presented in the manuscript. The corresponding author (M.E.O.) declares she had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. D. Storzbach and M. O'Neil contributed equally to this work. NR 25 TC 1 Z9 1 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 MAY PY 2015 VL 21 IS 5 BP 353 EP 363 DI 10.1017/S1355617715000326 PG 11 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA CL9QK UT WOS:000357313000004 PM 26029852 ER PT J AU Roshanravan, B Patel, KV Robinson-Cohen, C de Boer, IH O'Hare, AM Ferrucci, L Himmelfarb, J Kestenbaum, B AF Roshanravan, Baback Patel, Kushang V. Robinson-Cohen, Cassianne de Boer, Ian H. O'Hare, Ann M. Ferrucci, Luigi Himmelfarb, Jonathan Kestenbaum, Bryan TI Creatinine Clearance, Walking Speed, and Muscle Atrophy: A Cohort Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Physical performance; skeletal muscle composition; muscle strength; mobility impairment; muscle atrophy; longitudinal trajectory; creatinine clearance (Clcr); renal function; chronic kidney disease (CKD) ID CHRONIC KIDNEY-DISEASE; OLDER-ADULTS; BODY-COMPOSITION; CYSTATIN-C; GAIT-SPEED; PHYSICAL PERFORMANCE; GLUCOSE-INTOLERANCE; MOBILITY DISABILITY; PROTEIN-DEGRADATION; METABOLIC-ACIDOSIS AB Background: Chronic kidney disease is associated with malnutrition and inflammation. These processes may lead to loss of skeletal muscle and reduced physical performance. Associations of kidney function with muscle composition and longitudinal measures of physical performance are unknown. Study Design: Prospective cohort study. Setting & Participants: We evaluated 826 community-dwelling older adults enrolled in the Invecchiare in Chianti (InCHIANTI) Study who were free of baseline stroke or activities of daily living disability. Predictor: Baseline creatinine clearance (Clcr) based on 24-hour urine collection. Outcomes: Cross-sectional and longitudinal trajectories of physical performance measured by 7-m usual gait speed, 400-m fast gait speed, and knee extension strength using isometric dynamometry. Calf muscle composition assessed by quantitative computed tomography. Results: Mean age of participants was 74 +/- 7 (SD) years, with 183 having Clcr < 60 mL/min/1.73 m(2). After adjustment, each 10-mL/min/1.73 m(2) decrement in Clcr was associated with 0.01 (95% CI, 0.004-0.017) m/s slower 7-m usual walking speed and 0.008 (95% CI, 0.002-0.014) m/s slower 400-m walking speed. Each 10-mL/min/1.73 m(2) decrement in Clcr was associated with 28 (95% CI, 0.8-55) mm(2) lower muscle area and 0.15 (95% CI, 0.04-0.26) mg/cm(3) lower muscle density. After adjustment, lower Clcr was associated with slower mean 7-m (P = 0.005) and 400-m (P = 0.02) walk and knee extension strength (P = 0.001) during the course of follow-up. During a mean follow-up of 7.1 +/- 2.5 years, each 10-mL/min/1.73 m(2) lower baseline Clcr was associated with 0.024 (95% CI, 0.01-0.037) kg/y greater decline in knee strength. Limitations: Single baseline measurement of Clcr and 3-year interval between follow-up visits may lead to nondifferential misclassification and attenuation of estimates. Conclusions: Among older adults, lower Clcr is associated with muscle atrophy, reduced walking speed, and more rapid declines in lower-extremity strength over time. (C) 2015 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Roshanravan, Baback; Robinson-Cohen, Cassianne; de Boer, Ian H.; Himmelfarb, Jonathan; Kestenbaum, Bryan] Univ Washington, Div Nephrol, Kidney Res Inst, Dept Med, Seattle, WA 98104 USA. [Patel, Kushang V.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98104 USA. [O'Hare, Ann M.] Univ Washington, Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 98104 USA. [Ferrucci, Luigi] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Roshanravan, B (reprint author), Univ Washington, Div Nephrol, Kidney Res Inst, Box 359606,325 9th Ave, Seattle, WA 98104 USA. EM broshanr@u.washington.edu OI Robinson-Cohen, Cassianne/0000-0003-4783-7046 FU Italian Ministry of Health [ICS110.1/RF97.71]; National Institute on Aging (NIA), National Institutes of Health (NIH); NIA [N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002, 1 Z01 AG001050-01]; NIH [1K23DK099442-01] FX The InCHIANTI Study baseline (1998-2000) was supported as a "targeted project" by the Italian Ministry of Health (ICS110.1/RF97.71) and in part by the Intramural Research Program of the National Institute on Aging (NIA), National Institutes of Health (NIH); the InCHIANTI follow-ups were supported by the NIA (N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002, and 1 Z01 AG001050-01). This work was also supported by NIH 1K23DK099442-01 (Dr Rashanravan). NR 37 TC 7 Z9 7 U1 4 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 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2015 VL 65 IS 5 BP 737 EP 747 DI 10.1053/j.ajkd.2014.10.016 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA CL1SA UT WOS:000356723300016 PM 25542415 ER PT J AU Dalrymple, LS Mu, Y Romano, PS Nguyen, DV Chertow, GM Delgado, C Grimes, B Kaysen, GA Johansen, KL AF Dalrymple, Lorien S. Mu, Yi Romano, Patrick S. Nguyen, Danh V. Chertow, Glenn M. Delgado, Cynthia Grimes, Barbara Kaysen, George A. Johansen, Kirsten L. TI Outcomes of Infection-Related Hospitalization in Medicare Beneficiaries Receiving In-Center Hemodialysis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Infection; infection-related hospitalization; hospital readmission; transitions of care; survival; mortality; hemodialysis; end-stage renal disease (ESRD); Medicare beneficiaries; discharge diagnosis; dialysis access; sepsis ID UNITED-STATES; RATES; FACILITIES; QUALITY AB Background: Infection is a common cause of hospitalization in adults receiving hemodialysis. Limited data are available about downstream events resulting from or following these hospitalizations. Study Design: Retrospective cohort study using the US Renal Data System. Setting & Participants: Medicare beneficiaries initiating in-center hemodialysis therapy in 2005 to 2008. Factors: Demographics, dual Medicare/Medicaid eligibility, body mass index, comorbid conditions, initial vascular access type, nephrology care prior to dialysis therapy initiation, residence in a care facility, tobacco use, biochemical measures, and type of infection. Outcomes: 30-day hospital readmission or death following first infection-related hospitalization. Results: 60,270 Medicare beneficiaries had at least one hospitalization for infection. Of those who survived the initial hospitalization, 15,113(27%) were readmitted and survived the 30 days following hospital discharge, 1,624(3%) were readmitted to the hospital and then died within 30 days of discharge, and 2,425 (4%) died without hospital readmission. Complications related to dialysis access, sepsis, and heart failure accounted for 12%, 9%, and 7% of hospital readmissions, respectively. Factors associated with higher odds of 30-day readmission or death without readmission included non-Hispanic ethnicity, lower serum albumin level, inability to ambulate or transfer, limited nephrology care prior to dialysis therapy, and specific types of infection. In comparison, older age, select comorbid conditions, and institutionalization had stronger associations with death without readmission than with readmission. Limitations: Findings limited to Medicare beneficiaries receiving in-center hemodialysis. Conclusions: Hospitalizations for infection among patients receiving in-center hemodialysis are associated with exceptionally high rates of 30-day hospital readmission and death without readmission. (C) 2015 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Dalrymple, Lorien S.; Romano, Patrick S.; Kaysen, George A.] Univ Calif Davis, Dept Med, Davis, CA 95616 USA. [Mu, Yi] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Nguyen, Danh V.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA. [Delgado, Cynthia; Johansen, Kirsten L.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Delgado, Cynthia; Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Grimes, Barbara; Johansen, Kirsten L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Dalrymple, LS (reprint author), Div Nephrol, 4150 5 St,Ste 3500, Sacramento, CA 95817 USA. EM lorien.dalrymple@ucdmc.ucdavis.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK093584, K24 DK085153, K24 DK085446, R01 DK092232]; National Center for Advancing Translational Sciences [UL1 TR000002, UL1 TR000153]; Department of Veterans Affairs [1K2CX000527]; Dialysis Clinic Inc.; Department of Veterans Affairs, Clinical Science Research and Development Program [1IK2CX000527-01A2] FX This publication was made possible by grants K23 DK093584 (Dr Dalrymple), K24 DK085153 (Dr Johansen), K24 DK085446 (Dr Chertow). and R01 DK092232 (Dr Nguyen) from the National Institute of Diabetes and Digestive and Kidney Diseases; grants UL1 TR000002 (Drs Dalrymple and Nguyen) and UL1 TR000153 (Dr Nguyen) from the National Center for Advancing Translational Sciences; 1K2CX000527 from the Department of Veterans Affairs (Dr Delgado); and a research grant from Dialysis Clinic Inc. Dr Delgado's work is supported by the Department of Veterans Affairs, Clinical Science Research and Development Program under Career Development Award 1IK2CX000527-01A2. Her contribution is the result of work supported with the resources and the use of facilities at the San Francisco VA Medical Center. The funding sources were not involved in the design or conduct of the study; the collection and management of the data; data analysis and interpretation; and preparation, review, or approval of the manuscript. The data reported here have been supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government. NR 18 TC 4 Z9 5 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 MAY PY 2015 VL 65 IS 5 BP 754 EP 762 DI 10.1053/j.ajkd.2014.11.030 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CL1SA UT WOS:000356723300018 PM 25641061 ER PT J AU Howard, SA Rosenthal, MH Jagannathan, JP Krajewski, KM Shinagare, AB Ramaiya, NH Tirumani, SH AF Howard, Stephanie A. Rosenthal, Michael H. Jagannathan, Jyothi P. Krajewski, Katherine M. Shinagare, Atul B. Ramaiya, Nikhil H. Tirumani, Sree Harsha TI Beyond the Vascular Endothelial Growth Factor Axis: Update on Role of Imaging in Nonantiangiogenic Molecular Targeted Therapies in Oncology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE alternate tumor response criteria; anaplastic lymphoma kinase inhibitors; epidermal growth factor receptor inhibitors; immune modulators; mammalian target of rapamycin inhibitors; molecular targeted therapies ID RENAL-CELL CARCINOMA; METASTATIC COLORECTAL-CANCER; INTERSTITIAL LUNG-DISEASE; ANAPLASTIC LYMPHOMA KINASE; RESISTANT PROSTATE-CANCER; BREAST-CANCER; RESPONSE CRITERIA; TUMOR RESPONSE; EGFR-MUTATIONS; INTRAVENOUS BISPHOSPHONATES AB OBJECTIVE. This article provides a comprehensive review of molecular targeted therapies that do not act directly through vascular endothelial growth factor pathways, highlighting the role of imaging in assessment of treatment response and drug toxicities. CONCLUSION. A substantial number of molecular targeted therapies act on nonantiangiogenic pathways. Familiarity with these drugs, their personalized tumor response criteria, and class- and drug-specific toxicities will help radiologists to be an integral part of the multidisciplinary oncology team. C1 [Howard, Stephanie A.] Harvard Univ, Sch Med, Dept Imaging, Dana Farber Canc Inst,Brigham & Womens Hosp, Boston, MA 02215 USA. Harvard Univ, Dept Radiol, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02215 USA. RP Howard, SA (reprint author), Harvard Univ, Sch Med, Dept Imaging, Dana Farber Canc Inst,Brigham & Womens Hosp, 450 Brookline Ave, Boston, MA 02215 USA. EM sahoward@partners.org NR 96 TC 3 Z9 3 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2015 VL 204 IS 5 BP 919 EP 932 DI 10.2214/AJR.14.12876 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL2LZ UT WOS:000356776900024 PM 25905926 ER PT J AU Rosman, DA Nsiah, E Hughes, DR Duszak, R AF Rosman, David A. Nsiah, Eugene Hughes, Danny R. Duszak, Richard, Jr. TI Regional Variation in Medicare Payments for Medical Imaging: Radiologists Versus Nonradiologists SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE health care policy; imaging utilization; medical economics; medical imaging; Medicare payments ID TRENDS; CARE; CERTIFICATE; ANGIOGRAPHY; POPULATION; PHYSICIANS; MODALITIES; ULTRASOUND; COST AB OBJECTIVE. The purpose of this article was to study regional variation in Medicare Physician Fee Schedule (MPFS) payments for medical imaging to radiologists compared with nonradiologists. MATERIALS AND METHODS. Using a 5% random sample of all Medicare enrollees, which covered approximately 2.5 million Part B beneficiaries in 2011, total professional-only, technical-only, and global MPFS spending was calculated on a state-by-state and United States Census Bureau regional basis for all Medicare Berenson-Eggers Type of Service-defined medical imaging services. Payments to radiologists versus nonradiologists were identified and variation was analyzed. RESULTS. Nationally, mean MPFS medical imaging spending per Medicare beneficiary was $207.17 ($95.71 [46.2%] to radiologists vs $111.46 [53.8%] to nonradiologists). Of professional- only (typically interpretation) payments, 20.6% went to nonradiologists. Of technical-only (typically owned equipment) payments, 84.9% went to nonradiologists. Of global (both professional and technical) payments, 70.1% went to nonradiologists. The percentage of MPFS medical imaging spending on nonradiologists ranged from 32% (Minnesota) to 69.5% (South Carolina). The percentage of MPFS payments for medical imaging to nonradiologists exceeded those to radiologists in 58.8% of states. The relative percentage of MPFS payments to nonradiologists was highest in the South (58.5%) and lowest in the Northeast (48.0%). CONCLUSION. Nationally, 53.8% of MPFS payments for medical imaging services are made to nonradiologists, who claim a majority of MPFS payments in most states dominated by noninterpretive payments. This majority spending on nonradiologists may have implications in bundled and capitated payment models for radiology services. Medical imaging payment policy initiatives must consider the roles of all provider groups and associated regional variation. C1 [Rosman, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Nsiah, Eugene; Hughes, Danny R.; Duszak, Richard, Jr.] Harvey L Neiman Hlth Policy Inst, Reston, VA USA. [Hughes, Danny R.] George Mason Univ, Dept Hlth Adm & Policy, Fairfax, VA 22030 USA. [Duszak, Richard, Jr.] Emory Univ, Sch Med, Dept Radiol & Imaging Sci, Atlanta, GA USA. RP Rosman, DA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM drosman@partners.org RI Duszak, Richard/L-1811-2016 OI Duszak, Richard/0000-0003-0425-3008 FU Harvey L. Neiman Health Policy Institute FX D. A. Rosman is supported by a health policy research grant from the Harvey L. Neiman Health Policy Institute. NR 24 TC 5 Z9 5 U1 0 U2 7 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2015 VL 204 IS 5 BP 1042 EP 1048 DI 10.2214/AJR.14.13020 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL2LZ UT WOS:000356776900039 PM 25905939 ER PT J AU Andrabi, Y Pianykh, O Agrawal, M Kambadakone, A Blake, MA Sahani, DV AF Andrabi, Yasir Pianykh, Oleg Agrawal, Mukta Kambadakone, Avinash Blake, Michael A. Sahani, Dushyant V. TI Radiation Dose Consideration in Kidney Stone CT Examinations: Integration of Iterative Reconstruction Algorithms With Routine Clinical Practice SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; dose monitoring; iterative reconstruction; kidney stones; radiation dose ID FILTERED BACK-PROJECTION; UNENHANCED MULTIDETECTOR CT; HELICAL COMPUTED-TOMOGRAPHY; IMAGE QUALITY; FOLLOW-UP; EXPOSURE TRACKING; CANCER-RISKS; TUBE CURRENT; UROLITHIASIS; REDUCTION AB OBJECTIVE. The objective of our study was to evaluate three commercially available iterative reconstruction (IR) algorithms-ASiR, iDOSE, and SAFIRE-and conventional filtered back projection (FBP) on image quality and radiation dose in kidney stone CT examinations. MATERIALS AND METHODS. During the 6-month study period, 684 unenhanced kidney stone CT examinations of consecutive adults were performed on 17 CT scanners (GE Healthcare [vendor 1], n = 12 scanners; Philips Healthcare [vendor 2], n = 2; Siemens Healthcare [vendor 3], n = 3); these examinations were retrieved using dose-monitoring software (eXposure). A total of 347 kidney stone CT examinations were reconstructed using FBP, and 337 examinations were processed using IR (ASiR, n = 248; iDOSE, n = 50; SAFIRE, n = 39). The standard-dose scanning parameters for FBP scanners included a tube potential of 120 kVp, a tube current of 75-450 mA for vendor 1 and a Quality Reference mAs of 160-180 for vendor 3, and a slice thickness of 2.5 or 5 mm. The dose-modified protocol for the IR scanners included a higher noise index (1.4 times higher than the standard-dose FBP protocol) for vendor 1, a lower reference tube current-exposure time product for vendor 2 (150 reference mAs), and a lower Quality Reference mAs for vendor 3 (120 Quality Reference mAs). Three radiologists independently reviewed 60 randomly sampled kidney stone CT examinations for image quality, noise, and artifacts. Objective noise and attenuation were also determined. Size-specific dose estimates (SSDEs) were compared using ANOVA. RESULTS. Significantly higher subjective and objective measurements of image noise were found in FBP examinations compared with dose-modified IR examinations (p < 0.05). The radiation dose was substantially lower for the dose-modified IR examinations than the standard-dose FBP examinations (mean SSDE +/- SD: 8.1 +/- 3.8 vs 11.6 +/- 3.6 mGy, respectively) (p < 0.0001), but the radiation dose was comparable among the three IR techniques (ASiR, 7.8 +/- 3.1 mGy; iDOSE, 7.5 +/- 1.9 mGy; SAFIRE, 7.6 +/- 3.2 mGy) (p > 0.05). CONCLUSION. The three IRs enable 20-33% radiation dose reduction in kidney stone CT examinations compared with the FBP technique without any image quality concerns. The radiation dose and image quality were comparable among these three IR algorithms. C1 [Andrabi, Yasir; Pianykh, Oleg; Agrawal, Mukta; Kambadakone, Avinash; Blake, Michael A.; Sahani, Dushyant V.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@mgh.harvard.edu RI Pianykh, Oleg/N-2456-2015 OI Pianykh, Oleg/0000-0002-9107-5432 FU GE Healthcare FX D. V. Sahani received research grant support from GE Healthcare. NR 60 TC 4 Z9 4 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2015 VL 204 IS 5 BP 1055 EP 1063 DI 10.2214/AJR.14.13038 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL2LZ UT WOS:000356776900041 PM 25905941 ER PT J AU Timpone, VM Patel, SH AF Timpone, Vincent M. Patel, Sohil H. TI MRI of a Syrinx: Is Contrast Material Always Necessary? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE contrast-enhanced follow-up MRI; cystic intramedullary mass; diagnostic yield; syringohydromyelia; syrinx ID GADOLINIUM-DTPA; SYRINGOMYELIA; TUMORS AB OBJECTIVE. The workup of a syrinx often includes contrast-enhanced MRI to exclude the presence of an underlying mass. The diagnostic yield of performing these additional contrast-enhanced sequences is not well defined in the literature. We hypothesized that T2-weighted imaging alone could reliably exclude the presence of a syrinx-associated mass without the need for contrast-enhanced imaging sequences in all cases. MATERIALS AND METHODS. Two independent readers retrospectively analyzed contrast-enhanced MRI studies of 87 consecutive patients with syringes. The presence or absence of an associated spinal cord mass was determined using only T2-weighted imaging. The imaging features considered positive for a possible syrinx-associated lesion on T2-weighted imaging were syrinx nodularity, syrinx septations, and a spinal cord signal intensity abnormality or a mass separate from the syrinx. The size of the syrinx was also recorded. Using contrast-enhanced sequences as the reference standard, statistical analysis was performed to determine the accuracy of T2-weighted imaging in detecting a syrinx-associated mass. RESULTS. Of the 87 cases of syrinx, there were 23 mass lesions, 11 Chiari malformations, three spinal cord contusions, and 50 idiopathic syringes. Using T2-weighted imaging alone, readers detected no findings suspicious for a syrinx-associated mass in 55 cases and detected findings suspicious for a mass in 32 of 87 cases. Reader sensitivity for an underlying mass lesion was 100%; specificity, 86%; positive predictive value, 72%; and negative predictive value, 100%. Interreader agreement was excellent (kappa = 0.88). Syrinx size showed a positive correlation with the presence of a mass lesion (p < 0.0001). CONCLUSION. T2-weighted imaging alone appears to have a high sensitivity and high negative predictive value in evaluating for a syrinx-associated mass, and contrast-enhanced imaging may not be required for the workup of a syrinx. C1 [Timpone, Vincent M.; Patel, Sohil H.] Massachusetts Gen Hosp, Div Neuroradiol, Dept Radiol, Boston, MA 02114 USA. RP Timpone, VM (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, Dept Radiol, 55 Fruit St,Gray 2,Rm 273A, Boston, MA 02114 USA. EM vtimpone@mgh.harvard.edu NR 13 TC 1 Z9 1 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2015 VL 204 IS 5 BP 1082 EP 1085 DI 10.2214/AJR.14.13310 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL2LZ UT WOS:000356776900045 PM 25905945 ER PT J AU Abujudeh, HH Thrall, JH AF Abujudeh, Hani H. Thrall, James H. TI Reply to "The 'Abujudeh Curve' in Radiology Quality and Safety Research" SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter C1 [Abujudeh, Hani H.; Thrall, James H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Abujudeh, HH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2015 VL 204 IS 5 BP W607 EP W607 DI 10.2214/AJR.14.14186 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL2LZ UT WOS:000356776900017 PM 25905971 ER PT J AU Jakobiec, FA Rose, MF Trief, D Stagner, AM Kim, I Gragoudas, ES AF Jakobiec, Frederick A. Rose, Matthew F. Trief, Danielle Stagner, Anna M. Kim, Ivana Gragoudas, Evangelos S. TI Immunohistochemical investigations of adult intraocular medulloepitheliomas SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Letter ID NONPIGMENTED CILIARY EPITHELIUM; BODY MEDULLOEPITHELIOMA; TERATOID MEDULLOEPITHELIOMA; ADENOMA; TUMORS; DIFFERENTIATION; CRX C1 [Jakobiec, Frederick A.; Stagner, Anna M.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Gragoudas, Evangelos S.] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Trief, Danielle; Stagner, Anna M.; Kim, Ivana; Gragoudas, Evangelos S.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Rose, Matthew F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. OI Rose, Matthew/0000-0002-1148-4130 NR 25 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1442-6404 EI 1442-9071 J9 CLIN EXP OPHTHALMOL JI Clin. Exp. Ophthalmol. PD MAY-JUN PY 2015 VL 43 IS 4 BP 379 EP 385 DI 10.1111/ceo.12436 PG 7 WC Ophthalmology SC Ophthalmology GA CL2XE UT WOS:000356810200012 PM 25251824 ER PT J AU Stagner, AM Jakobiec, FA Yoon, MK AF Stagner, Anna M. Jakobiec, Frederick A. Yoon, Michael K. TI Ruptured canthal steatocystoma simplex presenting as a lacrimal sac mass SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Letter ID MULTIPLEX C1 [Stagner, Anna M.; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Yoon, Michael K.] Massachusetts Eye & Ear Infirm, Div Ophthalm Plast Surg, Boston, MA 02114 USA. [Stagner, Anna M.; Jakobiec, Frederick A.; Yoon, Michael K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Stagner, AM (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1442-6404 EI 1442-9071 J9 CLIN EXP OPHTHALMOL JI Clin. Exp. Ophthalmol. PD MAY-JUN PY 2015 VL 43 IS 4 BP 385 EP 387 DI 10.1111/ceo.12441 PG 3 WC Ophthalmology SC Ophthalmology GA CL2XE UT WOS:000356810200013 PM 25263655 ER PT J AU Lee, HS Hos, D Blanco, T Bock, F Reyes, NJ Mathew, R Cursiefen, C Dana, R Saban, DR AF Lee, Hyun-Soo Hos, Deniz Blanco, Tomas Bock, Felix Reyes, Nancy J. Mathew, Rose Cursiefen, Claus Dana, Reza Saban, Daniel R. TI Involvement of Corneal Lymphangiogenesis in a Mouse Model of Allergic Eye Disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE ocular allergy; lymphangiogenesis; Th2; VEGF; RTK inhibitor ID ENDOTHELIAL GROWTH-FACTOR; INFLAMMATORY LYMPHANGIOGENESIS; LYMPHATIC VESSELS; FACTOR RECEPTOR-3; MAST-CELLS; SKIN INFLAMMATION; DENDRITIC CELLS; TRANSGENIC MICE; FACTOR-C; VEGF AB PURPOSE. The contribution of lymphangiogenesis (LA) to allergy has received considerable attention and therapeutic inhibition of this process via targeting VEGF has been considered. Likewise, certain inflammatory settings affecting the ocular mucosa can trigger pathogenic LA in the naturally avascular cornea. Chronic inflammation in allergic eye disease (AED) impacts the conjunctiva and cornea, leading to sight threatening conditions. However, whether corneal LA is involved is completely unknown. We addressed this using a validated mouse model of AED. METHODS. Allergic eye disease was induced by ovalbumin (OVA) immunization and chronic OVA exposure. Confocal microscopy of LYVE-1-stained cornea allowed evaluation of corneal LA, and qRT-PCR was used to evaluate expression of VEGF-C, -D, and -R3 in these mice. Administration of VEGF receptor (R) inhibitor was incorporated to inhibit corneal LA in AED. Immune responses were evaluated by in vitro OVA recall responses of T cells, and IgE levels in the serum. RESULTS. Confocal microscopy of LYVE-1-stained cornea revealed the distinct presence of corneal LA in AED, and corroborated by increased corneal expression of VEGF-C, -D, and -R3. Importantly, prevention of corneal LA in AED via VEGFR inhibition was associated with decreased T helper two responses and IgE production. Furthermore, VEGFR inhibition led a significant reduction in clinical signs of AED. CONCLUSIONS. Collectively, these data reveal that there is a distinct involvement of corneal LA in AED. Furthermore, VEGFR inhibition prevents corneal LA and consequent immune responses in AED. C1 [Lee, Hyun-Soo; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Hos, Deniz; Bock, Felix; Cursiefen, Claus] Univ Cologne, Dept Ophthalmol, D-50931 Cologne, Germany. [Blanco, Tomas; Reyes, Nancy J.; Mathew, Rose; Saban, Daniel R.] Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC USA. [Saban, Daniel R.] Duke Univ, Sch Med, Dept Immunol, Durham, NC USA. RP Saban, DR (reprint author), Duke Univ, Sch Med, Dept Ophthalmol, 2351 Erwin Rd, Durham, NC USA. EM daniel.saban@duke.edu FU National Eye Institute, Bethesda, MD, USA [R01EY021798]; Research to Prevent Blindness (New York, NY, USA); Arshavsky; National Eye Institute [P30EY005722] FX Supported by grants from R01EY021798 (DRS; National Eye Institute, Bethesda, MD, USA), Research to Prevent Blindness (DRS; New York, NY, USA), and P30EY005722 (Arshavsky; National Eye Institute). NR 58 TC 8 Z9 8 U1 1 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2015 VL 56 IS 5 BP 3140 EP 3148 DI 10.1167/iovs.14-16186 PG 9 WC Ophthalmology SC Ophthalmology GA CK7UJ UT WOS:000356439200047 PM 26024097 ER PT J AU Choi, SY Baek, JI Zuo, XF Kim, SH Dunaief, JL Lipschutz, JH AF Choi, Soo Young Baek, Jeong-In Zuo, Xiaofeng Kim, Seok-Hyung Dunaief, Joshua L. Lipschutz, Joshua H. TI Cdc42 and sec10 Are Required for Normal Retinal Development in Zebrafish SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE zebrafish; connecting cilium; cdc42; sec10; retinal degeneration; protein trafficking ID OUTER SEGMENT DEVELOPMENT; BARDET-BIEDL-SYNDROME; PRIMARY CILIOGENESIS; RHODOPSIN TRANSPORT; KUPFFERS VESICLE; USHER-SYNDROME; SENSORY CILIA; PHOTORECEPTORS; COMPLEX; DEGENERATION AB PURPOSE. To characterize the function and mechanisms of cdc42 and sec10 in eye development in zebrafish. METHODS. Knockdown of zebrafish cdc42 and sec10 was carried out using antisense morpholino injection. The phenotype of morphants was characterized by histology, immunohistology, and transmission electron microscopy (TEM). To investigate a synergistic genetic interaction between cdc42 and sec10, we titrated suboptimal doses of cdc42 and sec10 morpholinos, and coinjected both morpholinos. To study trafficking, a melanosome transport assay was performed using epinephrine. RESULTS. Cdc42 and sec10 knockdown in zebrafish resulted in both abnormal eye development and increased retinal cell death. Cdc42 morphants had a relatively normal retinal structure, aside from the absence of most connecting cilia and outer segments, whereas in sec10 morphants, much of the outer nuclear layer, which is composed of the photoreceptor nuclei, was missing and RPE cell thickness was markedly irregular. Knockdown of cdc42 and sec10 also resulted in an intracellular transport defect affecting retrograde melanosome transport. Furthermore, there was a synergistic genetic interaction between zebrafish cdc42 and sec10, suggesting that cdc42 and sec10 act in the same pathway in retinal development. CONCLUSIONS. We propose a model whereby sec10 and cdc42 play a central role in development of the outer segment of the retinal photoreceptor cell by trafficking proteins necessary for ciliogenesis. C1 [Choi, Soo Young; Baek, Jeong-In; Zuo, Xiaofeng; Kim, Seok-Hyung; Lipschutz, Joshua H.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Dunaief, Joshua L.] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA. [Lipschutz, Joshua H.] Ralph H Johnson Vet Affairs Med Ctr, Dept Med, Charleston, SC USA. RP Lipschutz, JH (reprint author), Med Univ S Carolina, 96 Jonathan Lucas St,CSB 829, Charleston, SC 29425 USA. EM Lipschut@musc.edu FU Department of Veterans Affairs [I01, 2I01 BX000820]; National Institutes of Health [DK069909, DK070980]; Research to Prevent Blindness, Inc.; F.M. Kirby Foundation; Paul and Evanina Bell MacKall Foundation Trust FX Supported in part by Department of Veterans Affairs Merit Award I01 and 2I01 BX000820 (JHL), National Institutes of Health Grants DK069909 and DK070980 (JHL), Research to Prevent Blindness, Inc., the F.M. Kirby Foundation, and the Paul and Evanina Bell MacKall Foundation Trust (JLD). NR 54 TC 1 Z9 1 U1 2 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2015 VL 56 IS 5 BP 3361 EP 3370 DI 10.1167/iovs.14-15692 PG 10 WC Ophthalmology SC Ophthalmology GA CK7UJ UT WOS:000356439200074 PM 26024121 ER PT J AU Zhang, T Jin, SF Gu, YX He, Y Li, M Li, Y Fan, HF AF Zhang, Tao Jin, Shifeng Gu, Yuanxin He, Yao Li, Ming Li, Yang Fan, Haifu TI SFX analysis of non-biological polycrystalline samples SO IUCRJ LA English DT Article DE serial crystallography; X-ray powder diffraction; phase identification; structure solution ID PROTEIN NANOCRYSTALLOGRAPHY; SERIAL CRYSTALLOGRAPHY; SYNCHROTRON-RADIATION; POWDER DIFFRACTION; ZEOLITE AB Serial femtosecond crystallography (SFX) is capable of collecting three-dimensional single-crystal diffraction data using polycrystalline samples. This may dramatically enhance the power of X-ray powder diffraction. In this paper a test has been performed using simulated diffraction patterns. The test sample is a mixture of two zeolites with crystal grain sizes from 100 to 300 nm. X-ray diffraction snapshots by SFX were simulated and processed using the program suite CrystFEL. Identification according to the primitive unit-cell volume determined from individual snapshots was able to separate the whole set of snapshots into two subsets, which correspond to the two zeolites in the sample. Monte Carlo integration in CrystFEL was then applied to them separately. This led to two sets of three-dimensional single-crystal diffraction intensities, based on which crystal structures of the two zeolites were solved easily by direct methods implemented in the program SHELXD. C1 [Zhang, Tao; Jin, Shifeng; Gu, Yuanxin; He, Yao; Li, Ming; Fan, Haifu] Chinese Acad Sci, Inst Phys, Beijing 100190, Peoples R China. [Li, Yang] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Fan, HF (reprint author), Chinese Acad Sci, Inst Phys, 8,South 3rd St, Beijing 100190, Peoples R China. EM fanhf@cryst.iphy.ac.cn NR 14 TC 2 Z9 2 U1 0 U2 3 PU INT UNION CRYSTALLOGRAPHY PI CHESTER PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND SN 2052-2525 J9 IUCRJ JI IUCrJ PD MAY PY 2015 VL 2 BP 322 EP 326 DI 10.1107/S2052252515002146 PN 3 PG 5 WC Chemistry, Multidisciplinary; Crystallography; Materials Science, Multidisciplinary SC Chemistry; Crystallography; Materials Science GA CL3RB UT WOS:000356866900005 PM 25995841 ER PT J AU Warner, JL Maddux, SE Hughes, KS Krauss, JC Yu, PP Shulman, LN Mayer, DK Hogarth, M Shafarman, M Fiscalini, AS Esserman, L Alschuler, L Koromia, GA Gonzaga, Z Ambinder, EP AF Warner, Jeremy L. Maddux, Suzanne E. Hughes, Kevin S. Krauss, John C. Yu, Peter Paul Shulman, Lawrence N. Mayer, Deborah K. Hogarth, Mike Shafarman, Mark Fiscalini, Allison Stover Esserman, Laura Alschuler, Liora Koromia, George Augustine Gonzaga, Zabrina Ambinder, Edward P. TI Development, implementation, and initial evaluation of a foundational open interoperability standard for oncology treatment planning and summarization SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article DE Medical Oncology; Breast Neoplasms; Health Information Management; Electronic Health Records; Continuity of Patient Care; Information Science ID CLINICAL DOCUMENT ARCHITECTURE; SURVIVORSHIP CARE PLANS; RAPID-LEARNING-SYSTEM; CANCER SURVIVORS; PHYSICIANS; PROVIDERS; EXCHANGE; RECORDS; NETWORK AB Objective Develop and evaluate a foundational oncology-specific standard for the communication and coordination of care throughout the cancer journey, with early-stage breast cancer as the use case. Materials and Methods Owing to broad uptake of the Health Level Seven (HL7) Consolidated Clinical Document Architecture (C-CDA) by health information exchanges and large provider organizations, we developed an implementation guide in congruence with C-CDA. The resultant product was balloted through the HL7 process and subsequently implemented by two groups: the Health Story Project (Health Story) and the Athena Breast Health Network (Athena). Results The HL7 Implementation Guide for CDA, Release 2: Clinical Oncology Treatment Plan and Summary, DSTU Release 1 (eCOTPS) was successfully balloted and published as a Draft Standard for Trial Use (DSTU) in October 2013. Health Story successfully implemented the eCOTPS the 2014 meeting of the Healthcare Information and Management Systems Society (HIMSS) in a clinical vignette. During the evaluation and implementation of eCOPS, Athena identified two practical concerns: (1) the need for additional CDA templates specific to their use case; (2) the many-to-many mapping of Athena-defined data elements to eCOTPS. Discussion Early implementation of eCOTPS has demonstrated successful vendor-agnostic transmission of oncology-specific data. The modularity enabled by the C-CDA framework ensures the relatively straightforward expansion of the eCOTPS to include other cancer subtypes. Lessons learned during the process will strengthen future versions of the standard. Conclusion eCOTPS is the first oncology-specific CDA standard to achieve HL7 DSTU status. Oncology standards will improve care throughout the cancer journey by allowing the efficient transmission of reliable, meaningful, and current clinical data between the many involved stakeholders. C1 [Warner, Jeremy L.] Vanderbilt Univ, Dept Med, Div Hematol & Oncol, Nashville, TN 37232 USA. [Warner, Jeremy L.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37232 USA. [Maddux, Suzanne E.] Amer Soc Clin Oncol, Qual & Guidelines Div, Alexandria, VA USA. [Hughes, Kevin S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Krauss, John C.] Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA. [Yu, Peter Paul] Palo Alto Med Fdn, Sunnyvale, CA USA. [Shulman, Lawrence N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mayer, Deborah K.] UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Hogarth, Mike] Univ Calif Davis, Dept Pathol & Lab Med, Davis, CA 95616 USA. [Shafarman, Mark] Shafarman Consulting, Oakland, CA USA. [Fiscalini, Allison Stover; Esserman, Laura] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Esserman, Laura] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Alschuler, Liora; Koromia, George Augustine; Gonzaga, Zabrina] Lantana Consulting Grp, East Thetford, VT USA. [Ambinder, Edward P.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. RP Warner, JL (reprint author), Vanderbilt Univ, Med & Biomed Informat, 2220 Pierce Ave Preston Res Bldg 777, Nashville, TN 37232 USA. EM jeremy.warner@vanderbilt.edu FU ASCO; University of California Office of the President; Safeway Foundation; ONC [90HT0029/01-02] FX This work was supported in part by ASCO, the University of California Office of the President, the Safeway Foundation, and Grant 90HT0029/01-02 (ONC). S.E.M, an ASCO employee, assisted in the preparation of the manuscript. ASCO had no role in the study design, data collection and analysis, or decision to publish. The other funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 7 Z9 8 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY PY 2015 VL 22 IS 3 BP 577 EP 586 DI 10.1093/jamia/ocu015 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA CL1PV UT WOS:000356717100011 PM 25604811 ER PT J AU Stiers, W Barisa, M Stucky, K Pawlowski, C Van Tubbergen, M Turner, AP Hibbard, M Caplan, B AF Stiers, William Barisa, Mark Stucky, Kirk Pawlowski, Carey Van Tubbergen, Marie Turner, Aaron P. Hibbard, Mary Caplan, Bruce TI Guidelines for Competency Development and Measurement in Rehabilitation Psychology Postdoctoral Training SO REHABILITATION PSYCHOLOGY LA English DT Article DE rehabilitation psychology; psychology; training ID PROFESSIONAL-PSYCHOLOGY; NATIONAL-COUNCIL; EDUCATION; MODEL; BENCHMARKS; CULTURE; SCHOOLS AB Objective: This study describes the results of a multidisciplinary conference (the Baltimore Conference) that met to develop consensus guidelines for competency specification and measurement in postdoctoral training in rehabilitation psychology. Methods: Forty-six conference participants were chosen to include representatives of rehabilitation psychology training and practice communities, representatives of psychology accreditation and certification bodies, persons involved in medical education practice and research, and consumers of training programs (students). Results: Consensus education and training guidelines were developed that specify the key competencies in rehabilitation psychology postdoctoral training, and structured observation checklists were developed for their measurement. Discussion: This study continues the development of more than 50 years of thinking about education and training in rehabilitation psychology and builds on the existing work to further advance the development of guidelines in this area. The conference developed aspirational guidelines for competency specification and measurement in rehabilitation psychology postdoctoral training (i.e., for studying the outcomes of these training programs). Structured observation of trainee competencies allows examination of actual training outcomes in relation to intended outcomes and provides a methodology for studying how program outcomes are related to program structures and processes so that program improvement can occur. Best practices in applying program evaluation research methods to the study of professional training programs are discussed. C1 [Stiers, William] Johns Hopkins Univ, Dept Phys Med & Rehabil, Sch Med, Baltimore, MD 21239 USA. [Barisa, Mark] Baylor Inst Rehabil, Neuropsychol & Rehabil Psychol Serv, Dallas, TX USA. [Stucky, Kirk] Hurley Med Ctr, Dept Psychol, Flint, MI USA. [Stucky, Kirk] Michigan State Univ, Coll Human Med, Dept Med, E Lansing, MI 48824 USA. [Pawlowski, Carey] VA Palo Alto Hlth Care Syst, Polytrauma Transit Rehabil Program, Palo Alto, CA USA. [Van Tubbergen, Marie] Univ Michigan, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. [Turner, Aaron P.] VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA USA. [Turner, Aaron P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Hibbard, Mary] New York Langone Med Ctr, Dept Rehabil Med, New York, NY USA. RP Stiers, W (reprint author), Johns Hopkins Univ, Dept Phys Med & Rehabil, Sch Med, Suite 406-POB, Baltimore, MD 21239 USA. EM wstiers1@jhmi.edu OI Turner, Aaron/0000-0001-6897-8003; Stiers, William/0000-0002-1826-8350 FU Paralyzed Veterans of America (PVA Education Foundation Grant) [654] FX Conference funding for the activities reported here was provided by a grant from the Paralyzed Veterans of America (PVA Education Foundation Grant 654). NR 34 TC 5 Z9 5 U1 1 U2 6 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 EI 1939-1544 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD MAY PY 2015 VL 60 IS 2 BP 111 EP 122 DI 10.1037/a0038353 PG 12 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA CL5CG UT WOS:000356976800001 PM 25496436 ER PT J AU Roubinov, DS Turner, AP Williams, RM AF Roubinov, Danielle S. Turner, Aaron P. Williams, Rhonda M. TI Coping Among Individuals With Multiple Sclerosis: Evaluating a Goodness-of-Fit Model SO REHABILITATION PSYCHOLOGY LA English DT Article DE multiple sclerosis; goodness-of-fit; coping; depression; anxiety ID COGNITIVE DYSFUNCTION; PERCEIVED STRESS; COMMUNITY SAMPLE; PRIMARY-CARE; ADJUSTMENT; DEPRESSION; HYPOTHESIS; LIFE; CONTROLLABILITY; ACCEPTANCE AB Objective: Multiple sclerosis (MS) is a chronic illness involving both controllable and uncontrollable stressors. The goodness-of-fit hypothesis posits that managing stressors effectively requires the use of different coping approaches in the face of controllable and uncontrollable stressors. To test the applicability of the goodness-of-fit model in a sample of adults with MS, we evaluated the ratio of 2 types of coping (an active problem-solving approach and an emotion-based meaning-focused approach) as a moderator of the relations between stress uncontrollability and mental health outcomes. Methods: Participants were veterans with MS (N = 90) receiving medical services through the Veterans Health Administration who completed telephone-based interviews. Regression analyses tested the interaction of stress uncontrollability and the problem-and meaning-focused coping ratio on anxious and depressive symptoms. Significant interactions were probed at 1 SD above the mean of coping (use of predominantly problem-focused coping) and 1 SD below the mean of coping (use of predominantly meaning-focused coping). Results: Findings largely supported the goodness-of-fit hypothesis. Anxiety and depressive symptoms were elevated when participants used more problem-focused strategies relative to meaning-focused strategies in the face of perceived uncontrollable stress. Conversely, symptoms of anxiety and depression were lower when uncontrollable stress was met with predominantly meaning-focused coping; however, the relations did not reach statistical significance. Conclusions: The impact of uncontrollable stressors on mental health outcomes for individuals with MS may vary depending on the degree to which problem-focused versus meaning-focused coping strategies are employed, lending support to the goodness-of-fit model. C1 [Roubinov, Danielle S.; Turner, Aaron P.; Williams, Rhonda M.] Vet Affairs Puget Sound Healthcare Syst, Rehabil Care Serv, Seattle, WA 98108 USA. [Turner, Aaron P.; Williams, Rhonda M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Roubinov, DS (reprint author), Vet Affairs Puget Sound Healthcare Syst, Rehabil Care Serv, 1660 S Columbian Way,S-117-RCS, Seattle, WA 98108 USA. EM danielle.roubinov@va.gov NR 41 TC 2 Z9 2 U1 2 U2 8 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 EI 1939-1544 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD MAY PY 2015 VL 60 IS 2 BP 162 EP 168 DI 10.1037/rep0000032 PG 7 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA CL5CG UT WOS:000356976800008 PM 25822181 ER PT J AU Durpes, MC Morin, C Paquin-Veillet, J Beland, R Pare, M Guimond, MO Rekhter, M King, GL Geraldes, P AF Durpes, Marie-Claude Morin, Catherine Paquin-Veillet, Judith Beland, Raphael Pare, Martin Guimond, Marie-Odile Rekhter, Mark King, George L. Geraldes, Pedro TI PKC-beta activation inhibits IL-18-binding protein causing endothelial dysfunction and diabetic atherosclerosis SO CARDIOVASCULAR RESEARCH LA English DT Article DE Atherosclerosis; Protein kinase C beta; Endothelial dysfunction; IL-18-binding protein ID INTERLEUKIN-18 BINDING-PROTEIN; KINASE-C; INSULIN-RESISTANCE; TNF-ALPHA; PLASMA INTERLEUKIN-18; GENE-EXPRESSION; ADIPOSE-TISSUE; INFLAMMATION; CELLS; IL-18 AB Aims Clinical observations showed a correlation between accelerated atherosclerosis in diabetes and high plasmatic level of IL-18, a pro-inflammatory cytokine. IL-18 enhances the production of inflammatory cytokines and cellular adhesion molecules contributing to atherosclerotic plaque formation and instability. Previous studies indicated that protein kinase C (PKC)-beta inhibition prevented macrophage-induced cytokine expression involved in diabetic (DM) atherosclerotic plaque development. However, the role of PKC-beta activation on IL-18/IL-18-binding protein (IL-18BP) pathway causing endothelial dysfunction and monocyte adhesion in diabetes has never been explored. Methods and results Apoe(-/-) mice were rendered DM and fed with western diet containing ruboxistaurin (RBX), a PKC-beta inhibitor. After 20 weeks, atherosclerotic plaque composition was quantified. Compared with non-diabetic, DM mice exhibited elevated atherosclerotic plaque formation, cholestoryl ester content and macrophage infiltration, as well as reduced IL-18BP expression in the aorta which was prevented with RBX treatment. Endothelial cells (ECs) and macrophages were exposed to normal or high glucose (HG) levels with or without palmitate and recombinant IL-18 for 24 h. The combined HG and palmitate condition was required to increase IL-18 expression and secretion in macrophages, while it reduced IL-18BP expression in EC causing up-regulation of the vascular cell adhesion molecule (VCAM)-1 and monocyte adhesion. Elevated VCAM-1 expression and monocyte adherence were prevented by siRNA, RBX, and IL-18 neutralizing antibody. Conclusion Our study unrevealed a new mechanism by which PKC-beta activation promotes EC dysfunction caused by the de-regulation of the IL-18/IL-18BP pathway, leading to increased VCAM-1 expression, monocyte/macrophage adhesion, and accelerated atherosclerotic plaque formation in diabetes. C1 [Durpes, Marie-Claude; Morin, Catherine; Paquin-Veillet, Judith; Beland, Raphael; Pare, Martin; Guimond, Marie-Odile; Geraldes, Pedro] Univ Sherbrooke, CHU Sherbrooke, Res Ctr, Sherbrooke, PQ J1H 5N4, Canada. [Durpes, Marie-Claude; Morin, Catherine; Paquin-Veillet, Judith; Beland, Raphael; Pare, Martin; Guimond, Marie-Odile; Geraldes, Pedro] Univ Sherbrooke, Div Endocrinol, Dept Med, Sherbrooke, PQ J1H 5N4, Canada. [Rekhter, Mark] Lilly Res Labs, Cardiometab Dis & Complicat Diabet, Indianapolis, IN USA. [King, George L.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Geraldes, P (reprint author), Univ Sherbrooke, CHU Sherbrooke, Res Ctr, Sherbrooke, PQ J1H 5N4, Canada. EM pedro.geraldes@usherbrooke.ca FU Canadian Institute of Health Research [MOP 130334]; 'Fonds de Recherche du Quebec - Sante' (FRQS); 'Centre Hospitalier Universitaire de Sherbrooke' (CHUS) foundation; FRQS; Canadian Diabetes Association FX This study was supported by grants from the Canadian Institute of Health Research (MOP 130334 to P.G.), 'Fonds de Recherche du Quebec - Sante' (FRQS), and the 'Centre Hospitalier Universitaire de Sherbrooke' (CHUS) foundation to P.G. This work was performed at the CHUS research center, funded by the FRQS. P.G. is currently the holder of the Canadian Research Chair in Vascular Complications of Diabetes and the recipient of a Scholarship Award from the Canadian Diabetes Association. NR 44 TC 7 Z9 7 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 EI 1755-3245 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAY 1 PY 2015 VL 106 IS 2 BP 303 EP 313 DI 10.1093/cvr/cvv107 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CK4GT UT WOS:000356182900016 PM 25808972 ER PT J AU Mackie, S Winkelman, JW AF Mackie, Susan Winkelman, John W. TI Long-Term Treatment of Restless Legs Syndrome (RLS): An Approach to Management of Worsening Symptoms, Loss of Efficacy, and Augmentation SO CNS DRUGS LA English DT Article ID WILLIS-EKBOM DISEASE; OPEN-LABEL EXTENSION; DIAGNOSTIC-CRITERIA; CONTROLLED-TRIAL; DOUBLE-BLIND; PRAMIPEXOLE; CONSENSUS; SLEEP; LEVODOPA AB Restless legs syndrome (RLS) is a common, frequently chronic, sensorimotor neurological disorder characterized by nocturnal leg dysesthesias and an irresistible urge to move the legs, usually resulting in sleep disturbance. Dopaminergic agonists, alpha-2-delta calcium-channel ligands, and opioids have all demonstrated efficacy to relieve symptoms of RLS and improve sleep. However, long-term treatment with dopamine agonists (the most commonly prescribed agents) is often characterized by worsening symptoms and loss of efficacy. A more worrisome complication of dopaminergic agents is augmentation, an iatrogenic worsening of RLS symptoms that can produce progressively more severe symptoms resulting in around-the-clock restlessness and near sleeplessness. Recent research has yielded consensus regarding a precise definition of augmentation and has contributed to improved knowledge regarding strategies for preventing this complication. When RLS symptoms worsen during the course of treatment, the clinician must consider the myriad of environmental, medical, pharmacologic, and psychiatric factors that can exacerbate RLS. In the absence of fully developed, evidence-based guidelines there remains uncertainty regarding the optimal management strategy if augmentation develops. However, we discuss several key principles based on the available published data and the authors' clinical experience. We also explore the recent increasing interest in alternative initial treatment strategies that avoid dopamine agonists and their associated complications altogether. C1 [Mackie, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Winkelman, John W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Winkelman, John W.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Winkelman, John W.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Winkelman, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM semackie@partners.org; jwwinkelman@partners.org FU National Institute of Mental Health; Neurometrix; Purdue; UCB FX Dr. Winkelman reports receiving research support from the National Institute of Mental Health, Neurometrix, Purdue, and UCB, as well as consulting income from FlexPharma and UCB. NR 35 TC 4 Z9 4 U1 1 U2 4 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1172-7047 EI 1179-1934 J9 CNS DRUGS JI CNS Drugs PD MAY PY 2015 VL 29 IS 5 BP 351 EP 357 DI 10.1007/s40263-015-0250-2 PG 7 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CK5GG UT WOS:000356250500001 PM 26045290 ER PT J AU Mamoun, M Bergen, AW Shieh, J Wiggins, A Brody, AL AF Mamoun, Michael Bergen, Andrew W. Shieh, Jennifer Wiggins, Anna Brody, Arthur L. TI Biomarkers of Response to Smoking Cessation Pharmacotherapies: Progress to Date SO CNS DRUGS LA English DT Article ID NICOTINE METABOLITE RATIO; RANDOMIZED CONTROLLED-TRIAL; GENOME-WIDE ASSOCIATION; TREATMENT-SEEKING SMOKERS; CONTROLLED CLINICAL-TRIAL; PLACEBO-CONTROLLED TRIAL; TRANSDERMAL NICOTINE; GENETIC-VARIATION; CYP2A6 GENOTYPE; REPLACEMENT THERAPY AB For the past 30 years, research examining predictors of successful smoking cessation treatment response has focused primarily on clinical variables, such as levels of tobacco dependence, craving, and self-efficacy. However, recent research has begun to determine biomarkers (such as genotype, nicotine and metabolite levels, and brain imaging findings) that may have utility in predicting smoking cessation. For genotype, genes associated with nicotinic acetylcholine receptors (nAChRs) and related proteins have been found to predict response to first-line medications (e.g. nicotine replacement therapy [NRT], bupropion, or varenicline) or quitting over time without a controlled treatment trial. For nicotine and metabolite levels, function of the cytochrome P450 2A6 liver enzyme, which can be assessed with the nicotine metabolite ratio or via genotype, has been found to predict response, with slow nicotine metabolizers having less severe nicotine dependence and a greater likelihood of quitting with NRT than normal metabolizers. For brain imaging, decreased activation of brain regions associated with emotion regulation and increased connectivity in emotion regulation networks, increased responsiveness to pleasant cues, and altered activation with the Stroop effect have been found in smokers who quit with the first-line medications listed above or counseling. In addition, our group recently demonstrated that lower pre-treatment brain nAChR density is associated with a greater chance of quitting smoking with NRT or placebo. Several of these studies found that specific biomarkers may provide additional information for predicting response beyond subjective symptom or rating scale measures, thereby giving an initial indication that biomarkers may, in the future, be useful for guiding smoking cessation treatment intensity, duration, and type. C1 [Mamoun, Michael; Brody, Arthur L.] VA Greater Los Angeles Healthcare Syst, Dept Res & Psychiat, Los Angeles, CA 90073 USA. [Bergen, Andrew W.] SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA. [Shieh, Jennifer] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Wiggins, Anna] Univ So Calif, Dept Psychiat, Los Angeles, CA USA. [Brody, Arthur L.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. RP Brody, AL (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Res & Psychiat, Los Angeles, CA 90073 USA. EM abrody@ucla.edu OI Bergen, Andrew/0000-0002-1237-7644 FU National Institute on Drug Abuse [R01 DA20872, R21 DA33813]; Department of Veterans Affairs, Office of Research and Development [I01 CX000412]; Tobacco-Related Disease Research Program [23XT-0002] FX This work was supported by grants from the National Institute on Drug Abuse (R01 DA20872), the Department of Veterans Affairs, Office of Research and Development (CSR&D Merit Review Award I01 CX000412), and the Tobacco-Related Disease Research Program (#23XT-0002) to Arthur L. Brody, and a grant from the National Institute on Drug Abuse (R21 DA33813) to Andrew W. Bergen. Michael Mamoun, Andrew W. Bergen, Arthur L. Brody, Jennifer Shieh and Anna Wiggins report no conflicts of interest. NR 148 TC 4 Z9 4 U1 4 U2 14 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1172-7047 EI 1179-1934 J9 CNS DRUGS JI CNS Drugs PD MAY PY 2015 VL 29 IS 5 BP 359 EP 369 DI 10.1007/s40263-015-0243-1 PG 11 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CK5GG UT WOS:000356250500002 PM 25895022 ER PT J AU Kim, J Wu, Y Guo, YK Zheng, HR Sun, PZ AF Kim, Jinsuh Wu, Yin Guo, Yingkun Zheng, Hairong Sun, Phillip Zhe TI A review of optimization and quantification techniques for chemical exchange saturation transfer MRI toward sensitive in vivo imaging SO CONTRAST MEDIA & MOLECULAR IMAGING LA English DT Review DE chemical exchange saturatio transfer; MRI; amide proton transfer; quantitative chemical exchange saturatio transfer ID TRANSFER RATIO MEASUREMENTS; ACUTE CEREBRAL-ISCHEMIA; MAGNETIZATION-TRANSFER; CONTRAST AGENTS; 7 T; PARACEST AGENTS; TRANSFER CEST; HUMAN BRAIN; PROTON-EXCHANGE; FIELD-DEPENDENCE AB Chemical exchange saturation transfer (CEST) MRI is a versatile imaging method that probes the chemical exchange between bulk water and exchangeable protons. CEST imaging indirectly detects dilute labile protons via bulk water signal changes following selective saturation of exchangeable protons, which offers substantial sensitivity enhancement and has sparked numerous biomedical applications. Over the past decade, CEST imaging techniques have rapidly evolved owing to contributions from multiple domains, including the development of CEST mathematical models, innovative contrast agent designs, sensitive data acquisition schemes, efficient field inhomogeneity correction algorithms, and quantitative CEST (qCEST) analysis. The CEST system that underlies the apparent CEST-weighted effect, however, is complex. The experimentally measurable CEST effect depends not only on parameters such as CEST agent concentration, pH and temperature, but also on relaxation rate, magnetic field strength and more importantly, experimental parameters including repetition time, RF irradiation amplitude and scheme, and image readout. Thorough understanding of the underlying CEST system using qCEST analysis may augment the diagnostic capability of conventional imaging. In this review, we provide a concise explanation of CEST acquisition methods and processing algorithms, including their advantages and limitations, for optimization and quantification of CEST MRI experiments. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Kim, Jinsuh] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. [Wu, Yin; Zheng, Hairong] Chinese Acad Sci, Shenzhen Inst Adv Technol, Paul C Lauterbur Res Ctr Biomed Imaging, Shenzhen Key Lab MRI, Shenzhen, Peoples R China. [Wu, Yin; Guo, Yingkun; Sun, Phillip Zhe] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Wu, Yin; Guo, Yingkun; Sun, Phillip Zhe] Harvard Univ, Sch Med, Charlestown, MA USA. RP Sun, PZ (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Rm 2301,149 13th St, Charlestown, MA 02129 USA. EM pzhesun@nmr.mgh.harvard.edu FU China Scholarship Council; NSFC [81120108012]; 973 Program [2015CB755500]; NIH/NIBIB [1K01EB009771]; NIH/NINDS [1R01NS083654] FX This study was supported in part by grants from China Scholarship Council (Drs Wu and Guo), NSFC 81120108012 (Dr Wu), 973 Program 2015CB755500 (Dr Zheng) NIH/NIBIB 1K01EB009771 (Dr Sun) and NIH/NINDS 1R01NS083654 (Dr Sun). The authors wish to thank Ms Nichole Jenkins for editorial assistance. NR 145 TC 6 Z9 7 U1 9 U2 43 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1555-4309 EI 1555-4317 J9 CONTRAST MEDIA MOL I JI Contrast Media Mol. Imaging PD MAY-JUN PY 2015 VL 10 IS 3 BP 163 EP 178 DI 10.1002/cmmi.1628 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK6TT UT WOS:000356361800001 PM 25641791 ER PT J AU Greffier, J Macri, F Larbi, A Fernandez, A Khasanova, E Pereira, F Mekkaoui, C Beregi, JP AF Greffier, J. Macri, F. Larbi, A. Fernandez, A. Khasanova, E. Pereira, F. Mekkaoui, C. Beregi, J. P. TI Dose reduction with iterative reconstruction: Optimization of CT protocols in clinical practice SO DIAGNOSTIC AND INTERVENTIONAL IMAGING LA English DT Article DE Multidetector CT; Iterative reconstruction; Dose reduction; Image quality; Patient safety ID FILTERED BACK-PROJECTION; COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE; TO-NOISE; PERFORMANCE; PHANTOM; SYSTEM; MDCT; ALGORITHMS; SCANNERS AB Objectives: To create an adaptable and global approach for optimizing MDCT protocols by evaluating the influence of acquisition parameters and Iterative Reconstruction (IR) on dose reduction and image quality. Materials and methods: MDCT acquisitions were performed on quality image phantom by varying kVp, mAs, and pitch for the same collimation. The raw data were reconstructed by FBP and Sinogram Affirmed Iterative Reconstruction (SAFIRE) with different reconstruction kernel and thickness. A total of 4032 combinations of parameters were obtained. Indices of quality image (image noise, NCT, CNR, SNR, NPS and MTF) were analyzed. We developed a software in order to facilitate the optimization between dose reduction and image quality. Its outcomes were verified on an adult anthropomorphic phantom. Results: Dose reduction resulted in the increase of image noise and the decrease of SNR and CNR. The use of IR improved these indices for the same dose without affecting NCT and MTF. The image validation was performed by the anthropomorphic phantom. The software proposed combinations of parameters to reduce doses while keeping indices of the image quality adequate. We observed a CTDIvol reduction between -44% and -83% as compared to the French diagnostic reference levels (DRL) for different anatomical localization. Conclusion: The software developed in this study may help radiologists in selecting adequate combinations of parameters that allows to obtain an appropriate image with dose reduction. (C) 2015 Editions francaises de radiologie. Published by Elsevier Masson SAS. All rights reserved. C1 [Greffier, J.; Macri, F.; Larbi, A.; Fernandez, A.; Khasanova, E.; Pereira, F.; Mekkaoui, C.; Beregi, J. P.] Univ Hosp Ctr Nimes, Dept Radiol, EA 2415, F-30029 Nimes, France. [Khasanova, E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mekkaoui, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. RP Greffier, J (reprint author), CHU Nimes, Bd Prof Robert Debre, F-30029 Nimes 9, France. EM joel.greffier@chu-nimes.fr OI Greffier, Joel/0000-0002-1735-5129 NR 29 TC 18 Z9 18 U1 1 U2 4 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 2211-5684 J9 DIAGN INTERV IMAG JI Diagn. Interv. Imaging PD MAY PY 2015 VL 96 IS 5 BP 477 EP 486 DI 10.1016/j.diii.2015.02.007 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK2RJ UT WOS:000356059000008 PM 25797211 ER PT J AU Shah, SP Glenn, GL Hummel, EM Hamilton, JM Martine, RR Duda, JE Wilkinson, JR AF Shah, Shital P. Glenn, Gretchen L. Hummel, Eileen M. Hamilton, Jane M. Martine, Rebecca R. Duda, John E. Wilkinson, Jayne R. TI Caregiver tele-support group for Parkinson's disease: A pilot study SO GERIATRIC NURSING LA English DT Article DE Parkinson's disease; Telehealth; Caregiver; Support group; Telemedicine ID FAMILY CAREGIVERS; TELEPHONE SUPPORT; OLDER-ADULTS; BURDEN; DEPRESSION; DEMENTIA; CANCER; LIFE AB Background: Parkinson's disease (PD) is a disabling neurodegenerative disease that typically affects the geriatric population and requires a caregiver. Although caregiver burden reduces quality of life of the caregiver, support groups for caregivers have not been studied. Offering a tele-support group to PD caregivers would be an innovative approach to extending a novel resource. Methods: A single-center pilot study was conducted, enrolling caregivers in an 8-week tele-support group program. Mood state and caregiver burden were assessed at baseline and conclusion of the program using self-report questionnaires. Qualitative feedback was obtained at the conclusion of the program. Results: Seven female spouse caregivers enrolled: 86% completed the program. Although no statistically significant changes in questionnaire scores were found, the mean Geriatric Depression Scale decreased from 4.2 to 3 and qualitative feedback was universally positive. Conclusions: The use of tele-support groups for PD caregivers is a feasible and innovative resource to address caregiver burden. Published by Elsevier Inc. C1 [Shah, Shital P.; Glenn, Gretchen L.; Hummel, Eileen M.; Martine, Rebecca R.; Duda, John E.; Wilkinson, Jayne R.] Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Shah, Shital P.; Duda, John E.; Wilkinson, Jayne R.] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19107 USA. [Hamilton, Jane M.] Partners Path LLC, Gwynedd Valley, PA 19437 USA. RP Wilkinson, JR (reprint author), Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, 3900 Woodland Ave,Mail Stop 127, Philadelphia, PA 19104 USA. EM jayne.wilkinson@va.gov NR 30 TC 2 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4572 EI 1528-3984 J9 GERIATR NURS JI Geriatr. Nurs. PD MAY-JUN PY 2015 VL 36 IS 3 BP 207 EP 211 DI 10.1016/j.gerinurse.2015.02.002 PG 5 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA CK7HG UT WOS:000356402800007 PM 25744558 ER PT J AU Sadeghian, H Lacoste, B Qin, T Rosa, R Gu, C Ayata, C AF Sadeghian, H. Lacoste, B. Qin, T. Rosa, R. Gu, C. Ayata, C. TI Cortical Spreading Depression Induces a Transient Disruption of the Blood-brain Barrier Prevented by Rho-kinase Inhibition and Associated with Increased Transcytosis SO HEADACHE LA English DT Meeting Abstract CT 57th Annual Scientific Meeting of the American-Headache-Society CY JUN 18-21, 2015 CL Washington, DC SP Amer Headache Soc C1 [Sadeghian, H.; Qin, T.; Ayata, C.] Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, Boston, MA 02114 USA. [Lacoste, B.; Rosa, R.; Gu, C.] Harvard Univ, Sch Med, Dept Neurobiol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-8748 EI 1526-4610 J9 HEADACHE JI Headache PD MAY PY 2015 VL 55 SU 3 SI SI MA OR15 BP 133 EP 133 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA CK7RT UT WOS:000356430500016 ER PT J AU Chen, S Ay, I Sadeghian, H Qin, T Simon, B Eikermann-Haerter, K Ayata, C AF Chen, S. Ay, I Sadeghian, H. Qin, T. Simon, B. Eikermann-Haerter, K. Ayata, C. TI Vagus Nerve Stimulation Inhibits Cortical Spreading Depression SO HEADACHE LA English DT Meeting Abstract CT 57th Annual Scientific Meeting of the American-Headache-Society CY JUN 18-21, 2015 CL Washington, DC SP Amer Headache Soc C1 [Chen, S.; Ay, I; Sadeghian, H.; Qin, T.; Eikermann-Haerter, K.; Ayata, C.] Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, Boston, MA 02114 USA. [Simon, B.] ElectroCore LLC, Morris Plains, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-8748 EI 1526-4610 J9 HEADACHE JI Headache PD MAY PY 2015 VL 55 SU 3 SI SI MA PS25 BP 170 EP 171 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CK7RT UT WOS:000356430500108 ER PT J AU Sadeghian, H Harms, C Qin, T Ferrari, M van den Maagdenberg, A Endres, M Ayata, C AF Sadeghian, H. Harms, C. Qin, T. Ferrari, M. van den Maagdenberg, A. Endres, M. Ayata, C. TI Increased Susceptibility to Hypoxic/ischemic Injury in FHM1 Mutant Mice SO HEADACHE LA English DT Meeting Abstract CT 57th Annual Scientific Meeting of the American-Headache-Society CY JUN 18-21, 2015 CL Washington, DC SP Amer Headache Soc C1 [Sadeghian, H.; Qin, T.; Ayata, C.] Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, Boston, MA 02114 USA. [Harms, C.; Endres, M.] Charite, Ctr Stroke Res, Berlin, Germany. [Ferrari, M.; van den Maagdenberg, A.] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RA Leiden, Netherlands. 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 0017-8748 EI 1526-4610 J9 HEADACHE JI Headache PD MAY PY 2015 VL 55 SU 3 SI SI MA PS24 BP 170 EP 170 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA CK7RT UT WOS:000356430500107 ER PT J AU Seidel, J Balkaya, M Sadeghian, H Qin, T Eikermann-Haerter, K Ferrari, M van den Maagdenberg, A Ayata, C AF Seidel, J. Balkaya, M. Sadeghian, H. Qin, T. Eikermann-Haerter, K. Ferrari, M. van den Maagdenberg, A. Ayata, C. TI Effect of Environmental Stress on Spreading Depression SO HEADACHE LA English DT Meeting Abstract CT 57th Annual Scientific Meeting of the American-Headache-Society CY JUN 18-21, 2015 CL Washington, DC SP Amer Headache Soc C1 [Seidel, J.; Balkaya, M.; Sadeghian, H.; Qin, T.; Eikermann-Haerter, K.; Ayata, C.] Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, Boston, MA 02114 USA. [Ferrari, M.; van den Maagdenberg, A.] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RA Leiden, 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 0017-8748 EI 1526-4610 J9 HEADACHE JI Headache PD MAY PY 2015 VL 55 SU 3 SI SI MA PS23 BP 170 EP 170 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA CK7RT UT WOS:000356430500106 ER PT J AU Brigandi, SA Shao, H Qian, SY Shen, YP Wu, BL Kang, JX AF Brigandi, Sarah A. Shao, Hong Qian, Steven Y. Shen, Yiping Wu, Bai-Lin Kang, Jing X. TI Autistic Children Exhibit Decreased Levels of Essential Fatty Acids in Red Blood Cells SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE polyunsaturated fatty acids; omega-6 and omega-3 fatty acids; prostaglandin E2; lipid metabolism; neuroinflammation; autism ID INCREASED LIPID-PEROXIDATION; SPECTRUM DISORDERS; DOCOSAHEXAENOIC ACID; OXIDATIVE STRESS; ARACHIDONIC-ACID; DIETARY N-6; ERYTHROCYTE; BRAIN; PLASMA; PHOSPHOLIPIDS AB Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential nutrients for brain development and function. However, whether or not the levels of these fatty acids are altered in individuals with autism remains debatable. In this study, we compared the fatty acid contents between 121 autistic patients and 110 non-autistic, non-developmentally delayed controls, aged 3-17. Analysis of the fatty acid composition of red blood cell (RBC) membrane phospholipids showed that the percentage of total PUFA was lower in autistic patients than in controls; levels of n-6 arachidonic acid (AA) and n-3 docosahexaenoic acid (DHA) were particularly decreased (p < 0.001). In addition, plasma levels of the pro-inflammatory AA metabolite prostaglandin E2 (PGE2) were higher in a subset of the autistic participants (n = 20) compared to controls. Our study demonstrates an alteration in the PUFA profile and increased production of a PUFA-derived metabolite in autistic patients, supporting the hypothesis that abnormal lipid metabolism is implicated in autism. C1 [Brigandi, Sarah A.; Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Shao, Hong; Shen, Yiping; Wu, Bai-Lin] Childrens Hosp Boston, Dept Lab Med & Pathol, Genet Diagnost Lab, Boston, MA 02114 USA. [Shao, Hong; Shen, Yiping; Wu, Bai-Lin] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Qian, Steven Y.] N Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58108 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Dept Med, Lab Lipid Med & Technol, Boston, MA 02129 USA. EM sarah.brigandi@gmail.com; hongshao138@gmail.com; steven.qian@ndsu.edu; yiping.shen@childrens.harvard.edu; bai-lin.wu@childrens.harvard.edu; kang.jing@mgh.harvard.edu FU United States Department of Defense (DoD) Autism Research Program Idea Award [W81XWh-10-1-0788] FX This study was supported by the United States Department of Defense (DoD) Autism Research Program Idea Award (W81XWh-10-1-0788). The authors are also grateful to Marina Kang for her editorial assistance. NR 47 TC 17 Z9 17 U1 2 U2 9 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD MAY PY 2015 VL 16 IS 5 BP 10061 EP 10076 DI 10.3390/ijms160510061 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA CK5DC UT WOS:000356241400056 PM 25946342 ER PT J AU Ballard, ME Mandelkern, MA Monterosso, JR Hsu, E Robertson, CL Ishibashi, K Dean, AC London, ED AF Ballard, Michael E. Mandelkern, Mark A. Monterosso, John R. Hsu, Eustace Robertson, Chelsea L. Ishibashi, Kenji Dean, Andy C. London, Edythe D. TI Low Dopamine D-2/D-3 Receptor Availability is Associated with Steep Discounting of Delayed Rewards in Methamphetamine Dependence SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE addiction; delay discounting; dopamine; impulsivity; positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; REFERENCE TISSUE MODEL; D-3 RECEPTOR; NICOTINE DEPENDENCE; DISTRIBUTION VOLUME; IMPULSIVE BEHAVIOR; CIGARETTE-SMOKING; CHRONIC COCAINE; FUTURE REWARDS; BRAIN IMAGES AB Background: Individuals with substance use disorders typically exhibit a predilection toward instant gratification with apparent disregard for the future consequences of their actions. Indirect evidence suggests that low dopamine D-2-type receptor availability in the striatum contributes to the propensity of these individuals to sacrifice long-term goals for short-term gain; however, this possibility has not been tested directly. We investigated whether striatal D-2/D-3 receptor availability is negatively correlated with the preference for smaller, more immediate rewards over larger, delayed alternatives among research participants who met DSM-IV criteria for methamphetamine (MA) dependence. Methods: Fifty-four adults (n = 27 each: MA-dependent, non-user controls) completed the Kirby Monetary Choice Questionnaire, and underwent positron emission tomography scanning with [F-18] fallypride. Results: MA users displayed steeper temporal discounting (p = 0.030) and lower striatal D-2/D-3 receptor availability (p < 0.0005) than controls. Discount rate was negatively correlated with striatal D-2/D-3 receptor availability, with the relationship reaching statistical significance in the combined sample (r = -0.291, p = 0.016) and among MA users alone (r = -0.342, p = 0.041), but not among controls alone (r = -0.179, p = 0.185); the slopes did not differ significantly between MA users and controls (p = 0.5). Conclusions: These results provide the first direct evidence of a link between deficient D-2/D-3 receptor availability and steep temporal discounting. This finding fits with reports that low striatal D-2/D-3 receptor availability is associated with a higher risk of relapse among stimulant users, and may help to explain why some individuals choose to continue using drugs despite knowledge of their eventual negative consequences. Future research directions and therapeutic implications are discussed. C1 [Ballard, Michael E.; Ishibashi, Kenji; Dean, Andy C.; London, Edythe D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Robertson, Chelsea L.; London, Edythe D.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. [London, Edythe D.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [Ballard, Michael E.; Mandelkern, Mark A.; Robertson, Chelsea L.; Ishibashi, Kenji; London, Edythe D.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. [Monterosso, John R.; Hsu, Eustace] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. RP London, ED (reprint author), UCLA, Semel Inst Neurosci & Human Behav, 760 Westwood Plaza,C8-831, Los Angeles, CA 90024 USA. EM elondon@mednet.ucla.edu RI Ballard, Michael/F-9146-2013 OI Ballard, Michael/0000-0002-2651-6588 FU NIH [R01 DA020726, P20 DA022539, M0I RR00865]; [T32 DA024635] FX This research was supported by NIH grants R01 DA020726, P20 DA022539, M0I RR00865, and endowments from the Thomas P and Katherine K Pike Chair in Addiction Studies (Dr London), and the Marjorie M Greene Trust. Dr Ballard was supported by T32 DA024635. NR 77 TC 10 Z9 10 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD MAY PY 2015 VL 18 IS 7 DI 10.1093/ijnp/pyu119 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CL1KV UT WOS:000356702800004 ER PT J AU Grigoryan, KV Best, A Dellavalle, RP AF Grigoryan, Konstantin V. Best, Arthur Dellavalle, Robert P. TI University Tort Liability for Allowing College Debit Card Purchasing of Indoor UV Tanning Services SO JAMA DERMATOLOGY LA English DT Editorial Material C1 [Grigoryan, Konstantin V.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Best, Arthur] Univ Denver, Sturm Coll Law, Denver, CO USA. [Dellavalle, Robert P.] US Dept Vet Affairs, Eastern Colorado Hlth Care Syst, Dermatol Serv, Denver, CO USA. RP Dellavalle, RP (reprint author), US Dept Vet Affairs, Med Ctr, Dermatol Serv, 1055 Clermont St,Mail Code 165, Denver, CO 80220 USA. EM robert.dellavalle@ucdenver.edu NR 6 TC 1 Z9 1 U1 0 U2 1 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 MAY PY 2015 VL 151 IS 5 BP 479 EP 480 DI 10.1001/jamadermatol.2014.5350 PG 2 WC Dermatology SC Dermatology GA CK4FH UT WOS:000356176700002 PM 25650948 ER PT J AU Kourosh, AS Kvedar, JC AF Kourosh, A. Shadi Kvedar, Joseph C. TI Making Mobile Health Measure Up SO JAMA DERMATOLOGY LA English DT Editorial Material ID SUNSCREEN USE; SUN EXPOSURE; ATTITUDES; ADHERENCE; BEHAVIORS; KNOWLEDGE C1 [Kourosh, A. Shadi; Kvedar, Joseph C.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kourosh, A. Shadi; Kvedar, Joseph C.] Harvard Univ, Sch Med, Boston, MA USA. [Kourosh, A. Shadi; Kvedar, Joseph C.] Harvard Univ, Sch Med, Ctr Connected Hlth, Partners Ctr Connected Hlth, Boston, MA USA. RP Kvedar, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Connected Hlth,Partners Ctr Connected Hlth,De, Boston, MA 02114 USA. EM jkvedar@partners.org NR 13 TC 1 Z9 1 U1 1 U2 4 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 MAY PY 2015 VL 151 IS 5 BP 481 EP 482 DI 10.1001/jamadermatol.2014.3880 PG 2 WC Dermatology SC Dermatology GA CK4FH UT WOS:000356176700004 PM 25629289 ER PT J AU D'Souza, LS Jalian, HR Jalian, C Alam, M Eisen, DB Avram, MM Ibrahimi, OA AF D'Souza, Logan S. Jalian, H. Ray Jalian, Chris Alam, Murad Eisen, Daniel B. Avram, Mathew M. Ibrahimi, Omar A. TI Medical Professional Liability Claims for Mohs Micrographic Surgery From 1989 to 2011 SO JAMA DERMATOLOGY LA English DT Article ID MALPRACTICE; DERMATOLOGISTS; RISK AB IMPORTANCE Few studies specifically address lawsuits involving Mohs surgery. OBJECTIVE To better characterize the types of medical professional liability claims involving Mohs surgery. DESIGN, SETTING, AND PARTICIPANTS Retrospective legal document review of an online national database. Any legal proceeding involving the search words Mohs and cancer was included. MAIN OUTCOMES AND MEASURES Number of medical professional liability claims involving Mohs surgery for factors including year of litigation, location, physician specialty, injury sustained, cause of legal action, and verdict. RESULTS Forty-two cases were identified, which occurred from 1989 to 2011. Of the cases identified, 26 involved non-Mohs surgeons as the primary defendant, mostly due to a delay of or failure in diagnosis (n = 16), cosmetic outcome issues (n = 8), lack of informed consent (n = 7), and a delay of or failure in referral to a Mohs surgeon (n = 6). Common causes for litigation against Mohs surgeons as the primary defendant (n = 16) were lack of proper informed consent (n = 5) and cosmetic outcome issues (n = 4). Only 1 case against a Mohs surgeon was judged for the plaintiff. CONCLUSIONS AND RELEVANCE The most common lawsuits pertaining to Mohs surgery list non-Mohs surgeons as the primary defendants. Closer coordination between non-Mohs surgeons and Mohs surgeons may help minimize risk to both parties and lead to better patient care. Small sample size is the primary C1 [D'Souza, Logan S.] Univ Connecticut, Ctr Hlth, Dept Dermatol, Farmington, CT USA. [Jalian, H. Ray; Avram, Mathew M.; Ibrahimi, Omar A.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Jalian, H. Ray; Avram, Mathew M.; Ibrahimi, Omar A.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Jalian, H. Ray] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Los Angeles, CA 90095 USA. [Jalian, Chris] Paul Hastings LLC, New York, NY USA. [Alam, Murad] Northwestern Univ, Dept Dermatol, Chicago, IL 60611 USA. [Eisen, Daniel B.] Univ Calif Davis, Dept Dermatol, Sacramento, CA 95817 USA. [Ibrahimi, Omar A.] Connecticut Skin Inst, Stamford, CT 06905 USA. RP Ibrahimi, OA (reprint author), Connecticut Skin Inst, 999 Summer St,Ste 205, Stamford, CT 06905 USA. EM omar.ibrahimi@gmail.com OI Eisen, Daniel/0000-0001-6741-3182 NR 17 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD MAY PY 2015 VL 151 IS 5 BP 529 EP 532 DI 10.1001/jamadermatol.2014.4495 PG 4 WC Dermatology SC Dermatology GA CK4FH UT WOS:000356176700013 PM 25650805 ER PT J AU Kutner, JS Blatchford, PJ Taylor, DH Ritchie, CS Bull, JH Fairclough, DL Hanson, LC LeBlanc, TW Samsa, GP Wolf, S Aziz, NM Currow, DC Ferrell, B Wagner-Johnston, N Zafar, SY Cleary, JF Dev, S Goode, PS Kamal, AH Kassner, C Kvale, EA McCallum, JG Ogunseitan, AB Pantilat, SZ Portenoy, RK Prince-Paul, M Sloan, JA Swetz, KM Von Gunten, CF Abernethy, AP AF Kutner, Jean S. Blatchford, Patrick J. Taylor, Donald H., Jr. Ritchie, Christine S. Bull, Janet H. Fairclough, Diane L. Hanson, Laura C. LeBlanc, Thomas W. Samsa, Greg P. Wolf, Steven Aziz, Noreen M. Currow, David C. Ferrell, Betty Wagner-Johnston, Nina Zafar, S. Yousuf Cleary, James F. Dev, Sandesh Goode, Patricia S. Kamal, Arif H. Kassner, Cordt Kvale, Elizabeth A. McCallum, Janelle G. Ogunseitan, Adeboye B. Pantilat, Steven Z. Portenoy, Russell K. Prince-Paul, Maryjo Sloan, Jeff A. Swetz, Keith M. Von Gunten, Charles F. Abernethy, Amy P. TI Safety and Benefit of Discontinuing Statin Therapy in the Setting of Advanced, Life-Limiting Illness A Randomized Clinical Trial SO JAMA INTERNAL MEDICINE LA English DT Article ID SHARED DECISION-MAKING; PALLIATIVE CARE; SURPRISE QUESTION; OLDER PATIENTS; HEART-FAILURE; RISK; MEDICATIONS; DISEASE; METAANALYSIS; MEDICINE AB IMPORTANCE For patients with limited prognosis, some medication risks may outweigh the benefits, particularly when benefits take years to accrue; statins are one example. Data are lacking regarding the risks and benefits of discontinuing statin therapy for patients with limited life expectancy. OBJECTIVE To evaluate the safety, clinical, and cost impact of discontinuing statin medications for patients in the palliative care setting. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter, parallel-group, unblinded, pragmatic clinical trial. Eligibility included adults with an estimated life expectancy of between 1 month and 1 year, statin therapy for 3 months or more for primary or secondary prevention of cardiovascular disease, recent deterioration in functional status, and no recent active cardiovascular disease. Participants were randomized to either discontinue or continue statin therapy and were monitored monthly for up to 1 year. The study was conducted from June 3, 2011, to May 2, 2013. All analyses were performed using an intent-to-treat approach. INTERVENTIONS Statin therapy was withdrawn from eligible patients who were randomized to the discontinuation group. Patients in the continuation group continued to receive statins. MAIN OUTCOMES AND MEASURES Outcomes included death within 60 days (primary outcome), survival, cardiovascular events, performance status, quality of life (QOL), symptoms, number of nonstatin medications, and cost savings. RESULTS A total of 381 patients were enrolled; 189 of these were randomized to discontinue statins, and 192 were randomized to continue therapy. Mean (SD) age was 74.1 (11.6) years, 22.0% of the participants were cognitively impaired, and 48.8% had cancer. The proportion of participants in the discontinuation vs continuation groups who died within 60 days was not significantly different (23.8% vs 20.3%; 90% CI, -3.5% to 10.5%; P =.36) and did not meet the noninferiority end point. Total QOL was better for the group discontinuing statin therapy (mean McGill QOL score, 7.11 vs 6.85; P =.04). Few participants experienced cardiovascular events (13 in the discontinuation group vs 11 in the continuation group). Mean cost savings were $3.37 per day and $716 per patient. CONCLUSIONS AND RELEVANCE This pragmatic trial suggests that stopping statin medication therapy is safe and may be associated with benefits including improved QOL, use of fewer nonstatin medications, and a corresponding reduction in medication costs. Thoughtful patient-provider discussions regarding the uncertain benefit and potential decrement in QOL associated with statin continuation in this setting are warranted. C1 [Kutner, Jean S.] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. [Blatchford, Patrick J.; Fairclough, Diane L.] Colorado Sch Publ Hlth, Dept Biostat & Informat, Denver, CO USA. [Taylor, Donald H., Jr.] Duke Univ, Sanford Sch Publ Policy, Durham, NC 27710 USA. [Ritchie, Christine S.] San Francisco VA Med Ctr, Ctr Res Aging, Jewish Home San Francisco, San Francisco, CA USA. [Ritchie, Christine S.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Bull, Janet H.] Four Seasons Compass Life, Flat Rock, NC USA. [Hanson, Laura C.] Univ N Carolina, Div Geriatr Med, Chapel Hill, NC USA. [LeBlanc, Thomas W.; Zafar, S. Yousuf; Kamal, Arif H.; Abernethy, Amy P.] Duke Univ, Sch Med, Duke Clin Res Inst, Ctr Learning Hlth Care, Durham, NC 27710 USA. [Samsa, Greg P.; Wolf, Steven] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. [Aziz, Noreen M.] NINR, NIH, Bethesda, MD 20892 USA. [Currow, David C.] Flinders Univ S Australia, Discipline, Palliat Serv, Adelaide, SA 5001, Australia. [Currow, David C.] Flinders Univ S Australia, Discipline, Support Serv, Adelaide, SA 5001, Australia. [Ferrell, Betty] City Hope Natl Med Ctr, City Hope Med Ctr, Dept Nursing Res, Duarte, CA USA. [Wagner-Johnston, Nina] Washington Univ, Dept Med, St Louis, MO USA. [Cleary, James F.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Hematol Oncol, Madison, WI 53706 USA. [Dev, Sandesh] Phoenix Vet Affairs Hlth Care Syst, Dept Med, Phoenix, AZ USA. [Goode, Patricia S.; Kvale, Elizabeth A.] Birmingham Vet Affairs Med Ctr, Vet Affairs Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. [Goode, Patricia S.; Kvale, Elizabeth A.] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA. [Kassner, Cordt] Hosp Analyt, Denver, CO USA. [McCallum, Janelle G.] Denver Hosp, Denver, CO USA. [Ogunseitan, Adeboye B.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. [Pantilat, Steven Z.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Portenoy, Russell K.] Metropolitan Jewish Hlth Syst, Hosp & Palliat Care, New York, NY USA. [Prince-Paul, Maryjo] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA. [Sloan, Jeff A.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Swetz, Keith M.] Mayo Clin, Dept Med, Rochester, MN USA. [Von Gunten, Charles F.] OhioHealth, Dept Hosp & Palliat Med, Columbus, OH USA. RP Abernethy, AP (reprint author), Duke Univ, Sch Med, Duke Clin Res Inst, Ctr Learning Hlth Care, Durham, NC 27710 USA. EM amy.abernethy@duke.edu OI LeBlanc, Thomas/0000-0002-0546-7895; Currow, David/0000-0003-1988-1250 FU National Institute of Nursing Research [UC4-NR012584, U24-NR014637] FX This study received funding from the National Institute of Nursing Research (grants UC4-NR012584 and U24-NR014637). Furthermore, this work included the support of resources and facilities within the Veterans Affairs Health Care System (eg, Phoenix, Arizona, and Birmingham, Alabama). NR 45 TC 67 Z9 68 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAY PY 2015 VL 175 IS 5 BP 691 EP 700 DI 10.1001/jamainternmed.2015.0289 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CK4FQ UT WOS:000356178400004 PM 25798575 ER PT J AU Bekelman, DB Plomondon, ME Carey, EP Sullivan, MD Nelson, KM Hattler, B McBryde, CF Lehmann, KG Gianola, K Heidenreich, PA Rumsfeld, JS AF Bekelman, David B. Plomondon, Mary E. Carey, Evan P. Sullivan, Mark D. Nelson, Karin M. Hattler, Brack McBryde, Connor F. Lehmann, Kenneth G. Gianola, Katherine Heidenreich, Paul A. Rumsfeld, John S. TI Primary Results of the Patient-Centered Disease Management (PCDM) for Heart Failure Study A Randomized Clinical Trial SO JAMA INTERNAL MEDICINE LA English DT Article ID COLLABORATIVE CARE INTERVENTION; HOME-BASED INTERVENTION; HEALTH-STATUS; DEPRESSIVE SYMPTOMS; RESOURCE UTILIZATION; OUTCOMES; RISK; HOSPITALIZATION; METAANALYSIS; READMISSION AB IMPORTANCE Heart failure (HF) has a major effect on patients' health status, including their symptom burden, functional status, and health-related quality of life. OBJECTIVE To determine the effectiveness of a collaborative care patient-centered disease management (PCDM) intervention to improve the health status of patients with HF. DESIGN, SETTING, AND PARTICIPANTS The Patient-Centered Disease Management (PCDM) trial was a multisite randomized clinical trial comparing a collaborative care PCDM intervention with usual care in patients with HF. A population-based sample of 392 patients with an HF diagnosis from 4 Veterans Affairs centers who had a Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score of less than 60 (heavy symptom burden and impaired functional status and quality of life) were enrolled between May 2009 and June 2011. INTERVENTIONS The PCDM intervention included collaborative care by a multidisciplinary care team consisting of a nurse coordinator, cardiologist, psychiatrist, and primary care physician; home telemonitoring and patient self-management support; and screening and treatment for comorbid depression. MAIN OUTCOMES AND MEASURES The primary outcome was change in the KCCQ overall summary score at 1 year (a 5-point change is clinically significant). Mortality, hospitalization, and depressive symptoms (Patient Health Questionnaire 9) were secondary outcomes. RESULTS There were no significant differences in baseline characteristics between patients randomized to the PCDM intervention (n = 187) vs usual care (n = 197); baseline mean KCCQ overall summary scores were 37.9 vs 36.9 (P =.48). There was significant improvement in the KCCQ overall summary scores in both groups after 1 year (mean change, 13.5 points in each group), with no significant difference between groups (P =.97). The intervention was not associated with greater improvement in the KCCQ overall summary scores when the effect over time was estimated using 3-month, 6-month, and 12-month data (P =.74). Among secondary outcomes, there were significantly fewer deaths at 1 year in the intervention arm (8 of 187 [4.3%]) than in the usual care arm (19 of 197 [9.6%]) (P =.04). Among those who screened positive for depression, there was a greater improvement in the Patient Health Questionnaire 9 scores after 1 year in the intervention arm than in the usual care arm (2.1 points lower, P =.01). There was no significant difference in 1-year hospitalization rates between the intervention arm and the usual care arm (29.4% vs 29.9%, P =.87). CONCLUSIONS AND RELEVANCE This multisite randomized trial of a multifaceted HF PCDM intervention did not demonstrate improved patient health status compared with usual care. C1 [Bekelman, David B.; Plomondon, Mary E.; Carey, Evan P.; Hattler, Brack; McBryde, Connor F.; Rumsfeld, John S.] Vet Affairs Eastern Colorado Hlth Care Syst, Res Geriatr Ambulatory Care & Cardiol, Denver, CO 80220 USA. [Bekelman, David B.; Hattler, Brack; McBryde, Connor F.; Rumsfeld, John S.] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. [Bekelman, David B.; Plomondon, Mary E.; Carey, Evan P.; Nelson, Karin M.; Rumsfeld, John S.] Denver Seattle Ctr Innovat Vet Ctr & Value Driven, Denver, CO USA. [Sullivan, Mark D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Nelson, Karin M.; Lehmann, Kenneth G.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Lehmann, Kenneth G.] Univ Washington, Dept Med, Seattle, WA USA. [Gianola, Katherine] Richmond Vet Affairs Med Ctr, Richmond, VA USA. [Heidenreich, Paul A.] Vet Affairs Palo Alto Hlth Care Syst, Cardiol, Palo Alto, CA USA. RP Bekelman, DB (reprint author), Vet Affairs Eastern Colorado Hlth Care Syst, Res 151, 1055 Clermont St, Denver, CO 80220 USA. EM david.bekelman@va.gov FU Department of Veterans Affairs Health Services Research and Development [IIR 06-068, 08-022] FX The Patient-Centered Heart Failure Trial was funded by grant IIR 06-068 from the Department of Veterans Affairs Health Services Research and Development. Dr Bekelman was supported by Career Development Award 08-022 from the Department of Veterans Affairs Health Services Research and Development during this study. NR 44 TC 20 Z9 20 U1 4 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAY PY 2015 VL 175 IS 5 BP 725 EP 732 DI 10.1001/jamainternmed.2015.0315 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CK4FQ UT WOS:000356178400010 PM 25822284 ER PT J AU Mendu, ML Lundquist, A Aizer, AA Leaf, DE Robinson, E Steele, DJR Waikar, SS AF Mendu, Mallika L. Lundquist, Andrew Aizer, Ayal A. Leaf, David E. Robinson, Emily Steele, David J. R. Waikar, Sushrut S. TI The Usefulness of Diagnostic Testing in the Initial Evaluation of Chronic Kidney Disease SO JAMA INTERNAL MEDICINE LA English DT Letter ID PREVALENCE C1 [Mendu, Mallika L.; Leaf, David E.; Robinson, Emily; Waikar, Sushrut S.] Harvard Univ, Brigham & Womens Hosp, Div Renal Med, Sch Med, Boston, MA 02115 USA. [Lundquist, Andrew; Steele, David J. R.] Harvard Univ, Massachusetts Gen Hosp, Div Nephrol, Sch Med, Boston, MA 02115 USA. [Aizer, Ayal A.] Harvard Radiat Oncol Program, Boston, MA USA. RP Mendu, ML (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Renal Med, Sch Med, 75 Francis St,MRB 4, Boston, MA 02115 USA. EM mmendu@partners.org FU NIDDK NIH HHS [T32 DK007527, F32 DK103339] NR 6 TC 3 Z9 3 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAY PY 2015 VL 175 IS 5 BP 853 EP 856 DI 10.1001/jamainternmed.2015.17 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CK4FQ UT WOS:000356178400036 PM 25730699 ER PT J AU Khaleghi, M Furlong, C Ravicz, M Cheng, JT Rosowski, JJ AF Khaleghi, Morteza Furlong, Cosme Ravicz, Mike Cheng, Jeffrey Tao Rosowski, John J. TI Three-dimensional vibrometry of the human eardrum with stroboscopic lensless digital holography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE 3-D displacement measurements; digital holography; holographic contouring; stroboscopic measurements; tympanic membrane ID TYMPANIC-MEMBRANE; MOTION; VIBRATION; MALLEUS; SURFACE; INCUS; SHAPE AB The eardrum or tympanic membrane (TM) transforms acoustic energy at the ear canal into mechanical motions of the ossicles. The acousto-mechanical transformer behavior of the TM is determined by its shape, three-dimensional (3-D) motion, and mechanical properties. We have developed an optoelectronic holographic system to measure the shape and 3-D sound-induced displacements of the TM. The shape of the TM is measured with dual-wavelength holographic contouring using a tunable near IR laser source with a central wavelength of 780 nm. 3-D components of sound-induced displacements of the TM are measured with the method of multiple sensitivity vectors using stroboscopic holographic interferometry. To accurately obtain sensitivity vectors, a new technique is developed and used in which the sensitivity vectors are obtained from the images of a specular sphere that is being illuminated from different directions. Shape and 3-D acoustically induced displacement components of cadaveric human TMs at several excitation frequencies are measured at more than one million points on its surface. A numerical rotation matrix is used to rotate the original Euclidean coordinate of the measuring system in order to obtain in-plane and out-of-plane motion components. Results show that in-plane components of motion are much smaller (<20%) than the out-of-plane motions' components. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. C1 [Khaleghi, Morteza; Furlong, Cosme] Worcester Polytech Inst, Ctr Holog Studies & Laser Micromechatron, Dept Mech Engn, Worcester, MA 01609 USA. [Furlong, Cosme; Ravicz, Mike; Cheng, Jeffrey Tao; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Furlong, Cosme; Ravicz, Mike; Cheng, Jeffrey Tao; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Khaleghi, M (reprint author), Worcester Polytech Inst, Ctr Holog Studies & Laser Micromechatron, Dept Mech Engn, Worcester, MA 01609 USA. EM mkm@wpi.edu FU National Institute on Deafness and other Communication Disorders (NIDCD); National Institutes of Health (NIH); Massachusetts Eye and Ear Infirmary (MEEI); Mechanical Engineering Department at Worcester Polytechnic Institute FX This work was supported by the National Institute on Deafness and other Communication Disorders (NIDCD), the National Institutes of Health (NIH), Massachusetts Eye and Ear Infirmary (MEEI), and Mechanical Engineering Department at Worcester Polytechnic Institute. We also acknowledge the support of all of the members of the CHSLT labs at WPI and Eaton-Peabody labs at MEEI, in particular Ellery Harrington and Ivo Dobrev. NR 34 TC 9 Z9 9 U1 0 U2 7 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY PY 2015 VL 20 IS 5 AR 051028 DI 10.1117/1.JBO.20.5.051028 PG 11 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CK5DH UT WOS:000356241900033 PM 25652791 ER PT J AU Selb, J Yucel, MA Phillip, D Schytz, HW Iversen, HK Vangel, M Ashina, M Boas, DA AF Selb, Juliette Yuecel, Meryem A. Phillip, Dorte Schytz, Henrik W. Iversen, Helle K. Vangel, Mark Ashina, Messoud Boas, David A. TI Effect of motion artifacts and their correction on near-infrared spectroscopy oscillation data: a study in healthy subjects and stroke patients SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE near-infrared spectroscopy; functional brain imaging; motion artifacts; motion correction; resting state; hemodynamic oscillations; stroke ID LOW-FREQUENCY OSCILLATIONS; CEREBRAL HEMODYNAMICS; FUNCTIONAL CONNECTIVITY; MOVEMENT ARTIFACTS; BRAIN; NIRS; AUTOREGULATION; NETWORKS; DYNAMICS; FNIRS AB Functional near-infrared spectroscopy is prone to contamination by motion artifacts (MAs). Motion correction algorithms have previously been proposed and their respective performance compared for evoked brain activation studies. We study instead the effect of MAs on "oscillation" data which is at the basis of functional connectivity and autoregulation studies. We use as our metric of interest the interhemispheric correlation (IHC), the correlation coefficient between symmetrical time series of oxyhemoglobin oscillations. We show that increased motion content results in a decreased IHC. Using a set of motion-free data on which we add real MAs, we find that the best motion correction approach consists of discarding the segments of MAs following a careful approach to minimize the contamination due to band-pass filtering of data from "bad" segments spreading into adjacent "good" segments. Finally, we compare the IHC in a stroke group and in a healthy group that we artificially contaminated with the MA content of the stroke group, in order to avoid the confounding effect of increased motion incidence in the stroke patients. After motion correction, the IHC remains lower in the stroke group in the frequency band around 0.1 and 0.04 Hz, suggesting a physiological origin for the difference. We emphasize the importance of considering MAs as a confounding factor in oscillation-based functional near-infrared spectroscopy studies. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Selb, Juliette; Yuecel, Meryem A.; Vangel, Mark; Boas, David A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Phillip, Dorte; Schytz, Henrik W.; Ashina, Messoud] Univ Copenhagen, Rigshosp, Danish Headache Ctr, Fac Hlth Sci,Dept Neurol, DK-2600 Glostrup, Denmark. [Iversen, Helle K.] Univ Copenhagen, Rigshosp, Stroke Unit, Fac Hlth Sci,Dept Neurol, DK-2600 Glostrup, Denmark. RP Selb, J (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St, Charlestown, MA 02129 USA. EM juliette@nmr.mgh.harvard.edu OI Schytz, Henrik Winther/0000-0002-6262-2986 FU National Institutes of Health [P41EB015896, R01GM104986]; Lundbeck Foundation via the Lundbeck Foundation Center for Neurovascular Signaling (LUCENS); University of Copenhagen; Augustinus Foundation; Toyota Foundation FX J.S. is grateful to Silvina L. Ferradal, PhD, for useful parallels with fMRI studies regarding correlation computation after MA segment removal. This study was supported by the National Institutes of Health grants P41EB015896 and R01GM104986 (J.S., M.A.Y., and D.A.B.), and funding for data collection was provided by the Lundbeck Foundation via the Lundbeck Foundation Center for Neurovascular Signaling (LUCENS), the University of Copenhagen, the Augustinus Foundation and the Toyota Foundation (D.P., H.W.S., H.K.I., and M.A.). DAB is an inventor of continuous-wave near infrared spectroscopy technology licensed to TechEn, a company whose medical pursuits focus on noninvasive, optical brain monitoring. DAB's interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. NR 48 TC 1 Z9 1 U1 1 U2 9 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY PY 2015 VL 20 IS 5 AR 056011 DI 10.1117/1.JBO.20.5.056011 PG 13 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CK5DH UT WOS:000356241900066 PM 26018790 ER PT J AU Tsai, J Harpaz-Rotem, I Armour, C Southwick, SM Krystal, JH Pietrzak, RH AF Tsai, Jack Harpaz-Rotem, Ilan Armour, Cherie Southwick, Steven M. Krystal, John H. Pietrzak, Robert H. TI Dimensional Structure of DSM-5 Posttraumatic Stress Disorder Symptoms: Results From the National Health and Resilience in Veterans Study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COMORBIDITY SURVEY REPLICATION; ADMINISTERED PTSD SCALE; QUALITY-OF-LIFE; 5-FACTOR MODEL; PHENOTYPIC HETEROGENEITY; DYSPHORIC AROUSAL; FIT INDEXES; US VETERANS; SYMPTOMATOLOGY; AFGHANISTAN AB Objective: To evaluate the prevalence of DSM-5 posttraumatic stress disorder (PTSD) and factor structure of PTSD symptomatology in a nationally representative sample of US veterans and examine how PTSD symptom clusters are related to depression, anxiety, suicidal ideation, hostility, physical and mental health-related functioning, and quality of life. Method: Data were analyzed from the National Health and Resilience in Veterans Study, a nationally representative survey of 1,484 US veterans conducted from September through October 2013. Confirmatory factor analyses were conducted to evaluate the factor structure of PTSD symptoms, and structural equation models were constructed to examine the association between PTSD symptom clusters and external correlates. Results: 12.0% of veterans screened positive for lifetime PTSD and 5.2% for past-month PTSD. A 5-factor dysphoric arousal model and a newly proposed 6-factor model both fit the data significantly better than the 4-factor model of DSM-5. The 6-factor model fit the data best in the full sample, as well as in subsamples of female veterans and veterans with lifetime PTSD. The emotional numbing symptom cluster was more strongly related to depression (P < .001) and worse mental health-related functioning (P < .001) than other symptom clusters, while the externalizing behavior symptom cluster was more strongly related to hostility (P < .001). Conclusions: A total of 5.2% of US veterans screened positive for past-month DSM-5 PTSD. A 6-factor model of DSM-5 PTSD symptoms, which builds on extant models and includes a sixth externalizing behavior factor, provides the best dimensional representation of DSM-5 PTSD symptom clusters and demonstrates validity in assessing health outcomes of interest in this population. (C) Copyright 2014 Physicians Postgraduate Press, Inc. C1 [Tsai, Jack] US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, West Haven, CT USA. [Tsai, Jack; Harpaz-Rotem, Ilan; Southwick, Steven M.; Krystal, John H.; Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Harpaz-Rotem, Ilan; Southwick, Steven M.; Krystal, John H.; Pietrzak, Robert H.] VA Connecticut Healthcare Syst, Clin Neurosci Div, Natl Ctr Posttraumat Stress Disorder, US Dept Vet Affairs, West Haven, CT USA. [Armour, Cherie] Univ Ulster, Psychol Res Inst, Coleraine BT52 1SA, Londonderry, North Ireland. RP Tsai, J (reprint author), 950 Campbell Ave,151D, West Haven, CT 06516 USA. EM Jack.Tsai@yale.edu OI Armour, Cherie/0000-0001-7649-3874 FU Department of Veterans Affairs, via its funding of the VA National Center for PTSD; (Department of Defense) of the Coalition to Alleviate PTSD (CAP); National Institute on Alcohol Abuse and Alcoholism [3P50AA012870]; National Institute of Mental Health (FAST-PS); National Center for Advancing Translational Science [UH2TR000960-01, UL1 RR024139]; State of Connecticut Department of Mental Health and Addiction Services FX We gratefully acknowledge the Department of Veterans Affairs, via its funding of the VA National Center for PTSD and its joint funding (with the Department of Defense) of the Coalition to Alleviate PTSD (CAP), the National Institute on Alcohol Abuse and Alcoholism (3P50AA012870), National Institute of Mental Health (FAST-PS), the National Center for Advancing Translational Science (UH2TR000960-01; Clinical and Translational Science Award Grant No. UL1 RR024139), and support of the State of Connecticut Department of Mental Health and Addiction Services for its support of the Abraham Ribicoff Research Facilities of the Connecticut Mental Health Center. NR 51 TC 23 Z9 24 U1 6 U2 18 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2015 VL 76 IS 5 BP 546 EP 553 DI 10.4088/JCP.14m09091 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CK0ZT UT WOS:000355935300016 PM 25562376 ER PT J AU Kehl, KL Lamont, EB McNeil, BJ Bozeman, SR Kelley, MJ Keating, NL AF Kehl, Kenneth L. Lamont, Elizabeth B. McNeil, Barbara J. Bozeman, Samuel R. Kelley, Michael J. Keating, Nancy L. TI Comparing a medical records-based and a claims-based index for measuring comorbidity in patients with lung or colon cancer SO JOURNAL OF GERIATRIC ONCOLOGY LA English DT Article DE Comorbidity; Charlson; ACE-27; Lung cancer; Colon cancer; Veterans Affairs ID STAGE BREAST-CANCER; ADMINISTRATIVE DATA; PREDICTIVE CAPACITY; OLDER PATIENTS; CO-MORBIDITY; MORTALITY; DATABASES; CARCINOMA; DIAGNOSIS; OUTCOMES AB Objective: Ascertaining comorbid conditions in cancer patients is important for research and clinical quality measurement, and is particularly important for understanding care and outcomes for older patients and those with multi-morbidity. We compared the medical records-based ACE-27 index and the claims-based Charlson index in predicting receipt of therapy and survival for lung and colon cancer patients. Materials and Methods: We calculated the Charlson index using administrative data and the ACE-27 score using medical records for Veterans Affairs patients diagnosed with stage I/II non-small cell lung or stage III colon cancer from January 2003 to December 2004. We compared the proportion of patients identified by each index as having any comorbidity. We used multivariable logistic regression to ascertain the predictive power of each index regarding delivery of guideline-recommended therapies and two-year survival, comparing the c-statistic and the Akaike information criterion (AIC). Results: Overall, 97.2% of lung and 90.9% of colon cancer patients had any comorbidity according to the ACE-27 index, versus 59.5% and 49.7%, respectively, according to the Charlson. Multivariable models including the ACE-27 index outperformed Charlson-based models when assessing receipt of guideline-recommended therapies, with higher c-statistics and lower AICs. Neither index was clearly superior in prediction of two-year survival. Conclusions: The ACE-27 index measured using medical records captured more comorbidity and outperformed the Charlson index measured using administrative data for predicting receipt of guideline-recommended therapies, demonstrating the potential value of more detailed comorbidity data. However, the two indices had relatively similar performance when predicting survival. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Kehl, Kenneth L.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lamont, Elizabeth B.; McNeil, Barbara J.; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [McNeil, Barbara J.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Bozeman, Samuel R.] Abt Associates Inc, Cambridge, MA USA. [Kelley, Michael J.] Durham Vet Affairs Med Ctr, Durham, ND USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU Department of Veterans Affairs through the Office of Policy and Planning FX This work was funded by the Department of Veterans Affairs through the Office of Policy and Planning. We are grateful for helpful feedback from the VA Oncology Program Evaluation Team, especially members with extensive clinical oncology experience within the VA system, including, Dr. Albert Muhleman (Cincinnati VAMC), Dr. Nirmala Bhoopalam (Hines, IL VAMC), Dr. Paulette Mehta (VHA), Dr. Dawn Provenzale (VA HSR&D Researcher in Durham, NC), Dr. Robert Kerns (National Program Director for Pain Management, VHA), and the chief VACCR registrar, Raye Anne Dom (VHA-DC VAMC). We also thank Marshall Amesquita and Barbara Stephens, COTR, and the rest of our VA Oncology Program Evaluation Team: Stanlie Daniels (VHA), Heidi Martin (VHA), Diana Ordin (VHA), Karen Pane (VA), Dr. Archna Sharma (VHA), Anecia Thibodeau (VHA), and Patricia Vandenberg (VHA OP&P). NR 35 TC 2 Z9 2 U1 1 U2 1 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 MAY PY 2015 VL 6 IS 3 BP 202 EP 210 DI 10.1016/j.jgo.2015.01.005 PG 9 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA CK6DX UT WOS:000356319800005 PM 25662785 ER PT J AU Mroczek, DK Stawski, RS Turiano, NA Chan, W Almeida, DM Neupert, SD Spiro, A AF Mroczek, Daniel K. Stawski, Robert S. Turiano, Nicholas A. Chan, Wai Almeida, David M. Neupert, Shevaun D. Spiro, Avron, III TI Emotional Reactivity and Mortality: Longitudinal Findings From the VA Normative Aging Study SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE Emotion; Emotion Regulation; Longevity; Personality; Quantitative Methods ID PHYSICAL HEALTH; DAILY STRESSORS; NEGATIVE AFFECT; POSITIVE AFFECT; OLDER MEN; MINDFULNESS MEDITATION; IMMUNE FUNCTION; CHRONIC PAIN; PERSONALITY; LIFE AB Objectives. Evidence suggests a predictive association between emotion and mortality risk. However, no study has examined dynamic aspects of emotion in relation to mortality. This study used an index of emotional reactivity, defined as changes in positive or negative affect in response to daily stressors, to predict 10-year survival. Methods. An 8-day daily diary study was conducted in 2002 on 181 men aged 58-88. Multilevel models were employed to estimate emotional reactivity coefficients, which were subsequently entered into a Cox proportional hazards model to predict mortality. Results. Results indicated that positive emotional reactivity, that is, greater decreases in positive affect in response to daily stressors, increased mortality risk. Negative emotional reactivity did not predict mortality. Discussion. Findings highlight the potential importance of dynamic aspects of positive affect in prediction of physical health outcomes such as mortality. C1 [Mroczek, Daniel K.] Northwestern Univ, Dept Psychol, Weinberg Coll Arts & Sci, Evanston, IL 60208 USA. [Mroczek, Daniel K.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Evanston, IL 60208 USA. [Stawski, Robert S.] Oregon State Univ, Sch Social & Behav Hlth Sci, Corvallis, OR 97331 USA. [Turiano, Nicholas A.] Univ Rochester, Med Ctr, Dept Psychiat, New York, NY USA. [Chan, Wai] Purdue Univ, Dept Human Dev & Family Studies, W Lafayette, IN 47907 USA. [Almeida, David M.] Penn State Univ, Dept Human Dev & Family Studies, University Pk, PA 16802 USA. [Almeida, David M.] Penn State Univ, Ctr Hlth Aging, University Pk, PA 16802 USA. [Neupert, Shevaun D.] N Carolina State Univ, Dept Psychol, Raleigh, NC 27695 USA. [Spiro, Avron, III] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Spiro, Avron, III] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Mroczek, DK (reprint author), Northwestern Univ, Dept Psychol, Swift Hall,2029 Sheridan Rd, Evanston, IL 60208 USA. EM daniel.mroczek@northwestern.edu FU National Institute on Aging [R01-AG018436, P01-AG020166]; Clinical Science Research and Development Service of the U.S. Department of Veterans Affairs; Cooperative Studies Program/ERIC, U.S. Department of Veterans Affairs; Massachusetts Veterans Epidemiology Research and Information Center FX This study was supported by grants from the National Institute on Aging (R01-AG018436 and P01-AG020166) and by a Research Career Scientist Award from the Clinical Science Research and Development Service of the U.S. Department of Veterans Affairs. The VA Normative Aging Study (NAS) is supported by the Cooperative Studies Program/ERIC, U.S. Department of Veterans Affairs, and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center. The views expressed in this paper are those of the authors and do not necessarily represent the views of the U.S. Department of Veterans Affairs. NR 66 TC 14 Z9 14 U1 5 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 EI 1758-5368 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD MAY PY 2015 VL 70 IS 3 BP 398 EP 406 DI 10.1093/geronb/gbt107 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA CK9ZQ UT WOS:000356598500007 PM 24170714 ER PT J AU Zetterberg, H Gandy, S AF Zetterberg, Henrik Gandy, Sam TI Repetitive concussions - How dangerous are they? SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Editorial Material DE Concussion; Chronic traumatic encephalopathy; Amyloid; Tau; Risk factors ID CHRONIC TRAUMATIC ENCEPHALOPATHY; FOOTBALL-LEAGUE PLAYER; SEVERE BRAIN-INJURY C1 [Zetterberg, Henrik] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Clin Neurochem Lab, S-43180 Molndal, Sweden. [Zetterberg, Henrik] UCL Inst Neurol, London WC1N 3BG, England. [Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, Mt Sinai Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Gandy, Sam] James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Zetterberg, H (reprint author), Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-43180 Molndal, Sweden. EM henrik.zetterberg@gu.se FU NIA NIH HHS [P50 AG005138]; RRD VA [I01 RX000684] NR 12 TC 0 Z9 0 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 EI 1095-9327 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD MAY PY 2015 VL 66 SI SI BP 73 EP 74 DI 10.1016/j.mcn.2015.02.004 PN B PG 2 WC Neurosciences SC Neurosciences & Neurology GA CK7FT UT WOS:000356398900001 PM 25655012 ER PT J AU Gardner, RC Yaffe, K AF Gardner, Raquel C. Yaffe, Kristine TI Epidemiology of mild traumatic brain injury and neurodegenerative disease SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE Chronic traumatic encephalopathy; Traumatic brain injury; Mild traumatic brain injury; Concussion; Neurodegenerative disease; Epidemiology ID ENVIRONMENTAL RISK-FACTORS; FOOTBALL-LEAGUE PLAYER; HEAD-INJURY; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; CLINICAL-OUTCOMES; PUNCH DRUNK; HIGH-SCHOOL; ENCEPHALOPATHY AB Every year an estimated 42 million people worldwide suffer a mild traumatic brain injury (MTBI) or concussion. More severe traumatic brain injury (TBI) is a well-established risk factor for a variety of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Recently, large epidemiological studies have additionally identified MTBI as a risk factor for dementia. The role of MTBI in risk of PD or ALS is less well established. Repetitive MTBI and repetitive sub-concussive head trauma have been linked to increased risk for a variety of neurodegenerative diseases including chronic traumatic encephalopathy (CTE). CTE is a unique neurodegenerative tauopathy first described in boxers but more recently described in a variety of contact sport athletes, military veterans, and civilians exposed to repetitive MTBI. Studies of repetitive MTBI and CTE have been limited by referral bias, lack of consensus clinical criteria for CTE, challenges of quantifying MTBI exposure, and potential for confounding. The prevalence of CTE is unknown and the amount of MTBI or subconcussive trauma exposure necessary to produce CTE is unclear. This review will summarize the current literature regarding the epidemiology of MTBI, post-TBI dementia and Parkinson's disease, and CTE while highlighting methodological challenges and critical future directions of research in this field. This article is part of a Special Issue entitled SI:Traumatic Brain Injury. Published by Elsevier Inc. C1 [Gardner, Raquel C.; Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Gardner, RC (reprint author), 4150 Clement St, San Francisco, CA 94121 USA. EM raquel.gardner@ucsf.edu FU Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment; Medical Research Service of the San Francisco Veterans Affairs Medical Center; Department of Veterans Affairs Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC); National Institutes of Health (NIH) [K24 AG031155]; Department of Defense [W81XWH-12-1-0581]; Department of Veterans Affairs; California Department of Public Health; Bright Focus Foundation; Alzheimer's Association FX RCG is supported by the 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). KY has received research support from the National Institutes of Health (NIH) via K24 AG031155, the Department of Defense via W81XWH-12-1-0581, the Department of Veterans Affairs, the California Department of Public Health, the Bright Focus Foundation, and the Alzheimer's Association. NR 73 TC 30 Z9 30 U1 12 U2 57 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 EI 1095-9327 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD MAY PY 2015 VL 66 SI SI BP 75 EP 80 DI 10.1016/j.mcn.2015.03.001 PN B PG 6 WC Neurosciences SC Neurosciences & Neurology GA CK7FT UT WOS:000356398900002 PM 25748121 ER PT J AU Daneshvar, DH Goldstein, LE Kiernan, PT Stein, TD McKee, AC AF Daneshvar, Daniel H. Goldstein, Lee E. Kiernan, Patrick T. Stein, Thor D. McKee, Ann C. TI Post-traumatic neurodegeneration and chronic traumatic encephalopathy SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE Traumatic brain injury; Chronic traumatic encephalopathy; Axonal injury; Brain trauma; Posttraumatic neurodegeneration; Motor neuron disease; Tau protein; Concussion; Blast and impact neurotrauma ID AMYOTROPHIC-LATERAL-SCLEROSIS; PROFESSIONAL FOOTBALL PLAYERS; REPETITIVE HEAD-INJURY; HIGH-SCHOOL FOOTBALL; PROGRESSIVE SUPRANUCLEAR PALSY; YOUNG ONSET DEMENTIA; RETIRED NFL PLAYERS; SEVERE BRAIN-INJURY; ALZHEIMERS-DISEASE; AMYLOID-BETA AB Traumatic brain injury (TBI) is a leading cause of mortality and morbidity around the world. Concussive and subconcussive forms of closed-head injury due to impact or blast neurotrauma represent the most common types of TBI in civilian and military settings. It is becoming increasingly evident that TBI can lead to persistent, long-term debilitating effects, and in some cases, progressive neurodegeneration and chronic traumatic encephalopathy (CTE). The epidemiological literature suggests that a single moderate-to-severe TBI may be associated with accelerated neurodegeneration and increased risk of Alzheimer's disease, Parkinson's disease, or motor neuron disease. However, the pathologic phenotype of these post-traumatic neurodegenerations is largely unknown and there may be pathobiological differences between post-traumatic disease and the corresponding sporadic disorder. By contrast, the pathology of CTE is increasingly well known and is characterized by a distinctive pattern of progressive brain atrophy and accumulation of hyperphosphorylated tau neurofibrillary and glial tangles, dystrophic neurites, 43 kDa TAR DNA-binding protein (TDP-43) neuronal and glial aggregates, microvasculopathy, myelinated axonopathy, neuroinflammation, and white matter degeneration. Clinically, CTE is associated with behavioral changes, executive dysfunction, memory deficits, and cognitive impairments that begin insidiously and most often progress slowly over decades. Although research on the long-term effects of TBI is advancing quickly, the incidence and prevalence of post-traumatic neurodegeneration and CTE are unknown. Critical knowledge gaps include elucidation of pathogenic mechanisms, identification of genetic risk factors, and clarification of relevant variables-including age at exposure to trauma, history of prior and subsequent head trauma, substance use, gender, stress, and comorbidities-all of which may contribute to risk profiles and the development of post-traumatic neurodegeneration and CTE. This article is part of a Special Issue entitled 'Traumatic Brain Injury'. Published by Elsevier Inc. C1 [Daneshvar, Daniel H.; Goldstein, Lee E.; Kiernan, Patrick T.; Stein, Thor D.; McKee, Ann C.] Boston Univ, Sch Med, Chron Traumat Encephalopathy Program, Boston, MA 02118 USA. [Daneshvar, Daniel H.; Goldstein, Lee E.; Kiernan, Patrick T.; Stein, Thor D.; McKee, Ann C.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Daneshvar, Daniel H.; Goldstein, Lee E.; Kiernan, Patrick T.; McKee, Ann C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Goldstein, Lee E.; Stein, Thor D.; McKee, Ann C.] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [Goldstein, Lee E.] Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02118 USA. [Goldstein, Lee E.] Boston Univ, Sch Med, Dept Neurosurg, Boston, MA 02118 USA. [Goldstein, Lee E.] Boston Univ, Photon Ctr, Boston, MA 02115 USA. [Goldstein, Lee E.] Boston Univ, Dept Biomed Engn, Boston, MA 02115 USA. [Goldstein, Lee E.] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. [Goldstein, Lee E.] Boston Univ, Dept Mech Engn, Boston, MA 02115 USA. [Stein, Thor D.; McKee, Ann C.] VA Boston Healthcare Syst, Jamaica Plain, MA 02130 USA. RP McKee, AC (reprint author), Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. OI Stein, Thor/0000-0001-6954-4477; Daneshvar, Daniel/0000-0003-3691-9513 FU Department of Veterans Affairs; Veterans Affairs Biorepository [CSP 501]; Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B6796-C]; National Institute of Neurological Diseases and Stroke [1U01NS086659-01]; National Institute of Aging Boston University Alzheimer's Disease Center [P30AG13846, 0572063345-5]; National Institute of Aging Boston University Framingham Heart Study [R01 [AG1649]]; Sports Legacy Institute; National Operating Committee on Standards for Athletic Equipment; National Football League; Andlinger Foundation; WWE FX We gratefully acknowledge the use of resources and facilities at the Edith Nourse Rogers Memorial Veterans Hospital (Bedford, MA). We also gratefully acknowledge the help of all members of the Boston University and the Boston VA, and the individuals and families whose participation and contributions made this work possible. This work was supported by the Department of Veterans Affairs; Veterans Affairs Biorepository (CSP 501); Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C); National Institute of Neurological Diseases and Stroke 1U01NS086659-01, National Institute of Aging Boston University Alzheimer's Disease Center [P30AG13846; supplement 0572063345-5]; National Institute of Aging Boston University Framingham Heart Study R01 [AG1649]; Sports Legacy Institute; and National Operating Committee on Standards for Athletic Equipment. This work was also supported by an unrestricted gift from the National Football League, the Andlinger Foundation and the WWE. NR 120 TC 16 Z9 16 U1 14 U2 60 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 EI 1095-9327 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD MAY PY 2015 VL 66 SI SI BP 81 EP 90 DI 10.1016/j.mcn.2015.03.007 PN B PG 10 WC Neurosciences SC Neurosciences & Neurology GA CK7FT UT WOS:000356398900003 PM 25758552 ER PT J AU Sonpavde, G Bellmunt, J AF Sonpavde, Guru Bellmunt, Joaquim TI Salvage Systemic Therapy for Advanced Urothelial Carcinoma: On the Cusp of a Sea Change? SO ONCOLOGIST LA English DT Editorial Material DE Advanced urothelial cancer; Salvage therapy ID TRANSITIONAL-CELL CARCINOMA; PHASE-II TRIAL; 2ND-LINE TREATMENT; SINGLE GROUP; CANCER; CHEMOTHERAPY; PACLITAXEL; SURVIVAL; TRACT C1 [Sonpavde, Guru] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Bellmunt, Joaquim] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bellmunt, Joaquim] Harvard Univ, Sch Med, Boston, MA USA. RP Sonpavde, G (reprint author), Univ Alabama Birmingham, Ctr Comprehens Canc, 1720 2nd Ave South,NP2540B, Birmingham, AL 35294 USA. EM gsonpavde@uabmc.edu NR 20 TC 3 Z9 3 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 MAY PY 2015 VL 20 IS 5 BP 461 EP 463 DI 10.1634/theoncologist.2015-0077 PG 3 WC Oncology SC Oncology GA CL1DD UT WOS:000356681800006 PM 25845991 ER PT J AU Ali, SM Sanford, EM Klempner, SJ Rubinson, DA Wang, K Palma, NA Chmielecki, J Yelensky, R Palmer, GA Morosini, D Lipson, D Catenacci, DV Braiteh, F Erlich, R Stephens, PJ Ross, JS Ou, SHI Miller, VA AF Ali, Siraj M. Sanford, Eric M. Klempner, Samuel J. Rubinson, Douglas A. Wang, Kai Palma, Norma A. Chmielecki, Juliann Yelensky, Roman Palmer, Gary A. Morosini, Deborah Lipson, Doron Catenacci, Daniel V. Braiteh, Fadi Erlich, Rachel Stephens, Philip J. Ross, Jeffrey S. Ou, Sai-Hong Ignatius Miller, Vincent A. TI Prospective Comprehensive Genomic Profiling of Advanced Gastric Carcinoma Cases Reveals Frequent Clinically Relevant Genomic Alterations and New Routes for Targeted Therapies SO ONCOLOGIST LA English DT Article DE Gastric cancer; Sequencing; Targeted therapy; Mutation; Profiling; MET ID LABEL PHASE-3 TRIAL; GENE AMPLIFICATION; BREAST-CANCER; MOLECULAR CHARACTERIZATION; PERSONALIZED MEDICINE; SOMATIC MUTATIONS; UNITED-STATES; HER2; ADENOCARCINOMA; SURVIVAL AB Background. Gastric cancer (GC) is a major global cancer burden and the second most common cause of global cancer-related deaths. The addition of anti-ERBB2 (HER2) targeted therapy to chemotherapy improves survival for ERBB2-amplified advanced GC patients; however, the majority of GC patients do not harbor this alteration and thus cannot benefit from targeted therapy under current practice paradigms. Materials and Methods. Prospective comprehensive genomic profiling of 116 predominantly locally advanced or metastatic (90.0%) gastric cancer cases was performed to identify genomic alterations (GAs) associated with a potential response to targeted therapies approved by the U.S. Food and Drug Administration or targeted therapy-based clinical trials. Results. Overall, 78% of GC cases harbored one clinically relevant GA or more, with the most frequent alterations being found in TP53 (50%), ARID1A (24%), KRAS (16%), CDH1 (15%), CDKN2A (14%), CCND1 (9.5%), ERBB2 (8.5%), PIK3CA (8.6%), MLL2 (6.9%), FGFR2 (6.0%), and MET (6.0%). Receptor tyrosine kinase genomic alterations were detected in 20.6% of cases, primarily ERBB2, FGFR2, and MET amplification, with ERBB2 alterations evenly split between amplifications and base substitutions. Rare BRAF mutations (2.6%) were also observed. One MET-amplified GC patient responded for 5 months to crizotinib, a multitargeted ALK/ROS1/MET inhibitor. Conclusion. Comprehensive genomic profiling of GC identifies clinically relevant GAs that suggest benefit from targeted therapy including MET-amplified GC and ERBB2 base substitutions. C1 [Ali, Siraj M.; Sanford, Eric M.; Wang, Kai; Palma, Norma A.; Chmielecki, Juliann; Yelensky, Roman; Palmer, Gary A.; Morosini, Deborah; Lipson, Doron; Erlich, Rachel; Stephens, Philip J.; Ross, Jeffrey S.; Miller, Vincent A.] Fdn Med Inc, Cambridge, MA 02141 USA. [Klempner, Samuel J.; Ou, Sai-Hong Ignatius] Univ Calif Irvine, Sch Med, Dept Med, Chao Family Comprehens Canc Ctr,Div Hematol Oncol, Orange, CA 92668 USA. [Rubinson, Douglas A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Catenacci, Daniel V.] Univ Chicago, Chicago, IL 60637 USA. [Braiteh, Fadi] Comprehens Canc Ctr Nevada, Las Vegas, NV USA. [Ross, Jeffrey S.] Albany Med Coll, Dept Pathol & Lab Med, Albany, NY 12208 USA. RP Ali, SM (reprint author), Fdn Med Inc, 150 Second St, Cambridge, MA 02141 USA. EM Siraj@Foundationmedicine.com NR 54 TC 13 Z9 14 U1 1 U2 5 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD MAY PY 2015 VL 20 IS 5 BP 499 EP 507 DI 10.1634/theoncologist.2014-0378 PG 9 WC Oncology SC Oncology GA CL1DD UT WOS:000356681800014 PM 25882375 ER PT J AU Saigusa, T Bell, PD AF Saigusa, Takamitsu Bell, P. Darwin TI Molecular Pathways and Therapies in Autosomal-Dominant Polycystic Kidney Disease SO PHYSIOLOGY LA English DT Article ID PLANAR CELL POLARITY; RENIN-ANGIOTENSIN SYSTEM; CYST EPITHELIAL-CELLS; COLLECTING DUCT CELLS; RENAL-DISEASE; LIVER-DISEASE; BETA-CATENIN; CONDITIONAL INACTIVATION; SIGNALING PATHWAY; CFTR INHIBITORS AB Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent inherited renal disease, characterized by multiple cysts that can eventually lead to kidney failure. Studies investigating the role of primary cilia and polycystins have significantly advanced our understanding of the pathogenesis of PKD. This review will present clinical and basic aspects of ADPKD, review current concepts of PKD pathogenesis, evaluate potential therapeutic targets, and highlight challenges for future clinical studies. C1 [Saigusa, Takamitsu] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph Johnson VA Med Ctr, Charleston, SC USA. RP Saigusa, T (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. EM bellpd@musc.edu FU Veterans Affairs Merit Grant, National Institute of Diabetes and Digestive and Kidney Diseases Grant [P30 DK-074038]; Dialysis Clinic FX This study was supported by Veterans Affairs Merit Grant, National Institute of Diabetes and Digestive and Kidney Diseases Grant P30 DK-074038, and funds from Dialysis Clinic (to P.D.B.). NR 158 TC 9 Z9 9 U1 4 U2 15 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1548-9213 EI 1548-9221 J9 PHYSIOLOGY JI Physiology PD MAY 1 PY 2015 VL 30 IS 3 BP 195 EP 207 DI 10.1152/physiol.00032.2014 PG 13 WC Physiology SC Physiology GA CL1BK UT WOS:000356677200007 PM 25933820 ER PT J AU Harvey, HB Brink, JA Frush, DP AF Harvey, H. Benjamin Brink, James A. Frush, Donald P. TI Informed Consent for Radiation Risk from CT Is Unjustified Based on the Current Scientific Evidence SO RADIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY EXAMINATIONS; ATOMIC-BOMB SURVIVORS; IONIZING-RADIATION; ADAPTIVE RESPONSE; CANCER-RISKS; DECISION-MAKING; MICE; POPULATION; MORTALITY; EXPOSURE C1 [Harvey, H. Benjamin; Brink, James A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Frush, Donald P.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. RP Harvey, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 175 Cambridge St,Suite 200, Boston, MA 02114 USA. EM hbharvey@partners.org RI Frush, Donald/M-6457-2015 OI Frush, Donald/0000-0002-6928-4465 NR 55 TC 10 Z9 10 U1 2 U2 9 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 MAY PY 2015 VL 275 IS 2 BP 321 EP 325 DI 10.1148/radiol.2015142859 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK1SN UT WOS:000355987700003 PM 25906299 ER PT J AU Freer, PE Niell, B Rafferty, EA AF Freer, Phoebe E. Niell, Bethany Rafferty, Elizabeth A. TI Preoperative Tomosynthesis-guided Needle Localization of Mammographically and Sonographically Occult Breast Lesions SO RADIOLOGY LA English DT Article ID DIAGNOSTIC MAMMOGRAPHY; DIGITAL MAMMOGRAPHY; BIOPSY AB Purpose: To assess the feasibility and accuracy of digital breast tomosynthesis (DBT)-guided needle localization for DBT-detected suspicious abnormalities not visualized with other modalities and to analyze the imaging and pathologic characteristics of abnormalities detected only with DBT to determine the positive predictive value for malignancy. Materials and Methods: This HIPAA-compliant study was approved by the institutional review board, and the requirement to obtain informed consent was waived. A retrospective query of the imaging database identified 34 consecutive women (average age, 55 years; age range, 28-84 years) with 36 lesions who underwent DBT-guided needle localization between April 2011 and January 2013 with use of commercially available equipment. Imaging findings and medical records were reviewed. Findings that were attributable to previous surgical changes were classified as benign or probably benign and excluded from analysis because the lesions did not proceed to localization. Results: Architectural distortion was the imaging finding identified in all 36 abnormalities (100%). Findings from pathologic examination after the first attempt at localization were concordant with those from imaging in 35 of the 36 lesions (97%), which is suggestive of appropriate sampling. Histologic findings were malignant in 17 of the 36 lesions (47%; 95% confidence interval: 30.4%, 64.5%). Thirteen of the 17 lesions (76%; 95% confidence interval: 50.1%, 93.1%) were invasive malignancies. Twenty-two of the 36 abnormalities (61%) were either malignant or high-risk lesions (atypical ductal hyperplasia, lobular carcinoma in situ, atypical lobular hyperplasia). Conclusion: DBT-guided needle localization is an accurate and feasible method with which to biopsy DBT-detected suspicious architectural distortions not visualized at mammography or sonography. The high risk of malignancy in abnormalities detected only with DBT (47%) confirms that routine biopsy is required for histologic analysis. (C) RSNA, 2015 C1 [Freer, Phoebe E.; Niell, Bethany; Rafferty, Elizabeth A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Freer, PE (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM pfreer@partners.org OI Freer, Phoebe/0000-0001-6886-7100 FU Hologic FX P.E.F. disclosed no relevant relationships. B.N. disclosed no relevant relationships. E.A.R. Activities related to the present article: received a research grant from Hologic. Activities not related to the present article: none to disclose. Other relationships: none to disclose. NR 13 TC 10 Z9 10 U1 0 U2 1 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 MAY PY 2015 VL 275 IS 2 BP 377 EP 383 DI 10.1148/radiol.14140515 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK1SN UT WOS:000355987700009 PM 25575115 ER PT J AU Sistrom, CL Weilburg, JB Dreyer, KJ Ferris, TG AF Sistrom, Chris L. Weilburg, Jeffrey B. Dreyer, Keith J. Ferris, Timothy G. TI Provider Feedback about Imaging Appropriateness by Using Scores from Order Entry Decision Support: Raw Rates Misclassify Outliers SO RADIOLOGY LA English DT Article ID LOGISTIC-REGRESSION; RADIOLOGY; RELIABILITY; QUALITY; PATTERNS; IMPACT; YIELD; CT AB Purpose: To determine the relevant physician- and practice-related factors that jointly affect the rate of low-utility imaging examinations (score of 1-3 out of 9) ordered by means of an order entry system that provides normative appropriateness feedback. Materials and Methods: This HIPAA-compliant study was approved by the institutional review board under an expedited protocol for analyzing anonymous aggregated administrative data. This is a retrospective study of approximately 250 000 consecutive scheduled outpatient advanced imaging examinations (computed tomography, magnetic resonance imaging, nuclear medicine) ordered by 164 primary care and 379 medical specialty physicians from 2008 to 2012. A hierarchical logistic regression model was used to identify multiple predictors of the probability that an examination received a low utility score. Physician- and practice-specific random effects were estimated to articulate (odds ratio) and quantify (intraclass correlation) interphysician variation. Results: Fixed effects found to be statistically significant predictors of low-utility imaging included examination type, whether the examination was cancelled, status of the person entering the order, and the total number of examinations ordered by the clinician. Neither patient age nor sex had any effect, and there were no secular trends (year of study). The remaining amount of interphysician variation was moderate (intraclass correlation, 22%), whereas the variation between medical specialties and primary care practices was low (intraclass correlation, 5%). The estimated physician- specific effects had reliability of 70%, which makes them just suitable for identifying outliers. Conclusion: The authors found that 22% of the variation in the rate of low-utility examinations is attributable to ordering providers and 5% to their specialty or clinic. (C) RSNA, 2014 C1 [Sistrom, Chris L.; Weilburg, Jeffrey B.; Ferris, Timothy G.] Massachusetts Gen Hosp, Phys Org, Boston, MA 02114 USA. [Sistrom, Chris L.; Dreyer, Keith J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Sistrom, CL (reprint author), Univ Florida, Ctr Hlth, Dept Radiol, 1600 Archer Rd,POB 100374, Gainesville, FL 32610 USA. EM sistrc@radiology.ufl.edu NR 43 TC 1 Z9 2 U1 1 U2 1 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 MAY PY 2015 VL 275 IS 2 BP 469 EP 479 DI 10.1148/radiol.14141092 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK1SN UT WOS:000355987700019 PM 25423147 ER PT J AU Pulli, B Bure, L Wojtkiewicz, GR Iwamoto, Y Ali, M Li, D Schob, S Hsieh, KLC Jacobs, AH Chen, JW AF Pulli, Benjamin Bure, Lionel Wojtkiewicz, Gregory R. Iwamoto, Yoshiko Ali, Muhammad Li, Dan Schob, Stefan Hsieh, Kevin Li-Chun Jacobs, Andreas H. Chen, John W. TI Multiple Sclerosis: Myeloperoxidase Immunoradiology Improves Detection of Acute and Chronic Disease in Experimental Model SO RADIOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; WHITE-MATTER; INFLAMMATORY RESPONSE; GADOFLUORINE-M; LEWIS RATS; MRI; DISABILITY; MACROPHAGES; LESIONS AB Purpose: To test if MPO-Gd, a gadolinium-based magnetic resonance (MR) imaging probe that is sensitive and specific for the proinflammatory and oxidative enzyme myeloperoxidase (MPO), which is secreted by certain inflammatory cells, is more sensitive than diethylenetriaminepentaacetic acid (DTPA)-Gd in revealing early subclinical and chronic disease activity in the brain in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Materials and Methods: The protocol for animal experiments was approved by the institutional animal care committee. A total of 61 female SJL mice were induced with EAE. Mice underwent MPO-Gd- or DTPA-Gd-enhanced MR imaging on days 6, 8, and 10 after induction, before clinical disease develops, and during chronic disease at remission and the first relapse. Brains were harvested at these time points for flow cytometric evaluation of immune cell subtypes and immunohistochemistry. Statistical analysis was performed, and P < .05 was considered to indicate a significant difference. Results: MPO-Gd helps detect earlier (5.2 vs 2.3 days before symptom onset, P = .004) and more (3.1 vs 0.3, P = .008) subclinical inflammatory lesions compared with DTPA-Gd, including in cases in which there was no evidence of overt blood-brain barrier (BBB) breakdown detected with DTPA-Gd enhancement. The number of MPO-Gd- enhancing lesions correlated with early infiltration of MPO-secreting monocytes and neutrophils into the brain (r = 0.91). MPO-Gd also helped detect more lesions during subclinical disease at remission (5.5 vs 1.3, P = .006) and at the first relapse (9.0 vs 2.7, P = .03) than DTPA-Gd, which also correlated well with the presence and accumulation of MPO-secreting inflammatory cells in the brain (r = 0.93). Conclusion: MPO-Gd specifically reveals lesions with inflammatory monocytes and neutrophils, which actively secrete MPO. These results demonstrate the feasibility of detection of subclinical inflammatory disease activity in vivo, which is different from overt BBB breakdown. (C) RSNA, 2014 C1 [Pulli, Benjamin; Bure, Lionel; Wojtkiewicz, Gregory R.; Iwamoto, Yoshiko; Ali, Muhammad; Li, Dan; Schob, Stefan; Hsieh, Kevin Li-Chun; Chen, John W.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Pulli, Benjamin; Bure, Lionel; Wojtkiewicz, Gregory R.; Iwamoto, Yoshiko; Ali, Muhammad; Li, Dan; Schob, Stefan; Hsieh, Kevin Li-Chun; Chen, John W.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Pulli, Benjamin; Chen, John W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Jacobs, Andreas H.] Univ Munster, European Inst Mol Imaging, D-48149 Munster, Germany. RP Chen, JW (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM jwchen@mgh.harvard.edu FU National Institutes of Health [R01-NS070835, R01-NS072167] FX This research was supported by the National Institutes of Health (grants R01-NS070835 and R01-NS072167). NR 49 TC 7 Z9 7 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2015 VL 275 IS 2 BP 480 EP 489 DI 10.1148/radiol.14141495 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK1SN UT WOS:000355987700020 PM 25494298 ER PT J AU Ginat, DT Moonis, G AF Ginat, Daniel Thomas Moonis, Gul TI Case 217: Sinonasal Organized Hematoma SO RADIOLOGY LA English DT Article ID MAXILLARY SINUS; CT FINDINGS; INVERTED PAPILLOMA; MR; TUMOR; MASS AB History A 15-year-old boy presented to the emergency department with intractable epistaxis. He had a prior history of epistaxis typically lasting 5-10 minutes and consisting of up to four episodes per year for several years. Otherwise, the patient had no relevant medical history, and he denied having prior trauma, surgery, bleeding diathesis, fever, chills, or vision changes. Likewise, the patient had no relevant family history. The patient's coagulation panel was unremarkable and included a prothrombin time of 15.4 seconds, an international normalized ratio of 1.2, and a partial thromboplastin time of 29.3 seconds. A thin-section unenhanced sinus computed tomography (CT) examination was performed. In addition, magnetic resonance (MR) imaging of the sinuses without and with intravenous contrast material was performed. The epistaxis was treated with nasal packing, which prevented further bleeding. Biopsy of the lesion was subsequently performed. C1 [Ginat, Daniel Thomas] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Moonis, Gul] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Moonis, Gul] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Ginat, DT (reprint author), Univ Chicago, Dept Radiol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM dtg1@uchicago.edu NR 13 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2015 VL 275 IS 2 BP 613 EP 616 DI 10.1148/radiol.15132130 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK1SN UT WOS:000355987700035 PM 25906305 ER PT J AU Amorim, E Rittenberger, JC Baldwin, ME Callaway, CW Popescu, A AF Amorim, Edilberto Rittenberger, Jon C. Baldwin, Maria E. Callaway, Clifton W. Popescu, Alexandra CA Post Cardiac Arrest Serv TI Malignant EEG patterns in cardiac arrest patients treated with targeted temperature management who survive to hospital discharge SO RESUSCITATION LA English DT Article DE Cardiac arrest; Anoxic brain injury; Status epilepticus; Generalized epileptiform periodic discharges; Myoclonic status epilepticus; Suppression-burst ID POSTANOXIC STATUS EPILEPTICUS; THERAPEUTIC HYPOTHERMIA; CARDIOPULMONARY-RESUSCITATION; COMATOSE SURVIVORS; PROGNOSTIC VALUE; CLINICAL EXAMINATION; ASSOCIATION; MYOCLONUS; CARE; PREDICTION AB Background and purpose: Cardiac arrest patients treated with targeted temperature management (TTM) have improved neurological outcomes, however mortality remains high. EEG monitoring improves detection of malignant EEG patterns (MEPs), however their prevalence in patients surviving to hospital discharge is unknown. Design/methods: We examined consecutive cardiac arrest subjects who received TTM and continuous EEG monitoring at one academic center. Only subjects surviving to hospital discharge were included in the analysis. MEPs were defined as seizures, status epilepticus, myoclonic status epilepticus, or generalized periodic discharges. Subjects with suppression-burst (SB) without concomitant MEPs were categorized as having a "pure" SB pattern. Demographic, survival, hospital discharge disposition, and neurological function data were recorded retrospectively. Outcomes were assessed using the Glasgow-Pittsburgh Cerebral Performance Category (CPC). A CPC score of 1-2 was considered "good" neurological function, and a CPC of 3-4 "poor". Results: Of 364 admissions due to cardiac arrest screened, 120 (29.9%) survived to hospital discharge and met inclusion criteria. MEPs and pure SB were observed in 19 (15.8%) and 22 (18.3%) survivors respectively. Two subjects with MEP and eight subjects with pure SB had good neurological function at discharge, however all SB cases were confounded by the use of anesthetic agents. Presence of MEPs was not an independent predictor of poor neurological function (p = 0.1). Conclusions: MEPs are common among cardiac arrest patients treated with induced hypothermia who survive to hospital discharge. Poor neurological function at discharge was not associated with MEPs. Prospective studies assessing the role of EEG monitoring in cardiac arrest prognostication are warranted. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Amorim, Edilberto] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Amorim, Edilberto] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rittenberger, Jon C.; Callaway, Clifton W.] Univ Pittsburgh, Dept Emergency Med, Med Ctr, Pittsburgh, PA 15261 USA. [Baldwin, Maria E.; Popescu, Alexandra] Univ Pittsburgh, Dept Neurol, Med Ctr, Pittsburgh, PA 15261 USA. RP Rittenberger, JC (reprint author), Univ Pittsburgh, Dept Emergency Med, Iroquois Bldg,Suite 400A,3600 Forbes Ave, Pittsburgh, PA 15261 USA. EM rittjc@upmc.edu OI Molyneaux, Bradley/0000-0002-3377-1229; Dezfulian, Cameron/0000-0002-4486-0446 FU Continuous EEG Service; UPMC Presbyterian Hospital EEG laboratory; National Institutes of Health [UL1-TR-000005] FX The authors thank the Continuous EEG Service and the UPMC Presbyterian Hospital EEG laboratory for their support to this project. We also thank Mr. Yin Zhao for data abstraction. This publication was supported by the National Institutes of Health through Grant Number UL1-TR-000005. NR 39 TC 18 Z9 18 U1 2 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD MAY PY 2015 VL 90 BP 127 EP 132 DI 10.1016/j.resuscitation.2015.03.005 PG 6 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA CK0ZN UT WOS:000355934600030 PM 25779006 ER PT J AU Houde, AA Legare, C Biron, S Lescelleur, O Biertho, L Marceau, S Tchernof, A Vohl, MC Hivert, MF Bouchard, L AF Houde, Andree-Anne Legare, Cecilia Biron, Simon Lescelleur, Odette Biertho, Laurent Marceau, Simon Tchernof, Andre Vohl, Marie-Claude Hivert, Marie-France Bouchard, Luigi TI Leptin and adiponectin DNA methylation levels in adipose tissues and blood cells are associated with BMI, waist girth and LDL-cholesterol levels in severely obese men and women SO BMC MEDICAL GENETICS LA English DT Article DE Subcutaneous adipose tissue; Visceral adipose tissue; Epigenetic; Metabolic complications ID GENE-EXPRESSION; EPIGENETIC EPIDEMIOLOGY; METABOLIC SYNDROME; REGIONS TDMS; PROMOTER; WEIGHT; PATTERNS; RISK; PREADIPOCYTES; RESPONDERS AB Background: Leptin (LEP) and adiponectin (ADIPOQ) genes encode adipokines that are mainly secreted by adipose tissues, involved in energy balance and suspected to play a role in the pathways linking adiposity to impaired glucose and insulin homeostasis. We have thus hypothesized that LEP and ADIPOQ DNA methylation changes might be involved in obesity development and its related complications. The objective of this study was to assess whether LEP and ADIPOQ DNA methylation levels measured in subcutaneous (SAT) and visceral adipose tissues (VAT) are associated with anthropometric measures and metabolic profile in severely obese men and women. These analyses were repeated with DNA methylation profiles from blood cells obtained from the same individuals to determine whether they showed similarities. Methods: Paired SAT, VAT and blood samples were obtained from 73 severely obese patients undergoing a bioliopancreatic diversion with duodenal switch. LEP and ADIPOQ DNA methylation and mRNA levels were quantified using bisulfite-pyrosequencing and qRT-PCR respectively. Pearson's correlation coefficients were computed to determine the associations between LEP and ADIPOQ DNA methylation levels, anthropometric measures and metabolic profile. Results: DNA methylation levels at the ADIPOQ gene locus in SAT was positively associated with BMI and waist girth whereas LEP DNA methylation levels in blood cells were negatively associated with body mass index (BMI). Fasting LDL-C levels were found to be positively correlated with DNA methylation levels at LEP-CpG11 and -CpG17 in blood and SAT and with ADIPOQ DNA methylation levels in SAT (CpGE1 and CpGE3) and VAT (CpGE1). Conclusions: These results confirm that LEP and ADIPOQ epigenetic profiles are associated with obesity. We also report associations between LDL-C levels and both LEP and ADIPOQ DNA methylation levels suggesting that LDL-C might regulate their epigenetic profiles in adipose tissues. Furthermore, similar correlations were observed between LDL-C and LEP blood DNA methylation levels suggesting a common regulatory pathway of DNA methylation in both adipose tissues and blood. C1 [Houde, Andree-Anne; Legare, Cecilia; Bouchard, Luigi] Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ J1K 2R1, Canada. [Houde, Andree-Anne; Legare, Cecilia; Bouchard, Luigi] Chicoutimi Hosp, ECOGENE 21, Saguenay, PQ, Canada. [Houde, Andree-Anne; Legare, Cecilia; Bouchard, Luigi] Chicoutimi Hosp, Clin Res Ctr & Lipid Clin, Saguenay, PQ, Canada. [Biron, Simon; Lescelleur, Odette; Biertho, Laurent; Marceau, Simon; Tchernof, Andre] Quebec Heart & Lung Inst, Quebec City, PQ, Canada. [Biron, Simon; Lescelleur, Odette; Biertho, Laurent; Marceau, Simon] Univ Laval, Dept Surg, Quebec City, PQ G1K 7P4, Canada. [Tchernof, Andre; Vohl, Marie-Claude] Axe Endocrinol & Nephrol Ctr Rech CHU Quebec, Quebec City, PQ, Canada. [Tchernof, Andre; Vohl, Marie-Claude] Univ Laval, Dept Food Sci & Nutr, Quebec City, PQ, Canada. [Vohl, Marie-Claude] Univ Laval, Inst Nutr & Funct Foods, Quebec City, PQ, Canada. [Hivert, Marie-France] Univ Sherbrooke, Dept Med, Div Endocrinol, Sherbrooke, PQ J1K 2R1, Canada. [Hivert, Marie-France] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Hivert, Marie-France] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Bouchard, L (reprint author), Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ J1K 2R1, Canada. EM luigi.bouchard@usherbrooke.ca FU Canadian Diabetes Association; American Heart Association (AHA) award; American Diabetes Association (ADA) award; Centre de recherche du CHUS; Canada Research Chair in Genomics Applied to Nutrition and Health; FRQS; Faculte de Medecine et des Sciences de la Sante de l'Universite de Sherbrooke; Canadian Institutes of Health Research FX The Authors acknowledge the invaluable collaboration of the surgery team, bariatric surgeons (Hould F.S., Lebel S., Marceau P.) and biobank staff of the IUCPQ. The authors also express their gratitude to Celine Belanger, Chicoutimi Hospital, for her thoughtful language revision of the manuscript. L. Bouchard is a junior research scholar from the Fonds de la recherche du Quebec - sante (FRQS). M.F.H. was a FRSQ Research Scholar and was awarded Clinical Scientist award by the Canadian Diabetes Association; she is now supported by American Heart Association (AHA) and American Diabetes Association (ADA) awards. L. Bouchard and M.F.H. are members of the FRQS-funded Centre de recherche du CHUS. A.T. is the director of a Research Chair in Bariatric and Metabolic Surgery. M.C.V. is the recipient of the Canada Research Chair in Genomics Applied to Nutrition and Health. A.A.H. is the recipient of a doctoral training award from the FRQS and the Faculte de Medecine et des Sciences de la Sante de l'Universite de Sherbrooke. This project was supported by the Canadian Institutes of Health Research and the FRQS. NR 57 TC 12 Z9 12 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD MAY 1 PY 2015 VL 16 AR 29 DI 10.1186/s12881-015-0174-1 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA CK1TQ UT WOS:000355990700001 PM 25929254 ER PT J AU Karabanov, A Ziemann, U Hamada, M George, MS Quartarone, A Classen, J Massimini, M Rothwell, J Siebner, HR AF Karabanov, Anke Ziemann, Ulf Hamada, Masashi George, Mark S. Quartarone, Angelo Classen, Joseph Massimini, Marcello Rothwell, John Siebner, Hartwig Roman TI Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation SO BRAIN STIMULATION LA English DT Review DE Homeostatic plasticity; Non-invasive transcranial brain stimulation; Metaplasticity; Long-term potentiation; Long-term inhibition; Synaptic homeostasis hypothesis ID HUMAN MOTOR CORTEX; LONG-TERM POTENTIATION; THETA-BURST STIMULATION; PAIRED ASSOCIATIVE STIMULATION; BIDIRECTIONAL SYNAPTIC PLASTICITY; PARKINSONS-DISEASE PATIENTS; DEPRESSION-LIKE PLASTICITY; LOW-FREQUENCY STIMULATION; MAGNETIC STIMULATION; CORTICAL PLASTICITY AB Homeostatic plasticity is thought to stabilize neural activity around a set point within a physiologically reasonable dynamic range. Over the last ten years, a wide range of non-invasive transcranial brain stimulation (NTBS) techniques have been used to probe homeostatic control of cortical plasticity in the intact human brain. Here, we review different NTBS approaches to study homeostatic plasticity on a systems level and relate the findings to both, physiological evidence from in vitro studies and to a theoretical framework of homeostatic function. We highlight differences between homeostatic and other non-homeostatic forms of plasticity and we examine the contribution of sleep in restoring synaptic homeostasis. Finally, we discuss the growing number of studies showing that abnormal homeostatic plasticity may be associated to a range of neuropsychiatric diseases. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Karabanov, Anke; Siebner, Hartwig Roman] Copenhagen Univ Hosp, Danish Res Ctr Magnet Resonance, DK-2650 Hvidovre, Denmark. [Ziemann, Ulf] Univ Tubingen, Dept Neurol & Stroke, Tubingen, Germany. [Ziemann, Ulf] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany. [Hamada, Masashi] Natl Hosp Neurol & Neurosurg, London, England. [George, Mark S.] Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Quartarone, Angelo] Univ Messina, Dept Neurosci, I-98100 Messina, Italy. [Classen, Joseph] Univ Hosp Leipzig, Dept Neurol, Leipzig, Germany. [Massimini, Marcello] Univ Milan, Dept Clin Sci, I-20122 Milan, Italy. [Rothwell, John] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorde, London, England. [Siebner, Hartwig Roman] Copenhagen Univ Hosp Bispebjerg, Dept Neurol, Copenhagen, Denmark. RP Karabanov, A (reprint author), Copenhagen Univ Hosp, Danish Res Ctr Magnet Resonance, Kettegaard 30, DK-2650 Hvidovre, Denmark. EM ankenk@drcmr.dk OI Rothwell, John/0000-0003-1367-6467; QUARTARONE, Angelo/0000-0003-1485-6590; Karabanov, Anke Ninija/0000-0003-1874-393X FU Swedish Research Council FX AK was supported by the Swedish Research Council. NR 149 TC 17 Z9 17 U1 6 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD MAY-JUN PY 2015 VL 8 IS 3 BP 442 EP 454 DI 10.1016/j.brs.2015.01.404 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CJ8RX UT WOS:000355772300002 PM 26050599 ER PT J AU San-Juan, D Morales-Quezada, L Garduno, AJO Alonso-Vanegas, M Gonzalez-Aragon, MF Lopez, DAE Gregorio, RV Anschel, DJ Fregni, F AF San-juan, Daniel Morales-Quezada, Leon Orozco Garduno, Adolfo Josue Alonso-Vanegas, Mario Fernandez Gonzalez-Aragon, Maricarmen Espinoza Lopez, Dulce Anabel Vazquez Gregorio, Rafael Anschel, David J. Fregni, Felipe TI Transcranial Direct Current Stimulation in Epilepsy SO BRAIN STIMULATION LA English DT Article DE Transcranial direct current stimulation; tDCS; Brain polarization; Galvanic stimulation; Epilepsy ID HUMAN MOTOR CORTEX; DEEP BRAIN-STIMULATION; MAGNETIC STIMULATION; EPILEPTIFORM ACTIVITY; HIPPOCAMPAL SLICES; CORTICAL EXCITABILITY; NERVE-STIMULATION; DC POLARIZATION; FOCAL EPILEPSY; IN-VITRO AB Background: Transcranial direct current stimulation (tDCS) is an emerging non-invasive neuromodulation therapy in epilepsy with conflicting results in terms of efficacy and safety. Objective: Review the literature about the efficacy and safety of tDCS in epilepsy in humans and animals. Methods: We searched studies in PubMed, MedLine, Scopus, Web of Science and Google Scholar (January 1969 to October 2013) using the keywords 'transcranial direct current stimulation' or 'tDCS' or 'brain polarization' or 'galvanic stimulation' and 'epilepsy' in animals and humans. Original articles that reported tDCS safety and efficacy in epileptic animals or humans were included. Four review authors independently selected the studies, extracted data and assessed the methodological quality of the studies using the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines and Jadad Scale. A meta-analysis was not possible due to methodological, clinical and statistical heterogeneity of included studies. Results: We analyzed 9 articles with different methodologies (3 animals/6 humans) with a total of 174 stimulated individuals; 109 animals and 65 humans. In vivo and in vitro animal studies showed that direct current stimulation can successfully induce suppression of epileptiform activity without neurological injury and 4/6 (67%) clinical studies showed an effective decrease in epileptic seizures and 5/6 (83%) reduction of inter-ictal epileptiform activity. All patients tolerated tDCS well. Conclusions: tDCS trials have demonstrated preliminary safety and efficacy in animals and patients with epilepsy. Further larger studies are needed to define the best stimulation protocols and long-term follow-up. (C) 2015 Elsevier Inc. All rights reserved. C1 [San-juan, Daniel; Orozco Garduno, Adolfo Josue; Fernandez Gonzalez-Aragon, Maricarmen; Espinoza Lopez, Dulce Anabel; Vazquez Gregorio, Rafael] Natl Inst Neurol & Neurosurg Manuel Velasco Suare, Dept Neurophysiol, Mexico City 14269, DF, Mexico. [Morales-Quezada, Leon; Fregni, Felipe] Harvard Univ, Sch Med, Lab Neuromodulat, Dept Phys Med & Rehabil,Spaulding Rehabil Hosp, Charlestown, MA 02129 USA. [Morales-Quezada, Leon; Fregni, Felipe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Alonso-Vanegas, Mario] Natl Inst Neurol & Neurosurg Manuel Velasco Suare, Dept Neurosurg, Mexico City 14269, DF, Mexico. [Anschel, David J.] St Charles Hosp, Comprehens Epilepsy Ctr Long Isl, Port Jefferson, NY 11777 USA. RP San-Juan, D (reprint author), Natl Inst Neurol & Neurosurg Manuel Velasco Suare, Dept Neurophysiol, Av Insurgentes 3877,Col La Fama, Mexico City 14269, DF, Mexico. EM pegaso31@yahoo.com NR 58 TC 19 Z9 20 U1 4 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD MAY-JUN PY 2015 VL 8 IS 3 BP 455 EP 464 DI 10.1016/j.brs.2015.01.001 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CJ8RX UT WOS:000355772300003 PM 25697590 ER PT J AU Sahlem, GL Badran, BW Halford, JJ Williams, NR Korte, JE Leslie, K Strachan, M Breedlove, JL Runion, J Bachman, DL Uhde, TW Borckardt, JJ George, MS AF Sahlem, Gregory L. Badran, Bashar W. Halford, Jonathan J. Williams, Nolan R. Korte, Jeffrey E. Leslie, Kimberly Strachan, Martha Breedlove, Jesse L. Runion, Jennifer Bachman, David L. Uhde, Thomas W. Borckardt, Jeffery J. George, Mark S. TI Oscillating Square Wave Transcranial Direct Current Stimulation (tDCS) Delivered During Slow Wave Sleep Does Not Improve Declarative Memory More Than Sham: A Randomized Sham Controlled Crossover Study SO BRAIN STIMULATION LA English DT Article DE Transcranial direct current stimulation; Sleep; Slow wave sleep; Memory consolidation; Cognitive enhancement ID CONSOLIDATION AB Background: A 2006 trial in healthy medical students found that anodal slow oscillating tDCS delivered bi-frontally during slow wave sleep had an enhancing effect in declarative, but not procedural memory. Although there have been supporting animal studies, and similar findings in pathological groups, this study has not been replicated, or refuted, in the intervening years. We therefore tested these earlier results for replication using similar methods with the exception of current waveform (square in our study, nearly sinusoidal in the original). Objective/hypothesis: Our objective was to test the findings of a 2006 trial suggesting bi-frontal anodal tDCS during slow wave sleep enhances declarative memory. Methods: Twelve students (mean age 25, 9 women) free of medical problems underwent two testing conditions (active, sham) in a randomized counterbalanced fashion. Active stimulation consisted of oscillating square wave tDCS delivered during early Non-Rapid Eye Movement (NREM) sleep. The sham condition consisted of setting-up the tDCS device and electrodes, but not turning it on during sleep. tDCS was delivered bi-frontally with anodes placed at F3/F4, and cathodes placed at mastoids. Current density was 0.517 mA/cm(2), and oscillated between zero and maximal current at a frequency of 0.75 Hz. Stimulation occurred during five-five minute blocks with 1-min inter-block intervals (25 min total stimulation). The primary outcomes were both declarative memory consolidation measured by a paired word association test (PWA), and non-declarative memory, measured by a non-dominant finger-tapping test (FTT). We also recorded and analyzed sleep EEG. Results: There was no difference in the number of paired word associations remembered before compared to after sleep [(active = 3.1 +/- 3.0 SD more associations) (sham = 3.8 +/- 3.1 SD more associations)]. Finger tapping improved, (non-significantly) following active stimulation [(3.6 +/- 2.7 SD correctly typed sequences) compared to sham stimulation (2.3 +/- 2.2 SD correctly typed sequences)]. Conclusion: In this study, we failed to find improvements in declarative or performance memory and could not replicate an earlier study using nearly identical settings. Specifically we failed to find a beneficial effect on either overnight declarative or non-declarative memory consolidation via squarewave oscillating tDCS intervention applied bi-frontally during early NREM sleep. It is unclear if the morphology of the tDCS pulse is critical in any memory related improvements. (C) 2015 Elsevier Inc. All rights reserved. C1 [Sahlem, Gregory L.; Badran, Bashar W.; Williams, Nolan R.; Leslie, Kimberly; Strachan, Martha; Runion, Jennifer; Uhde, Thomas W.; Borckardt, Jeffery J.; George, Mark S.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Halford, Jonathan J.; Williams, Nolan R.; Bachman, David L.; George, Mark S.] Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. [Korte, Jeffrey E.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Badran, Bashar W.; Breedlove, Jesse L.; George, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Sahlem, GL (reprint author), Med Univ S Carolina, Dept Psychiat, 67 President St,502N, Charleston, SC 29425 USA. EM sahlem@musc.edu OI Williams, Nolan/0000-0003-4368-3203 FU MUSC Drug and Alcohol Research Training Program [NIDA R25 DA020537-06] FX We would like to thank the MUSC Sleep and Anxiety Treatment and Research Program for all of their help in the development, and implementation of this project. We would also like to thank the MUSC Drug and Alcohol Research Training Program with special thanks to Nicky Thornley and Drs. Sudie Back, Sarah Book, and Kathleen Brady along with the grant that supports it (NIDA R25 DA020537-06 (PI's Back and Brady)). NR 12 TC 9 Z9 9 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD MAY-JUN PY 2015 VL 8 IS 3 BP 528 EP 534 DI 10.1016/j.brs.2015.01.414 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CJ8RX UT WOS:000355772300013 PM 25795621 ER PT J AU Carvalho, S Goncalves, OF Soares, JM Sampaio, A Macedo, F Fregni, F Leite, J AF Carvalho, Sandra Goncalves, Oscar F. Soares, Jose Miguel Sampaio, Adriana Macedo, Fernando Fregni, Felipe Leite, Jorge TI Sustained Effects of a Neural-based Intervention in a Refractory Case of Tourette Syndrome SO BRAIN STIMULATION LA English DT Letter ID TICS C1 [Carvalho, Sandra; Goncalves, Oscar F.; Fregni, Felipe; Leite, Jorge] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Spaulding Neuromodulat Ctr, Boston, MA USA. [Carvalho, Sandra; Goncalves, Oscar F.; Fregni, Felipe; Leite, Jorge] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Carvalho, Sandra; Goncalves, Oscar F.; Sampaio, Adriana; Macedo, Fernando; Leite, Jorge] Univ Minho, Sch Psychol EPsi, Neuropsychophysiol Lab, CIPsi, P-4710057 Braga, Portugal. [Goncalves, Oscar F.] Northeastern Univ, Bouve Coll Hlth Sci, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. [Soares, Jose Miguel] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, P-4710057 Braga, Portugal. [Soares, Jose Miguel] PT Govt Assoc Lab, ICVS 3Bs, Braga, Portugal. [Soares, Jose Miguel] Clin Acad Ctr, Braga, Portugal. RP Carvalho, S (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Neuromodulat Ctr,Dept Phys Med & Rehabil, 79-96 13th St, Charlestown, MA 02129 USA. EM scarvalho@partners.org RI Goncalves, Oscar/G-5278-2010; Sampaio, Adriana/C-8361-2011; Leite, Jorge/E-4404-2013; OI Carvalho, Sandra/0000-0003-1759-5146; Goncalves, Oscar/0000-0003-2735-9155; Sampaio, Adriana/0000-0001-7347-1282; Leite, Jorge/0000-0002-0323-9012; Soares, Jose Miguel/0000-0001-6558-4973 NR 8 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD MAY-JUN PY 2015 VL 8 IS 3 BP 657 EP 659 DI 10.1016/j.brs.2014.12.008 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CJ8RX UT WOS:000355772300028 PM 25616936 ER PT J AU Blais, M Blagys, MD Rivas-Vazquez, R Bello, I Sinclair, SJ AF Blais, Mark Blagys, Matthew D. Rivas-Vazquez, Rafael Bello, Iruma Sinclair, Samuel J. TI Development and Initial Validation of a Brief Symptom Measure SO CLINICAL PSYCHOLOGY & PSYCHOTHERAPY LA English DT Article DE Brief Outcomes Measure; Bifactor Model; Phase Model of Change; Symptom Severity ID PHASE MODEL; PSYCHOTHERAPY; SCALE; OUTCOMES; COMPONENTS; INVENTORY AB Self-report measures of psychiatric symptomatology are important components of treatment monitoring and service evaluation programs. However, the currently available measures have numerous limitations including being symptom or disorder specific, suited to a limited range of clinical settings, and having excessive burden. Consequently, there is a need for a brief and psychometrically robust measure of global symptomatology that is applicable across diverse clinical settings, therapeutic modalities and patient populations. This paper presents the development and initial validation of such a scale, the Brief Symptom Measure-25 (BSM-25). We report findings from multiple samples examining the reliability, validity, sensitivity to change and factor structure of the new instrument. The results suggest that the BSM-25 has good reliability, is suitable to multiple levels of care, sensitive to treatment induced change and has promising validity. Exploratory bifactor modelling revealed that all items loaded strongly on a general factor (bifactor) while also forming two minor group factors. Potential limitations of this study along with future research and clinical applications of the BSM-25 are discussed. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Blais, Mark] Mass Gen Hosp, Psychiat, Boston, MA 02114 USA. [Blagys, Matthew D.] Alta Mira Recovery Programs, Sausalito, CA USA. [Rivas-Vazquez, Rafael] Citrus Hlth Network Inc, Miami, FL USA. [Bello, Iruma] NYU, Med Ctr, Bellevue Hosp, Psychiat, New York, NY 10016 USA. [Sinclair, Samuel J.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. RP Blais, M (reprint author), Mass Gen Hosp, Psychiat, Boston, MA 02114 USA. EM MBLAIS@partners.org NR 39 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1063-3995 EI 1099-0879 J9 CLIN PSYCHOL PSYCHOT JI Clin. Psychol. Psychother. PD MAY-JUN PY 2015 VL 22 IS 3 BP 267 EP 277 DI 10.1002/cpp.1876 PG 11 WC Psychology, Clinical SC Psychology GA CK1PG UT WOS:000355978700008 PM 26061651 ER PT J AU Rohde, NN Baca, CB Van Cott, AC Parko, KL Amuan, ME Pugh, MJ AF Rohde, Natalie N. Baca, Christine B. Van Cott, Anne C. Parko, Karen L. Amuan, Megan E. Pugh, Mary Jo TI Antiepileptic drug prescribing patterns in Iraq and Afghanistan war veterans with epilepsy SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy/seizures; Antiepileptic drugs; Cohort studies; Afghanistan war veterans; Iraq war veterans; Medical care ID NEW-ONSET EPILEPSY; QUALITY STANDARDS SUBCOMMITTEE; OLDER VETERANS; GERIATRIC EPILEPSY; AMERICAN ACADEMY; RISK-FACTORS; HEALTH-CARE; TRENDS; LEVETIRACETAM; EFFICACY AB Objective: We examined patterns of antiepileptic drug (AED) use in a cohort of Iraq/Afghanistan war veterans (IAVs) who were previously identified as having epilepsy. We hypothesized that clinicians would be more likely to prescribe newer AEDs and would select specific AEDs to treat seizures based on patient characteristics including gender and comorbidities. Methods: From the cohort of IAVs previously identified with epilepsy between fiscal years 2009 and 2010, we selected those who received AEDs from the Veterans Health Administration in FY2010. Regimens were classified as monotherapy or polytherapy, and specific AED use was examine overall and by gender. Multivariable logistic regression examined associations of age; gender; race/ethnicity; medical, psychiatric, and neurological comorbidities; and receipt of neurology specialty care associated with the six most commonly used AEDs. Results: Among 256,284 IAVs, 2123 met inclusion criteria (mean age: 33 years; 89% men). Seventy-two percent (n = 1526) received monotherapy, most commonly valproate (N = 425) and levetiracetam(n = 347). Sixty-one percent of those on monotherapy received a newer AED (levetiracetam, topiramate, lamotrigine, zonisamide, oxcarbazepine). Although fewer women than men received valproate, nearly 90% (N = 45) were of reproductive age (<= 45 years). Antiepileptic drug prescribing patterns were associated with posttraumatic stress disorder, bipolar disorder, cerebrovascular disease, dementia/cognitive impairment, headache, and receipt of neurological specialty care (all p < 0.01). Significance: In this cohort of veterans with epilepsy, most received AED monotherapy and newer AEDs. Prescribing patterns were different for men and women. The patterns observed between AEDs and neurological/psychiatric comorbidities suggest that clinicians are practicing rational prescribing. (C) 2015 Published by Elsevier Inc. C1 [Rohde, Natalie N.; Pugh, Mary Jo] South Texas Vet Hlth Care Syst, VA Epilepsy Ctr Excellence, San Antonio, TX 78229 USA. [Rohde, Natalie N.; Pugh, Mary Jo] UTHSCSA, Dept Epidemiol & Biostat, San Antonio, TX USA. [Baca, Christine B.] VAGLAHS, VA Epilepsy Ctr Excellence, Los Angeles, CA USA. [Baca, Christine B.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Van Cott, Anne C.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Van Cott, Anne C.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15240 USA. [Parko, Karen L.] San Francisco VA Hlth Care Syst, VA Epilepsy Ctr Excellence, San Francisco, CA 94121 USA. [Parko, Karen L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Amuan, Megan E.] ENRM VAMC, CHOIR, Bedford, MA USA. [Pugh, Mary Jo] Texas A&M Hlth Sci Ctr, Dept Med, Bryan, TX USA. [Amuan, Megan E.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. RP Pugh, MJ (reprint author), South Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM Natalie.Rohde@VA.gov; CBower@mednet.ucla.edu; Anne.VanCott@va.gov; karen.parko@ucsf.edu; megan.amuan@va.gov; MaryJo.Pugh2@VA.gov OI Pugh, Mary Jo/0000-0003-4196-7763 NR 38 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD MAY PY 2015 VL 46 BP 133 EP 139 DI 10.1016/j.yebeh.2015.03.027 PG 7 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA CJ7MD UT WOS:000355678600023 PM 25911209 ER PT J AU Tat, Y Weinberg, I Ben-Yehuda, A Duvdevani, M AF Tat, Yuvat Weinberg, Ido Ben-Yehuda, Arie Duvdevani, Mordechai TI Unilateral, Obstructive Urinothorax Secondary to Colorectal Carcinoma SO ISRAEL MEDICAL ASSOCIATION JOURNAL LA English DT Article DE urinothorax; urinary tract obstruction; colorectal carcinoma; pleural effusion C1 [Tat, Yuvat; Ben-Yehuda, Arie] Hadassah Hebrew Univ, Med Ctr, Div Internal Med, IL-91120 Jerusalem, Israel. [Duvdevani, Mordechai] Hadassah Hebrew Univ, Med Ctr, Dept Urol, IL-91120 Jerusalem, Israel. [Weinberg, Ido] Massachusetts Gen Hosp, Sect Vasc Med, Boston, MA 02114 USA. RP Tat, Y (reprint author), Hadassah Hebrew Univ, Med Ctr, Dept Med, Allergy & Clin Immunol Unit, Ein Kerem Campus,POB 12000, IL-91120 Jerusalem, Israel. EM yuvalt@hadassah.org.il NR 5 TC 0 Z9 0 U1 0 U2 0 PU ISRAEL MEDICAL ASSOC JOURNAL PI RAMAT GAN PA 2 TWIN TOWERS, 11TH FL, 35 JABOTINSKY ST, PO BOX 3604, RAMAT GAN 52136, ISRAEL SN 1565-1088 J9 ISR MED ASSOC J JI Isr. Med. Assoc. J. PD MAY PY 2015 VL 17 IS 5 BP 321 EP 322 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CK6DW UT WOS:000356319700013 ER PT J AU Silva, PS Aiello, LP AF Silva, Paolo S. Aiello, Lloyd Paul TI Telemedicine and Eye Examinations for Diabetic Retinopathy A Time to Maximize Real-World Outcomes SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID POPULATION C1 [Silva, Paolo S.; Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Silva, Paolo S.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. RP Aiello, LP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, One Joslin Pl, Boston, MA 02215 USA. EM lpaiello@joslin.harvard.edu NR 8 TC 5 Z9 5 U1 1 U2 1 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 MAY PY 2015 VL 133 IS 5 BP 525 EP 526 DI 10.1001/jamaophthalmol.2015.0333 PG 3 WC Ophthalmology SC Ophthalmology GA CK2NF UT WOS:000356046700004 PM 25742322 ER PT J AU Jakobiec, FA Stagner, AM Nowak, MA Rubin, PAD AF Jakobiec, Frederick A. Stagner, Anna M. Nowak, Michael A. Rubin, Peter A. D. TI Presumed Primary Papillary Sebaceous Carcinoma of the Palpebral Conjunctiva SO JAMA OPHTHALMOLOGY LA English DT Letter C1 [Jakobiec, Frederick A.; Stagner, Anna M.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02115 USA. [Nowak, Michael A.] Palm Beach Dermatol Diagnost Dermatopathol, W Palm Beach, FL USA. [Rubin, Peter A. D.] Ophthalm Plast Surg, Palm Beach Gardens, FL USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Ste 328, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD MAY PY 2015 VL 133 IS 5 BP 612 EP 614 DI 10.1001/jamaophthalmol.2014.5870 PG 4 WC Ophthalmology SC Ophthalmology GA CK2NF UT WOS:000356046700021 PM 25654538 ER PT J AU Rattanaumpawan, P Nachamkin, I Bilker, WB Roy, JA Metlay, JP Zaoutis, TE Lautenbach, E AF Rattanaumpawan, Pinyo Nachamkin, Irving Bilker, Warren B. Roy, Jason A. Metlay, Joshua P. Zaoutis, Theoklis E. Lautenbach, Ebbing CA CDC Prevention Epictr Program TI Risk factors for ambulatory urinary tract infections caused by high-MIC fluoroquinolone-susceptible Escherichia coli in women: results from a large case-control study SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE fluoroquinolone resistance; UTIs; Escherichia coli ID HOSPITALIZED-PATIENTS; RESISTANCE; EPIDEMIOLOGY; ICD-9-CM AB Objectives: The prevalence of high-MIC fluoroquinolone-susceptible Escherichia coli (FQSEC) has been increasing. These isolates are one step closer to full fluoroquinolone (FQ) resistance and may lead to delayed response to FQ therapy. Our study aimed to investigate the epidemiology of high-MIC FQSEC in ambulatory urinary tract infections (UTIs). Patients and methods: A case-control study was conducted at outpatient services within the University of Pennsylvania Health System, Philadelphia. All female subjects with non-recurrent UTI caused by FQSEC (levofloxacin MIC<4 mg/L) were enrolled. Cases were subjects with high-MIC FQSEC UTI (levofloxacin MIC >0.12 but <4 mg/L) and controls were subjects with low-MIC FQSEC UTI (levofloxacin MIC <= 0.12 mg/L). Data on microbiology results and baseline characteristics were extracted from electronic medical records. Results: During the 3 year study period (May 2008-April 2011), 11287 episodes of E. coli bacteriuria were identified. The prevalence of FQSEC, FQ-intermediate susceptible E. coli and FQ-resistant E. coli was 75.0%, 0.4% and 24.6%, respectively. A total of 2001 female subjects with FQSEC UTI were enrolled into our study (165 cases and 1836 controls). Independent risk factors for high-MIC FQ susceptibility included Asian race (OR = 2.92; 95% CI = 1.29-6.58; P = 0.02), underlying renal disease (OR = 2.18; 95% CI = 1.15-4.14; P = 0.02) and previous nitrofurantoin exposure (OR = 8.86; 95% CI = 1.95-40.29; P = 0.005). Conclusions: Asian race, underlying renal disease and previous exposure to nitrofurantoin were identified as independent risk factors for high-MIC FQSEC. There may be some factors that are more common in Asians, which may result in the selection of high-MIC FQSEC. Further studies are necessary to explore these findings. C1 [Rattanaumpawan, Pinyo; Zaoutis, Theoklis E.; Lautenbach, Ebbing] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Rattanaumpawan, Pinyo] Mahidol Univ, Siriraj Hosp, Div Infect Dis & Trop Med, Dept Med,Fac Med, Bangkok 10700, Thailand. [Nachamkin, Irving] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Bilker, Warren B.; Roy, Jason A.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Metlay, Joshua P.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Lautenbach, Ebbing] Univ Penn, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. RP Rattanaumpawan, P (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. EM pinyo@mail.med.upenn.edu FU National Institutes of Health [R21-AI103497, K24-AI080942]; Pennsylvania Department of Health; CDC Prevention Epicenters Program [U54-CK000163] FX This study was supported by the National Institutes of Health [R21-AI103497 (E. L.); K24-AI080942 (E. L.)]. It was also supported in part by a Commonwealth University Health Enhancement (CURE) grant from the Pennsylvania Department of Health and by the CDC Prevention Epicenters Program [U54-CK000163 (E. L.)]. The study sponsors had no role in study design, data collection, analysis or interpretation, or writing of the report. NR 16 TC 3 Z9 3 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD MAY PY 2015 VL 70 IS 5 BP 1547 EP 1551 DI 10.1093/jac/dku548 PG 5 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA CK0YW UT WOS:000355932800037 PM 25630645 ER PT J AU Hajjarian, Z Tripathi, MM Nadkarni, SK AF Hajjarian, Zeinab Tripathi, Markandey M. Nadkarni, Seemantini K. TI Optical Thromboelastography to evaluate whole blood coagulation SO JOURNAL OF BIOPHOTONICS LA English DT Article DE Blood; coagulation; laser speckle; optical thromboelastography; rheology; thromboelastography; viscoelasticity ID DIFFUSING-WAVE-SPECTROSCOPY; DYNAMIC LIGHT-SCATTERING; LASER SPECKLE RHEOLOGY; COMPLEX FLUIDS; ATHEROSCLEROTIC PLAQUES; VISCOELASTIC MODULI; TISSUE; MICRORHEOLOGY; PHANTOMS; DEVICES AB Measurement of blood viscoelasticity during clotting provides a direct metric of haemostatic conditions. Therefore, technologies that quantify blood viscoelasticity at the point-of-care are invaluable for diagnosing coagulopathies. We present a new approach, Optical Thromboelastography (OTEG) that measures the viscoelastic properties of coagulating blood by evaluating temporal laser speckle fluctuations, reflected from a few blood drops. During coagulation, platelet-fibrin clot formation restricts the mean square displacements (MSD) of scatterers and decelerates speckle fluctuations. Cross-correlation analysis of speckle frames provides the speckle intensity temporal autocorrelation, g(2)(t), from which MSD is deduced and the viscoelastic modulus of blood is estimated. Our results demonstrate a close correspondence between blood viscoelasticity evaluated by OTEG and mechanical rheometry. Spatio-temporal speckle analyses yield 2-dimensional maps of clot viscoelasticity, enabling the identification of micro-clot formation at distinct rates in normal and coagulopathic specimens. These findings confirm the unique capability of OTEG for the rapid evaluation of patients' coagulation status and highlight the potential for point-of-care use. C1 [Hajjarian, Zeinab; Tripathi, Markandey M.; Nadkarni, Seemantini K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02138 USA. RP Nadkarni, SK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02138 USA. EM snadkarni@mgh.harvard.edu FU NIH [U54 EB015408 02]; Air Force office of scientific research [FA9550-11-1-0331]; Partners healthcare systems Inc. FX This work is supported by research funding obtained from the NIH U54 EB015408 02 grant (S.N), Air Force office of scientific research FA9550-11-1-0331 (S.N), and Partners healthcare systems Inc. (S.N). We thank Dr. Elizabeth M. van Cott and Blake S. Maddux at the MGH special coagulation laboratory for their help in providing the discarded blood specimens. We wish to acknowledge Haemonetics Corporation for genereously providing reagents and supplies. NR 48 TC 4 Z9 4 U1 1 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1864-063X EI 1864-0648 J9 J BIOPHOTONICS JI J. Biophotonics PD MAY PY 2015 VL 8 IS 5 BP 372 EP 381 DI 10.1002/jbio.201300197 PG 10 WC Biochemical Research Methods; Biophysics; Optics SC Biochemistry & Molecular Biology; Biophysics; Optics GA CK1RD UT WOS:000355983800002 PM 24700701 ER PT J AU Choi, EY Walton, DS AF Choi, Eun Young Walton, David S. TI Goniotomy for Steroid-Induced Glaucoma: Clinical and Tonographic Evidence to Support Therapeutic Goniotomy SO JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS LA English DT Article ID SIMULATING CONGENITAL GLAUCOMA; TRABECULAR MESHWORK CELLS; INTRAOCULAR-PRESSURE; HUMAN EYES; CORTICOSTEROIDS; DEXAMETHASONE; MITOMYCIN AB Purpose: To report the surgical results of goniotomy for corticosteroid-induced glaucoma and to provide evidence to support its use as initial surgical therapy. Methods: The medical records of 5 patients with a history of goniosurgery for steroid-induced glaucoma were reviewed. Preoperative and postoperative clinical findings were reviewed, including the topical use of steroids, tonometric and gonioscopic findings, goniosurgery, and postoperative results. In addition, tonography was performed on one patient to document the improved facility of outflow following successful goniosurgery. Results: Surgical success was achieved in all patients, with intraocular pressures less than 18 mm Hg without the use of medication for an average follow-up period of 11.5 years (range: 9 months to 30 years). A normal postoperative facility of outflow (C = 0.30 mm(3)/min/mm Hg) was determined in one patient. No complications of surgery were experienced. Conclusion: Goniotomy is an effective procedure for persistent steroid-induced glaucoma, and should be considered for initial surgical treatment. C1 [Choi, Eun Young; Walton, David S.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA. RP Walton, DS (reprint author), 2 Longfellow Pl,Suite 201, Boston, MA 02114 USA. EM walton.blackeye@gmail.com NR 23 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0191-3913 EI 1938-2405 J9 J PEDIAT OPHTH STRAB JI J. Pediatr. Ophthalmol. Strabismus. PD MAY-JUN PY 2015 VL 52 IS 3 BP 183 EP 188 DI 10.3928/01913913-20150427-05 PG 6 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA CK3WE UT WOS:000356146400012 PM 26053210 ER PT J AU Tangutoori, S Baldwin, P Sridhar, S AF Tangutoori, Shifalika Baldwin, Paige Sridhar, Srinivas TI PARP inhibitors: A new era of targeted therapy SO MATURITAS LA English DT Review DE PARP inhibitors; Lynparza; Olaparib; BMN-673; Personalized medicine ID POLY(ADP-RIBOSE) POLYMERASE INHIBITOR; PROSTATE-CANCER; TEMOZOLOMIDE; TUMORS; GLIOBLASTOMA; MECHANISMS; RESISTANCE; RUCAPARIB; OLAPARIB; ABT-888 AB Personalized medicine seeks to utilize targeted therapies with increased selectivity and efficacy in pre-selected patient cohorts. One such molecularly targeted therapy is enabled by inhibiting the enzyme poly(ADP-ribose) polymerase (PARP) by small molecule inhibitors in tumors which have a defect in the homologous DNA recombination pathway, most characteristically due to BRCA mutations. Olaparib, a highly potent PARP inhibitor, has recently been the approved for ovarian cancer therapy by the FDA and European commission in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer with BRCA1 or BRCA2 mutations. Currently, clinical trials with several PARP inhibitors are being conducted to assess the toxicities, the efficacies and the benefit of the drugs as monotherapies or combined with radiation or other chemotherapeutic agents, in ovarian, breast, prostate, rectal, lung, pancreatic, peritoneal, head and neck, brain, squamous cell carcinomas and sarcomas, to list a few. In this review, our focus is to outline the emerging molecular mechanisms, preclinical evidence and clinical applications of PARP inhibitors especially in nonBRCA cancers, and review the combination strategies compatible with PARP inhibitor therapy. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Tangutoori, Shifalika; Baldwin, Paige; Sridhar, Srinivas] Northeastern Univ, Nanomed Sci & Technol Ctr, Boston, MA 02115 USA. [Tangutoori, Shifalika] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Sridhar, Srinivas] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Sridhar, S (reprint author), Northeastern Univ, Nanomed Sci & Technol Ctr, Boston, MA 02115 USA. EM s.sridhar@neu.edu FU Ovarian Cancer Research Program Army [W81XWH-14-1-0092]; David Mazzone Awards program of Prostate Cancer Research Foundations; NSF-DGE [0965843] FX This work was supported by Ovarian Cancer Research Program Army-W81XWH-14-1-0092, the David Mazzone Awards program of Prostate Cancer Research Foundations, and NSF-DGE-0965843. NR 29 TC 27 Z9 30 U1 6 U2 41 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-5122 EI 1873-4111 J9 MATURITAS JI Maturitas PD MAY PY 2015 VL 81 IS 1 BP 5 EP 9 DI 10.1016/j.maturitas.2015.01.015 PG 5 WC Geriatrics & Gerontology; Obstetrics & Gynecology SC Geriatrics & Gerontology; Obstetrics & Gynecology GA CK0HL UT WOS:000355886200003 PM 25708226 ER PT J AU Struzyna, LA Harris, JP Katiyar, KS Chen, HI Cullen, DK AF Struzyna, Laura A. Harris, James P. Katiyar, Kritika S. Chen, H. Isaac Cullen, D. Kacy TI Restoring nervous system structure and function using tissue engineered living scaffolds SO NEURAL REGENERATION RESEARCH LA English DT Article DE living scaffolds; neural tissue engineering; cell transplant; biomaterials; regeneration; neurotrauma; neurodegeneration; axon pathfinding; cell migration ID LONG-TERM SURVIVAL; SPINAL-CORD INJURY; NEURAL STEM-CELLS; IN-VITRO; NEUROTROPHIC FACTORS; CHONDROITINASE ABC; AXON REGENERATION; GROWTH CONES; NEURONS; RECOVERY AB Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following nervous system injury or neurodegenerative disease. Disconnection of axon pathways - the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals - is a common feature of many neurological disorders and injury. However, functional axonal regeneration rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engineered "living scaffolds", which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration - mimicking key developmental mechanisms- or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal clusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in preclinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery. C1 [Struzyna, Laura A.; Harris, James P.; Katiyar, Kritika S.; Chen, H. Isaac; Cullen, D. Kacy] Univ Penn, Dept Neurosurg, Perelman Sch Med, Ctr Brain Injury & Repair, Philadelphia, PA 19104 USA. [Struzyna, Laura A.; Harris, James P.; Chen, H. Isaac; Cullen, D. Kacy] Philadelphia Vet Affairs Med Ctr, Ctr Neurotrauma Neurodegenerat & Restorat, Philadelphia, PA USA. [Katiyar, Kritika S.] Drexel Univ, Sch Biomed Engn, Philadelphia, PA 19104 USA. RP Cullen, DK (reprint author), Univ Penn, Dept Neurosurg, Perelman Sch Med, Ctr Brain Injury & Repair, Philadelphia, PA 19104 USA. EM dkacy@mail.med.upenn.edu FU U.S. Army Medical Research and Materiel Command through the Joint Warfighter Medical Research Program [W81XWH-13-13207004]; Axonia Medical, Inc.; Department of Veterans Affairs (RRD Merit Review) [B1097-I]; National Institutes of Health [NINDS T32-NS043126]; Penn Medicine Neuroscience Center; National Science Foundation [DGE-1321851] FX This work was made possible due to financial support provided by the U.S. Army Medical Research and Materiel Command through the Joint Warfighter Medical Research Program (#W81XWH-13-13207004); Axonia Medical, Inc.; Department of Veterans Affairs (RR&D Merit Review #B1097-I); National Institutes of Health (NINDS T32-NS043126); Penn Medicine Neuroscience Center; and the National Science Foundation (Graduate Research Fellowship DGE-1321851). NR 61 TC 3 Z9 4 U1 4 U2 16 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1673-5374 EI 1876-7958 J9 NEURAL REGEN RES JI Neural Regen. Res. PD MAY PY 2015 VL 10 IS 5 BP 679 EP 685 DI 10.4103/1673-5374.156943 PG 7 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA CK1JU UT WOS:000355964400002 PM 26109930 ER PT J AU Puhalla, S Elmquist, W Freyer, D Kleinberg, L Adkins, C Lockman, P McGregor, J Muldoon, L Nesbit, G Peereboom, D Smith, Q Walker, S Neuwelt, E AF Puhalla, Shannon Elmquist, William Freyer, David Kleinberg, Lawrence Adkins, Chris Lockman, Paul McGregor, John Muldoon, Leslie Nesbit, Gary Peereboom, David Smith, Quentin Walker, Sara Neuwelt, Edward TI Unsanctifying the sanctuary: challenges and opportunities with brain metastases SO NEURO-ONCOLOGY LA English DT Article DE brain metastases; CNS sanctuary; imaging; prevention; therapy ID CELL LUNG-CANCER; CENTRAL-NERVOUS-SYSTEM; HER2-POSITIVE BREAST-CANCER; PHASE-II TRIAL; INTERSTITIAL THERMAL THERAPY; LAPATINIB PLUS CAPECITABINE; TUMOR BARRIER PERMEABILITY; TYROSINE KINASE INHIBITORS; BLOOD-VOLUME MAPS; RADIATION-THERAPY AB While the use of targeted therapies, particularly radiosurgery, has broadened therapeutic options for CNS metastases, patients respond minimally and prognosis remains poor. The inability of many systemic chemotherapeutic agents to penetrate the blood-brain barrier (BBB) has limited their use and allowed brain metastases to become a burgeoning clinical challenge. Adequate preclinical models that appropriately mimic the metastatic process, the BBB, and blood-tumor barriers (BTB) are needed to better evaluate therapies that have the ability to enhance delivery through or penetrate into these barriers and to understand the mechanisms of resistance to therapy. The heterogeneity among and within different solid tumors and subtypes of solid tumors further adds to the difficulties in determining the most appropriate treatment approaches and methods of laboratory and clinical studies. This review article discusses therapies focused on prevention and treatment of CNS metastases, particularly regarding the BBB, and the challenges and opportunities these therapies present. C1 [Puhalla, Shannon] Univ Pittsburgh, Div Hematol Oncol, Pittsburgh, PA USA. [Elmquist, William] Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA. [Freyer, David] Childrens Hosp Los Angeles, Dept Hematol Oncol, Los Angeles, CA 90027 USA. [Kleinberg, Lawrence] Johns Hopkins Univ, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD USA. [Adkins, Chris] Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX USA. [Lockman, Paul] W Virginia Univ, Sch Pharm, Dept Pharmaceut Sci, Morgantown, WV 26506 USA. [Lockman, Paul] Mary Babb Randolph Canc Ctr, Morgantown, WV USA. [McGregor, John] Ohio State Univ, Med Ctr, Dept Neurol Surg, Columbus, OH 43210 USA. [Muldoon, Leslie; Neuwelt, Edward] Oregon Hlth & Sci Univ, Blood Brain Barrier Program, Portland, OR 97239 USA. [Nesbit, Gary] Oregon Hlth & Sci Univ, Dotter Radiol Neuroradiol, Portland, OR 97239 USA. [Peereboom, David] Cleveland Clin Fdn, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44195 USA. [Smith, Quentin] Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Amarillo, TX USA. [Walker, Sara] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Neuwelt, Edward] Portland VA Med Ctr, Portland, OR USA. RP Neuwelt, E (reprint author), Oregon Hlth & Sci Univ, Blood Brain Barrier Program, 3181 SW Sam Jackson Pk Rd,L603, Portland, OR 97239 USA. EM neuwelte@ohsu.edu FU National Institutes of Health NIH/NIGMS [U54GM104942, R13 NS076353]; Walter S. and Lucienne Driskill Foundation; R13 grant FX Grants from the National Institutes of Health NIH/NIGMS U54GM104942, and R13 NS076353 (E.N.) and the Walter S. and Lucienne Driskill Foundation (E.N.). This report was based on presentations at the 19th Annual Meeting of the Blood-Brain Barrier Consortium (March 21-23, 2013, Stevenson, Washington), which was partially funded by the R13 grant. NR 100 TC 8 Z9 8 U1 1 U2 8 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 MAY PY 2015 VL 17 IS 5 BP 639 EP 651 DI 10.1093/neuonc/nov023 PG 13 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CK5KO UT WOS:000356263100004 PM 25846288 ER PT J AU Green, AL Ramkissoon, SH McCauley, D Jones, K Perry, JA Hsu, JHR Ramkissoon, LA Maire, CL Hubbell-Engler, B Knoff, DS Shacham, S Ligon, KL Kung, AL AF Green, Adam L. Ramkissoon, Shakti H. McCauley, Dilara Jones, Kristen Perry, Jennifer A. Hsu, Jessie Hao-Ru Ramkissoon, Lori A. Maire, Cecile L. Hubbell-Engler, Benjamin Knoff, David S. Shacham, Sharon Ligon, Keith L. Kung, Andrew L. TI Preclinical antitumor efficacy of selective exportin 1 inhibitors in glioblastoma SO NEURO-ONCOLOGY LA English DT Article DE apoptosis; exportin 1; glioblastoma; patient-derived xenograft; SINE ID CENTRAL-NERVOUS-SYSTEM; ACUTE MYELOID-LEUKEMIA; NUCLEAR EXPORT; MALIGNANT GLIOMA; CRM1; CANCER; EXPRESSION; RADIOTHERAPY; CONCOMITANT; PROGNOSIS AB Background. Glioblastoma (GBM) is poorly responsive to current chemotherapy. The nuclear transporter exportin 1 (XPO1, CRM1) is often highly expressed in GBM, which may portend a poor prognosis. Here, we determine the efficacy of novel selective inhibitors of nuclear export (SINE) specific to XPO1 in preclinical models of GBM. Methods. Seven patient-derived GBM lines were treated with 3 SINE compounds (KPT-251, KPT-276, and Selinexor) in neurosphere culture conditions. KPT-276 and Selinexor were also evaluated in a murine orthotopic patient-derived xenograft (PDX) model of GBM. Cell cycle effects were assayed by flow cytometry in vitro and immunohistochemistry in vivo. Apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase 3/7 activity assays. Results. Treatment of GBM neurosphere cultures with KPT-276, Selinexor, and KPT-251 revealed dose-responsive growth inhibition in all 7 GBM lines [ range of half-maximal inhibitory concentration (IC50), 6-354 nM]. In an orthotopic PDX model, treatment with KPT-276 and Selinexor demonstrated pharmacodynamic efficacy, significantly suppressed tumor growth, and prolonged animal survival. Cellular proliferation was not altered with SINE treatment. Instead, induction of apoptosis was apparent both in vitro and in vivo with SINE treatment, without overt evidence of neurotoxicity. Conclusions. SINE compounds show preclinical efficacy utilizing in vitro and in vivo models of GBM, with induction of apoptosis as the mechanism of action. Selinexor is now in early clinical trials in solid and hematological malignancies. Based on these preclinical data and excellent brain penetration, we have initiated clinical trials of Selinexor in patients with relapsed GBM. C1 [Green, Adam L.; Perry, Jennifer A.; Hsu, Jessie Hao-Ru; Hubbell-Engler, Benjamin] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Green, Adam L.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Ramkissoon, Shakti H.; Ramkissoon, Lori A.; Maire, Cecile L.; Knoff, David S.; Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ramkissoon, Shakti H.; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [McCauley, Dilara; Shacham, Sharon] Karyopharm Therapeut, Natick, MA USA. [Jones, Kristen] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA. [Ligon, Keith L.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Kung, Andrew L.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA. RP Kung, AL (reprint author), 3959 Broadway,CHN 10-01, New York, NY 10032 USA. EM akung@columbia.edu OI Knoff, David/0000-0001-6233-2893; Kung, Andrew/0000-0002-9091-488X FU St. Baldrick's Foundation; Pedals for Pediatrics; TeamConnor; Stahl Family Foundation FX This work was supported by St. Baldrick's Foundation (A.L.K., A.L.G.), Pedals for Pediatrics (A.L.G.), TeamConnor (A.L.G.), and the Stahl Family Foundation (A.L.G.). NR 31 TC 8 Z9 9 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 MAY PY 2015 VL 17 IS 5 BP 697 EP 707 DI 10.1093/neuonc/nou303 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CK5KO UT WOS:000356263100010 PM 25366336 ER PT J AU Nabors, LB Fink, KL Mikkelsen, T Grujicic, D Tarnawski, R Nam, DH Mazurkiewicz, M Salacz, M Ashby, L Zagonel, V Depenni, R Perry, JR Hicking, C Picard, M Hegi, ME Lhermitte, B Reardon, DA AF Nabors, L. Burt Fink, Karen L. Mikkelsen, Tom Grujicic, Danica Tarnawski, Rafal Nam, Do Hyun Mazurkiewicz, Maria Salacz, Michael Ashby, Lynn Zagonel, Vittorina Depenni, Roberta Perry, James R. Hicking, Christine Picard, Martin Hegi, Monika E. Lhermitte, Benoit Reardon, David A. TI Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study SO NEURO-ONCOLOGY LA English DT Article DE cilengitide; newly diagnosed glioblastoma; randomized phase II study; unmethylated MGMT promoter ID RECURRENT GLIOBLASTOMA; MALIGNANT GLIOMA; TEMOZOLOMIDE; TRIAL; EXPRESSION; CRITERIA AB Background. Survival outcomes for patients with glioblastoma remain poor, particularly for patients with unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with standard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter. Methods. Overall, 265 patients were randomized (1: 1: 1) to standard cilengitide (2000 mg 2x/wk; n = 88), intensive cilengitide (2000 mg 5x/wk during wk 1-6, thereafter 2x/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89). Cilengitide was administered intravenously in combination with daily temozolomide (TMZ) and concomitant radiotherapy (RT; wk 126), followed by TMZ maintenance therapy (TMZ/RT -> TMZ). The primary endpoint was overall survival; secondary endpoints included progression-free survival, pharmacokinetics, and safety and tolerability. Results. Median overall survival was 16.3 months in the standard cilengitide arm (hazard ratio [HR], 0.686; 95% CI: 0.484, 0.972; P = .032) and 14.5 months in the intensive cilengitide arm (HR, 0.858; 95% CI: 0.612, 1.204; P = .3771) versus 13.4 months in the control arm. Median progression-free survival assessed per independent review committee was 5.6 months (HR, 0.822; 95% CI: 0.595, 1.134) and 5.9 months (HR, 0.794; 95% CI: 0.575, 1.096) in the standard and intensive cilengitide arms, respectively, versus 4.1 months in the control arm. Cilengitide was well tolerated. Conclusions. Standard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT -> TMZ. Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II study. C1 [Nabors, L. Burt] Univ Alabama Birmingham, Birmingham, AL USA. [Fink, Karen L.] Baylor Univ, Med Ctr, Dallas, TX USA. [Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [Grujicic, Danica] Univ Belgrade, Fac Med, Clin Ctr Serbia, Clin Neurosurg, Belgrade, Serbia. [Tarnawski, Rafal] Maria Sklodowska Curie Mem Canc Ctr, Gliwice, Poland. [Tarnawski, Rafal] Inst Oncol, Gliwice Branch, Radiotherapy & Chemotherapy Clin, Gliwice, Poland. [Nam, Do Hyun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Mazurkiewicz, Maria] Ctr Onkol Ziemi Lubelskiej, Lublin, Poland. [Salacz, Michael] St Lukes Hosp, St Lukes Brain Tumor Ctr, Kansas City, MO USA. [Ashby, Lynn] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Zagonel, Vittorina] IRCCS, IOV, Med Oncol Unit 1, Padua, Italy. [Depenni, Roberta] Policlin Modena, Modena, Italy. [Perry, James R.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Hicking, Christine; Picard, Martin] Merck KGaA, Darmstadt, Germany. [Hegi, Monika E.] Univ Lausanne Hosp, Dept Clin Neurosci, Lausanne, Switzerland. [Lhermitte, Benoit] Univ Lausanne Hosp, Inst Pathol, Lausanne, Switzerland. [Reardon, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nabors, LB (reprint author), UAB Dept Neurol, SC 350,1720 2nd Ave South, Birmingham, AL 35294 USA. EM bnabors@uab.edu RI zagonel, vittorina/F-4226-2014; Hegi, Monika/O-4796-2015; Tarnawski, Rafal/N-7526-2016 OI zagonel, vittorina/0000-0002-0829-2525; Hegi, Monika/0000-0003-0855-6495; FU Merck KGaA, Darmstadt, Germany FX The trial was sponsored by Merck KGaA, Darmstadt, Germany. NR 19 TC 29 Z9 29 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 MAY PY 2015 VL 17 IS 5 BP 708 EP 717 DI 10.1093/neuonc/nou356 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CK5KO UT WOS:000356263100011 PM 25762461 ER PT J AU Han, KL Ren, M Wick, W Abrey, L Das, A Jin, J Reardon, DA AF Han, Kelong Ren, Melanie Wick, Wolfgang Abrey, Lauren Das, Asha Jin, Jin Reardon, David A. TI Interpretation of meta-analysis evaluating progression-free survival as a surrogate endpoint for overall survival in glioblastoma SO NEURO-ONCOLOGY LA English DT Letter ID TRIALS C1 [Han, Kelong; Das, Asha; Jin, Jin] Genentech Inc, San Francisco, CA 94080 USA. [Ren, Melanie] Stanford Univ, Palo Alto, CA 94304 USA. [Wick, Wolfgang] Univ Med Ctr, Heidelberg, Germany. [Wick, Wolfgang] DKFZ, Heidelberg, Germany. [Abrey, Lauren] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. [Reardon, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Han, KL (reprint author), Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA. EM han.kelong@gene.com NR 7 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAY PY 2015 VL 17 IS 5 BP 764 EP 765 DI 10.1093/neuonc/nov021 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CK5KO UT WOS:000356263100018 PM 25722425 ER PT J AU Alexander, BM Trippa, L AF Alexander, Brian M. Trippa, Lorenzo TI Getting it first versus getting it right: weighing the value of and evidence for progression-free survival as a surrogate endpoint for overall survival in glioblastoma SO NEURO-ONCOLOGY LA English DT Letter ID NEWLY-DIAGNOSED GLIOBLASTOMA; TEMOZOLOMIDE; BEVACIZUMAB; TRIALS C1 [Alexander, Brian M.] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Trippa, Lorenzo] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Trippa, Lorenzo] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Alexander, BM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM bmalexander@lroc.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAY PY 2015 VL 17 IS 5 BP 765 EP 766 DI 10.1093/neuonc/nov024 PG 3 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CK5KO UT WOS:000356263100019 PM 25846289 ER PT J AU Sarwar, A Boland, G Monks, A Kruskal, JB AF Sarwar, Ammar Boland, Giles Monks, Annamarie Kruskal, Jonathan B. TI Metrics for Radiologists in the Era of Value-based Health Care Delivery SO RADIOGRAPHICS LA English DT Article ID DEPARTMENTS; QUALITY AB Accelerated by the Patient Protection and Affordable Care Act of 2010, health care delivery in the United States is poised to move from a model that rewards the volume of services provided to one that rewards the value provided by such services. Radiology department operations are currently managed by an array of metrics that assess various departmental missions, but many of these metrics do not measure value. Regulators and other stakeholders also influence what metrics are used to assess medical imaging. Metrics such as the Physician Quality Reporting System are increasingly being linked to financial penalties. In addition, metrics assessing radiology's contribution to cost or outcomes are currently lacking. In fact, radiology is widely viewed as a contributor to health care costs without an adequate understanding of its contribution to downstream cost savings or improvement in patient outcomes. The new value-based system of health care delivery and reimbursement will measure a provider's contribution to reducing costs and improving patient outcomes with the intention of making reimbursement commensurate with adherence to these metrics. The authors describe existing metrics and their application to the practice of radiology, discuss the so-called value equation, and suggest possible metrics that will be useful for demonstrating the value of radiologists' services to their patients. (C) RSNA, 2015 . radiographics.rsna.org C1 [Sarwar, Ammar; Monks, Annamarie; Kruskal, Jonathan B.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Boland, Giles] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sarwar, Ammar; Boland, Giles; Kruskal, Jonathan B.] Harvard Univ, Sch Med, Boston, MA USA. RP Sarwar, A (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 1 Deaconess Rd, Boston, MA 02215 USA. EM asarwar@bidmc.harvard.edu NR 18 TC 18 Z9 18 U1 1 U2 3 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 MAY-JUN PY 2015 VL 35 IS 3 BP 866 EP U226 DI 10.1148/rg.2015140221 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK2KW UT WOS:000356040300015 PM 25839737 ER PT J AU Margulies, SS Kilbaugh, T Sullivan, S Smith, C Propert, K Byro, M Saliga, K Costine, BA Duhaime, AC AF Margulies, Susan S. Kilbaugh, Todd Sullivan, Sarah Smith, Colin Propert, Kathleen Byro, Melissa Saliga, Kristen Costine, Beth A. Duhaime, Ann-Christine TI Establishing a Clinically Relevant Large Animal Model Platform for TBI Therapy Development: Using Cyclosporin A as a Case Study SO BRAIN PATHOLOGY LA English DT Article DE brain injury; pediatric; preclinical trials; treatment; TBI ID TRAUMATIC BRAIN-INJURY; CLOSED-HEAD INJURY; MATURATION-DEPENDENT RESPONSE; HIGH-DOSE CYCLOSPORINE; DIFFUSE AXONAL INJURY; MITOCHONDRIAL DYSFUNCTION; NEONATAL PIG; CELL-DEATH; PERMEABILITY TRANSITION; CEREBRAL-ISCHEMIA AB We have developed the first immature large animal translational treatment trial of a pharmacologic intervention for traumatic brain injury (TBI) in children. The preclinical trial design includes multiple doses of the intervention in two different injury types (focal and diffuse) to bracket the range seen in clinical injury and uses two post-TBI delays to drug administration. Cyclosporin A (CsA) was used as a case study in our first implementation of the platform because of its success in multiple preclinical adult rodent TBI models and its current use in children for other indications. Tier 1 of the therapy development platform assessed the short-term treatment efficacy after 24h of agent administration. Positive responses to treatment were compared with injured controls using an objective effect threshold established prior to the study. Effective CsA doses were identified to study in Tier 2. In the Tier 2 paradigm, agent is administered in a porcine intensive care unit utilizing neurological monitoring and clinically relevant management strategies, and intervention efficacy is defined as improvement in longer term behavioral endpoints above untreated injured animals. In summary, this innovative large animal preclinical study design can be applied to future evaluations of other agents that promote recovery or repair after TBI. C1 [Margulies, Susan S.; Sullivan, Sarah; Propert, Kathleen; Byro, Melissa] Univ Penn, Philadelphia, PA 19104 USA. [Kilbaugh, Todd] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Smith, Colin] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Saliga, Kristen; Costine, Beth A.; Duhaime, Ann-Christine] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Margulies, SS (reprint author), Univ Penn, Dept Bioengn, 210 S 33rd St,240 Skirkanich Hall, Philadelphia, PA 19104 USA. EM margulies@seas.upenn.edu FU NIH [U01NS069545] FX The preclinical study was supported by the NIH grant U01NS069545. We thank our NIH partners Drs Ramona Hicks and Linda McGavern for their insightful questions that shaped our study design and their long-standing support for the project. We are grateful for the expert technical assistance, many long hours of participation and deep dedication to the project by Courtney Robertson, Athena Zuppa, Jill Ralston, Ashley Bebee, Kortne Hudick, Sabrina Taylor, Christopher Seufert, Carter Dodge, Marissa Fiorello and Jamie Rose. We appreciate the long, tedious hours contributed by Erica Hummel, Jesi Kim, Peter Chhour, Susie Cha and Rachel Margulies digitizing photographs of injured brain sections to determine lesion volume pathology values. NR 96 TC 5 Z9 5 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 EI 1750-3639 J9 BRAIN PATHOL JI Brain Pathol. PD MAY PY 2015 VL 25 IS 3 BP 289 EP 303 DI 10.1111/bpa.12247 PG 15 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA CG6CX UT WOS:000353384200007 PM 25904045 ER PT J AU Koerte, IK Lin, AP Willems, A Muehlmann, M Hufschmidt, J Coleman, MJ Green, I Liao, HJ Tate, DF Wilde, EA Pasternak, O Bouix, S Rathi, Y Bigler, ED Stern, RA Shenton, ME AF Koerte, Inga K. Lin, Alexander P. Willems, Anna Muehlmann, Marc Hufschmidt, Jakob Coleman, Michael J. Green, Isobel Liao, Huijun Tate, David F. Wilde, Elisabeth A. Pasternak, Ofer Bouix, Sylvain Rathi, Yogesh Bigler, Erin D. Stern, Robert A. Shenton, Martha E. TI A Review of Neuroimaging Findings in Repetitive Brain Trauma SO BRAIN PATHOLOGY LA English DT Article DE neuroimaging; repetitive head injury ID MILD COGNITIVE IMPAIRMENT; PROFESSIONAL FOOTBALL PLAYERS; CEREBRAL GLUCOSE-METABOLISM; WHITE-MATTER INTEGRITY; HIGH-SCHOOL FOOTBALL; PHF-TAU RADIOLIGAND; 2ND IMPACT SYNDROME; ICE HOCKEY PLAYERS; ALZHEIMERS-DISEASE; SOCCER PLAYERS AB Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease confirmed at postmortem. Those at highest risk are professional athletes who participate in contact sports and military personnel who are exposed to repetitive blast events. All neuropathologically confirmed CTE cases, to date, have had a history of repetitive head impacts. This suggests that repetitive head impacts may be necessary for the initiation of the pathogenetic cascade that, in some cases, leads to CTE. Importantly, while all CTE appears to result from repetitive brain trauma, not all repetitive brain trauma results in CTE. Magnetic resonance imaging has great potential for understanding better the underlying mechanisms of repetitive brain trauma. In this review, we provide an overview of advanced imaging techniques currently used to investigate brain anomalies. We also provide an overview of neuroimaging findings in those exposed to repetitive head impacts in the acute/subacute and chronic phase of injury and in more neurodegenerative phases of injury, as well as in military personnel exposed to repetitive head impacts. Finally, we discuss future directions for research that will likely lead to a better understanding of the underlying mechanisms separating those who recover from repetitive brain trauma vs. those who go on to develop CTE. C1 [Koerte, Inga K.; Lin, Alexander P.; Willems, Anna; Muehlmann, Marc; Hufschmidt, Jakob; Coleman, Michael J.; Green, Isobel; Pasternak, Ofer; Bouix, Sylvain; Rathi, Yogesh; Shenton, Martha E.] Brigham & Womens Hosp, Dept Psychiat, Psychiat Neuroimaging Lab, Boston, MA 02215 USA. [Koerte, Inga K.; Lin, Alexander P.; Willems, Anna; Muehlmann, Marc; Hufschmidt, Jakob; Coleman, Michael J.; Green, Isobel; Pasternak, Ofer; Bouix, Sylvain; Rathi, Yogesh; Shenton, Martha E.] Brigham & Womens Hosp, Dept Radiol, Psychiat Neuroimaging Lab, Boston, MA 02215 USA. [Lin, Alexander P.; Liao, Huijun] Brigham & Womens Hosp, Dept Radiol, Ctr Clin Spect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. [Stern, Robert A.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Dept Neurol, Boston, MA 02118 USA. [Stern, Robert A.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Dept Neurosurg, Boston, MA 02118 USA. [Stern, Robert A.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Shenton, Martha E.] VA Boston Healthcare Syst, Boston, MA USA. [Koerte, Inga K.; Willems, Anna; Muehlmann, Marc] Univ Munich, Dr von Hauner Childrens Hosp, Dept Child & Adolescent Psychiat Psychosomat & Ps, Munich, Germany. [Hufschmidt, Jakob] Univ Munich, Dr von Hauner Childrens Hosp, Dept Pediat Neurol, Munich, Germany. [Tate, David F.] San Antonio Mil Med Ctr, Def Ctr, San Antonio, TX USA. [Tate, David F.] San Antonio Mil Med Ctr, Vet Brain Injury Ctr, San Antonio, TX USA. [Wilde, Elisabeth A.] Baylor Coll Med, Dept Phys Med & Rehabil, San Antonio, TX USA. [Wilde, Elisabeth A.] Baylor Coll Med, Dept Neurol, San Antonio, TX USA. [Wilde, Elisabeth A.] Baylor Coll Med, Dept Radiol, San Antonio, TX USA. [Wilde, Elisabeth A.] Michael E DeBakey VA Med Ctr, San Antonio, TX USA. [Bigler, Erin D.] Brigham Young Univ, Ctr Neurosci, Provo, UT 84602 USA. [Bigler, Erin D.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. RP Koerte, IK (reprint author), Brigham & Womens Hosp, Dept Psychiat, Psychiat Neuroimaging Lab, 1249 Boylston St, Boston, MA 02215 USA. EM ikoerte@bwh.harvard.edu RI Tate, David/I-3963-2013; OI Stern, Robert/0000-0002-5008-077X; Tate, David/0000-0003-0213-1920 FU Else Kroner-Fresenius-Stiftung, Germany; Department of Defense [W81XWH-10-1-0835, X81XWH-07-CC-CSDoD]; National Institutes of Health [R01-NS078337, U01-NS086659]; VA Merit Award FX This study was supported by the Else Kroner-Fresenius-Stiftung, Germany (IK, MM). This work was also partially funded by grants from the Department of Defense (W81XWH-10-1-0835: APL; X81XWH-07-CC-CSDoD; MES, RAS), the National Institutes of Health (R01-NS078337: APL, MES, RAS; U01-NS086659: RAS) and a VA Merit Award (MES). NR 173 TC 8 Z9 8 U1 4 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 EI 1750-3639 J9 BRAIN PATHOL JI Brain Pathol. PD MAY PY 2015 VL 25 IS 3 BP 318 EP 349 DI 10.1111/bpa.12249 PG 32 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA CG6CX UT WOS:000353384200009 PM 25904047 ER PT J AU McKee, AC Stein, TD Kiernan, PT Alvarez, VE AF McKee, Ann C. Stein, Thor D. Kiernan, Patrick T. Alvarez, Victor E. TI The Neuropathology of Chronic Traumatic Encephalopathy SO BRAIN PATHOLOGY LA English DT Article DE Alzheimer's disease; chronic traumatic encephalopathy; tauopathy; TDP-43; traumatic brain injury ID COLLEGIATE FOOTBALL PLAYERS; ALZHEIMER-RELATED CHANGES; REPETITIVE HEAD-INJURY; BRAIN-INJURY; DEMENTIA-PUGILISTICA; TAU PATHOLOGY; AXONAL INJURY; AMYLOID-BETA; PUNCH-DRUNK; NEUROFIBRILLARY TANGLES AB Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE). Most instances of CTE occur in association with the play of sports, but CTE has also been reported in association with blast injuries and other neurotrauma. Symptoms of CTE include behavioral and mood changes, memory loss, cognitive impairment and dementia. Like many other neurodegenerative diseases, CTE is diagnosed with certainty only by neuropathological examination of brain tissue. CTE is a tauopathy characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles, astrocytic tangles and neurites in striking clusters around small blood vessels of the cortex, typically at the sulcal depths. Severely affected cases show p-tau pathology throughout the brain. Abnormalities in phosphorylated 43kDa TAR DNA-binding protein are found in most cases of CTE; beta-amyloid is identified in 43%, associated with age. Given the importance of sports participation and physical exercise to physical and psychological health as well as disease resilience, it is critical to identify the genetic risk factors for CTE as well as to understand how other variables, such as stress, age at exposure, gender, substance abuse and other exposures, contribute to the development of CTE. C1 [McKee, Ann C.; Stein, Thor D.] VA Boston Healthcare Syst, Boston, MA USA. [McKee, Ann C.; Stein, Thor D.] Boston Univ, Sch Med, Dept Pathol & Lab Sci, Boston, MA 02118 USA. [McKee, Ann C.; Kiernan, Patrick T.; Alvarez, Victor E.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [McKee, Ann C.; Stein, Thor D.] Boston Univ, Alzheimers Dis Ctr, Boston, MA 02215 USA. [McKee, Ann C.; Stein, Thor D.; Kiernan, Patrick T.; Alvarez, Victor E.] Boston Univ, Chron Traumat Encephalopathy Ctr Program, Boston, MA 02215 USA. RP McKee, AC (reprint author), 72 E Concord St,Suite B-7800, Boston, MA 02118 USA. EM amckee@bu.edu OI Stein, Thor/0000-0001-6954-4477 FU National Institute of Neurological Disorders and Stroke [1UO1NS086659-01]; Department of Veterans Affairs, the Veterans Affairs Biorepository [CSP 501]; Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS), Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B6796-C]; National Institute of Aging Boston University Alzheimer's Disease Center [P30AG13846, 0572063345-5]; National Institute of Aging Boston University Framingham Heart Study [AG1649]; National Operating Committee on Standards for Athletic Equipment; Sports Legacy Institute; Andlinger Foundation; WWE; National Football League FX The authors gratefully acknowledge the use of the resources and facilities at the Edith Nourse Rogers Memorial Veterans Hospital (Bedford, MA, USA). We also gratefully acknowledge the help of all members of the Chronic Traumatic Encephalopathy Program at Boston University School of Medicine, the Boston VA, as well as the individuals and families whose participation and contributions made this work possible. This work was supported by the National Institute of Neurological Disorders and Stroke (1UO1NS086659-01), Department of Veterans Affairs, the Veterans Affairs Biorepository (CSP 501), the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS), Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C), the National Institute of Aging Boston University Alzheimer's Disease Center (P30AG13846; supplement 0572063345-5), the National Institute of Aging Boston University Framingham Heart Study R01 (AG1649), the National Operating Committee on Standards for Athletic Equipment and the Sports Legacy Institute. This work was also supported by unrestricted gifts from the Andlinger Foundation, the WWE and the National Football League. NR 105 TC 41 Z9 41 U1 12 U2 32 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 EI 1750-3639 J9 BRAIN PATHOL JI Brain Pathol. PD MAY PY 2015 VL 25 IS 3 BP 350 EP 364 DI 10.1111/bpa.12248 PG 15 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA CG6CX UT WOS:000353384200010 PM 25904048 ER PT J AU Doumit, G Gharb, BB Rampazzo, A McBride, J Papay, F Zins, J Yaremchuk, M AF Doumit, Gaby Gharb, Bahar Bassiri Rampazzo, Antonio McBride, Jennifer Papay, Francis Zins, James Yaremchuk, Michael TI Surgical Anatomy Relevant to the Transpalpebral Subperiosteal Elevation of the Midface SO AESTHETIC SURGERY JOURNAL LA English DT Article ID SUPERFICIAL MUSCULOAPONEUROTIC SYSTEM; FACIAL SKELETON RATIONALE; RETAINING LIGAMENTS; SMAS DISSECTION; LIFT; FIXATION; SURGERY; FACE; RHYTIDECTOMY; EXPERIENCE AB Background: The surgical anatomy of the midface relevant to its subperiosteal elevation and repositioning is assessed. Objectives: The aim of this study is to give more details on the anatomy relevant to the midface lift. Methods: Twenty hemifacial dissections were performed. The location of the zygomatic branches of the facial nerve (ZBFN) and the terminal branches of the infraorbital nerve (ION) were dissected. The location of the masseteric and zygomatic ligaments and the elevation of midface following their release were documented. Results: On average, there were 3 branches of the facial nerve innervating the zygomatic major muscle and 1.8 branches entering the muscle superior to the caudal origin of the zygomaticomaxillary (ZM) suture. The most superior ZBFN was found to lie at an average of 6.2 +/- 1.6 mm cranial to ZM suture and 1.4 +/- 0.4 mm superficial to the bone. The most inferior branch was at a mean of 4.8 +/- 3.3 mm inferior to ZM suture. On average the ION had 5.2 branches that traveled for 10.2 mm above the periosteum before they passed into a superficial plane. Division of the zygomatico-masseteric retaining ligaments allowed for elevation of the midface by 4.8 +/- 1.0 mm medially and 5.5 +/- .9 mm laterally. Conclusions: Branches of the ZBFN and ION lie in close proximity to the subperiosteal plane in the midface. These branches are at risk for damage during release of the upper zygomatic ligaments and placement of the periosteal suspension sutures during midface elevation procedures. C1 [Doumit, Gaby] Cleveland Clin, Craniofacial Surg, Cleveland, OH 44195 USA. [Gharb, Bahar Bassiri; Rampazzo, Antonio; Zins, James] Cleveland Clin, Dept Plast Surg, Cleveland, OH 44195 USA. [McBride, Jennifer] Cleveland Clin, Histol, Cleveland, OH 44195 USA. [McBride, Jennifer] Cleveland Clin, Surg, Cleveland, OH 44195 USA. [Papay, Francis] Cleveland Clin, Dermatol & Plast Surg Inst, Cleveland, OH 44195 USA. [Yaremchuk, Michael] Massachusetts Gen Hosp, Craniofacial Surg, Boston, MA 02114 USA. RP Doumit, G (reprint author), Cleveland Clin, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM doumitg@ccf.org NR 28 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1090-820X EI 1527-330X J9 AESTHET SURG J JI Aesthet. Surg. J. PD MAY-JUN PY 2015 VL 35 IS 4 BP 353 EP 358 DI 10.1093/asj/sju106 PG 6 WC Surgery SC Surgery GA CJ7DA UT WOS:000355653100003 PM 25908695 ER PT J AU Monis, EL Mannstadt, M AF Monis, Elizabeth L. Mannstadt, Michael TI Hypoparathyroidism - disease update and emerging treatments SO ANNALES D ENDOCRINOLOGIE LA English DT Article DE Hypoparathyroidism; Complications of therapy; rhPTH(1-84) ID PARATHYROID-HORMONE 1-34; RANDOMIZED CONTROLLED-TRIAL; CALCIUM-SENSING RECEPTOR; LONG-TERM TREATMENT; QUALITY-OF-LIFE; REPLACEMENT THERAPY; CROSSOVER TRIAL; PTH(1-84); CALCITRIOL; MUTATIONS AB Parathyroid hormone (PTH) is the primary regulator of blood calcium levels and bone metabolism. Insufficient levels of PTH lead to hypoparathyroidism, characterized by low serum calcium and elevated serum phosphate levels. It is most commonly caused by the inadvertent damage to the parathyroid glands during thyroid surgery. Patients with hypoparathyroidism are currently being treated with oral calcium and active vitamin D, and to avoid worsening hypercalciuria, target serum calcium levels are within the lower end of normal. With current treatment, patients may suffer from large swings in serum calcium and are at a substantial risk of chronic renal failure, nephrocalcinosis, and kidney stones. The recent FDA approval of recombinant human (rh) PTH(1-84) for the treatment of hypoparathyroidism adds PTH replacement therapy to the endocrinologist's armamentarium to treat this chronic disease. (C) 2015 Published by Elsevier Masson SAS. C1 [Monis, Elizabeth L.; Mannstadt, Michael] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Mannstadt, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1051,50 Blossom St, Boston, MA 02114 USA. EM mannstadt@mgh.harvard.edu NR 45 TC 2 Z9 2 U1 1 U2 2 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0003-4266 EI 2213-3941 J9 ANN ENDOCRINOL-PARIS JI Ann Endocrinol. PD MAY PY 2015 VL 76 IS 2 BP 84 EP 88 DI 10.1016/j.ando.2015.03.009 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CJ6YM UT WOS:000355641100003 PM 25882889 ER PT J AU Juppner, H AF Jueppner, Harald TI Genetic and epigenetic defects at the GNAS locus cause different forms of pseudohypoparathyroidism SO ANNALES D ENDOCRINOLOGIE LA English DT Article DE Calcium; Phosphate; PTH; PTHrP; PTH/PTHrP receptor; Pseudohypoparathyroidism type Ia and Ib; Pseudopseudohypoparathyroidism; GNAS; Stimulatory G protein (Gs alpha); Imprinting; Syntaxin 16 (STX16); Parent-specific DNA methylation; Genetic disease; cAMP signaling pathway; Albright hereditary osteodystrophy (AHO) ID ALBRIGHTS HEREDITARY OSTEODYSTROPHY; IMPRINTING CONTROL ELEMENT; XL-ALPHA-S; AUTOSOMAL-DOMINANT; GROWTH-RETARDATION; GLUCOSE-METABOLISM; PATERNAL DELETION; CONTROL REGION; IB; METHYLATION C1 [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM HJUEPPNER@mgh.harvard.edu NR 41 TC 2 Z9 2 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0003-4266 EI 2213-3941 J9 ANN ENDOCRINOL-PARIS JI Ann Endocrinol. PD MAY PY 2015 VL 76 IS 2 BP 92 EP 97 DI 10.1016/j.ando.2015.03.011 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CJ6YM UT WOS:000355641100005 PM 25882888 ER PT J AU Hendrickx, DM Aerts, HJWL Caiment, F Clark, D Ebbels, TMD Evelo, CT Gmuender, H Hebels, DGAJ Herwig, R Hescheler, J Jennen, DGJ Jetten, MJA Kanterakis, S Keun, HC Matser, V Overington, JP Pilicheva, E Sarkans, U Segura-Lepe, MP Sotiriadou, I Wittenberger, T Wittwehr, C Zanzi, A Kleinjans, JCS AF Hendrickx, Diana M. Aerts, Hugo J. W. L. Caiment, Florian Clark, Dominic Ebbels, Timothy M. D. Evelo, Chris T. Gmuender, Hans Hebels, Dennie G. A. J. Herwig, Ralf Hescheler, Juergen Jennen, Danyel G. J. Jetten, Marlon J. A. Kanterakis, Stathis Keun, Hector C. Matser, Vera Overington, John P. Pilicheva, Ekaterina Sarkans, Ugis Segura-Lepe, Marcelo P. Sotiriadou, Isaia Wittenberger, Timo Wittwehr, Clemens Zanzi, Antonella Kleinjans, Jos C. S. TI diXa: a data infrastructure for chemical safety assessment SO BIOINFORMATICS LA English DT Article ID TOXICOLOGY AB Motivation: The field of toxicogenomics (the application of '-omics' technologies to risk assessment of compound toxicities) has expanded in the last decade, partly driven by new legislation, aimed at reducing animal testing in chemical risk assessment but mainly as a result of a paradigm change in toxicology towards the use and integration of genome wide data. Many research groups worldwide have generated large amounts of such toxicogenomics data. However, there is no centralized repository for archiving and making these data and associated tools for their analysis easily available. Results: The Data Infrastructure for Chemical Safety Assessment (diXa) is a robust and sustainable infrastructure storing toxicogenomics data. A central data warehouse is connected to a portal with links to chemical information and molecular and phenotype data. diXa is publicly available through a user-friendly web interface. New data can be readily deposited into diXa using guidelines and templates available online. Analysis descriptions and tools for interrogating the data are available via the diXa portal. C1 [Hendrickx, Diana M.; Caiment, Florian; Hebels, Dennie G. A. J.; Jennen, Danyel G. J.; Jetten, Marlon J. A.; Kleinjans, Jos C. S.] Maastricht Univ, Sch Oncol & Dev Biol GROW, Dept Toxicogen, NL-6200 MD Maastricht, Netherlands. [Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Clark, Dominic; Kanterakis, Stathis; Matser, Vera; Overington, John P.; Pilicheva, Ekaterina; Sarkans, Ugis] European Bioinformat Inst, European Mol Biol Lab, Hinxton CB10 1SD, Cambs, England. [Ebbels, Timothy M. D.; Keun, Hector C.; Segura-Lepe, Marcelo P.] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Computat & Syst Med, London SW7 2AZ, England. [Evelo, Chris T.] Maastricht Univ, Dept Bioinformat BiGCaT, NL-6200 MD Maastricht, Netherlands. [Gmuender, Hans; Wittenberger, Timo] Genedata AG, CH-4053 Basel, Switzerland. [Herwig, Ralf] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany. [Hescheler, Juergen; Sotiriadou, Isaia] Univ Cologne, Inst Neurophysiol, Ctr Physiol & Pathophysiol, D-50931 Cologne, Germany. [Wittwehr, Clemens; Zanzi, Antonella] European Commiss, Joint Res Ctr, I-21027 Ispra, VA, Italy. RP Hendrickx, DM (reprint author), Maastricht Univ, Sch Oncol & Dev Biol GROW, Dept Toxicogen, NL-6200 MD Maastricht, Netherlands. EM d.hendrickx@maastrichtuniversity.nl RI Evelo, Chris/D-2914-2009; Overington, John/G-8607-2015; caiment, florian/N-7623-2015; Aerts, Hugo/P-6350-2015 OI Evelo, Chris/0000-0002-5301-3142; Caiment, Florian/0000-0002-3325-0466; Sarkans, Ugis/0000-0001-9227-8488; Matser, Vera/0000-0002-2010-6844; Hendrickx, Diana/0000-0001-7225-4307; Overington, John/0000-0002-5859-1064; Aerts, Hugo/0000-0002-2122-2003 FU diXa, EU Seventh Framework Programme [RI-283775] FX This work was supported by diXa, a part of the EU Seventh Framework Programme, under grant agreement number RI-283775. NR 11 TC 5 Z9 5 U1 0 U2 7 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 MAY 1 PY 2015 VL 31 IS 9 BP 1505 EP 1507 DI 10.1093/bioinformatics/btu827 PG 3 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 CJ7HP UT WOS:000355665800031 PM 25505093 ER PT J AU Jain, RK Fukumura, D Duda, DG AF Jain, Rakesh K. Fukumura, Dai Duda, Dan G. TI Lessons From 30 Years of Teaching About the Microenvironment of Tumors SO CANCER JOURNAL LA English DT Editorial Material C1 Massachusetts Gen Hosp, Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Edwin L Steele Labs, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu FU NCI NIH HHS [R01 CA159258, P01 CA080124, R01 CA115767] NR 0 TC 1 Z9 1 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD MAY-JUN PY 2015 VL 21 IS 3 BP 137 EP 137 DI 10.1097/PPO.0000000000000119 PG 1 WC Oncology SC Oncology GA CJ7EU UT WOS:000355658000001 PM 26049690 ER PT J AU Mallidi, S Spring, BQ Chang, S Vakoc, B Hasan, T AF Mallidi, Srivalleesha Spring, Bryan Q. Chang, Sung Vakoc, Benjamin Hasan, Tayyaba TI Optical Imaging, Photodynamic Therapy and Optically Triggered Combination Treatments SO CANCER JOURNAL LA English DT Review ID FLUORESCENCE-GUIDED SURGERY; EPITHELIAL OVARIAN-CANCER; ENDOTHELIAL GROWTH-FACTOR; IN-VIVO FLUORESCENCE; COHERENCE TOMOGRAPHY; MONOCLONAL-ANTIBODY; PERITONEAL CARCINOMATOSIS; TREATMENT RESPONSE; PROSTATE-CANCER; CONTRAST AGENTS AB Optical imaging is becoming increasingly promising for real-time image-guided resections, and combined with photodynamic therapy (PDT), a photochemistry-based treatment modality, optical approaches can be intrinsically "theranostic." Challenges in PDT include precise light delivery, dosimetry, and photosensitizer tumor localization to establish tumor selectivity, and like all other modalities, incomplete treatment and subsequent activation of molecular escape pathways are often attributable to tumor heterogeneity. Key advances in molecular imaging, target-activatable photosensitizers, and optically active nanoparticles that provide both cytotoxicity and a drug release mechanism have opened exciting avenues to meet these challenges. The focus of the review is optical imaging in the context of PDT, but the general principles presented are applicable to many of the conventional approaches to cancer management. We highlight the role of optical imaging in providing structural, functional, and molecular information regarding photodynamic mechanisms of action, thereby advancing PDT and PDT-based combination therapies of cancer. These advances represent a PDT renaissance with increasing applications of clinical PDT as a frontline cancer therapy working in concert with fluorescence-guided surgery, chemotherapy, and radiation. C1 [Mallidi, Srivalleesha; Spring, Bryan Q.; Chang, Sung; Vakoc, Benjamin; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 40 Blossom St,Bartlett 314, Boston, MA 02114 USA. EM thasan@mgh.harvard.edu FU NIH [F32CA165881, 5P01CA084203, R01CA156177, R01CA158415, R01CA160998, P41EB015903, R01CA163528]; Canon USA Inc. FX This work was supported by NIH grants F32CA165881 (to Dr Mallidi), 5P01CA084203, R01CA156177, R01CA158415, R01CA160998 (to Dr Hasan) NIH grants P41EB015903 and R01CA163528 (to Dr. Vakoc), and funds from Canon USA Inc. NR 100 TC 7 Z9 8 U1 6 U2 50 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD MAY-JUN PY 2015 VL 21 IS 3 BP 194 EP 205 DI 10.1097/PPO.0000000000000117 PG 12 WC Oncology SC Oncology GA CJ7EU UT WOS:000355658000010 PM 26049699 ER PT J AU Moriarty, PM Hemphill, L AF Moriarty, Patrick M. Hemphill, Linda TI Lipoprotein Apheresis SO CARDIOLOGY CLINICS LA English DT Article DE Lipoprotein apheresis; Familial hypercholesterolemia; LDL-C; CVD; Atherosclerosis; Lp(a) ID LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; SUDDEN HEARING-LOSS; HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; DEXTRAN SULFATE ADSORPTION; LDL PRECIPITATION HELP; LIPID-LOWERING THERAPY; ARTERIOSCLEROSIS OBLITERANS; CHOLESTEROL APHERESIS; NEPHROTIC SYNDROME AB Patients with familial hypercholesterolemia (FH) have early development of atherosclerosis and cardiovascular disease (CVD). Lipid lowering medications are not always successful in reducing increased low-density lipoprotein C (LDL-C) levels. Lipoprotein apheresis (LA) therapy lowers LDL-C by more than 60%. LA has proven its clinical benefit in reducing CVD events for patients with FH and hypercholesterolemia. LA also reduces Lp(a) levels, inflammatory markers and blood viscosity. C1 [Moriarty, Patrick M.] Univ Kansas, Med Ctr, Div Clin Pharmacol, Kansas City, KS 66160 USA. [Moriarty, Patrick M.] Univ Kansas, Atherosclerosis Lipoprot Apheresis Ctr, Med Ctr, Kansas City, KS 66160 USA. [Hemphill, Linda] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Moriarty, PM (reprint author), Univ Kansas, Atherosclerosis Lipoprot Apheresis Ctr, Med Ctr, 3901 Rainbow Blvd,Mail Stop 3008, Kansas City, KS 66160 USA. EM pmoriart@kumc.edu NR 96 TC 6 Z9 6 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 EI 1558-2264 J9 CARDIOL CLIN JI Cardiol. Clin. PD MAY PY 2015 VL 33 IS 2 BP 197 EP + DI 10.1016/j.ccl.2015.02.002 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CJ8SV UT WOS:000355774700004 PM 25939293 ER PT J AU Alatrakchi, N AF Alatrakchi, Nadia TI Bregs in Chronic HBV: Is It Time for Bragging Rights? SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material ID REGULATORY B-CELLS; CHRONIC HEPATITIS-B; CD4(+) T-CELLS; TRANSPLANTATION; FREQUENCY; TOLERANCE; DISEASE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Alatrakchi, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, GI Unit Warren 10,55 Fruit St, Boston, MA 02114 USA. EM nalatrakchi@mgh.harvard.edu NR 17 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2015 VL 60 IS 5 BP 1115 EP 1117 DI 10.1007/s10620-015-3584-1 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CJ5YN UT WOS:000355570200001 PM 25686744 ER PT J AU Barshop, K Kuo, B AF Barshop, Kenneth Kuo, Braden TI Connecting the Dots Between Gastrointestinal Motility and Symptoms Using Wireless Motility Capsule Testing SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material ID GASTROPARESIS C1 [Barshop, Kenneth] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Kuo, Braden] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Kuo, B (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM bkuo@mgh.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2015 VL 60 IS 5 BP 1120 EP 1122 DI 10.1007/s10620-014-3519-2 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CJ5YN UT WOS:000355570200003 PM 25577271 ER PT J AU Rogal, SS Bielefeldt, K Wasan, AD Szigethy, E Lotrich, F DiMartini, AF AF Rogal, Shari S. Bielefeldt, Klaus Wasan, Ajay D. Szigethy, Eva Lotrich, Francis DiMartini, Andrea F. TI Fibromyalgia Symptoms and Cirrhosis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Widespread pain; Opioids; Steatohepatitis; Hepatitis C virus ID ALCOHOLIC LIVER-DISEASE; SLEEP QUALITY INDEX; DEPRESSION SCALE; HOSPITAL ANXIETY; PAIN; CYTOKINES; CORTISOL; QUESTIONNAIRE; TESTOSTERONE; PATHOGENESIS AB Background An association between fibromyalgia and hepatitis C virus (HCV) has been previously described. However, the relationship between nonalcoholic steatohepatitis (NASH) and fibromyalgia symptoms has not been assessed, though they share several risk factors. Aim We aimed to assess the factors associated with fibromyalgia symptoms across etiologies of liver disease. Methods Patients with cirrhosis due to HCV, NASH, or alcohol were recruited from an outpatient hepatology clinic and administered the Hospital Anxiety and Depression Score, Pittsburgh Sleep Quality Index, and the modified 2010 American College of Rheumatology Diagnostic Criteria for Fibromyalgia. Serum inflammatory markers were measured with standard luminex assays. Results Of 193 participants, 53 (27 %) met criteria for fibromyalgia. Fibromyalgia symptoms were significantly associated with etiology of liver disease (HCV: 35 %, NASH: 30 %, alcohol-related liver disease: 12 %, p < 0.01). Using logistic regression, mood symptoms (OR 1.14, 95 % CI 1.06, 1.22), sleep disturbance (OR 1.32, 95 % CI 1.16, 1.52), and etiology of liver disease (NASH vs. HCV not different, alcohol vs. HCV OR 0.19, 95 % CI 0.05, 0.63) were associated with fibromyalgia symptoms. If abdominal pain was included in the model, etiology became nonsignificant, indicating that it may be central sensitization due to abdominal pain in patients with chronic liver disease that explains fibromyalgia symptoms rather than the etiology of liver disease or inflammation. Conclusions Fibromyalgia symptoms were significantly associated with HCV and NASH cirrhosis and with psychiatric symptoms. Future work should focus on the underlying pathophysiology and management of widespread pain in patients with cirrhosis. C1 [Rogal, Shari S.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. [Rogal, Shari S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Bielefeldt, Klaus] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Wasan, Ajay D.] Univ Pittsburgh, Dept Anesthesia, Pittsburgh, PA USA. [Szigethy, Eva; Lotrich, Francis; DiMartini, Andrea F.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RP Rogal, SS (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Univ Dr 151C, Pittsburgh, PA 15240 USA. EM rogalss@upmc.edu; bielefeldtk@upmc.edu; wasanad@upmc.edu; szigetheye@upmc.edu; lotrichfe@upmc.edu; dimartiniaf@upmc.edu FU Starzl Transplantation Institute Young Investigator Award, NIH [T32-DK063922] FX We would like to thank Amy Schmotzer and Sharon Boggiano for their help with this project. This project was supported by the Starzl Transplantation Institute Young Investigator Award, NIH grant T32-DK063922. NR 48 TC 1 Z9 2 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2015 VL 60 IS 5 BP 1482 EP 1489 DI 10.1007/s10620-014-3453-3 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CJ5YN UT WOS:000355570200048 PM 25433921 ER PT J AU Biagioli, M Ferrari, F Mendenhall, EM Zhang, YJ Erdin, S Vijayvargia, R Vallabh, SM Solomos, N Manavalan, P Ragavendran, A Ozsolak, F Lee, JM Talkowski, ME Gusella, JF Macdonald, ME Park, PJ Seong, IS AF Biagioli, Marta Ferrari, Francesco Mendenhall, Eric M. Zhang, Yijing Erdin, Serkan Vijayvargia, Ravi Vallabh, Sonia M. Solomos, Nicole Manavalan, Poornima Ragavendran, Ashok Ozsolak, Fatih Lee, Jong Min Talkowski, Michael E. Gusella, James F. Macdonald, Marcy E. Park, Peter J. Seong, Ihn Sik TI Htt CAG repeat expansion confers pleiotropic gains of mutant huntingtin function in chromatin regulation SO HUMAN MOLECULAR GENETICS LA English DT Article ID EMBRYONIC STEM-CELLS; DISEASE GENE HOMOLOG; REPRESSIVE COMPLEX 2; KNOCK-IN MOUSE; METHYLTRANSFERASE ACTIVITY; TRINUCLEOTIDE REPEAT; DIFFERENTIATION; NEURONS; MICE; HD AB The CAG repeat expansion in the Huntington's disease gene HTT extends a polyglutamine tract in mutant huntingtin that enhances its ability to facilitate polycomb repressive complex 2 (PRC2). To gain insight into this dominant gain of function, we mapped histone modifications genome-wide across an isogenic panel of mouse embryonic stem cell (ESC) and neuronal progenitor cell (NPC) lines, comparing the effects of Htt null and different size Htt CAG mutations. We found that Htt is required in ESC for the proper deposition of histone H3K27me3 at a subset of 'bivalent' loci but in NPC it is needed at 'bivalent' loci for both the proper maintenance and the appropriate removal of this mark. In contrast, Htt CAG size, though changing histone H3K27me3, is prominently associated with altered histone H3K4me3 at 'active' loci. The sets of ESC and NPC genes with altered histone marks delineated by the lack of huntingtin or the presence of mutant huntingtin, though distinct, are enriched in similar pathways with apoptosis specifically highlighted for the CAG mutation. Thus, the manner by which huntingtin function facilitates PRC2 may afford mutant huntingtin with multiple opportunities to impinge upon the broader machinery that orchestrates developmentally appropriate chromatin status. C1 [Biagioli, Marta; Zhang, Yijing; Erdin, Serkan; Vijayvargia, Ravi; Vallabh, Sonia M.; Solomos, Nicole; Manavalan, Poornima; Ragavendran, Ashok; Lee, Jong Min; Talkowski, Michael E.; Gusella, James F.; Macdonald, Marcy E.; Seong, Ihn Sik] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Biagioli, Marta; Vijayvargia, Ravi; Lee, Jong Min; Macdonald, Marcy E.; Seong, Ihn Sik] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Ferrari, Francesco; Park, Peter J.] Ctr Biomed Informat, Boston, MA 02114 USA. [Mendenhall, Eric M.] Univ Alabama, Huntsville, AL 35805 USA. [Ozsolak, Fatih] RaNA Therapeut, Cambridge, MA 02139 USA. [Talkowski, Michael E.; Gusella, James F.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Gusella, James F.; Macdonald, Marcy E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Park, Peter J.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. RP Seong, IS (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM iseong@mgh.harvard.edu RI Erdin, Serkan/B-4988-2008; Ferrari, Francesco/H-5007-2012; OI Erdin, Serkan/0000-0001-6587-2625; Ferrari, Francesco/0000-0002-9811-3753; Mendenhall, Eric/0000-0002-7395-6295 FU CHDI Foundation Inc.; Huntington's Society of Canada; National Institutes of Health/National Institute of Neurological Disorders and Stroke [R01 NS32765, R01 NS079651] FX This work was supported by CHDI Foundation Inc.; and the Huntington's Society of Canada; and National Institutes of Health/National Institute of Neurological Disorders and Stroke (R01 NS32765 to M.E.M., R01 NS079651 to I.S.S.). NR 55 TC 12 Z9 12 U1 0 U2 10 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 MAY 1 PY 2015 VL 24 IS 9 BP 2442 EP 2457 DI 10.1093/hmg/ddv006 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CJ2OX UT WOS:000355325400003 PM 25574027 ER PT J AU Patel, MS Volpp, KG AF Patel, Mitesh S. Volpp, Kevin G. TI Nudging Students Toward Healthier Food Choices-Applying Insights From Behavioral Economics SO JAMA PEDIATRICS LA English DT Editorial Material ID CONSUMPTION; SCHOOL; ARCHITECTURE; INTERVENTION; ADOLESCENTS; CHILDREN; IMPACT; CHEF C1 [Patel, Mitesh S.; Volpp, Kevin G.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Patel, Mitesh S.; Volpp, Kevin G.] Univ Penn, Ctr Hlth Incent & Behav Econ, Leonard Davis Inst, Philadelphia, PA 19104 USA. [Patel, Mitesh S.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Patel, Mitesh S.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. RP Patel, MS (reprint author), Univ Penn, Philadelphia Vet Affairs Med Ctr, 423 Guardian Dr,13th Floor Blockley Hall, Philadelphia, PA 19104 USA. EM mpatel@upenn.edu NR 25 TC 0 Z9 0 U1 12 U2 39 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 MAY PY 2015 VL 169 IS 5 BP 425 EP 426 DI 10.1001/jamapediatrics.2015.0217 PG 2 WC Pediatrics SC Pediatrics GA CJ8EX UT WOS:000355734000008 PM 25798795 ER PT J AU Cohen, JFW Richardson, SA Cluggish, SA Parker, E Catalano, PJ Rimm, EB AF Cohen, Juliana F. W. Richardson, Scott A. Cluggish, Sarah A. Parker, Ellen Catalano, Paul J. Rimm, Eric B. TI Effects of Choice Architecture and Chef-Enhanced Meals on the Selection and Consumption of Healthier School Foods A Randomized Clinical Trial SO JAMA PEDIATRICS LA English DT Article ID PLATE WASTE; CHILDREN; LUNCHES AB IMPORTANCE Little is known about the long-term effect of a chef-enhanced menu on healthier food selection and consumption in school lunchrooms. In addition, it remains unclear if extended exposure to other strategies to promote healthier foods (eg, choice architecture) also improves food selection or consumption. OBJECTIVE To evaluate the short-and long-term effects of chef-enhanced meals and extended exposure to choice architecture on healthier school food selection and consumption. DESIGN, SETTING, AND PARTICIPANTS A school-based randomized clinical trial was conducted during the 2011-2012 school year among 14 elementary and middle schools in 2 urban, low-income school districts (intent-to-treat analysis). Included in the study were 2638 students in grades 3 through 8 attending participating schools (38.4% of eligible participants). INTERVENTIONS Schools were first randomized to receive a professional chef to improve school meal palatability (chef schools) or to a delayed intervention (control group). To assess the effect of choice architecture (smart cafe), all schools after 3 months were then randomized to the smart cafe intervention or to the control group. MAIN OUTCOMES AND MEASURES School food selection was recorded, and consumption was measured using plate waste methods. RESULTS After 3 months, vegetable selection increased in chef vs control schools (odds ratio [OR], 1.75; 95% CI, 1.36-2.24), but there was no effect on the selection of other components or on meal consumption. After long-term or extended exposure to the chef or smart cafe intervention, fruit selection increased in the chef (OR, 3.08; 95% CI, 2.23-4.25), smart cafe (OR, 1.45; 95% CI, 1.13-1.87), and chef plus smart cafe (OR, 3.10; 95% CI, 2.26-4.25) schools compared with the control schools, and consumption increased in the chef schools (OR, 0.17; 95% CI, 0.03-0.30 cups/d). Vegetable selection increased in the chef (OR, 2.54; 95% CI, 1.83-3.54), smart cafe (OR, 1.91; 95% CI, 1.46-2.50), and chef plus smart cafe schools (OR, 7.38, 95% CI, 5.26-10.35) compared with the control schools, and consumption also increased in the chef (OR, 0.16; 95% CI, 0.09-0.22 cups/d) and chef plus smart cafe (OR, 0.13; 95% CI, 0.05-0.19 cups/d) schools; however, the smart cafe intervention alone had no effect on consumption. CONCLUSIONS AND RELEVANCE Schools should consider both collaborating with chefs and using choice architecture to increase fruit and vegetable selection. Efforts to improve the taste of school foods through chef-enhanced meals should remain a priority because this was the only method that also increased consumption. This was observed only after students were repeatedly exposed to the new foods for 7 months. Therefore, schools should not abandon healthier options if they are initially met with resistance. C1 [Cohen, Juliana F. W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Richardson, Scott A.; Cluggish, Sarah A.; Parker, Ellen] Project Bread, Boston, MA USA. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Rimm, Eric B.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Rimm, Eric B.] Harvard Univ, Sch Med, Boston, MA USA. RP Cohen, JFW (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 677 Huntington Ave, Boston, MA 02115 USA. EM jcohen@hsph.harvard.edu FU Arbella Insurance; Nutritional Epidemiology of Cancer Education and Career Development Program [R25 CA 098566] FX This study was funded by a grant from Arbella Insurance. Dr Cohen is supported by grant R25 CA 098566 from the Nutritional Epidemiology of Cancer Education and Career Development Program. NR 17 TC 7 Z9 7 U1 9 U2 26 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 MAY PY 2015 VL 169 IS 5 BP 431 EP 437 DI 10.1001/jamapediatrics.2014.3805 PG 7 WC Pediatrics SC Pediatrics GA CJ8EX UT WOS:000355734000011 PM 25798990 ER PT J AU Thordardottir, EB Valdimarsdottir, UA Hansdottir, I Resnick, H Shipherd, JC Gudmundsdottir, B AF Thordardottir, Edda Bjork Valdimarsdottir, Unnur Anna Hansdottir, Ingunn Resnick, Heidi Shipherd, Jillian C. Gudmundsdottir, Berglind TI Posttraumatic stress and other health consequences of catastrophic avalanches: A 16-year follow-up of survivors SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Disaster; Avalanche; Posttraumatic stress disorder; Mental health; Physical health ID SLEEP QUALITY INDEX; MENTAL-HEALTH; PSYCHOMETRIC PROPERTIES; PHYSICAL SYMPTOMS; SERVICE USE; DISASTER; DISORDER; ANXIETY; DEPRESSION; SAMPLE AB To date, no study has investigated the effects of avalanches on survivor's health beyond the first years. The aim of this study was to examine long-term health status 16 years after exposure to avalanches using a matched cohort design. Mental health, sleep quality and somatic symptoms among avalanche survivors (n = 286) and non-exposed controls (n = 357) were examined. Results showed that 16% of survivors currently experience avalanche-specific PTSD symptoms (PDS score > 14). In addition, survivors presented with increased risk of PTSD hyperarousal symptoms (>85th percentile) (aRR = 1.83; 98.3% CI [1.23-2.74]); sleep-related problems (PSQI score >5) (aRR= 1.34; 95% Cl [1.05-1.70]); PTSD-related sleep disturbances (PSQI-A score >= 4) (aRR= 1.86; 95% CI [1.30-2.67]); musculoskeletal and nervous system problems (aRR 1.43; 99% CI 1.06-1.93) and gastrointestinal problems (aRR 2.16; 99% Cl 1.21-3.86) compared to the unexposed group. Results highlight the need for treatment for long-term PTSD symptoms and sleep disruption in disaster communities. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Thordardottir, Edda Bjork; Valdimarsdottir, Unnur Anna; Gudmundsdottir, Berglind] Univ Iceland, Ctr Publ Hlth Sci, Fac Med, Sch Hlth Sci, IS-101 Reykjavik, Iceland. [Thordardottir, Edda Bjork; Hansdottir, Ingunn; Gudmundsdottir, Berglind] Univ Iceland, Fac Psychol, Sch Hlth Sci, IS-101 Reykjavik, Iceland. [Valdimarsdottir, Unnur Anna] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Resnick, Heidi] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29403 USA. [Shipherd, Jillian C.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Shipherd, Jillian C.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Gudmundsdottir, Berglind] Landspitali Natl Univ Hosp Iceland, Mental Hlth Serv, Reykjavik, Iceland. RP Thordardottir, EB (reprint author), Univ Iceland, Ctr Publ Hlth Sci, Stapi V Hringbraut, IS-101 Reykjavik, Iceland. EM eddat@hi.is RI Hansdottir, Ingunn/A-6735-2012 FU University of Iceland Research Fund; Icelandic Research Fund for Graduate Students (Rannis); Landspitali University Hospital Research Fund FX We would like to thank Harpa Jonsdottir for her help in collecting data and the late Jakob Smari for his invaluable support in initiating and designing this study. This study was funded by the University of Iceland Research Fund, the Icelandic Research Fund for Graduate Students (Rannis) and the Landspitali University Hospital Research Fund. NR 57 TC 5 Z9 5 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD MAY PY 2015 VL 32 BP 103 EP 111 DI 10.1016/j.janxdis.2015.03.005 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CJ7UZ UT WOS:000355707100013 PM 25935315 ER PT J AU Moin, T Ertl, K Schneider, J Vasti, E Makki, F Richardson, C Havens, K Damschroder, L AF Moin, Tannaz Ertl, Kristyn Schneider, Jessica Vasti, Elena Makki, Fatima Richardson, Caroline Havens, Kathryn Damschroder, Laura TI Women Veterans' Experience With a Web-Based Diabetes Prevention Program: A Qualitative Study to Inform Future Practice SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE prediabetic state; disease management; risk reduction behavior; program evaluation; patient satisfaction; attitude to computers; computers; Internet ID LIFE-STYLE INTERVENTIONS; IMPAIRED GLUCOSE-TOLERANCE; FOLLOW-UP; CLINICAL-PRACTICE; RISK-FACTORS; WEIGHT-LOSS; REDUCTION; OUTCOMES; METAANALYSIS; ADHERENCE AB Background: Diabetes prevention is a national goal and particularly important in the Veterans Health Administration (VHA) where 1 in 4 veterans has diabetes. There is growing evidence to support the use of Web-based diabetes prevention program (DPP) interventions, shown to be as effective and often more feasible than in-person interventions. Objective: Our primary objective was to qualitatively explore women veterans' early experiences with a Web-based DPP intervention. Our secondary objective was to estimate weight loss, participation, and engagement to provide context for our qualitative findings. Methods: We conducted and analyzed semistructured interviews and collected data on weight change, participation, and engagement. A total of 17 women veterans with prediabetes from a Midwest VA Women's Health Clinic were eligible to participate; 15 completed interviews. Results: Participants perceived the DPP program as an appealing way of initiating lifestyle changes and made them feel accountable in achieving their daily goals. The online program was convenient because it could be accessed at any time, and many found that it integrated well into daily life. However, some did not like the logging aspect and some found it to be too impersonal. Participants logged in a mean 76 times, posted a mean 46 group messages, and sent a mean 20.5 private messages to the health coach over 16 weeks. Participants lost 5.24% of baseline weight, and 82% (14/17) of participants completed at least 9 of 16 core modules. Conclusions: Women veterans' early experiences with a Web-based DPP intervention were generally positive. Accountability and convenience were key enabling factors for participation and engagement. A Web-based DPP intervention appears to be a promising means of translating the DPP for women veterans with prediabetes. C1 [Moin, Tannaz] VA Greater Los Angeles Healthcare Syst, VA Greater Los Angeles, VA Hlth Serv Res & Dev HSR&D, Ctr Healthcare Innovat Implementat & Policy, Los Angeles, CA 90073 USA. [Moin, Tannaz] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Ertl, Kristyn] Clement J Zablocki VA Med Ctr, Dept Res, Milwaukee, WI USA. [Ertl, Kristyn] Med Coll Wisconsin, Ctr Patient Care & Outcomes Res, Milwaukee, WI 53226 USA. [Schneider, Jessica; Havens, Kathryn] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Schneider, Jessica; Havens, Kathryn] Clement J Zablocki VA Med Ctr, Womens Hlth Clin, Milwaukee, WI USA. [Vasti, Elena] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Makki, Fatima; Damschroder, Laura] VA Ann Arbor Ctr Clin Management Res, Ann Arbor, MI USA. [Richardson, Caroline] Univ Michigan, VA Ann Arbor Ctr Clin Management Res, Dept Family Med, Ann Arbor, MI 48109 USA. RP Moin, T (reprint author), VA Greater Los Angeles Healthcare Syst, VA Greater Los Angeles, VA Hlth Serv Res & Dev HSR&D, Ctr Healthcare Innovat Implementat & Policy, Los Angeles, CA 90073 USA. EM TMoin@mednet.ucla.edu OI Damschroder, Laura/0000-0002-3657-8459 FU VA Health Services Research Development [SDR 13-320]; VA Diabetes QUERI; VA Office of Academic Affiliations through the VA Health Services Research and Development Advanced Fellowship Program [TPM65-010]; VA Greater Los Angeles FX This project would not have been possible without project support from the VA Health Services Research & Development (SDR 13-320) and VA Diabetes QUERI. TM was supported by the VA Office of Academic Affiliations through the VA Health Services Research and Development Advanced Fellowship Program (TPM65-010), VA Greater Los Angeles from 2011-2014. NR 43 TC 4 Z9 4 U1 1 U2 4 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD MAY PY 2015 VL 17 IS 5 AR e127 DI 10.2196/jmir.4332 PG 12 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA CJ5MH UT WOS:000355531200002 PM 26006697 ER PT J AU Vasterling, JJ Proctor, SP Aslan, M Ko, J Jakupcak, M Harte, CB Marx, BP Concato, J AF Vasterling, Jennifer J. Proctor, Susan P. Aslan, Mihaela Ko, John Jakupcak, Matthew Harte, Christopher B. Marx, Brian P. Concato, John TI Military, Demographic, and Psychosocial Predictors of Military Retention in Enlisted Army Soldiers 12 Months After Deployment to Iraq SO MILITARY MEDICINE LA English DT Article ID NATIONAL-GUARD SOLDIERS; HEALTH-CARE UTILIZATION; TRAUMATIC BRAIN-INJURY; MENTAL-HEALTH; US MILITARY; PTSD SYMPTOMS; UNIT COHESION; ATTRITION; AFGHANISTAN; VETERANS AB Objective: To examine military, demographic, and psychosocial predictors of military retention following operational deployment. Methods: Military status 12 months following return from Iraq deployment was assessed via service records in 740 regular active duty Army Soldiers. Potential predictors of military retention were derived from prospectively administered in-person interviews and questionnaires conducted within 3 months following return from Iraq. Results: At 12 months following return from deployment, 18.1% (n = 134) of the sample had separated from military service. Cox proportional hazards analyses, adjusting for demographic, military, and psychosocial predictors, identified several factors that were independently associated with military attrition: less than (vs. equal to or more than) 6 years military experience (hazards ratio [HR], 3.98; 95% CI, 2.12-7.45); unmarried (vs. married) status (HR, 1.51; 95% CI, 1.06-2.16); and lower (vs. higher) levels of self-reported unit support during deployment (HR, 2.22; 95% CI, 1.42-3.47). Conclusions: Service members early in their career may be especially prone to military attrition. With regard to military retention, our findings suggest that it may be particularly important to develop initiatives that target organizational cohesion and support. C1 [Vasterling, Jennifer J.; Harte, Christopher B.; Marx, Brian P.] VA Boston Healthcare Syst, Natl Ctr PTSD & Psychol, Boston, MA 02130 USA. [Vasterling, Jennifer J.; Harte, Christopher B.; Marx, Brian P.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Proctor, Susan P.] US Army Res Inst Environm Med, Natick, MA 01760 USA. [Proctor, Susan P.] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Proctor, Susan P.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02118 USA. [Aslan, Mihaela; Ko, John; Concato, John] VA Connecticut Healthcare Syst, Clin Epidemiol Res Ctr, West Haven, CT 06516 USA. [Aslan, Mihaela] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Jakupcak, Matthew] VA Puget Sound Healthcare Syst, Seattle, WA 98108 USA. [Jakupcak, Matthew] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Vasterling, JJ (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD & Psychol, 150 South Huntington Ave, Boston, MA 02130 USA. FU U.S. Army Medical Research and Materiel Command [DAMD 17-03-0020]; Department of Veterans Affairs Clinical Sciences Research and Development; Clinical Epidemiology Research Center, VA Cooperative Studies Program FX We appreciate the support of the Defense Manpower Data Center in obtaining military service status data. We are also grateful to the Soldiers who comprise the Neurocognition Deployment Health Study cohort for volunteering their time to participate in the study and for their military service more generally. Funding for the collection of primary assessment data was provided by the U.S. Army Medical Research and Materiel Command (DAMD 17-03-0020) and the Department of Veterans Affairs Clinical Sciences Research and Development. Data analyses and collection of secondary data from military administrative records were supported by the Clinical Epidemiology Research Center, VA Cooperative Studies Program. The primary funding organizations had no role in the scientific aspects of the study or the preparation of the manuscript. The manuscript underwent scientific and administrative review within the U.S. Army Research Institute for Environmental Medicine. NR 29 TC 2 Z9 2 U1 1 U2 6 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD MAY PY 2015 VL 180 IS 5 BP 524 EP 532 DI 10.7205/MILMED-D-14-00468 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CJ5WF UT WOS:000355562600016 PM 25939106 ER PT J AU Lambert, J Rodriguez, A Pearcy-Baluyot, M Shahi, SK AF Lambert, Jessica Rodriguez, Alexis Pearcy-Baluyot, Mischelle Shahi, Sanjeet K. TI Chronic Iritis Associated With Cutaneous Leukocytoclastic Vasculitis SO MILITARY MEDICINE LA English DT Article ID SMALL-VESSEL VASCULITIS; MANAGEMENT AB Cutaneous leukocytoclastic vasculitis (LCV) is a systemic condition that can be associated with iritis. LCV is characterized as a small-vessel vasculitis of the cutaneous area. The disease demonstrates purple lesions on the skin due to the destruction of small cutaneous blood vessels. These lesions are palpable and most often coalesce forming larger patches on the surface of the skin. During early stages of LCV, the disease can be undetected due to the infrequency and small size of the skin lesions. As such, the patient might go undiagnosed for years while having symptoms of LCV or iritis of unknown etiology. This article discusses the correlation seen with LCV and iritis. We report a case on a patient that presented to our clinic with a history of bilateral chronic iritis. After extensive laboratory testing, we concluded that the chronicity of her iritis was due to her LCV. The correlation between LCV and iritis was not evident for several years in our patient. We also discuss the correlation with systemic Sjogren's syndrome and LVC and how these two separate diseases are linked in many patients. We will illustrate the importance of serological testing, imaging, and skin lesion biopsy for the diagnosis of LCV. C1 [Lambert, Jessica; Rodriguez, Alexis; Pearcy-Baluyot, Mischelle] US Dept Vet Affairs, Malcom Randall VAMC, VA Optometry Clin, Gainesville, FL 32607 USA. [Shahi, Sanjeet K.] US Dept Vet Affairs, Ocala Community Based Outpatient Clin, Ocala, FL 34471 USA. RP Lambert, J (reprint author), US Dept Vet Affairs, Malcom Randall VAMC, VA Optometry Clin, 5533 SW 64th St, Gainesville, FL 32607 USA. NR 21 TC 0 Z9 0 U1 0 U2 2 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD MAY PY 2015 VL 180 IS 5 BP E622 EP E625 DI 10.7205/MILMED-D-14-00287 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CJ5WF UT WOS:000355562600007 PM 25939124 ER PT J AU Ahmad, OS Morris, JA Mujammami, M Forgetta, V Leong, A Li, R Turgeon, M Greenwood, CMT Thanassoulis, G Meigs, JB Sladek, R Richards, JB AF Ahmad, Omar S. Morris, John A. Mujammami, Muhammad Forgetta, Vincenzo Leong, Aaron Li, Rui Turgeon, Maxime Greenwood, Celia M. T. Thanassoulis, George Meigs, James B. Sladek, Robert Richards, J. Brent TI A Mendelian randomization study of the effect of type-2 diabetes on coronary heart disease SO NATURE COMMUNICATIONS LA English DT Article ID SCALE ASSOCIATION ANALYSIS; MULTIPLE GENETIC-VARIANTS; ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; INSTRUMENTAL VARIABLES; MYOCARDIAL-INFARCTION; SUSCEPTIBILITY LOCI; INSULIN-RESISTANCE; ADIPONECTIN LEVELS AB In observational studies, type-2 diabetes (T2D) is associated with an increased risk of coronary heart disease (CHD), yet interventional trials have shown no clear effect of glucose-lowering on CHD. Confounding may have therefore influenced these observational estimates. Here we use Mendelian randomization to obtain unconfounded estimates of the influence of T2D and fasting glucose (FG) on CHD risk. Using multiple genetic variants associated with T2D and FG, we find that risk of T2D increases CHD risk (odds ratio (OR) = 1.11 (1.05-1.17), per unit increase in odds of T2D, P = 8.8 x 10(-5); using data from 34,840/114,981 T2D cases/controls and 63,746/130,681 CHD cases/controls). FG in non-diabetic individuals tends to increase CHD risk (OR = 1.15 (1.00-1.32), per mmol . per l, P = 0.05; 133,010 non-diabetic individuals and 63,746/130,681 CHD cases/controls). These findings provide evidence supporting a causal relationship between T2D and CHD and suggest that long-term trials may be required to discern the effects of T2D therapies on CHD risk . C1 [Ahmad, Omar S.; Morris, John A.; Mujammami, Muhammad; Forgetta, Vincenzo; Li, Rui; Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Ctr Clin Epidemiol, Montreal, PQ H3A 0G4, Canada. [Ahmad, Omar S.; Mujammami, Muhammad; Forgetta, Vincenzo; Li, Rui; Thanassoulis, George; Sladek, Robert; Richards, J. Brent] McGill Univ, Dept Med, Montreal, PQ H3A 0G4, Canada. [Morris, John A.; Li, Rui; Thanassoulis, George; Sladek, Robert; Richards, J. Brent] McGill Univ, Dept Human Genet, Montreal, PQ H3A 0G4, Canada. [Leong, Aaron; Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Internal Med, Boston, MA 02115 USA. [Leong, Aaron; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Turgeon, Maxime; Greenwood, Celia M. T.] McGill Univ, Dept Oncol Epidemiol Biostat & Occupat Hlth & Hum, Montreal, PQ H3A 0G4, Canada. [Richards, J. Brent] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England. RP Richards, JB (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Ctr Clin Epidemiol, Montreal, PQ H3A 0G4, Canada. EM brent.richards@mcgill.ca OI Turgeon, Maxime/0000-0003-4863-6035; Forgetta, Vincenzo/0000-0002-6061-4720; Morris, John/0000-0003-2769-8202 FU NIH [K24 DK080140]; CIHR; FRSQ; CF; Lady Davis Institute FX We wish to thank the CARDIOGRAMplusC4D, DIAGRAM and MAGIC consortia for access to their data. J.B.M. is supported by the NIH Grant: K24 DK080140. J.B.R. is supported by the CIHR, FRSQ, CF and the Lady Davis Institute. NR 58 TC 15 Z9 15 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAY PY 2015 VL 6 AR 7060 DI 10.1038/ncomms8060 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ5ME UT WOS:000355530900011 PM 26017687 ER PT J AU Barzel, B Liu, YY Barabasi, AL AF Barzel, Baruch Liu, Yang-Yu Barabasi, Albert-Laszlo TI Constructing minimal models for complex system dynamics SO NATURE COMMUNICATIONS LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; REGULATORY NETWORKS; PHYSICS AB One of the strengths of statistical physics is the ability to reduce macroscopic observations into microscopic models, offering a mechanistic description of a system's dynamics. This paradigm, rooted in Boltzmann's gas theory, has found applications from magnetic phenomena to subcellular processes and epidemic spreading. Yet, each of these advances were the result of decades of meticulous model building and validation, which are impossible to replicate in most complex biological, social or technological systems that lack accurate microscopic models. Here we develop a method to infer the microscopic dynamics of a complex system from observations of its response to external perturbations, allowing us to construct the most general class of nonlinear pairwise dynamics that are guaranteed to recover the observed behaviour. The result, which we test against both numerical and empirical data, is an effective dynamic model that can predict the system's behaviour and provide crucial insights into its inner workings. C1 [Barzel, Baruch] Bar Ilan Univ, Dept Math, IL-52900 Ramat Gan, Israel. [Liu, Yang-Yu] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Cent European Univ, Ctr Network Sci, H-1052 Budapest, Hungary. RP Liu, YY (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. EM yyl@channing.harvard.edu FU Templeton Foundation: Mathematical and Physical Sciences [PFI-777]; Army Research Laboratories (ARL) Network Science (NS) Collaborative Technology Alliance (CTA) [ARL NS-CTA W911NF-09-2-0053]; European Union [FP7 317532] FX This work was supported by the Templeton Foundation: Mathematical and Physical Sciences grant no. PFI-777; Army Research Laboratories (ARL) Network Science (NS) Collaborative Technology Alliance (CTA) grant: ARL NS-CTA W911NF-09-2-0053; European Union grant no. FP7 317532 (MULTIPLEX). NR 46 TC 8 Z9 8 U1 2 U2 37 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 MAY PY 2015 VL 6 AR 7186 DI 10.1038/ncomms8186 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ5OI UT WOS:000355536900005 PM 25990707 ER PT J AU Beliveau, BJ Boettiger, AN Avendano, MS Jungmann, R McCole, RB Joyce, EF Kim-Kiselak, C Bantignies, F Fonseka, CY Erceg, J Hannan, MA Hoang, HG Colognori, D Lee, JT Shih, WM Yin, P Zhuang, XW Wu, CT AF Beliveau, Brian J. Boettiger, Alistair N. Avendano, Maier S. Jungmann, Ralf McCole, Ruth B. Joyce, Eric F. Kim-Kiselak, Caroline Bantignies, Frederic Fonseka, Chamith Y. Erceg, Jelena Hannan, Mohammed A. Hoang, Hien G. Colognori, David Lee, Jeannie T. Shih, William M. Yin, Peng Zhuang, Xiaowei Wu, Chao-ting TI Single-molecule super-resolution imaging of chromosomes and in situ haplotype visualization using Oligopaint FISH probes SO NATURE COMMUNICATIONS LA English DT Article ID STRUCTURED-ILLUMINATION MICROSCOPY; ALLELE-SPECIFIC DETECTION; OLIGONUCLEOTIDE PROBES; NUCLEAR ARCHITECTURE; BITHORAX COMPLEX; PADLOCK PROBES; REVEALS; HYBRIDIZATION; RESOLUTION; DYNAMICS AB Fluorescence in situ hybridization (FISH) is a powerful single-cell technique for studying nuclear structure and organization. Here we report two advances in FISH-based imaging. We first describe the in situ visualization of single-copy regions of the genome using two single-molecule super-resolution methodologies. We then introduce a robust and reliable system that harnesses single-nucleotide polymorphisms (SNPs) to visually distinguish the maternal and paternal homologous chromosomes in mammalian and insect systems. Both of these new technologies are enabled by renewable, bioinformatically designed, oligonucleotide-based Oligopaint probes, which we augment with a strategy that uses secondary oligonucleotides (oligos) to produce and enhance fluorescent signals. These advances should substantially expand the capability to query parent-of-origin-specific chromosome positioning and gene expression on a cell-by-cell basis. C1 [Beliveau, Brian J.; McCole, Ruth B.; Joyce, Eric F.; Kim-Kiselak, Caroline; Bantignies, Frederic; Fonseka, Chamith Y.; Erceg, Jelena; Hannan, Mohammed A.; Hoang, Hien G.; Colognori, David; Lee, Jeannie T.; Wu, Chao-ting] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Boettiger, Alistair N.; Zhuang, Xiaowei] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Boettiger, Alistair N.; Zhuang, Xiaowei] Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Avendano, Maier S.; Jungmann, Ralf; Yin, Peng] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Avendano, Maier S.; Jungmann, Ralf; Yin, Peng] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Bantignies, Frederic] CNRS, UPR 1142, Inst Genet Humaine, F-34396 Montpellier, France. [Colognori, David; Lee, Jeannie T.] Howard Hughes Med Inst, Boston, MA 02114 USA. [Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Zhuang, Xiaowei] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. RP Wu, CT (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM twu@genetics.med.harvard.edu OI Avendano, Mauricio/0000-0002-7295-2911 FU NIH/NIGMS [RO1GM61936, 5DP1GM106412]; Harvard Medical School (HMS); NIH/NCI [F32CA157188]; Centre National de la Recherche Scientifique; Fulbright Visiting Scholar Program; NIH [1DP2OD007292, 1R01EB018659, 5R21HD072481, 1DP2OD004641, RO1-GM090278]; HHMI; Damon Runyon Cancer Research Foundation; ONR [N000141110914, N000141010827, N000141310593]; NSF [CCF1054898, CCF1162459]; Wyss Institute for Biologically Engineering; Alexander von Humboldt-Foundation FX We thank members of the Wu lab, K. Ahmad, N. Apostolopoulos, L. Cai, M. Cowley, S. Elledge, R. Kingston, D. Moazed, R. Oakey, G. Orsi, T. Schmidt and D. Zhang for helpful discussions; G. Church, B. Harada, P. Huang, S. Kennedy, S. McCarroll, D. Reich, C. Seidman, J. Seidman and F. Winston for discussion, equipment and technical assistance; S. Clewley and J.H. McDonald for computational assistance. Finally, we express belated appreciation to Rachel O'Neill and Judy Brown, who tested our original Oligopaints technology when it was first developed. B.J.B., R.B.M., E.F.J., C.K.-K., F.B., C.Y.F., J.E., M.A.H., H.G.H. and C.-t.W. were supported by awards from NIH/NIGMS (RO1GM61936, 5DP1GM106412) and Harvard Medical School (HMS) to C.-t.W., NIH/NCI (F32CA157188) to E.F.J., HMS to C.K.-K., and the Centre National de la Recherche Scientifique and the Fulbright Visiting Scholar Program to F.B. A.N.B. and X.Z. were supported by awards from the NIH and HHMI to X.Z. and the Damon Runyon Cancer Research Foundation to A.N.B. R.J., M.S.A. and P.Y. were supported by awards from NIH (1DP2OD007292, 1R01EB018659, 5R21HD072481), ONR (N000141110914, N000141010827, N000141310593), and NSF (CCF1054898, CCF1162459) to P.Y. R.J. and W.M.S. were supported by an award from NIH (1DP2OD004641) to W.M.S. P.Y. and W.M.S. were also supported by the Wyss Institute for Biologically Engineering. R.J. and M.S.A. were also supported by the Alexander von Humboldt-Foundation and the HHMI, respectively. D.C. and J.T.L. were supported by an NIH grant, RO1-GM090278 and the HHMI. NR 67 TC 22 Z9 24 U1 12 U2 83 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 MAY PY 2015 VL 6 AR 7147 DI 10.1038/ncomms8147 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ5ND UT WOS:000355533700006 PM 25962338 ER PT J AU Lai, CP Kim, EY Badr, CE Weissleder, R Mempel, TR Tannous, BA Breakefield, XO AF Lai, Charles P. Kim, Edward Y. Badr, Christian E. Weissleder, Ralph Mempel, Thorsten R. Tannous, Bakhos A. Breakefield, Xandra O. TI Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters SO NATURE COMMUNICATIONS LA English DT Article ID ANTIGEN-PRESENTING CELLS; IN-VIVO; MEMBRANE-VESICLES; CANCER-THERAPY; MESSENGER-RNA; EXOSOMES; ENDOCYTOSIS; MICROVESICLES; LOCALIZATION; PROTEINS AB Accurate spatiotemporal assessment of extracellular vesicle (EV) delivery and cargo RNA translation requires specific and robust live-cell imaging technologies. Here we engineer optical reporters to label multiple EV populations for visualization and tracking of tumour EV release, uptake and exchange between cell populations both in culture and in vivo. Enhanced green fluorescence protein (EGFP) and tandem dimer Tomato (tdTomato) were fused at NH2-termini with a palmitoylation signal (PalmGFP, PalmtdTomato) for EV membrane labelling. To monitor EV-RNA cargo, transcripts encoding PalmtdTomato were tagged with MS2 RNA binding sequences and detected by co-expression of bacteriophage MS2 coat protein fused with EGFP. By multiplexing fluorescent and bioluminescent EV membrane reporters, we reveal the rapid dynamics of both EV uptake and translation of EV-delivered cargo mRNAs in cancer cells that occurred within 1-hour post-horizontal transfer between cells. These studies confirm that EV-mediated communication is dynamic and multidirectional between cells with delivery of functional mRNA. C1 [Lai, Charles P.; Badr, Christian E.; Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol & Radiol, Charlestown, MA 02129 USA. [Lai, Charles P.; Badr, Christian E.; Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Program Neurosci, Sch Med, Charlestown, MA 02129 USA. [Kim, Edward Y.; Mempel, Thorsten R.] Harvard Univ, Ctr Immunol & Inflammatory Dis, Sch Med, Charlestown, MA 02129 USA. [Kim, Edward Y.; Mempel, Thorsten R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Charlestown, MA 02129 USA. [Kim, Edward Y.; Mempel, Thorsten R.] Harvard Univ, Program Immunol, Sch Med, Charlestown, MA 02129 USA. [Weissleder, Ralph] Harvard Univ, Ctr Syst Biol, Sch Med, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Weissleder, Ralph] Harvard Univ, Dept Syst Biol, Sch Med, Charlestown, MA 02129 USA. RP Lai, CP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol & Radiol, 149 13th St, Charlestown, MA 02129 USA. EM drcplai@gmail.com; breakefield@hms.harvard.edu RI Lai, Charles/D-5442-2017 FU NIH [CA069246, 1S10RR023440-01A1]; NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH [U19CA179563]; Voices Against Brain Cancer; Canadian Institutes of Health Research (CIHR); NIH/NINDS [P30NS045776]; [CA150975]; [CA179563]; [AI073457] FX This work was supported by NIH grants CA069246 (X.O.B., B.A.T. and R.W.), U19CA179563 (supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director; X.O.B. and T.R.M.), Voices Against Brain Cancer (X.O.B. and C.P.L.), and CA150975, CA179563, and AI073457 (T.R.M.). C.P.L was supported by the Canadian Institutes of Health Research (CIHR). We also thank D. Morse and K. Conway for the production of lentivirus at the MGH Vector Core, Charlestown, MA, USA supported by NIH/NINDS P30NS045776 (X.O.B. and B.A.T.); I. Armata, K.E. van der Vos and O. Mardini for technical assistance; M. Ericsson for electron microscopy (Conventional Electron Microscopy Core, Harvard Medical School, Boston, MA); T. Diefenbach for microscope assistance (Ragon Institute Microscopy Core, Cambridge, MA, USA); and R. Mylvaganam and C. Luo for flow cytometry assistance (MGH FACS Core, Charlestown, MA, USA supported by NIH 1S10RR023440-01A1). NR 64 TC 40 Z9 40 U1 14 U2 56 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 MAY PY 2015 VL 6 AR 7029 DI 10.1038/ncomms8029 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ5LX UT WOS:000355530100003 PM 25967391 ER PT J AU O-Sullivan, I Zhang, WW Wasserman, DH Liew, CW Liu, J Paik, J DePinho, RA Stolz, DB Kahn, CR Schwartz, MW Unterman, TG AF O-Sullivan, Insug Zhang, Wenwei Wasserman, David H. Liew, Chong Wee Liu, Jonathan Paik, Jihye DePinho, Ronald A. Stolz, Donna Beer Kahn, C. Ronald Schwartz, Michael W. Unterman, Terry G. TI FoxO1 integrates direct and indirect effects of insulin on hepatic glucose production and glucose utilization SO NATURE COMMUNICATIONS LA English DT Article ID PYRUVATE-DEHYDROGENASE KINASE; FORKHEAD TRANSCRIPTION FACTOR; METABOLISM IN-VIVO; GENE-EXPRESSION; B-ALPHA; LIVER; MICE; INACTIVATION; HOMEOSTASIS; STARVATION AB FoxO proteins are major targets of insulin action. To better define the role of FoxO1 in mediating insulin effects in the liver, we generated liver-specific insulin receptor knockout (LIRKO) and IR/FoxO1 double knockout (LIRFKO) mice. Here we show that LIRKO mice are severely insulin resistant based on glucose, insulin and C-peptide levels, and glucose and insulin tolerance tests, and genetic deletion of hepatic FoxO1 reverses these effects. C-13-glucose and insulin clamp studies indicate that regulation of both hepatic glucose production (HGP) and glucose utilization is impaired in LIRKO mice, and these defects are also restored in LIRFKO mice corresponding to changes in gene expression. We conclude that (1) inhibition of FoxO1 is critical for both direct (hepatic) and indirect effects of insulin on HGP and utilization, and (2) extrahepatic effects of insulin are sufficient to maintain normal whole-body and hepatic glucose metabolism when liver FoxO1 activity is disrupted. C1 [O-Sullivan, Insug; Zhang, Wenwei; Liu, Jonathan; Unterman, Terry G.] Univ Illinois, Coll Med, Dept Med, Sect Endocrinol Diabet & Metab, Chicago, IL 60612 USA. [Wasserman, David H.] Vanderbilt Univ Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Liew, Chong Wee] Univ Illinois, Coll Med, Dept Physiol & Biophys, Chicago, IL 60612 USA. [Paik, Jihye; DePinho, Ronald A.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Stolz, Donna Beer] Univ Pittsburgh, Ctr Biol Imaging, Dept Cell Biol, Pittsburgh, PA 15261 USA. [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Schwartz, Michael W.] Univ Washington, Diabet & Obes Ctr Excellence, Seattle, WA 98104 USA. [Unterman, Terry G.] Jesse Brown VA Med Ctr, Med Serv, Chicago, IL 60612 USA. RP Unterman, TG (reprint author), Univ Illinois, Coll Med, Dept Med, Sect Endocrinol Diabet & Metab, Chicago, IL 60612 USA. EM unterman@uic.edu FU Department of Veterans Affairs Merit Review Program; Novo Nordisk Research Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [R00DK090210, DK068384, DK083042, DK090320, DK101997]; University of Washington Nutrition Obesity Research Center [DK035816]; Priority Research Centers Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2010-0029692] FX We gratefully acknowledge the Vanderbilt University Mouse Metabolic Phenotyping Center (DK059637) for the performance of insulin clamp studies, and the Yale University Mouse Metabolic Phenotyping Center (DK076169) for the analysis of liver glycogen content, the University of Michigan Metabolomics Core (R24DK097153), the University of Illinois Functional Genomics Center for the performance of gene array studies, Jenny Drnevich Zadeh for the analysis of gene array studies and Jacob Bar-Tana for helpful discussions. This work was supported in part by research grants from the Department of Veterans Affairs Merit Review Program (T.G.U.), Novo Nordisk Research Foundation (T.G.U.), the National Institute of Diabetes and Digestive and Kidney Diseases Grant Nos. R00DK090210 (to C.W.L.), DK068384, DK083042, DK090320, DK101997 (to M.W.S.) and the University of Washington Nutrition Obesity Research Center (DK035816). I.O.-S. was supported in part by the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0029692). NR 32 TC 14 Z9 14 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAY PY 2015 VL 6 AR 7079 DI 10.1038/ncomms8079 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ5MJ UT WOS:000355531400005 PM 25963540 ER PT J AU Shao, HL Chung, J Lee, K Balaj, L Min, C Carter, BS Hochberg, FH Breakefield, XO Lee, H Weissleder, R AF Shao, Huilin Chung, Jaehoon Lee, Kyungheon Balaj, Leonora Min, Changwook Carter, Bob S. Hochberg, Fred H. Breakefield, Xandra O. Lee, Hakho Weissleder, Ralph TI Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma SO NATURE COMMUNICATIONS LA English DT Article ID MOLECULAR MARKER; MICROVESICLES; EXPRESSION; MULTIFORME; GLIOMA; CELLS; TEMOZOLOMIDE; BIOMARKERS; CISPLATIN; PROTEINS AB Real-time monitoring of drug efficacy in glioblastoma multiforme (GBM) is a major clinical problem as serial re-biopsy of primary tumours is often not a clinical option. MGMT (O-6-methylguanine DNA methyltransferase) and APNG (alkylpurine-DNA-N-glycosylase) are key enzymes capable of repairing temozolomide-induced DNA damages and their levels in tissue are inversely related to treatment efficacy. Yet, serial clinical analysis remains difficult, and, when done, primarily relies on promoter methylation studies of tumour biopsy material at the time of initial surgery. Here we present a microfluidic chip to analyse mRNA levels of MGMT and APNG in enriched tumour exosomes obtained from blood. We show that exosomal mRNA levels of these enzymes correlate well with levels found in parental cells and that levels change considerably during treatment of seven patients. We propose that if validated on a larger cohort of patients, the method may be used to predict drug response in GBM patients. C1 [Shao, Huilin; Chung, Jaehoon; Lee, Kyungheon; Min, Changwook; Lee, Hakho; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Balaj, Leonora; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Balaj, Leonora; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Carter, Bob S.; Hochberg, Fred H.] Univ Calif San Diego, Sch Med, Div Neurol Surg, San Diego, CA 92103 USA. [Hochberg, Fred H.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Breakefield, Xandra O.; Lee, Hakho; Weissleder, Ralph] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Shao, HL (reprint author), Agcy Sci Technol & Res, Inst Mol & Cell Biol, 61 Biopolis Dr, Singapore 138673, Singapore. EM hlee@mgh.harvard.edu; rweissleder@mgh.harvard.edu FU NIH grants [R01 HL113156, P01 CA069246, U54 CA151884]; DoD OCRP Award [W81XWH-14-1-0279]; NIH/NCI grants through the NIH Common Fund, the Office of Strategic Coordination/Office of the NIH Director [P01 CA069246, U19 CA179563] FX We thank Y. Iwamoto (Massachusetts General Hospital, MGH) for expert histology, S. Sivaraman (MGH) for assistance with clinical sample collection, and M. Pittet (MGH), T. Chan (Memorial Sloan-Kettering Cancer Center) and A. Charest (Tufts University) for providing GBM cell lines. This work was supported in parts by NIH grants R01 HL113156 (H.L.), P01 CA069246 (R.W.), U54 CA151884 (R.W.), and DoD OCRP Award W81XWH-14-1-0279 (H.L.). X.O.B. is supported by NIH/NCI grants-P01 CA069246 and U19 CA179563 through the NIH Common Fund, the Office of Strategic Coordination/Office of the NIH Director. NR 35 TC 37 Z9 37 U1 22 U2 85 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 MAY PY 2015 VL 6 AR 6999 DI 10.1038/ncomms7999 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ5LO UT WOS:000355529100002 PM 25959588 ER PT J AU Chao, LDL Zhang, Y Buckley, S AF Chao, Linda L. Zhang, Yu Buckley, Shannon TI Effects of low-level sarin and cyclosarin exposure on white matter integrity in Gulf War Veterans SO NEUROTOXICOLOGY LA English DT Article DE Diffusion tensor imaging; White matter; Sarin; Cyclosarin; Gulf War veterans ID DIFFUSION-TENSOR MRI; TRAUMATIC BRAIN-INJURY; US ARMY VETERANS; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; RADIAL DIFFUSIVITY; AXONAL INJURY; DEGENERATION; SCLEROSIS; RECOVERY AB Background: We previously found evidence of reduced gray and white matter volume in Gulf War (GW) veterans with predicted low-level exposure to sarin (GB) and cyclosarin (GF). Because loss of white matter tissue integrity has been linked to both gray and white matter atrophy, the current study sought to test the hypothesis that GW veterans with predicted GB/CF exposure have evidence of disrupted white matter microstructural integrity. Methods: Measures of fractional anisotropy and directional (i.e., axial and radial) diffusivity were assessed from the 4 T diffusion tensor images (DTI) of 59 GW veterans with predicted GB/CF exposure and 59 "matched" unexposed GW veterans (mean age: 48 +/- 7 years). The DTI data were analyzed using regions of interest (ROI) analyses that accounted for age, sex, total brain gray and white matter volume, trauma exposure, posttraumatic stress disorder, current major depression, and chronic multisymptom illness status. Results: There were no significant group differences in fractional anisotropy or radial diffusivity. However, there was increased axial diffusivity in GW veterans with predicted GB/GF exposure compared to matched, unexposed veterans throughout the brain, including the temporal stem, corona radiata, superior and inferior (hippocampal) cingulum, inferior and superior fronto-occipital fasciculus, internal and external capsule, and superficial cortical white matter blades. Post hoc analysis revealed significant correlations between higher fractional anisotropy and lower radial diffusivity with better neurobehavioral performance in unexposed GW veterans. In contrast, only increased axial diffusivity in posterior limb of the internal capsule was associated with better psychomotor function in GW veterans with predicted GB/CF exposure. Conclusions: The finding that increased axial diffusivity in a region of the brain that contains descending corticospinal fibers was associated with better psychomotor function and the lack of significant neurobehavioral deficits in veterans with predicted GB/CF exposure hint at the possibility that the widespread increases in axial diffusivity that we observed in GW veterans with predicted GB/GF exposure relative to unexposed controls may reflect white matter reorganization after brain injury (i.e., exposure to GB/GF). Published by Elsevier Inc. C1 [Chao, Linda L.; Zhang, Yu; Buckley, Shannon] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Chao, Linda L.; Zhang, Yu] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Chao, Linda L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Chao, LDL (reprint author), 4150 Clement St,114M, San Francisco, CA 94121 USA. EM linda.chao@ucsf.edu FU Department of Defense [DAMD17-01-1-0764]; US Army Medical Research and Materiel Command; Department of Veterans Affairs VA GWI [B3776]; VA grant [I01BX007080] FX The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the Army, Department of Defense, or Department of Veterans Affairs. This study also supported by Department of Defense grant DAMD17-01-1-0764 entitled 'Magnetic Resonance and Spectroscopy of the Human Brain in Gulf War Illness,' awarded to the Northern California Institute for Research and Education from the Department of Defense Gulf War Illnesses Research Program, US Army Medical Research and Materiel Command and a Department of Veterans Affairs grant VA GWI No. B3776 entitled 'Effects of Gulf War Illness on Brain Structure Function and Metabolism: MRI/MRS at 4 T', and VA grant No. I01BX007080 entitled 'Longitudinal Assessment of Gulf War Veterans with Suspected Sarin Exposure.' This material is the result of work supported with resources and the use of facilities at the San Francisco Veterans Affairs Medical Center. The authors would like to thank Dr. Michael Weiner for his support and the Gulf War veterans who participated in these studies. NR 57 TC 3 Z9 3 U1 5 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X EI 1872-9711 J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAY PY 2015 VL 48 BP 239 EP 248 DI 10.1016/j.neuro.2015.04.005 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA CJ6YR UT WOS:000355641600026 PM 25929683 ER PT J AU Singh, V Trescot, A Nishio, I AF Singh, Virtaj Trescot, Andrea Nishio, Isuta TI Injections for Chronic Pain SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA LA English DT Article DE Chronic pain; Regenerative injections; Trigger point injections; Botulinum toxins ID LOW-BACK-PAIN; MYOFASCIAL TRIGGER POINT; FIBRO-OSSEOUS PROLIFERATION; DEXTROSE PROLOTHERAPY; LATERAL EPICONDYLOSIS; ACUPUNCTURE ANALGESIA; PIRIFORMIS SYNDROME; SCLEROSING AGENT; META-ANALYSIS; THERAPY AB Although interventional procedures should be used cautiously in the setting of chronic pain, there is a role for a variety of injections to facilitate a patient's overall rehabilitation program. There are many resources available, including a prior issue of Physical Medicine and Rehabilitation Clinics of North America, which discuss the more conventional spinal injections. The focus of this article is on lesser-known injection options for treating chronic pain. The authors separately discuss trigger point injections, regenerative injections (prolotherapy), and injections using botulin toxins. C1 [Singh, Virtaj] Univ Washington, Seattle Spine & Sports Med, Dept Rehabil Med, Seattle, WA 98102 USA. [Trescot, Andrea] Pain & Headache Ctr, Wasilla, AK 99654 USA. [Nishio, Isuta] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Anesthesiol & Pain Med, Seattle, WA 98108 USA. RP Singh, V (reprint author), Univ Washington, Seattle Spine & Sports Med, Dept Rehabil Med, 3213 Eastlake Ave East,Suite A, Seattle, WA 98102 USA. EM vsingh@seattlespine.com NR 54 TC 1 Z9 1 U1 2 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1047-9651 EI 1558-1381 J9 PHYS MED REH CLIN N JI Phys. Med. Rehabil. Clin. N. Am. PD MAY PY 2015 VL 26 IS 2 BP 249 EP + DI 10.1016/j.pmr.2015.01.004 PG 14 WC Rehabilitation SC Rehabilitation GA CJ3AV UT WOS:000355356700008 PM 25952063 ER PT J AU Wey, HY Wang, CN Schroeder, FA Logan, J Price, JC Hooker, JM AF Wey, Hsiao-Ying Wang, Changning Schroeder, Frederick A. Logan, Jean Price, Julie C. Hooker, Jacob M. TI Kinetic Analysis and Quantification of [C-11]Martinostat for in Vivo HDAC Imaging of the Brain SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Epigenetic regulation; histone deacetylases; PET; kinetic model; occupancy ID HISTONE DEACETYLASE; EPIGENETIC MECHANISMS; PET; METHYLATION; RADIOLIGANDS; EXTINCTION; PLASTICITY; LIGAND; BABOON; ACID AB Epigenetic mechanisms mediated by histone deacetylases (HDACs) have been implicated in a wide-range of CNS disorders and may offer new therapeutic opportunities. In vivo evaluation of HDAC density and drug occupancy has become possible with [C-11]Martinostat, which exhibits selectivity for a subset of class I/IIb HDAC enzymes. In this study, we characterize the kinetic properties of [C-11]Martinostat in the nonhuman primate (NHP) brain in preparation for human neuroimaging studies. The goal of this work was to determine whether classic compartmental analysis techniques were appropriate and to further determine if arterial plasma is required for future NHP studies. Using an arterial plasma input function, several analysis approaches were evaluated for robust outcome measurements. [C-11]Martinostat showed high baseline distribution volume (V-T) ranging from 29.9 to 54.4 mL/cm(3) in the brain and large changes in occupancy (up to 99%) with a blocking dose approaching full enzyme saturation. An averaged nondisplaceable tissue uptake (V-ND) of 8.6 +/- 3.7 mL/cm(3) suggests high specific binding of [C-11]Martinostat. From a two-tissue compartment model, [C-11]Martinostat exhibits a high K-1 (averaged K-1 of 0.65 mL/cm(3)/min) and a small k(4) (average of 0.0085 min(-1)). Our study supports that [C-11]Martinostat can be used to detect changes in HDAC density and occupancy in vivo and that simplified analysis not using arterial blood could be appropriate. C1 [Wey, Hsiao-Ying; Wang, Changning; Schroeder, Frederick A.; Hooker, Jacob M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. [Logan, Jean] NYU, Sch Med, Ctr Biomed Imaging, Dept Radiol, New York, NY 10016 USA. [Price, Julie C.] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA 15213 USA. RP Wey, HY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. EM wey@nmr.mgh.harvard.edu; hooker@nmr.mgh.harvard.edu OI Logan, Jean/0000-0002-6993-9994 FU National Institute of Drug Abuse (NIDA) of the National Institutes of Health [R01DA030321]; Harvard/MGH Nuclear Medicine Training Program from the Department of Energy [DE-SC0008430]; NIDA [K99DA037928] FX This research was supported by the National Institute of Drug Abuse (NIDA) of the National Institutes of Health under Grant Number R01DA030321 (J.M.H.). H.-Y.W. and C.W. were supported by the Harvard/MGH Nuclear Medicine Training Program from the Department of Energy (DE-SC0008430). H.-Y.W. is supported by NIDA K99DA037928. NR 32 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 MAY PY 2015 VL 6 IS 5 BP 708 EP 715 DI 10.1021/acschemneuro.5b00066 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA CI9CE UT WOS:000355067200003 PM 25768025 ER PT J AU Hatcher, JM Zhang, JW Choi, HG Ito, G Alessi, DR Gray, NS AF Hatcher, John M. Zhang, Jinwei Choi, Hwan Geun Ito, Genta Alessi, Dario R. Gray, Nathanael S. TI Discovery of a Pyrrolopyrimidine (JH-II-127), a Highly Potent, Selective, and Brain Penetrant LRRK2 Inhibitor SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE LRRK2; leucine-rich repeat kinase 2; Parkinson's disease; pharmacokinetics ID KINASE 2 LRRK2; PARKINSONS-DISEASE; IN-VIVO AB Activating mutations in leucine-rich repeat kinase 2 (LRRK2) are present in a subset of Parkinson's disease (PD) patients and may represent an attractive therapeutic target. Here we report a 2-anilino-4-methylamino-5-chloropyrrolopyrimidine, JH-II-127 (18), as a potent and selective inhibitor of both wild-type and G2019S mutant LRRK2. Compound 18 substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at a concentration of 0.1-0.3 mu M in a variety of cell types and is capable of inhibiting Ser935 phosphorylation in mouse brain following oral delivery of doses as low as 30 mg/kg. C1 [Hatcher, John M.; Choi, Hwan Geun; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Hatcher, John M.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhang, Jinwei; Ito, Genta; Alessi, Dario R.] Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland. RP Alessi, DR (reprint author), Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat Unit, Dow St, Dundee DD1 5EH, Scotland. EM d.r.alessi@dundee.ac.uk; nathanael_gray@dfci.harvard.edu RI Ito, Genta/L-2581-2015; OI Zhang, Jinwei/0000-0001-8683-509X FU NIH [P41 GM079575-03]; Medical Research Council; Michael J. Fox Foundation for Parkinson's disease research; AstraZeneca; Boehringer-Ingelheim; GlaxoSmithKline; Merck KgaA; Pfizer FX This work was supported by NIH grant P41 GM079575-03 (to N.G.), the Medical Research Council (to D.A.), the Michael J. Fox Foundation for Parkinson's disease research (to N.G. and D.A.), the pharmaceutical companies supporting the DSTT (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KgaA, and Pfizer) (to D.A.). NR 31 TC 7 Z9 7 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD MAY PY 2015 VL 6 IS 5 BP 584 EP 589 DI 10.1021/acsmedchemlett.5b00064 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CI6ZO UT WOS:000354912900021 PM 26005538 ER PT J AU Khanfar, MA Quinti, L Wang, H Nobles, J Kazantsev, AG Silverman, RB AF Khanfar, Mohammad A. Quinti, Luisa Wang, Hua Nobles, Johnathan Kazantsev, Aleksey G. Silverman, Richard B. TI Design and Evaluation of 3-(Benzylthio)benzamide Derivatives as Potent and Selective SIRT2 Inhibitors SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE SIRT2; Huntington's disease; docking; 3-(benzylthio)benzamide; polyglutamine aggregation ID DISEASE; POLYGLUTAMINE; DEACETYLASES; MODELS; CELLS AB Inhibitors of sirtuin-2 (SIRT2) deacetylase have been shown to be protective in various models of Huntington's disease (HD) by decreasing polyglutamine aggregation, a hallmark of HD pathology. The present study was directed at optimizing the potency of SIRT2 inhibitors containing the 3-(benzylsulfonamido)benzamide scaffold and improving their metabolic stability. Molecular modeling and docking studies revealed an unfavorable role of the sulfonamide moiety for SIRT2 binding. This prompted us to replace the sulfonamide with thioether, sulfoxide, or sulfone groups. The thioether analogues were the most potent SIRT2 inhibitors with a two- to three-fold increase in potency relative to their corresponding sulfonamide analogues. The newly synthesized compounds also demonstrated higher SIRT2 selectivity over SIRT1 and SIRT3. Two thioether-derived compounds (17 and 18) increased a-tubulin acetylation in a dose-dependent manner in at least one neuronal cell line, and 18 was found to inhibit polyglutamine aggregation in PC12 cells. C1 [Khanfar, Mohammad A.; Wang, Hua; Silverman, Richard B.] Northwestern Univ, Dept Chem, Dept Mol Biosci, Chem Life Proc Inst,Ctr Mol Innovat & Drug Discov, Evanston, IL 60208 USA. [Khanfar, Mohammad A.] Univ Jordan, Dept Pharmaceut Sci, Amman, Jordan. [Quinti, Luisa; Nobles, Johnathan; Kazantsev, Aleksey G.] Harvard Univ, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. [Quinti, Luisa; Nobles, Johnathan; Kazantsev, Aleksey G.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Kazantsev, AG (reprint author), Harvard Univ, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. EM akazantsev@mgh.harvard.edu; agman@chem.northwestern.edu FU National Institutes of Health [U01 NS066912] FX The authors are grateful to the National Institutes of Health (Grant U01 NS066912) for financial support of this research. NR 17 TC 3 Z9 3 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD MAY PY 2015 VL 6 IS 5 BP 607 EP 611 DI 10.1021/acsmedchemlett.5b00075 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CI6ZO UT WOS:000354912900025 PM 26005542 ER PT J AU Lin, GC Sedaghat, AR Bleier, BS Holbrook, EH Busaba, NY Yoon, MK Gray, ST AF Lin, Giant C. Sedaghat, Ahmad R. Bleier, Benjamin S. Holbrook, Eric H. Busaba, Nicolas Y. Yoon, Michael K. Gray, Stacey T. TI Volumetric analysis of chronic maxillary atelectasis SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID SILENT SINUS SYNDROME; ORBITAL FLOOR; ENOPHTHALMOS; MANAGEMENT; PRESSURE AB Background: The relationship between orbit and maxillary sinus volumes in patients with chronic maxillary atelectasis (CMA), commonly known as silent sinus syndrome if enophthalmos is present, is poorly understood. Methods: A retrospective review of 22 patients who underwent endoscopic sinus surgery (ESS) for CMA from 2005 to 2013 was performed. Computed tomography (CT) images were analyzed using OsiriX 5.8.2 software for volumetric analysis of the orbit and maxillary sinus at presentation and after surgical treatment with ESS. Results: Pretreatment mean orbit volumes on the diseased side (DS) and the contralateral side (CS) were 29.22 and 26.50 mL, respectively (p < 0.001); mean sinus volumes on the DS and CS were 8.51 and 17.20 mL, respectively (p < 0.001); and pretreatment mean midorbit heights (MOHs) on the DS and CS were 3.39 cm and 3.07 cm, respectively (p < 0.001). The percent decrease in sinus volume on the DS compared to that on the CS did not correlate significantly with the percent orbit-volume increase. Enophthalmos was present in nine (41%) patients, and diplopia was present in three (14%) patients. The measured degree of increased orbit volume and decreased sinus volume secondary to CMA did not significantly predict the presence of enophthalmos at presentation. Seven patients underwent sinus CT more than 6 months after ESS. In these patients, orbit volume on the DS decreased from 29.67 to 27.52 mL (p = 0.005), and sinus volume on the DS increased from 9.78 to 11.84 mL (p = 0.08). Conclusions: Volumetric analysis is a powerful and novel method for objectively demonstrating the degree of orbit expansion and maxillary sinus contraction seen with CMA. Spontaneous maxillary sinus expansion and a decrease in orbit volume can occur after ESS, but post-ESS volumes do not return to the normal volume of the CS. C1 [Lin, Giant C.; Sedaghat, Ahmad R.; Bleier, Benjamin S.; Holbrook, Eric H.; Busaba, Nicolas Y.; Gray, Stacey T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Lin, Giant C.; Sedaghat, Ahmad R.; Bleier, Benjamin S.; Holbrook, Eric H.; Busaba, Nicolas Y.; Gray, Stacey T.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Yoon, Michael K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Gray, ST (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM stacey_gray@meei.harvard.edu NR 17 TC 2 Z9 2 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD MAY-JUN PY 2015 VL 29 IS 3 BP 166 EP 169 DI 10.2500/ajra.2013.27.4173 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA CJ2TK UT WOS:000355337200008 PM 25975247 ER PT J AU Hideshima, T Cottini, F Ohguchi, H Jakubikova, J Gorgun, G Mimura, N Tai, YT Munshi, NC Richardson, PG Anderson, KC AF Hideshima, T. Cottini, F. Ohguchi, H. Jakubikova, J. Gorgun, G. Mimura, N. Tai, Y-T Munshi, N. C. Richardson, P. G. Anderson, K. C. TI Rational combination treatment with histone deacetylase inhibitors and immunomodulatory drugs in multiple myeloma SO BLOOD CANCER JOURNAL LA English DT Article ID C-MYC; HDAC6 INHIBITOR; DOWN-REGULATION; IN-VITRO; LENALIDOMIDE; BORTEZOMIB; CELLS; DEXAMETHASONE; CEREBLON; TARGET AB Immunomodulatory drugs (IMiDs) thalidomide, lenalidomide (Len) and pomalidomide trigger anti-tumor activities in multiple myeloma (MM) by targetting cereblon and thereby impacting IZF1/3, c-Myc and IRF4. Histone deacetylase inhibitors (HDACi) also downregulate c-Myc. We therefore determined whether IMiDs with HDACi trigger significant MM cell growth inhibition by inhibiting or downregulating c-Myc. Combination treatment of Len with non-selective HDACi suberoylanilide hydroxamic acid or class-I HDAC-selective inhibitor MS275 induces synergic cytotoxicity, associated with downregulation of c-Myc. Unexpectedly, we observed that decreased levels of cereblon (CRBN), a primary target protein of IMiDs, was triggered by these agents. Indeed, sequential treatment of MM cells with MS275 followed by Len shows less efficacy than simultaneous treatment with this combination. Importantly ACY1215, an HDAC6 inhibitor with minimal effects on class-I HDACs, together with Len induces synergistic MM cytotoxicity without alteration of CRBN expression. Our results showed that only modest class-I HDAC inhibition is able to induce synergistic MM cytotoxicity in combination with Len. These studies may provide the framework for utilizing HDACi in combination with Len to both avoid CRBN downregulation and enhance anti-MM activities. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU National Institute of Health [SPORE-P50100707, P01-CA078378, R01-CA050947, R01 -CA178264] FX This study was supported by the National Institute of Health Grants; SPORE-P50100707 (KCA), P01-CA078378 (KCA), R01-CA050947 (KCA) and R01 -CA178264 (TH and KCA). KCA is an American Cancer Society Clinical Research Professor. NR 41 TC 14 Z9 14 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD MAY PY 2015 VL 5 AR e312 DI 10.1038/bcj.2015.38 PG 9 WC Oncology SC Oncology GA CJ2AG UT WOS:000355285800004 PM 25978432 ER PT J AU Rohatgi, S Howard, SA Tirumani, SH Ramaiya, NH Krajewski, KM AF Rohatgi, Saurabh Howard, Stephanie A. Tirumani, Sree Harsha Ramaiya, Nikhil H. Krajewski, Katherine M. TI Multimodality Imaging of Tumour Thrombus SO CANADIAN ASSOCIATION OF RADIOLOGISTS JOURNAL-JOURNAL DE L ASSOCIATION CANADIENNE DES RADIOLOGISTES LA English DT Article DE Thrombus; Tumoural thrombus; Bland thrombus; Imaging ID RENAL-CELL CARCINOMA; PORTAL-VEIN THROMBOSIS; HEPATOCELLULAR-CARCINOMA; VENOUS THROMBOSIS; SPECTRUM; CT; MANAGEMENT; CANCER; BENIGN AB Vascular thrombosis occurs commonly in cancer patients. Once the diagnosis of thrombosis is established, it is important to characterize the nature of thrombus, tumoural versus bland, as each have a different prognosis, clinical significance, and management. This review paper discusses the imaging spectrum of tumour thrombus and its clinical significance emphasizing the role of imaging in differentiating tumour from bland thrombus. (C) 2015 Canadian Association of Radiologists. All rights reserved. C1 [Rohatgi, Saurabh; Howard, Stephanie A.; Tirumani, Sree Harsha; Ramaiya, Nikhil H.; Krajewski, Katherine M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Tirumani, SH (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM sreeharsha_tirumani@dfci.harvard.edu NR 23 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0846-5371 EI 1488-2361 J9 CAN ASSOC RADIOL J JI Can. Assoc. Radiol. J.-J. Assoc. Can. Radiol. PD MAY PY 2015 VL 66 IS 2 BP 121 EP 129 DI 10.1016/j.carj.2014.11.001 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CI9AH UT WOS:000355062300006 PM 25660299 ER PT J AU Tirumani, H Rosenthal, MH Tirumani, SH Shinagare, AB Krajewski, KM Ramaiya, NH AF Tirumani, Harika Rosenthal, Michael H. Tirumani, Sree Harsha Shinagare, Atul B. Krajewski, Katherine M. Ramaiya, Nikhil H. TI Esophageal Carcinoma: Current Concepts in the Role of Imaging in Staging and Management SO CANADIAN ASSOCIATION OF RADIOLOGISTS JOURNAL-JOURNAL DE L ASSOCIATION CANADIENNE DES RADIOLOGISTES LA English DT Article DE Esophageal cancer; TNM staging; Computed tomography; Endoscopic ultrasound; Positron emission tomography/computed tomography ID POSITRON-EMISSION-TOMOGRAPHY; MULTICENTER PHASE-II; LONG-TERM SURVIVAL; RESPONSE ASSESSMENT; CANCER; THERAPY; ADENOCARCINOMA; JUNCTION; CHEMORADIATION; CETUXIMAB AB Over the past few decades, the survival of esophageal cancer patients has improved owing to early detection and advances in multimodality treatment strategies. Imaging plays an important role in every step in the management of esophageal cancer, including diagnosis, staging, assessment of treatment response, and post-treatment surveillance. In this article, we provide a comprehensive review of the role of imaging in these various time points of esophageal cancer management. (C) 2015 Canadian Association of Radiologists. All rights reserved. C1 [Tirumani, Harika; Rosenthal, Michael H.; Tirumani, Sree Harsha; Shinagare, Atul B.; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Rosenthal, Michael H.; Tirumani, Sree Harsha; Shinagare, Atul B.; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Tirumani, SH (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM stirumani@partners.org NR 39 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0846-5371 EI 1488-2361 J9 CAN ASSOC RADIOL J JI Can. Assoc. Radiol. J.-J. Assoc. Can. Radiol. PD MAY PY 2015 VL 66 IS 2 BP 130 EP 139 DI 10.1016/j.carj.2014.08.006 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CI9AH UT WOS:000355062300007 PM 25770628 ER PT J AU Flaherty, KT AF Flaherty, Keith T. TI When are signal transduction targeted therapies acting as immunotherapy? SO CANCER BIOLOGY & THERAPY LA English DT Article DE BRAF inhibitor; interleukin-2; ipilimumab; melanoma; synergy ID METASTATIC MELANOMA; BRAF INHIBITORS C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Flaherty, KT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM kflaherty@mgh.harvard.edu NR 10 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAY PY 2015 VL 16 IS 5 BP 645 EP 647 DI 10.1080/15384047.2015.1030553 PG 3 WC Oncology SC Oncology GA CI7XY UT WOS:000354981300001 PM 25807058 ER PT J AU Lian, ZR Lee, EK Bass, AJ Wong, KK Klein-Szanto, AJP Rustgi, AK Diehl, JA AF Lian, Zhaorui Lee, Eric K. Bass, Adam J. Wong, Kwok K. Klein-Szanto, Andres J. P. Rustgi, Anil K. Diehl, J. Alan TI FBXO4 loss facilitates carcinogen induced papilloma development in mice SO CANCER BIOLOGY & THERAPY LA English DT Article DE cyclin D1; CDK4; ESCC; FBXO4; PD0332991 ID RAT ESOPHAGEAL CARCINOGENESIS; CYCLIN D1 OVEREXPRESSION; N-NITROSOMETHYLBENZYLAMINE; BLACK-RASPBERRIES; CULTURED HUMAN; CANCER; DNA; METHYLBENZYLNITROSAMINE; O-6-METHYLGUANINE; CHEMOPREVENTION AB Cyclin D1 is frequently overexpressed in esophageal squamous cell carcinoma (ESCC) and is considered a key driver of this disease. Mutations in FBXO4, F-box specificity factor that directs SCF-mediated ubiquitylation of cyclin D1, occur in ESCC with concurrent overexpression of cyclin D1 suggesting a potential tumor suppressor role for FBXO4. To evaluate the contribution of FBXO4-dependent regulation cyclin D1 in esophageal squamous cell homeostasis, we exposed FBXO4 knockout mice to N-nitrosomethylbenzylamine (NMBA), an esophageal carcinogen. Our results revealed that loss of FBXO4 function facilitates NMBA induced papillomas in FBXO4 het (+/-) and null (-/-) mice both by numbers and sizes 11 months after single dose NMBA treatment at 2mg/kg by gavage when compared to that in wt (+/+) mice (P < 0.01). No significant difference was noted between heterozygous or nullizygous mice consistent with previous work. To assess cyclin D1/CDK4 dependence, mice were treated with the CDK4/6 specific inhibitor, PD0332991, for 4 weeks. PD0332991 treatment (150mg/kg daily), reduced tumor size and tumor number. Collectively, our data support a role for FBXO4 as a suppressor of esophageal tumorigenesis. C1 [Lian, Zhaorui] Univ Penn, Sch Med, Inst Regenerat Med, Philadelphia, PA 19104 USA. [Lee, Eric K.] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA. [Bass, Adam J.; Wong, Kwok K.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bass, Adam J.; Wong, Kwok K.] Dana Farber Canc Inst, Div Cellular & Mol Oncol, Boston, MA 02115 USA. [Klein-Szanto, Andres J. P.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Rustgi, Anil K.] Univ Penn, Dept Med, Div Gastroenterol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Rustgi, Anil K.] Univ Penn, Dept Genet, Div Gastroenterol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Rustgi, Anil K.] Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Diehl, J. Alan] Med Univ S Carolina, Charleston, SC 29425 USA. [Diehl, J. Alan] Hollings Canc Ctr, Charleston, SC USA. RP Diehl, JA (reprint author), Med Univ S Carolina, Charleston, SC 29425 USA. EM diehl@musc.edu FU [P01-CA098101] FX This work was supported by P01-CA098101 (JAD, AKR, AJPK, AJB, KKW). We thank NIH-P30-DK050306, the Molecular Pathology and Imaging, Molecular Biology and Cell Culture Core Facilities. NR 27 TC 3 Z9 3 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAY PY 2015 VL 16 IS 5 BP 750 EP 755 DI 10.1080/15384047.2015.1026512 PG 6 WC Oncology SC Oncology GA CI7XY UT WOS:000354981300015 PM 25801820 ER PT J AU Garcia, L Jaff, MR Metzger, C Sedillo, G Pershad, A Zidar, F Patlola, R Wilkins, RG Espinoza, A Iskander, A Khammar, GS Khatib, Y Beasley, R Makam, S Kovach, R Kamat, S Leon, LR Eaves, WB Popma, JJ Mauri, L Donohoe, D Base, CC Rosenfield, K AF Garcia, Lawrence Jaff, Michael R. Metzger, Christopher Sedillo, Gino Pershad, Ashish Zidar, Frank Patlola, Raghotham Wilkins, Robert G. Espinoza, Andrey Iskander, Ayman Khammar, George S. Khatib, Yazan Beasley, Robert Makam, Satyaprakash Kovach, Richard Kamat, Suraj Leon, Luis R., Jr. Eaves, William Britton Popma, Jeffrey J. Mauri, Laura Donohoe, Dennis Base, Carol C. Rosenfield, Kenneth CA SUPERB Trial Investigators TI Wire-Interwoven Nitinol Stent Outcome in the Superficial Femoral and Proximal Popliteal Arteries Twelve-Month Results of the SUPERB Trial SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE biological mimetic; femoral artery; peripheral artery disease; stent ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; BALLOON ANGIOPLASTY; HEALTH-STATUS; DISEASE; LESIONS; IMPLANTATION; CONSENSUS; REGISTRY; MODEL; TASC AB Background-Stent-based therapy in the superficial femoral and popliteal arteries in patients with peripheral artery disease is compromised by restenosis and risk of stent fracture or distortion. A novel self-expanding nitinol stent was developed that incorporates an interwoven-wire design (Supera stent, IDEV Technologies, Inc, Webster, TX) to confer greater radial strength, flexibility, and fracture resistance. Methods and Results-This prospective, multicenter, investigational device exemption, single-arm trial enrolled 264 patients with symptomatic peripheral artery disease undergoing percutaneous treatment of de novo or restenotic lesions of the superficial femoral or proximal popliteal (femoropopliteal) artery. Freedom from death, target lesion revascularization, or any amputation of the index limb at 30 days (+7 days) postprocedure was achieved in 99.2% (258/260) of patients (P<0.001). Primary patency at 12 months (360 +/- 30 days) was achieved in 78.9% (180/228) of the population (P<0.001). Primary patency by Kaplan-Meier analysis at 12 months (360 days) was 86.3%. No stent fracture was observed by independent core laboratory analysis in the 243 stents (228 patients) evaluated at 12 months. Clinical assessment at 12 months demonstrated improvement by at least 1 Rutherford-Becker category in 88.7% of patients. Conclusions-The SUPERB Trial, an investigational device exemption study using an interwoven nitinol wire stent in the femoropopliteal artery, achieved the efficacy and safety performance goals predesignated by the Food and Drug Administration. On the basis of the high primary patency rate, absence of stent fracture, and significant improvements in functional and quality-of-life measures, the Supera stent provides safe and effective treatment of femoropopliteal lesions in symptomatic patients with peripheral artery disease. C1 [Garcia, Lawrence] Tufts Univ, Sch Med, St Elizabeth Med Ctr, Div Cardiol, Boston, MA 02111 USA. [Jaff, Michael R.; Rosenfield, Kenneth] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Metzger, Christopher] Wellmont Holston Valley Med Ctr, Div Cardiol, Kingsport, TN USA. [Sedillo, Gino] CardioVasc Solut Inst, Bradenton, FL USA. [Pershad, Ashish] Banner Good Samaritan Med Ctr, Div Cardiol, Phoenix, AZ USA. [Zidar, Frank] Austin Heart PA, Austin, TX USA. [Patlola, Raghotham] Cardiovasc Inst South, Lafayette, LA USA. [Wilkins, Robert G.] Hattiesburg Clin PA, Div Cardiol, Hattiesburg, MS USA. [Espinoza, Andrey] Hunterdon Cardiovasc Associates PA, Flemington, NJ USA. [Iskander, Ayman] St Josephs Hosp Cardiol Associates, Liverpool, NY USA. [Khammar, George S.] Plaza Med Ctr Ft Worth, Div Cardiol, Ft Worth, TX USA. [Khatib, Yazan] First Coast Cardiovasc Inst, Jacksonville, FL USA. [Beasley, Robert] Mt Sinai Med Ctr, Div Cardiol, Miami Beach, FL 33140 USA. [Makam, Satyaprakash] Cardiovasc Res NW Indiana LLC, Munster, IN USA. [Kovach, Richard] Deborah Heart & Lung Ctr, Div Cardiol, Browns Mills, NJ USA. [Kamat, Suraj] Alice Heart Ctr, Div Cardiol, Alice, TX USA. [Leon, Luis R., Jr.] Tucson Med Ctr, Div Cardiol, Tucson, AZ USA. [Eaves, William Britton] Willis Knighton Bossier Med Ctr, Div Cardiol, Bossier City, LA USA. [Popma, Jeffrey J.] Beth Israel & Deaconess Med Ctr, Div Cardiol, Boston, MA USA. [Mauri, Laura] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Mauri, Laura] Harvard Clin Res Inst, Boston, MA USA. [Donohoe, Dennis; Base, Carol C.] IDEV Technol Inc, Webster, TX USA. RP Rosenfield, K (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM krosenfield1@mgh.harvard.edu FU IDEV Technologies, Inc, Webster, TX FX This trial was sponsored by IDEV Technologies, Inc, Webster, TX. NR 31 TC 12 Z9 12 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD MAY PY 2015 VL 8 IS 5 AR e000937 DI 10.1161/CIRCINTERVENTIONS.113.000937 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CI4TT UT WOS:000354747400002 ER PT J AU Sokol, CL Luster, AD AF Sokol, Caroline L. Luster, Andrew D. TI The Chemokine System in Innate Immunity SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID INDUCED AIRWAY INFLAMMATION; INFL AMMATORY ARTHRITIS; NATURAL-KILLER-CELLS; HUMAN MAST-CELLS; CD8(+) T-CELLS; DENDRITIC CELLS; LYMPHOID-CELLS; BONE-MARROW; NEUTROPHIL RECRUITMENT; MONOCYTE RECRUITMENT AB Chemokines are chemotactic cytokines that control the migration and positioning of immune cells in tissues and are critical for the function of the innate immune system. Chemokines control the release of innate immune cells from the bone marrow during homeostasis as well as in response to infection and inflammation. They also recruit innate immune effectors out of the circulation and into the tissue where, in collaboration with other chemoattractants, they guide these cells to the very sites of tissue injury. Chemokine function is also critical for the positioning of innate immune sentinels in peripheral tissue and then, following innate immune activation, guiding these activated cells to the draining lymph node to initiate and imprint an adaptive immune response. In this review, we will highlight recent advances in understanding how chemokine function regulates the movement and positioning of innate immune cells at homeostasis and in response to acute inflammation, and then we will review how chemokine-mediated innate immune cell trafficking plays an essential role in linking the innate and adaptive immune responses. C1 [Sokol, Caroline L.; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. RP Luster, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. EM aluster@mgh.harvard.edu FU National Institutes of Health; Asthma and Allergy Foundation of America FX The writers are supported by grants from the National Institutes of Health, and C.L.S. is also supported by the Asthma and Allergy Foundation of America. We thank Jason Griffith for helpful discussions in the preparation of this manuscript. NR 109 TC 10 Z9 10 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD MAY PY 2015 VL 7 IS 5 AR a016303 DI 10.1101/cshperspect.a016303 PG 19 WC Cell Biology SC Cell Biology GA CJ0VM UT WOS:000355197000002 ER PT J AU Hage, FG Iskandrian, AE AF Hage, Fadi G. Iskandrian, Ami E. TI Multimodality Imaging for CAD Detection Before Renal Transplantation SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE coronary angiography; coronary computed tomography angiography; renal transplantation; sensitivity and specificity; single-photon emission computed tomography ID PROGNOSTIC VALUE; KIDNEY-TRANSPLANTATION; LIVER-TRANSPLANTATION; HEART-DISEASE; PREDICTORS; CANDIDATES; SURVIVAL C1 [Hage, Fadi G.; Iskandrian, Ami E.] Univ Alabama Birmingham, Div Cardiovasc Dis, Dept Med, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Sect Cardiol, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Lyons Harrison Res Bldg 314,1900 Univ Blvd, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 14 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 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAY PY 2015 VL 8 IS 5 BP 563 EP 565 DI 10.1016/j.jcmg.2015.01.017 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CI9CR UT WOS:000355068500010 PM 25937194 ER PT J AU te Riele, ASJM Tandri, H Sanborn, DM Bluemke, DA AF te Riele, Anneline S. J. M. Tandri, Harikrishna Sanborn, Danita M. Bluemke, David A. TI Noninvasive Multimodality Imaging in ARVD/C SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE arrhythmogenic right ventricular dysplasia/cardiomyopathy; cardiac magnetic resonance; computed tomography; echocardiography; imaging ID RIGHT-VENTRICULAR DYSPLASIA; CARDIOVASCULAR MAGNETIC-RESONANCE; TASK-FORCE CRITERIA; MYOCARDIAL PERFORMANCE INDEX; IN-VIVO VALIDATION; COMPUTED-TOMOGRAPHY; 3-DIMENSIONAL ECHOCARDIOGRAPHY; AMERICAN-SOCIETY; SUDDEN-DEATH; EUROPEAN-ASSOCIATION AB Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a familial cardiomyopathy resulting in progressive right ventricular (RV) dysfunction and malignant ventricular arrhythmias. Although ARVD/C is generally considered an inherited cardiomyopathy, the arrhythmogenic nature of the disease is striking. Affected individuals typically present in the second to fourth decade of Life with arrhythmias originating from the right ventricle. Over the past decade, pathogenic ARVD/C-causing mutations have been identified in 5 genes encoding the cardiac desmosome. Disruption of the desmosomal connection system between cardiomyocytes may be represented structurally by ventricular enlargement, global or regional contraction abnormalities; RV-aneurysms, or fibrofatty replacement. These abnormalities are typically observed in predilection areas, including the subtricuspid region, basal RV free wall, and Left ventricular posterolateral wall. As such, structural and functional abnormalities on cardiac imaging constitute an important diagnostic criterion for the disease. This paper discusses the current status and role of echocardiography, cardiac magnetic resonance imaging, and computed tomography for suspected ARVD/C. (C) 2015 by the American College of Cardiology Foundation. C1 [te Riele, Anneline S. J. M.; Tandri, Harikrishna] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [te Riele, Anneline S. J. M.] Univ Med Ctr Utrecht, Dept Med, Div Cardiol, Utrecht, Netherlands. [Sanborn, Danita M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Boston, MA USA. [Bluemke, David A.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Bluemke, David A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Bluemke, DA (reprint author), NIH, Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. EM david.bluemke@nih.gov RI 刘, 李陆/H-8469-2015; OI Bluemke, David/0000-0002-8323-8086 FU Dr. Francis P. Chiaramonte Private Foundation; St. Jude Medical, Inc.; Medtronic, Inc.; Leyla Erkan Family Fund for ARVD research; Dr. Satish, Rupal, and Robin Shah ARVD Fund at Johns Hopkins; Bogle Foundation; Healing Hearts Foundation; Campanella family; Patrick J. Harrison Family; Peter French Memorial Foundation; Wilmerding Endowments FX This work was performed during Dr. te Riele's tenure as the Mark Josephson and Hein Wellens Research Fellow of the Heart Rhythm Society. Funding was received from the Dr. Francis P. Chiaramonte Private Foundation, St. Jude Medical, Inc., and Medtronic, Inc. The Johns Hopkins ARVD/C Program is supported by the Leyla Erkan Family Fund for ARVD research, the Dr. Satish, Rupal, and Robin Shah ARVD Fund at Johns Hopkins, the Bogle Foundation, the Healing Hearts Foundation, the Campanella family, the Patrick J. Harrison Family, the Peter French Memorial Foundation, and the Wilmerding Endowments. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 82 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAY PY 2015 VL 8 IS 5 BP 597 EP 611 DI 10.1016/j.jcmg.2015.02.007 PG 15 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CI9CR UT WOS:000355068500014 PM 25937197 ER PT J AU Blanke, P Dvir, D Cheung, A Levine, RA Thompson, C Webb, JG Leipsic, J AF Blanke, Philipp Dvir, Danny Cheung, Anson Levine, Robert A. Thompson, Christopher Webb, John G. Leipsic, Jonathon TI Mitral Annular Evaluation With CT in the Context of Transcatheter Mitral Valve Replacement SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE mitral regurgitation; TMVI; TMVR; transcatheter mitral valve implantation; transcatheter mitral valve replacement C1 [Blanke, Philipp; Dvir, Danny; Cheung, Anson; Thompson, Christopher; Webb, John G.; Leipsic, Jonathon] Univ British Columbia, Ctr Heart Valve Innovat, St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. [Levine, Robert A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, Boston, MA USA. RP Leipsic, J (reprint author), Univ British Columbia, Ctr Heart Valve Innovat, St Pauls Hosp, Dept Radiol, 1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada. EM jleipsic@providencehealth.bc.ca RI Thompson, Christopher/F-3967-2010 OI Thompson, Christopher/0000-0001-9206-376X NR 2 TC 13 Z9 13 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAY PY 2015 VL 8 IS 5 BP 612 EP 615 DI 10.1016/j.jcmg.2014.07.028 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CI9CR UT WOS:000355068500015 PM 25937198 ER PT J AU Betof, AS Lascola, CD Weitzel, D Landon, C Scarbrough, PM Devi, GR Palmer, G Jones, LW Dewhirst, MW AF Betof, Allison S. Lascola, Christopher D. Weitzel, Douglas Landon, Chelsea Scarbrough, Peter M. Devi, Gayathri R. Palmer, Gregory Jones, Lee W. Dewhirst, Mark W. TI Modulation of Murine Breast Tumor Vascularity, Hypoxia, and Chemotherapeutic Response by Exercise SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELL LUNG-CANCER; METASTATIC COLORECTAL-CANCER; PHYSICAL-ACTIVITY; 1ST-LINE THERAPY; PHASE-III; BEVACIZUMAB; OXYGEN; NORMALIZATION; MECHANISMS; PACLITAXEL AB Exercise has been shown to improve postischemia perfusion of normal tissues; we investigated whether these effects extend to solid tumors. Estrogen receptor-negative (ER-, 4T1) and ER+ (E0771) tumor cells were implanted orthotopically into syngeneic mice (BALB/c, N = 11-12 per group) randomly assigned to exercise or sedentary control. Tumor growth, perfusion, hypoxia, and components of the angiogenic and apoptotic cascades were assessed by MRI, immunohistochemistry, western blotting, and quantitative polymerase chain reaction and analyzed with one-way and repeated measures analysis of variance and linear regression. All statistical tests were two-sided. Exercise statistically significantly reduced tumor growth and was associated with a 1.4-fold increase in apoptosis (sedentary vs exercise: 1544 cells/mm(2), 95% CI = 1223 to 1865 vs 2168 cells/mm(2), 95% CI = 1620 to 2717; P = .048), increased microvessel density (P = .004), vessel maturity (P = .006) and perfusion, and reduced intratumoral hypoxia (P = .012), compared with sedentary controls. We also tested whether exercise could improve chemotherapy (cyclophosphamide) efficacy. Exercise plus chemotherapy prolonged growth delay compared with chemotherapy alone (P < .001) in the orthotopic 4T1 model (n = 17 per group). Exercise is a potential novel adjuvant treatment of breast cancer. C1 [Betof, Allison S.; Lascola, Christopher D.; Weitzel, Douglas; Landon, Chelsea; Scarbrough, Peter M.; Devi, Gayathri R.; Palmer, Gregory; Dewhirst, Mark W.] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA. [Betof, Allison S.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Jones, Lee W.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Dewhirst, MW (reprint author), Duke Univ, Box 3455,Med Sci Res Bldg, Durham, NC 27708 USA. EM dewhirst@radonc.duke.edu RI Lascola, Christopher/B-9126-2017; OI Lascola, Christopher/0000-0002-8031-782X; Palmer, Gregory/0000-0003-2955-8297 FU DOD [BC093532]; National Cancer Institute; NIH [CA40355] FX ASB was supported by DOD BC093532. LWJ is supported by grants from the National Cancer Institute. MWD is supported by NIH CA40355. NR 32 TC 10 Z9 10 U1 2 U2 10 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 MAY PY 2015 VL 107 IS 5 AR djv040 DI 10.1093/jnci/djv040 PG 5 WC Oncology SC Oncology GA CI9KJ UT WOS:000355088600011 ER PT J AU Gray, SW Cronin, A Bair, E Lindeman, N Viswanath, V Janeway, KA AF Gray, Stacy W. Cronin, Angel Bair, Elizabeth Lindeman, Neal Viswanath, Vish Janeway, Katherine A. TI Marketing of Personalized Cancer Care on the Web: An Analysis of Internet Websites SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CHEMOTHERAPY SENSITIVITY; RESISTANCE ASSAYS; AMERICAN-SOCIETY; HEALTH-CARE; CONSUMER; PHYSICIANS; IMPACT; ORGANIZATION; PERCEPTIONS; AWARENESS AB Internet marketing may accelerate the use of care based on genomic or tumor-derived data. However, online marketing may be detrimental if it endorses products of unproven benefit. We conducted an analysis of Internet websites to identify personalized cancer medicine (PCM) products and claims. A Delphi Panel categorized PCM as standard or nonstandard based on evidence of clinical utility. Fifty-five websites, sponsored by commercial entities, academic institutions, physicians, research institutes, and organizations, that marketed PCM included somatic (58%) and germline (20%) analysis, interpretive services (15%), and physicians/institutions offering personalized care (44%). Of 32 sites offering somatic analysis, 56% included specific test information (range 1-152 tests). All statistical tests were two-sided, and comparisons of website content were conducted using McNemar's test. More websites contained information about the benefits than limitations of PCM (85% vs 27%, P < .001). Websites specifying somatic analysis were statistically significantly more likely to market one or more nonstandard tests as compared with standard tests (88% vs 44%, P = .04). C1 [Gray, Stacy W.; Cronin, Angel; Bair, Elizabeth; Viswanath, Vish] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Gray, Stacy W.; Lindeman, Neal; Janeway, Katherine A.] Harvard Univ, Sch Med, Boston, MA USA. [Gray, Stacy W.; Lindeman, Neal] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Viswanath, Vish] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Janeway, Katherine A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Janeway, Katherine A.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. RP Gray, SW (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Ctr Populat Sci, 450 Brookline Ave,Dana 1123-A, Boston, MA 02215 USA. EM stacyw_gray@dfci.harvard.edu FU American Cancer Society [120529-MRSG-11-006-01-CPPB]; National Human Genome Research Institute [U01HG006492] FX This work was supported by the American Cancer Society (120529-MRSG-11-006-01-CPPB). Dr. Gray is also supported by the National Human Genome Research Institute (U01HG006492). NR 33 TC 1 Z9 1 U1 1 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 MAY PY 2015 VL 107 IS 5 AR djv030 DI 10.1093/jnci/djv030 PG 5 WC Oncology SC Oncology GA CI9KJ UT WOS:000355088600004 ER PT J AU Hiatt, RA Tai, CG Blayney, DW Deapen, D Hogarth, M Kizer, KW Lipscomb, J Malin, J Phillips, SK Santa, J Schrag, D AF Hiatt, Robert A. Tai, Caroline G. Blayney, Douglas W. Deapen, Dennis Hogarth, Michael Kizer, Kenneth W. Lipscomb, Joseph Malin, Jennifer Phillips, Stephen K. Santa, John Schrag, Deborah TI Leveraging State Cancer Registries to Measure and Improve the Quality of Cancer Care: A Potential Strategy for California and Beyond SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID COLORECTAL-CANCER; OUTCOMES RESEARCH; BREAST-CANCER; PERFORMANCE AB Despite recent increased attention to healthcare performance and the burden of disease from cancer, measures of quality of cancer care are not readily available. In 2013, the California HealthCare Foundation convened an expert workgroup to explore the potential for leveraging data in the California Cancer Registry (CCR), one of the world's largest population-based cancer registries, for measuring and improving the quality of cancer care. The workgroup assessed current registry operations, the value to be gained by linking CCR data with health insurance claims or encounter data and clinical data contained in health system electronic health records, and potential barriers to these linkages. The workgroup concluded that: 1) The CCR mandate should be expanded to include use of its data for quality of cancer care measurement and public reporting; and 2) a system should be developed to support linkage of registry data with both claims data and provider electronic health record data. C1 [Hiatt, Robert A.; Tai, Caroline G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Blayney, Douglas W.] Stanford Univ, Stanford Canc Inst, Stanford, CA 94305 USA. [Deapen, Dennis] Univ So Calif, Div Epidemiol, Prevent Med, Los Angeles, CA USA. [Hogarth, Michael] Univ Calif Davis, Dept Pathol & Lab Med, Sacramento, CA 95817 USA. [Kizer, Kenneth W.] Univ Calif Davis, Inst Populat Hlth Improvement, Sacramento, CA 95817 USA. [Lipscomb, Joseph] Emory Univ, Winship Canc Inst, Rollins Sch Publ Hlth, Dept Hlth Policy & Management, Atlanta, GA 30322 USA. [Malin, Jennifer] WellPoint Inc, Oncol & Care Management, Thousand Oaks, CA USA. [Phillips, Stephen K.] Hooper Lundy & Bookman PC, San Francisco, CA USA. [Santa, John] Consumer Reports Hlth, Yonkers, NY USA. [Schrag, Deborah] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Hiatt, RA (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, Mission Hall,550 16th St,Box 0560, San Francisco, CA 94143 USA. EM robert.hiatt@ucsf.edu NR 40 TC 3 Z9 3 U1 1 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 MAY PY 2015 VL 107 IS 5 AR djv047 DI 10.1093/jnci/djv047 PG 7 WC Oncology SC Oncology GA CI9KJ UT WOS:000355088600016 ER PT J AU Rae, JM Leyland-Jones, B Regan, M Thompson, AM AF Rae, James M. Leyland-Jones, Brian Regan, Meredith Thompson, Alastair M. TI RE: Loss of Heterozygosity at the CYP2D6 Locus in Breast Cancer: Implications for Germline Pharmacogenetic Studies SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID TAMOXIFEN C1 [Rae, James M.] Univ Michigan, Internal Med & Pharmacol, Sch Med, Ann Arbor, MI 48109 USA. [Leyland-Jones, Brian] Sanford Hlth & Res, Edith Sanford Breast Canc Res, Sioux Falls, SD USA. [Regan, Meredith] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Thompson, Alastair M.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. RP Rae, JM (reprint author), Univ Michigan, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM jimmyrae@umich.edu NR 7 TC 1 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD MAY PY 2015 VL 107 IS 5 AR djv065 DI 10.1093/jnci/djv065 PG 2 WC Oncology SC Oncology GA CI9KJ UT WOS:000355088600022 ER PT J AU Abramson, ZR Susarla, SM Lawler, ME Choudhri, AF Peacock, ZS AF Abramson, Zachary R. Susarla, Srinivas M. Lawler, Matthew E. Choudhri, Asim F. Peacock, Zachary S. TI Geometry of Anterior Open Bite Correction SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Anterior open bite; geometry; orthognathic surgery; Le Fort I osteotomy; cephalometric analysis ID MALOCCLUSION; STABILITY AB Correction of anterior open bite is a frequently encountered and challenging problem for the craniomaxillofacial surgeon and orthodontist. Accurate clinical evaluation, including cephalometric assessment, is paramount for establishing the diagnosis and appropriate treatment plan. The purposes of this technical note were to discuss the basic geometric principles involved in the surgical correction of skeletal anterior open bites and to offer a simple mathematical model for predicting the amount of posterior maxillary impaction with concomitant mandibular rotation required to establish an adequate overbite. Using standard geometric principles, a mathematical model was created to demonstrate the relationship between the magnitude of the open bite and the magnitude of the rotational movements required for correction. This model was then validated using a clinical case. In summary, the amount of open bite closure for a given amount of posterior maxillary impaction depends on anatomic variables, which can be obtained from a lateral cephalogram. The clinical implication of this relationship is as follows: patients with small mandibles and steep mandibular occlusal planes will require greater amounts of posterior impaction. C1 [Abramson, Zachary R.] Univ Tennessee, Ctr Hlth Sci, Dept Med, Memphis, TN 38163 USA. [Susarla, Srinivas M.] Johns Hopkins Univ Hosp, Johns Hopkins Med Sch, Dept Plast & Reconstruct Surg, Baltimore, MD 21287 USA. [Lawler, Matthew E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Oral & Maxillofacial Surg, Boston, MA USA. [Choudhri, Asim F.] Univ Tennessee, Ctr Hlth Sci, Dept Radiol, Memphis, TN 38163 USA. [Choudhri, Asim F.] Univ Tennessee, Ctr Hlth Sci, Dept Ophthalmol, Memphis, TN 38163 USA. [Choudhri, Asim F.] Univ Tennessee, Ctr Hlth Sci, Dept Neurosurg, Memphis, TN 38163 USA. [Choudhri, Asim F.] Le Bonheur Childrens Hosp, Le Bonheur Neurosci Inst, Memphis, TN USA. [Peacock, Zachary S.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Peacock, Zachary S.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, WRN1201, Boston, MA 02114 USA. EM zpeacock@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 NR 6 TC 1 Z9 1 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1049-2275 EI 1536-3732 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD MAY PY 2015 VL 26 IS 3 BP E223 EP E225 DI 10.1097/SCS.0000000000001440 PG 3 WC Surgery SC Surgery GA CJ1IG UT WOS:000355236700011 PM 25950521 ER PT J AU Tulsky, DS Kisala, PA Victorson, D Tate, DG Heinemann, AW Charlifue, S Kirshblum, SC Fyffe, D Gershon, R Spungen, AM Bombardier, CH Dyson-Hudson, TA Amtmann, D Kalpakjian, CZ Choi, SW Jette, AM Forchheimer, M Cella, D AF Tulsky, David S. Kisala, Pamela A. Victorson, David Tate, Denise G. Heinemann, Allen W. Charlifue, Susan Kirshblum, Steve C. Fyffe, Denise Gershon, Richard Spungen, Ann M. Bombardier, Charles H. Dyson-Hudson, Trevor A. Amtmann, Dagmar Kalpakjian, Claire Z. Choi, Seung W. Jette, Alan M. Forchheimer, Martin Cella, David TI Overview of the Spinal Cord Injury - Quality of Life (SCI-QOL) measurement system SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Computer Adaptive Testing; Health-Related Quality of Life; Item Response Theory; Patient Reported Outcomes; Spinal Cord Injury ID PATIENT-REPORTED OUTCOMES; ITEM RESPONSE THEORY; COMPUTERIZED ADAPTIVE ASSESSMENT; LONGITUDINAL ANALYSIS; CLINICAL-TRIALS; FUNCTIONAL INDEX; RISK-FACTORS; HEALTH; DEPRESSION; PROMIS AB Context/Objective: The Spinal Cord Injury - Quality of Life (SCI-QOL) measurement system was developed to address the shortage of relevant and psychometrically sound patient reported outcome (PRO) measures available for clinical care and research in spinal cord injury (SCI) rehabilitation. Using a computer adaptive testing (CAT) approach, the SCI-QOL builds on the Patient Reported Outcomes Measurement Information System (PROMIS) and the Quality of Life in Neurological Disorders (Neuro-QOL) initiative. This initial manuscript introduces the background and development of the SCI-QOL measurement system. Greater detail is presented in the additional manuscripts of this special issue. Design: Classical and contemporary test development methodologies were employed. Qualitative input was obtained from individuals with SCI and clinicians through interviews, focus groups, and cognitive debriefing. Item pools were field tested in a multi-site sample (n = 877) and calibrated using item response theory methods. Initial reliability and validity testing was performed in a new sample of individuals with traumatic SCI (n = 245). Setting: Five Model SCI System centers and one Department of Veterans Affairs Medical Center across the United States. Participants: Adults with traumatic SCI. Interventions: n/a Outcome Measures: n/a Results: The SCI-QOL consists of 19 item banks, including the SCI-Functional Index banks, and 3 fixed-length scales measuring physical, emotional, and social aspects of health-related QOL (HRQOL). Conclusion: The SCI-QOL measurement system consists of psychometrically sound measures for individuals with SCI. The manuscripts in this special issue provide evidence of the reliability and initial validity of this measurement system. The SCI-QOL also links to other measures designed for a general medical population. C1 [Tulsky, David S.; Kisala, Pamela A.] Univ Delaware, Coll Hlth Sci, Dept Phys Therapy, Newark, DE 19713 USA. [Tulsky, David S.; Fyffe, Denise; Dyson-Hudson, Trevor A.] Kessler Fdn, W Orange, NJ USA. [Victorson, David; Heinemann, Allen W.; Gershon, Richard; Cella, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Tate, Denise G.; Kalpakjian, Claire Z.; Forchheimer, Martin] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Heinemann, Allen W.] Rehabil Inst Chicago, Chicago, IL 60611 USA. [Charlifue, Susan] Craig Hosp, Englewood, CO USA. [Kirshblum, Steve C.] Kessler Inst Rehabil, W Orange, NJ USA. [Fyffe, Denise] Rutgers State Univ, New Jersey Med Sch, Newark, NJ 07102 USA. [Spungen, Ann M.] James J Peters VA Med Ctr, Bronx, NY USA. [Bombardier, Charles H.; Amtmann, Dagmar] Univ Washington, Seattle, WA 98195 USA. [Choi, Seung W.] CTB McGraw Hill LLC, Monterey, CA USA. [Jette, Alan M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Tulsky, DS (reprint author), Univ Delaware, Ctr Assessment Res & Translat, STAR Campus,540 S Coll Ave, Newark, DE 19713 USA. EM dtulsky@udel.edu OI Heinemann, Allen/0000-0003-2782-7326 FU National Institute of Child Health and Human Development/National Center on Medical Rehabilitation Research; National Institute of Neurological Disorders and Stroke (NINDS) [5R01HD0054659]; National Institute on Disability and Rehabilitation Research [H133N060022, H133N060024, H133N060014, H133N060005, H133N060027, H133N060032]; Department of Veterans Affairs, Rehabilitation Research & Development National Center of Excellence for the Medical Consequences of Spinal Cord Injury [B8212-C] FX This work was co-funded by the National Institute of Child Health and Human Development/National Center on Medical Rehabilitation Research and the National Institute of Neurological Disorders and Stroke (NINDS) (Grant #5R01HD0054659). Additionally, funding for the development of the SCIFI physical functioning item banks was provided by the National Institute on Disability and Rehabilitation Research (Grant #s H133N060022, H133N060024, H133N060014, H133N060005, H133N060027, and H133N060032), and funding to expand the calibration sample into the VA was provided by the Department of Veterans Affairs, Rehabilitation Research & Development National Center of Excellence for the Medical Consequences of Spinal Cord Injury (Grant #B8212-C). NR 99 TC 16 Z9 16 U1 5 U2 20 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD MAY PY 2015 VL 38 IS 3 BP 257 EP 269 DI 10.1179/2045772315Y.0000000023 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA CJ0TV UT WOS:000355192100002 PM 26010962 ER PT J AU Tulsky, DS Kisala, PA Tate, DG Spungen, AM Kirshblum, SC AF Tulsky, David S. Kisala, Pamela A. Tate, Denise G. Spungen, Ann M. Kirshblum, Steven C. TI Development and psychometric characteristics of the SCI-QOL Bladder Management Difficulties and Bowel Management Difficulties item banks and short forms and the SCI-QOL Bladder Complications scale SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Spinal cord injuries; Urinary bladder; Neurogenic; Neurogenic bowel; Patient reported outcomes assessment; Quality of life; Psychometrics ID SPINAL-CORD-INJURY; QUALITY-OF-LIFE; NEUROGENIC BOWEL; INTERMITTENT CATHETERIZATION; NEUROPATHIC BLADDER; FOLLOW-UP; DYSFUNCTION; VALIDATION; QUESTIONNAIRE; MULTICENTER AB Objective: To describe the development and psychometric properties of the Spinal Cord Injury - Quality of Life (SCI-QOL) Bladder Management Difficulties and Bowel Management Difficulties item banks and Bladder Complications scale. Design: Using a mixed-methods design, a pool of items assessing bladder and bowel-related concerns were developed using focus groups with individuals with spinal cord injury (SCI) and SCI clinicians, cognitive interviews, and item response theory (IRT) analytic approaches, including tests of model fit and differential item functioning. Setting: Thirty-eight bladder items and 52 bowel items were tested at the University of Michigan, Kessler Foundation Research Center, the Rehabilitation Institute of Chicago, the University of Washington, Craig Hospital, and the James J. Peters VA Medical Center, Bronx, NY. Participants: Seven hundred fifty-seven adults with traumatic SCI. Results: The final item banks demonstrated unidimensionality (Bladder Management Difficulties CFI = 0.965; RMSEA = 0.093; Bowel Management Difficulties CFI = 0.955; RMSEA = 0.078) and acceptable fit to a graded response IRT model. The final calibrated Bladder Management Difficulties bank includes 15 items, and the final Bowel Management Difficulties item bank consists of 26 items. Additionally, 5 items related to urinary tract infections (UTI) did not fit with the larger Bladder Management Difficulties item bank but performed relatively well independently (CFI = 0.992, RMSEA = 0.050) and were thus retained as a separate scale. Conclusion: The SCI-QOL Bladder Management Difficulties and Bowel Management Difficulties item banks are psychometrically robust and are available as computer adaptive tests or short forms. The SCI-QOL Bladder Complications scale is a brief, fixed-length outcomes instrument for individuals with a UTI. C1 [Tulsky, David S.; Kisala, Pamela A.] Univ Delaware, Dept Phys Therapy, Newark, DE 19713 USA. [Tulsky, David S.] Kessler Fdn, Res Ctr, W Orange, NJ USA. [Tate, Denise G.] Univ Michigan, Sch Med, Dept Phys Med & Rehabil, Ann Arbor, MI USA. [Spungen, Ann M.] VA RR&D Ctr Excellence Med Consequences Spinal Co, James J Peters VA Med Ctr, Bronx, NY USA. [Spungen, Ann M.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Spungen, Ann M.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, Steven C.] Rutgers New Jersey Med Sch, Dept Phys Med & Rehabil, Newark, NJ USA. RP Tulsky, DS (reprint author), Univ Delaware, Ctr Assessment Res & Translat, STAR Campus,540 S Coll Ave, Newark, DE 19713 USA. EM dtulsky@udel.edu FU National Institutes of Health [5R01HD054659] FX This study was supported by National Institutes of Health grant number 5R01HD054659 (Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Center on Medical Rehabilitation Research and the National Institute on Neurological Disorders and Stroke). NR 62 TC 3 Z9 3 U1 1 U2 5 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD MAY PY 2015 VL 38 IS 3 BP 288 EP 302 DI 10.1179/2045772315Y.0000000030 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA CJ0TV UT WOS:000355192100004 PM 26010964 ER PT J AU Rosendorff, C AF Rosendorff, Clive TI Blood pressure targets in patients with diabetes - a new perspective SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION LA English DT Editorial Material ID AMERICAN SOCIETY; EUROPEAN-SOCIETY; TASK-FORCE; HYPERTENSION; MANAGEMENT; CARDIOLOGY; ASSOCIATION; PREVENTION; GUIDELINES; STATEMENT C1 [Rosendorff, Clive] Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, Mt Sinai Heart, New York, NY 10029 USA. [Rosendorff, Clive] James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Rosendorff, C (reprint author), James J Peters VA Med Ctr, Med 111, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM clive.rosendorff@va.gov NR 10 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 1933-1711 EI 1878-7436 J9 J AM SOC HYPERTENS JI J. Am. Soc. Hypertens. PD MAY PY 2015 VL 9 IS 5 BP 334 EP 336 DI 10.1016/j.jash.2015.03.003 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CI9DJ UT WOS:000355070300003 PM 25979409 ER PT J AU Anderson, KC AF Anderson, Kenneth C. TI Multiple Myeloma: New Uses for Available Agents, Excitement for the Future SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID AUTOLOGOUS TRANSPLANTATION; MAINTENANCE THERAPY; DEXAMETHASONE; LENALIDOMIDE; BORTEZOMIB AB With the availability of a new proteasome inhibitor, carfilzomib, and a new immunomodulatory drug, pomalidomide, the treatment of multiple myeloma has become more effective. The updated NCCN Clinical Practice Guidelines in Oncology for Multiple Myeloma provide new recommendations for use of carfilzomib and pomalidomide. As new classes of drugs such as monoclonal antibodies become available, the treatment landscape will be rendered even brighter. C1 [Anderson, Kenneth C.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, Lebow Inst Myeloma Therapeut, Boston, MA 02215 USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM kenneth_anderson@dfci.harvard.edu FU Acetylon Pharmaceuticals, Inc.; Celgene Corporation; Gilead; Multiple Myeloma Research Foundation; OncoPep; Onyx Pharmaceuticals, Inc.; sanofi-aventis U.S. FX Dr. Anderson has disclosed that he has served as a paid scientific advisor to Acetylon Pharmaceuticals, Inc., Celgene Corporation, Gilead, Multiple Myeloma Research Foundation, OncoPep, Onyx Pharmaceuticals, Inc., and sanofi-aventis U.S., and received other financial benefit from Acetylon Pharmaceuticals, Inc. and OncoPep. NR 13 TC 2 Z9 2 U1 0 U2 3 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAY PY 2015 VL 13 IS 5.5 BP 694 EP 696 PG 3 WC Oncology SC Oncology GA CJ1JQ UT WOS:000355240300020 PM 25995433 ER PT J AU Mulshine, JL Avila, R Yankelevitz, D Baer, TM Estepar, RS Ambrose, LF Aldige, CR AF Mulshine, James L. Avila, Rick Yankelevitz, David Baer, Thomas M. Estepar, Raul San Jose Ambrose, Laurie Fenton Aldige, Carolyn R. TI Lung Cancer Workshop XI Tobacco-Induced Disease: Advances in Policy, Early Detection and Management SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung cancer; Screening; Low Dose CT; Quantitative imaging; Volumetric CT ID IMAGING BIOMARKER; DRUG DEVELOPMENT; VOLUMETRIC CT; LOBECTOMY; PROGRESS; SMOKERS AB The Prevent Cancer Foundation Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management was held in New York, NY on May 16 and 17, 2014. The two goals of the Workshop were to define strategies to drive innovation in precompetitive quantitative research on the use of imaging to assess new therapies for management of early lung cancer and to discuss a process to implement a national program to provide high quality computed tomography imaging for lung cancer and other tobacco-induced disease. With the central importance of computed tomography imaging for both early detection and volumetric lung cancer assessment, strategic issues around the development of imaging and ensuring its quality are critical to ensure continued progress against this most lethal cancer. C1 [Mulshine, James L.] Rush Univ, Chicago, IL 60612 USA. [Avila, Rick] US Dept Vet Affairs, Washington, DC USA. [Yankelevitz, David] Mt Sinai Sch Med, Dept Radiol, New York, NY USA. [Baer, Thomas M.] Stanford Univ, Photon Res Ctr, Palo Alto, CA 94304 USA. [Estepar, Raul San Jose] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Ambrose, Laurie Fenton] Lung Canc Alliance, Washington, DC USA. [Aldige, Carolyn R.] Prevent Canc Fdn, Alexandria, VA USA. RP Mulshine, JL (reprint author), Rush Univ, 1735 West Harrison St,Suite 206, Chicago, IL 60612 USA. EM jmulshin@rush.edu FU Prevent Cancer Foundation FX Riccardo S Avila has moved to become CEO, Accumetra since the time of the Workshop. The other authors declare no conflict of interest. This Workshop was supported through unrestricted grants to the Prevent Cancer Foundation. NR 24 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAY PY 2015 VL 10 IS 5 BP 762 EP 767 DI 10.1097/JTO.0000000000000489 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CI8AP UT WOS:000354990100016 PM 25898957 ER PT J AU Sholl, LM Aisner, DL Varella-Garcia, M Berry, LD Dias-Santagata, D Wistuba, II Chen, HD Fujimoto, J Kugler, K Franklin, WA Iafrate, AJ Ladanyi, M Kris, MG Johnson, BE Bunn, PA Minna, JD Kwiatkowski, DJ AF Sholl, Lynette M. Aisner, Dara L. Varella-Garcia, Marileila Berry, Lynne D. Dias-Santagata, Dora Wistuba, Ignacio I. Chen, Heidi Fujimoto, Junya Kugler, Kelly Franklin, Wilbur A. Iafrate, A. John Ladanyi, Marc Kris, Mark G. Johnson, Bruce E. Bunn, Paul A. Minna, John D. Kwiatkowski, David J. CA LCMC Investigators TI Multi-institutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma The Lung Cancer Mutation Consortium Experience SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung adenocarcinoma; Mutation; FISH; Genotyping; LCMC ID GROWTH-FACTOR-RECEPTOR; KINASE INHIBITORS; EGFR MUTATIONS; INTERNATIONAL-ASSOCIATION; GEFITINIB RESISTANCE; MOLECULAR-PATHOLOGY; ALK REARRANGEMENTS; HISTOLOGIC SUBTYPE; GENE; VALIDATION AB Introduction: Molecular genetic analyses of lung adenocarcinoma have recently become standard of care for treatment selection. The Lung Cancer Mutation Consortium was formed to enable collaborative multi-institutional analyses of 10 potential oncogenic driver mutations. Technical aspects of testing and clinicopathologic correlations are presented. Methods: Mutation testing in at least one of the eight genes (epidermal growth factor receptor [EGFR], KRAS, ERBB2, AKT1, BRAF, MEK1, NRAS, and PIK3CA) using SNaPshot, mass spectrometry, Sanger sequencing+/-peptide nucleic acid and/or sizing assays, along with anaplastic lymphoma kinase (ALK) and/or MET fluorescence in situ hybridization, were performed in six labs on 1007 patients from 14 institutions. Results: In all, 1007 specimens had mutation analysis performed, and 733 specimens had all 10 genes analyzed. Mutation identification rates did not vary by analytic method. Biopsy and cytology specimens were inadequate for testing in 26% and 35% of cases compared with 5% of surgical specimens. Among the 1007 cases with mutation analysis performed, EGFR, KRAS, ALK, and ERBB2 alterations were detected in 22%, 25%, 8.5%, and 2.4% of cases, respectively. EGFR mutations were highly associated with female sex, Asian race, and never-smoking status; and less strongly associated with stage IV disease, presence of bone metastases, and absence of adrenal metastases. ALK rearrangements were strongly associated with never-smoking status and more weakly associated with presence of liver metastases. ERBB2 mutations were strongly associated with Asian race and never-smoking status. Two mutations were seen in 2.7% of samples, all but one of which involved one or more of PIK3CA, ALK, or MET. Conclusion: Multi-institutional molecular analysis across multiple platforms, sample types, and institutions can yield consistent results and novel clinicopathological observations. C1 [Sholl, Lynette M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Aisner, Dara L.; Varella-Garcia, Marileila; Franklin, Wilbur A.] Univ Colorado, Dept Pathol, Aurora, CO USA. [Varella-Garcia, Marileila; Kugler, Kelly] Univ Colorado, Div Med Oncol, Dept Med, Aurora, CO USA. [Dias-Santagata, Dora; Iafrate, A. John] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Dias-Santagata, Dora; Iafrate, A. John] Harvard Univ, Sch Med, Boston, MA USA. [Wistuba, Ignacio I.; Fujimoto, Junya] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA. [Ladanyi, Marc; Kris, Mark G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Johnson, Bruce E.; Kwiatkowski, David J.] Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bunn, Paul A.] Univ Colorado, Ctr Canc, Lung Canc Mutat Consortium, Aurora, CO USA. [Minna, John D.] Univ Texas Southwestern, Dallas, TX USA. RP Kwiatkowski, DJ (reprint author), Brigham & Womens Hosp, Dept Med, 1 Blackfan Circle,Karp Bldg 6th Floor,Rm 213, Boston, MA 02115 USA. EM dk@rics.bwh.harvard.edu OI Kris, Mark/0000-0002-7317-5341 FU University of Colorado Lung Cancer SPORE [P50CA058187]; University of Colorado Cancer Center Molecular Pathology Shared Resource [CCSG P30CA046934]; Dana Farber/Harvard Cancer Center SPORE in Lung Cancer [2P50CA090578-11]; Lung Cancer Mutation Analysis [1RC2 CA148394] FX This study was supported by University of Colorado Lung Cancer SPORE (P50CA058187 PI: Paul A. Bunn); University of Colorado Cancer Center Molecular Pathology Shared Resource (CCSG P30CA046934); Dana Farber/Harvard Cancer Center SPORE in Lung Cancer (2P50CA090578-11 PI: Bruce E. Johnson); The Lung Cancer Mutation Analysis (1RC2 CA148394 PI: Paul A. Bunn); and a generous gift from Scott Semel (David J. Kwiatkowski). NR 40 TC 53 Z9 54 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAY PY 2015 VL 10 IS 5 BP 768 EP 777 DI 10.1097/JTO.0000000000000516 PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CI8AP UT WOS:000354990100017 PM 25738220 ER PT J AU Arrieta, O Cardona, AF Martin, C Mas-Lopez, L Corrales-Rodriguez, L Bramuglia, G Castillo-Fernandez, O Meyerson, M Amieva-Rivera, E Campos-Parra, AD Carranza, H de la Torre, JCG Powazniak, Y Aldaco-Sarvide, F Vargas, C Trigo, M Magallanes-Maciel, M Otero, J Sanchez-Reyes, R Cuello, M AF Arrieta, Oscar Cardona, Andres F. Martin, Claudio Mas-Lopez, Luis Corrales-Rodriguez, Luis Bramuglia, Guillermo Castillo-Fernandez, Omar Meyerson, Matthew Amieva-Rivera, Eduardo Delia Campos-Parra, Alma Carranza, Hernn Carlos Gomez de la Torre, Juan Powazniak, Yanina Aldaco-Sarvide, Fernando Vargas, Carlos Trigo, Mariana Magallanes-Maciel, Manuel Otero, Jorge Sanchez-Reyes, Roberto Cuello, Mauricio TI Updated Frequency of EGFR and KRAS Mutations in NonSmall-Cell Lung Cancer in Latin America The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Non small-cell lung cancer; Epidermal growth factor; Anaplastic lymphoma kinase; Mutation; Frequency ID RECEPTOR GENE-MUTATIONS; WOOD-SMOKE EXPOSURE; ADENOCARCINOMA; GEFITINIB; ERLOTINIB; HISTOLOGY; SURVIVAL; FEATURES; OUTCOMES AB Introduction: Previously, we reported the frequency of epidermal growth factor receptor (EGFR) and KRAS mutations in nonsmall-cell lung cancer (NSCLC) patients in Latin America. The EGFR mutation frequency was found between Asian (40%) and Caucasian (15%) populations. Here, we report the updated distribution of NSCLC mutations. Methods: A total of 5738 samples from NSCLC patients from Argentina (1713), Mexico (1417), Colombia (1939), Peru (393), Panama (174), and Costa Rica (102) were genotyped for EGFR and KRAS. Results: The median patient age was 62.2 +/- 12.3 years; 53.5% were women, 46.7% had a history of smoking, and 95.2% had adenocarcinoma histology. The frequency of EGFR mutations was 26.0% (95% confidence interval [CI], 24.9-27.1; Argentina, 14.4% [12.8-15.6]; Mexico, 34.3% [31.9-36.7]; Colombia, 24.7% [22.8-26.6]; Peru, 51.1% [46.2-55.9]; Panama, 27.3 [20.7-33.9]; and Costa Rica, 31.4% [22.4-40.4]). The frequency of KRAS mutations was 14.0% (9.1-18.9). In patients with adenocarcinoma, EGFR mutations were independently associated with gender (30.7% females vs. 18.4% males; p < 0.001), nonsmoker status (27.4% vs. 17.1%, p < 0.001), ethnicity (mestizo/indigenous, 35.3% vs. Caucasian, 13.7%, p < 0.001), and the absence of KRAS mutation (38.1% vs. 4.7%; p < 0.001). The overall response rate to EGFR tyrosine kinase inhibitors was 60.6% (95% CI, 52-69), with a median progression-free survival and overall survival of 15.9 (95% CI, 12.420.6) and 32 months (95% CI, 26.5-37.6), respectively. Conclusion: Our findings support the genetic heterogeneity of NSCLC in Latin America, confirming that the frequency of EGFR mutations is intermediate between that observed in the Asian and Caucasian populations. C1 [Arrieta, Oscar; Amieva-Rivera, Eduardo; Delia Campos-Parra, Alma; Sanchez-Reyes, Roberto] Inst Nacl Cancerol Mexico, Thorac Oncol Clin, Mexico City, DF, Mexico. [Arrieta, Oscar; Amieva-Rivera, Eduardo; Delia Campos-Parra, Alma; Sanchez-Reyes, Roberto] Inst Nacl Cancerol Mexico, Expt Oncol Lab, Mexico City, DF, Mexico. [Cardona, Andres F.; Otero, Jorge] Fdn Santa Fe Bogota, Clin & Translat Oncol Grp, Bogota, Colombia. [Martin, Claudio] Alexander Fleming Inst, Dept Oncol, Buenos Aires, DF, Argentina. [Mas-Lopez, Luis; Carlos Gomez de la Torre, Juan] Inst Enfermedades Neoplas, Dept Clin Oncol, Lima, Peru. [Martin, Claudio; Corrales-Rodriguez, Luis; Bramuglia, Guillermo] Hosp San Juan Dios, Oncol Med, San Jose, Costa Rica. [Bramuglia, Guillermo; Powazniak, Yanina; Trigo, Mariana] Univ Buenos Aires, Catedra Farmacol, Fac Farm & Bioquim, Fdn Investigar, Buenos Aires, DF, Argentina. [Castillo-Fernandez, Omar] Inst Oncol Nacl, Ancona, Panama. [Meyerson, Matthew] MIT, Broad Inst Harvard, Cambridge, MA 02139 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Aldaco-Sarvide, Fernando; Magallanes-Maciel, Manuel] ISSSTE, Ctr Med Nacl Noviembre Mexico 20, Mexico City, DF, Mexico. [Cuello, Mauricio] Hosp Clin UdelaR, Dept Med, Montevideo, Uruguay. Clin Hosp Britan Buenos Aires, Buenos Aires, DF, Argentina. RP Arrieta, O (reprint author), Inst Nacl Cancerol INCan, Thorac Oncol Unit, San Fernando 22,Col Secc 16, Mexico City 14080, DF, Mexico. EM ogar@unam.mx NR 32 TC 18 Z9 20 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAY PY 2015 VL 10 IS 5 BP 838 EP 843 DI 10.1097/JTO.0000000000000481 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CI8AP UT WOS:000354990100027 PM 25634006 ER PT J AU Ackman, JB AF Ackman, Jeanne B. TI MR Imaging of Mediastinal Masses SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA LA English DT Article DE MR imaging; Mediastinal mass; Tissue characterization; Cystic; Fibrous; Hemorrhagic; Diagnostic specificity; Clinical management ID RADIOLOGIC-PATHOLOGICAL CORRELATION; CELL LUNG-CANCER; MAGNETIC-RESONANCE; COMPUTED-TOMOGRAPHY; CHEST-WALL; BRONCHOGENIC-CARCINOMA; CAVERNOUS HEMANGIOMA; THYMIC HYPERPLASIA; SIGNAL INTENSITY; CYSTIC MASSES AB The high soft tissue contrast of MR imaging enables superior tissue characterization of mediastinal masses, adding diagnostic specificity and often changing and benefiting clinical management. MR imaging can better discern cystic from solid content and can detect microscopic fat, hemorrhage, and fibrous content within lesions. In many cases, mediastinal MR imaging may prevent unnecessary diagnostic intervention. In other cases, MR imaging may indicate the optimal site for biopsy or the correct compartment for resection. Awareness of the efficacy of MR imaging with regard to mediastinal mass characterization and judicious MR imaging utilization should further improve patient care. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Imaging & Intervent,Dept Radiol, Boston, MA 02114 USA. RP Ackman, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Imaging & Intervent,Dept Radiol, Founders 202,55 Fruit St, Boston, MA 02114 USA. EM jackman@mgh.harvard.edu NR 50 TC 5 Z9 6 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-9689 EI 1557-9786 J9 MAGN RESON IMAGING C JI Magn. Reson. Imaging Clin. N. Am. PD MAY PY 2015 VL 23 IS 2 BP 141 EP + DI 10.1016/j.mric.2015.01.002 PG 25 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CJ3BG UT WOS:000355357800004 PM 25952512 ER PT J AU Pan, W Zhu, S Dai, D Liu, Z Li, D Li, B Gagliani, N Zheng, YJ Tang, YJ Weirauch, MT Chen, XT Zhu, W Wang, Y Chen, B Qian, YC Chen, YX Fang, JY Herbst, R Richman, L Jallal, B Harley, JB Flavell, RA Yao, YH Shen, N AF Pan, Wen Zhu, Shu Dai, Dai Liu, Zheng Li, Dan Li, Bin Gagliani, Nicola Zheng, Yunjiang Tang, Yuanjia Weirauch, Matthew T. Chen, Xiaoting Zhu, Wei Wang, Yue Chen, Bo Qian, Youcun Chen, Yingxuan Fang, Jingyuan Herbst, Ronald Richman, Laura Jallal, Bahija Harley, John B. Flavell, Richard A. Yao, Yihong Shen, Nan TI MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis SO NATURE COMMUNICATIONS LA English DT Article ID REGULATORY T-CELLS; DEVELOPING MICRORNA THERAPEUTICS; SYSTEM AUTOIMMUNE-DISEASE; ROR-GAMMA-T; MULTIPLE-SCLEROSIS; LINEAGE COMMITMENT; TGF-BETA; ENHANCER LANDSCAPE; FOXP3; TRANSCRIPTION AB Although different autoimmune diseases show discrete clinical features, there are common molecular pathways intimately involved. Here we show that miR-125a is downregulated in peripheral CD4(+) T cells of human autoimmune diseases including systemic lupus erythematosus and Crohn's disease, and relevant autoimmune mouse models. miR-125a stabilizes both the commitment and immunoregulatory capacity of Treg cells. In miR-125a-deficient mice, the balance appears to shift from immune suppression to inflammation, and results in more severe pathogenesis of colitis and experimental autoimmune encephalomyelitis (EAE). The genome-wide target analysis reveals that miR-125a suppresses several effector T-cell factors including Stat3, Ifng and Il13. Using a chemically synthesized miR-125a analogue, we show potential to re-programme the immune homeostasis in EAE models. These findings point to miR-125a as a critical factor that controls autoimmune diseases by stabilizing Treg-mediated immune homeostasis. C1 [Pan, Wen; Dai, Dai; Tang, Yuanjia; Qian, Youcun; Shen, Nan] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai Canc Inst,State Key Lab Oncogenes & Rela, Shanghai 200032, Peoples R China. [Pan, Wen; Dai, Dai; Tang, Yuanjia; Shen, Nan] Chinese Acad Sci, Inst Hlth Sci, Joint Mol Rheumatol Lab, Shanghai 200025, Peoples R China. [Pan, Wen; Dai, Dai; Tang, Yuanjia; Shen, Nan] Chinese Acad Sci, Shanghai Renji Hosp, Shanghai Inst Biol Sci, Shanghai 200025, Peoples R China. [Pan, Wen; Dai, Dai; Tang, Yuanjia; Shen, Nan] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200025, Peoples R China. [Pan, Wen] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. [Zhu, Shu; Gagliani, Nicola; Zheng, Yunjiang; Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA. [Liu, Zheng; Zhu, Wei; Wang, Yue; Chen, Bo; Herbst, Ronald; Richman, Laura; Jallal, Bahija; Yao, Yihong] MedImmune LLC, Gaithersburg, MD 20878 USA. [Li, Dan; Li, Bin] Chinese Acad Sci, Inst Pasteur Shanghai, Shanghai 200025, Peoples R China. [Weirauch, Matthew T.; Harley, John B.; Shen, Nan] Cincinnati Childrens Hosp Med Ctr, CAGE, Cincinnati, OH 45229 USA. [Chen, Xiaoting] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA. [Chen, Yingxuan; Fang, Jingyuan] Univ Cincinnati, Sch Elect & Comp Syst, Cincinnati, OH 45221 USA. [Chen, Xiaoting] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Inst Digest Dis,Div Gastroenterol & Hepa, Shanghai 200001, Peoples R China. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH 45220 USA. [Shen, Nan] Shanghai Jiao Tong Univ, Collaborat Innovat Ctr Syst Biomed, Shanghai 200240, Peoples R China. RP Shen, N (reprint author), Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai Canc Inst,State Key Lab Oncogenes & Rela, Shanghai 200032, Peoples R China. EM YaoY@medimmune.com; nanshensibs@gmail.com RI Pan, Wen/I-9965-2016 FU 973 programme [2014CB541902, 2014CB541901]; National Natural Science Foundation of China [81230072, 81421001, 81025016, 31370880]; Key Research Program of the Chinese Academy of Sciences [KSZD-EW-Z-003-3]; State Key Laboratory of Oncogenes and Related Genes [91-14-05]; Chinese Ministry of Health [201202008]; Program of the Shanghai Commission of Science and Technology [12431900703, 12JC1406000, 12ZR1435900]; Leukemia and Lymphoma Society; Howard Hughes Medical Institute-The Helen Hay Whitney Foundation; Shenzhen Foundation of Science and Technology [GJHZ2014041417082192] FX We thank Robert Georgantas and Philip Brohawn for their helpful discussions, technical expertise and/or review of this manuscript. This work is supported by grants from 973 programme (2014CB541902 and 2014CB541901), National Natural Science Foundation of China (81230072, 81421001, 81025016 and 31370880), the Key Research Program of the Chinese Academy of Sciences (KSZD-EW-Z-003-3), the grants from the State Key Laboratory of Oncogenes and Related Genes (No. 91-14-05) as well as Chinese Ministry of Health (201202008) and the Program of the Shanghai Commission of Science and Technology (12431900703, 12JC1406000 and 12ZR1435900). W.P. is supported by a fellowship from Leukemia and Lymphoma Society. S.Z. is supported by a fellowship from Howard Hughes Medical Institute-The Helen Hay Whitney Foundation and Shenzhen Foundation of Science and Technology (grant number GJHZ2014041417082192). NR 49 TC 9 Z9 10 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 MAY PY 2015 VL 6 AR 7096 DI 10.1038/ncomms8096 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ5ML UT WOS:000355531600004 PM 25963922 ER PT J AU McDonald, LT Russell, DL Kelly, RR Xiong, Y Motamarry, A Patel, RK Jones, JA Watson, PM Turner, DP Watson, DK Soloff, AC Findlay, VJ LaRue, AC AF McDonald, Lindsay T. Russell, Dayvia L. Kelly, Ryan R. Xiong, Ying Motamarry, Anjan Patel, Risha K. Jones, Jeffrey A. Watson, Patricia M. Turner, David P. Watson, Dennis K. Soloff, Adam C. Findlay, Victoria J. LaRue, Amanda C. TI Hematopoietic Stem Cell-Derived Cancer-Associated Fibroblasts Are Novel Contributors to the Pro-Tumorigenic Microenvironment SO NEOPLASIA LA English DT Article ID CARCINOMA-ASSOCIATED FIBROBLASTS; ENDOTHELIAL GROWTH-FACTOR; HUMAN BREAST-CANCER; GENE-EXPRESSION SIGNATURE; PROMOTE TUMOR-GROWTH; MESENCHYMAL TRANSITION; STROMAL FIBROBLASTS; MICROVESSEL DENSITY; ANGIOGENIC SWITCH; POOR-PROGNOSIS AB Targeting the tumor microenvironment is critical toward improving the effectiveness of cancer therapeutics. Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types of the tumor microenvironment, playing an important role in tumor progression. Multiple origins for CAFs have been proposed including resident fibroblasts, adipocytes, and bonemarrow. Our laboratory previously identified a novel hematopoietic stem cell (HSC) origin for CAFs; however, the functional roles of HSC-derived CAFs (HSC-CAFs) in tumor progression have not yet been examined. To test the hypothesis that HSC-CAFs promote tumor progression through contribution to extracellular matrix (ECM) and paracrine production of pro-angiogenic factors, we developed a method to isolate HSC-CAFs. HSC-CAFs were profiled on the basis of their expression of hematopoietic and fibroblastic markers in two murine tumor models. Profiling revealed production of factors associated with ECM deposition and remodeling. Functional in vivo studies showed that co-injection of HSC-CAFs with tumor cells resulted in increased tumor growth rate and significantly larger tumors than tumor cells alone. Immunohistochemical studies revealed increased blood vessel density with co-injection, demonstrating a role for HSC-CAFs in tumor vascularization. Mechanistic in vitro studies indicated that HSC-CAFs play a role in producing vascular endothelial growth factor A and transforming growth factor-beta 1 in endothelial tube formation and patterning. In vitro and in vivo findings suggest that HSC-CAFs are a critical component of the tumor microenvironment and suggest that targeting the novel HSC-CAF may be a promising therapeutic strategy. C1 [McDonald, Lindsay T.; Russell, Dayvia L.; Kelly, Ryan R.; Xiong, Ying; LaRue, Amanda C.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29425 USA. [McDonald, Lindsay T.; Russell, Dayvia L.; Kelly, Ryan R.; Xiong, Ying; Turner, David P.; Watson, Dennis K.; Findlay, Victoria J.; LaRue, Amanda C.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [McDonald, Lindsay T.; Russell, Dayvia L.; Kelly, Ryan R.; Xiong, Ying; Watson, Patricia M.; Turner, David P.; Watson, Dennis K.; Soloff, Adam C.; Findlay, Victoria J.; LaRue, Amanda C.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Motamarry, Anjan] Med Univ S Carolina, Coll Grad Studies, Charleston, SC 29425 USA. [Patel, Risha K.; Jones, Jeffrey A.] Med Univ S Carolina, Dept Surg, Div Cardiothorac Res, Charleston, SC 29425 USA. [Watson, Patricia M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Soloff, Adam C.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP LaRue, AC (reprint author), Ralph H Johnson Vet Affairs Med Ctr, 109 Bee St,Res 151, Charleston, SC 29425 USA. EM laruerc@musc.edu OI Soloff, Adam/0000-0002-1467-8168 FU NIH (National Institutes of Health)/NCI (National Cancer Institute) [R01 CA148772]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs; Hollings Cancer Center [P30 CA138313] FX This work is supported in part by the NIH (National Institutes of Health)/NCI (National Cancer Institute) (R01 CA148772, A.C.L.), the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs (Merit Awards, A.C.L.), and the Hollings Cancer Center (Translational Research Pilot Project, P30 CA138313, A.C.L.). NR 73 TC 4 Z9 4 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1476-5586 J9 NEOPLASIA JI Neoplasia PD MAY PY 2015 VL 17 IS 5 BP 434 EP 448 DI 10.1016/j.neo.2015.04.004 PG 15 WC Oncology SC Oncology GA CJ1BN UT WOS:000355216700004 PM 26025666 ER PT J AU Rhee, CM Brent, GA Kovesdy, CP Soldin, OP Nguyen, D Budoff, MJ Brunelli, SM Kalantar-Zadeh, K AF Rhee, Connie M. Brent, Gregory A. Kovesdy, Csaba P. Soldin, Offie P. Danh Nguyen Budoff, Matthew J. Brunelli, Steven M. Kalantar-Zadeh, Kamyar TI Thyroid functional disease: an under-recognized cardiovascular risk factor in kidney disease patients SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Review DE cardiovascular risk; hyperthyrotropinemia; hypothyroidism; renal failure; thyroid functional disease ID STAGE RENAL-DISEASE; AMBULATORY PERITONEAL-DIALYSIS; HORMONE REPLACEMENT THERAPY; TANDEM MASS-SPECTROMETRY; MEAN PLATELET VOLUME; ALL-CAUSE MORTALITY; C-REACTIVE PROTEIN; CORONARY-ARTERY-DISEASE; HUMAN RECOMBINANT ERYTHROPOIETIN; INCIDENT HEMODIALYSIS-PATIENTS AB Thyroid functional disease, and in particular hypothyroidism, is highly prevalent among chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In the general population, hypothyroidism is associated with impaired cardiac contractility, endothelial dysfunction, atherosclerosis and possibly higher cardiovascular mortality. It has been hypothesized that hypothyroidism is an under-recognized, modifiable risk factor for the enormous burden of cardiovascular disease and death in CKD and ESRD, but this has been difficult to test due to the challenge of accurate thyroid functional assessment in uremia. Low thyroid hormone levels (i.e. triiodothyronine) have been associated with adverse cardiovascular sequelae in CKD and ESRD patients, but these metrics are confounded by malnutrition, inflammation and comorbid states, and hence may signify nonthyroidal illness (i.e. thyroid functional test derangements associated with underlying ill health in the absence of thyroid pathology). Thyrotropin is considered a sensitive and specific thyroid function measure that may more accurately classify hypothyroidism, but few studies have examined the clinical significance of thyrotropin-defined hypothyroidism in CKD and ESRD. Of even greater uncertainty are the risks and benefits of thyroid hormone replacement, which bear a narrow therapeutic-to-toxic window and are frequently prescribed to CKD and ESRD patients. In this review, we discuss mechanisms by which hypothyroidism adversely affects cardiovascular health; examine the prognostic implications of hypothyroidism, thyroid hormone alterations and exogenous thyroid hormone replacement in CKD and ESRD; and identify areas of uncertainty related to the interplay between hypothyroidism, cardiovascular disease and kidney disease requiring further investigation. C1 [Rhee, Connie M.; Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Div Nephrol & Hypertens, Harold Simmons Ctr Kidney Dis Res & Epidemiol, Orange, CA 92668 USA. [Brent, Gregory A.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Kovesdy, Csaba P.] Memphis Vet Affairs Med Ctr, Div Nephrol, Memphis, TN USA. [Kovesdy, Csaba P.] Univ Tennessee, Hlth Sci Ctr, Div Nephrol, Memphis, TN USA. [Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Danh Nguyen] Univ Calif Irvine, Dept Med, Orange, CA 92668 USA. [Budoff, Matthew J.] Harbor UCLA Med Ctr, Div Cardiol, LA Biomed Res Inst, Los Angeles, CA USA. [Brunelli, Steven M.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA. [Brunelli, Steven M.] DaVita Clin Res, Minneapolis, MN USA. [Kalantar-Zadeh, Kamyar] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. RP Rhee, CM (reprint author), Univ Calif Irvine, Div Nephrol & Hypertens, Harold Simmons Ctr Kidney Dis Res & Epidemiol, Orange, CA 92668 USA. EM crhee1@uci.edu OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 FU National Institutes of Health [F32 DK093201, R01 DK078106, K24 DK091419]; National Center for Advancing Translational Sciences grant [UL1 TR000153] FX CMR was supported by a National Institutes of Health grant (F32 DK093201). DVN is supported by a National Center for Advancing Translational Sciences grant (UL1 TR000153). KKZ is supported by research grants from the National Institutes of Health (R01 DK078106, K24 DK091419) and a philanthropist grant from Mr. Harold Simmons. NR 187 TC 10 Z9 11 U1 0 U2 4 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 MAY PY 2015 VL 30 IS 5 BP 724 EP 737 DI 10.1093/ndt/gfu024 PG 14 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA CJ2LE UT WOS:000355315300007 PM 24574542 ER PT J AU Nuhi, V Parnell, A MacKenzie, E Macumber, M Castle, S AF Nuhi, Veldana Parnell, Anne MacKenzie, Elizabeth Macumber, Michelle Castle, Sharon TI Impact of a pharmacy technician admission medication history pilot program in a Veterans Affairs medical center. SO PHARMACOTHERAPY LA English DT Meeting Abstract C1 [Nuhi, Veldana; Parnell, Anne; MacKenzie, Elizabeth; Macumber, Michelle; Castle, Sharon] Ralph H Johnson Vet Affairs Med Ctr, Dept Pharm, Charleston, SC 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 MAY PY 2015 VL 35 IS 5 MA 50 BP E80 EP E80 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CJ1IC UT WOS:000355236300050 ER PT J AU Rahman, SH Kuehle, J Reimann, C Mlambo, T Alzubi, J Maeder, ML Riedel, H Fisch, P Cantz, T Rudolph, C Mussolino, C Joung, JK Schambach, A Cathomen, T AF Rahman, Shamim H. Kuehle, Johannes Reimann, Christian Mlambo, Tafadzwa Alzubi, Jamal Maeder, Morgan L. Riedel, Heimo Fisch, Paul Cantz, Tobias Rudolph, Cornelia Mussolino, Claudio Joung, J. Keith Schambach, Axel Cathomen, Toni TI Rescue of DNA-PK Signaling and T-Cell Differentiation by Targeted Genome Editing in a prkdc Deficient iPSC Disease Model SO PLOS GENETICS LA English DT Article ID PLURIPOTENT STEM-CELLS; ZINC-FINGER NUCLEASES; DEPENDENT PROTEIN-KINASE; COMBINED IMMUNE-DEFICIENCY; IN-VITRO; HEMATOPOIETIC-CELLS; V(D)J RECOMBINATION; GENETIC CORRECTION; SCID MUTATION; GENERATION AB In vitro disease modeling based on induced pluripotent stem cells (iPSCs) provides a powerful system to study cellular pathophysiology, especially in combination with targeted genome editing and protocols to differentiate iPSCs into affected cell types. In this study, we established zinc-finger nuclease-mediated genome editing in primary fibroblasts and iPSCs generated from a mouse model for radiosensitive severe combined immunodeficiency (RS-SCID), a rare disorder characterized by cellular sensitivity to radiation and the absence of lymphocytes due to impaired DNA-dependent protein kinase (DNA-PK) activity. Our results demonstrate that gene editing in RS-SCID fibroblasts rescued DNA-PK dependent signaling to overcome radiosensitivity. Furthermore, in vitro T-cell differentiation from iPSCs was employed to model the stage-specific T-cell maturation block induced by the disease causing mutation. Genetic correction of the RS-SCID iPSCs restored T-lymphocyte maturation, polyclonal V(D)J recombination of the T-cell receptor followed by successful beta-selection. In conclusion, we provide proof that iPSC-based in vitro T-cell differentiation is a valuable paradigm for SCID disease modeling, which can be utilized to investigate disorders of T-cell development and to validate gene therapy strategies for T-cell deficiencies. Moreover, this study emphasizes the significance of designer nucleases as a tool for generating isogenic disease models and their future role in producing autologous, genetically corrected transplants for various clinical applications. C1 [Rahman, Shamim H.; Reimann, Christian; Mlambo, Tafadzwa; Alzubi, Jamal; Mussolino, Claudio; Cathomen, Toni] Univ Med Ctr Freiburg, Inst Cell & Gene Therapy, Freiburg, Germany. [Rahman, Shamim H.; Reimann, Christian; Mlambo, Tafadzwa; Alzubi, Jamal; Mussolino, Claudio; Cathomen, Toni] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany. [Rahman, Shamim H.; Kuehle, Johannes; Alzubi, Jamal; Riedel, Heimo; Schambach, Axel; Cathomen, Toni] Hannover Med Sch, Inst Expt Hematol, Hannover, Germany. [Mlambo, Tafadzwa] Univ Freiburg, Spemann Grad Sch Biol & Med SGBM, D-79106 Freiburg, Germany. [Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Riedel, Heimo] W Virginia Univ, Dept Biochem, Morgantown, WV 26506 USA. [Riedel, Heimo] W Virginia Univ, Mary Babb Randolph Canc Ctr, Robert C Byrd Hlth Sci Ctr, Morgantown, WV 26506 USA. [Fisch, Paul] Univ Med Ctr Freiburg, Inst Pathol, Freiburg, Germany. [Cantz, Tobias] Hannover Med Sch, Translat Hepatol & Stem Cell Biol, REBIRTH Cluster Excellence, Hannover, Germany. [Rudolph, Cornelia] Hannover Med Sch, Inst Cellular & Mol Pathol, Hannover, Germany. RP Rahman, SH (reprint author), Univ Med Ctr Freiburg, Inst Cell & Gene Therapy, Freiburg, Germany. EM Schambach.Axel@mh-hannover.de; Toni.Cathomen@uniklinik-freiburg.de OI Cathomen, Toni/0000-0002-7757-4630 FU German Research Foundation [SPP1230Ca311/2, SFB 738C9, EXC 62/1]; German Federal Ministry of Education and Research [BMBF 01EO0803, ReGene-01GN1003D]; German Academic Exchange Service [DAAD]; European Commission1s 7th Framework Program [PERSIST-222878]; National Institutes of Health [R01 GM088040]; National Science Foundation FX This work was supported by the German Research Foundation [SPP1230Ca311/2 to TCat; SFB 738C9 to AS and TCat; the REBIRTH Cluster of Excellence to AS and TCan (EXC 62/1) and JA and JK (fellowships)], the German Federal Ministry of Education and Research [BMBF 01EO0803 to TCat; ReGene-01GN1003D to TCat and AS], the German Academic Exchange Service [DAAD fellowship to TM], the European Commission1s 7th Framework Program [PERSIST-222878 to TCat], the National Institutes of Health [R01 GM088040 to JKJ], and the National Science Foundation [Graduate Research Fellowship to MLM]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 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 MAY PY 2015 VL 11 IS 5 AR UNSP e1005239 DI 10.1371/journal.pgen.1005239 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA CJ2HQ UT WOS:000355305200049 PM 26000857 ER PT J AU Brown, LE Frits, ML Iannaccone, CK Weinblatt, ME Shadick, NA Liao, KP AF Brown, Lindsay E. Frits, Michelle L. Iannaccone, Christine K. Weinblatt, Michael E. Shadick, Nancy A. Liao, Katherine P. TI Clinical characteristics of RA patients with secondary SS and association with joint damage SO RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; Sjogren's syndrome; synovium; hand; radiology ID RHEUMATOID-ARTHRITIS; SJOGRENS-SYNDROME; CLASSIFICATION CRITERIA; SICCA SYMPTOMS; DISEASE; VARIABLES; COHORT AB Objectives. Secondary SS (sSS) is a common extra-articular manifestation of RA. There are conflicting data regarding the association of sSS with worse joint damage. This study aims to characterize sSS patients in an RA cohort and study the association between sSS and joint damage. Methods. We conducted a cross-sectional study of RA patients with a parts per thousand yen1 year of follow-up at a large academic centre. Subjects with co-morbid diseases that can also result in sicca symptoms were excluded from the analysis. Subjects were considered to have sSS if they were reported as having sSS by their rheumatologist at recruitment into the cohort and had the diagnosis confirmed by chart review. The primary outcome was Sharp score using bilateral hand radiographs at recruitment. We constructed a linear regression model to determine the association of sSS status and Sharp score adjusted by age, gender, disease duration and ACPA and RF status. Results. We studied 829 RA subjects, mean age 57 years, 83% female, mean RA duration 13 years, 74% seropositive; 85 subjects (10.3%) had sSS. We observed a female predominance (95.3%), longer mean disease duration (16.9 years) and higher frequency of RF or ACPA positive among patients with sSS and RA. Having sSS at baseline was associated with higher Sharp scores (P = 0.03), independent of age, gender, RA disease duration and seropositive disease. Conclusion. In our RA cohort, RA subjects with sSS had worse joint damage, suggesting that sSS is a marker of more aggressive disease. C1 [Brown, Lindsay E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Frits, Michelle L.; Iannaccone, Christine K.; Weinblatt, Michael E.; Shadick, Nancy A.; Liao, Katherine P.] Brigham & Womens Hosp, Div Rheumatol, Dept Med Immunol & Allergy, Boston, MA 02115 USA. RP Liao, KP (reprint author), Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, 75 Francis St,PBB B3, Boston, MA 02115 USA. EM kliao@partners.org FU National Institutes of Health [K08 AR060257]; Harold and Duval Bowen Fund FX The work was supported under Dr Liao, who is funded by the National Institutes of Health (K08 AR060257) and the Harold and Duval Bowen Fund. NR 18 TC 1 Z9 1 U1 2 U2 5 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 MAY PY 2015 VL 54 IS 5 BP 816 EP 820 DI 10.1093/rheumatology/keu400 PG 5 WC Rheumatology SC Rheumatology GA CI8IY UT WOS:000355017200010 PM 25313147 ER PT J AU Whitaker, RM Korrapati, MC Stallons, LJ Jesinkey, SR Arthur, JM Beeson, CC Zhong, Z Schnellmann, RG AF Whitaker, Ryan M. Korrapati, Midhun C. Stallons, Lindsey J. Jesinkey, Sean R. Arthur, John M. Beeson, Craig C. Zhong, Zhi Schnellmann, Rick G. TI Urinary ATP Synthase Subunit beta Is a Novel Biomarker of Renal Mitochondrial Dysfunction in Acute Kidney Injury SO TOXICOLOGICAL SCIENCES LA English DT Article DE acute kidney injury; ischemia-reperfusion; mitochondria; biomarker; ATP synthase beta ID ISCHEMIA-REPERFUSION INJURY; PATHOPHYSIOLOGY; BIOGENESIS; AKI; HOMEOSTASIS; RECOVERY; DISEASES; CELLS AB Although the importance of mitochondrial dysfunction in acute kidney injury (AKI) has been documented, noninvasive early biomarkers of mitochondrial damage are needed. We examined urinary ATP synthase subunit beta (ATPS beta) as a biomarker of renal mitochondrial dysfunction during AKI. Mice underwent sham surgery or varying degrees (5, 10, or 15 min ischemia) of ischemia/reperfusion (I/R)-induced AKI. Serum creatinine, BUN, and neutrophil gelatinase-associated lipocalin were elevated only in the 15 min I/R group at 24 h. Immunoblot analysis of urinary ATPS beta revealed two bands (full length similar to 52 kDa and cleaved similar to 25 kDa), both confirmed as ATPS beta by LC-MS/MS, that increased at 24 h in 10- and 15-min I/R groups. These changes were associated with mitochondrial dysfunction evidenced by reduced renal cortical expression of mitochondrial proteins, ATPS beta and COX1, proximal tubular oxygen consumption, and ATP. Furthermore, in the 15-min I/R group, urinary ATPS beta was elevated until 72 h before returning to baseline 144 h after reperfusion with recovery of renal function. Evaluation of urinary ATPS beta in a nonalcoholic steatohepatitis model of liver injury only revealed cleaved ATPS beta, suggesting specificity of full-length ATPS beta for renal injury. Immunoblot analyses of patient urine samples collected 36 h after cardiac surgery revealed increased urinary ATPS beta levels in patients with postcardiac surgery-induced AKI. LC-MS/MS urinalysis in human subjects with AKI confirmed increased ATPS beta. These translational studies provide evidence that ATPS beta may be a novel and sensitive urinary biomarker of renal mitochondrial dysfunction and could serve as valuable tool for the testing of potential therapies for AKI and chemical-induced nephrotoxicity. C1 [Whitaker, Ryan M.; Korrapati, Midhun C.; Stallons, Lindsey J.; Jesinkey, Sean R.; Beeson, Craig C.; Zhong, Zhi; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Arthur, John M.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Arthur, John M.; Schnellmann, Rick G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29425 USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institute of Environmental Health and Sciences [SBIR/STTR ES023767-01]; South Carolina Clinical and Translational Research (SCTR) Institute; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs FX National Institute of Environmental Health and Sciences (SBIR/STTR ES023767-01 to R.G.S.); the South Carolina Clinical and Translational Research (SCTR) Institute, which has an academic home at the Medical University of South Carolina CTSA; the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. NR 26 TC 2 Z9 2 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2015 VL 145 IS 1 BP 108 EP 117 DI 10.1093/toxsci/kfv038 PG 10 WC Toxicology SC Toxicology GA CJ1YL UT WOS:000355280900012 PM 25666834 ER PT J AU Cheng, Y Nebeker, JR Knippenberg, KA Nelson, RE Goetz, MB LaFleur, J AF Cheng, Y. Nebeker, J. R. Knippenberg, K. A. Nelson, R. E. Goetz, M. B. LaFleur, J. TI PREDICTING HUMAN IMMUNODEFICIENCY VIRUS VETERANS' ADHERENCE TO ANTIRETROVIRAL AGENTS VIA OPTIMAL DATA ANALYSIS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Cheng, Y.; Nebeker, J. R.; Knippenberg, K. A.; Nelson, R. E.; LaFleur, J.] Univ Utah, Salt Lake City, UT USA. [Goetz, M. B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2015 VL 18 IS 3 MA PIN78 BP A241 EP A241 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA CI1IZ UT WOS:000354498504090 ER PT J AU Epstein, AJ Wong, Y Mitra, N Vachani, A Hin, S Yang, L Smith-McLallen, A Armstrong, K Groeneveld, PW AF Epstein, A. J. Wong, Y. Mitra, N. Vachani, A. Hin, S. Yang, L. Smith-McLallen, A. Armstrong, K. Groeneveld, P. W. TI THE IMPACT OF GENOMIC TESTING ON CHEMOTHERAPY USE AND MEDICAL SPENDING IN A COMMERCIALLY-INSURED POPULATION OF BREAST CANCER PATIENTS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Epstein, A. J.; Mitra, N.; Vachani, A.; Hin, S.; Yang, L.; Groeneveld, P. W.] Univ Penn, Philadelphia, PA 19104 USA. [Wong, Y.] Temple Univ Hlth Syst, Philadelphia, PA USA. [Smith-McLallen, A.] Independence Blue Cross, Philadelphia, PA USA. [Armstrong, 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 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2015 VL 18 IS 3 MA PCN164 BP A217 EP A218 PG 4 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA CI1IZ UT WOS:000354498503273 ER PT J AU Harrow, B Sedaghat, AR Munzel, U Tarr, A Gever, L Hofmeister, J Dufour, R AF Harrow, B. Sedaghat, A. R. Munzel, U. Tarr, A. Gever, L. Hofmeister, J. Dufour, R. TI HEALTH-CARE COSTS OF ASTHMA ARE LOWER USING MP29-02*VS. SEQUENTIAL SPRAYS FOR ALLERGIC RHINITIS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Harrow, B.; Gever, L.; Hofmeister, J.; Dufour, R.] Meda Pharmaceut, Somerset, NJ USA. [Sedaghat, A. R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Sedaghat, A. R.] Harvard Univ, Sch Med, Boston, MA USA. [Munzel, U.] MEDA Pharma GmbH & Co KG, Bad Homburg, Germany. [Tarr, A.] Comprehens Hlth Insights Inc, Louisville, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2015 VL 18 IS 3 MA PRS19 BP A172 EP A172 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA CI1IZ UT WOS:000354498503027 ER PT J AU Kageleiry, A Samuelson, D Duh, MS Lefebvre, P DerSarkissian, M Campbell, JY Skotko, BG AF Kageleiry, A. Samuelson, D. Duh, M. S. Lefebvre, P. DerSarkissian, M. Campbell, J. Y. Skotko, B. G. TI OUT-OF-POCKET MEDICAL COSTS FOR PARENTS WITH CHILDREN WITH DOWN SYNDROME IN THE UNITED STATES SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Kageleiry, A.; Samuelson, D.; Duh, M. S.] Anal Grp Inc, Boston, MA USA. [Lefebvre, P.] Grp Anal Ltee, Montreal, PQ, Canada. [DerSarkissian, M.] Anal Grp, Los Angeles, CA USA. [Campbell, J. Y.] Harvard Univ, Cambridge, MA 02138 USA. [Skotko, B. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Skotko, B. G.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2015 VL 18 IS 3 MA PHS67 BP A258 EP A258 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA CI1IZ UT WOS:000354498504187 ER PT J AU Mhatre, SK Sansgiry, S Serna, O Sansgiry, SS AF Mhatre, S. K. Sansgiry, S. Serna, O. Sansgiry, S. S. TI VALIDATION OF PRESCRIPTION MEDICATION ADHERENCE PREDICTION TOOL (RXAPT) TO PREDICT NON-ADHERENCE AMONG DIABETES PATIENTS ENROLLED IN MEDICARE SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Mhatre, S. K.; Sansgiry, S. S.] Univ Houston, Houston, TX USA. [Sansgiry, S.] VA Med Ctr, Houston, TX USA. [Serna, O.] Cigna HealthSpring, Houston, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2015 VL 18 IS 3 MA PDB69 BP A64 EP + PG 4 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA CI1IZ UT WOS:000354498501054 ER PT J AU Romanus, D Cutler, D Keating, NL Lennes, IT Lamont, E Gazelle, GS Landrum, MB AF Romanus, D. Cutler, D. Keating, N. L. Lennes, I. T. Lamont, E. Gazelle, G. S. Landrum, M. B. TI USE OF MOLECULAR TESTING PRIOR TO FIRST-LINE ERLOTINIB THERAPY AMONG MEDICARE PATIENTS WITH STAGE IV NON-SMALL CELL LUNG CANCER SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Romanus, D.; Cutler, D.; Keating, N. L.; Lamont, E.; Landrum, M. B.] Harvard Univ, Boston, MA 02115 USA. [Lennes, I. T.; Gazelle, G. S.] 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 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2015 VL 18 IS 3 MA PCN182 BP A220 EP A220 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA CI1IZ UT WOS:000354498503289 ER PT J AU Romanus, D Cardarella, S Cutler, D Landrum, MB Lindeman, N Gazelle, GS AF Romanus, D. Cardarella, S. Cutler, D. Landrum, M. B. Lindeman, N. Gazelle, G. S. TI COST-EFFECTIVENESS OF MULTIPLEXED PREDICTIVE BIOMARKER SCREENING IN NON-SMALL CELL LUNG CANCER SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Romanus, D.; Cutler, D.; Landrum, M. B.] Harvard Univ, Boston, MA 02115 USA. [Cardarella, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lindeman, N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gazelle, G. S.] 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 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2015 VL 18 IS 3 MA PCN87 BP A204 EP A204 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA CI1IZ UT WOS:000354498503202 ER PT J AU Suda, KJ Hunkler, RJ Matusiak, L Vermeulen, L Schumock, G AF Suda, K. J. Hunkler, R. J. Matusiak, L. Vermeulen, L. Schumock, G. TI SPENDING ON HEPATITIS C ANTIVIRALS IN THE UNITED STATES, 2008-2014 SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Suda, K. J.] US Dept Vet Affairs, Hines, IL USA. [Suda, K. J.] Univ Illinois, Hines, IL USA. [Hunkler, R. J.; Matusiak, L.] IMS Hlth, Plymouth Meeting, PA USA. [Vermeulen, L.] UW Hosp & Clin, Madison, WI USA. [Schumock, G.] Univ Illinois, Chicago, IL 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 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2015 VL 18 IS 3 MA PGI36 BP A228 EP A228 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA CI1IZ UT WOS:000354498504018 ER PT J AU Zhang, Y AF Zhang, Y. TI ESTIMATION OF MEDICAL EXPENDITURE ASOCIATED WITH OPIOIDS USAGE IN CHRONIC NON-CANCER PAIN: A CROSS-SECTIONAL STUDY BASED ON MEDICAL EXPENDITURE SURVEY AND PANEL DATA SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Zhang, Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2015 VL 18 IS 3 MA PSY67 BP A303 EP A303 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA CI1IZ UT WOS:000354498505118 ER PT J AU Reeves, AZ Spears, WE Du, J Tan, KY Wagers, AJ Lesser, CF AF Reeves, Analise Z. Spears, William E. Du, Juan Tan, Kah Yong Wagers, Amy J. Lesser, Cammie F. TI Engineering Escherichia coli into a Protein Delivery System for Mammalian Cells SO ACS SYNTHETIC BIOLOGY LA English DT Article DE synthetic biology; type 3 secretion system; protein delivery; bacterial engineering ID III SECRETION SYSTEM; SHIGELLA-FLEXNERI; YERSINIA-ENTEROCOLITICA; HETEROLOGOUS PROTEINS; BACTERIAL INJECTION; VACCINE DEVELOPMENT; CHROMOSOMAL GENES; HELA-CELLS; SALMONELLA; INVASION AB Many Gram-negative pathogens encode type 3 secretion systems, sophisticated nanomachines that deliver proteins directly into the cytoplasm of mammalian cells. These systems present attractive opportunities for therapeutic protein delivery applications; however, their utility has been limited by their inherent pathogenicity. Here, we report the reengineering of a laboratory strain of Escherichia colt with a tunable type 3 secretion system that can efficiently deliver heterologous proteins into mammalian cells, thereby circumventing the need for virulence attenuation. We first introduced a 31 kB region of Shigella flexneri DNA that encodes all of the information needed to form the secretion nanomachine onto a plasmid that can be directly propagated within E. coil or integrated into the E. coli chromosome. To provide flexible control over type 3 secretion and protein delivery, we generated plasmids expressing master regulators of the type 3 system from either constitutive or inducible promoters. We then constructed a Gateway-compatible plasmid library of type 3 secretion sequences to enable rapid screening and identification of sequences that do not perturb function when fused to heterologous protein substrates and optimized their delivery into mammalian cells. Combining these elements, we found that coordinated expression of the type 3 secretion system and modified target protein substrates produces a nonpathogenic strain that expresses, secretes, and delivers heterologous proteins into mammalian cells. This reengineered system thus provides a highly flexible protein delivery platform with potential for future therapeutic applications. C1 [Reeves, Analise Z.; Spears, William E.; Du, Juan; Lesser, Cammie F.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA. [Reeves, Analise Z.; Du, Juan; Lesser, Cammie F.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Cambridge, MA 02138 USA. [Tan, Kah Yong; Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Tan, Kah Yong; Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Tan, Kah Yong; Wagers, Amy J.; Lesser, Cammie F.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Tan, Kah Yong; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Lesser, CF (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA. EM clesser@mgh.harvard.edu OI Du, Juan/0000-0001-7649-9571 FU NIH [GM094941, AI064285, DP2 OD004345, DK036836]; HSCI pilot grant FX The authors would like to thank Marcia Goldberg for providing pMBG324, a pACYC-based plasmid that constitutively expresses VirF, Wendy Picking for the anti-IpaB and anti-IpaD antibodies, and Wendy Garrett for critical reading of the manuscript. Richard Lee provided the cardiac reprogramming factor template plasmids, and Keith Joung provided the Tale template plasmid. This work was supported by NIH GM094941, NIH AI064285, NIH DP2 OD004345, DK036836, and a HSCI pilot grant. A.J.W. is an Early Career Scientist of the Howard Hughes Medical Institute. Content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funding agencies. NR 55 TC 2 Z9 2 U1 2 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2161-5063 J9 ACS SYNTH BIOL JI ACS Synth. Biol. PD MAY PY 2015 VL 4 IS 5 BP 644 EP 654 DI 10.1021/acssynbio.5b00002 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CI6ZP UT WOS:000354913000017 PM 25853840 ER PT J AU Maier-Hein, KH Westin, CF Shenton, ME Weiner, MW Raj, A Thomann, P Kikinis, R Stieltjes, B Pasternak, O AF Maier-Hein, Klaus H. Westin, Carl-Fredrik Shenton, Martha E. Weiner, Michael W. Raj, Ashish Thomann, Philipp Kikinis, Ron Stieltjes, Bram Pasternak, Ofer TI Widespread white matter degeneration preceding the onset of dementia SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Mild cognitive impairment; Diffusion tensor imaging; Partial volume elimination; Free-water imaging ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; HIPPOCAMPAL VOLUME; DIFFUSION MRI; BRAIN; PROGRESSION; PREDICT; CONVERSION; DIAGNOSIS; REVEALS AB Background: Brain atrophy in subjects with mild cognitive impairment (MCI) introduces partial volume effects, limiting the sensitivity of diffusion tensor imaging to white matter microstructural degeneration. Appropriate correction isolates microstructural effects in MCI that might be precursors of Alzheimer's disease (AD). Methods: Forty-eight participants (18 MCI, 15 AD, and 15 healthy controls) had magnetic resonance imaging scans and clinical evaluations at baseline and follow-up after 36 months. Ten MCI subjects were diagnosed with AD at follow-up and eight remained MCI. Free-water (FW) corrected measures on the white matter skeleton were compared between groups. Results: FW corrected radial diffusivity, but not uncorrected radial diffusivity, was increased across the brain of the converted group compared with the nonconverted group (P < .05). The extent of increases was similar to that found comparing AD with controls. Conclusion: Partial volume elimination reveals microstructural alterations preceding dementia. These alterations may prove to be an effective and feasible early biomarker of AD. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Maier-Hein, Klaus H.; Westin, Carl-Fredrik; Shenton, Martha E.; Kikinis, Ron; Pasternak, Ofer] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Maier-Hein, Klaus H.] German Canc Res Ctr, Jr Grp Med Image Comp, Heidelberg, Germany. [Maier-Hein, Klaus H.; Stieltjes, Bram] German Canc Res Ctr, Jr Grp Quantitat Image Based Dis Characterizat, Heidelberg, Germany. [Shenton, Martha E.; Pasternak, Ofer] Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp, Boston, MA 02115 USA. [Shenton, Martha E.] Vet Affairs Boston Healthcare Syst, Brockton Div, Brockton, MA USA. [Weiner, Michael W.] Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94143 USA. [Raj, Ashish] Weill Cornell Med Coll, IDEAL, New York, NY USA. [Thomann, Philipp] Heidelberg Univ, Dept Gen Psychiat, Sect Geriatr Psychiat, Heidelberg, Germany. RP Maier-Hein, KH (reprint author), Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. EM k.maier-hein@dkfz.de RI Maier-Hein, Klaus/M-6250-2016 OI Maier-Hein, Klaus/0000-0002-6626-2463 FU National Institutes of Health [R01MH074794, P41RR013218, P41EB015902]; German Research Foundation (DFG) [ME 833/15-1]; NARSAD Young Investigator grant from the Brain and Behavior Research Foundation FX This work was supported in part by National Institutes of Health grants (R01MH074794, P41RR013218, and P41EB015902); by the German Research Foundation (DFG) grant (ME 833/15-1) (to K.H.M.H. and B.S.); and by a NARSAD Young Investigator grant from the Brain and Behavior Research Foundation (to O.P.). NR 37 TC 9 Z9 9 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2015 VL 11 IS 5 BP 485 EP 493 DI 10.1016/j.jalz.2014.04.518 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CI8KN UT WOS:000355021300003 PM 25035154 ER PT J AU Willette, AA Johnson, SC Birdsill, AC Sager, MA Christian, B Baker, LD Craft, S Oh, J Statz, E Hermann, BP Jonaitis, EM Koscik, RL La Rue, A Asthana, S Bendlin, BB AF Willette, Auriel A. Johnson, Sterling C. Birdsill, Alex C. Sager, Mark A. Christian, Bradley Baker, Laura D. Craft, Suzanne Oh, Jennifer Statz, Eric Hermann, Bruce P. Jonaitis, Erin M. Koscik, Rebecca L. La Rue, Asenath Asthana, Sanjay Bendlin, Barbara B. TI Insulin resistance predicts brain amyloid deposition in late middle-aged adults SO ALZHEIMERS & DEMENTIA LA English DT Article DE Insulin resistance; Amyloid; PiB; Alzheimer's disease; Cognitively normal; Prefrontal ID PITTSBURGH COMPOUND-B; GRAY-MATTER VOLUME; ALZHEIMERS-DISEASE; DEGRADING ENZYME; IN-VIVO; RISK; PET; METABOLISM; COGNITION; DEMENTIA AB Background: Insulin resistance (IR) increases Alzheimer's disease (AD) risk. IR is related to greater amyloid burden post-mortem and increased deposition within areas affected by early AD. No studies have examined if IR is associated with an in vivo index of amyloid in the human brain in late middle-aged participants at risk for AD. Methods: Asymptomatic, late middle-aged adults (N = 186) from the Wisconsin Registry for Alzheimer's Prevention underwent [C-11]Pittsburgh compound B (PiB) positron emission tomography. The cross-sectional design tested the interaction between insulin resistance and glycemic status on PiB distribution volume ratio in three regions of interest (frontal, parietal, and temporal). Results: In participants with normoglycemia but not hyperglycemia, higher insulin resistance corresponded to higher PiB uptake in frontal and temporal areas, reflecting increased amyloirl deposition. Conclusions: This is the first human study to demonstrate that insulin resistance may contribute to amyloid deposition in brain regions affected by AD. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Willette, Auriel A.; Johnson, Sterling C.; Birdsill, Alex C.; Oh, Jennifer; Statz, Eric; Asthana, Sanjay; Bendlin, Barbara B.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. [Willette, Auriel A.; Johnson, Sterling C.; Birdsill, Alex C.; Sager, Mark A.; Oh, Jennifer; Statz, Eric; Hermann, Bruce P.; Asthana, Sanjay; Bendlin, Barbara B.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Willette, Auriel A.] NIA, Lab Neurosci, Baltimore, MD 21224 USA. [Johnson, Sterling C.] Univ Wisconsin, Waisman Lab Brain Imaging & Behav, Madison, WI USA. [Johnson, Sterling C.; Sager, Mark A.; Hermann, Bruce P.; Jonaitis, Erin M.; Koscik, Rebecca L.; La Rue, Asenath] Wisconsin Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI USA. [Christian, Bradley] Wisconsin Sch Med & Publ Hlth, Dept Med Phys, Madison, WI USA. [Baker, Laura D.; Craft, Suzanne] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. RP Bendlin, BB (reprint author), William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. EM bbb@medicine.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU National Institute on Aging [R01 AG027161]; ADRC [P50 AG033514, R01 AG021155]; University of Wisconsin Institute for Clinical and Translational Research; National Center for Research Resources/National Institutes of Health Clinical and Translational Science Award [1UL1RR025011]; National Center for Research Resources, United States National Institutes of Health FX The authors gratefully acknowledge Nancy Davenport-Sis, Amy Hawley, Sandra Harding, Caitlin Cleary, Chuck Illingworth, and the support of researchers and staff at the Waisman Center, University of Wisconsin Madison, for their assistance in recruitment, data collection, and data analysis. Above all, we wish to thank our dedicated volunteers for their participation in this research. This project was supported by the National Institute on Aging (R01 AG027161 [M.A.S.], ADRC P50 AG033514 [S.A.], R01 AG021155 [S.C.J.], the University of Wisconsin Institute for Clinical and Translational Research, funded through a National Center for Research Resources/National Institutes of Health Clinical and Translational Science Award, 1UL1RR025011, a program of the National Center for Research Resources, United States National Institutes of Health), and by the facilities and resources at the Geriatric Research, Education, and Clinical Center (GRECC) of the William S. Middleton Memorial Veterans Hospital, Madison, WI. Barbara Bendlin had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 40 TC 31 Z9 31 U1 6 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2015 VL 11 IS 5 BP 504 EP 510 DI 10.1016/j.jalz.2014.03.011 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CI8KN UT WOS:000355021300005 PM 25043908 ER PT J AU Gonzalez, RG AF Gonzalez, R. G. TI Imaging Biomarkers in Ischemic Stroke Clinical Trials: An Opportunity for Rigor SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material ID MRI; SELECTION; THERAPY; VOLUME C1 [Gonzalez, R. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gonzalez, R. G.] Harvard Univ, Sch Med, Boston, MA USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 2015 VL 36 IS 5 BP 844 EP 845 DI 10.3174/ajnr.A4269 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CI5VU UT WOS:000354828700007 PM 25742981 ER PT J AU Mingkwansook, V Curtin, HD Kelly, HR AF Mingkwansook, V. Curtin, H. D. Kelly, H. R. TI CT Findings in the External Auditory Canal after Transcanal Surgery SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID POSTOPERATIVE MIDDLE-EAR; TEMPORAL BONE; CHOLESTEATOMA; CARCINOMA; ANATOMY AB BACKGROUND AND PURPOSE: Middle ear surgery is often performed through the external auditory canal, and the CT appearance of the external auditory canal after transcanal middle ear surgery can mimic erosive pathology such as carcinoma, external auditory canal cholesteatoma, or necrotizing external otitis. We reviewed the CT findings in a group of patients following transcanal surgery to highlight this potential pitfall in interpretation. MATERIALS AND METHODS: Twenty-seven temporal bones in 25 patients with a history of a transcanal approach to the middle ear and available postoperative CT imaging were identified. Images were assessed for changes along or involving the walls of the external auditory canal, including widening, irregularity, bony defects, and soft tissue opacification. RESULTS: Osseous changes along the floor of the external auditory canal were demonstrated in 25 of 27(92.6%) temporal bone CT scans. Similar changes were present in the superior and anterior walls of the external auditory canal in 21 and 18 temporal bones, respectively. The anterior wall was the most common site for complete bony defects (10 of 27 temporal bones). The posterior wall was the least often involved, with osseous changes in 15 of 27 temporal bones and bony defects in 3 cases. Soft tissue thickening was seen most commonly along the floor. No patient was found to have a superimposed pathologic process of the external auditory canal. CONCLUSIONS: CT findings in the external auditory canal after transcanal surgery include thinning, irregularity and/or flattening of the bone, soft tissue thickening, and bony wall defects. Although these changes may be subtle, they may mimic pathology and should be included in the differential diagnosis of osseous abnormality of the external auditory canal. C1 [Mingkwansook, V.] Thammasat Univ Hosp, Dept Radiol, Pathum Thani, Thailand. [Mingkwansook, V.; Curtin, H. D.; Kelly, H. R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Radiol, Boston, MA USA. [Kelly, H. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroradiol, Boston, MA USA. RP Kelly, HR (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, 55 Fruit St,GRB-273A, Boston, MA 02114 USA. EM hillary.kelly@mgh.harvard.edu NR 19 TC 0 Z9 0 U1 1 U2 2 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 MAY PY 2015 VL 36 IS 5 BP 982 EP 986 DI 10.3174/ajnr.A4226 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CI5VU UT WOS:000354828700032 PM 25634720 ER PT J AU Anderson, BJ Hill, EG Sweeney, RE Wahlquist, AE Marshall, DT O'Carroll, KFS Cole, DJ Camp, ER AF Anderson, Brandon J. Hill, Elizabeth G. Sweeney, Robert E. Wahlquist, Amy E. Marshall, David T. O'Carroll, Kevin F. Staveley Cole, David J. Camp, Ernest Ramsay TI The Impact of Surgical Diversion Before Neoadjuvant Therapy for Rectal Cancer SO AMERICAN SURGEON LA English DT Article ID TOTAL MESORECTAL EXCISION; LOW ANTERIOR RESECTION; PREOPERATIVE CHEMORADIATION; ANASTOMOTIC LEAKAGE; DEFUNCTIONING STOMA; SURVIVAL; SURGERY; RECURRENCE; DISTAL AB Up-front fecal diversion can palliate emergent symptoms related to locally advanced rectal cancer (LARC) allowing patients to receive neoadjuvant chemoradiation therapy (nCRT). We analyzed outcomes of pretreatment-diverted LARC patients relative to nondiverted patients to define the impact of this management strategy. We retrospectively collected data on 103 LARC patients treated with nCRTand surgery. Medical records were reviewed for patient characteristics, staging, treatment plan, and outcomes. Thirteen LARC patients underwent pretreatment diversion for urgent symptoms and 90 LARC patients proceeded directly to nCRT. In all, 50 per cent of diverted patients presented with T4 tumor compared with 14 per cent in the nondiverted patients (P = 0.003). Diverted patients experienced a delay in time-to-treatment initiation of 12 days, although this difference was not statistically significant. Similar rates of chemoradiation and surgical toxicities were observed. Even though diverted patients demonstrated less pathologic response to nCRT compared with nondiverted patients (P = 0.04), there was no significant difference in overall survival. In conclusion, our study demonstrates the effectiveness of up-front fecal diversion at managing emergent obstructive symptoms related to advanced rectal cancer without additional complications, allowing patients to proceed with nCRT followed by radical surgery. C1 [Anderson, Brandon J.; O'Carroll, Kevin F. Staveley; Cole, David J.; Camp, Ernest Ramsay] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [Hill, Elizabeth G.; Wahlquist, Amy E.; O'Carroll, Kevin F. Staveley] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Hill, Elizabeth G.; Wahlquist, Amy E.; O'Carroll, Kevin F. Staveley; Cole, David J.; Camp, Ernest Ramsay] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Marshall, David T.] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. [Camp, Ernest Ramsay] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Sweeney, Robert E.] Icahn Sch Med Mt Sinai, Dept Surg, New York, NY 10029 USA. RP Camp, ER (reprint author), Med Univ S Carolina, Dept Surg, Surg Oncol, 25 Courtenay Dr,Room 7018,MSC 295, Charleston, SC 29425 USA. EM campe@musc.edu FU Biostatistics Shared Resource as part of the Hollings Cancer Center at the Medical University of South Carolina - Cancer Center Support Grant [P30 CA138313] FX The research presented in this manuscript was supported in part by the Biostatistics Shared Resource as part of the Hollings Cancer Center at the Medical University of South Carolina, which is funded by a Cancer Center Support Grant P30 CA138313. NR 23 TC 0 Z9 0 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI CUMMING PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA SN 0003-1348 EI 1555-9823 J9 AM SURGEON JI Am. Surg. PD MAY PY 2015 VL 81 IS 5 BP 444 EP 449 PG 6 WC Surgery SC Surgery GA CI6TS UT WOS:000354895700022 PM 25975325 ER PT J AU Nyer, M Mischoulon, D Alpert, JE Holt, DJ Brill, CD Yeung, A Pedrelli, P Baer, L Dording, C Huz, I Fisher, L Fava, M Farabaugh, A AF Nyer, Maren Mischoulon, David Alpert, Jonathan E. Holt, Daphne J. Brill, Charlotte D. Yeung, Albert Pedrelli, Paola Baer, Lee Dording, Christina Huz, Ilana Fisher, Lauren Fava, Maurizio Farabaugh, Amy TI College students with depressive symptoms with and without fatigue: Differences in functioning, suicidality, anxiety, and depressive severity SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article ID RECURRENT MAJOR DEPRESSION; ANTIDEPRESSANT TREATMENT; RESIDUAL SYMPTOMS; PHYSICAL-ACTIVITY; DISORDER; QUESTIONNAIRE; COMMUNITY; SLEEP; CLASSIFICATION; PERFORMANCE AB BACKGROUND: We examined whether fatigue was associated with greater symptomatic burden and functional impairment in college students with depressive symptoms. METHODS: Using data from the self-report Beck Depression Inventory (BDI), we stratified a group of 287 students endorsing significant symptoms of depression (BDI score >= 13) into 3 levels: no fatigue, mild fatigue, or moderate/severe fatigue. We then compared the 3 levels of fatigue across a battery of psychiatric and functional outcome measures. RESULTS: Approximately 87% of students endorsed at least mild fatigue. Students with moderate/severe fatigue had significantly greater depressive symptom severity compared with those with mild or no fatigue and scored higher on a suicide risk measure than those with mild fatigue. Students with severe fatigue evidenced greater frequency and intensity of anxiety than those with mild or no fatigue. Reported cognitive and functional impairment increased significantly as fatigue worsened. CONCLUSIONS: Depressed college students with symptoms of fatigue demonstrated functional impairment and symptomatic burden that worsened with increasing levels of fatigue. Assessing and treating symptoms of fatigue appears warranted within this population. C1 [Nyer, Maren; Mischoulon, David; Alpert, Jonathan E.; Holt, Daphne J.; Brill, Charlotte D.; Yeung, Albert; Pedrelli, Paola; Baer, Lee; Dording, Christina; Huz, Ilana; Fisher, Lauren; Fava, Maurizio; Farabaugh, Amy] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nyer, M (reprint author), Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM mnyer@partners.org OI Alpert, Jonathan/0000-0002-4332-908X FU Jed Foundation FX This work was supported by a grant from The Jed Foundation, a nonprofit organization whose mission is to promote emotional health and prevent suicide among college students. NR 49 TC 2 Z9 2 U1 1 U2 10 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 1040-1237 EI 1547-3325 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD MAY PY 2015 VL 27 IS 2 BP 100 EP 107 PG 8 WC Psychiatry SC Psychiatry GA CI1KU UT WOS:000354503900004 PM 25954936 ER PT J AU Farabaugh, A Fisher, L Nyer, M Holt, D Cohen, M Baer, L Shapero, BG Huz, I Cardoos, A Fava, M Alpert, JE AF Farabaugh, Amy Fisher, Lauren Nyer, Maren Holt, Daphne Cohen, Mariana Baer, Lee Shapero, Benjamin G. Huz, Ilana Cardoos, Amber Fava, Maurizio Alpert, Jonathan E. TI Similar changes in cognitions following cognitive-behavioral therapy or escitalopram for major depressive disorder: Implications for mechanisms of change SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article ID ANTIDEPRESSANT MEDICATION; INCREASED AMYGDALA; PHARMACOTHERAPY; PSYCHOTHERAPY; HOPELESSNESS; METAANALYSIS; COMBINATION; SYMPTOMS; EFFICACY; TRIAL AB BACKGROUND: Psychosocial treatments and medications both have been shown to be effective in treating major depressive disorder. We hypothesized that cognitive-behavioral therapy (CBT) would outperform medication on measures of cognitive change. METHODS: We randomized depressed individuals to 12 weeks of CBT (n = 15) or escitalopram (n = 11). In an intent-to-treat analysis (n = 26), we conducted a repeated measures analysis of variance to examine changes in depressive symptoms (le, 17-item Hamilton Depression Rating Scale, Beck Depression Inventory), anhedonia (ie, Snaith-Hamilton Pleasure Scale), cognitive measures (ie, Dysfunctional Attitudes Scale, Automatic Thoughts Questionnaire, Perceived Stress Scale), and quality of life (ie, Quality of Life Enjoyment and Satisfaction Questionnaire) at 4 time points: baseline, week 4, week 8, and week 12. Treatment for both groups started at baseline, and patients received either 12 weeks of individual CBT or 12 weeks of escitalopram with flexible dosing (10 to 20 mg). RESULTS: Collapsing the escitalopram and CBT groups, there were statistically significant pre-post changes on all outcome measures. However, there were no statistically significant differences between treatment groups on any of the outcome measures, including cognitive measures across time points. CONCLUSIONS: Our results suggest that both CBT and escitalopram have similar effects across a variety of domains and that, in contrast to our a priori hypothesis, CBT and escitalopram were associated with comparable changes on cognitive measures. C1 [Farabaugh, Amy; Fisher, Lauren; Nyer, Maren; Holt, Daphne; Cohen, Mariana; Baer, Lee; Shapero, Benjamin G.; Huz, Ilana; Cardoos, Amber; Fava, Maurizio; Alpert, Jonathan E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. RP Farabaugh, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM afarabaugh@partners.org OI Alpert, Jonathan/0000-0002-4332-908X FU NARSAD [2007A004632] FX This article was funded by a NARSAD Young Investigator Award 2007A004632. NR 48 TC 0 Z9 0 U1 5 U2 9 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 1040-1237 EI 1547-3325 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD MAY PY 2015 VL 27 IS 2 BP 118 EP 125 PG 8 WC Psychiatry SC Psychiatry GA CI1KU UT WOS:000354503900006 PM 25954938 ER PT J AU Nearing, BD Verrier, RL AF Nearing, Bruce D. Verrier, Richard L. TI Multilead Template-Derived Residua of Surface ECGS for Quantitative Assessment of Arrhythmia Risk SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE repolarization; depolarization; heterogeneity; risk stratification; ventricular tachycardia; ventricular fibrillation ID T-WAVE ALTERNANS; AMERICAN-HEART-ASSOCIATION; SUDDEN CARDIAC DEATH; REPOLARIZATION HETEROGENEITY; VENTRICULAR-FIBRILLATION; STRATIFICATION; CARDIOMYOPATHY; INSTABILITY; PREVENTION; SOCIETY AB BackgroundContemporary electrocardiographic (ECG) markers including ventricular ectopy and arrhythmias have not proved reliable in risk assessment for life-threatening arrhythmias. MethodsWe developed the Multilead ECG Template-Derived Residua approach to remove intrinsic morphologic differences and allow calculation of pathologic ECG heterogeneities among spatially separated leads. Prediction by R-wave and T-wave heterogeneity (RWH, TWH) analysis was tested in simulated and clinical ECGs. ResultsAn enabling description of the Residua algorithm is provided. Simulated ECGs with but not without Residua produced a linear relationship (correlation coefficient r(2) = 0.999) between input and output RWH and TWH values. In heart failure patients, Residua disclosed a marked crescendo in RWH from 164.1 33.1 at baseline to 299.8 +/- 54.5 V and TWH from 134.5 +/- 20.6 at baseline to 239.2 +/- 37.0 V at 30-45 minutes before the arrhythmia (both, P < 0.05), which remained elevated until arrhythmia onset. Without Residua, mean RWH and TWH were elevated at 1061.0 +/- 222.9 and 882.5 +/- 375.2 V, respectively, throughout the recording and were not different prior to ventricular tachycardia onset. ConclusionsCalculation of ECG-template derived Residua provides a highly accurate means for assessing arrhythmia risk from standard ECGs. Potential widespread applications include resting diagnostic 12-lead, ambulatory, and exercise ECGs, electrophysiologic study laboratory recordings, and implantable devices. C1 [Nearing, Bruce D.; Verrier, Richard L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Harvard Thorndike Electrophysiol Inst, Div Cardiovasc Med,Sch Med,Dept Med, Boston, MA 02215 USA. RP Verrier, RL (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Harvard Thorndike Electrophysiol Inst, Div Cardiovasc Med,Sch Med,Med, 99 Brookline Ave,RN 301, Boston, MA 02215 USA. EM rverrier@bidmc.harvard.edu NR 17 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1082-720X EI 1542-474X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD MAY PY 2015 VL 20 IS 3 BP 273 EP 281 DI 10.1111/anec.12205 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CI6NU UT WOS:000354877600007 PM 25236344 ER PT J AU Stachler, M Jia, YH Sharaf, N Wade, J Longtine, J Garcia, E Sholl, LM AF Stachler, Matthew Jia, Yonghui Sharaf, Nematullah Wade, Jacqueline Longtine, Janina Garcia, Elizabeth Sholl, Lynette M. TI Filter Paper-based Nucleic Acid Storage in High-throughput Solid Tumor Genotyping SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LA English DT Article DE cancer; genotyping; filter paper ID LUNG-CANCER; INFANTS; DIAGNOSIS; KRAS; EGFR; DNA AB Molecular testing of tumors from formalin-fixed paraffin-embedded (FFPE) tissue blocks is central to clinical practice; however, it requires histology support and increases test turnaround time. Prospective fresh frozen tissue collection requires special handling, additional storage space, and may not be feasible for small specimens. Filter paper-based collection of tumor DNA reduces the need for histology support, requires little storage space, and preserves high-quality nucleic acid. We investigated the performance of tumor smears on filter paper in solid tumor genotyping, as compared with paired FFPE samples. Whatman FTA Micro Card (FTA preps) smears were prepared from 21 fresh tumor samples. A corresponding cytology smear was used to assess tumor cellularity and necrosis. DNA was isolated from FTA preps and FFPE core samples using automated methods and quantified using SYBR green dsDNA detection. Samples were genotyped for 471 mutations on a mass spectrophotometry-based platform (Sequenom). DNA concentrations from FTA preps and FFPE correlated for untreated carcinomas but not for mesenchymal tumors (Spearman sigma = 0.39 and sigma = -0.1, respectively). Average DNA concentrations were lower from FTA preps as compared with FFPE, but DNA quality was higher with less fragmentation. Seventy-six percent of FTA preps and 86% of FFPE samples generated adequate DNA for genotyping. FTA preps tended to perform poorly for collection of DNA from pretreated carcinomas and mesenchymal neoplasms. Of the 16 paired DNA samples that were genotyped, 15 (94%) gave entirely concordant results. Filter paper-based sample preservation is a feasible alternative to FFPE for use in automated, high-throughput genotyping of carcinomas. C1 [Stachler, Matthew; Sholl, Lynette M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Stachler, Matthew; Sholl, Lynette M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Jia, Yonghui; Garcia, Elizabeth] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sharaf, Nematullah] Case Western Reserve Sch Med, Cleveland, OH USA. [Wade, Jacqueline] Univ Vermont, Coll Med, Burlington, VT USA. [Longtine, Janina] Mt Sinai Med Ctr, New York, NY 10029 USA. RP Sholl, LM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM lmsholl@partners.org NR 10 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 1541-2016 EI 1533-4058 J9 APPL IMMUNOHISTO M M JI Appl. Immunohistochem. PD MAY-JUN PY 2015 VL 23 IS 5 BP 389 EP 396 PG 8 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA CI6QP UT WOS:000354886100010 PM 25221956 ER PT J AU Schifman, RB Meier, FA Souers, RJ AF Schifman, Ron B. Meier, Frederick A. Souers, Rhona J. TI Timeliness and Accuracy of Reporting Preliminary Blood Culture Results SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID GRAM-POSITIVE COCCI; RAPID IDENTIFICATION; ANTIBIOTIC-THERAPY; STREAM INFECTIONS; SEVERE SEPSIS; IMPACT; BOTTLES; STAIN; BACTEREMIA; NOTIFICATION AB Context.-The speed and accuracy of preliminary blood culture reports impacts patient management and outcomes. Objective.-To evaluate the accuracy and timeliness of preliminary blood culture results among multiple laboratories. Design.-Q-Probes participants collected turnaround time (TAT) data on preliminary Gram stains, compared accuracy of up to 100 preliminary to final culture Gram stain results, and described blood culture laboratory practices. Results.-Sixty-four laboratories and 5031 blood cultures were evaluated. All participants used continuously monitoring blood culture systems. Median TAT from initial growth detection to notification of results was 45 minutes, with the longest component being preparation of Gram stains (median time = 25 minutes). Participants (N = 40) reporting a continuous schedule for processing blood cultures had significantly lower overall TAT (median = 37 minutes) compared with 15 participants with intermittent processing schedules (median = 124 minutes), P = .003. Time to complete Gram stain processing was lower (median time = 21 minutes) for 39 participants using continuous processing schedule compared with 14 others (median time = 67 minutes), P = .03. Goals for total TAT were used by 27 of 56 participants (48.2%). Having goals did not significantly affect TAT. A total of 4962 of 5021 Gram stain results (98.8%) agreed with final culture results. The highest discrepancy rates occurred among gram-positive bacilli (20 of 335; 6.0%) and mixed cultures (22 of 106; 20.8%). Conclusions.-This study provides benchmarks for assessing blood culture quality performance. Timeliness and accuracy of preliminary blood culture reports were excellent. However, nearly one-third of laboratories did not process blood cultures continuously. This significantly prolonged reporting results, which could affect patient outcomes. C1 [Schifman, Ron B.] Univ Arizona, Coll Med, So Arizona VA Healthcare Syst, Diagnost, Tucson, AZ 85723 USA. [Meier, Frederick A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Souers, Rhona J.] Coll Amer Pathologists, Dept Biostat, Northfield, IL USA. RP Schifman, RB (reprint author), Univ Arizona, Coll Med, So Arizona VA Healthcare Syst, Diagnost, 3601 S 6th Ave, Tucson, AZ 85723 USA. EM Ronald.Schifman@VA.gov NR 30 TC 1 Z9 1 U1 0 U2 1 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 MAY PY 2015 VL 139 IS 5 BP 621 EP 626 DI 10.5858/arpa.2014-0258-CP PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA CI6EL UT WOS:000354851400016 PM 25927146 ER PT J AU Jones, NC Nazarian, RM Duncan, LM Kamionek, M Lauwers, GY Tambouret, RH Wu, CL Nielsen, GP Brachtel, EF Mark, EJ Sadow, PM Grabbe, JP Wilbur, DC AF Jones, Nicholas C. Nazarian, Rosalynn M. Duncan, Lyn M. Kamionek, Michal Lauwers, Gregory Y. Tambouret, Rosemary H. Wu, Chin-Lee Nielsen, G. Petur Brachtel, Elena F. Mark, Eugene J. Sadow, Peter M. Grabbe, John P. Wilbur, David C. TI Interinstitutional Whole Slide Imaging Teleconsultation Service Development Assessment Using Internal Training and Clinical Consultation Cases SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID SURGICAL PATHOLOGY; VIRTUAL SLIDE; MICROSCOPY; VALIDATION; DIAGNOSIS; PLATFORM AB Context.-Assessment of accuracy and feasibility of whole slide imaging (WSI) for interinstitutional consultation in surgical pathology. Objectives.-To train technical and pathologist staff in WSI technology, establish and evaluate a WSI workflow using training cases and second-opinion consultations, and assess diagnostic accuracy. Design.-First, WSI training and evaluation using selected subspecialty service cases were performed and compared with the clinical glass slide (GS) diagnosis. Second, WSI and GS diagnoses of consecutive, second-opinion consultation cases were compared. Discrepancies underwent adjudication to determine a reference diagnosis. Participant observations on WSI initiation to practice were gathered. Results.-There were 130 cases evaluated, with 123 correlations (94.6%) and 6 minor (4.6%) and 1 major (0.8%) discrepancies. The 74 consultation cases interpreted had 52 correlations (70.3%), and 18 minor (24.3%) and 4 major (5.4%) discrepancies. The WSI and GS adjusted major discrepancy rates in second-opinion consultations were 2.7% (2 of 74) and 4.1% (3 of 74), respectively. Statistical analysis showed that WSI was not inferior to GS interpretation. Pathologists agreed the software was easy to use and the images were adequate, but more time was spent rendering WSI interpretations. Conclusions.-A significant learning curve was observed in the transition from the training set to clinical consultation cases associated both with WSI interpretation and adjustments to the digital analogs of routine GS workflow. Results from second-opinion consultations indicated that WSI interpretation was as accurate as GS interpretation among properly trained and experienced users. Overall, WSI-based practice appears feasible for second-opinion consultations. C1 [Jones, Nicholas C.; Nazarian, Rosalynn M.; Duncan, Lyn M.; Kamionek, Michal; Lauwers, Gregory Y.; Tambouret, Rosemary H.; Wu, Chin-Lee; Nielsen, G. Petur; Brachtel, Elena F.; Mark, Eugene J.; Sadow, Peter M.; Grabbe, John P.; Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Jones, Nicholas C.; Nazarian, Rosalynn M.; Duncan, Lyn M.; Kamionek, Michal; Lauwers, Gregory Y.; Tambouret, Rosemary H.; Wu, Chin-Lee; Nielsen, G. Petur; Brachtel, Elena F.; Mark, Eugene J.; Sadow, Peter M.; Grabbe, John P.; Wilbur, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Grabbe, John P.] Cambridge Hlth Alliance, Dept Pathol, Cambridge, MA USA. RP Jones, NC (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Gray Jackson 249C, Boston, MA 02114 USA. EM ncjones@partners.org NR 22 TC 4 Z9 4 U1 1 U2 2 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2015 VL 139 IS 5 BP 627 EP 635 DI 10.5858/arpa.2014-0133-OA PG 9 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA CI6EL UT WOS:000354851400017 PM 25415180 ER PT J AU Zhang, DH Jiang, W AF Zhang, Donghui Jiang, Wei TI From One-Cell to Tissue: Reprogramming, Cell Differentiation and Tissue Engineering SO BIOSCIENCE LA English DT Article DE stem cells; tissue engineering; cell differentiation; cell reprogramming; induced pluripotent stem cells (iPSCs) ID PLURIPOTENT STEM-CELLS; NUCLEAR TRANSFER; ORTHOTOPIC TRANSPLANTATION; DIRECTED DIFFERENTIATION; DEFINED FACTORS; SOMATIC-CELLS; HUMAN LIVER; IN-VITRO; MATRIX; CARDIOMYOCYTES AB Adult somatic cells can be reprogrammed into pluripotent stem cells, which can indefinitely proliferate in a dish and differentiate into almost all the cell types that constitute the human body. These cells hold great promise for cell therapy and regenerative medicine, as well as drug screening and disease modeling. Theoretically, we can create a source of versatile, therapeutic cells that could be genetically matched to any patient. These pluripotent stem cells can be differentiated into desired cell types and eventually used to reconstruct a tissue or an organ with insights gained from tissue engineering. Inspired by the pioneering work in stem cells, particularly the remarkable reprogramming technique, the fields of regenerative medicine and tissue engineering have advanced rapidly in the past several years. Here recent progress in the fields of induced pluripotent stem cells and tissue engineering is reviewed, with a focus on applications in medicine. C1 [Zhang, Donghui] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Jiang, Wei] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. RP Zhang, DH (reprint author), Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. EM donghui.zhang@childrens.harvard.edu; wei.jiang@childrens.harvard.edu RI Jiang, Wei/J-7993-2012 OI Jiang, Wei/0000-0002-6463-7356 FU Juvenile Diabetes Research Foundation FX We thank Katie Kester for critical reading. We apologize for papers that are not directly cited because of space limitations. WJ is supported by a Juvenile Diabetes Research Foundation postdoctoral fellowship. The authors declare no competing financial interests. NR 69 TC 1 Z9 1 U1 5 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3568 EI 1525-3244 J9 BIOSCIENCE JI Bioscience PD MAY PY 2015 VL 65 IS 5 BP 468 EP 475 DI 10.1093/biosci/biv016 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CI4XD UT WOS:000354756300005 ER PT J AU Holmes, LB Meedzan, B Beroukhim, R AF Holmes, L. B. Meedzan, B. Beroukhim, R. TI Classification of "Mild" Heart Defects: Challenge for Pregnancy Registries SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Holmes, L. B.; Meedzan, B.] MassGen Hosp Children, North Amer AED Pregnancy Registry, Boston, MA USA. [Beroukhim, R.] MassGen Hosp Children, Pediat Cardiol, 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 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2015 VL 103 IS 5 MA 32 BP 391 EP 391 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA CI4SD UT WOS:000354742400081 ER PT J AU Toufaily, MH Roberts, DJ Westgate, MN Holmes, LB AF Toufaily, M. H. Roberts, D. J. Westgate, M. N. Holmes, L. B. TI Urethral Atresia: Prenatal Diagnosis, Clinical Presentation, and Outcome SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Toufaily, M. H.; Westgate, M. N.; Holmes, L. B.] MassGen Hosp Children, Med Genet Unit, Boston, MA USA. [Toufaily, M. H.; Westgate, M. N.; Holmes, L. B.] Brigham & Womens Hosp, Dept Pediat Newborn Med, Boston, MA 02115 USA. [Roberts, D. J.] Massachusetts Gen Hosp, Dept Pathol, 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 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2015 VL 103 IS 5 MA P31 BP 417 EP 417 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA CI4SD UT WOS:000354742400131 ER PT J AU Toufaily, MH Roberts, DJ Westgate, MN Holmes, LB AF Toufaily, M. H. Roberts, D. J. Westgate, M. N. Holmes, L. B. TI Antenatal Suspicion and Postnatal Presentation of Scimitar Syndrome SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Toufaily, M. H.; Westgate, M. N.; Holmes, L. B.] MassGen Hosp Children, Med Genet Unit, Boston, MA USA. [Toufaily, M. H.; Westgate, M. N.; Holmes, L. B.] Brigham & Womens Hosp, Dept Pediat Newborn Med, Boston, MA 02115 USA. [Roberts, D. J.] Massachusetts Gen Hosp, Dept Pathol, 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 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2015 VL 103 IS 5 MA P30 BP 417 EP 417 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA CI4SD UT WOS:000354742400130 ER PT J AU Sadeghian, H Seidel, JL Balkaya, M Qin, T Eikermann-Haerter, K Ferrari, MD van den Maagdenberg, AMJM Ayata, C AF Sadeghian, H. Seidel, J. L. Balkaya, M. Qin, T. Eikermann-Haerter, K. Ferrari, M. D. van den Maagdenberg, A. M. J. M. Ayata, C. TI Environmental stress and spreading depression SO CEPHALALGIA LA English DT Meeting Abstract CT International Headache Congress of the International-Headache-Society CY MAY 14-17, 2015 CL Valencia, SPAIN SP Int Headache Soc C1 [Sadeghian, H.; Seidel, J. L.; Balkaya, M.; Qin, T.; Eikermann-Haerter, K.] Massachusetts Gen Hosp, Neurovasc Res Lab, Charlestown, MA USA. [Ferrari, M. D.; van den Maagdenberg, A. M. J. M.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands. [Ayata, C.] Massachusetts Gen Hosp, Stroke Serv & Neurosci Intens Care Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 EI 1468-2982 J9 CEPHALALGIA JI Cephalalgia PD MAY PY 2015 VL 35 SU 6 MA PO084 BP 56 EP 56 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CI2FC UT WOS:000354559400113 ER PT J AU Chen, SP Ay, I Sadeghian, H Qin, T Simon, B Eikermann-Kaerter, K Ayata, C AF Chen, S. P. Ay, I. Sadeghian, H. Qin, T. Simon, B. Eikermann-Kaerter, K. Ayata, C. TI Vagus nerve stimulation inhibits cortical spreading depression SO CEPHALALGIA LA English DT Meeting Abstract CT International Headache Congress of the International-Headache-Society CY MAY 14-17, 2015 CL Valencia, SPAIN SP Int Headache Soc C1 [Chen, S. P.] Taipei Vet Gen Hosp, Dept Neurol, Taipei, Taiwan. [Ay, I.] MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Dept Radiol, Boston, MA USA. [Chen, S. P.; Sadeghian, H.; Qin, T.; Eikermann-Kaerter, K.; Ayata, C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurovasc Res Lab, Boston, MA USA. [Simon, B.] ElectroCore LLC, Dept Res, Basking Ridge, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 EI 1468-2982 J9 CEPHALALGIA JI Cephalalgia PD MAY PY 2015 VL 35 SU 6 MA PO421 BP 219 EP 221 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CI2FC UT WOS:000354559400438 ER PT J AU Mawet, J Eikermann-Haerter, K Park, KY Helenius, J Daneshmand, A Pearlman, L Avery, R Negro, A Velioglu, M Arsava, EM Ay, H Ayata, C AF Mawet, J. Eikermann-Haerter, K. Park, K. Y. Helenius, J. Daneshmand, A. Pearlman, L. Avery, R. Negro, A. Velioglu, M. Arsava, E. M. Ay, H. Ayata, C. TI Increased tissue vulnerability to acute cerebral ischemic injury in migraineurs SO CEPHALALGIA LA English DT Meeting Abstract CT International Headache Congress of the International-Headache-Society CY MAY 14-17, 2015 CL Valencia, SPAIN SP Int Headache Soc C1 [Mawet, J.] Hop Lariboisiere, Emergency Headache Ctr, F-75475 Paris, France. [Eikermann-Haerter, K.; Daneshmand, A.; Pearlman, L.; Negro, A.; Ayata, C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurovasc Res Lab,Dept Radiol, Boston, MA USA. [Park, K. Y.; Helenius, J.; Avery, R.; Velioglu, M.; Arsava, E. M.; Ay, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging & Stroke Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 EI 1468-2982 J9 CEPHALALGIA JI Cephalalgia PD MAY PY 2015 VL 35 SU 6 MA PO441 BP 230 EP 230 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CI2FC UT WOS:000354559400456 ER PT J AU Sadeghian, H Harms, C Qin, T Ferrari, MD van den Maagdenberg, AMJM Endres, M Ayata, C AF Sadeghian, H. Harms, C. Qin, T. Ferrari, M. D. van den Maagdenberg, A. M. J. M. Endres, M. Ayata, C. TI Increased susceptibility to hypoxic/ischemic injury in FHM1 mutant mice SO CEPHALALGIA LA English DT Meeting Abstract CT International Headache Congress of the International-Headache-Society CY MAY 14-17, 2015 CL Valencia, SPAIN SP Int Headache Soc C1 [Sadeghian, H.; Qin, T.; Ayata, C.] Massachusetts Gen Hosp, Neurovasc Res Lab, Charlestown, MA USA. [Harms, C.; Endres, M.] Charite, Ctr Stroke Res, D-13353 Berlin, Germany. [Ferrari, M. D.; van den Maagdenberg, A. M. J. M.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 EI 1468-2982 J9 CEPHALALGIA JI Cephalalgia PD MAY PY 2015 VL 35 SU 6 MA PO451 BP 234 EP 235 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CI2FC UT WOS:000354559400465 ER PT J AU Sadeghian, H Lacoste, B Qin, T Rosa, R Gu, C Ayata, C AF Sadeghian, H. Lacoste, B. Qin, T. Rosa, R. Gu, C. Ayata, C. TI Spreading depression-induced blood brain barrier disruption is prevented by RHO-Kinase inhibition and associated with increased transendothelial pinocytosis SO CEPHALALGIA LA English DT Meeting Abstract CT International Headache Congress of the International-Headache-Society CY MAY 14-17, 2015 CL Valencia, SPAIN SP Int Headache Soc C1 [Sadeghian, H.; Qin, T.; Ayata, C.] Massachusetts Gen Hosp, Neurovasc Res Lab, Charlestown, MA USA. [Lacoste, B.; Rosa, R.; Gu, C.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 EI 1468-2982 J9 CEPHALALGIA JI Cephalalgia PD MAY PY 2015 VL 35 SU 6 MA PO452 BP 235 EP 235 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CI2FC UT WOS:000354559400466 ER PT J AU Vargas, M Pelosi, P Tessitore, G Aloj, F Brunetti, I Arditi, E Salami, D Kacmarek, RM Servillo, G AF Vargas, Maria Pelosi, Paolo Tessitore, Gaetano Aloj, Fulvio Brunetti, Iole Arditi, Enrico Salami, Dorino Kacmarek, Robert M. Servillo, Giuseppe TI Percutaneous Dilatational Tracheostomy With a Double-Lumen Endotracheal Tube A Comparison of Feasibility, Gas Exchange, and Airway Pressures SO CHEST LA English DT Article ID LARYNGEAL MASK AIRWAY; DILATIONAL TRACHEOSTOMY; FIBEROPTIC BRONCHOSCOPY; MECHANICAL VENTILATION; RESPIRATORY-FAILURE; CRITICALLY-ILL; LUNG MODEL; SAFETY; PEEP AB OBJECTIVE: Gas exchange and airway pressures are markedly altered during percutaneous dilatational tracheostomy (PDT). A double-lumen endotracheal tube (DLET) has been developed for better airway management during PDT. The current study prospectively evaluated the in vivo feasibility, gas exchange, and airway pressures during PDT with DLET compared with a conventional endotracheal tube (ETT). METHODS: According to eligibility criteria, patients were divided into a case group (those receiving PDT with DLET) and a control group (those receiving PDT with a conventional ETT). The Ciaglia single-dilator technique was used for PDT in both groups. The primary end point of this study was the feasibility of tracheostomy with DLET. The secondary end points were a comparison of gas exchange, airway pressures, minute volume, and tidal volume before, during, and aft er PDT performed with DLET and conventional ETT. RESULTS: Ten patients meeting the inclusion criteria were assigned to each group. PDTs were performed without difficulties in nine patients in the DLET group and 10 patients in the conventional ETT group. During PDT, gas exchange, airway pressures, and minute ventilation remained more stable in the DLET group and were significantly different from those in the conventional ETT group. CONCLUSIONS: PDT with DLET can be performed safely without difficulties limiting the technique. Furthermore, during PDT, the use of the DLET resulted in more stable gas exchange, airway pressures, and ventilation than PDT with a conventional ETT. C1 [Vargas, Maria; Tessitore, Gaetano; Servillo, Giuseppe] Univ Naples Federico II, Dept Neurosci, Reprod & Odonthostomatol Sci, I-80138 Naples, Italy. [Vargas, Maria; Pelosi, Paolo] Univ Genoa, IRCCS AOU San Martino IST, Dept Surg Sci & Integrated Diagnost, Genoa, Italy. [Aloj, Fulvio; Servillo, Giuseppe] IRCCS Neuromed, Anesthesia & Intens Care Unit, Pozzilli, IS, Italy. [Brunetti, Iole; Arditi, Enrico; Salami, Dorino] IRCCS AOC San Martino IST, Intens Care Unit, Genoa, Italy. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. RP Servillo, G (reprint author), Univ Naples Federico II, Dept Neurosci Reprod & Odonthostomatol Sci, Corso Umberto I 40, I-80138 Naples, Italy. EM servillo@unina.it RI Vargas, Maria/H-6876-2014; Servillo, Giuseppe/M-9132-2016 OI Vargas, Maria/0000-0001-7652-970X; Servillo, Giuseppe/0000-0002-4618-3434 NR 25 TC 6 Z9 6 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2015 VL 147 IS 5 BP 1267 EP 1274 DI 10.1378/chest.14-1465 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CI2VW UT WOS:000354606600031 PM 25375865 ER PT J AU O'Conor, R Wolf, MS Smith, SG Martynenko, M Vicencio, DP Sano, M Wisnivesky, JP Federman, AD AF O'Conor, Rachel Wolf, Michael S. Smith, Samuel G. Martynenko, Melissa Vicencio, Daniel P. Sano, Mary Wisnivesky, Juan P. Federman, Alex D. TI Health Literacy, Cognitive Function, Proper Use, and Adherence to Inhaled Asthma Controller Medications Among Older Adults With Asthma SO CHEST LA English DT Article ID METERED-DOSE INHALERS; SELF-MANAGEMENT; MEMORY; ASSOCIATION; EDUCATION; STEROIDS; OUTCOMES; THERAPY; RISK; CARE AB BACKGROUND: We sought to investigate the degree to which cognitive skills explain associations between health literacy and asthma-related medication use among older adults with asthma. METHODS: Patients aged >= 60 years receiving care at eight outpatient clinics (primary care, geriatrics, pulmonology, allergy, and immunology) in New York, New York, and Chicago, Illinois, were recruited to participate in structured, in-person interviews as part of the Asthma Beliefs and Literacy in the Elderly (ABLE) study (n = 425). Behaviors related to medication use were investigated, including adherence to prescribed regimens, metered-dose inhaler (MDI) technique, and dry powder inhaler (DPI) technique. Health literacy was measured using the Short Test of Functional Health Literacy in Adults. Cognitive function was assessed in terms of fluid (working memory, processing speed, executive function) and crystallized (verbal) ability. RESULTS: The mean age of participants was 68 years; 40% were Hispanic and 30% non-Hispanic black. More than one-third (38%) were adherent to their controller medication, 53% demonstrated proper DPI technique, and 38% demonstrated correct MDI technique. In multivariable analyses, limited literacy was associated with poorer adherence to controller medication (OR, 2.3; 95% CI, 1.29-4.08) and incorrect DPI (OR, 3.51; 95% CI, 1.81-6.83) and MDI (OR, 1.64; 95% CI, 1.01-2.65) techniques. Fluid and crystallized abilities were independently associated with medication behaviors. However, when fluid abilities were added to the model, literacy associations were reduced. CONCLUSIONS: Among older patients with asthma, interventions to promote proper medication use should simplify tasks and patient roles to overcome cognitive load and suboptimal performance in self-care. C1 [O'Conor, Rachel; Wolf, Michael S.; Smith, Samuel G.] Northwestern Univ, Feinberg Sch Med, Div Gen Internal Med, Chicago, IL 60611 USA. [Martynenko, Melissa; Wisnivesky, Juan P.; Federman, Alex D.] Icahn Sch Med Mt Sinai, Div Gen Internal Med, New York, NY 10029 USA. [Sano, Mary] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Wisnivesky, Juan P.] Icahn Sch Med Mt Sinai, Div Pulm Crit Care & Sleep Med, New York, NY 10029 USA. [Vicencio, Daniel P.] Mercy Hosp & Med Ctr, Dept Med, Chicago, IL USA. [Sano, Mary] James J Peters VA Med Ctr, Bronx, NY USA. RP O'Conor, R (reprint author), Northwestern Univ, Feinberg Sch Med, Div Gen Internal Med & Geriatr, 750 N Lakeshore Dr,10th Floor, Chicago, IL 60611 USA. EM r-oconor@northwestern.edu FU National Heart, Lung, and Blood Institute [5R01HL096612-04] FX Funding was provided by the National Heart, Lung, and Blood Institute [5R01HL096612-04]. NR 49 TC 11 Z9 11 U1 6 U2 14 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2015 VL 147 IS 5 BP 1307 EP 1315 DI 10.1378/chest.14-0914 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CI2VW UT WOS:000354606600035 PM 25275432 ER PT J AU Vargas, M Pelosi, P Kacmarek, RM Servillo, G AF Vargas, Maria Pelosi, Paolo Kacmarek, Robert M. Servillo, Giuseppe TI Double-Lumen Endotracheal Tube Device for Percutaneous Dilatational Tracheostomy An Inventor's Perspective Response SO CHEST LA English DT Letter C1 [Vargas, Maria; Servillo, Giuseppe] Univ Naples Federico II, Dept Neurosci Reprod & Odonthostomatol Sci, I-80138 Naples, Italy. [Vargas, Maria; Pelosi, Paolo] Univ Genoa, IRCCS AOU San Martino IST, Dept Surg Sci & Integrated Diagnost, I-16126 Genoa, Italy. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. RP Servillo, G (reprint author), Univ Naples Federico II, Dept Neurosci Reprod & Odonthostomatol Sci, Corso Umberto I 40, I-80138 Naples, Italy. EM servillo@unina.it NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2015 VL 147 IS 5 BP E193 EP E193 DI 10.1378/chest.15-0185 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CI2VW UT WOS:000354606600011 PM 25940268 ER PT J AU Afilalo, J Grapsa, J Nihoyannopoulos, P Beaudoin, J Gibbs, JSR Channick, RN Langleben, D Rudski, LG Hua, L Handschumacher, MD Picard, MH Levine, RA AF Afilalo, Jonathan Grapsa, Julia Nihoyannopoulos, Petros Beaudoin, Jonathan Gibbs, J. Simon R. Channick, Richard N. Langleben, David Rudski, Lawrence G. Hua, Lanqi Handschumacher, Mark D. Picard, Michael H. Levine, Robert A. TI Leaflet Area as a Determinant of Tricuspid Regurgitation Severity in Patients With Pulmonary Hypertension SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE echocardiography; pulmonary hypertension; tricuspid regurgitation ID FUNCTIONAL MITRAL REGURGITATION; DOPPLER COLOR-FLOW; 3-DIMENSIONAL ECHOCARDIOGRAPHY; COMPENSATORY MECHANISM; VALVE REGURGITATION; PATCH AUGMENTATION; VENA CONTRACTA; ADAPTATION; REPAIR; ASSOCIATION AB Background-Tricuspid regurgitation (TR) is a risk factor for mortality in pulmonary hypertension (PH). TR severity varies among patients with comparable degrees of PH and right ventricular remodeling. The contribution of leaflet adaptation to the pathophysiology of TR has yet to be examined. We hypothesized that tricuspid leaflet area (TLA) is increased in PH, and that the adequacy of this increase relative to right ventricular remodeling determines TR severity. Methods and Results-A prospective cohort of 255 patients with PH from pre and postcapillary pathogeneses was assembled from 2 centers. Patients underwent a 3-dimensional echocardiogram focused on the tricuspid apparatus. TLA was measured with the Omni 4D software package. Compared with normal controls, patients with PH had a 2-fold increase in right ventricular volumes, 62% increase in annular area, and 49% increase in TLA. Those with severe TR demonstrated inadequate increase in TLA relative to the closure area, such that the ratio of TLA: closure area < 1.78 was highly predictive of severe TR (odds ratio, 68.7; 95% confidence interval, 16.2-292.7). The median vena contracta width was 8.5 mm in the group with small TLA and large closure area as opposed to 4.8 mm in the group with large TLA and large closure area. Conclusions-TLA plays a significant role in determining which patients with PH develop severe functional TR. The ratio of TLA: closure area, reflecting the balance between leaflet adaptation versus annular dilation and tethering forces, is an indicator of TR severity that may identify which patients stand to benefit from leaflet augmentation during tricuspid valve repair. C1 [Afilalo, Jonathan; Langleben, David; Rudski, Lawrence G.] McGill Univ, Jewish Gen Hosp, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Grapsa, Julia; Nihoyannopoulos, Petros] Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, Cardiac Ultrasound Lab, Div Cardiol, London, England. [Gibbs, J. Simon R.] Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, Natl Pulm Hypertens Serv, Div Cardiol, London, England. [Channick, Richard N.] Harvard Univ, Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Pulm Hypertens & Thromboendarterect Program, Boston, MA USA. [Afilalo, Jonathan; Beaudoin, Jonathan; Hua, Lanqi; Handschumacher, Mark D.; Picard, Michael H.; Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Boston, MA USA. RP Afilalo, J (reprint author), 3755 Cote Ste Catherine,E-222, Montreal, PQ H3T 1E2, Canada. EM jonathan.afilalo@mcgill.ca OI Picard, Michael/0000-0002-9264-3243 FU Fonds de la Recherche en Sante du Quebec; Leducq Transatlantic Mitral Network, Leducq Foundation, Paris, France [07CVD04]; National Institutes of Health, Bethesda, MD [R01 HL109506] FX Dr Afilalo holds a Clinical Research Scholars Junior I Career Award from the Fonds de la Recherche en Sante du Quebec. This work was supported in part by grant 07CVD04 from the Leducq Transatlantic Mitral Network, Leducq Foundation, Paris, France, and by grant R01 HL109506 from the National Institutes of Health, Bethesda, MD. NR 36 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAY PY 2015 VL 8 IS 5 AR e002714 DI 10.1161/CIRCIMAGING.114.002714 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CI4SA UT WOS:000354742100006 ER PT J AU Hagege, AA Carpentier, A Levine, RA AF Hagege, Albert A. Carpentier, Alain Levine, Robert A. TI Dynamic Changes of the Mitral Valve Annulus New Look at Mitral Valve Diseases SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE Editorials; echocardiography; mitral valve; mitral valve annuloplasty; mitral valve insufficiency ID COMPENSATORY MECHANISM; PROLAPSE; REGURGITATION; LEAFLET; PATHOGENESIS; SEVERITY; INSIGHTS; REPAIR; LOCUS C1 [Hagege, Albert A.; Carpentier, Alain; Levine, Robert A.] Univ Paris 05, Sorbonne Paris Cite, Fac Med, Paris, France. [Hagege, Albert A.] Hop Europeen Georges Pompidou, Paris Cardiovasc Res Ctr, INSERM, U970, F-75015 Paris, France. [Hagege, Albert A.] Hop Europeen Georges Pompidou, AP HP, Dept Cardiol, F-75015 Paris, France. [Carpentier, Alain] Hop Europeen Georges Pompidou, AP HP, Dept Cardiovasc Surg, F-75015 Paris, France. [Levine, Robert A.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Levine, Robert A.] Harvard Univ, Sch Med, Boston, MA USA. RP Hagege, AA (reprint author), Hop Europeen Georges Pompidou, Dept Cardiol, 20 Rue Leblanc, F-75015 Paris, France. EM albert.hagege@egp.aphp.fr NR 30 TC 0 Z9 1 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAY PY 2015 VL 8 IS 5 AR e003539 DI 10.1161/CIRCIMAGING.115.003539 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CI4SA UT WOS:000354742100015 ER PT J AU Reynolds, HR Picard, MH Hochman, JS AF Reynolds, Harmony R. Picard, Michael H. Hochman, Judith S. TI Ischemia Burden in Stable Coronary Artery Disease Does Not Effectively Identify Revascularization Candidates SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article ID OPTIMAL MEDICAL THERAPY; OUTCOMES UTILIZING REVASCULARIZATION; DOBUTAMINE STRESS ECHOCARDIOGRAPHY; MYOCARDIAL-PERFUSION SCINTIGRAPHY; EMISSION COMPUTED-TOMOGRAPHY; FRACTIONAL FLOW RESERVE; BARI 2D TRIAL; PROGNOSTIC VALUE; COURAGE TRIAL; HEART-DISEASE C1 [Reynolds, Harmony R.; Hochman, Judith S.] NYU, Langone Med Ctr, Cardiovasc Clin Res Ctr, Leon Charney Div Cardiol, New York, NY USA. [Reynolds, Harmony R.; Hochman, Judith S.] NYU, Langone Med Ctr, Dept Med, New York, NY USA. [Picard, Michael H.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Picard, Michael H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Picard, Michael H.] Harvard Univ, Sch Med, Boston, MA USA. RP Reynolds, HR (reprint author), 530 First Ave,SKI 9R, New York, NY 10016 USA. EM Harmony.Reynolds@NYUMC.org OI Reynolds, Harmony/0000-0003-0284-0655 FU National Institutes of Health [5U01HL105907-03, 5U01HL105561-03] FX This article refers to work supported by National Institutes of Health grants 5U01HL105907-03 and 5U01HL105561-03. NR 48 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAY PY 2015 VL 8 IS 5 AR e000362 DI 10.1161/CIRCIMAGING.113.000362 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CI4SA UT WOS:000354742100003 ER PT J AU Golden-Mason, L Hurtado, CEW Cheng, LL Rosen, HR AF Golden-Mason, Lucy Hurtado, Christine E. Waasdorp Cheng, Linling Rosen, Hugo R. TI Hepatitis C viral infection is associated with activated cytolytic natural killer cells expressing high levels of T cell immunoglobulin- and mucin-domain-containing molecule-3 SO CLINICAL IMMUNOLOGY LA English DT Article DE Human; HCV; Natural cytotoxicity receptors; Cytotoxicity; IFN-gamma ID VIRUS-INFECTION; TIM-3 EXPRESSION; NK CELLS; RECEPTOR EXPRESSION; IN-VITRO; CYTOTOXICITY; IMMUNITY; INNATE; RESPONSES; BLOCKADE AB T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) is an inhibitory receptor implicated in T cell exhaustion characteristic of chronic viral infection. Limited data exist on NK cell Tim-3 expression and functional consequences. In chronic hepatitis C virus (HCV)-infected subjects, we found increased Tim-3 on NKs, which was associated with an activated phenotype. The high level of Tim-3 was not reversed by successful IFN-alpha-based antiviral therapy. Tim-3(high) NK cells up-regulated TRAIL in response to IFN-alpha to a greater extent and demonstrated greater lymphokine-activated killing activity, viral control, and degranulation but similar cytokine production than their Tim-3(low) counterparts. Our results suggest that Tim-3 on NKs is associated with activation of this innate lymphocyte population that is polarized towards cytotoxicity in chronic HCV. These findings reveal roles for Tim-3 in the regulation of NKs that might represent targets for treatment of chronic viral infections. (C) 2015 Published by Elsevier Inc. C1 [Golden-Mason, Lucy; Cheng, Linling; Rosen, Hugo R.] Univ Colorado Denver, Dept Med, Hepatitis C Ctr, Div Gastroenterol & Hepatol, Aurora, CO 80045 USA. [Hurtado, Christine E. Waasdorp] Childrens Hosp Colorado, Digest Hlth Inst, Pediat Gastroenterol, Aurora, CO USA. [Rosen, Hugo R.] Denver VA Med Ctr, Denver, CO USA. RP Rosen, HR (reprint author), Div GI Hepatol B 158, Acad Off Bldg 1,12631 E 17th Ave,Rm 7614,POB 6511, Aurora, CO 80045 USA. EM Hugo.Rosen@UCDENVER.edu FU VA Merit Review grant; [U19 AI 1066328]; [K24AI083742] FX This study was supported by U19 AI 1066328, K24AI083742, and VA Merit Review grant (HRR). NR 46 TC 8 Z9 8 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 1521-6616 EI 1521-7035 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAY PY 2015 VL 158 IS 1 BP 114 EP 125 DI 10.1016/j.clim.2015.03.008 PG 12 WC Immunology SC Immunology GA CI2QR UT WOS:000354592600014 PM 25797693 ER PT J AU Schapira, L AF Schapira, Lidia TI Communications by Professionals in Palliative Care SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Geriatric; Palliative care; Clinical practice; Communication; Caregiver; Family ageism; Uncertainty; End of life ID OF-LIFE CARE; HEALTH-CARE; FAMILY CONFERENCES; DECISION-MAKING; ADVANCED CANCER; ADVANCE DIRECTIVES; OLDER-ADULTS; END; CAREGIVERS; NONABANDONMENT AB In this article, the author first examines the ageist bias that is prevalent in clinics today. The author then reviews the basic communication principles and strategies that can help clinicians make their conversations with patients more focused and meaningful, thereby preparing patients and their family caregivers to make decisions in a crisis and to engage in planning for end-of-life care as early and intensively as possible. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Schapira, L (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, 55 Fruit St,Yawkey 9-A, Boston, MA 02114 USA. EM lschapira@partners.org NR 43 TC 0 Z9 0 U1 5 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 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2015 VL 31 IS 2 BP 231 EP + DI 10.1016/j.cger.2015.01.005 PG 14 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA CI4WC UT WOS:000354753600007 PM 25920058 ER PT J AU Callegari, LS Zhao, XH Nelson, KM Borrero, S AF Callegari, Lisa S. Zhao, Xinhua Nelson, Karin M. Borrero, Sonya TI Contraceptive adherence among women Veterans with mental illness and substance use disorder SO CONTRACEPTION LA English DT Article DE Medication adherence; Contraception; Veterans health; Mental illness; Alcohol-related disorders; Substance-related disorders ID POSTTRAUMATIC-STRESS-DISORDER; UNINTENDED PREGNANCY; ADMINISTRATIVE DATA; UNITED-STATES; BIRTH-WEIGHT; HEALTH; AFGHANISTAN; DEPRESSION; ALCOHOL; IRAQ AB Objective: Emerging data suggest that mental illness and substance use disorder (SUD) are important risk factors for inconsistent contraceptive use. We investigated whether mental illness without or with SUD is associated with contraceptive adherence and continuation of hormonal methods among women Veterans. Study design: We conducted a retrospective analysis of national Veteran's Administration data among women aged 18-45 with a hormonal contraceptive prescription (pill/patch/ring/injectable) during the first week of fiscal year 2013. We tested associations between mental illness diagnoses (depression, posttraumatic stress disorder, anxiety, bipolar disorder, schizophrenia, adjustment disorder) without or with SUD diagnoses (drug/alcohol abuse) and 12-month contraceptive adherence (number and length of gaps 7 days between refills and months of contraceptive coverage) using multivariable regression models. Results: Among 9780 Veterans, 43.6% had mental illness alone, 9.4% comorbid mental illness and SUD, and 47.0% neither diagnosis. In adjusted analyses, compared to women with neither diagnosis, women with mental illness alone had a similar rate of gaps but increased odds of having gaps longer than 30 days [odds ratio (OR): 1.35, 95% confidence interval (Cl): 1.10-1.52] and fewer months of contraceptive coverage (beta_coefficient: -0.39, 95% CI: -0.56 to -0.23). Women with mental illness and SUD experienced more gaps (incidence rate ratio: 1.12, 95% CI: 1.03-1.21), increased odds of gaps longer than 30 days (OR: 1.46, 95% CI: 1.10-1.79), fewer months of contraceptive coverage ((beta_coefficient: -0.90, 95% CI: -1.20 to -0.62) and reduced odds of continuous 12-month coverage (adjusted OR: 0.76, 95% CI: 0.63-0.93). Conclusions: Mental illness, particularly with comorbid SUD, is associated with reduced contraceptive adherence and continuation among women Veterans. Women with these risk factors could potentially benefit from use of long-acting reversible methods. Implications: Women Veterans have a high burden of mental illness and SUD, which we found are associated with inconsistent contraceptive use. Efforts to improve adherence to hormonal contraceptives and to increase availability of long-acting reversible methods in this vulnerable population are warranted. Published by Elsevier Inc. C1 [Callegari, Lisa S.; Nelson, Karin M.] Dept Vet Affairs VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Callegari, Lisa S.] Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Zhao, Xinhua; Borrero, Sonya] VA Pittsburgh Hlth Care Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Nelson, Karin M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Borrero, Sonya] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15217 USA. RP Callegari, LS (reprint author), VA Puget Sound Hlth Care Syst, Seattle HSR&D Ctr, 1660 S Columbian Way S-152, Seattle, WA 98108 USA. EM lisa.callegari@va.gov FU Department of Veterans Affairs, Veteran Health Administration, Health Services Research and Development Merit Review Award [II 12-124]; VA Health Services Research and Development Postdoctoral Fellowship [TPM 61-041] FX This study was supported by a Department of Veterans Affairs, Veteran Health Administration, Health Services Research and Development Merit Review Award (II 12-124, PI: S.B.). L.S.C. was supported by a VA Health Services Research and Development Postdoctoral Fellowship (TPM 61-041). NR 38 TC 3 Z9 3 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 EI 1879-0518 J9 CONTRACEPTION JI Contraception PD MAY PY 2015 VL 91 IS 5 BP 386 EP 392 DI 10.1016/j.contraception.2015.01.013 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CH4OI UT WOS:000354012400006 PM 25636807 ER PT J AU Wasfy, MM Baggish, A AF Wasfy, Meagan M. Baggish, Aaron TI Chest Pain in Athletes from Personal History Section (Medical Causes) SO CURRENT SPORTS MEDICINE REPORTS LA English DT Review C1 [Wasfy, Meagan M.; Baggish, Aaron] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. RP Wasfy, MM (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1537-890X EI 1537-8918 J9 CURR SPORT MED REP JI Curr. Sport. Med. Rep. PD MAY-JUN PY 2015 VL 14 IS 3 BP 248 EP 252 PG 5 WC Sport Sciences SC Sport Sciences GA CI2CC UT WOS:000354551400024 PM 25968863 ER PT J AU Pisano, T Numis, AL Heavin, SB Weckhuysen, S Angriman, M Suls, A Podesta, B Thibert, RL Shapiro, KA Guerrini, R Scheffer, IE Marini, C Cilio, MR AF Pisano, Tiziana Numis, Adam L. Heavin, Sinead B. Weckhuysen, Sarah Angriman, Marco Suls, Arvid Podesta, Barbara Thibert, Ronald L. Shapiro, Kevin A. Guerrini, Renzo Scheffer, Ingrid E. Marini, Carla Cilio, Maria Roberta TI Early and effective treatment of KCNQ2 encephalopathy SO EPILEPSIA LA English DT Article DE Epilepsy; KCNQ2 encephalopathy; Antiepileptic drug treatment ID DE-NOVO MUTATIONS; FAMILIAL NEONATAL CONVULSIONS; EPILEPTIC ENCEPHALOPATHIES; PHENOTYPE; CHANNELS; MECHANISM; SPECTRUM; GENE AB ObjectivesTo describe the antiepileptic drug (AED) treatment of patients with early infantile epileptic encephalopathy due to KCNQ2 mutations during the neonatal phase and the first year of life. MethodsWe identified 15 patients and reviewed the electroclinical, neuroimaging, and AED treatment data. ResultsSeizure onset was between 1 and 4days of age with daily tonic asymmetric, focal and clonic seizures in nine patients and status epilepticus in the remaining six. Electroencephalography (EEG) showed multifocal epileptiform abnormalities in nine patients and a burst-suppression pattern in six. All patients were trialed with adequate daily doses of several AEDs before they reached seizure freedom. Six patients (40%) achieved seizure control within 2weeks of carbamazepine (CBZ) administration and five (33%) were seizure-free with phenytoin (PHT). The last four patients (27%) were successfully treated with topiramate (TPM) (two patients), levetiracetam (LEV) (one), and a combination of LEV with TPM (one). Most patients reached seizure freedom within the first year of life and remained seizure-free thereafter. Twelve patients had moderate-to-severe developmental delay at follow-up. However, the two patients whose seizures ceased within a few days of onset showed only mild cognitive impairment. SignificanceOur findings suggest that drugs acting on sodium channels including CBZ and PHT should be considered as first-line treatment in patients with KCNQ2 encephalopathy. Voltage-gated sodium and potassium channels co-localize at the neuronal membrane. Therefore, the efficacy of drugs acting as sodium-channel blockers could be linked to their modulating effect on both channels. The type of KCNQ2 mutation might influence AED response as well as developmental outcome. Early recognition of KCNQ2 encephalopathy followed by the most appropriate and effective treatment may be important for reducing the neurodevelopmental impairment associated with this disorder. C1 [Pisano, Tiziana; Guerrini, Renzo; Marini, Carla] A Meyer Childrens Hosp, Neurol Unit & Labs, Florence, Italy. [Numis, Adam L.; Shapiro, Kevin A.; Cilio, Maria Roberta] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Heavin, Sinead B.; Scheffer, Ingrid E.] Austin Hlth, Florey Inst, Dept Med, Melbourne, Vic, Australia. [Heavin, Sinead B.; Scheffer, Ingrid E.] Austin Hlth, Florey Inst, Dept Paediat, Melbourne, Vic, Australia. [Heavin, Sinead B.; Scheffer, Ingrid E.] Univ Melbourne, Royal Childrens Hosp, Melbourne, Vic, Australia. [Weckhuysen, Sarah; Suls, Arvid] VIB, Dept Mol Genet, Neurogenet Grp, Antwerp, Belgium. [Weckhuysen, Sarah; Suls, Arvid] Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium. [Angriman, Marco] Cent Hosp Bolzano, Bolzano, Italy. [Podesta, Barbara] S Croce & S Carlo Hosp, Child Neurol & Psychiat Unit, Cuneo, Italy. [Thibert, Ronald L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Epilepsy Program, Boston, MA USA. [Guerrini, Renzo] Univ Florence, Florence, Italy. [Cilio, Maria Roberta] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. RP Marini, C (reprint author), A Meyer Childrens Hosp, Neurol Unit, Viale Pieraccini 24, Florence, Italy. EM c.marini@meyer.it FU Italian Ministry of Health and Education [RF-2009-152669]; National Health and Medical Research Council of Australia; Italian Ministry of Health; European Community Sixth and Seventh Framework Thematic Priority Health; Italian Ministry of Education, University and Research; Tuscany Region; Telethon Foundation; Mariani Foundation; UCB; Athena Diagnostics; GlaxoSmithKline; Janssen-Cilag EMEA; Transgenomics; Biocodex FX We thank the patients and their families for participating in our research. We thank Piras Maria Francesca for technical support. The study was supported by the RF-2009-152669 grant from the Italian Ministry of Health and Education and the National Health and Medical Research Council of Australia. AS is a postdoctoral fellow of the National Fund for Scientific Research Flanders (FWO).; Prof Guerrini received honoraria from Biocodex, UCB, Eisai Inc., Value-Box, and ViroPharma, and research support from the Italian Ministry of Health, the European Community Sixth and Seventh Framework Thematic Priority Health, the Italian Ministry of Education, University and Research, the Tuscany Region, the Telethon Foundation, and the Mariani Foundation.; Prof Scheffer has received support from, and/or has served as a paid consultant for UCB, Athena Diagnostics, GlaxoSmithKline, Janssen-Cilag EMEA, and Transgenomics and Biocodex. NR 26 TC 14 Z9 14 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD MAY PY 2015 VL 56 IS 5 BP 685 EP 691 DI 10.1111/epi.12984 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CI3IP UT WOS:000354641700009 PM 25880994 ER PT J AU Levesque, AY de la Torre, JI AF Levesque, Andre Yuan de la Torre, Jorge I. TI Midface Anatomy, Aging, and Aesthetic Analysis SO FACIAL PLASTIC SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Midface anatomy; Facial aging; Aesthetic analysis; Malar fat pad; Sub-orbicularis oculi fat ID APONEUROTIC SYSTEM SMAS; FACE LIFT FLAP; SURGICAL ANATOMY; CLINICAL-IMPLICATIONS; PHOTOGRAPHIC STANDARDS; LYMPHATIC DRAINAGE; PREMASSETER SPACE; FAT COMPARTMENTS; PLASTIC-SURGERY; REJUVENATION AB This article reviews the key anatomic structures in the region of the midface, including important surface and bony landmarks, innervation, blood supply, muscle layers, and fat compartments. It also discusses changes in these structures related to the aging process and aesthetic analysis of the midface to aid with operative planning. C1 [Levesque, Andre Yuan] Univ Alabama Birmingham, Div Plast Surg, Birmingham, AL 35210 USA. [de la Torre, Jorge I.] Univ Alabama Birmingham, Birmingham VA Med Ctr, Div Plast Surg, Birmingham, AL 35210 USA. RP de la Torre, JI (reprint author), Univ Alabama Birmingham, Birmingham VA Med Ctr, Div Plast Surg, 1102 Fac Off Tower,510 20th St South, Birmingham, AL 35210 USA. EM jdlt@uab.edu NR 42 TC 2 Z9 2 U1 3 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-7406 J9 FACIAL PLAST SURG CL JI Facial Plast. Surg. Clin. N. Am. PD MAY PY 2015 VL 23 IS 2 BP 129 EP + DI 10.1016/j.fsc.2015.01.002 PG 9 WC Surgery SC Surgery GA CI8XK UT WOS:000355054800003 PM 25921564 ER PT J AU Liu, H Chen, J Li, WJ Rose, ME Shinde, SN Balasubramani, M Uechi, GT Mutus, B Graham, SH Hickey, RW AF Liu, Hao Chen, Jie Li, Wenjin Rose, Marie E. Shinde, Sunita N. Balasubramani, Manimalha Uechi, Guy T. Mutus, Buelent Graham, Steven H. Hickey, Robert W. TI Protein disulfide isomerase as a novel target for cyclopentenone prostaglandins: implications for hypoxic ischemic injury SO FEBS JOURNAL LA English DT Article DE brain; cyclooxygenase; cyclopentenone; ischemia; protein disulfide isomerase ID 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); CYSTEINE MODIFICATION; NEURONAL APOPTOSIS; CEREBRAL-ISCHEMIA; PDI FAMILY; IN-VIVO; AGGREGATION; CYCLOOXYGENASE-2; NEURODEGENERATION; INHIBITION AB Cyclooxygenase-2 (COX-2) is an important contributor to ischemic brain injury. Identification of the downstream mediators of COX-2 toxicity may allow the development of targeted therapies. Of particular interest is the cyclopentenone family of prostaglandin metabolites. Cyclopentenone prostaglandins (CyPGs) are highly reactive molecules that form covalent bonds with cellular thiols. Protein disulfide isomerase (PDI) is an important molecule for the restoration of denatured proteins following ischemia. Because PDI has several thiols, including thiols within the active thioredoxin-like domain, we hypothesized that PDI is a target of CyPGs and that CyPG binding of PDI is detrimental. CyPG-PDI binding was detected in vitro via immunoprecipitation and MS. CyPG-PDI binding decreased PDI enzymatic activity in recombinant PDI treated with CyPG, and PDI immunoprecipitated from neuronal culture treated with CyPG or anoxia. Toxic effects of binding were demonstrated in experiments showing that: (a) pharmacologic inhibition of PDI increased cell death in anoxic neurons, (b) PDI overexpression protected neurons exposed to anoxia and SH-SY5Y cells exposed to CyPG, and (c) PDI overexpression in SH-SY5Y cells attenuated ubiquitination of proteins and decreased activation of pro-apoptotic caspases. In conclusion, CyPG production and subsequent binding of PDI is a novel and potentially important mechanism of ischemic brain injury. We show that CyPGs bind to PDI, cyclopentenones inhibit PDI activity, and CyPG-PDI binding is associated with increased neuronal susceptibility to anoxia. Additional studies are necessary to determine the relative role of CyPG-dependent inhibition of PDI activity in ischemia and other neurodegenerative disorders. C1 [Liu, Hao; Li, Wenjin; Rose, Marie E.; Graham, Steven H.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Liu, Hao; Chen, Jie; Li, Wenjin; Rose, Marie E.; Graham, Steven H.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15224 USA. [Chen, Jie; Shinde, Sunita N.; Hickey, Robert W.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15224 USA. [Balasubramani, Manimalha; Uechi, Guy T.] Univ Pittsburgh, Biomed Mass Spectrometry Ctr, Pittsburgh, PA 15224 USA. [Mutus, Buelent] Univ Windsor, Dept Chem & Biochem, Windsor, ON N9B 3P4, Canada. RP Hickey, RW (reprint author), Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Dept Pediat, Adm Off Bldg,Suite 2400,4401 Penn Ave, Pittsburgh, PA 15224 USA. EM robert.hickey@chp.edu FU National Institutes of Health, National Institute of Child Health and Human Development; National Institute of Neurological Disorders and Stroke [R21HD058846, R01NS37549]; VA Merit Review program; Cancer Center Support Grant, National Cancer Institute [P30CA047904] FX This work was supported by National Institutes of Health, National Institute of Child Health and Human Development and National Institute of Neurological Disorders and Stroke: R21HD058846 (RWH), R01NS37549 (SHG) and the VA Merit Review program (SHG). The work done by the Biomedical Mass Spectrometry Center was supported in part by the Cancer Center Support Grant P30CA047904, National Cancer Institute. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 54 TC 3 Z9 3 U1 1 U2 6 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 MAY PY 2015 VL 282 IS 10 BP 2045 EP 2059 DI 10.1111/febs.13259 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI5PG UT WOS:000354809700015 PM 25754985 ER PT J AU Palmer, J Chai, XY Martin, PJ Weisdorf, D Inamoto, Y Pidala, J Jagasia, M Pavletic, S Cutler, C Vogelsang, G Arai, S Flowers, MED Lee, SJ AF Palmer, Jeanne Chai, Xiaoyu Martin, Paul J. Weisdorf, Daniel Inamoto, Yoshihiro Pidala, Joseph Jagasia, Madan Pavletic, Steven Cutler, Corey Vogelsang, Georgia Arai, Sally Flowers, Mary E. D. Lee, Stephanie J. TI Failure-free survival in a prospective cohort of patients with chronic graft-versus-host disease SO HAEMATOLOGICA LA English DT Article ID STEM-CELL TRANSPLANTATION; LONG-TERM SURVIVAL; CHRONIC GVHD; SYSTEMIC TREATMENT; LATE DEATHS; CONSORTIUM; PROGNOSIS; SEVERITY; CRITERIA; OUTCOMES AB Failure-free survival, defined as the absence of relapse, non-relapse mortality or addition of another systemic therapy, has been proposed as a potential endpoint for clinical trials, but its use has only been reported for single-center studies. We measured failure-free survival in a prospective observational cohort of patients (n= 575) with both newly diagnosed and existing chronic graft-versus-host disease from nine centers. Failure was observed in 389 (68%) patients during the observation period. The median follow up of all patients was 30.9 months, and the median failure-free survival was 9.8 months (63% at 6 months, 45% at 1 year, and 29% at 2 years). Of the variables measured at enrollment, ten were associated with shorter failure-free survival: higher National Institutes of Health 0-3 skin score, higher National Institutes of Health 0-3 gastrointestinal score, worse range of motion summary score, lower forced vital capacity (%), bronchiolitis obliterans syndrome, worse quality of life, moderate to severe hepatic dysfunction, absence of treatment for gastric acid, female donor for male recipient, and prior grade II-IV acute graft-versus-host disease. Addition of a new systemic treatment, the major cause of failure, was associated with an increased risk of subsequent non-relapse mortality (hazard ratio= 2.06, 95% confidence interval: 1.29-3.32; P< 0.003) and decreased survival (hazard ratio= 1.51, 95% confidence interval: 1.04-2.18; P< 0.03). These results show that fewer than half of patients on systemic treatment will be failure-free survivors at 1 year, and fewer than a third will reach 2 years without experiencing failure. Better treatments are needed for chronic graft-versus-host disease. C1 [Palmer, Jeanne] Mayo Clin Phoenix, Div Hematol Oncol, Phoenix, AZ 85054 USA. [Chai, Xiaoyu; Martin, Paul J.; Inamoto, Yoshihiro; Flowers, Mary E. D.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Weisdorf, Daniel] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA. [Inamoto, Yoshihiro] Natl Canc Ctr, Div Hematopoiet Stem Cell Transplantat, Tokyo, Japan. [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Blood & Marrow Transplantat, Tampa, FL 33682 USA. [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplant Program, Nashville, TN USA. [Pavletic, Steven] NCI, NIH, Bethesda, MD 20892 USA. [Cutler, Corey] Dana Farber Canc Inst, Hematol Malignancies, Boston, MA 02115 USA. [Vogelsang, Georgia] Johns Hopkins Univ Hosp, Div Oncol, Baltimore, MD 21287 USA. [Arai, Sally] Stanford Univ, Med Ctr, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA. RP Palmer, J (reprint author), Mayo Clin Phoenix, Div Hematol Oncol, Phoenix, AZ 85054 USA. EM palmer.jeanne@mayo.edu FU Chronic GVHD Consortium, National Institutes of Health Rare Disease Clinical Research Network [U54 CA163438]; [CA118953] FX The Chronic GVHD Consortium (U54 CA163438) is a part of the National Institutes of Health Rare Disease Clinical Research Network, supported through a collaboration between the Office of Rare Diseases Research, NCATS, and the National Cancer Institute. This work was also supported by CA118953 NR 23 TC 7 Z9 7 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD MAY PY 2015 VL 100 IS 5 BP 690 EP 695 DI 10.3324/haematol.2014.117283 PG 6 WC Hematology SC Hematology GA CI5IE UT WOS:000354788000035 PM 25715403 ER PT J AU Kuhn, MWM Hadler, MJ Daigle, SR Koche, RP Krivtsov, AV Olhava, EJ Caligiuri, MA Huang, G Bradner, JE Pollock, RM Armstrong, SA AF Kuehn, Michael W. M. Hadler, Michael J. Daigle, Scott R. Koche, Richard P. Krivtsov, Andrei V. Olhava, Edward J. Caligiuri, Michael A. Huang, Gang Bradner, James E. Pollock, Roy M. Armstrong, Scott A. TI MLL partial tandem duplication leukemia cells are sensitive to small molecule DOT1L inhibition SO HAEMATOLOGICA LA English DT Letter DE DOT1L inhibition; MLL-PTD; leukemia ID ACUTE MYELOID-LEUKEMIA; MIXED LINEAGE LEUKEMIA; H3K79 METHYLTRANSFERASE C1 [Kuehn, Michael W. M.; Hadler, Michael J.; Koche, Richard P.; Krivtsov, Andrei V.; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Daigle, Scott R.; Olhava, Edward J.; Pollock, Roy M.] Epizyme Inc, Cambridge, MA USA. [Caligiuri, Michael A.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Huang, Gang] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol, Cincinnati, OH 45229 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. RP Armstrong, SA (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA. EM armstros@mskcc.org NR 15 TC 4 Z9 4 U1 0 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD MAY PY 2015 VL 100 IS 5 DI 10.3324/haematol.2014.115337 PG 4 WC Hematology SC Hematology GA CI5IE UT WOS:000354788000009 ER PT J AU Eberlin, KR Ring, D AF Eberlin, Kyle R. Ring, David TI Infection After Hand Surgery SO HAND CLINICS LA English DT Article DE Perioperative antibiotics; Hand infections; Prophylactic measures; Surgical site infection; Postoperative infection ID RESISTANT STAPHYLOCOCCUS-AUREUS; SURGICAL-WOUND-INFECTION; PLACEBO-CONTROLLED TRIAL; CARPAL-TUNNEL RELEASE; POSTOPERATIVE INFECTION; ANTIBIOTIC-PROPHYLAXIS; DOUBLE-BLIND; DISTAL PHALANX; OPEN FRACTURES; COMPLICATIONS AB Postoperative infections are uncommon after hand surgery. Infection can delay recovery and contribute to scarring and stiffness. Measures intended to reduce the risk of infection after hand surgery include hand washing, skin preparation, sterile technique, and prophylactic antibiotics. The role of prophylactic antibiotics for small, clean, elective hand surgery procedures lasting less than 2 hours is debated. C1 [Eberlin, Kyle R.; Ring, David] Massachusetts Gen Hosp, Hand Surg Serv, Boston, MA 02114 USA. [Eberlin, Kyle R.] Harvard Univ, Div Plast & Reconstruct Surg, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ring, David] Harvard Univ, Dept Orthoped Surg, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Eberlin, KR (reprint author), Harvard Univ, Div Plast & Reconstruct Surg, Sch Med, Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 435,15 Parkman St, Boston, MA 02114 USA. EM keberlin@mgh.harvard.edu NR 54 TC 0 Z9 0 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0712 EI 1558-1969 J9 HAND CLIN JI Hand Clin. PD MAY PY 2015 VL 31 IS 2 BP 355 EP + DI 10.1016/j.hcl.2014.12.007 PG 8 WC Orthopedics SC Orthopedics GA CI8NF UT WOS:000355028300020 PM 25934209 ER PT J AU Yarlagadda, BB Hatton, E Huettig, J Deschler, D AF Yarlagadda, Bharat Bhushan Hatton, Elissa Huettig, Janet Deschler, Daniel TI Patient and Staff Perceptions of Social Worker Counseling before Surgical Therapy for Head and Neck Cancer SO HEALTH & SOCIAL WORK LA English DT Article DE counseling; oncology; psychosocial distress; surgery ID INFORMATION AB Patients who undergo surgical therapy for head and neck cancer often face a tremendous challenge involving considerable psychological distress and impaired social functioning. These difficulties are often compounded by logistical difficulties such as transportation, financial assistance, and continuity of care after the acute hospitalization. Social workers have a unique opportunity to address the psychosocial and logistical issues facing these patients through preadmission counseling and coordination. The study reported in this article aimed to assess the effect of preadmission counseling for patients planning to undergo major surgical therapy for head and neck cancer. Ten patients who received preadmission counseling were surveyed to ascertain the utility of it in regard to multiple social and logistical factors. Comparisons were made with patients who did not receive such counseling. Staff perceptions were likewise obtained. The surveys indicated that preadmission counseling helped in regard to improving peri-admission support and access to financial and logistical resources, and lowered levels of anxiety during admission. Areas of potential improvement were identified, including addressing substance abuse issues in a timely manner. C1 [Yarlagadda, Bharat Bhushan] Massachusetts Eye & Ear Infirm, Ontolaryngol Head & Neck Surg, Head & Neck Surg Oncol & Microvasc Reconstruct, Boston, MA 02114 USA. [Yarlagadda, Bharat Bhushan; Hatton, Elissa] Massachusetts Eye & Ear Infirm, Ontolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Huettig, Janet] Massachusetts Eye & Ear Infirm, Ontolaryngol Head & Neck Surg, Social Work & Care Coordinat, Boston, MA 02114 USA. [Deschler, Daniel] Massachusetts Eye & Ear Infirm, Ontolaryngol Head & Neck Surg, Head & Neck Surg Oncol, Boston, MA 02114 USA. RP Yarlagadda, BB (reprint author), Massachusetts Eye & Ear Infirm, Ontolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM yarlagb@gmail.com NR 6 TC 1 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0360-7283 EI 1545-6854 J9 HEALTH SOC WORK JI Health Soc. Work PD MAY PY 2015 VL 40 IS 2 BP 120 EP 124 DI 10.1093/hsw/hlv015 PG 5 WC Social Work SC Social Work GA CI4UI UT WOS:000354748900014 PM 26027420 ER PT J AU Benzer, J Horner, M AF Benzer, Justin Horner, Margaret TI A Meta-analytic Integration and Test of Psychological Climate Dimensionality SO HUMAN RESOURCE MANAGEMENT LA English DT Article DE culture and climate; HR measurement issues ID PERCEIVED ORGANIZATIONAL SUPPORT; WORK-ENVIRONMENT PERCEPTIONS; LEADER-MEMBER EXCHANGE; JOB-SATISFACTION; EMPLOYEE PERCEPTIONS; OCCUPATIONAL STRAIN; SOCIAL-ENVIRONMENT; PATH-ANALYSIS; TEAM CLIMATE; CROSS-LEVEL AB There is no consensus as to what constructs should be considered to be psychological climate. Further, there is no clear taxonomy of psychological climate, although the climate literature suggests that psychological climate perceptions should form higher-order (i.e., abstract, broad) dimensions. Two meta-analyses have been conducted to evaluate higher-order frameworks, but neither study tested the psychometric structure of their hypothesized models. The current meta-analysis estimated the intercorrelations and criterion-related validity of 23 psychological climate constructs in order to test the theoretical frameworks proposed by prior meta-analyses. Confirmatory factor analyses supplemented by a method analogous to item-to-scale correlations indicated little empirical support for the a priori frameworks. Results suggest that that psychological climate may be parsimoniously represented by two dimensions. Task climate was most strongly indicated by supervisor goal setting, innovation, and organizational responsiveness. Relational climate was most strongly indicated by work group warmth and social rewards. A path analysis was estimated to test whether job satisfaction partially mediated the association between psychological climate and the outcomes of job performance, turnover intentions, and psychological well-being. Results provide guidance to researchers and practitioners interested in measuring perceptions of the work environment. (c) 2014 Wiley Periodicals, Inc. C1 [Benzer, Justin] Boston Univ, Ctr Healthcare Org & Implementat Res, Dept Veteran Affairs, VA Boston Healthcare Syst, Boston, MA USA. [Benzer, Justin] Boston Univ, Dept Hlth Policy & Management, Boston, MA USA. [Horner, Margaret] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. [Horner, Margaret] Blinn Coll, Brenham, TX USA. RP Benzer, J (reprint author), Boston Univ, Dept Hlth Policy & Management, Dept Veteran Affairs, VA Boston Healthcare Syst, 150 S Huntington Ave 152-M, Boston, MA USA. EM justin.benzer@va.gov OI Benzer, Justin/0000-0001-5151-2127 FU Department of Veterans Affairs Office of Academic Affiliations HSR&D postdoctoral fellowship FX Financial support was provided in part from a Department of Veterans Affairs Office of Academic Affiliations HSR&D postdoctoral fellowship. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. The authors gratefully acknowledge the intellectual contributions and resource support from Christopher Hopwood, and the editorial contributions of Mindy Bergman, David Mohr, and Stephanie Payne as well as the constructive advice from two anonymous reviewers. NR 177 TC 2 Z9 2 U1 4 U2 32 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 0090-4848 EI 1099-050X J9 HUM RESOUR MANAGE-US JI Hum. Resour. Manage. PD MAY-JUN PY 2015 VL 54 IS 3 BP 457 EP 482 DI 10.1002/hrm.21645 PG 26 WC Psychology, Applied; Management SC Psychology; Business & Economics GA CI5UP UT WOS:000354825600008 ER PT J AU Hawkins, BM Kennedy, KF Aronow, HD Nguyen, LL White, CJ Rosenfield, K Normand, SLT Spertus, JA Yeh, RW AF Hawkins, Beau M. Kennedy, Kevin F. Aronow, Herbert D. Nguyen, Louis L. White, Christopher J. Rosenfield, Kenneth Normand, Sharon-Lise T. Spertus, John A. Yeh, Robert W. TI Hospital Variation in Carotid Stenting Outcomes SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE carotid stenosis; carotid stenting; hospital quality; stroke ID MEDICARE BENEFICIARIES; READMISSION RATES; ENDARTERECTOMY; POPULATION; MORTALITY; QUALITY; HEALTH; CARE AB OBJECTIVES The aim of this study was to examine variation in outcomes for patients receiving carotid artery stenting (CAS) across a sample of U.S. hospitals and assess the extent to which this variation was attributable to differences in case mix and procedural volume. BACKGROUND As CAS is increasingly being used throughout the United States, assessing hospital variation in CAS outcomes is critical to understanding and improving the quality of care for patients with carotid artery disease. METHODS Hospitals participating in the National Cardiovascular Data Registry-Carotid Artery Endarterectomy and Revascularization Registry contributing more than 5 CAS procedures from 2005 through 2013 were eligible for inclusion. We estimated unadjusted and risk-standardized rates of in-hospital stroke or death for each participating hospital using a previously validated prediction model and applying hospital-level random effects. RESULTS There were 188 hospitals contributing 19,381 CAS procedures during the period of interest. Unadjusted and risk-standardized in-hospital stroke or death rates ranged from 0% to 18.8% and 1.2% to 4.7%, respectively. Operator and hospital volumes were not significant predictors of outcomes after adjustment for case mix (p = 0.15 and p = 0.09, respectively). CONCLUSIONS CAS outcomes vary 4-fold among hospitals, even after adjustment for differences in case mix. Future work is needed to identify the sources of this variation and develop initiatives to improve patient outcomes. (C) 2015 by the American College of Cardiology Foundation. C1 [Hawkins, Beau M.] Univ Oklahoma, Hlth Sci Ctr, Cardiovasc Sect, Oklahoma City, OK USA. [Kennedy, Kevin F.; Spertus, John A.] Univ Missouri, St Lukes Mid Amer Heart Inst, Kansas City, MO 64110 USA. [Aronow, Herbert D.] St Joseph Mercy Hosp, Michigan Heart Div, Ann Arbor, MI 48104 USA. [Nguyen, Louis L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [White, Christopher J.] Ochsner Med Ctr, John Ochsner Heart & Vasc Inst, New Orleans, LA USA. [Rosenfield, Kenneth; Yeh, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy Biostat, Boston, MA USA. RP Yeh, RW (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 8-843, Boston, MA 02114 USA. EM ryeh@mgh.harvard.edu FU American College of Cardiology Foundation's National Cardiovascular Data Registry (NCDR); Abbott Vascular; Bard Peripheral Vascular; Medtronic/Invatec; Atrium; Boston Scientific; Complete Conference Management; Harvard Clinical Research Institute; Contego; Micell; Becker Ventures; American College of Cardiology Foundation FX This research was supported by the American College of Cardiology Foundation's National Cardiovascular Data Registry (NCDR). The views expressed in this manuscript represent those of the author(s) and do not necessarily represent the official views of the NCDR or its associated professional societies identified at www.ncdr.com. The CARE Registry is an initiative of the American College of Cardiology Foundation, The Society for Cardiovascular Angiography and Interventions, the Society of Interventional Radiology, the American Academy of Neurology, the American Association of Neurological Surgeons/Congress of Neurological Surgeons, the Society for Vascular Medicine, and the Society of Vascular and Interventional Neurology. Dr. Aronow is a nonpaid consultant for Silk Road Medical, Inc. Dr. Rosenfield has received research grants from Abbott Vascular, Bard Peripheral Vascular, Medtronic/Invatec, and Atrium; has received consulting/advisory board fees from Abbott Vascular, Boston Scientific, Complete Conference Management, Harvard Clinical Research Institute, Contego, Micell, and Becker Ventures; has equity in Lumen Biomedical, Medical Stimulation Corp, Angioguard (Cordis), and Micell; and has served on the Board of Directors of VIVA Physicians (501C3). Dr. Normand is on the Board of Directors of Frontier Science Technology and Research Foundation. Dr. Spertus has received a research contract from the American College of Cardiology Foundation to analyze the NCDR Registry. Dr. Yeh is an investigator at the Harvard Clinical Research Institute. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 14 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD MAY PY 2015 VL 8 IS 6 BP 858 EP 863 DI 10.1016/j.jcin.2015.01.026 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CI5DX UT WOS:000354774300023 PM 25999111 ER PT J AU Haykal, S Arad, E Bagher, S Lai, C Hohman, M Hadlock, T Zuker, RM Borschel, GH AF Haykal, Siba Arad, Ehud Bagher, Shaghayegh Lai, Carolyn Hohman, Marc Hadlock, Tessa Zuker, Ronald M. Borschel, Gregory H. TI The Role of Botulinum Toxin A in the Establishment of Symmetry in Pediatric Paralysis of the Lower Lip SO JAMA FACIAL PLASTIC SURGERY LA English DT Article ID FACIAL-NERVE PALSY; SYNKINESIS; ASYMMETRY; INJECTION; RECONSTRUCTION; REANIMATION; STRATEGIES AB IMPORTANCE Botulinum toxin A has been described as an effective adjunct treatment for achieving symmetry in adults with facial paralysis. Few investigators have described the use of botulinum toxin A in pediatric patients with facial paralysis. OBJECTIVE To present our preliminary experience with botulinum toxin A in pediatric patients presenting with asymmetry of the lower lip. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective medical record review of all pediatric patients (age range, 4-17 years; mean [SD] age, 11.2 [4.7] years) with facial paralysis who were treated with botulinum toxin A injections from January 1, 2004, through December 31, 2012. Patients presented for treatment at The Hospital for Sick Children, Toronto, Ontario, Canada, or the Massachusetts Eye and Ear Infirmary, Boston. MAIN OUTCOMES AND MEASURES Using facial analysis software, we measured lower lip asymmetry in the patients' photographs before and after treatment, at rest, and in a dynamic state. We performed analysis of variance to assess for improvement in symmetry. RESULTS We identified 18 patients with the following 3 primary indications for treatment: focal lip asymmetry (n = 11), extensive hemifacial asymmetry (n = 5), and focal synkinesis (n = 2). We found no complications related to botulinum toxin A treatment. The mean (SD) dynamic deviation before the injection was 3.5 (1.7) mm, whereas the mean dynamic deviation after the injection was 1.5 (0.8) mm. The mean (SD) deviation correction was evaluated at 61%(6%) and was statistically significant (P = .04). CONCLUSIONS AND RELEVANCE Botulinum toxin A injection is a safe procedure for improving localized asymmetry in pediatric patients with facial paralysis. Preliminary results indicate that botulinum toxin Amay be an effective treatment for lower lip asymmetry in children and adolescents. C1 [Haykal, Siba; Bagher, Shaghayegh; Lai, Carolyn; Zuker, Ronald M.; Borschel, Gregory H.] Hosp Sick Children, Div Plast Surg, Toronto, ON M5G 1X8, Canada. [Haykal, Siba; Bagher, Shaghayegh; Lai, Carolyn; Zuker, Ronald M.; Borschel, Gregory H.] Univ Toronto, Dept Surg, Div Plast & Reconstruct Surg, Toronto, ON M5G 1P7, Canada. [Arad, Ehud] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Plast Surg, IL-69978 Tel Aviv, Israel. [Hohman, Marc; Hadlock, Tessa] Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, Boston, MA 02114 USA. RP Haykal, S (reprint author), Univ Toronto, Dept Surg, Div Plast & Reconstruct Surg, 111 Elizabeth St, Toronto, ON M5G 1P7, Canada. EM siba.haykal@utoronto.ca NR 21 TC 4 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD MAY-JUN PY 2015 VL 17 IS 3 BP 174 EP 178 DI 10.1001/jamafacial.2015.10 PG 5 WC Surgery SC Surgery GA CI8CT UT WOS:000354996300003 PM 25742503 ER PT J AU Iacolucci, CM Banks, C Jowett, N Kozin, ED Bhama, PK Barbara, M Hadlock, TA AF Iacolucci, Carlo M. Banks, Caroline Jowett, Nate Kozin, Elliott D. Bhama, Prabhat K. Barbara, Maurizio Hadlock, Tessa A. TI Development and Validation of a Spontaneous Smile Assay SO JAMA FACIAL PLASTIC SURGERY LA English DT Article ID GRACILIS MUSCLE TRANSFER; QUALITY-OF-LIFE; FACIAL PARALYSIS; NERVE; REANIMATION; RESTORATION; ADAPTATION; EXPRESSION; MASSETER; EMOTION AB IMPORTANCE Smiling can be a voluntary or involuntary movement. Facial reanimation procedures differ in their ability to restore a spontaneous smile, and an assay designed to evoke and evaluate a spontaneous smile is not available. OBJECTIVE To develop and validate an assay to assess the spontaneous smile of patients with facial paralysis. DESIGN, SETTING, AND PARTICIPANTS This was an exploratory cohort study. A series of short video clips were administered to laypersons via an online survey service from January 1, 2014, to March 31, 2014. Respondents rated how funny each video was on a visual analog scale from 0 to 100. The 4 funniest videos were selected to generate a 11/2-minute spontaneous smile assay. The assay was then administered from July 1, 2014, to December 31, 2014, to 2 different study groups: the first was composed of 100 healthy individuals (control group) and the second was composed of 30 patients with facial paralysis. We analyzed the capability of this assay to provoke at least 1 spontaneous smile and calculated smile excursion in both groups. Statistical analysis was performed using analysis of variance. INTERVENTION Spontaneous smile assay administered to both healthy and diseased groups. MAIN OUTCOMES AND MEASURES Ability of the assay to elicit smiles, as defined by an oral commissure excursion greater than 3 mm, as well as difference in commissure excursion. RESULTS Ninety-five (95.0%) participants in the control group and 29 (96.7%) patients with facial paralysis experienced at least 1 oral commissure excursion that appeared to be a spontaneous smile while viewing the assay. Mean oral commissure excursion with spontaneous smile was 9.08mm(95% CI, 2.77-15.39) in controls, 6.72 mm(95% CI, 3.13-10.31) on the healthy side in patients with flaccid facial paralysis (P=.004 vs controls), and 9.64 mm(95% CI, 3.52-15.76) on the healthy side in patients with nonflaccid facial paralysis (P=.74). Among patients with flaccid facial paralysis, a statistically significant difference was found between smile excursion of the affected and the unaffected sides (P=.03). There was no statistically significant difference in the measurement between sides for the control group (P=.67). CONCLUSIONS AND RELEVANCE Although humor is a challenging construct to universalize, our assay was able to elicit a smile in almost all individuals in the group with facial paralysis and the control group. The spontaneous smile assay will facilitate future research on the ability of facial reanimation procedures and other interventions to restore a spontaneous smile. C1 [Iacolucci, Carlo M.; Banks, Caroline; Jowett, Nate; Kozin, Elliott D.; Hadlock, Tessa A.] Harvard Univ, Sch Med, Div Facial Plast & Reconstruct Surg, Massachusetts Eye & Ear Infirm,Dept Otolaryngol, Boston, MA 02114 USA. [Iacolucci, Carlo M.; Barbara, Maurizio] Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sense Organs, St Andrea Hosp, I-00185 Rome, Italy. [Bhama, Prabhat K.] Alaska Nat Tribal Hlth Consortium, Dept Otolaryngol Head & Neck Surg, Anchorage, AK USA. RP Banks, C (reprint author), Harvard Univ, Sch Med, Div Facial Plast & Reconstruct Surg, Massachusetts Eye & Ear Infirm,Dept Otolaryngol, Boston, MA 02114 USA. EM caroline_banks@meei.harvard.edu RI Kozin, Elliott/J-1225-2014 OI Kozin, Elliott/0000-0002-0305-0682 NR 15 TC 4 Z9 4 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD MAY-JUN PY 2015 VL 17 IS 3 BP 191 EP 196 DI 10.1001/jamafacial.2015.0083 PG 6 WC Surgery SC Surgery GA CI8CT UT WOS:000354996300007 PM 25811938 ER PT J AU Toledo, JB Bjerke, M Da, XA Landau, SM Foster, NL Jagust, W Jack, C Weiner, M Davatzikos, C Shaw, LM Trojanowski, JQ AF Toledo, Jon B. Bjerke, Maria Da, Xiao Landau, Susan M. Foster, Norman L. Jagust, William Jack, Clifford, Jr. Weiner, Michael Davatzikos, Christos Shaw, Leslie M. Trojanowski, John Q. TI Nonlinear Association Between Cerebrospinal Fluid and Florbetapir F-18 beta-Amyloid Measures Across the Spectrum of Alzheimer Disease SO JAMA NEUROLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT; NATIONAL INSTITUTE; CSF BIOMARKERS; NEUROPATHOLOGIC ASSESSMENT; CLINICAL CHARACTERIZATION; APOLIPOPROTEIN-E; BRAIN; PATHOLOGY; TAU AB IMPORTANCE Cerebrospinal fluid (CSF) and positron emission tomographic (PET) amyloid biomarkers have been proposed for the detection of Alzheimer disease (AD) pathology in living patients and for the tracking of longitudinal changes, but the relation between biomarkers needs further study. OBJECTIVE To determine the association between CSF and PET amyloid biomarkers (cross-sectional and longitudinal measures) and compare the cutoffs for these measures. DESIGN, SETTING, AND PARTICIPANTS Longitudinal clinical cohort study from 2005 to 2014 including 820 participants with at least 1 florbetapir F-18 (hereafter referred to as simply florbetapir)-PET scan and at least 1 CSF beta-amyloid 1-42 (A beta 1-42) sample obtained within 30 days of each other (501 participants had a second PET scan after 2 years, including 150 participants with CSF A beta 1-42 measurements). Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database. MAIN OUTCOMES AND MEASURES Four different PET scans processing pipelines from 2 different laboratories were compared. The PET cutoff values were established using a mixture-modeling approach, and different mathematical models were applied to define the association between CSF and PET amyloid measures. RESULTS The values of the CSF A beta 1-42 samples and florbetapir-PET scans showed a nonlinear association (R-2 = 0.48-0.66), with the strongest association for values in the middle range. The presence of a larger dynamic range of florbetapir-PET scan values in the higher range compared with the CSF A beta 1-42 plateau explained the differences in correlation with cognition (R-2 = 0.36 and R-2 = 0.25, respectively). The APOE genotype significantly modified the association between both biomarkers. The PET cutoff values derived from an unsupervised classifier converged with previous PET cutoff values and the established CSF A beta 1-42 cutoff levels. There was no association between longitudinal A beta 1-42 levels and standardized uptake value ratios during follow-up. CONCLUSIONS AND RELEVANCE The association between both biomarkers is limited to a middle range of values, is modified by the APOE genotype, and is absent for longitudinal changes; 4 different approaches in 2 different platforms converge on similar pathological A beta cutoff levels; and different pipelines to process PET scans showed correlated but not identical results. Our findings suggest that both biomarkers measure different aspects of AD A beta pathology. C1 [Toledo, Jon B.; Bjerke, Maria; Shaw, Leslie M.; Trojanowski, John Q.] Univ Penn, Perelman Sch Med, Ctr Neurodegenerat Dis Res, Inst Aging,Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Da, Xiao; Davatzikos, Christos] Univ Penn, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA. [Landau, Susan M.; Jagust, William] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Foster, Norman L.] Univ Utah, Ctr Alzheimers Care Imaging & Res, Dept Neurol, Salt Lake City, UT USA. [Jack, Clifford, Jr.] Mayo Clin, Coll Med, Rochester, MN USA. [Weiner, Michael] Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, Dept Radiol, San Francisco, CA 94143 USA. RP Trojanowski, JQ (reprint author), Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, 3600 Spruce St,3 Maloney Bldg, Philadelphia, PA 19104 USA. EM trojanow@mail.med.upenn.edu RI Da, Xiao/F-8738-2015; Jack, Clifford/F-2508-2010; Kowall, Neil/G-6364-2012; OI Da, Xiao/0000-0001-9898-8130; Jack, Clifford/0000-0001-7916-622X; Kowall, Neil/0000-0002-6624-0213; Toledo, Jon/0000-0003-4366-9268 FU Swedish Brain Foundation; Sweden-America Foundation; ADNI [U01 AG024904]; US Department of Defense ADNI [W81XWH-12-2-0012]; National Institutes of Health [R01-AG011378, U01-HL096917, U01-AG024904, R01 AG041851, R01 AG37551, R01AG043392, U01-AG06786]; Mayo Foundation; [P01 AG032953]; [P01 AG017586]; [P30 AG010124]; [P50 NS053488] FX Dr Toledo is supported by grants P01 AG032953, P01 AG017586, P30 AG010124, and P50 NS053488. Dr Bjerke is supported by the Swedish Brain Foundation and the Sweden-America Foundation. Data collection and sharing for this project was funded by the ADNI (National Institutes of Health grant U01 AG024904) and US Department of Defense ADNI (Department of Defense award W81XWH-12-2-0012). Dr Jack receives research funding from the National Institutes of Health (grants R01-AG011378, U01-HL096917, U01-AG024904, R01 AG041851, R01 AG37551, R01AG043392, and U01-AG06786) and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Foundation. NR 49 TC 23 Z9 24 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD MAY PY 2015 VL 72 IS 5 BP 571 EP 581 DI 10.1001/jamaneurol.2014.4829 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA CH9MY UT WOS:000354361000015 PM 25822737 ER PT J AU Oslin, DW Leong, SH Lynch, KG Berrettini, W O'Brien, CP Gordon, AJ Rukstalis, M AF Oslin, David W. Leong, Shirley H. Lynch, Kevin G. Berrettini, Wade O'Brien, Charles P. Gordon, Adam J. Rukstalis, Margaret TI Naltrexone vs Placebo for the Treatment of Alcohol Dependence A Randomized Clinical Trial SO JAMA PSYCHIATRY LA English DT Article ID OPIOID RECEPTOR GENE; FUNCTIONAL POLYMORPHISM; OPRM1; RELIABILITY; WARFARIN; PHARMACOTHERAPY; INTERVENTION; METAANALYSIS; SENSITIVITY; SETTINGS AB IMPORTANCE Alcohol use disorder is one of the leading causes of disability worldwide. While effective pharmacological treatments exist, they are efficacious only in certain individuals, contributing to their limited use. Secondary analysis of clinical trial data suggests that a functional polymorphism (rs1799971, Asn40Asp) of the mu-opioid receptor gene (OPRM1) is associated with the risk of relapse to heavy drinking following treatment with the opioid antagonist naltrexone. OBJECTIVE To prospectively examine whether rs1799971 is predictive of naltrexone treatment response. DESIGN, SETTING, AND PARTICIPANTS We conducted a 12-week, double-blind, randomized clinical trial of naltrexone vs placebo in individuals with alcohol dependence (intent-to-treat analysis). Participants were randomly assigned to study treatment based on the presence of 1 or 2 copies of the Asp40 allele compared with those homozygous for the Asn40 allele (2 x 2 cell design). Recruitment occurred between January 2009 and September 2013. All participants were seen in an outpatient clinical setting. A convenience sample of participants (n = 221) was recruited from 5 sites. All participants met DSM-IV criteria for alcohol dependence, with no concurrent psychotic or manic symptoms, no use of concurrent psychotropic medications, and no current dependence on illicit substances. I INTERVENTIONS The study drug was naltrexone (50 mg) given once daily or corresponding placebo. MAIN OUTCOMES AND MEASURES The primary study outcome measure was relapse to heavy drinking measured using the timeline follow-back method. RESULTS There was no evidence of a genotype x treatment interaction on the primary outcome of heavy drinking (P = .32). In the Asn40 group, the observed effect of naltrexone was similar to that in previous trials (odds ratio, 0.69; 95% CI, 0.41-1.18; P = .17), with a very small naltrexone effect in the Asp40 group (odds ratio, 1.10; 95% CI, 0.52-2.31; P = .80), contrary to the pattern expected a priori. A significant reduction in heavy drinking occurred across all groups (P = .001). Other drinking outcomes, and all secondary outcomes, demonstrated similar time effects, with no genotype x treatment interaction. CONCLUSIONS AND RELEVANCE The results of this study do not support the hypothesis that the Asp40 allele moderates the response to naltrexone treatment. It is premature to use the Asn40Asp polymorphism as a biomarker to predict the response to naltrexone treatment of alcohol dependence. C1 [Oslin, David W.; Lynch, Kevin G.; Berrettini, Wade; O'Brien, Charles P.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Oslin, David W.; Leong, Shirley H.] Philadelphia Vet Affairs Med Ctr, Ctr Excellence Subst Abuse Treatment & Evaluat, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Gordon, Adam J.] Vet Affairs Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [Gordon, Adam J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Rukstalis, Margaret] Wake Forest Univ, Dept Psychiat, Winston Salem, NC 27109 USA. RP Oslin, DW (reprint author), Univ Penn, Perelman Sch Med, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM oslin@upenn.edu FU National Institute on Alcohol Abuse and Alcoholism [AA017164]; Veterans Integrated Service Network 4 Mental Illness Research, Education, and Clinical Center FX This study was supported in part by grant AA017164 from the National Institute on Alcohol Abuse and Alcoholism and by the Veterans Integrated Service Network 4 Mental Illness Research, Education, and Clinical Center. NR 41 TC 16 Z9 18 U1 2 U2 10 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 MAY PY 2015 VL 72 IS 5 BP 430 EP 437 DI 10.1001/jamapsychiatry.2014.3053 PG 8 WC Psychiatry SC Psychiatry GA CH6YC UT WOS:000354181400005 PM 25760804 ER PT J AU Bebko, SP Green, DM Awad, SS AF Bebko, Serge P. Green, David M. Awad, Samir S. TI Effect of a Preoperative Decontamination Protocol on Surgical Site Infections in Patients Undergoing Elective Orthopedic Surgery With Hardware Implantation SO JAMA SURGERY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; INTRANASAL MUPIROCIN; EPIDEMIOLOGY; PREVENTION; ERADICATION; CARRIERS AB IMPORTANCE Surgical site infections (SSIs), commonly caused by methicillin-resistant Staphylococcus aureus (MRSA), are associated with significant morbidity and mortality, specifically when hardware is implanted in the patient. Previously, we have demonstrated that a preoperative decontamination protocol using chlorhexidine gluconate washcloths and intranasal antiseptic ointment is effective in eradicating MRSA in the nose and on the skin of patients. OBJECTIVE To examine the effect of a decontamination protocol on SSIs in patients undergoing elective orthopedic surgery with hardware implantation. DESIGN, SETTING, AND PARTICIPANTS A prospective database of patients undergoing elective orthopedic surgery with hardware implantation at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas, was analyzed from October 1, 2012, to December 31, 2013. Cohort groups before and after the intervention were compared. INTERVENTIONS Starting in May 2013, during their preoperative visit, all of the patients watched an educational video about MRSA decontamination and were given chlorhexidine washcloths and oral rinse and nasal povidone-iodine solution to be used the night before and the morning of scheduled surgery. MAIN OUTCOMES AND MEASURES Thirty-day SSI rates were collected according to the definitions of the Centers for Disease Control and Prevention National Nosocomial Infections Surveillance. Data on demographics, comorbidities such as chronic obstructive pulmonary disease and coronary artery disease, tobacco use, alcohol use, and body mass index were also collected. Univariate analysis was performed between the 2 groups of patients. Multivariate analysis was used to identify independent predictors of SSI. RESULTS A total of 709 patients were analyzed (344 controls and 365 patients who were decolonized). Both groups were well matched with no significant differences in age, body mass index, sex, or comorbidities. All of the patients (100%) completed the MRSA decontamination protocol. The SSI rate in the intervention group was significantly lower (1.1%; 4 of 365 patients developed an SSI) than the SSI rate in the control group (3.8%; 13 of 344 patients developed an SSI) (P =.02). Multivariate logistic regression identified MRSA decontamination as an independent predictor of not developing an SSI (adjusted odds ratio, 0.24 [95% CI, 0.08-0.77]; P =.02). CONCLUSIONS AND RELEVANCE Our study demonstrates that preoperative MRSA decontamination with chlorhexidine washcloths and oral rinse and intranasal povidone-iodine decreased the SSI rate by more than 50% among patients undergoing elective orthopedic surgery with hardware implantation. Universal decontamination using this low-cost protocol may be considered as an additional prevention strategy for SSIs in patients undergoing orthopedic surgery with hardware implantation and warrants further study. C1 [Bebko, Serge P.; Awad, Samir S.] Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. [Bebko, Serge P.; Green, David M.; Awad, Samir S.] Michael E DeBakey VA Med Ctr, Dept Surg, Houston, TX USA. RP Awad, SS (reprint author), Baylor Coll Med, Dept Surg, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,Room 5A-350, Houston, TX 77030 USA. EM sawad@bcm.edu NR 22 TC 4 Z9 4 U1 1 U2 11 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 MAY PY 2015 VL 150 IS 5 BP 390 EP 395 DI 10.1001/jamasurg.2014.3480 PG 6 WC Surgery SC Surgery GA CI7RY UT WOS:000354963300004 PM 25738898 ER PT J AU Anderson, CE Nicksa, GA Stewart, L AF Anderson, Cristan E. Nicksa, Grace A. Stewart, Lygia TI Distractions During Resident Handoffs Incidence, Sources, and Influence on Handoff Quality and Effectiveness SO JAMA SURGERY LA English DT Article ID SIGN-OUT; TASK INTERRUPTION; PATIENT HANDOFFS; I-PASS; MULTITASKING; CARE; COMMUNICATION; INFORMATION; MEMORY; IMPACT AB IMPORTANCE Handoffs have significantly increased in number following Accreditation Council for Graduate Medical Education (ACGME) work-hour restrictions. Studies have shown correlations between the number of handoffs and errors/patient harm. Distractions are common during handoffs and may interfere with handoff quality and effectiveness. OBJECTIVE To examine the frequency of distractions and their impact on handoff quality. DESIGN, SETTING, AND PARTICIPANTS In this prospective observational study, a total of 214 surgical resident handoffs (residents = 184; Bay area residents [moonlighters] = 30) were observed over 18 months (July 11, 2012-December 19, 2014) by 2 independent observers in 3 teaching hospitals (university, county, and veterans). MAIN OUTCOMES AND MEASURES Handoff quality (both giver and receiver) was assessed using a standardized scoring system. The number and types of distractions were recorded. RESULTS Pages were the most common distraction (37.5%), followed by telephone calls (32.8%), residents/medical students (9.3%), talking (5.2%), and noise (4.1%). Distractions from attending physicians, electronics, nursing, consults, and room changes were less common (collectively 11%, each < 3%). Distractions were present in 102 resident handoffs (48%) (16% with 1 distraction; 15% with 2; 6% with 3, and 11% with >= 4). Distractions occurred in 54% of junior resident handoffs (mean, 1.4/handoff), 30% of moonlighter handoffs (mean, 0.5/handoff), and 38% of senior resident handoffs (mean, 0.89/handoff) (P =.01, junior vs moonlighter/senior). Distractions were more common during evening than morning handoffs (52% vs 36%; P =.045) and during team vs individual handoffs (58% vs 44%; P <.10). Handoffs without distractions were shorter in length (13.2 minutes without distractions vs 21.5 minutes with distractions; P <.001) and minutes per patient (1.78 without vs 2.15 with distractions; P =.04). Handoff quality was not diminished by distractions, as measured by handoff giver score (15.41 without vs 15.47 with distractions; P =.90) and receiver score (7.42 without vs 7.25 with distractions; P =.45). CONCLUSIONS AND RELEVANCE To our knowledge, this is the largest study of distractions during surgical resident handoffs. Distractions were very common during handoffs; they were more common in the evening when junior residents more commonly performed the handoff and they increased the handoff length. However, distractions did not negatively affect the quality of resident handoffs. This may demonstrate the resilience of surgical residents to distractions. C1 San Francisco VA Med Ctr, Dept Surg, San Francisco, CA USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94121 USA. RP Stewart, L (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Surg 112, 4150 Clement St, San Francisco, CA 94121 USA. EM lygia.stewart@va.gov NR 34 TC 4 Z9 4 U1 3 U2 11 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 MAY PY 2015 VL 150 IS 5 BP 396 EP 401 DI 10.1001/jamasurg.2014.2459 PG 6 WC Surgery SC Surgery GA CI7RY UT WOS:000354963300005 PM 25738805 ER PT J AU Luo, S Lobo, AZC Tanabe, KK Muzikansky, A Durazzo, T Sober, A Tsao, H Cosimi, AB Lawrence, DP Duncan, LM AF Luo, Su Lobo, Alice Z. C. Tanabe, Kenneth K. Muzikansky, Alona Durazzo, Tyler Sober, Arthur Tsao, Hensin Cosimi, A. Benedict Lawrence, Donald P. Duncan, Lyn M. TI Clinical Significance of Microscopic Melanoma Metastases in the Nonhottest Sentinel Lymph Nodes SO JAMA SURGERY LA English DT Article ID EARLY-STAGE MELANOMA; PRIMARY CUTANEOUS MELANOMA; MULTICENTER TRIAL; THIN MELANOMA; BIOPSY; LYMPHADENECTOMY; DISSECTION; ACCURACY; RECURRENCE; EXPERIENCE AB IMPORTANCE A practice gap exists in the surgical removal of sentinel lymph nodes, from removal of only the most radioactive (hottest) lymph node to removal of all lymph nodes with radioactivity greater than 10% of the hottest lymph node. OBJECTIVE To determine the clinical significance of melanoma in sentinel lymph nodes that are not the hottest sentinel node and to determine the risk for disease progression based on sentinel lymph node status and primary tumor characteristics. DESIGN, SETTING, AND PARTICIPANTS Consecutive patients with cutaneous melanoma with sentinel lymph nodes resected from January 5, 2004, to June 30, 2008, with a mean follow-up of 59 months, at Massachusetts General Hospital were included in this retrospective review. The last year of follow-up was 2012. The operative protocol led to resection of all sentinel lymph nodes with radioactivity greater than 10% of the hottest lymph node. The number of lymph nodes removed, technetium-99m counts for each sentinel lymph node, presence or absence of sentinel lymph node metastases, primary tumor characteristics, disease progression, and melanoma-specific survival were recorded. MAIN OUTCOMES AND MEASURES Microscopic melanoma metastases in the hottest and nonhottest sentinel lymph nodes and factors that correlate with disease progression and mortality. RESULTS A total of 1575 sentinel lymph nodes were analyzed in 475 patients. Ninety-one patients (19%) had positive sentinel lymph nodes. Of these, 72 (79%) had metastases in the hottest sentinel lymph node. Of 19 cases with tumor present, but not in the hottest sentinel lymph node, counts ranged from 26% to 97% of the hottest node. Progression occurred in 43% of patients with sentinel node metastasis, regardless of whether the hottest lymph node was positive. In patients with negative sentinel lymph nodes, 11% developed metastases beyond the sentinel lymph node basin and 3.4% recurred in the basin. Mitogenicity of the primary tumor was associated with mortality (odds ratio, 2.435; 95% CI, 1.351-4.391; P <.001). Removing only the hottest sentinel lymph node would have led to false-negative results in 19 of 475 (4%) of all patients and 19 of 91 patients (21%) with positive sentinel lymph nodes. The 8-year survival in patients with at least 1 positive sentinel lymph node was less than 55%. The presence of more than 1 mitosis per square millimeter in the primary cutaneous melanoma was associated with decreased survival. CONCLUSIONS AND RELEVANCE Microscopic melanoma metastases was associated with disease progression and mortality, whether present in the hottest sentinel lymph node or not. These observations emphasize the importance of removing the less hot nodes, addressing a practice gap in the surgical approach to patients with melanoma. C1 [Luo, Su; Durazzo, Tyler; Sober, Arthur; Tsao, Hensin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02115 USA. [Lobo, Alice Z. C.; Duncan, Lyn M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02115 USA. [Lobo, Alice Z. C.; Duncan, Lyn M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02115 USA. [Lobo, Alice Z. C.] Univ Sao Paulo, Dept Dermatol, Sao Paulo, Brazil. [Tanabe, Kenneth K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02115 USA. [Muzikansky, Alona] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02115 USA. [Cosimi, A. Benedict] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02115 USA. [Lawrence, Donald P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Melanoma, Boston, MA 02115 USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit WRN 825, 55 Fruit St, Boston, MA 02114 USA. EM duncan@helix.mgh.harvard.edu FU Dermatopathology Unit of the Pathology Service, Massachusetts General Hospital, Boston FX This study was supported by departmental research funds from the Dermatopathology Unit of the Pathology Service, Massachusetts General Hospital, Boston. NR 42 TC 1 Z9 1 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 MAY PY 2015 VL 150 IS 5 BP 465 EP 472 DI 10.1001/jamasurg.2014.3843 PG 8 WC Surgery SC Surgery GA CI7RY UT WOS:000354963300018 PM 25831227 ER PT J AU Kim, RY Kwakye, G Kwok, AC Baltaga, R Ciobanu, G Merry, AF Funk, LM Lipsitz, SR Gawande, AA Berry, WR Haynes, AB AF Kim, Rebecca Y. Kwakye, Gifty Kwok, Alvin C. Baltaga, Ruslan Ciobanu, Gheorghe Merry, Alan F. Funk, Luke M. Lipsitz, Stuart R. Gawande, Atul A. Berry, William R. Haynes, Alex B. TI Sustainability and Long-term Effectiveness of the WHO Surgical Safety Checklist Combined With Pulse Oximetry in a Resource-Limited Setting Two-Year Update From Moldova SO JAMA SURGERY LA English DT Article ID IMPLEMENTATION; POPULATION; HOSPITALS; MORTALITY; SURGERY; CARE AB IMPORTANCE Little is known about the sustainability and long-term effect of surgical safety checklists when implemented in resource-limited settings. A previous study demonstrated the marked, short-term effect of a structured hospital-wide implementation of a surgical safety checklist in Moldova, a lower-middle-income country, as have studies in other low-resource settings. OBJECTIVES To assess the long-term reduction in perioperative harm following the introduction of a checklist-based surgical quality improvement program in a resource-limited setting and to understand the long-term effects of such programs. DESIGN, SETTING, AND PARTICIPANTS Twenty months after the initial implementation of a surgical safety checklist and the provision of pulse oximetry at a referral hospital in Moldova, a lower-middle-income, resource-limited country in Eastern Europe, we conducted a prospective study of perioperative care and outcomes of 637 consecutive patients undergoing noncardiac surgery (the long-term follow-up group), and we compared the findings with those from 2106 patients who underwent surgery shortly after implementation (the short-term follow-up group). Preintervention data were collected from March to July 2010. Data collection during the short-term follow-up period was performed from October 2010 to January 2011, beginning 1 month after the implementation of the launch period. Data collection during the long-term follow-up period took place from May 25 to July 6, 2012, beginning 20 months after the initial intervention. MAIN OUTCOMES AND MEASURES The primary end points of interest were surgical morbidity (ie, the complication rate), adherence to safety process measures, and frequency of hypoxemia. RESULTS Between the short-and long-term follow-up groups, the complication rate decreased 30.7%(P =.03). Surgical site infections decreased 40.4%(P =.05). The mean (SD) rate of completion of the checklist items increased from 88%(14%) in the short-term follow-up group to 92%(11%) in the long-term follow-up group (P <.001). The rate of hypoxemic events continued to decrease (from 8.1 events per 100 hours of oximetry for the short-term follow-up group to 6.8 events per 100 hours of oximetry for the long-term follow-up group; P =.10). CONCLUSIONS AND RELEVANCE Sustained use of the checklist was observed with continued improvements in process measures and reductions in 30-day surgical complications almost 2 years after a structured implementation effort that demonstrated marked, short-term reductions in harm. The sustained effect occurred despite the absence of continued oversight by the research team, indicating the important role that local leadership and local champions play in the success of quality improvement initiatives, especially in resource-limited settings. C1 [Kim, Rebecca Y.; Berry, William R.] Harvard Univ, Sch Publ Hlth, Ariadne Labs, Boston, MA 02115 USA. [Kim, Rebecca Y.] Stanford Univ, Sch Med, Dept Surg, Boston, MA USA. [Kwakye, Gifty; Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Ariadne Labs, Boston, MA 02115 USA. [Kwok, Alvin C.] Univ Utah, Sch Med, Dept Surg, Salt Lake City, UT USA. [Baltaga, Ruslan] State Univ Med & Pharm, Natl Sci & Pract Ctr Emergency Med, Anaesthesiol Intens Care Valeriu Ghereg, Chisinau, Maldives. [Ciobanu, Gheorghe] State Univ Med & Pharm Nicolae Testemitanu, Natl Sci & Pract Ctr Emergency Med, Chisinau, Maldives. [Merry, Alan F.] Univ Auckland, Dept Anesthesia, Auckland 1, New Zealand. [Merry, Alan F.] Auckland City Hosp, Auckland, New Zealand. [Funk, Luke M.] Univ Wisconsin, Dept Surg, Madison, WI 53706 USA. [Lipsitz, Stuart R.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Haynes, Alex B.] Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Dept Surg, Ariadne Labs, Boston, MA 02215 USA. RP Haynes, AB (reprint author), Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Dept Surg, Ariadne Labs, 401 Pk Dr,3rd Floor E, Boston, MA 02215 USA. EM abhaynes@partners.org OI Merry, Alan/0000-0001-7100-009X NR 21 TC 2 Z9 2 U1 1 U2 4 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 MAY PY 2015 VL 150 IS 5 BP 473 EP 479 DI 10.1001/jamasurg.2014.3848 PG 7 WC Surgery SC Surgery GA CI7RY UT WOS:000354963300019 PM 25806951 ER PT J AU Mohanty, S Liu, YM Paruch, JL Kmiecik, TE Cohen, ME Ko, CY Bilimoria, KY AF Mohanty, Sanjay Liu, Yaoming Paruch, Jennifer L. Kmiecik, Thomas E. Cohen, Mark E. Ko, Clifford Y. Bilimoria, Karl Y. TI Risk of Discharge to Postacute Care A Patient-Centered Outcome for the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator SO JAMA SURGERY LA English DT Article ID ELDER LIFE PROGRAM; KNEE ARTHROPLASTY; FUNCTIONAL DECLINE; NSQIP; HOME; HIP; SAFETY AB IMPORTANCE Individualized risk prediction tools have an important role as decision aids for use by patients and surgeons before surgery. Patient-centered outcomes should be incorporated into such tools to widen their appeal and improve their usability. OBJECTIVE To develop a patient-centered outcome for the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Surgical Risk Calculator, a web-based, individualized risk prediction tool. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using data from the ACS NSQIP, a national clinical data registry. A total of 973 211 patients from July 2010 to June 2012, encompassing 392 hospitals, were used in this analysis. MAIN OUTCOMES AND MEASURES Risk of discharge to a postacute care setting. RESULTS The overall rate of discharge to postacute care was 8.8%. Significant predictors of discharge to postacute care included being 85 years or older (odds ratio [OR] = 9.17; 95% CI, 8.84-9.50), the presence of septic shock (OR = 2.43; 95% CI, 2.20-2.69) or ventilator dependence (OR = 2.81; 95% CI, 2.56-3.09) preoperatively, American Society of Anesthesiologists class of 4 or 5 (OR = 3.59; 95% CI, 3.46-3.71), and totally dependent functional status (OR = 2.27; 95% CI, 2.11-2.44). The final model predicted risk of discharge to postacute care with excellent accuracy (C statistic = 0.924) and calibration (Brier score = 0.05). CONCLUSIONS AND RELEVANCE Individualized risk of discharge to postacute care can be predicted with excellent accuracy. This outcome will be incorporated into the ACS NSQIP Surgical Risk Calculator. C1 [Mohanty, Sanjay] Henry Ford Hosp, Dept Surg, Detroit, MI 48202 USA. [Mohanty, Sanjay; Liu, Yaoming; Paruch, Jennifer L.; Cohen, Mark E.; Ko, Clifford Y.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Kmiecik, Thomas E.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. RP Mohanty, S (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair,22nd Floor, Chicago, IL 60611 USA. EM smohanty@facs.org FU American College of Surgeons; American Geriatric Society; Hartford Foundation FX Dr Mohanty is supported by the Clinical Scholar in Residence Program from the American College of Surgeons and by the American Geriatric Society and the Hartford Foundation. NR 15 TC 6 Z9 6 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 MAY PY 2015 VL 150 IS 5 BP 480 EP 484 DI 10.1001/jamasurg.2014.3176 PG 5 WC Surgery SC Surgery GA CI7RY UT WOS:000354963300020 PM 25806660 ER PT J AU Hinkofer, LC Hummel, AM Stone, JH Hoffman, GS Merkel, PA Spiera, ERF St Clair, W McCune, JW Davis, JC Specks, U Jenne, DE AF Hinkofer, Lisa C. Hummel, Amber M. Stone, John H. Hoffman, Gary S. Merkel, Peter A. Spiera, E. Robert F. St Clair, William McCune, Joseph W. Davis, John C. Specks, Ulrich Jenne, Dieter E. TI Allosteric modulation of proteinase 3 activity by anti-neutrophil cytoplasmic antibodies in granulomatosis with polyangiitis SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Granulomatosis with polyangiitis; ANCA; Proteinase 3; Inhibition; Disease activity ID ANCA-ASSOCIATED VASCULITIS; WEGENERS-GRANULOMATOSIS; DISEASE-ACTIVITY; INHIBITION; REMISSION; PR3-ANCA; PR3 AB Anti-neutrophil cytoplasmic antibodies (ANCA) with proteinase 3 (PR3) specificity are a useful laboratory biomarker for the diagnosis of Granulomatosis with Polyangiitis (GPA) and are believed to be implicated in the pathogenesis. It has been repeatedly suggested that disease activity of GPA is more closely related to the appearance and rise of PR3-inhibiting ANCA than to an increase of total ANCA. Previous studies on a limited number of patient samples, however, have yielded inconclusive results. To overcome the previous methodological limitations, we established a new ultrasensitive method to quantify the inhibitory capacity of PR3-ANCA using small volumes of plasma from patients with GPA. A large collection of longitudinally-collected samples from the Wegener Granulomatosis Etanercept Trial (WGET) became available to us to determine the functional effects of ANCA on PR3 in comparison to clinical disease manifestations. In these patient samples we not only detected PR3-ANCA with inhibitory capacity, but also PR3-ANCA with enhancing effects on PR3 activity. However no correlation of these activity-modulating PR3-ANCA with disease activity at either the time of enrollment or over the course of disease was found. Only patients with pulmonary involvement, especially patients with nodule formation in the respiratory tract, showed a slight, but not significant, decrease of inhibitory capacity. Epitope mapping of the activity-modulating PR3-ANCA revealed a binding on the active site surface of PR3. Yet these ANCA were able to bind to PR3 with an occupied active site cleft, indicating an allosteric mechanism of inhibition. The recently described signal ratio between the MCPR3-3 and MCPR3-2 capture ELISA was consistent with the binding of activity-modulating ANCA to the active site surface. Evidence for a shared epitope between activity-modulating PR3-ANCA and MCPR3-7, however, was very limited, suggesting that a majority of PR3-ANCA species do not inhibit PR3 by the same mechanism as previously reported for MCPR3-7. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Hinkofer, Lisa C.; Jenne, Dieter E.] Univ Munich, Univ Hosp, Inst Lung Biol & Dis iLBD, Comprehens Pneumol Ctr, D-81377 Munich, Germany. [Hinkofer, Lisa C.; Jenne, Dieter E.] Helmholtz Zentrum Munchen, D-81377 Munich, Germany. [Hummel, Amber M.; Specks, Ulrich] Mayo Clin & Mayo Fdn, Div Pulm & Crit Care Med, Thorac Dis Res Unit, Rochester, MN 55905 USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hoffman, Gary S.] Cleveland Clin, Ctr Vasculitis Care & Res, Cleveland, OH 44195 USA. [Merkel, Peter A.] Univ Penn, Vasculitis Ctr, Div Rheumatol, Philadelphia, PA 19104 USA. [Merkel, Peter A.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Spiera, E. Robert F.] Hosp Special Surg, New York, NY 10021 USA. [St Clair, William] Duke Univ, Med Ctr, Div Rheumatol & Immunol, Durham, NC 27708 USA. [McCune, Joseph W.] Univ Michigan, Ann Arbor, MI 48109 USA. [Davis, John C.] Genentech Inc, San Francisco, CA 94080 USA. [Davis, John C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Jenne, Dieter E.] Max Planck Inst Neurobiol, Planegg Martinsried, Germany. RP Jenne, DE (reprint author), Helmholtz Zentrum Munchen, Comprehens Pneumol Ctr, Max Lebsche Pl 31, D-81377 Munich, Germany. EM dieter.jenne@helmholtz-muenchen.de FU European Union Seventh Framework Programme (FP7) [261382 (INTRICATE)]; National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH [N01-AR92240]; Office of Orphan Products, FDA [FD-R-001652]; General Clinical Research Center from the National Center for Research Resources/NIH [M01-RRO-00533, M01-RRO-0042, MO1-RR-30, M01-RRO-2719] FX The authors thank Heike Kittel for her excellent technical assistance, Oliver Eickelberg for his continuous interest in the project and Karl-Heinz Wiesmuller, EMC Microcollections, for the design and synthesis of FRET-substrates. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no 261382 (INTRICATE). The WGET trial was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH N01-AR92240 and the Office of Orphan Products, FDA (grant FD-R-001652), General Clinical Research Center Grants M01-RRO-00533 (Boston University), M01-RRO-0042 (The University of Michigan), MO1-RR-30 (Duke University), and M01-RRO-2719 (Johns Hopkins University School of Medicine), from the National Center for Research Resources/NIH. NR 21 TC 1 Z9 1 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 EI 1095-9157 J9 J AUTOIMMUN JI J. Autoimmun. PD MAY PY 2015 VL 59 BP 43 EP 52 DI 10.1016/j.jaut.2015.02.002 PG 10 WC Immunology SC Immunology GA CI8SV UT WOS:000355042900006 PM 25744251 ER PT J AU Pursnani, A Schlett, CL Mayrhofer, T Celeng, C Zakroysky, P Bamberg, F Nagurney, JT Truong, QA Hoffmann, U AF Pursnani, Amit Schlett, Christopher L. Mayrhofer, Thomas Celeng, Csilla Zakroysky, Pearl Bamberg, Fabian Nagurney, John T. Truong, Quynh A. Hoffmann, Udo TI Potential for coronary CT angiography to tailor medical therapy beyond preventive guideline-based recommendations: Insights from the ROMICAT I trial SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Coronary CT angiography; Coronary artery disease; Prevention; Guidelines; Aspirin; Statin ID COMPUTED TOMOGRAPHIC ANGIOGRAPHY; ACUTE CHEST-PAIN; ATHEROSCLEROTIC VASCULAR-DISEASE; ARTERY-DISEASE; PROGNOSTIC VALUE; SECONDARY PREVENTION; DIAGNOSTIC PERFORMANCE; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; MORTALITY INCIDENCE AB Background: Coronary CT angiography (CCTA) is used in the emergency department to rule out acute coronary syndrome in low-intermediate risk patients. Objectives: We evaluated the potential of CCTA to tailor aspirin (ASA) and statin therapy in acute chest pain patients. Methods: We included all patients in the ROMICAT I trial who underwent CCTA before admission. Results of CCTA were blinded to caretakers. We documented ASA and statin therapy at admission and discharge and determined change in medications during hospitalization, agreement of discharge medications with contemporaneous guidelines, and agreement with the presence and severity of coronary artery disease (CAD) as determined by CCTA. Results: We included 368 patients (53 +/- 12 years; 61% male). Baseline medical therapy at presentation included 27% on ASA and 24% on statin. Most patients who qualified for secondary prevention were on ASA and statin therapy at discharge (95% and 80%, respectively), whereas among those qualifying for primary prevention therapy, only 59% of patients were on aspirin and 33% were on statin at discharge. Excluding secondary prevention patients, among those with CCTA-detected CAD, only 66/131 (50%) were on ASA at discharge and only 53/131 (40%) were on statin. Conversely, in those without CCTA-detected CAD, 54/156 (35%) were on ASA and 20/151 (13%) were on statin at discharge. Conclusion: There are significant discrepancies between discharge prescription of statin and ASA with the presence and extent of CAD. CCTA presents an efficient opportunity to tailor medical therapy to CAD in patients undergoing CCTA as part of their acute chest pain evaluation. (C) 2015 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Pursnani, Amit; Mayrhofer, Thomas; Celeng, Csilla; Truong, Quynh A.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Pursnani, Amit; Mayrhofer, Thomas; Celeng, Csilla; Zakroysky, Pearl; Nagurney, John T.; Truong, Quynh A.; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Pursnani, Amit] Evanston Hosp Corp, Div Cardiol, Evanston, IL 60201 USA. [Schlett, Christopher L.] Univ Heidelberg Hosp, Dept Diagnost & Intervent Radiol, Heidelberg, Germany. [Zakroysky, Pearl] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Bamberg, Fabian] Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, D-80539 Munich, Germany. [Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Truong, Quynh A.] New York Presbyterian Hosp, Weill Cornell Med Coll, Dalio Inst Cardiovasc Imaging, New York, NY USA. RP Pursnani, A (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM apursnani@northshore.org FU National Heart, Lung, and Blood Institute [R01 HL080053, 5K24HL113128] FX This work was supported by grants from the National Heart, Lung, and Blood Institute (R01 HL080053 and 5K24HL113128). NR 35 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD MAY-JUN PY 2015 VL 9 IS 3 BP 193 EP 201 DI 10.1016/j.jcct.2015.02.006 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CI3SZ UT WOS:000354669000004 PM 25846248 ER PT J AU Metelo, AM Noonan, HR Li, X Jin, YN Baker, R Kamentsky, L Zhang, YY van Rooijen, E Shin, J Carpenter, AE Yeh, JR Peterson, RT Iliopoulos, O AF Metelo, Ana Martins Noonan, Haley R. Li, Xiang Jin, Youngnam Baker, Rania Kamentsky, Lee Zhang, Yiyun van Rooijen, Ellen Shin, Jordan Carpenter, Anne E. Yeh, Jing-Ruey Peterson, Randall T. Iliopoulos, Othon TI Pharmacological HIF2 alpha inhibition improves VHL disease-associated phenotypes in zebrafish model SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HIPPEL-LINDAU-DISEASE; HYPOXIA-INDUCIBLE FACTOR-2; RENAL-CELL CARCINOMA; CONGESTIVE-HEART-FAILURE; IN-VIVO; TUMOR-SUPPRESSOR; CAUSES POLYCYTHEMIA; CANCER; IRON; HIF-2-ALPHA AB Patients with a germline mutation in von Hippel-Lindau (VHL) develop renal cell cancers and hypervascular tumors of the brain, adrenal glands, and pancreas as well as erythrocytosis. These phenotypes are driven by aberrant expression of HIF2 alpha, which induces expression of genes involved in cell proliferation, angiogenesis, and red blood cell production. Currently, there are no effective treatments available for VHL disease. Here, using an animal model of VHL, we report a marked improvement of VHL-associated phenotypes following treatment with HIF2 alpha inhibitors. Inactivation of vhl in zebrafish led to constitutive activation of HIF2 alpha orthologs and modeled several aspects of the human disease, including erythrocytosis, pathologic angiogenesis in the brain and retina, and aberrant kidney and liver proliferation. Treatment of vh(-/-) mutant embryos with HIF2 alpha-specific inhibitors downregulated Hif target gene expression in a dose-dependent manner, improved abnormal hematopoiesis, and substantially suppressed erythrocytosis and angiogenic sprouting. Moreover, pharmacologic inhibition of HIF2 alpha reversed the compromised cardiac contractility of vhl(-/-) embryos and partially rescued early lethality. This study demonstrates that small-molecule targeting of HIF2 alpha improves VHL-related phenotypes in a vertebrate animal model and supports further exploration of this strategy for treating VHL disease. C1 [Metelo, Ana Martins; Noonan, Haley R.; Li, Xiang; Jin, Youngnam; Baker, Rania; Peterson, Randall T.; Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Boston, MA USA. [Metelo, Ana Martins; Li, Xiang; Jin, Youngnam; Zhang, Yiyun; Shin, Jordan; Yeh, Jing-Ruey; Peterson, Randall T.; Iliopoulos, Othon] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Metelo, Ana Martins] Univ Coimbra, Fac Sci & Technol, Dept Life Sci, Coimbra, Portugal. [Li, Xiang; Jin, Youngnam; Zhang, Yiyun; Shin, Jordan; Yeh, Jing-Ruey; Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Li, Xiang; Jin, Youngnam; Peterson, Randall T.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Kamentsky, Lee; Carpenter, Anne E.] Broad Inst Harvard & MIT, Imaging Platform, Cambridge, MA USA. [van Rooijen, Ellen] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Iliopoulos, Othon] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Iliopoulos, O (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, 149 13th St, Charlestown, MA 02129 USA. EM oiliopoulos@partners.org RI Carpenter, Anne/C-4982-2008 OI Carpenter, Anne/0000-0003-1555-8261 FU NIH [R01 GM095672]; Fundacao para a Ciencia e Tecnologia, Portugal - POPH/FSE, Programa Operacional e da Uniao Europeia [SFRH/BD/70002/2010]; Massachusetts General Hospital federal share of program income [C06 CA059267]; VHL Alliance Research Award FX We would like to thank Fredericus van Eeden (Utrecht, Netherlands) for providing the vhl mutant zebrafish line. We also would like to thank David Langeneau and Eleanor Chen (Langeneau Lab, Massachusetts General Hospital Cancer Center) for advice and the Tg (GFP-fli1) zebrafish line as well as Colleen Brady and Andrew Rennekamp (Peterson Lab, Massachusetts General Hospital Cardiovascular Research Center) and Alexa Burger (Haber Lab, Massachusetts General Hospital Cancer Center) for technical suggestions and reagents. L.E. Kamentsky and A.E. Carpenter were supported by NIH R01 GM095672 (PI: Carolina Wahlby). A.M. Metelo was supported by a PhD fellowship from Fundacao para a Ciencia e Tecnologia, Portugal, with reference SFRH/BD/70002/2010, funded by POPH/FSE, Programa Operacional e da Uniao Europeia. This work was supported by the Massachusetts General Hospital federal share of program income under C06 CA059267 and the 2014 VHL Alliance Research Award (both awarded to O. Iliopoulos). NR 54 TC 6 Z9 7 U1 0 U2 6 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 MAY PY 2015 VL 125 IS 5 BP 1987 EP 1997 DI 10.1172/JCI73665 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CH5JK UT WOS:000354071700021 PM 25866969 ER PT J AU Escudero, MO Juliano, AF Curtin, HD AF Escudero, Martin Ochoa Juliano, Amy F. Curtin, Hugh D. TI Inferior Displacement of the Lower Belly of the Lateral Pterygoid Muscle: A Sign of Temporomandibular Joint Lesions SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE temporomandibular joint; lateral pterygoid muscle AB Objective: The purposes of this article are to report the imaging finding of inferior displacement of the lower belly of the lateral pterygoid muscle (LPM) in patients with lesions arising from the temporomandibular joint (TMJ) and to propose that this imaging finding is suggestive of the presence of a TMJ lesion. Materials and methods: We reviewed computed tomographic and magnetic resonance images of 9 patients with lesions involving the TMJ. Images were evaluated for identification of an inferiorly displaced lower belly of the LPM. Pathology reports were reviewed to determine the histopathologic diagnosis of the TMJ lesion. Results: Inferior displacement of the lower belly of the LPM was observed in all cases on magnetic resonance images, computed tomographic images, or both. In 2 cases, the diagnosis was calcium pyrophosphate deposition disease. The remaining cases were ganglion cyst, joint effusion due to dermatomyositis, septic arthritis, chondromyxoid fibroma, synovial chondromatosis, pigmented villonodular synovitis, and giant cell tumor of bone. Conclusions: Inferior displacement of the lower belly of the LPM is a useful radiologic sign to suggest that a lesion arises from the TMJ. C1 [Escudero, Martin Ochoa] Hosp Pablo Tobon Uribe, Dept Radiol, Medellin, Colombia. [Juliano, Amy F.; Curtin, Hugh D.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Juliano, Amy F.; Curtin, Hugh D.] Harvard Univ, Sch Med, Boston, MA USA. RP Escudero, MO (reprint author), Hosp Pablo Tobon Uribe, Dept Radiol, Medellin, Colombia. EM martin127d@gmail.com NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 2015 VL 39 IS 3 BP 340 EP 342 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CI4KS UT WOS:000354718100008 ER PT J AU Lee, HJ Preda, A Ford, JM Mathalon, DH Keator, DB van Erp, TGM Turner, JA Potkin, SG AF Lee, Hyo Jong Preda, Adrian Ford, Judith M. Mathalon, Daniel H. Keator, David B. van Erp, Theo G. M. Turner, Jessica A. Potkin, Steven G. TI Functional Magnetic Resonance Imaging of Motor Cortex Activation in Schizophrenia SO JOURNAL OF KOREAN MEDICAL SCIENCE LA English DT Article DE Motor Cortex; Schizophrenia; Motor Dysfunction; Functional MRI; Laterality Quotient; Power Analysis ID SENSORIMOTOR CORTEX; CORTICAL RESPONSE; BRAIN; DYSFUNCTION; LATERALIZATION; STIMULATION; PERFORMANCE; ROBUST AB Previous fMRI studies of sensorimotor activation in schizophrenia have found in some cases hypoactivity, no difference, or hyperactivity when comparing patients with controls; similar disagreement exists in studies of motor laterality. In this multi-site fMRI study of a sensorimotor task in individuals with chronic schizophrenia and matched healthy controls, subjects responded with a right-handed finger press to an irregularly flashing visual checker board. The analysis includes eighty-five subjects with schizophrenia diagnosed according to the DSM-IV criteria and eighty-six healthy volunteer subjects. Voxel-wise statistical parametric maps were generated for each subject and analyzed for group differences; the percent Blood Oxygenation Level Dependent (BOLD) signal changes were also calculated over predefined anatomical regions of the primary sensory, motor, and visual cortex. Both healthy controls and subjects with schizophrenia showed strongly lateralized activation in the precentral gyrus, inferior frontal gyrus, and inferior parietal lobule, and strong activations in the visual cortex. There were no significant differences between subjects with schizophrenia and controls in this multi-site fMRI study. Furthermore, there was no significant difference in laterality found between healthy controls and schizophrenic subjects. This study can serve as a baseline measurement of schizophrenic dysfunction in other cognitive processes. C1 [Lee, Hyo Jong] Chonbuk Natl Univ, Div Comp Sci & Engn, CAIIT, Jeonju 561756, South Korea. [Preda, Adrian; Keator, David B.; van Erp, Theo G. M.; Potkin, Steven G.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Ford, Judith M.; Mathalon, Daniel H.] San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA USA. [Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Turner, Jessica A.] Georgia State Univ, Dept Psychol & Neurosci, Atlanta, GA 30303 USA. RP Lee, HJ (reprint author), Chonbuk Natl Univ, Div Comp Sci & Engn, 567 Baekje Daero, Jeonju 561756, South Korea. EM hlee@chonbuk.ac.kr OI Keator, David/0000-0001-5281-5576; Preda, Adrian /0000-0003-3373-2438 FU National Research Foundation of Korea (NRF) grant - Korea government (MEST) [2012R1A2A2A03]; [U24-RR021992] FX This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2012R1A2A2A03). Data used for this study were supported by grants to the Function BIRN (U24-RR021992). NR 33 TC 0 Z9 0 U1 1 U2 6 PU KOREAN ACAD MEDICAL SCIENCES PI SEOUL PA 302 75 DONG DU ICHON, DONG YONGSAN KU, SEOUL 140 031, SOUTH KOREA SN 1011-8934 EI 1598-6357 J9 J KOREAN MED SCI JI J. Korean Med. Sci. PD MAY PY 2015 VL 30 IS 5 BP 625 EP 631 DI 10.3346/jkms.2015.30.5.625 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CI7YB UT WOS:000354981600017 PM 25931795 ER PT J AU Lym, RL Ostrom, QT Kruchko, C Couce, M Brat, DJ Louis, DN Barnholtz-Sloan, JS AF Lym, Ryan L. Ostrom, Quinn T. Kruchko, Carol Couce, Marta Brat, Daniel J. Louis, David N. Barnholtz-Sloan, Jill S. TI Completeness and concordancy of WHO grade assignment for brain and central nervous system tumors in the United States, 2004-2011 SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE World Health Organization (WHO) grade; World Health Organization (WHO) histological type; Central nervous system tumors; Neuropathology; Cancer registry ID CLASSIFICATION; MENINGIOMAS; RADIOTHERAPY AB Central nervous system (CNS) tumors are categorized and graded for clinical and research purposes according to the World Health Organization (WHO) scheme which segregates tumors by histological type and predicted biological behavior. However, reporting of WHO grade in pathological reports is inconsistent despite its collection in cancer registration. We studied the completeness, concordancy, and yearly trends in the collection of WHO grade for primary CNS tumors between 2004 and 2011. Data from the Surveillance, Epidemiology and End Results program were analyzed for the percentage of histologically diagnosed primary CNS tumor cases with concordantly documented WHO grades between 2004 and 2011. Yearly trends were calculated with annual percentage changes (APC) and 95 % confidence intervals (95 % CI). Completeness and concordancy of the collection of WHO grade varied significantly by histological type and year. The percentage of cases with documented WHO grade increased significantly from 2004 to 2011: 39.0 % of cases in 2004 had documented WHO grade, while 77.5 % of cases had documented grade in 2011 (APC, 10.3; 95 % CI: 9.0, 11.5). Among cases with documented WHO grade, the percentage graded concordantly increased significantly from 89.1 % in 2004 to 93.7 % in 2007 (APC, 1.8; 95 % CI: 1.0, 2.6) and these values varied over time by histological type. One common trend among all histologies was a significant increase in the percentage of cases with documented WHO grade. A sizeable proportion of reported CNS tumors collected by cancer registrars have undocumented WHO grade, while a much smaller proportion are graded discordantly. Data collection on grade has improved in completeness and concordancy over time. Efforts to further improve collection of this variable are essential for clinical care and the epidemiological surveillance of CNS tumors. C1 [Lym, Ryan L.] Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. [Ostrom, Quinn T.; Couce, Marta; Barnholtz-Sloan, Jill S.] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH USA. [Ostrom, Quinn T.; Kruchko, Carol; Barnholtz-Sloan, Jill S.] Cent Brain Tumor Registry United States, Hinsdale, IL USA. [Couce, Marta] Univ Hosp Case Med Ctr, Dept Pathol, Cleveland, OH USA. [Brat, Daniel J.] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. [Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Louis, David N.] Harvard Univ, Sch Med, Boston, MA USA. RP Lym, RL (reprint author), Case Western Reserve Univ, Sch Med, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM rll63@case.edu; jsb42@case.edu FU Centers for Disease Control and Prevention (CDC) [5U58DP00381-04]; Sontag Foundation; Pediatric Brain Tumor Foundation; Novocure,Inc; Musella Foundation; Voices Against Brain Cancer; Elekta FX The following organizations contributed to the maintenance of the CBTRUS database: the Centers for Disease Control and Prevention (CDC) under Agreement 5U58DP00381-04, The Sontag Foundation (www.sontagfoundation.org), Genentech (www.gene.com), the Pediatric Brain Tumor Foundation (www.curethekids.org), Novocure,Inc. (www.novocure.com), along with the Musella Foundation (www.virtualtrials.com), Voices Against Brain Cancer (www.voicesagainstbraincancer.org), Elekta (www.elekta.com), as well as private and in kind donations. Contents are solely the responsibility of the authors and do not necessarily represent the official views of the CDC. NR 23 TC 4 Z9 4 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2015 VL 123 IS 1 BP 43 EP 51 DI 10.1007/s11060-015-1775-4 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CI6TC UT WOS:000354893700005 PM 25864099 ER PT J AU Wattson, DA Sullivan, RJ Niemierko, A Merritt, RM Lawrence, DP Oh, KS Flaherty, KT Shih, HA AF Wattson, Daniel A. Sullivan, Ryan J. Niemierko, Andrzej Merritt, Ryan M. Lawrence, Donald P. Oh, Kevin S. Flaherty, Keith T. Shih, Helen A. TI Survival patterns following brain metastases for patients with melanoma in the MAP-kinase inhibitor era SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Melanoma; Brain metastases; MAP-kinase inhibitors; Immunotherapy; Radiotherapy ID MALIGNANT-MELANOMA; MEK INHIBITION; OPEN-LABEL; PHASE-II; DABRAFENIB; VEMURAFENIB; THERAPY; TUMORS; MULTICENTER; DACARBAZINE AB Survival with BRAF-mutant metastatic melanoma is prolonged with MAP-kinase pathway inhibitors (MAPKi). Among patients with brain metastases (BM), however, the clinical course of MAPKi-treated patients is not well described. We therefore explored these patients' survival patterns compared to contemporary patients not treated with MAPKi. We analyzed 106 patients who developed melanoma BM between 2007 and 2013. Of these, 37 (35 %) received de novo MAPKi for BRAF-mutant disease, which preceded BM in 49 %. Immunotherapy was given to 54 % of MAPKi-treated patients and 94 % of those who did not receive MAPKi. We evaluated the potential influence of patient characteristics, systemic therapies, and BM-directed treatments on time to appearance of new BM and overall survival. With a median follow-up of 8.0 months after initial BM, MAPKi use was an independent predictor of prolonged survival after BM diagnosis (median 14.1 vs 7.0 months, P = 0.03, adjusted hazard ratio 0.39). This survival advantage was driven by the 16.6-month median survival of patients who initiated MAPKi after BM were diagnosed, versus 5.6 months if initiated prior to BM development (P = 0.03). Median survival from the onset of any systemic metastases was 22 months regardless of the timing of MAPKi relative to BM appearance. Time to in-brain progression was longer among patients whose MAPKi course was started after BM diagnosis, but MAPKi initiation prior to BM diagnosis was associated with longer time to intracranial involvement. These findings are consistent with potential MAPKi activity in intracranial melanoma. C1 [Wattson, Daniel A.] Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Sullivan, Ryan J.; Merritt, Ryan M.; Lawrence, Donald P.; Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Niemierko, Andrzej; Oh, Kevin S.; Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Shih, HA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM hshih@mgh.harvard.edu FU Roche/Genentech; GlaxoSmithKline FX Keith T. Flaherty is a paid consultant to Roche/Genentech and GlaxoSmithKline. NR 37 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2015 VL 123 IS 1 BP 75 EP 84 DI 10.1007/s11060-015-1761-x PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CI6TC UT WOS:000354893700008 PM 25864098 ER PT J AU Eaton, BR La Riviere, MJ Kim, S Prabhu, RS Patel, K Kandula, S Oyesiku, N Olson, J Curran, W Shu, HK Crocker, I AF Eaton, Bree R. La Riviere, Michael J. Kim, Sungjin Prabhu, Roshan S. Patel, Kirtesh Kandula, Shravan Oyesiku, Nelson Olson, Jeffrey Curran, Walter Shu, Hui-Kuo Crocker, Ian TI Hypofractionated radiosurgery has a better safety profile than single fraction radiosurgery for large resected brain metastases SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Hypofractionated; Radiosurgery; Brain; Central nervous system; Metastases ID STEREOTACTIC RADIOSURGERY; SURGICAL RESECTION; RADIATION-THERAPY; COMPETING RISK; RADIOTHERAPY; CAVITY; TRIAL AB The purpose of this study is to compare the safety and efficacy of single fraction radiosurgery (SFR) with hypofractionated radiosurgery (HR) for the adjuvant treatment of large, surgically resected brain metastases. Seventy-five patients with 76 resection cavities a parts per thousand yen 3 cm received 15 Gray (Gy) x 1 SFR (n = 40) or 5-8 Gy x 3-5 HR (n = 36). Cumulative incidence of local failure (LF) and radiation necrosis (RN) was estimated accounting for death as a competing risk and compared with Gray's test. The effect of multiple covariates was evaluated with the Fine-Gray proportional hazards model. The most common HR dose-fractionation schedules were 6 Gy x 5 (44 %), 7-8 Gy x 3 (36 %), and 6 Gy x 4 (8 %). The median follow-up was 11 months (range 2-71). HR patients had larger median resection cavity volumes (24.0 vs. 13.3 cc, p < 0.001), planning target volumes (PTV) (37.7 vs. 20.5 cc, p < 0.001), and cavity to PTV expansion margins (2 vs. 1.5 mm, p = 0.002) than SFR patients. Cumulative incidence of LF (95 % CI) at 6 and 12-months for HR versus SFR was 18.9 % (0.07-0.34) versus 15.9 % (0.06-0.29), and 25.6 % (0.12-0.42) versus 27.2 % (0.14-0.42), p = 0.80. Cumulative incidence of RN (95 % CI) at 6 and 12 months for HR vs. SFR was 3.3 % (0.00-0.15) versus 10.7 % (0.03-0.23), and 10.3 % (0.02-0.25) versus 19.2 % (0.08-0.34), p = 0.28. On multivariable analysis, SFR was significantly associated with an increased risk of RN, with a HR of 3.81 (95 % CI 1.04-13.93, p = 0.043). Hypofractionated radiosurgery may be the more favorable treatment approach for radiosurgery of cavities 3-4 cm in size and greater. C1 [Eaton, Bree R.; La Riviere, Michael J.; Prabhu, Roshan S.; Patel, Kirtesh; Kandula, Shravan; Curran, Walter; Shu, Hui-Kuo; Crocker, Ian] Emory Univ, Dept Radiat Oncol, Winship Canc Inst, Atlanta, GA 30322 USA. [Kim, Sungjin] Emory Univ, Winship Canc Inst, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. [Oyesiku, Nelson; Olson, Jeffrey] Emory Univ, Dept Neurosurg, Winship Canc Inst, Atlanta, GA 30322 USA. [Eaton, Bree R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Kim, Sungjin] Cedars Sinai Med Ctr, Biostat & Bioinformat Res Ctr, Los Angeles, CA 90048 USA. [Prabhu, Roshan S.] Levine Canc Inst, Southeastern Radiat Oncol Grp, Charlotte, NC USA. RP Eaton, BR (reprint author), Emory Univ, Dept Radiat Oncol, Winship Canc Inst, Atlanta, GA 30322 USA. EM brupper@emory.edu NR 30 TC 11 Z9 11 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2015 VL 123 IS 1 BP 103 EP 111 DI 10.1007/s11060-015-1767-4 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CI6TC UT WOS:000354893700011 PM 25862006 ER PT J AU Eaton, BR LaRiviere, MJ Kim, S Prabhu, RS Patel, K Kandula, S Oyesiku, N Olson, J Curran, W Shu, HK Crocker, I AF Eaton, Bree R. LaRiviere, Michael J. Kim, Sungjin Prabhu, Roshan S. Patel, Kirtesh Kandula, Shravan Oyesiku, Nelson Olson, Jeffrey Curran, Walter Shu, Hui-Kuo Crocker, Ian TI Erratum to: Hypofractionated radiosurgery has a better safety profile than single fraction radiosurgery for large resected brain metastases (vol 123, pg 103, 2015) SO JOURNAL OF NEURO-ONCOLOGY LA English DT Correction C1 [Eaton, Bree R.; LaRiviere, Michael J.; Prabhu, Roshan S.; Patel, Kirtesh; Kandula, Shravan; Curran, Walter; Shu, Hui-Kuo; Crocker, Ian] Emory Univ, Dept Radiat Oncol, Winship Canc Inst, Atlanta, GA 30322 USA. [Kim, Sungjin] Emory Univ, Dept Biostat & Bioinformat, Winship Canc Inst, Atlanta, GA 30322 USA. [Oyesiku, Nelson; Olson, Jeffrey] Emory Univ, Dept Neurosurg, Winship Canc Inst, Atlanta, GA 30322 USA. [Eaton, Bree R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Kim, Sungjin] Cedars Sinai Med Ctr, Biostat & Bioinformat Res Ctr, Los Angeles, CA 90048 USA. [Prabhu, Roshan S.] Levine Canc Inst, Southeastern Radiat Oncol Grp, Charlotte, NC USA. RP Eaton, BR (reprint author), Emory Univ, Dept Radiat Oncol, Winship Canc Inst, Atlanta, GA 30322 USA. EM brupper@emory.edu NR 1 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2015 VL 123 IS 1 BP 113 EP 113 DI 10.1007/s11060-015-1785-2 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CI6TC UT WOS:000354893700012 PM 25903656 ER PT J AU Garrido, MM Balboni, TA Maciejewski, PK Bao, YH Prigerson, HG AF Garrido, Melissa M. Balboni, Tracy A. Maciejewski, Paul K. Bao, Yuhua Prigerson, Holly G. TI Quality of Life and Cost of Care at the End of Life: The Role of Advance Directives SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Quality of life; end-of-life care; advance directives; costs of care; DNR ID CANCER-PATIENTS; ASSOCIATIONS; SAVINGS; EXPENDITURES; PREFERENCES; ILLUSION; DEATH AB Context. Advance directives (ADs) are expected to improve patients' end-of-life outcomes, but retrospective analyses, surrogate recall of patients' preferences, and selection bias have hampered efforts to determine ADs' effects on patient outcomes. Objectives. The aim was to examine associations among ADs, quality of life, and estimated costs of care in the week before death. Methods. We used prospective data from interviews of 336 patients with advanced cancer and their caregivers and analyzed patient baseline interview and caregiver and provider post-mortem evaluation data from the Coping with Cancer study. Cost estimates were from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample and published Medicare payment rates and cost estimates. Outcomes were quality of life (range 0-10) and estimated costs of care received in the week before death. Because patient end-of-life care preferences influence both AD completion and care use, analyses were stratified by preferences regarding heroic end-of-life measures (everything possible to remain alive). Results. Most patients did not want heroic measures (76%). Do-not-resuscitate (DNR) orders were associated with higher quality of life (beta = 0.75, standard error = 0.30, P = 0.01) across the entire sample. There were no statistically significant relationships between DNR orders and outcomes among patients when we stratified by patient preference or between living wills/durable powers of attorney and outcomes in any of the patient groups. Conclusion. The associations between DNR orders and better quality of life in the week before death indicate that documenting preferences against resuscitation in medical orders may be beneficial to many patients. (C) 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Garrido, Melissa M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Garrido, Melissa M.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Balboni, Tracy A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Balboni, Tracy A.] Harvard Univ, Sch Med, Boston, MA USA. [Maciejewski, Paul K.; Bao, Yuhua; Prigerson, Holly G.] Weill Cornell Med Coll, New York, NY 10065 USA. RP Prigerson, HG (reprint author), Weill Cornell Med Coll, Ctr Res End Life Care, 525 East 68th St,Box 39, New York, NY 10065 USA. EM hgp2001@med.cornell.edu OI Garrido, Melissa/0000-0002-8986-3536 FU National Institute of Mental Health [MH63892, MH090087]; National Cancer Institute [CA 106370, CA 156732]; Center for Research on End of Life Care at Cornell; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service [CDA 11-201/CDP 12-255]; Icahn School of Medicine at Mount Sinai Claude D. Pepper Older Americans Independence Center [NIH/NIA P30 AG028741-01A2]; American Society of Clinical Oncology Conquer Cancer Foundation Career Development Award; Healthcare Chaplaincy/John Templeton Foundation Award; Translational Research Institute on Pain in Late Life (TRIPLL) at Weill Cornell Medical College [5P30AG022845] FX This research was supported in part by the following grants to Dr. Prigerson: MH63892 from the National Institute of Mental Health and CA 106370 and CA 156732 from the National Cancer Institute; and the Center for Research on End of Life Care at Cornell. Dr. Garrido is supported by CDA 11-201/CDP 12-255 from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service and the Icahn School of Medicine at Mount Sinai Claude D. Pepper Older Americans Independence Center (NIH/NIA P30 AG028741-01A2). Dr. Balboni is supported by an American Society of Clinical Oncology Conquer Cancer Foundation Career Development Award and a Healthcare Chaplaincy/John Templeton Foundation Award. Dr. Bao is supported by a career development award from the National Institute of Mental Health (K01 MH090087) and a pilot award from the Translational Research Institute on Pain in Late Life (TRIPLL) at Weill Cornell Medical College (5P30AG022845). The sponsors had no involvement in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Dr. Garrido had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. None of the authors have relationships with any entities having financial interest in this topic. NR 42 TC 12 Z9 13 U1 4 U2 15 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 MAY PY 2015 VL 49 IS 5 BP 828 EP 835 DI 10.1016/j.jpainsymman.2014.09.015 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CI5VI UT WOS:000354827500009 PM 25498855 ER PT J AU Lendon, JP Ahluwalia, SC Walling, AM Lorenz, KA Oluwatola, OA Price, RA Quigley, D Teno, JM AF Lendon, Jessica Penn Ahluwalia, Sangeeta C. Walling, Anne M. Lorenz, Karl A. Oluwatola, Oluwatobi A. Price, Rebecca Anhang Quigley, Denise Teno, Joan M. TI Measuring Experience With End-of-Life Care: A Systematic Literature Review SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Review DE End-of-life care; assessment; family caregivers ID INFORMAL CAREGIVERS SATISFACTION; BEREAVED FAMILY-MEMBERS; DYING CANCER-PATIENTS; PALLIATIVE CARE; PERCEPTIONS AB Context. Increasing interest in end-of-life care has resulted in many tools to measure the quality of care. An important outcome measure of end-of-life care is the family members' or caregivers' experiences of care. Objectives. To evaluate the instruments currently in use to inform next steps for research and policy in this area. Methods. We conducted a systematic review of PubMed, PsycINFO, and PsycTESTS (R) for all English-language articles published after 1990 using instruments to measure adult patient, family, or informal caregiver experiences with end-of-life care. Survey items were abstracted and categorized into content areas identified through an iterative method using three independent reviewers. We also abstracted information from the most frequently used surveys about the identification of proxy respondents for after-death surveys, the timing and method of survey administration, and the health care setting being assessed. Results. We identified 88 articles containing 51 unique surveys with available content. We characterized 14 content areas variably present across the 51 surveys. Information and care planning, provider care, symptom management, and overall experience were the most frequent areas addressed. There was also considerable variation across the surveys in the identification of proxy respondents, the timing of survey administration, and in the health care settings and services being evaluated. Conclusion. This review identified several comprehensive surveys aimed at measuring the experiences of end-of-life care, covering a variety of content areas and practical issues for survey administration. Future work should focus on standardizing surveys and administration methods so that experiences of care can be reliably measured and compared across care settings. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine. C1 [Lendon, Jessica Penn; Walling, Anne M.; Lorenz, Karl A.] VA Greater Los Angeles, Los Angeles, CA 90073 USA. [Walling, Anne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Ahluwalia, Sangeeta C.; Walling, Anne M.; Oluwatola, Oluwatobi A.; Quigley, Denise] RAND Corp, Santa Monica, CA USA. [Price, Rebecca Anhang] RAND Corp, Arlington, VA USA. [Teno, Joan M.] Brown Univ, Providence, RI 02912 USA. RP Lendon, JP (reprint author), VA Greater Los Angeles, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jessicapenn@gmail.com FU Centers for Medicare and Medicaid Services, Department of Health and Human Services [HHSM-500-2012-00126G]; Veterans Affairs (VA) Office of Academic Affiliations through the VA Health Services Research and Development Advanced Fellowship Program; National Institutes of Health (NIH)/National Center for Advancing Translational Science UCLA CTSI grant [UL1TR000124]; NIH loan repayment program; National Palliative Care Research Center FX The literature review on which this publication is based was performed under Contract HHSM-500-2012-00126G, entitled, "Hospice Experience of Care Survey," funded by the Centers for Medicare and Medicaid Services, Department of Health and Human Services. The content of this publication neither necessarily reflect the views or policies of the Department of Health and Human Services nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The authors assume full responsibility for the accuracy and completeness of the ideas presented. Dr. Lendon was supported by the Veterans Affairs (VA) Office of Academic Affiliations through the VA Health Services Research and Development Advanced Fellowship Program. Dr. Walling was supported by National Institutes of Health (NIH)/National Center for Advancing Translational Science UCLA CTSI grant no. UL1TR000124 and the NIH loan repayment program. Dr. Ahluwalia was supported by a Career Development Award from the National Palliative Care Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 20 TC 4 Z9 4 U1 0 U2 9 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 MAY PY 2015 VL 49 IS 5 BP 904 EP + DI 10.1016/j.jpainsymman.2014.10.018 PG 15 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CI5VI UT WOS:000354827500018 PM 25543110 ER PT J AU Krakauer, EL Cham, NTP Husain, SA Yen, NTH Joranson, DE Khue, LN Maurer, MA AF Krakauer, Eric L. Nguyen Thi Phuong Cham Husain, Syeda Asra Nguyen Thi Hai Yen Joranson, David E. Luong Ngoc Khue Maurer, Martha A. TI Toward Safe Accessibility of Opioid Pain Medicines in Vietnam and Other Developing Countries: A Balanced Policy Method SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Pain; palliative care; opioid; morphine; global health; policy; cancer; AIDS ID PALLIATIVE CARE; AVAILABILITY; CANCER AB Moderate or severe pain is common among people with advanced cancer and other life-threatening illnesses. Yet despite agreement that pain relief is a human right, the poorest 80% of the world's population rarely have access to strong opioid analgesics. Excessively restrictive opioid policies, especially in developing countries, both stem from and propagate misguided fears about opioids, so-called opiophobia. Because opiophobia, like any norm, is historically, socially, and culturally situated, efforts to change opiophobic policies will be most effective if guided by awareness of their historical, social, and cultural determinants. We describe some of these determinants in Vietnam and report on results of an ongoing project there to allay opiophobia and improve safe access to opioids for medical uses. We used a method that entails working with committed local partners, including a high-level official from the Ministry of Health, to review all Vietnamese policies governing opioid accessibility to identify the barriers; devising an action plan to safely reduce or circumnavigate the barriers; obtaining buy-in for the plan from all stakeholders, including drug regulators and the police; and assisting the Ministry of Health to implement the plan. Since the start of the project, morphine consumption has increased each year and as of 2010 was ninefold greater than in 2003, and the number of hospitals offering palliative care has increased from three to 15. We conclude that this balanced policy method appears to be helping to reduce barriers to opioid access in Vietnam and should be used in other developing countries. (C) 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Krakauer, Eric L.] Massachusetts Gen Hosp, Div Palliat Care, Boston, MA 02114 USA. [Nguyen Thi Phuong Cham] Ctr Community Hlth Dev, Hanoi, Vietnam. [Husain, Syeda Asra; Joranson, David E.; Maurer, Martha A.] Univ Wisconsin, Carbone Canc Ctr, Pain & Policy Studies Grp, Madison, WI USA. [Husain, Syeda Asra; Maurer, Martha A.] WHO, Collaborating Ctr Pain Policy Palliat Care, Madison, WI USA. [Nguyen Thi Hai Yen; Luong Ngoc Khue] Minist Hlth, Vietnam Adm Med Serv, Hanoi, Vietnam. RP Krakauer, EL (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, 641 Huntington Ave, Boston, MA 02115 USA. EM ekrakauer@hms.harvard.edu FU IPPF from the Open Society Foundations; Livestrong Foundation; Purdue Pharma FX The authors gratefully acknowledge funding for the IPPF from the Open Society Foundations and the Livestrong Foundation. The University of Wisconsin Carbone Cancer Center has received unrestricted educational grants from Purdue Pharma to support the work of the PPSG; this relationship ended in 2010. The authors declare no conflicts of interest. NR 36 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAY PY 2015 VL 49 IS 5 BP 916 EP 922 DI 10.1016/j.jpainsymman.2014.10.012 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CI5VI UT WOS:000354827500019 PM 25523889 ER PT J AU Jacobsen, J Whitlock, SN Lee, H Lindvall, C Jackson, V AF Jacobsen, Juliet Whitlock, Sandra N. Lee, Hang Lindvall, Charlotta Jackson, Vicki TI Teaching Colleagues How to Discuss Prognosis as Part of a Hospital-Wide Quality Improvement Project: The Positive Impact of a 90-Minute Workshop SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Communication; prognosis; quality improvement; colleagues ID COMMUNICATION; INFORMATION; TALKING; CANCER; WANT; CARE; LIFE; END AB Background. Many physicians have difficulty with discussions about prognosis. The aims of this study were to evaluate why physicians struggle to discuss prognosis and to measure the effect of a 90-minute communication workshop on self-reported skill. Measures. An evaluation study was used with three measurement points: before the 90-minute communication workshop (e-mail survey); immediately after the workshop (paper survey); and one month after the workshop (e-mail survey). Intervention. Physicians from diverse specialties at a single academic institution were paid to participate in a 90-minute communication workshop on discussing prognosis. Outcomes. Physicians identified several reasons why discussions of prognosis are hard: "I am not sure of the actual prognosis" (58.9%; 95% CI, 50.9, 66.5), "I worry I will take away hope (42.9%; 95% CI, 35.2, 50.9), and "I worry the patient is not ready to hear the information" (42.9%; 95% CI, 35.2, 50.9). Physicians who attended this short workshop reported that they could apply what was learned to their work immediately (4.6, range 1-5). One month after the workshop, 91% of respondents reported trying a skill learned in the workshop. The most frequently used skill was Ask/Tell/Ask (61.5%; 95% CI, 51.6, 70.6). Conclusions/Lessons Learned. A short workshop on discussing prognosis was highly valued by physicians from diverse specialties and a majority reported using at least one of the communication skills learned. (C) 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Jacobsen, Juliet; Lindvall, Charlotta; Jackson, Vicki] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Whitlock, Sandra N.] Four Seasons Palliat Care, Flat Rock, NC USA. [Lee, Hang] MGH Biostat Ctr, Boston, MA USA. [Lee, Hang] Harvard Univ, Sch Med, Boston, MA USA. RP Jacobsen, J (reprint author), Massachusetts Gen Hosp, Palliat Med, Founders 600,55 Fruit St, Boston, MA 02114 USA. EM jjacobsen@partners.org NR 14 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAY PY 2015 VL 49 IS 5 BP 960 EP 963 DI 10.1016/j.jpainsymman.2014.11.301 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CI5VI UT WOS:000354827500026 PM 25666518 ER PT J AU Rosenberg, AR Wolfe, J AF Rosenberg, Abby R. Wolfe, Joanne TI Re: Long-Term Psychosocial Outcomes Among Bereaved Siblings of Children With Cancer Response to van der Geest et al SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Letter ID STRESS C1 [Rosenberg, Abby R.] Univ Washington, Seattle Childrens Hosp, Canc & Blood Disorders Ctr, Seattle, WA 98195 USA. [Rosenberg, Abby R.] Fred Hutchinson Canc Res Ctr, Treuman Katz Ctr Pediat Bioeth, Dept Pediat, Seattle, WA 98104 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. EM joanne_wolfe@dfci.harvard.edu FU NCI NIH HHS [L40 CA170049] NR 8 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAY PY 2015 VL 49 IS 5 BP E7 EP E9 DI 10.1016/j.jpainsymman.2015.02.014 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CI5VI UT WOS:000354827500005 PM 25757836 ER PT J AU Northman, L Ross, S Morris, M Tarquini, S AF Northman, Lisa Ross, Sarah Morris, Marybeth Tarquini, Sarah TI Supporting Pediatric Cancer Survivors With Neurocognitive Late Effects: A Model of Care SO JOURNAL OF PEDIATRIC ONCOLOGY NURSING LA English DT Article DE pediatric cancer; pediatric brain tumor; cognitive late effects; neurocognitive effects; educational support; special education ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LONG-TERM SURVIVORS; CRANIAL IRRADIATION; CHILDHOOD-CANCER; BRAIN-TUMOR; CHILDREN AB Educational difficulties are common for childhood survivors of central nervous system (CNS) cancers. Children who have been treated for brain tumors and those who have received treatments involving the CNS are at increased risk of developing neurocognitive late effects including difficulties with attention, executive functioning, speed of processing, and academic functioning. These children are also at risk for difficulties with social functioning and social isolation. This hospital's School Liaison Program (SLP) provides ongoing psychoeducation, advocacy, and consultation services for parents, schools, and medical staff to address the educational needs associated with the late effects of treatment for pediatric CNS-involved patients. This article provides an overview of the SLP model of care and discusses parent-perceived quality and program effectiveness. In general, parents attributed SLP involvement to improved academic performance, home-school communication, and school-level understanding of unique student cognitive profiles and learning needs. C1 [Northman, Lisa; Ross, Sarah; Morris, Marybeth; Tarquini, Sarah] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Northman, L (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,SW341, Boston, MA 02215 USA. EM lisa_northman@dfci.harvard.edu NR 13 TC 3 Z9 3 U1 3 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1043-4542 EI 1532-8457 J9 J PEDIATR ONCOL NURS JI J. Pediatr. Oncol. Nurs. PD MAY-JUN PY 2015 VL 32 IS 3 BP 134 EP 142 DI 10.1177/1043454214554012 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA CI6CE UT WOS:000354845500002 PM 25416520 ER PT J AU White, HR Jiao, Y Ray, AE Huh, D Atkins, DC Larimer, ME Fromme, K Corbin, WR Baer, JS LaBrie, JW Mun, EY AF White, Helene R. Jiao, Yang Ray, Anne E. Huh, David Atkins, David C. Larimer, Mary E. Fromme, Kim Corbin, William R. Baer, John S. LaBrie, Joseph W. Mun, Eun-Young TI Are There Secondary Effects on Marijuana Use From Brief Alcohol Interventions for College Students? SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; REDUCING DRUG CONSUMPTION; SUBSTANCE USE; EMERGENCY-DEPARTMENT; PRIMARY-CARE; CANNABIS DEPENDENCE; HEAVY-DRINKING; YOUNG-PEOPLE; FEEDBACK; RISK AB Objective: This study examined whether brief motivational interventions (BMIs) designed for reducing heavy drinking among college students have secondary effects on reducing marijuana use. Method: The data came from Project INTEGRATE, which combined data from 24 independent trials of HMIs and other individual-focused interventions designed to reduce heavy drinking and related problems among college students. We analyzed data from 10 samples across nine studies that used random assignment of participants into either a BMI or a control group and assessed marijuana use outcomes (N = 6,768; 41.5% men; 73.2% White; 57.7% first-year students; 19.2% current marijuana users at baseline). We derived three marijuana use groups within studies by cross-tabulating baseline and follow-up data: Nonusers, Reducers, and Stayers/Increasers. Results: Peto's one-step odds ratio analyses for meta-analysis revealed no significant intervention effects on marijuana use at either short-term (1-3 month) or long-term (6-12 month) follow-up. Subsequent exploratory analyses showed that those who reduced drinking were more likely to be a marijuana Reducer or Nonuser, compared with a Stayer/Increaser, at both follow-ups. Conclusions: The BMIs to reduce heavy drinking evaluated in this study did not reduce marijuana use. However, our exploratory results suggest that if we can develop interventions for college students that effectively reduce drinking, we may also reduce their marijuana use. Furthermore, as recreational use of marijuana becomes legal or decriminalized and marijuana becomes more readily available, it may be necessary to develop interventions specifically targeting marijuana use among college students. C1 [White, Helene R.; Jiao, Yang; Ray, Anne E.; Mun, Eun-Young] Rutgers State Univ, Ctr Alcohol Studies, Piscataway, NJ 08854 USA. [Huh, David; Atkins, David C.; Larimer, Mary E.] Univ Washington, Dept Psychiat & Behav Sci, Ctr Study Hlth & Risk Behav, Seattle, WA 98195 USA. [Fromme, Kim] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Corbin, William R.] Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. [Baer, John S.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Baer, John S.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [LaBrie, Joseph W.] Loyola Marymount Univ, Dept Psychol, Los Angeles, CA 90045 USA. RP White, HR (reprint author), Rutgers State Univ, Ctr Alcohol Studies, 607 Allison Rd, Piscataway, NJ 08854 USA. EM hewhite@rci.rutgers.edu OI Atkins, David/0000-0002-5781-9880 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R01 AA019511]; National Institute on Drug Abuse (NIDA) [R01 DA034608] FX Project INTEGRATE was supported by National Institute on Alcohol Abuse and Alcoholism (NIAAA) Grant R01 AA019511. In addition, the writing of the article was supported, in part, by National Institute on Drug Abuse (NIDA) Grant R01 DA034608. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAAA, NIDA, or National Institutes of Health. NR 60 TC 1 Z9 1 U1 4 U2 6 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 EI 1938-4114 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAY PY 2015 VL 76 IS 3 BP 367 EP 377 PG 11 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA CI4WR UT WOS:000354755100004 PM 25978822 ER PT J AU Perron, BE Bohnert, K Perone, AK Bonn-Miller, MO Ilgen, M AF Perron, Brian E. Bohnert, Kipling Perone, Angela K. Bonn-Miller, Marcel O. Ilgen, Mark TI Use Of Prescription Pain Medications Among Medical Cannabis Patients: Comparisons of Pain Levels, Functioning, and Patterns of Alcohol and Other Drug Use SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID COLLEGE-STUDENTS; CONTROLLED-TRIAL; MARIJUANA USE; FEASIBILITY; RELIABILITY; COMBINATION; POPULATION; ADULTS; AUDIT AB Objective: Management of chronic pain is one of the most common reasons given by individuals seeking medical cannabis. However, very little information exists about the concurrent use of cannabis and prescription pain medication (PPM). This study fills this gap in knowledge by systematically comparing medical cannabis users who use or do not use PPM, with an emphasis on understanding whether concurrent use of cannabis and PPM is associated with more serious forms of alcohol and other drug involvement. Method: Data from this study were collected from a medical cannabis clinic in southwestern Michigan (N = 273). Systematic comparisons were made on measures of sociodemographics, reasons for substance use, pain, functioning, and perceptions of PPM and medical cannabis efficacy. Results: PPM users tended to be older and reported higher levels of pain and lower levels of functioning. The overall sample exhibited higher lifetime and past-3-month rates of alcohol and other noncannabis drug use than did the general population. Approximately 40% of subjects reported combining cannabis with alcohol, but no significant difference was observed between PPM users and nonusers. PPM users and nonusers did not exhibit any difference in either lifetime or past-3-month use of other drugs, including cocaine, sedatives, street opioids, and amphetamines. PPM users rated the efficacy of cannabis higher than PPM for pain management and indicated a strong desire to reduce PPM usage. Conclusions: Use of PPM among medical cannabis users was not identified as a correlate for more serious forms of alcohol and other drug involvement. However, longitudinal study designs are needed to better understand the trajectories of alcohol and other drug involvement over time among medical cannabis users. C1 [Perron, Brian E.; Perone, Angela K.] Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA. [Bohnert, Kipling; Ilgen, Mark] Dept Vet Affairs Healthcare Syst, Vet Affairs VA Serious Mental Illness Treatment R, Ann Arbor, MI USA. [Bohnert, Kipling; Ilgen, Mark] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Bonn-Miller, Marcel O.] Philadelphia VA Med Ctr, Ctr Excellence Subst Abuse Treatment & Educ, Philadelphia, PA USA. [Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Palo Alto, CA USA. [Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Palo Alto, CA USA. [Bonn-Miller, Marcel O.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Perron, BE (reprint author), Univ Michigan, Sch Social Work, 1080 S Univ Ave, Ann Arbor, MI 48109 USA. EM beperron@umich.edu FU National Institute on Drug Abuse [R01 DA033397] FX This work was supported by the National Institute on Drug Abuse grant R01 DA033397 to Mark Ilgen. NR 34 TC 1 Z9 1 U1 2 U2 5 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 EI 1938-4114 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAY PY 2015 VL 76 IS 3 BP 406 EP 413 PG 8 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA CI4WR UT WOS:000354755100008 PM 25978826 ER PT J AU Lai, ECC Wong, MB Iwata, I Zhang, YH Hsieh, CY Yang, YHK Setoguchi, S AF Lai, Edward Chia-Cheng Wong, Monera B. Iwata, Isao Zhang, Yinghong Hsieh, Cheng-Yang Yang, Yea-Huei Kao Setoguchi, Soko TI Risk of Pneumonia in New Users of Cholinesterase Inhibitors for Dementia SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cholinesterase inhibitors; cohort studies; dementia; Medicare; pneumonia ID MODERATE ALZHEIMERS-DISEASE; ANTIPSYCHOTIC-DRUG USE; ASPIRATION PNEUMONIA; PARKINSONS-DISEASE; ADMINISTRATIVE DATA; ELDERLY-PEOPLE; DOUBLE-BLIND; DONEPEZIL; RIVASTIGMINE; SAFETY AB ObjectivesTo compare the risk of pneumonia in older adults receiving donepezil, galantamine, or rivastigmine for dementia. DesignRetrospective cohort study. SettingNationally representative 5% sample of Medicare databases. ParticipantsMedicare beneficiaries aged 65 and older who newly initiated cholinesterase inhibitor therapy between 2006 and 2009. MeasurementsPneumonia, defined as the presence of a diagnosis code for pneumonia as the primary diagnosis on an inpatient claim or on an emergency department claim followed by dispensing of appropriate antibiotics. Cox proportional hazards models were used to estimate the risk of pneumonia. Subgroup analyses and sensitivity analyses were conducted using alternative pneumonia definitions and adjustments using high-dimensional propensity scores to test the robustness of the results. ResultsThe mean age of 35,570 new users of cholinesterase inhibitors (30,174 users of donepezil, 1,176 users of galantamine, 4,220 users of rivastigmine) was 82; 75% were women, and 82% were white. The cumulative incidence of pneumonia was 51.9 per 1,000 person-years. The risk of pneumonia for rivastigmine users was 24% lower than that of donepezil users (hazard ratio (HR)=0.75, 95% confidence interval (CI)=0.60-0.93). Risk in galantamine users (HR=0.87, 95% CI=0.62-1.23) was not significantly different from risk in donepezil users. Results of subgroup and sensitivity analyses were similar to the primary results. ConclusionThe risk of pneumonia was lower in individuals receiving rivastigmine than in those receiving donepezil. Additional studies are needed to confirm the findings of pneumonia risk between the oral and transdermal forms of rivastigmine and in users of galantamine. C1 [Lai, Edward Chia-Cheng; Zhang, Yinghong; Setoguchi, Soko] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Lai, Edward Chia-Cheng; Hsieh, Cheng-Yang; Yang, Yea-Huei Kao] Natl Cheng Kung Univ, Sch Pharm, Tainan 70101, Taiwan. [Lai, Edward Chia-Cheng; Hsieh, Cheng-Yang; Yang, Yea-Huei Kao] Natl Cheng Kung Univ, Inst Clin Pharm & Pharmaceut Sci, Tainan 70101, Taiwan. [Wong, Monera B.] Massachusetts Gen Hosp, Geriatr Med Unit, Boston, MA 02114 USA. [Iwata, Isao; Yang, Yea-Huei Kao] Natl Cheng Kung Univ, Hlth Outcome Res Ctr, Tainan 70101, Taiwan. [Iwata, Isao] Univ N Carolina, Div Geriatr Med, Chapel Hill, NC USA. [Hsieh, Cheng-Yang] Tainan Sin Lau Hosp, Dept Neurol, Tainan, Taiwan. [Setoguchi, Soko] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. RP Setoguchi, S (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM soko.setoguchi@duke.edu OI Iwata, Isao/0000-0002-3732-9526 FU Duke Clinical Research Institute; National Center for Advancing Translational Sciences [UL1TR001117] FX This work was supported internally by the Duke Clinical Research Institute and by Grant UL1TR001117 from the National Center for Advancing Translational Sciences. NR 45 TC 4 Z9 4 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2015 VL 63 IS 5 BP 869 EP 876 DI 10.1111/jgs.13380 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CI4NH UT WOS:000354726400004 PM 25912671 ER PT J AU Leff, B Weston, CM Garrigues, S Patel, K Ritchie, C AF Leff, Bruce Weston, Christine M. Garrigues, Sarah Patel, Kanan Ritchie, Christine CA Natl Home-Based Primary Care TI Home-Based Primary Care Practices in the United States: Current State and Quality Improvement Approaches SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE house calls; home-based primary care; home-based palliative care; quality of care ID STANDARDS; VETERANS; HEALTH AB ObjectivesTo describe the characteristics of home-based primary care practices: staffing, administrative, population served, care practices, and quality of care challenges. DesignSurvey of home-based primary care practices. SettingHome-based primary care practices in the United States. ParticipantsMembers of the American Academy of Home Care Medicine and nonmember providers identified by surveyed members. MeasurementsA 58-item questionnaire that assessed practice characteristics, care provided by the practice, and how the quality of care that the practice provided was assessed. ResultsSurvey response rate was 47.9%, representing 272 medical house calls practices. Mean average daily census was 457 patients (median 100 patients, range 1-30,972 patients). Eighty-eight percent of practices offered around-the-clock coverage for urgent concerns, 60% held regularly scheduled team meetings, 89% used an electronic medical record, and one-third used a defined quality improvement process. The following factors were associated with practices that used a defined quality improvement process: practice holds regularly scheduled team meetings to discuss specific patients (odds ratio (OR)=2.07, 95% confidence interval (CI)=1.02-4.21), practice conducts surveys of patients (OR=8.53, 95% CI=4.07-17.88), and practice is involved in National Committee for Quality Assurance patient-centered medical home (OR=3.27, 95% CI=1.18-9.07). Ninety percent of practices would or might participate in quality improvement activities that would provide them timely feedback on patient and setting-appropriate quality indicators. ConclusionsThere is a substantial heterogeneity of home-based primary care practice types. Most practices perform activities that lend themselves to robust quality improvement efforts, and nearly all indicated interest in a national registry to inform quality improvement. C1 [Leff, Bruce] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. [Leff, Bruce; Weston, Christine M.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD 21224 USA. [Leff, Bruce] Johns Hopkins Univ, Sch Nursing, Dept Community & Publ Hlth, Baltimore, MD 21224 USA. [Garrigues, Sarah; Patel, Kanan; Ritchie, Christine] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Garrigues, Sarah; Patel, Kanan; Ritchie, Christine] San Francisco VA Med Ctr, San Francisco, CA USA. [Garrigues, Sarah; Patel, Kanan; Ritchie, Christine] Jewish Home San Francisco, San Francisco, CA USA. RP Leff, B (reprint author), Johns Hopkins Univ, Sch Med, Div Geriatr Med, 5505 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM bleff@jhmi.edu FU Commonwealth Fund, Retirement Research Foundation; Retirement Research Foundation; Commonwealth Fund, a national private foundation based in New York City FX The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Dr. Leff is a member of the Board of Directors of the American Academy of Home Care Medicine. Bruce Leff, Christine M. Weston, Sarah Garrigues, and Kanan Patel were funded by the Commonwealth Fund, Retirement Research Foundation.; This work was supported by the Retirement Research Foundation and the Commonwealth Fund, a national private foundation based in New York City that supports independent research on healthcare and makes grants to improve healthcare practice and policy. The views presented here are those of the authors and not necessarily those of the Commonwealth Fund, its directors, officers, or staff. We acknowledge the contributions made by members of the National Home-Based Primary Care and Palliative Care Network to the development of the survey instrument: Gresham Bayne, MD, Nant Health; Lynn Beatty, MD, Visiting Physicians Association; Peter A. Boling, MD, Virginia Commonwealth University; Tom Cornwell, MD, Home Centered Care Institute; Eric De Jonge, MD, Medstar Washington Hospital Center Medical House Call Program; Tom Edes, MD, FACP, U.S. Department of Veterans Affairs; Lynn Friss Feinberg, AARP Public Policy Institute; Alanna Goldstein, MPH, American Geriatrics Society; Jen Hayashi, MD, Johns Hopkins Elder House Call Program; Benneth Husted, DO, Housecall Providers; Julia Jung, CPA, House Call Doctors; Tricia Neuman, ScD, Kaiser Family Foundation; Patricia Tomsko Nay, MD, CMD, American Academy of Hospice and Palliative Medicine; Tom Reed, Senior Advocate Resources; Constance Row, American Academy of Home Care Medicine; Christine Broderick, National Partnership For Women & Families; Theresa Soriano, MD, MPH, Mount Sinai Visiting Doctors Program; Robert Sowislo, Visiting Physicians Association. NR 13 TC 4 Z9 4 U1 2 U2 8 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 MAY PY 2015 VL 63 IS 5 BP 963 EP 969 DI 10.1111/jgs.13382 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CI4NH UT WOS:000354726400016 PM 25940131 ER EF