FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Talkowski, ME Maussion, G Crapper, L Rosenfeld, JA Blumenthal, I Hanscom, C Chiang, C Lindgren, A Pereira, S Ruderfer, D Diallo, AB Lopez, JP Turecki, G Chen, ES Gigek, C Harris, DJ Lip, V An, Y Biagioli, M MacDonald, ME Lin, M Haggarty, SJ Sklar, P Purcell, S Kellis, M Schwartz, S Shaffer, LG Natowicz, MR Shen, YP Morton, CC Gusella, JF Ernst, C AF Talkowski, Michael E. Maussion, Gilles Crapper, Liam Rosenfeld, Jill A. Blumenthal, Ian Hanscom, Carrie Chiang, Colby Lindgren, Amelia Pereira, Shahrin Ruderfer, Douglas Diallo, Alpha B. Lopez, Juan Pablo Turecki, Gustavo Chen, Elizabeth S. Gigek, Carolina Harris, David J. Lip, Va An, Yu Biagioli, Marta MacDonald, Marcy E. Lin, Michael Haggarty, Stephen J. Sklar, Pamela Purcell, Shaun Kellis, Manolis Schwartz, Stuart Shaffer, Lisa G. Natowicz, Marvin R. Shen, Yiping Morton, Cynthia C. Gusella, James F. Ernst, Carl TI Disruption of a Large Intergenic Noncoding RNA in Subjects with Neurodevelopmental Disabilities SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENE-EXPRESSION; CHROMATIN; REARRANGEMENTS; REVEALS; GENOME AB Large intergenic noncoding (linc) RNAs represent a newly described class of ribonucleic acid whose importance in human disease remains undefined. We identified a severely developmentally delayed 16-year-old female with karyotype 46,XX,t(2;11)(p25.1;p15.1)dn in the absence of clinically significant copy number variants (CNVs). DNA capture followed by next-generation sequencing of the translocation breakpoints revealed disruption of a single noncoding gene on chromosome 2, LINC00299, whose RNA product is expressed in all tissues measured, but most abundantly in brain. Among a series of additional, unrelated subjects referred for clinical diagnostic testing who showed CNV affecting this locus, we identified four with exon-crossing deletions in association with neurodevelopmental abnormalities. No disruption of the LINC00299 coding sequence was seen in almost 14,000 control subjects. Together, these subjects with disruption of LINC00299 implicate this particular noncoding RNA in brain development and raise the possibility that, as a class, abnormalities of lincRNAs may play a significant role in human developmental disorders. C1 [Maussion, Gilles; Crapper, Liam; Diallo, Alpha B.; Lopez, Juan Pablo; Turecki, Gustavo; Chen, Elizabeth S.; Gigek, Carolina; Ernst, Carl] McGill Univ, Douglas Hosp, Res Inst, Dept Psychiat, Quebec City, ON H4H 1R3, Canada. [Talkowski, Michael E.; Blumenthal, Ian; Hanscom, Carrie; Chiang, Colby; Biagioli, Marta; MacDonald, Marcy E.; Haggarty, Stephen J.; Purcell, Shaun; Shen, Yiping; Ernst, Carl] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Talkowski, Michael E.; Biagioli, Marta; MacDonald, Marcy E.; Haggarty, Stephen J.; Gusella, James F.] Harvard Univ, Dept Neurol & Genet, Boston, MA 02114 USA. [Talkowski, Michael E.; MacDonald, Marcy E.; Lin, Michael; Purcell, Shaun; Kellis, Manolis; Morton, Cynthia C.; Gusella, James F.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02114 USA. [Rosenfeld, Jill A.; Shaffer, Lisa G.] Signature Genom Inc, PerkinElmer, Spokane, WA 99207 USA. [Lindgren, Amelia; Pereira, Shahrin; Morton, Cynthia C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Lindgren, Amelia; Pereira, Shahrin; Morton, Cynthia C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ruderfer, Douglas; Sklar, Pamela; Purcell, Shaun] Mt Sinai Sch Med, Dept Psychiat & Genet, New York, NY 10029 USA. [Ruderfer, Douglas; Sklar, Pamela; Purcell, Shaun] Mt Sinai Sch Med, Dept Genom Sci, New York, NY 10029 USA. [Harris, David J.; Lip, Va; An, Yu; Shen, Yiping] Harvard Univ, Sch Med, Dept Lab Med, Boston Childrens Hosp, Boston, MA 02115 USA. [Harris, David J.; Lip, Va; Shen, Yiping] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [An, Yu] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China. [An, Yu] Fudan Univ, MOE Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China. [Lin, Michael; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02114 USA. [Schwartz, Stuart] Genzyme Genet Inc, Labcorp, Res Triangle Pk, NC 27709 USA. [Natowicz, Marvin R.] Cleveland Clin, Inst Pathol & Lab Med, Cleveland, OH 44195 USA. [Natowicz, Marvin R.] Cleveland Clin, Inst Genom Med, Cleveland, OH 44195 USA. [Shen, Yiping] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Shanghai 200127, Peoples R China. [Natowicz, Marvin R.] Cleveland Clin, Inst Neurol & Pediat, Cleveland, OH 44195 USA. RP Ernst, C (reprint author), McGill Univ, Douglas Hosp, Res Inst, Dept Psychiat, Quebec City, ON H4H 1R3, Canada. EM carl.ernst@mcgill.ca RI Ruderfer, Douglas/M-5795-2016; OI Ruderfer, Douglas/0000-0002-2365-386X; Chiang, Colby/0000-0002-4113-6065; Chen, Elizabeth/0000-0002-3573-0164; Haggarty, Stephen J./0000-0002-7872-168X FU NIH [GM061354, HD065286, K99MH095867, R33MH087896]; Simons Foundation for Autism Research; Nancy Lurie Marks Family Foundation; Canada Institute of Health Research Canada Research Chair in Psychiatric Genetics FX We thank the subjects and their families for participating in this study. This work was funded by NIH GM061354 (J.F.G. and C.C.M.), HD065286 (J.F.G.), K99MH095867 (M.E.T.), and R33MH087896 (S.J.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. M.E.T. and J.F.G. are supported by the Simons Foundation for Autism Research and the Nancy Lurie Marks Family Foundation. C.E. is funded by a Canada Institute of Health Research Canada Research Chair in Psychiatric Genetics. NR 15 TC 24 Z9 24 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC 7 PY 2012 VL 91 IS 6 BP 1128 EP 1134 DI 10.1016/j.ajhg.2012.10.016 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 055LI UT WOS:000312417400018 PM 23217328 ER PT J AU Elbers, CC Guo, YR Tragante, V van Iperen, EPA Lanktree, MB Castillo, BA Chen, F Yanek, LR Wojczynski, MK Li, YR Ferwerda, B Ballantyne, CM Buxbaum, SG Chen, YDI Chen, WM Cupples, LA Cushman, M Duan, YA Duggan, D Evans, MK Fernandes, JK Fornage, M Garcia, M Garvey, WT Glazer, N Gomez, F Harris, TB Halder, I Howard, VJ Keller, MF Kamboh, MI Kooperberg, C Kritchevsky, SB LaCroix, A Liu, K Liu, YM Musunuru, K Newman, AB Onland-Moret, NC Ordovas, J Peter, I Post, W Redline, S Reis, SE Saxena, R Schreiner, PJ Volcik, KA Wang, XB Yusuf, S Zonderland, AB Anand, SS Becker, DM Psaty, B Rader, DJ Reiner, AP Rich, SS Rotter, JI Sale, MM Tsai, MY Borecki, IB Hegele, RA Kathiresan, S Nalls, MA Taylor, HA Hakonarson, H Sivapalaratnam, S Asselbergs, FW Drenos, F Wilson, JG Keating, BJ AF Elbers, Clara C. Guo, Yiran Tragante, Vinicius van Iperen, Erik P. A. Lanktree, Matthew B. Castillo, Berta Almoguera Chen, Fang Yanek, Lisa R. Wojczynski, Mary K. Li, Yun R. Ferwerda, Bart Ballantyne, Christie M. Buxbaum, Sarah G. Chen, Yii-Der Ida Chen, Wei-Min Cupples, L. Adrienne Cushman, Mary Duan, Yanan Duggan, David Evans, Michele K. Fernandes, Jyotika K. Fornage, Myriam Garcia, Melissa Garvey, W. Timothy Glazer, Nicole Gomez, Felicia Harris, Tamara B. Halder, Indrani Howard, Virginia J. Keller, Margaux F. Kamboh, M. Ilyas Kooperberg, Charles Kritchevsky, Stephen B. LaCroix, Andrea Liu, Kiang Liu, Yongmei Musunuru, Kiran Newman, Anne B. Onland-Moret, N. Charlotte Ordovas, Jose Peter, Inga Post, Wendy Redline, Susan Reis, Steven E. Saxena, Richa Schreiner, Pamela J. Volcik, Kelly A. Wang, Xingbin Yusuf, Salim Zonderland, Alan B. Anand, Sonia S. Becker, Diane M. Psaty, Bruce Rader, Daniel J. Reiner, Alex P. Rich, Stephen S. Rotter, Jerome I. Sale, Michele M. Tsai, Michael Y. Borecki, Ingrid B. Hegele, Robert A. Kathiresan, Sekar Nalls, Michael A. Taylor, Herman A., Jr. Hakonarson, Hakon Sivapalaratnam, Suthesh Asselbergs, Folkert W. Drenos, Fotios Wilson, James G. Keating, Brendan J. TI Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations SO PLOS ONE LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; DENSITY-LIPOPROTEIN-CHOLESTEROL; SINGLE-NUCLEOTIDE POLYMORPHISM; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; CHAIN FATTY-ACIDS; METABOLIC SYNDROME; ASSOCIATION RESOURCE; NATURAL-SELECTION; YOUNG-ADULTS AB Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of similar to 2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom similar to 50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p = 8.8x10(-7) and p = 1.5x10(-6) respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 13.5x10(-1)2). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report. C1 [Elbers, Clara C.; Ferwerda, Bart; Gomez, Felicia] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [Elbers, Clara C.; Tragante, Vinicius; Onland-Moret, N. Charlotte; Asselbergs, Folkert W.] Univ Med Ctr, Dept Med Genet, Utrecht, Netherlands. [Elbers, Clara C.; Onland-Moret, N. Charlotte; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Guo, Yiran; Castillo, Berta Almoguera; Li, Yun R.; Hakonarson, Hakon; Keating, Brendan J.] Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Gen, Philadelphia, PA 19104 USA. [Guo, Yiran] BGI Shenzhen, Shenzhen, Peoples R China. [Tragante, Vinicius; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands. [van Iperen, Erik P. A.] Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, NL-1105 AZ Amsterdam, Netherlands. [Lanktree, Matthew B.] Univ Western Ontario, Dept Med, Schulich Sch Med & Dent, London, ON, Canada. [Lanktree, Matthew B.] Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON, Canada. [Chen, Fang; Chen, Wei-Min; Rich, Stephen S.; Sale, Michele M.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Yanek, Lisa R.; Becker, Diane M.] Johns Hopkins Sch Med, GeneSTAR Res Program, Div Gen Internal Med, Baltimore, MD USA. [Wojczynski, Mary K.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [Ballantyne, Christie M.] Baylor Coll Med, Houston, TX 77030 USA. [Buxbaum, Sarah G.] Jackson State Univ, Jackson Heart Study, Jackson, MS USA. [Chen, Yii-Der Ida; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Chen, Wei-Min] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Cupples, L. Adrienne; Glazer, Nicole] Boston Univ, Boston, MA 02215 USA. [Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA. [Wojczynski, Mary K.; Duan, Yanan; Borecki, Ingrid B.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA. [Wojczynski, Mary K.; Duan, Yanan; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Duggan, David] Translat Genom Res Inst, Phoenix, AZ USA. [Garcia, Melissa; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Reis, Steven E.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kooperberg, Charles; LaCroix, Andrea; Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Kritchevsky, Stephen B.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Liu, Kiang] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Liu, Yongmei] Wake Forest Univ, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Kamboh, M. Ilyas; Wang, Xingbin] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Ordovas, Jose] Tufts Univ, JM USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Post, Wendy] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA. [Redline, Susan] Brigham & Womens Hosp, Boston, MA 02115 USA. [Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Saxena, Richa] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Schreiner, Pamela J.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Volcik, Kelly A.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA. [Yusuf, Salim; Anand, Sonia S.] McMaster Univ, Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada. [Psaty, Bruce] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA. [Psaty, Bruce] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Rader, Daniel J.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA USA. [Sale, Michele M.] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA. [Sale, Michele M.] Univ Virginia, Dept Med, Charlottesville, VA USA. [Tsai, Michael Y.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Hegele, Robert A.] Univ Western Ontario, Robarts Res Inst, London, ON, Canada. [Keller, Margaux F.; Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Taylor, Herman A., Jr.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Taylor, Herman A., Jr.] Jackson State Univ, Tougaloo Coll, Jackson, MS USA. [Sivapalaratnam, Suthesh] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Drenos, Fotios] UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Cushman, Mary] Univ Vermont, Dept Med, Thrombosis & Hemostasis Program, Burlington, VT USA. [Fernandes, Jyotika K.] Med Univ S Carolina, Coll Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Howard, Virginia J.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Zonderland, Alan B.] NIA, Lab Personal & Cognit, NIH, Bethesda, MD 20892 USA. [Evans, Michele K.] NIA, Hlth Dispar Unit, NIH, Baltimore, MD 21224 USA. [Halder, Indrani] Univ Pittsburgh, Inst Heart & Vasc, Sch Med, Pittsburgh, PA USA. [Buxbaum, Sarah G.] Jackson State Univ, Sch Hlth Sci, Dept Epidemiol & Biostat, Jackson, MS USA. RP Elbers, CC (reprint author), Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. EM bkeating@mail.med.upenn.edu RI Newman, Anne/C-6408-2013; Reis, Steven/J-3957-2014; Guo, Yiran/H-4120-2011; Onland-Moret, N. Charlotte/G-9185-2011; Hegele, Robert/G-3301-2011; Buxbaum, Sarah/E-1970-2013 OI Newman, Anne/0000-0002-0106-1150; Lanktree, Matthew/0000-0002-5750-6286; Kritchevsky, Stephen/0000-0003-3336-6781; van Iperen, Erik/0000-0001-7107-3168; Guo, Yiran/0000-0002-6549-8589; Cupples, L. Adrienne/0000-0003-0273-7965; Kamboh, M. Ilyas/0000-0002-3453-1438; Buxbaum, Sarah/0000-0002-4886-3564 FU National Heart, Lung, and Blood Institute; Massachusetts Institute of Technology - Broad Institute [N01-HC-65226]; Netherlands Organization for Scientific Research (NWO); Netherlands Organisation for Health Research and Development (ZonMw) [90700342] FX The CARe Consortium wishes to acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the research institutions, study investigators, field staff and study participants in creating this resource for biomedical research. The following nine parent studies have contributed parent study data, ancillary study data, and DNA samples through the Massachusetts Institute of Technology - Broad Institute (N01-HC-65226) to create this genotype/phenotype database for wide dissemination to the biomedical research community: the Atherosclerosis Risk in Communities (ARIC) study, the Cardiovascular Health Study (CHS), the Cleveland Family Study (CFS), the Cooperative Study of Sickle Cell Disease (CSSCD), the Coronary Artery Risk Development in Young Adults (CARDIA) study, the Framingham Heart Study (FHS), the Jackson Heart Study (JHS), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Sleep Heart Health Study (SHHS). C. C. E is supported by a Rubicon grant from the Netherlands Organization for Scientific Research (NWO). F. W. A. is supported by a clinical fellowship from the Netherlands Organisation for Health Research and Development (ZonMw grant 90700342). Additional funding information can be found in the Supporting Information S1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 16 Z9 16 U1 2 U2 21 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 DEC 7 PY 2012 VL 7 IS 12 AR e50198 DI 10.1371/journal.pone.0050198 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 050OT UT WOS:000312064100013 PM 23236364 ER PT J AU Daley, GQ AF Daley, George Q. TI Cellular Alchemy and the Golden Age of Reprogramming SO CELL LA English DT Editorial Material ID EMBRYONIC STEM-CELLS; NUCLEAR TRANSPLANTATION; PARKINSONIAN MICE; DEFINED FACTORS; SOMATIC-CELLS; FIBROBLASTS AB The 2012 Nobel Prize in Medicine or Physiology recognizes the architects of two of the great paradigm-shifting discoveries of the last half-century of biology. In experiments performed nearly 50 years apart, Gurdon and Yamanaka made feasible the reawakening of pluripotency inherent in all cells and challenged forever our notions of cellular identity. C1 [Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, Boston, MA 02115 USA. [Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Daley, George Q.] Broad Inst, Boston, MA 02115 USA. [Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu FU Howard Hughes Medical Institute NR 20 TC 8 Z9 9 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD DEC 7 PY 2012 VL 151 IS 6 BP 1151 EP 1154 DI 10.1016/j.cell.2012.11.016 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 049RA UT WOS:000311999900002 PM 23217698 ER PT J AU Sebastian, C Zwaans, BMM Silberman, DM Gymrek, M Goren, A Zhong, L Ram, O Truelove, J Guimaraes, AR Toiber, D Cosentino, C Greenson, JK MacDonald, AI McGlynn, L Maxwell, F Edwards, J Giacosa, S Guccione, E Weissleder, R Bernstein, BE Regev, A Shiels, PG Lombard, DB Mostoslavsky, R AF Sebastian, Carlos Zwaans, Bernadette M. M. Silberman, Dafne M. Gymrek, Melissa Goren, Alon Zhong, Lei Ram, Oren Truelove, Jessica Guimaraes, Alexander R. Toiber, Debra Cosentino, Claudia Greenson, Joel K. MacDonald, Alasdair I. McGlynn, Liane Maxwell, Fraser Edwards, Joanne Giacosa, Sofia Guccione, Ernesto Weissleder, Ralph Bernstein, Bradley E. Regev, Aviv Shiels, Paul G. Lombard, David B. Mostoslavsky, Raul TI The Histone Deacetylase SIRT6 Is a Tumor Suppressor that Controls Cancer Metabolism SO CELL LA English DT Article ID MULTIPLE INTESTINAL NEOPLASIA; RNA-POLYMERASE-I; C-MYC; GENE-EXPRESSION; RIBOSOMAL DNA; LIFE-SPAN; GROWTH; TRANSCRIPTION; STRESS; PROLIFERATION AB Reprogramming of cellular metabolism is a key event during tumorigenesis. Despite being known for decades (Warburg effect), the molecular mechanisms regulating this switch remained unexplored. Here, we identify SIRT6 as a tumor suppressor that regulates aerobic glycolysis in cancer cells. Importantly, loss of SIRT6 leads to tumor formation without activation of known oncogenes, whereas transformed SIRT6-deficient cells display increased glycolysis and tumor growth, suggesting that SIRT6 plays a role in both establishment and maintenance of cancer. By using a conditional SIRT6 allele, we show that SIRT6 deletion in vivo increases the number, size, and aggressiveness of tumors. SIRT6 also functions as a regulator of ribosome metabolism by corepressing MYC transcriptional activity. Lastly, Sirt6 is selectively downregulated in several human cancers, and expression levels of SIRT6 predict prognosis and tumor-free survival rates, highlighting SIRT6 as a critical modulator of cancer metabolism. Our studies reveal SIRT6 to be a potent tumor suppressor acting to suppress cancer metabolism. C1 [Zwaans, Bernadette M. M.; Greenson, Joel K.; Lombard, David B.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Lombard, David B.] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. [Sebastian, Carlos; Silberman, Dafne M.; Goren, Alon; Zhong, Lei; Ram, Oren; Toiber, Debra; Cosentino, Claudia; Giacosa, Sofia; Bernstein, Bradley E.; Mostoslavsky, Raul] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Goren, Alon; Ram, Oren; Bernstein, Bradley E.; Regev, Aviv] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Gymrek, Melissa; Bernstein, Bradley E.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Gymrek, Melissa] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Goren, Alon; Ram, Oren; Regev, Aviv] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Goren, Alon; Ram, Oren; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Goren, Alon; Ram, Oren; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Goren, Alon; Ram, Oren; Truelove, Jessica; Guimaraes, Alexander R.; Weissleder, Ralph; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Regev, Aviv] MIT, Dept Biol, Cambridge, MA 02140 USA. [MacDonald, Alasdair I.; McGlynn, Liane; Maxwell, Fraser; Edwards, Joanne; Shiels, Paul G.] Univ Glasgow, MVLS, Inst Canc Sci, Glasgow G12 8QQ, Lanark, Scotland. [Guccione, Ernesto] Inst Mol & Cell Biol, Proteos 138673, Singapore. [Silberman, Dafne M.] CEFyBO UBA CONICET, Sch Med, Dept Human Biochem, Buenos Aires, DF, Argentina. RP Lombard, DB (reprint author), Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. EM davidlom@umich.edu; rmostoslavsky@mgh.harvard.edu RI ASTAR, IMCB/E-2320-2012; Edwards, Joanne/J-1903-2015; OI Edwards, Joanne/0000-0002-7192-6906; /0000-0002-6086-3903 FU NIH [GM093072-01, DK088190-01A1, GM101171]; Sidney Kimmel Cancer Research Foundation; Richard D. and Katherine M. O'Connor Research Fund of the University of Michigan Comprehensive Cancer Center; Nathan Shock Center [AG013283]; Pardee Foundation; Beatriu de Pinos Postdoctoral Fellowship (Generalitat de Catalunya); National Defense Science and Engineering Graduate Fellowship; Brain Power for Israel Foundation; Fondazione Umberto Veronesi; NHGRI Center of Excellence in Genome Science [P50HG006193] FX This work was supported by NIH awards GM093072-01 and DK088190-01A1 (R.M.) and GM101171 (D.B.L.), the Sidney Kimmel Cancer Research Foundation (R.M.), the Richard D. and Katherine M. O'Connor Research Fund of the University of Michigan Comprehensive Cancer Center (D.B.L.), the Nathan Shock Center (AG013283; D.B.L.), and the Pardee Foundation (D.B.L.). R.M. is a Howard Goodman Scholar and an MGH Research Scholar. D.B.L. is a New Scholar in Aging of the Ellison Medical Foundation. C.S. is the recipient of a Beatriu de Pinos Postdoctoral Fellowship (Generalitat de Catalunya). M.G. is supported by a National Defense Science and Engineering Graduate Fellowship. D.T. is the recipient of the Brain Power for Israel Foundation. C.C. is supported by a Fellowship from the Fondazione Umberto Veronesi. A.R. is supported by a P50HG006193 from the NHGRI Center of Excellence in Genome Science. D.B.L. would like to thank Dr. Chuxia Deng (NIDDK/NIH) for the floxed SIRT6 mouse strain. We thank Nabeel Bardeesy, Eric Fearon, Alexandros Tzatsos, Polina Paskaleva, Kevin Haigis, Agustina D'Urso, Marco Bezzi, and the Mostoslavsky and Lombard labs for technical advice, reagents, and helpful discussions. We thank the ENCODE Chromatin Project at the Broad Institute for data sharing. R.M. is a member of Sirtris scientific advisory board. NR 44 TC 216 Z9 226 U1 3 U2 125 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD DEC 7 PY 2012 VL 151 IS 6 BP 1185 EP 1199 DI 10.1016/j.cell.2012.10.047 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 049RA UT WOS:000311999900010 PM 23217706 ER PT J AU Xu, YF Xu, C Kato, A Tempel, W Abreu, JG Bian, CB Hu, YG Hu, D Zhao, B Cerovina, T Diao, JB Wu, FZ He, HH Cui, QY Clark, E Ma, C Barbara, A Veenstra, GJC Xu, GL Kaiser, UB Liu, XS Sugrue, SP He, X Min, JR Kato, Y Shi, YG AF Xu, Yufei Xu, Chao Kato, Akiko Tempel, Wolfram Abreu, Jose Garcia Bian, Chuanbing Hu, Yeguang Hu, Di Zhao, Bin Cerovina, Tanja Diao, Jianbo Wu, Feizhen He, Housheng Hansen Cui, Qingyan Clark, Erin Ma, Chun Barbara, Andrew Veenstra, Gert Jan C. Xu, Guoliang Kaiser, Ursula B. Liu, X. Shirley Sugrue, Stephen P. He, Xi Min, Jinrong Kato, Yoichi Shi, Yujiang Geno TI Tet3 CXXC Domain and Dioxygenase Activity Cooperatively Regulate Key Genes for Xenopus Eye and Neural Development SO CELL LA English DT Article ID EMBRYONIC STEM-CELLS; DNA METHYLATION; MAMMALIAN DNA; SELF-RENEWAL; 5-HYDROXYMETHYLCYTOSINE; MOUSE; 5-METHYLCYTOSINE; PROTEINS; GENOME; 5-CARBOXYLCYTOSINE AB Ten-Eleven Translocation (Tet) family of dioxygenases dynamically regulates DNA methylation and has been implicated in cell lineage differentiation and oncogenesis. Yet their functions and mechanisms of action in gene regulation and embryonic development are largely unknown. Here, we report that Xenopus Tet3 plays an essential role in early eye and neural development by directly regulating a set of key developmental genes. Tet3 is an active 5mC hydroxylase regulating the 5mC/5hmC status at target gene promoters. Biochemical and structural studies further demonstrate that the Tet3 CXXC domain is critical for specific Tet3 targeting. Finally, we show that the enzymatic activity and CXXC domain are both crucial for Tet3's biological function. Together, these findings define Tet3 as a transcription regulator and reveal a molecular mechanism by which the 5mC hydroxylase and DNA binding activities of Tet3 cooperate to control target gene expression and embryonic development. C1 [Xu, Chao; Tempel, Wolfram; Bian, Chuanbing; Cerovina, Tanja; Min, Jinrong] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada. [Xu, Yufei; Hu, Yeguang; Hu, Di; Clark, Erin; Ma, Chun; Barbara, Andrew; Kaiser, Ursula B.; Shi, Yujiang Geno] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens,Dept Med, Boston, MA 02115 USA. [Xu, Chao; Tempel, Wolfram; Bian, Chuanbing; Cerovina, Tanja; Min, Jinrong] Univ Toronto, Dept Physiol, Toronto, ON M5G 1L7, Canada. [Kato, Akiko; Kato, Yoichi] Florida State Univ, Coll Med, Dept Biomed Sci, Tallahassee, FL 32306 USA. [Abreu, Jose Garcia; He, Xi] Harvard Univ, Sch Med, Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Hu, Di; Zhao, Bin; Diao, Jianbo; Wu, Feizhen; Ma, Chun] Fudan Univ, Inst Biomed Sci, Lab Epigenet, Shanghai 200032, Peoples R China. [He, Housheng Hansen; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [He, Housheng Hansen; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Cui, Qingyan; Xu, Guoliang] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China. [Veenstra, Gert Jan C.] Radboud Univ Nijmegen, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands. [Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Sugrue, Stephen P.] Univ Florida, Dept Anat & Cell Biol, Gainesville, FL 32610 USA. RP Min, JR (reprint author), Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada. EM jr.min@utoronto.ca; yoichi.kato@med.fsu.edu; yujiang_shi@hms.harvard.edu RI PCM, PG/D-1034-2013; Neurociencia, Inct/I-1011-2013; Min, Jinrong/G-3449-2011; Abreu, Jose/G-6159-2010; Veenstra, Gert Jan C./D-4963-2012; Xu, Chao/G-3885-2010 OI Abreu, Jose/0000-0002-9875-7786; Veenstra, Gert Jan C./0000-0002-7787-4940; Xu, Chao/0000-0003-0444-7080 FU NIH [GM078458, GM087641, GM074241]; Brigham and Women's Hospital Biomedical Research Institute; Chinese Ministry of Education Project 985; CNPq (Brazil); Boston Children's Hospital Intellectual and Developmental Disabilities Research Center [P30 HD-18655]; Canadian Institutes for Health Research; Canadian Foundation for Innovation; Genome Canada through Ontario Genomics Institute; GlaxoSmithKline; Eli Lilly; Pfizer; Novartis Research Foundation; Life Technologies; Ontario Innovation Trust; Ontario Ministry for Research and Innovation; Wellcome Trust; U.S. Department of Energy, Office of Biological and Environmental Research [DE-AC02-06CH11357] FX We thank R. Harland for helpful discussions, A Khorasani for critical reading of the manuscript and Q. Xu and L. Jiang for statistical analyses. We also thank R. Moon, W. Harris, J. Yang, X. Wang, M. Vetter and J.-P. Saint-Jeannet for valuable discussions and technical help. This work was supported by NIH grants GM078458 to Y.G.S., GM087641 to Y.K., and GM074241 to X.H., Brigham and Women's Hospital Biomedical Research Institute fund to sustain research excellence to Y.G.S., and Chinese Ministry of Education Project 985 to Biomedical Core Facility, Fudan University. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. J. G. A. was funded partially by CNPq (Brazil). Y.G.S. is a Pew Scholar. X. H. acknowledges support by Boston Children's Hospital Intellectual and Developmental Disabilities Research Center (P30 HD-18655). The Structural Genomics Consortium is a registered charity (No. 1097737) that receives funds from Canadian Institutes for Health Research, Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Eli Lilly, Pfizer, Novartis Research Foundation, Life Technologies, Ontario Innovation Trust, Ontario Ministry for Research and Innovation and Wellcome Trust (JM). Argonne National Laboratory is operated by UChicago Argonne, LLC, for the U.S. Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357. NR 30 TC 97 Z9 102 U1 2 U2 58 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD DEC 7 PY 2012 VL 151 IS 6 BP 1200 EP 1213 DI 10.1016/j.cell.2012.11.014 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 049RA UT WOS:000311999900011 PM 23217707 ER PT J AU Ruas, JL White, JP Rao, RR Kleiner, S Brannan, KT Harrison, BC Greene, NP Wu, J Estall, JL Irving, BA Lanza, IR Rasbach, KA Okutsu, M Nair, KS Yan, Z Leinwand, LA Spiegelman, BM AF Ruas, Jorge L. White, James P. Rao, Rajesh R. Kleiner, Sandra Brannan, Kevin T. Harrison, Brooke C. Greene, Nicholas P. Wu, Jun Estall, Jennifer L. Irving, Brian A. Lanza, Ian R. Rasbach, Kyle A. Okutsu, Mitsuharu Nair, K. Sreekumaran Yan, Zhen Leinwand, Leslie A. Spiegelman, Bruce M. TI A PGC-1 alpha Isoform Induced by Resistance Training Regulates Skeletal Muscle Hypertrophy SO CELL LA English DT Article ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; MICE; ATROPHY; GROWTH; FIBERS; MASS; HOMEOSTASIS; METABOLISM; EXPRESSION; MYOSTATIN AB PGC-1 alpha is a transcriptional coactivator induced by exercise that gives muscle many of the best known adaptations to endurance-type exercise but has no effects on muscle strength or hypertrophy. We have identified a form of PGC-1 alpha (PGC-1 alpha 4) that results from alternative promoter usage and splicing of the primary transcript. PGC-1 alpha 4 is highly expressed in exercised muscle but does not regulate most known PGC-1 alpha targets such as the mitochondrial OXPHOS genes. Rather, it specifically induces IGF1 and represses myostatin, and expression of PGC-1 alpha 4 in vitro and in vivo induces robust skeletal muscle hypertrophy. Importantly, mice with skeletal muscle-specific transgenic expression of PGC-1 alpha 4 show increased muscle mass and strength and dramatic resistance to the muscle wasting of cancer cachexia. Expression of PGC-1 alpha 4 is preferentially induced in mouse and human muscle during resistance exercise. These studies identify a PGC-1 alpha protein that regulates and coordinates factors involved in skeletal muscle hypertrophy. C1 [Ruas, Jorge L.; White, James P.; Rao, Rajesh R.; Kleiner, Sandra; Brannan, Kevin T.; Wu, Jun; Estall, Jennifer L.; Rasbach, Kyle A.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. [Harrison, Brooke C.; Leinwand, Leslie A.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. [Greene, Nicholas P.; Okutsu, Mitsuharu; Yan, Zhen] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA. [Irving, Brian A.; Lanza, Ian R.; Nair, K. Sreekumaran] Mayo Clin, Div Endocrinol, Endocrine Res Unit, Rochester, MN 55905 USA. RP Ruas, JL (reprint author), Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden. EM jorge.ruas@ki.se; bruce_spiegelman@dfci.harvard.edu RI Greene, Nicholas/A-6076-2013; Greene, Nicholas/G-7399-2015; Irving, Brian/B-9683-2016; OI Greene, Nicholas/0000-0002-9504-9362; Irving, Brian/0000-0002-4131-9523; LEINWAND, LESLIE/0000-0003-1470-4810; Ruas, Jorge/0000-0002-1110-2606 FU NIH [DK061562, 5K01AR55676-2, T32HL07284, AR050429, GM29090]; Novartis; Wenner-Gren Foundations, Sweden; AHA [09POST2010078, 12SDG8070003]; Novartis, Inc.; [RR024151]; [AG09531] FX We thank Drs. Srikripa Devarakonda and Sibylle Jager for valuable discussions. ERR alpha and ERR gamma KO myoblasts were a kind gift from Dr. Zhidan Wu (Novartis Institutes for Biomedical Research). The MEF2C/Myogenin promoter cassette was kindly provided by Dr. Eric Olson (University of Texas Southwestern Medical Center). LLC cells were kindly donated by Dr. Jose M. Garcia (Baylor College of Medicine). This project was supported by grants (DK061562) from the NIH and from Novartis to B.M.S. J.L.R. was supported in part by a grant from the Wenner-Gren Foundations, Sweden. This research was supported in part by grants to B. C. H. (NIH, 5K01AR55676-2), N.P.G. (NIH, T32HL07284), J.W. (AHA, 09POST2010078 and 12SDG8070003), B.A.I. (RR024151 and AG09531), Z.Y. (NIH, AR050429), and L. A. L. (NIH, GM29090). B. M. S. is a shareholder and consultant to Ember Therapeutics and has received funding in the form of sponsored research from Novartis, Inc. NR 40 TC 172 Z9 176 U1 3 U2 48 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD DEC 7 PY 2012 VL 151 IS 6 BP 1319 EP 1331 DI 10.1016/j.cell.2012.10.050 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 049RA UT WOS:000311999900020 PM 23217713 ER PT J AU Han, D Ybanez, MD Johnson, HS McDonald, JN Mesropyan, L Sancheti, H Martin, G Martin, A Lim, AM Dara, L Cadenas, E Tsukamoto, H Kaplowitz, N AF Han, Derick Ybanez, Maria D. Johnson, Heather S. McDonald, Jeniece N. Mesropyan, Lusine Sancheti, Harsh Martin, Gary Martin, Alanna Lim, Atalie M. Dara, Lily Cadenas, Enrique Tsukamoto, Hidekazu Kaplowitz, Neil TI Dynamic Adaptation of Liver Mitochondria to Chronic Alcohol Feeding in Mice BIOGENESIS, REMODELING, AND FUNCTIONAL ALTERATIONS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SKELETAL-MUSCLE MITOCHONDRIA; CHRONIC ETHANOL-CONSUMPTION; RAT-LIVER; ENERGY-METABOLISM; DEPENDENT HEPATOTOXICITY; SUPEROXIDE ANION; SWIFT INCREASE; FAT DIET; NECROSIS; EXERCISE AB Liver mitochondria undergo dynamic alterations following chronic alcohol feeding to mice. Intragastric alcohol feeding to mice resulted in 1) increased state III respiration (109% compared with control) in isolated liver mitochondria, probably due to increased levels of complexes I, IV, and V being incorporated into the respiratory chain; 2) increased mitochondrial NAD(+) and NADH levels (similar to 2-fold), with no change in the redox status; 3) alteration in mitochondrial morphology, with increased numbers of elongated mitochondria; and 4) enhanced mitochondrial biogenesis in the liver, which corresponded with an up-regulation of PGC-1 alpha (peroxisome proliferator-activated receptor gamma coactivator-1 alpha). Oral alcohol feeding to mice, which is associated with less liver injury and steatosis, slightly enhanced respiration in isolated liver mitochondria (30.8% compared with control), lower than the striking increase caused by intragastric alcohol feeding. Mitochondrial respiration increased with both oral and intragastric alcohol feeding despite extensive N-acetylation of mitochondrial proteins. The alcohol-induced mitochondrial alterations are probably an adaptive response to enhance alcohol metabolism in the liver. Isolated liver mitochondria from alcohol-treated mice had a greater rate of acetaldehyde metabolism and respiration when treated with acetaldehyde than control. Aldehyde dehydrogenase-2 levels were unaltered in response to alcohol, suggesting that the greater acetaldehyde metabolism by isolated mitochondria from alcohol-treated mice was due to increased mitochondrial respiration that regenerated NAD(+), the rate-limiting substrate in alcohol/acetaldehyde metabolism. Overall, our work suggests that mitochondrial plasticity in the liver may be an important adaptive response to the metabolic stress caused by alcohol intake and could potentially play a role in many other vital functions performed by the liver. C1 [Han, Derick; Lim, Atalie M.; Dara, Lily; Kaplowitz, Neil] Univ So Calif, Keck Sch Med, Res Ctr Liver Dis, Los Angeles, CA 90089 USA. [Lim, Atalie M.; Dara, Lily; Kaplowitz, Neil] Univ So Calif, Keck Sch Med, So Calif Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA 90089 USA. [Sancheti, Harsh; Cadenas, Enrique] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA. [Martin, Gary; Martin, Alanna] Occidental Coll, Dept Biol, Los Angeles, CA 90041 USA. [Tsukamoto, Hidekazu] Univ So Calif, Keck Sch Med, So Calif Res Ctr Alcohol Liver & Pancreat Dis & C, Los Angeles, CA 90089 USA. [Tsukamoto, Hidekazu] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90089 USA. [Tsukamoto, Hidekazu] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90089 USA. RP Han, D (reprint author), Univ So Calif, Keck Sch Med, Res Ctr Liver Dis, 2011 Zonal Ave,HMR 101, Los Angeles, CA 90089 USA. EM derickh@usc.edu OI Sancheti, Harsh/0000-0001-8084-4550 FU National Institutes of Health Grant [AA016911, AA14428, P50AA11999] FX This work was supported, in whole or in part, by National Institutes of Health Grant AA016911 (to D. H.), AA14428 (to N. K.), and P50AA11999 (to H. T.). NR 57 TC 23 Z9 23 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 7 PY 2012 VL 287 IS 50 BP 42165 EP 42179 DI 10.1074/jbc.M112.377374 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 051CT UT WOS:000312103000054 PM 23086958 ER PT J AU Kimani, S Ghosh, G Ghogare, A Rudshteyn, B Bartusik, D Hasan, T Greer, A AF Kimani, Stanley Ghosh, Goutam Ghogare, Ashwini Rudshteyn, Benjamin Bartusik, Dorota Hasan, Tayyaba Greer, Alexander TI Synthesis and Characterization of Mono-, Di-, and Tri-Poly(ethylene glycol) Chlorin e(6) Conjugates for the Photokilling of Human Ovarian Cancer Cells SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SINGLET OXYGEN; PHOTODYNAMIC THERAPY; SUBCELLULAR-LOCALIZATION; CELLULAR UPTAKE; DERIVATIVES; LIFETIME; DYES; PH; E6; PHOTOSENSITIZER AB PEGylated chlorin e(6) photosensitizers were synthesized with tri(ethylene glycol) attached at the ester bond(s) for a 1:1 conjugate at the 173-position, a 2:1 conjugate at the 15(2)- and 17(3)-positions, and a 3:1 conjugate at the 13(1)-, 15(2)-, and 17(3)-positions. These chlorin sensitizers were studied for hydrolytic stability and solubility, as well as ovarian OVCAR-5 cancer cell uptake, localization, and phototoxicity. Increasing numbers of the PEG groups in the mono-, di-, and tri-PEG chlorin conjugates increased the water solubility and sensitivity to hydrolysis and uptake into the ovarian cancer cells. The PEG chlorin conjugates accumulated in the cytoplasm and mitrochondria, but not in lysosomes. Higher phototoxicity was roughly correlated with higher numbers of PEG groups, with the tri-PEG chlorin conjugate showing the best overall ovarian cancer cell photokilling of the series. Singlet oxygen lifetimes, solvent deuteration, and the effects of additives azide ion and D-mannitol were examined to help clarify the photokilling mechanisms. A Type-II (singlet oxygen) photosensitized mechanism is suggested for the di- and tri-PEG chlorin conjugates; however, a more complicated process based in part on a Type-I (radicals or radical ions) mechanism is suggested for the parent chlorin e6 and the mono-PEG chlorin conjugate. C1 [Kimani, Stanley; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kimani, Stanley; Hasan, Tayyaba] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kimani, Stanley; Ghosh, Goutam; Ghogare, Ashwini; Rudshteyn, Benjamin; Bartusik, Dorota; Greer, Alexander] CUNY Brooklyn Coll, Dept Chem, Brooklyn, NY 11210 USA. [Kimani, Stanley; Ghosh, Goutam; Ghogare, Ashwini; Rudshteyn, Benjamin; Bartusik, Dorota; Greer, Alexander] CUNY Brooklyn Coll, Grad Ctr, Brooklyn, NY 11210 USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM thasan@partners.org; agreer@brooklyn.cuny.edu FU NIH-National Institute of General Medical Sciences [SC1GM093830]; NIH-National Cancer Institute [5R01CA160998]; Barry M. Goldwater Scholarship; Arnold and Ruth T. Kaufman Undergraduate Chemistry Research Award at Brooklyn College FX S.K., G.G., A.G., B.R., D.B., and A.G. acknowledge support from the NIH-National Institute of General Medical Sciences (SC1GM093830). Grant support to T.H. was provided by the NIH-National Cancer Institute (5R01CA160998). B.R. is the recipient of a Barry M. Goldwater Scholarship and the Arnold and Ruth T. Kaufman Undergraduate Chemistry Research Award at Brooklyn College. Computational support was provided by the College of Staten Island CUNY High Performance Computing Facility. We also thank Leda Lee for the graphic arts work. NR 44 TC 9 Z9 9 U1 2 U2 35 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD DEC 7 PY 2012 VL 77 IS 23 BP 10638 EP 10647 DI 10.1021/jo301889s PG 10 WC Chemistry, Organic SC Chemistry GA 048PX UT WOS:000311926100018 PM 23126407 ER PT J AU Moseley, CK Carlin, SM Neelamegam, R Hooker, JM AF Moseley, Christian K. Carlin, Stephen M. Neelamegam, Ramesh Hooker, Jacob M. TI An Efficient and Practical Radiosynthesis of [C-11]Temozolomide SO ORGANIC LETTERS LA English DT Article ID ANTITUMOR DRUG TEMOZOLOMIDE; POSITRON-EMISSION-TOMOGRAPHY; IMIDAZOTETRAZINES; ACTIVATION; ROUTES AB Temozolomide (TMZ) is a prodrug for an alkylating agent used for the treatment of malignant brain tumors. A positron emitting version, [C-11]TMZ, has been utilized to help elucidate the mechanism and biodistribution of TMZ. Challenges in [C-11]TMZ synthesis and reformulation make it difficult for routine production. A highly reproducible one-pot radiosynthesis of [C-11]TMZ with a radiochemical yield of 17 +/- 5% and >= 97% radiochemical purity is reported. C1 [Moseley, Christian K.; Carlin, Stephen M.; Neelamegam, Ramesh; Hooker, Jacob M.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Hooker, JM (reprint author), Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM hooker@nmr.mgh.harvard.edu OI Hooker, Jacob/0000-0002-9394-7708 FU NCRR NIH HHS [S10 RR026666, S10 RR017208] NR 15 TC 5 Z9 5 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD DEC 7 PY 2012 VL 14 IS 23 BP 5872 EP 5875 DI 10.1021/ol302791x PG 4 WC Chemistry, Organic SC Chemistry GA 048PW UT WOS:000311926000016 PM 23151019 ER PT J AU Jia, X Schumann, J Paganetti, H Jiang, SB AF Jia, Xun Schuemann, Jan Paganetti, Harald Jiang, Steve B. TI GPU-based fast Monte Carlo dose calculation for proton therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID DEFORMABLE IMAGE REGISTRATION; TRACK-REPEATING ALGORITHM; CLINICAL IMPLEMENTATION; GRAPHICS HARDWARE; PLAN OPTIMIZATION; RADIATION-THERAPY; BEAM THERAPY; RECONSTRUCTION; RADIOTHERAPY; SIMULATION AB Accurate radiation dose calculation is essential for successful proton radiotherapy. Monte Carlo (MC) simulation is considered to be the most accurate method. However, the long computation time limits it from routine clinical applications. Recently, graphics processing units (GPUs) have been widely used to accelerate computationally intensive tasks in radiotherapy. We have developed a fast MC dose calculation package, gPMC, for proton dose calculation on a GPU. In gPMC, proton transport is modeled by the class II condensed history simulation scheme with a continuous slowing down approximation. Ionization, elastic and inelastic proton nucleus interactions are considered. Energy straggling and multiple scattering are modeled. Secondary electrons are not transported and their energies are locally deposited. After an inelastic nuclear interaction event, a variety of products are generated using an empirical model. Among them, charged nuclear fragments are terminated with energy locally deposited. Secondary protons are stored in a stack and transported after finishing transport of the primary protons, while secondary neutral particles are neglected. gPMC is implemented on the GPU under the CUDA platform. We have validated gPMC using the TOPAS/Geant4 MC code as the gold standard. For various cases including homogeneous and inhomogeneous phantoms as well as a patient case, good agreements between gPMC and TOPAS/Geant4 are observed. The gamma passing rate for the 2%/2 mm criterion is over 98.7% in the region with dose greater than 10% maximum dose in all cases, excluding low-density air regions. With gPMC it takes only 6-22 s to simulate 10 million source protons to achieve similar to 1% relative statistical uncertainty, depending on the phantoms and energy. This is an extremely high efficiency compared to the computational time of tens of CPU hours for TOPAS/Geant4. Our fast GPU-based code can thus facilitate the routine use of MC dose calculation in proton therapy. C1 [Jia, Xun; Jiang, Steve B.] Univ Calif San Diego, Ctr Adv Radiotherapy Technol, Dept Radiat Med & Appl Sci, La Jolla, CA 92037 USA. [Schuemann, Jan; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Schuemann, Jan; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jia, X (reprint author), Univ Calif San Diego, Ctr Adv Radiotherapy Technol, Dept Radiat Med & Appl Sci, La Jolla, CA 92037 USA. EM xunjia@ucsd.edu; jschuemann@partners.org; hpaganetti@partners.org; sbjiang@ucsd.edu FU University of California; [R01 CA140735] FX This work is supported in part by the University of California Lab Fees Research Program and in part by R01 CA140735 ('PBeam: Fast and Easy Monte Carlo System for Proton Therapy'). NR 41 TC 49 Z9 50 U1 2 U2 26 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD DEC 7 PY 2012 VL 57 IS 23 BP 7783 EP 7797 DI 10.1088/0031-9155/57/23/7783 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 040UX UT WOS:000311351400009 PM 23128424 ER PT J AU Norton, WE McCannon, CJ Schall, MW Mittman, BS AF Norton, Wynne E. McCannon, C. Joseph Schall, Marie W. Mittman, Brian S. TI A stakeholder-driven agenda for advancing the science and practice of scale-up and spread in health SO IMPLEMENTATION SCIENCE LA English DT Article DE Scale-up; Spread; Healthcare; Public health; Improvement; Implementation; Dissemination; Health systems research; Healthcare delivery ID INTERNATIONAL HEALTH; IMPROVEMENT; CARE; RECOMMENDATIONS; ORGANIZATIONS; INNOVATIONS; SERVICES AB Background: Although significant advances have been made in implementation science, comparatively less attention has been paid to broader scale-up and spread of effective health programs at the regional, national, or international level. To address this gap in research, practice and policy attention, representatives from key stakeholder groups launched an initiative to identify gaps and stimulate additional interest and activity in scale-up and spread of effective health programs. We describe the background and motivation for this initiative and the content, process, and outcomes of two main phases comprising the core of the initiative: a state-of-the-art conference to develop recommendations for advancing scale-up and spread and a follow-up activity to operationalize and prioritize the recommendations. The conference was held in Washington, D. C. during July 2010 and attended by 100 representatives from research, practice, policy, public health, healthcare, and international health communities; the follow-up activity was conducted remotely the following year. Discussion: Conference attendees identified and prioritized five recommendations (and corresponding sub-recommendations) for advancing scale-up and spread in health: increase awareness, facilitate information exchange, develop new methods, apply new approaches for evaluation, and expand capacity. In the follow-up activity, 'develop new methods' was rated as most important recommendation; expanding capacity was rated as least important, although differences were relatively minor. Summary: Based on the results of these efforts, we discuss priority activities that are needed to advance research, practice and policy to accelerate the scale-up and spread of effective health programs. C1 [Norton, Wynne E.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Hlth Behav, Birmingham, AL 35294 USA. [McCannon, C. Joseph; Schall, Marie W.] Inst Healthcare Improvement, Cambridge, MA 02138 USA. [Mittman, Brian S.] VA Greater Los Angeles Healthcare Syst, VA Ctr Implementat Practice & Res Support, North Hills, CA 91343 USA. RP Norton, WE (reprint author), Univ Alabama Birmingham, Sch Publ Hlth, Dept Hlth Behav, 1665 Univ Blvd, Birmingham, AL 35294 USA. EM wenorton@uab.edu OI Mittman, Brian/0000-0003-3589-9178 FU Agency for Healthcare Research and Quality [1R13HS019422-01]; Commonwealth Fund [20100353]; Veterans Health Administration; Quality Enhancement Research Initiative; John A. Hartford Foundation; Patrick and Catherine Weldon Donaghue Medical Research Foundation FX The state-of-the-art conference on scale-up/spread was supported by grant 1R13HS019422-01 from the Agency for Healthcare Research and Quality (PI: McCannon); grant #20100353 from the Commonwealth Fund (PI: McCannon); funding from The Veterans Health Administration, Quality Enhancement Research Initiative, The John A. Hartford Foundation, and The Patrick and Catherine Weldon Donaghue Medical Research Foundation. Views expressed in this paper do not necessarily reflect the official policies of the Department of Health and Human Services or Department of Veterans Affairs; nor does mention of trade names, commercial practices, or organizations imply endorsement by the US Government. NR 33 TC 6 Z9 6 U1 1 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD DEC 6 PY 2012 VL 7 AR 118 DI 10.1186/1748-5908-7-118 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 104AY UT WOS:000315962700001 PM 23216748 ER PT J AU Huang, J Sabater-Lleal, M Asselbergs, FW Tregouet, D Shin, SY Ding, JZ Baumert, J Oudot-Mellakh, T Folkersen, L Johnson, AD Smith, NL Williams, SM Ikram, MA Kleber, ME Becker, DM Truong, V Mychaleckyj, JC Tang, WH Yang, Q Sennblad, B Moore, JH Williams, FMK Dehghan, A Silbernagel, G Schrijvers, EMC Smith, S Karakas, M Tofler, GH Silveira, A Navis, GJ Lohman, K Chen, MH Peters, A Goel, A Hopewell, JC Chambers, JC Saleheen, D Lundmark, P Psaty, BM Strawbridge, RJ Boehm, BO Carter, AM Meisinger, C Peden, JF Bis, JC McKnight, B Ohrvik, J Taylor, K Franzosi, MG Seedorf, U Collins, R Franco-Cereceda, A Syvanen, AC Goodall, AH Yanek, LR Cushman, M Muller-Nurasyid, M Folsom, AR Basu, S Matijevic, N van Gilst, WH Kooner, JS Hofman, A Danesh, J Clarke, R Meigs, JB Kathiresan, S Reilly, MP Klopp, N Harris, TB Winkelmann, BR Grant, PJ Hillege, HL Watkins, H Spector, TD Becker, LC Tracy, RP Marz, W Uitterlinden, AG Eriksson, P Cambien, F Morange, PE Koenig, W Soranzo, N van der Harst, P Liu, YM O'Donnell, CJ Hamsten, A AF Huang, Jie Sabater-Lleal, Maria Asselbergs, Folkert W. Tregouet, David Shin, So-Youn Ding, Jingzhong Baumert, Jens Oudot-Mellakh, Tiphaine Folkersen, Lasse Johnson, Andrew D. Smith, Nicholas L. Williams, Scott M. Ikram, Mohammad A. Kleber, Marcus E. Becker, Diane M. Vinh Truong Mychaleckyj, Josyf C. Tang, Weihong Yang, Qiong Sennblad, Bengt Moore, Jason H. Williams, Frances M. K. Dehghan, Abbas Silbernagel, Guenther Schrijvers, Elisabeth M. C. Smith, Shelly Karakas, Mahir Tofler, Geoffrey H. Silveira, Angela Navis, Gerjan J. Lohman, Kurt Chen, Ming-Huei Peters, Annette Goel, Anuj Hopewell, Jemma C. Chambers, John C. Saleheen, Danish Lundmark, Per Psaty, Bruce M. Strawbridge, Rona J. Boehm, Bernhard O. Carter, Angela M. Meisinger, Christa Peden, John F. Bis, Joshua C. McKnight, Barbara Ohrvik, John Taylor, Kent Franzosi, Maria Grazia Seedorf, Udo Collins, Rory Franco-Cereceda, Anders Syvaenen, Ann-Christine Goodall, Alison H. Yanek, Lisa R. Cushman, Mary Mueller-Nurasyid, Martina Folsom, Aaron R. Basu, Saonli Matijevic, Nena van Gilst, Wiek H. Kooner, Jaspal S. Hofman, Albert Danesh, John Clarke, Robert Meigs, James B. Kathiresan, Sekar Reilly, Muredach P. Klopp, Norman Harris, Tamara B. Winkelmann, Bernhard R. Grant, Peter J. Hillege, Hans L. Watkins, Hugh Spector, Timothy D. Becker, Lewis C. Tracy, Russell P. Maerz, Winfried Uitterlinden, Andre G. Eriksson, Per Cambien, Francois Morange, Pierre-Emmanuel Koenig, Wolfgang Soranzo, Nicole van der Harst, Pim Liu, Yongmei O'Donnell, Christopher J. Hamsten, Anders CA DIAGRAM Consortium CARDIoGRAM Consortium C4D Consortium CARDIOGENICS Consortium TI Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation SO BLOOD LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; CORONARY-ARTERY-DISEASE; MYOCARDIAL-INFARCTION; GENETIC-VARIATION; SUSCEPTIBILITY LOCI; TYPE-1 EXPRESSION; CIRCADIAN CLOCK; PLASMA-LEVELS; TISSUE; RISK AB We conducted a genome-wide association study to identify novel associations between genetic variants and circulating plasminogen activator inhibitor-1 (PAI-1) concentration, and examined functional implications of variants and genes that were discovered. A discovery meta-analysis was performed in 19 599 subjects, followed by replication analysis of genome-wide significant (P < 5 x 10(-8)) single nucleotide polymorphisms (SNPs) in 10 796 independent samples. We further examined associations with type 2 diabetes and coronary artery disease, assessed the functional significance of the SNPs for gene expression in human tissues, and conducted RNA-silencing experiments for one novel association. We confirmed the association of the 4G/5G proxy SNP rs2227631 in the promoter region of SERPINE1 (7q22.1) and discovered genome-wide significant associations at 3 additional loci: chromosome 7q22.1 close to SERPINE1 (rs6976053, discovery P = 3.4 x 10(-10)); chromosome 11p15.2 within ARNTL (rs6486122, discovery P = 3.0 x 10(-8)); and chromosome 3p25.2 within PPARG (rs11128603, dis-covery P = 2.9 x 10(-8)). Replication was achieved for the 7q22.1 and 11p15.2 loci. There was nominal association with type 2 diabetes and coronary artery disease at ARNTL (P < .05). Functional studies identified MUC3 as a candidate gene for the second association signal on 7q22.1. In summary, SNPs in SERPINE1 and ARNTL and an SNP associated with the expression of MUC3 were robustly associated with circulating levels of PAI-1. (Blood. 2012;120(24):4873-4881) C1 [Huang, Jie; Johnson, Andrew D.; Yang, Qiong; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Hamsten, Anders] Karolinska Inst, Atherosclerosis Res Unit, Ctr Mol Med, Karolinska Univ Hosp Solna,Dept Med, S-17176 Stockholm, Sweden. [Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands. [Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Asselbergs, Folkert W.] Univ Med Ctr, Dept Med Genet, Utrecht, Netherlands. [Tregouet, David; Oudot-Mellakh, Tiphaine; Vinh Truong; Cambien, Francois] Univ Paris 06, INSERM, UMR S 937, ICAN Inst, Paris, France. [Shin, So-Youn; Soranzo, Nicole] Wellcome Trust Sanger Inst, Hinxton, England. [Ding, Jingzhong] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Baumert, Jens; Peters, Annette; Meisinger, Christa] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Smith, Nicholas L.; Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. [Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, VA Off Res & Dev, Seattle, WA USA. [Williams, Scott M.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Ikram, Mohammad A.; Dehghan, Abbas; Schrijvers, Elisabeth M. C.; Hofman, Albert] Erasmus Med Ctr MC Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, Mohammad A.; Uitterlinden, Andre G.] Erasmus MC Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Kleber, Marcus E.] Ludwigshafen Risk & Cardiovasc Hlth LURIC Study N, Freiburg, Germany. [Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Fac Med, Mannheim Inst Publ Hlth, Mannheim, Germany. [Becker, Diane M.; Yanek, Lisa R.] Johns Hopkins Sch Med, Div Internal Med, Baltimore, MD USA. [Mychaleckyj, Josyf C.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Tang, Weihong; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Yang, Qiong; Chen, Ming-Huei] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Moore, Jason H.] Dartmouth Med Sch, Dept Genet, Lebanon, NH USA. [Moore, Jason H.] Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH USA. [Williams, Frances M. K.; Spector, Timothy D.; Soranzo, Nicole] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Dehghan, Abbas; Schrijvers, Elisabeth M. C.; Hofman, Albert; Uitterlinden, Andre G.] Netherlands Consortium Hlth Aging, Leiden, Netherlands. [Silbernagel, Guenther] Univ Tubingen, Dept Internal Med, Div Endocrinol Diabetol Nephrol Vasc Dis & Clin C, Tubingen, Germany. [Smith, Shelly; Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Karakas, Mahir; Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany. [Tofler, Geoffrey H.] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [Navis, Gerjan J.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands. [Lohman, Kurt] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Goel, Anuj; Peden, John F.; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Oxford, England. [Goel, Anuj; Peden, John F.; Watkins, Hugh] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England. [Hopewell, Jemma C.; Collins, Rory; Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, London, England. [Saleheen, Danish] Ctr Noncommunicable Dis Pakistan, Karachi, Pakistan. [Saleheen, Danish; Danesh, John] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England. [Lundmark, Per; Syvaenen, Ann-Christine] Uppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, Uppsala, Sweden. [Psaty, Bruce M.; Bis, Joshua C.] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Boehm, Bernhard O.] Univ Ulm, Grad Sch Mol Diabetol & Endocrinol, Div Endocrinol Diabet & Metab, D-89069 Ulm, Germany. [Carter, Angela M.; Grant, Peter J.] Univ Leeds, Div Cardiovasc & Diabet Res, Leeds, W Yorkshire, England. [McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Taylor, Kent] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Franzosi, Maria Grazia] Ist Mario Negri, Dept Cardiovasc Res, Milan, Italy. [Seedorf, Udo] Univ Munster, LIFA, Gesell Arterioskleroseforsch 5, D-48149 Munster, Germany. [Franco-Cereceda, Anders] Karolinska Inst, Dept Mol Med & Surg, Cardiothorac Surg Unit, S-17176 Stockholm, Sweden. [Goodall, Alison H.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA. [Cushman, Mary] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Mueller-Nurasyid, Martina] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Chair Genet Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Basu, Saonli] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Matijevic, Nena] Univ Texas Hlth Sci Ctr Houston, Hemostasis Lab, Houston, TX USA. [van Gilst, Wiek H.; Hillege, Hans L.; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Broad Inst Harvard & Massachusetts Inst Technol M, Program Med & Populat Genet, Cambridge, MA USA. [Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Klopp, Norman] German Resrarch Ctr Environm Hlth, Helmholtz Zentrum Munchen, Div Mol Epidemiol, Neuherberg, Germany. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Winkelmann, Bernhard R.] Cardiol Team Sachsenhausen, Frankfurt, Germany. [Becker, Lewis C.] Johns Hopkins Sch Med, Div Cardiol, Baltimore, MD USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol & Biochem, Burlington, VT USA. [Maerz, Winfried] Synlab Acad, Mannheim, Germany. [Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria. [Morange, Pierre-Emmanuel] Univ Aix Marseille 2, UMR S 626, INSERM, Marseille, France. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Hamsten, A (reprint author), Karolinska Inst, Atherosclerosis Res Unit, Ctr Mol Med, Karolinska Univ Hosp Solna,Dept Med, Bldg L8-03, S-17176 Stockholm, Sweden. EM odonnellc@nhlbi.nih.gov; anders.hamsten@ki.se RI Meisinger, Christine/B-5358-2014; Yang, Qiong/G-5438-2014; Strawbridge, Rona/H-5422-2012; Boehm, Bernhard/F-8750-2015; Peters, Annette/A-6117-2011; Tregouet, David-Alexandre/E-3961-2016; Williams, Scott/B-9491-2012; Johnson, Andrew/G-6520-2013; Sabater-Lleal, Maria/I-5832-2013; OI Strawbridge, Rona/0000-0001-8506-3585; Williams, Frances/0000-0002-2998-2744; Ikram, Mohammad Arfan/0000-0003-0372-8585; Seedorf, Udo/0000-0003-4652-5358; Folkersen, Lasse/0000-0003-0708-9530; Soranzo, Nicole/0000-0003-1095-3852; Meisinger, Christa/0000-0002-9026-6544; Watkins, Hugh/0000-0002-5287-9016; Ouwehand, Willem/0000-0002-7744-1790; Kleber, Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X; Sabater Lleal, Maria/0000-0002-0128-379X FU Biotechnology and Biological Sciences Research Council; British Heart Foundation [, RG/08/014/24067]; Department of Health; Intramural NIH HHS; Medical Research Council [, G0700931, MC_U137686857]; NCATS NIH HHS [UL1 TR000124]; NCRR NIH HHS [M01 RR00052, RR-024156, RR018787, UL1-RR-025005]; NHGRI NIH HHS [U01-HG-004402]; NHLBI NIH HHS [N01-HC-85084, 1U01 HL072518, HL080295, HL087652, HL105756, HL65234, HL67466, N01 HC-15103, N01 HC-55222, N01 HC085086, N01 HC095166, N01-HC-25195, N01-HC-35129, N01-HC-45133, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-HC-75150, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85085, N01-HC-85086, N01-HC-85239, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, N02-HL-6-4278, P01 HL074940, R01 HL095603, R01 HL095796, R01 HL59684, R01-HL-086694, R01-HL-087641, R01-HL-59367, R01-HL59367, R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258, R01HL071259, U01 HL072518]; NIA NIH HHS [1R01AG032098-01A1, AG-023629, AG-027058, AG-15928, AG-20098, N01AG62101, N01AG62103, N01AG62106]; NIDDK NIH HHS [DK063491, K24 DK080140]; NIGMS NIH HHS [P20 GM103534, T32 GM080178]; NLM NIH HHS [LM010098, R01 LM010098]; PHS HHS [HHSN268200625226C, HHSN268200782096C, HHSN268201200036C]; Wellcome Trust [, 090532] NR 37 TC 26 Z9 27 U1 0 U2 17 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 6 PY 2012 VL 120 IS 24 BP 4873 EP 4881 DI 10.1182/blood-2012-06-436188 PG 9 WC Hematology SC Hematology GA 064ZO UT WOS:000313115300031 PM 22990020 ER PT J AU Castellanos-Rizaldos, E Milbury, CA Makrigiorgos, GM AF Castellanos-Rizaldos, Elena Milbury, Coren Audrey Makrigiorgos, G. Mike TI Enrichment of Mutations in Multiple DNA Sequences Using COLD-PCR in Emulsion SO PLOS ONE LA English DT Article ID RESOLUTION MELTING ANALYSIS; COLORECTAL-CANCER; AMPLIFICATION; KRAS; IDENTIFICATION; SENSITIVITY; PROTOCOL; SAMPLES AB Background: Multiplex detection of low-level mutant alleles in the presence of wild-type DNA would be useful for several fields of medicine including cancer, pre-natal diagnosis and infectious diseases. COLD-PCR is a recently developed method that enriches low-level mutations during PCR cycling, thus enhancing downstream detection without the need for special reagents or equipment. The approach relies on the differential denaturation of DNA strands which contain Tm-lowering mutations or mismatches, versus 'homo-duplex' wild-type DNA. Enabling multiplex-COLD-PCR that can enrich mutations in several amplicons simultaneously is desirable but technically difficult to accomplish. Here we describe the proof of principle of an emulsion-PCR based approach that demonstrates the feasibility of multiplexed-COLD-PCR within a single tube, using commercially available mutated cell lines. This method works best with short amplicons; therefore, it could potentially be used on highly fragmented samples obtained from biological material or FFPE specimens. Methods: Following a multiplex pre-amplification of TP53 exons from genomic DNA, emulsions which incorporate the multiplex product, PCR reagents and primers specific for a given TP53 exon are prepared. Emulsions with different TP53 targets are then combined in a single tube and a fast-COLD-PCR program that gradually ramps up the denaturation temperature over several PCR cycles is applied (temperature-tolerant, TT-fast-eCOLD-PCR). The range of denaturation temperatures applied encompasses the critical denaturation temperature (T-c) corresponding to all the amplicons included in the reaction, resulting to a gradual enrichment of mutations within all amplicons encompassed by emulsion. Results: Validation for TT-fast-eCOLD-PCR is provided for TP53 exons 6-9. Using dilutions of mutated cell-line into wild-type DNA, we demonstrate simultaneous mutation enrichment between 7 to 15-fold in all amplicons examined. Conclusions: TT-fast-eCOLD-PCR expands the versatility of COLD-PCR and enables high-throughput enrichment of low-level mutant alleles over multiple sequences in a single tube. Citation: Castellanos-Rizaldos E, Milbury CA, Makrigiorgos GM (2012) Enrichment of Mutations in Multiple DNA Sequences Using COLD-PCR in Emulsion. PLoS ONE 7(12): e51362. doi:10.1371/journal.pone.0051362 C1 [Castellanos-Rizaldos, Elena; Milbury, Coren Audrey; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div DNA Repair & Genome Stabil,Dept Radiat Oncol, Boston, MA 02115 USA. [Makrigiorgos, G. Mike] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Med Phys & Biophys, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div DNA Repair & Genome Stabil,Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM mmakrigiorgos@lroc.harvard.edu FU Innovative Molecular Analysis Technologies Program of the National Cancer Institute (NCI) [CA-111994, CA-151164] FX This work was supported by the Innovative Molecular Analysis Technologies Program of the National Cancer Institute (NCI), grants CA-111994 and CA-151164 (GMM). The contents of this manuscript do not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 1 Z9 2 U1 1 U2 22 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 DEC 6 PY 2012 VL 7 IS 12 AR e51362 DI 10.1371/journal.pone.0051362 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 057UO UT WOS:000312589700039 PM 23236486 ER PT J AU Kim, J Keay, SK You, S Loda, M Freeman, MR AF Kim, Jayoung Keay, Susan K. You, Sungyong Loda, Massimo Freeman, Michael R. TI A Synthetic Form of Frizzled 8-Associated Antiproliferative Factor Enhances p53 Stability through USP2a and MDM2 SO PLOS ONE LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; BLADDER EPITHELIAL-CELLS; INTERSTITIAL CYSTITIS PATIENTS; DEUBIQUITINATING ENZYME USP2A; TUMOR-SUPPRESSOR; CARCINOMA CELLS; PROSTATE-CANCER; URINE MARKERS; CYCLIN D1; PROTEIN AB Frizzled 8-associated Antiproliferative Factor (APF) is a sialoglycopeptide urinary biomarker of interstitial cystitis/painful bladder syndrome (IC/PBS), a chronic condition of unknown etiology with variable symptoms that generally include pelvic and/or perineal pain, urinary frequency, and urgency. We previously reported that native human APF suppresses the proliferation of normal bladder epithelial cells through a mechanism that involves increased levels of p53. The goal of this study was to delineate the regulatory mechanism whereby p53 expression is regulated by APF. Two APF-responsive cell lines (T24 bladder carcinoma cells and the immortalized human bladder epithelial cell line, TRT-HU1) were treated with asialo-APF (as-APF), a chemically synthesized form of APF. Biochemical analysis revealed that as-APF increased p53 levels in two ways: by decreasing ubiquitin specific protease 2a (USP2a) expression leading to enhanced ubiquitination of murine double minute 2 E3 ubiquitin ligase (MDM2), and by suppressing association of p53 with MDM2, thus impairing p53 ubiquitination. Biological responses to as-APF were suppressed by increased expression of wild type, but not mutant USP2a, which enhanced cell growth via upregulation of a cell cycle mediator, cyclin D1, at both transcription and protein levels. Consistent with this, gene silencing of USP2a with siRNA arrested cell proliferation. Our findings suggest that APF upregulates cellular p53 levels via functional attenuation of the USP2a-MDM2 pathway, resulting in p53 accumulation and growth arrest. These data also imply that targeting USP2a, MDM2, p53 and/or complex formation by these molecules may be relevant in the development of novel therapeutic approaches to IC/PBS. Citation: Kim J, Keay SK, You S, Loda M, Freeman MR (2012) A Synthetic Form of Frizzled 8-Associated Antiproliferative Factor Enhances p53 Stability through USP2a and MDM2. PLoS ONE 7(12): e50392. doi:10.1371/journal.pone.0050392 C1 [Kim, Jayoung; You, Sungyong; Freeman, Michael R.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Dept Surg, Div Canc Biol & Therapeut, Los Angeles, CA 90048 USA. [Kim, Jayoung; You, Sungyong; Freeman, Michael R.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Dept Biomed Sci, Los Angeles, CA 90048 USA. [Kim, Jayoung; Freeman, Michael R.] Childrens Hosp, Urol Dis Res Ctr, Boston, MA 02115 USA. [Kim, Jayoung; Freeman, Michael R.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Kim, Jayoung; Freeman, Michael R.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Keay, Susan K.] Univ Maryland, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21201 USA. [Keay, Susan K.] VA Maryland Hlth Care Ctr, Baltimore, MD USA. [Loda, Massimo] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA USA. [Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kim, J (reprint author), Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Dept Surg, Div Canc Biol & Therapeut, Los Angeles, CA 90048 USA. EM Jayoung.Kim@cshs.org FU NIH [R37 DK47556, R01 DK57691, P50 DK65298, R01 CA131945, R01 DK52596]; Fishbein Family IC Research Foundation/Interstitial Cystitis Association; New York Academy of Medicine; Children's Hospital Boston Faculty Development FX This research was supported by: NIH grants R37 DK47556, R01 DK57691, P50 DK65298 (to MRF); R01 CA131945 (to ML); R01 DK52596 (to SKK); and the Fishbein Family IC Research Foundation/Interstitial Cystitis Association; New York Academy of Medicine; and Children's Hospital Boston Faculty Development (to JK); JK is an American Urological Association Foundation Research Scholar and an Eleanor and Miles Shore Scholar of Harvard Medical School. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 3 Z9 3 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 DEC 6 PY 2012 VL 7 IS 12 AR e50392 DI 10.1371/journal.pone.0050392 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 057UO UT WOS:000312589700014 PM 23236372 ER PT J AU Talkowski, ME Ordulu, Z Pillalamarri, V Benson, CB Blumenthal, I Connolly, S Hanscom, C Hussain, N Pereira, S Picker, J Rosenfeld, JA Shaffer, LG Wilkins-Haug, LE Gusella, JF Morton, CC AF Talkowski, Michael E. Ordulu, Zehra Pillalamarri, Vamsee Benson, Carol B. Blumenthal, Ian Connolly, Susan Hanscom, Carrie Hussain, Naveed Pereira, Shahrin Picker, Jonathan Rosenfeld, Jill A. Shaffer, Lisa G. Wilkins-Haug, Louise E. Gusella, James F. Morton, Cynthia C. TI Clinical Diagnosis by Whole-Genome Sequencing of a Prenatal Sample SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BALANCED CHROMOSOME REARRANGEMENTS; CHARGE ASSOCIATION; ROUTINE; UPDATE; CHD7 AB Conventional cytogenetic testing offers low-resolution detection of balanced karyotypic abnormalities but cannot provide the precise, gene-level knowledge required to predict outcomes. The use of high-resolution whole-genome deep sequencing is currently impractical for the purpose of routine clinical care. We show here that whole-genome "jumping libraries" can offer an immediately applicable, nucleotide-level complement to conventional genetic diagnostics within a time frame that allows for clinical action. We performed large-insert sequencing of DNA extracted from amniotic-fluid cells with a balanced de novo translocation. The amniotic-fluid sample was from a patient in the third trimester of pregnancy who underwent amniocentesis because of severe polyhydramnios after multiple fetal anomalies had been detected on ultrasonography. Using a 13-day sequence and analysis pipeline, we discovered direct disruption of CHD7, a causal locus in the CHARGE syndrome (coloboma of the eye, heart anomaly, atresia of the choanae, retardation, and genital and ear anomalies). Clinical findings at birth were consistent with the CHARGE syndrome, a diagnosis that could not have been reliably inferred from the cytogenetic breakpoint. This case study illustrates the potential power of customized whole-genome jumping libraries when used to augment prenatal karyotyping. C1 [Talkowski, Michael E.; Gusella, James F.; Morton, Cynthia C.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Talkowski, Michael E.; Pillalamarri, Vamsee; Blumenthal, Ian; Hanscom, Carrie; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Talkowski, Michael E.; Gusella, James F.; Morton, Cynthia C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Ordulu, Zehra; Pereira, Shahrin; Wilkins-Haug, Louise E.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Benson, Carol B.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Connolly, Susan] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Picker, Jonathan] Childrens Hosp, Dept Psychiat, Div Genet, Boston, MA 02115 USA. [Hussain, Naveed] Univ Connecticut, Dept Pediat, Farmington, CT USA. [Rosenfeld, Jill A.; Shaffer, Lisa G.] PerkinElmer, Signature Genom Labs, Spokane, WA USA. RP Morton, CC (reprint author), Harvard Univ, Sch Med, Dept Neurol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cmorton@partners.org OI Hussain, Naveed/0000-0002-1809-5760 FU National Institutes of Health [GM061354, HD065286, MH087123, MH095867]; Simons Foundation for Autism Research; Nancy Lurie Marks Family Foundation FX Supported by grants from the National Institutes of Health (GM061354, to Drs. Morton and Gusella; HD065286, to Dr. Gusella; and MH087123 and MH095867, to Dr. Talkowski). Drs. Talkowski and Gusella are supported by the Simons Foundation for Autism Research and the Nancy Lurie Marks Family Foundation. NR 19 TC 60 Z9 65 U1 1 U2 17 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 6 PY 2012 VL 367 IS 23 BP 2226 EP 2232 DI 10.1056/NEJMoa1208594 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 048DO UT WOS:000311890600009 PM 23215558 ER PT J AU Treon, SP Xu, L Hunter, ZR AF Treon, Steven P. Xu, Lian Hunter, Zachary R. TI MYD88 L265P Somatic Mutation in IgM MGUS Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Treon, Steven P.; Xu, Lian; Hunter, Zachary R.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 3 TC 2 Z9 2 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 DEC 6 PY 2012 VL 367 IS 23 BP 2256 EP 2257 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 048DO UT WOS:000311890600021 ER PT J AU Winters-Stone, KM Li, FZ Horak, F Luoh, SW Bennett, JA Nail, L Dieckmann, N AF Winters-Stone, Kerri M. Li, Fuzhong Horak, Fay Luoh, Shiuh-Wen Bennett, Jill A. Nail, Lillian Dieckmann, Nathan TI Comparison of tai chi vs. strength training for fall prevention among female cancer survivors: study protocol for the GET FIT trial SO BMC CANCER LA English DT Article DE Resistance training; Exercise; Physical function; Postural stability; Muscle strength; Chemotherapy; Neoplasm; Fracture ID RANDOMIZED CONTROLLED-TRIAL; LOWER-EXTREMITY FUNCTION; RECEIVING ADJUVANT CHEMOTHERAPY; PHYSICAL PERFORMANCE BATTERY; BREAST-CANCER; OLDER-ADULTS; EXERCISE PROGRAM; BODY-COMPOSITION; ENERGY-BALANCE; WOMENS HEALTH AB Background: Women with cancer are significantly more likely to fall than women without cancer placing them at higher risk of fall-related fractures, other injuries and disability. Currently, no evidence-based fall prevention strategies exist that specifically target female cancer survivors. The purpose of the GET FIT (Group Exercise Training for Functional Improvement after Treatment) trial is to compare the efficacy of two distinct types of exercise, tai chi versus strength training, to prevent falls in women who have completed treatment for cancer. The specific aims of this study are to: 1) Determine and compare the efficacy of both tai chi training and strength training to reduce falls in older female cancer survivors, 2) Determine the mechanism(s) by which tai chi and strength training each reduces falls and, 3) Determine whether or not the benefits of each intervention last after structured training stops. Methods/Design: We will conduct a three-group, single-blind, parallel design, randomized controlled trial in women, aged 50-75 years old, who have completed chemotherapy for cancer comparing 1) tai chi 2) strength training and 3) a placebo control group of seated stretching exercise. Women will participate in supervised study programs twice per week for six months and will be followed for an additional six months after formal training stops. The primary outcome in this study is falls, which will be prospectively tracked by monthly self-report. Secondary outcomes are maximal leg strength measured by isokinetic dynamometry, postural stability measured by computerized dynamic posturography and physical function measured by the Physical Performance Battery, all measured at baseline, 3, 6 and 12 months. The sample for this trial (N=429, assuming 25% attrition) will provide adequate statistical power to detect at least a 47% reduction in the fall rate over 1 year by being in either of the 2 exercise groups versus the control group. Discussion: The GET FIT trial will provide important new knowledge about preventing falls using accessible and implementable exercise interventions for women following chemotherapy for cancer. ClinicalTrials.gov NCT01635413 C1 [Winters-Stone, Kerri M.; Bennett, Jill A.; Nail, Lillian; Dieckmann, Nathan] Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97239 USA. [Winters-Stone, Kerri M.; Luoh, Shiuh-Wen; Bennett, Jill A.; Nail, Lillian] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Li, Fuzhong] Oregon Res Inst, Eugene, OR 97403 USA. [Horak, Fay] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97239 USA. [Luoh, Shiuh-Wen] Portland VA Med Ctr, Portland, OR 97239 USA. RP Winters-Stone, KM (reprint author), Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97239 USA. EM wintersk@ohsu.edu OI Li, Fuzhong/0000-0001-6644-4702 FU NCI NIH HHS [R01 CA163474]; NIA NIH HHS [R37 AG006457] NR 78 TC 8 Z9 9 U1 7 U2 41 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD DEC 5 PY 2012 VL 12 AR 577 DI 10.1186/1471-2407-12-577 PG 10 WC Oncology SC Oncology GA 067CJ UT WOS:000313270100001 PM 23217054 ER PT J AU Boros, E Polasek, M Zhang, ZD Caravan, P AF Boros, Eszter Polasek, Miloslav Zhang, Zhaoda Caravan, Peter TI Gd(DOTAla): A Single Amino Acid Gd-complex as a Modular Tool for High Relaxivity MR Contrast Agent Development SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SOLID-PHASE SYNTHESIS; HIGH MAGNETIC-FIELD; WATER EXCHANGE; SERUM-ALBUMIN; GADOLINIUM COMPLEXES; STRUCTURAL ENTRY; LANTHANIDE; BINDING; MS-325; OPTIMIZATION AB MR imaging at high magnetic fields benefits from an increased signal-to-noise ratio; however T-1-based MR contrast agents show decreasing relaxivity (r(1)) at higher fields. High field, high relaxivity contrast agents can be designed by carefully controlling the rotational dynamics of the molecule. To this end, we investigated applications of the alanine analogue of Gd(DOTA), Gd(DOTAla). Fmoc-protected DOTAla suitable for solid phase peptide synthesis was synthesized and integrated into polypeptide structures. Gd(III) coordination results in very rigid attachment of the metal chelate to the peptide backbone through both the amino acid side chain and coordination of the amide carbonyl. Linear and cyclic monomers (GdL1, GdC1), dimers (Gd(2)L2, Gd(2)C2), and trimers (Gd(3)L3, Gd(3)C3) were prepared and relaxivities were determined at different field strengths ranging from 0.47 to 11.7 T. Amide carbonyl coordination was indirectly confirmed by determination of the hydration number q for the EuL1 integrated into a peptide backbone, q = 0.96 +/- 0.09. The water residency time of GdL1 at 37 degrees C was optimal for relaxivity, tau(M) = 17 +/- 2 ns. Increased molecular size leads to increased per Gd relaxivity (from r(1) = 7.5 for GdLl to 12.9 mM(-1) s(-1) for Gd(3)L3 at 1.4 T, 37 degrees C). The cyclic, multimeric derivatives exhibited slightly higher relaxivities than the corresponding linearized multimers (Gd(2)C2: r(1) = 10.5 mM(-1) s(-1) versus Gd(2)C2-red r(1) = 9 mM(-1) s(-1) at 1.4 T, 37 degrees C). Overall, all six synthesized Gd complexes had higher relaxivities at low, intermediate, and high fields than the clinically used small molecule contrast agent [Gd(HP-DO3A)(H2O)]. C1 [Boros, Eszter; Polasek, Miloslav; Zhang, Zhaoda; Caravan, Peter] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, Charlestown, MA 02129 USA. RP Caravan, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu RI Polasek, Miloslav/G-5949-2014 FU National Institute of Biomedical Imaging and Bioengineering [R01EB009062]; National Center for Research Resources [P41RR14075]; Swiss National Science Foundation FX Dr. Mohammad A. Yaseen is warmly acknowledged for measurement of the luminescence lifetimes of Eu(LI). Dr. Daniel Schuhle is acknowledged for helpful discussions. This work was supported in part by awards R01EB009062 from the National Institute of Biomedical Imaging and Bioengineering and P41RR14075 from the National Center for Research Resources. E.B. acknowledges the Swiss National Science Foundation for a fellowship for prospective researchers. NR 52 TC 38 Z9 38 U1 0 U2 84 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 5 PY 2012 VL 134 IS 48 BP 19858 EP 19868 DI 10.1021/ja309187m PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA 047VM UT WOS:000311869600055 PM 23157602 ER PT J AU Vernochet, C Mourier, A Bezy, O Macotela, Y Boucher, J Rardin, MJ An, D Lee, KY Ilkayeva, OR Zingaretti, CM Emanuelli, B Smyth, G Cinti, S Newgard, CB Gibson, BW Larsson, NG Kahn, R AF Vernochet, Cecile Mourier, Arnaud Bezy, Olivier Macotela, Yazmin Boucher, Jeremie Rardin, Matthew J. An, Ding Lee, Kevin Y. Ilkayeva, Olga R. Zingaretti, Cristina M. Emanuelli, Brice Smyth, Graham Cinti, Saverio Newgard, Christopher B. Gibson, Bradford W. Larsson, Nils-Goeran Kahn, Ronald TI Adipose-Specific Deletion of TFAM Increases Mitochondrial Oxidation and Protects Mice against Obesity and Insulin Resistance SO CELL METABOLISM LA English DT Article ID ELECTRON-TRANSPORT CHAIN; SKELETAL-MUSCLE; KNOCKOUT MICE; COMPLEX-I; GENE-EXPRESSION; TISSUE; WHITE; FAT; DYSFUNCTION; PGC-1-ALPHA AB Obesity and type 2 diabetes are associated with mitochondrial dysfunction in adipose tissue, but the role for adipose tissue mitochondria in the development of these disorders is currently unknown. To understand the impact of adipose tissue mitochondria on whole-body metabolism, we have generated a mouse model with disruption of the mitochondrial transcription factor A (TFAM) specifically in fat. F-TFKO adipose tissue exhibit decreased mtDNA copy number, altered levels of proteins of the electron transport chain, and perturbed mitochondrial function with decreased complex I activity and greater oxygen consumption and uncoupling. As a result, F-TFKO mice exhibit higher energy expenditure and are protected from age- and diet-induced obesity, insulin resistance, and hepatosteatosis, despite a greater food intake. Thus, TFAM deletion in the adipose tissue increases mitochondrial oxidation that has positive metabolic effects, suggesting that regulation of adipose tissue mitochondria may be a potential therapeutic target for the treatment of obesity. C1 [Vernochet, Cecile; Bezy, Olivier; Macotela, Yazmin; Boucher, Jeremie; An, Ding; Lee, Kevin Y.; Emanuelli, Brice; Smyth, Graham; Kahn, Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. [Mourier, Arnaud; Larsson, Nils-Goeran] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany. [Rardin, Matthew J.; Gibson, Bradford W.] Buck Inst Res Aging, Novato, CA 94945 USA. [Ilkayeva, Olga R.; Newgard, Christopher B.] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27704 USA. [Zingaretti, Cristina M.; Cinti, Saverio] United Hosp Ancona, Department Expt & Clin Med, I-60020 Ancona, Italy. [Zingaretti, Cristina M.; Cinti, Saverio] United Hosp Ancona, Diagnost Electron Microscopy Unit, I-60020 Ancona, Italy. [Cinti, Saverio] IRCCS San Raffaele Pisana, Adipose Organ Lab, I-00163 Rome, Italy. [Bezy, Olivier] Pfizer, Cardiovasc Metab & Endocrine Dis, Cambridge, MA 02139 USA. [Macotela, Yazmin] UNAM, Inst Neurobiol, Queretaro 76230, Mexico. RP Kahn, R (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. EM c.ronald.kahn@joslin.harvard.edu RI MOURIER, Arnaud/I-8117-2012; Emanuelli, Brice/M-2097-2016; Smyth, Gordon/B-5276-2008; OI MOURIER, Arnaud/0000-0002-5413-611X; Smyth, Gordon/0000-0001-9221-2892; Emanuelli, Brice/0000-0001-5795-5666 FU Joslin Diabetes Microscopy Core [P30 DK36836]; NIH [S10-RR025545, DK-082659]; Eli Lilly Foundation; European Community [Health-F2-2011-278373]; Mary K. Iacocca Professorship FX The authors are grateful to Alison Burkart for helpful discussion and manuscript editing; Siegfried Ussar for help with mitochondria isolation; Michael Rourk for animal care; Chris Cahill for confocal microscopy assistance (Joslin Diabetes Microscopy Core, P30 DK36836 and NIH S10-RR025545); Girijesh Buruzula and Joyce LaVecchio for flow cytometry assistance; Alan Clermont (DERC Physiology Core); and H. Li (DERC Specialized Assay Core). This work was supported by NIH grant DK-082659, a grant from the Eli Lilly Foundation, the European Community's FP7, Grant Health-F2-2011-278373 to S.C., and the Mary K. Iacocca Professorship to C.R.K. C.R.K. is a founder and SAB member of Ember Therapeutics. NR 48 TC 53 Z9 57 U1 3 U2 25 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD DEC 5 PY 2012 VL 16 IS 6 BP 765 EP 776 DI 10.1016/j.cmet.2012.10.016 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 055ML UT WOS:000312420600009 PM 23168219 ER PT J AU Derecka, M Gornicka, A Koralov, SB Szczepanek, K Morgan, M Raje, V Sisler, J Zhang, QF Otero, D Cichy, J Rajewsky, K Shimoda, K Poli, V Strobl, B Pellegrini, S Harris, TE Seale, P Russell, AP McAinch, AJ O'Brien, PE Keller, SR Croniger, CM Kordula, T Larner, AC AF Derecka, Marta Gornicka, Agnieszka Koralov, Sergei B. Szczepanek, Karol Morgan, Magdalena Raje, Vidisha Sisler, Jennifer Zhang, Qifang Otero, Dennis Cichy, Joanna Rajewsky, Klaus Shimoda, Kazuya Poli, Valeria Strobl, Birgit Pellegrini, Sandra Harris, Thurl E. Seale, Patrick Russell, Aaron P. McAinch, Andrew J. O'Brien, Paul E. Keller, Susanna R. Croniger, Colleen M. Kordula, Tomasz Larner, Andrew C. TI Tyk2 and Stat3 Regulate Brown Adipose Tissue Differentiation and Obesity SO CELL METABOLISM LA English DT Article ID ADULT HUMANS; SKELETAL-MUSCLE; WHITE 3T3-L1; PPAR-GAMMA; RECEPTOR; GENE; ADIPOCYTES; INTERFERON; EXPRESSION; FAT AB Mice lacking the Jak tyrosine kinase member Tyk2 become progressively obese due to aberrant development of Myf5+ brown adipose tissue (BAT). Tyk2 RNA levels in BAT and skeletal muscle, which shares a common progenitor with BAT, are dramatically decreased in mice placed on a high-fat diet and in obese humans. Expression of Tyk2 or the constitutively active form of the transcription factor Stat3 (CAStat3) restores differentiation in Tyk2(-/-) brown preadipocytes. Furthermore, Tyk2(-/-) mice expressing CAStat3 transgene in BAT also show improved BAT development, normal levels of insulin, and significantly lower body weights. Stat3 binds to PRDM16, a master regulator of BAT differentiation, and enhances the stability of PRDM16 protein. These results define Tyk2 and Stat3 as critical determinants of brown fat lineage and suggest that altered levels of Tyk2 are associated with obesity in both rodents and humans. C1 [Derecka, Marta; Szczepanek, Karol; Morgan, Magdalena; Raje, Vidisha; Sisler, Jennifer; Zhang, Qifang; Kordula, Tomasz; Larner, Andrew C.] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. [Derecka, Marta; Szczepanek, Karol; Morgan, Magdalena; Raje, Vidisha; Sisler, Jennifer; Zhang, Qifang; Kordula, Tomasz; Larner, Andrew C.] Virginia Commonwealth Univ, Mol Biol & Massey Canc Ctr, Richmond, VA 23298 USA. [Gornicka, Agnieszka] Cleveland Clin Fdn, Dept Immunol, Cleveland, OH 44195 USA. [Koralov, Sergei B.] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Otero, Dennis] Univ Calif San Diego, Dept Biol Sci, La Jolla, CA 92093 USA. [Cichy, Joanna] Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Immunol, PL-30387 Krakow, Poland. [Rajewsky, Klaus] Harvard Univ, Sch Med, Children Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Shimoda, Kazuya] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Shimoda, Kazuya] Miyazaki Univ, Fac Med, Dept Gastroenterol & Hematol, Kiyotake, Miyazaki 8891692, Japan. [Poli, Valeria] Univ Turin, Ctr Mol Biotechnol, Dept Genet Biol & Biochem, I-10126 Turin, Italy. [Strobl, Birgit] Univ Vet Med Vienna, Dept Biomed Sci, Inst Anim Breeding & Genet, A-1210 Vienna, Austria. [Pellegrini, Sandra] Inst Pasteur, Dept Immunol, F-75724 Paris, France. [Harris, Thurl E.] Univ Virginia, Sch Med, Dept Pharmacol, Charlottesville, VA 22903 USA. [Seale, Patrick] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Russell, Aaron P.] Deakin Univ, Sch Exercise & Nutr Sci, Ctr Phys Activ & Nutr CPAN Res, Burwood 3125, Australia. [McAinch, Andrew J.] Victoria Univ, Sch Biomed & Hlth Sci, Biomed & Lifestyle Dis BioLED Unit, St Albans 3021, Australia. [O'Brien, Paul E.] Monash Univ, CORE, Alfred Hosp, Melbourne, Vic 3004, Australia. [Keller, Susanna R.] Univ Virginia, Sch Med, Dept Med, Charlottesville, VA 22908 USA. [Croniger, Colleen M.] Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH 44106 USA. RP Larner, AC (reprint author), Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM alarner@vcu.edu RI zhang, qifang/F-9857-2013; zhang, qifang/H-5691-2013; Pellegrini, Sandra/G-5546-2015; Poli, Valeria/A-9215-2012; OI Pellegrini, Sandra/0000-0001-5837-7589; Poli, Valeria/0000-0002-3739-3966; Strobl, Birgit/0000-0001-5716-3212; McAinch, Andrew/0000-0002-8762-4865; Raje, Vidisha/0000-0003-1808-6511 FU Austrian Science Fund [FWF SFB-F28]; [R01 AI059710-01]; [R21 AI088487] FX This work was supported in part by R01 AI059710-01 and R21 AI088487 to A.C.L. B.S. was supported by the Austrian Science Fund (FWF SFB-F28). We would like to thank Dr. Bruce Spiegelman for his advice. NR 41 TC 21 Z9 22 U1 1 U2 27 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD DEC 5 PY 2012 VL 16 IS 6 BP 814 EP 824 DI 10.1016/j.cmet.2012.11.005 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 055ML UT WOS:000312420600013 PM 23217260 ER PT J AU Shanmugasundararaj, S Das, J Sandberg, WS Zhou, XJ Wang, D Messing, RO Bruzik, KS Stehle, T Miller, KW AF Shanmugasundararaj, Sivananthaperumal Das, Joydip Sandberg, Warren S. Zhou, Xiaojuan Wang, Dan Messing, Robert O. Bruzik, Karol S. Stehle, Thilo Miller, Keith W. TI Structural and Functional Characterization of an Anesthetic Binding Site in the Second Cysteine-Rich Domain of Protein Kinase C delta SO BIOPHYSICAL JOURNAL LA English DT Article ID GATED ION-CHANNEL; X-RAY-STRUCTURE; HYDROGEN-BONDS; INHALED ANESTHETICS; FIREFLY LUCIFERASE; CRYSTAL-STRUCTURES; PHORBOL ESTERS; ACTIVATION; ALPHA; DIACYLGLYCEROL AB Elucidating the principles governing anesthetic-protein interactions requires structural determinations at high resolutions not yet achieved with ion channels. Protein kinase C (PKC) activity is modulated by general anesthetics. We solved the structure of the phorbol-binding domain (C1B) of PKC delta complexed with an ether (methoxymethylcycloprane) and with an alcohol (cyclopropylmethanol) at 1.36-angstrom resolution. The cyclopropane rings of both agents displace a single water molecule in a surface pocket adjacent to the phorbol-binding site, making van der Waals contacts with the backbone and/or side chains of residues Asn-237 to Ser-240. Surprisingly, two water molecules anchored in a hydrogen-bonded chain between Thr-242 and Lys-260 impart elasticity to one side of the binding pocket. The cyclopropane ring takes part in pi-acceptor hydrogen bonds with the amide of Met-239. There is a crucial hydrogen bond between the oxygen atoms of the anesthetics and the hydroxyl of Tyr-236. A Tyr-236-Phe mutation results in loss of binding. Thus, both van der Waals interactions and hydrogen-bonding are essential for binding to occur. Ethanol failed to bind because it is too short to benefit from both interactions. Cyclopropylmethanol inhibited phorbol-ester-induced PKC delta activity, but failed to do so in PKC delta containing the Tyr-236-Phe mutation. C1 [Shanmugasundararaj, Sivananthaperumal; Das, Joydip; Sandberg, Warren S.; Zhou, Xiaojuan; Miller, Keith W.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Stehle, Thilo] Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. [Sandberg, Warren S.; Miller, Keith W.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Wang, Dan; Messing, Robert O.] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Emeryville, CA USA. [Bruzik, Karol S.] Univ Illinois, Coll Pharm, Chicago, IL USA. RP Miller, KW (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM k_miller@helix.mgh.harvard.edu RI Messing, Robert/D-3642-2015 OI Messing, Robert/0000-0002-5345-4431 FU U.S. Public Health Service [GM 069726, AA018316]; Foundation for Anesthesia Education and Research award; Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital; State of California for medical research on alcohol and substance abuse through University of California, San Francisco; National Center for Research Resources at the National Institutes of Health [RR-15301]; National Institute of General Medical Sciences, National Institutes of Health [GM-0080]; U.S. Department of Energy [DE-AC02-98CH10886] FX We thank Elizabeth Kelly for assistance with the anesthetic potency measurements, Dr. Peter M. Blumberg for providing the PKCd C1B construct and Dr. David Jones for providing us with the structure factor file for his LUSH structure. Molecular graphics images were produced using the University of California, San Francisco, Chimera package (59) from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH P41 RR01081) or using Pymol (60). S. S. thanks V. Stojanoff, M. Allaire, J. Jakoncic, and F. Yokaichiya of beam line X6A, and N. Sukumar of BM8, for their support during data collection.; This research was supported by grants from the U.S. Public Health Service to K. W. M. (GM 069726) and R.O.M. (AA018316), by a Foundation for Anesthesia Education and Research award to W. S. S., by the Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital, and by funds provided by the State of California for medical research on alcohol and substance abuse through University of California, San Francisco, to R.O.M. This work is based upon research conducted at the Northeastern Collaborative Access Team beam lines (BM8) of the Advanced Photon Source, which is supported by award RR-15301 from the National Center for Research Resources at the National Institutes of Health. Research carried out (in whole or in part) at X6A beam line was funded by the National Institute of General Medical Sciences, National Institutes of Health, under agreement GM-0080. The National Synchrotron Light Source, Brookhaven National Laboratory is supported by the U.S. Department of Energy under contract no. DE-AC02-98CH10886. NR 61 TC 10 Z9 10 U1 0 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC 5 PY 2012 VL 103 IS 11 BP 2331 EP 2340 DI 10.1016/j.bpj.2012.10.034 PG 10 WC Biophysics SC Biophysics GA 049DX UT WOS:000311963300012 PM 23283232 ER PT J AU Egawa, K Kitagawa, K Inoue, K Takayama, M Takayama, C Saitoh, S Kishino, T Kitagawa, M Fukuda, A AF Egawa, Kiyoshi Kitagawa, Kyoko Inoue, Koichi Takayama, Masakazu Takayama, Chitoshi Saitoh, Shinji Kishino, Tatsuya Kitagawa, Masatoshi Fukuda, Atsuo TI Decreased Tonic Inhibition in Cerebellar Granule Cells Causes Motor Dysfunction in a Mouse Model of Angelman Syndrome SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID UBIQUITIN-DEPENDENT DEGRADATION; AMINOBUTYRIC-ACID TRANSPORTER-1; GABA(A) RECEPTORS; PURKINJE NEURONS; RAT CEREBELLUM; A RECEPTORS; UBE3A; EXPRESSION; BINDING; LIGASE AB Angelman syndrome is a neurodevelopmental disorder caused by loss of function of the UBE3A gene encoding a ubiquitin E3 ligase. Motor dysfunction is a characteristic feature of Angelman syndrome, but neither the mechanisms of action nor effective therapeutic strategies have yet been elucidated. We report that tonic inhibition is specifically decreased in cerebellar granule cells of Ube3a-deficient mice, a model of Angelman syndrome. As a mechanism underlying this decrease in tonic inhibition, we show that Ube3a controls degradation of gamma-aminobutyric acid (GABA) transporter 1 (GAT1) and that deficiency of Ube3a induces a surplus of GAT1 that results in a decrease in GABA concentrations in the extrasynaptic space. Administering low doses of 4,5,6,7-tetrahydroisothiazolo-[5,4-c]pyridin-3-ol (THIP), a selective extrasynaptic GABA(A) receptor agonist, improves the abnormal firing properties of a population of Purkinje cells in cerebellar brain slices and reduces cerebellar ataxia in Ube3a-deficient mice in vivo. These results suggest that pharmacologically increasing tonic inhibition may be a useful strategy for alleviating motor dysfunction in Angelman syndrome. C1 [Egawa, Kiyoshi; Inoue, Koichi; Takayama, Masakazu; Fukuda, Atsuo] Hamamatsu Univ Sch Med, Dept Neurophysiol, Hamamatsu, Shizuoka 4313192, Japan. [Kitagawa, Kyoko; Kitagawa, Masatoshi] Hamamatsu Univ Sch Med, Dept Mol Biol, Hamamatsu, Shizuoka 4313192, Japan. [Takayama, Chitoshi] Univ Ryukyus, Sch Med, Dept Mol Anat, Nishihara, Okinawa 9030215, Japan. [Saitoh, Shinji] Nagoya City Univ, Grad Sch Med Sci, Dept Pediat & Neonatol, Nagoya, Aichi 4678601, Japan. [Kishino, Tatsuya] Nagasaki Univ, Ctr Frontier Life Sci, Nagasaki 8528523, Japan. RP Egawa, K (reprint author), Massachusetts Gen Hosp, Dept Neurol, 16th St,CNY B-114, Boston, MA 02114 USA. EM cdh67560@par.odn.ne.jp; axfukuda@hama-med.ac.jp OI Fukuda, Atsuo/0000-0001-7112-4834; Saitoh, Shinji/0000-0001-6911-3351 FU Japan Society for the Promotion of Science [23791166, 22390041]; Ministry of Education, Culture, Sports, Science, and Technology, Japan [21026013, 23115506] FX This work was supported by a Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science #23791166 (K.E.); Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, #21026013 and 23115506 (to A.F.); and Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science #22390041 (to A.F.). NR 63 TC 24 Z9 24 U1 3 U2 24 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD DEC 5 PY 2012 VL 4 IS 163 AR 163ra157 DI 10.1126/scitranslmed.3004655 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 049PU UT WOS:000311996700004 PM 23220633 ER PT J AU Traverso, G McMahon, GT AF Traverso, Giovanni McMahon, Graham T. TI Residency Training and International Medical Graduates Coming to America No More SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID EDUCATION C1 [McMahon, Graham T.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Traverso, Giovanni] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Traverso, Giovanni; McMahon, Graham T.] Harvard Univ, Sch Med, Boston, MA USA. [Traverso, Giovanni] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Traverso, Giovanni] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP McMahon, GT (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, 221 Longwood Ave, Boston, MA 02115 USA. EM gmcmahon@partners.org RI McMahon, Graham/D-3740-2009 OI McMahon, Graham/0000-0003-4288-6535 FU NIDDK NIH HHS [T32 DK007191] NR 10 TC 9 Z9 9 U1 3 U2 16 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 DEC 5 PY 2012 VL 308 IS 21 BP 2193 EP 2194 DI 10.1001/jama.2012.14681 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 047HI UT WOS:000311829500008 PM 23212494 ER PT J AU Volpp, KG Shea, JA Small, DS Basner, M Zhu, JS Norton, L Ecker, A Novak, C Bellini, LM Dine, CJ Mollicone, DJ Dinges, DF AF Volpp, Kevin G. Shea, Judy A. Small, Dylan S. Basner, Mathias Zhu, Jingsan Norton, Laurie Ecker, Adrian Novak, Cristina Bellini, Lisa M. Dine, C. Jessica Mollicone, Daniel J. Dinges, David F. TI Effect of a Protected Sleep Period on Hours Slept During Extended Overnight In-hospital Duty Hours Among Medical Interns A Randomized Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID VIGILANCE TEST PVT; PSYCHOMOTOR VIGILANCE; DOSE-RESPONSE; WORK; RESTRICTION; ALERTNESS; MORTALITY; RECOVERY; DURATION; REFORM AB Context A 2009 Institute of Medicine report recommended protected sleep periods for medicine trainees on extended overnight shifts, a position reinforced by new Accreditation Council for Graduate Medical Education requirements. Objective To evaluate the feasibility and consequences of protected sleep periods during extended duty. Design, Setting, and Participants Randomized controlled trial conducted at the Philadelphia VA Medical Center medical service and Oncology Unit of the Hospital of the University of Pennsylvania (2009-2010). Of the 106 interns and senior medical students who consented, 3 were not scheduled on any study rotations. Among the others, 44 worked at the VA center, 16 at the university hospital, and 43 at both. Intervention Twelve 4-week blocks were randomly assigned to either a standard intern schedule (extended duty overnight shifts of up to 30 hours; equivalent to 1200 overnight intern shifts at each site), or a protected sleep period (protected time from 12: 30 AM to 5: 30 AM with handover of work cell phone; equivalent to 1200 overnight intern shifts at each site). Participants were asked to wear wrist actigraphs and complete sleep diaries. Main Outcome Measures Primary outcome was hours slept during the protected period on extended duty overnight shifts. Secondary outcome measures included hours slept during a 24-hour period (noon to noon) by day of call cycle and Karolinska sleepiness scale. Results For 98.3% of on-call nights, cell phones were signed out as designed. At the VA center, participants with protected sleep had a mean 2.86 hours (95% CI, 2.57-3.10 hours) of sleep vs 1.98 hours (95% CI, 1.68-2.28 hours) among those who did not have protected hours of sleep (P<.001). At the university hospital, participants with protected sleep had a mean 3.04 hours (95% CI, 2.77-3.45 hours) of sleep vs 2.04 hours (95% CI, 1.79-2.24) among those who did not have protected sleep (P<.001). Participants with protected sleep were significantly less likely to have call nights with no sleep: 5.8% (95% CI, 3.0%-8.5%) vs 18.6% (95% CI, 13.9%-23.2%) at the VA center (P<.001) and 5.9% (95% CI, 3.1%-8.7%) vs 14.2% (95% CI, 9.9%-18.4%) at the university hospital (P=.001). Participants felt less sleepy after on-call nights in the intervention group, with Karolinska sleepiness scale scores of 6.65 (95% CI, 6.35-6.97) vs 7.10 (95% CI, 6.85-7.33; P=.01) at the VA center and 5.91 (95% CI, 5.64-6.16) vs 6.79 (95% CI, 6.57-7.04; P<.001) at the university hospital. Conclusions For internal medicine services at 2 hospitals, implementation of a protected sleep period while on call resulted in an increase in overnight sleep duration and improved alertness the next morning. C1 [Volpp, Kevin G.; Shea, Judy A.; Norton, Laurie; Novak, Cristina] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Shea, Judy A.; Zhu, Jingsan; Norton, Laurie; Novak, Cristina; Bellini, Lisa M.; Dine, C. Jessica] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Basner, Mathias; Ecker, Adrian; Dinges, David F.] Univ Penn, Perelman Sch Med, Dept Psychiat, Div Sleep & Chronobiol, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Small, Dylan S.] Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Shea, Judy A.; Small, Dylan S.; Zhu, Jingsan; Norton, Laurie; Novak, Cristina] Univ Penn, Leonard Davis Inst, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Mollicone, Daniel J.] Pulsar Informat Inc, Philadelphia, PA USA. RP Volpp, KG (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, 1120 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu RI Emchi, Karma/Q-1952-2016 FU Veterans Affairs Health Services Research and Development Service [08-429]; National Institutes of Health [NR004281] FX This work was funded by educational grant 08-429 from the Veterans Affairs Health Services Research and Development Service. Dr Dinges was also supported in part by grant NR004281 from the National Institutes of Health. NR 34 TC 12 Z9 12 U1 1 U2 20 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 DEC 5 PY 2012 VL 308 IS 21 BP 2208 EP 2217 DI 10.1001/jama.2012.34490 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 047HI UT WOS:000311829500012 PM 23212498 ER PT J AU Lubitz, SA Ellinor, PT AF Lubitz, Steven A. Ellinor, Patrick T. TI Personalized medicine and atrial fibrillation: will it ever happen? SO BMC MEDICINE LA English DT Review DE Atrial fibrillation; genetics; personalized medicine; risk prediction; pharmacogenetics ID OF-FUNCTION MUTATION; EXPERT CONSENSUS STATEMENT; SUDDEN CARDIAC DEATH; SHORT QT SYNDROME; DILATED CARDIOMYOPATHY; FAMILIAL AGGREGATION; CHROMOSOME 4Q25; KCNQ1 MUTATION; RISK-FACTOR; ANTICOAGULATION CONTROL AB Atrial fibrillation (AF) is a common arrhythmia of substantial public health importance. Recent evidence demonstrates a heritable component underlying AF, and genetic discoveries have identified common variants associated with the arrhythmia. Ultimately one hopes that the consideration of genetic variation in clinical practice may enhance care and improve health outcomes. In this review we explore areas of potential clinical utility in AF management including those relating to pharmacogenetics and risk prediction. C1 [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Charlestown, MA 02129 USA. RP Lubitz, SA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,4th Floor, Charlestown, MA 02129 USA. EM slubitz@partners.org FU NIH [1RO1HL092577, 1RO1HL104156, 5R21DA027021, 1K24HL105780]; AHA grant [12FTF11350014]; Corrigan Minehan Innovation in Cardiovascular Research Spark Award FX PTE is supported by NIH grants 1RO1HL092577, 1RO1HL104156, 5R21DA027021 and 1K24HL105780. SAL is supported by an AHA grant 12FTF11350014 and a Corrigan Minehan Innovation in Cardiovascular Research Spark Award. NR 103 TC 6 Z9 6 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD DEC 4 PY 2012 VL 10 AR 155 DI 10.1186/1741-7015-10-155 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 103YK UT WOS:000315955300001 PM 23210687 ER PT J AU Szymanski, C Bel, A Cohen, I Touchot, B Handschumacher, MD Desnos, M Carpentier, A Menasche, P Hagege, AA Levine, RA Messas, E AF Szymanski, Catherine Bel, Alain Cohen, Iris Touchot, Bernard Handschumacher, Mark D. Desnos, Michel Carpentier, Alain Menasche, Philippe Hagege, Albert A. Levine, Robert A. Messas, Emmanuel CA Leducq Fdn MITRAL Transatlantic TI Comprehensive Annular and Subvalvular Repair of Chronic Ischemic Mitral Regurgitation Improves Long-Term Results With the Least Ventricular Remodeling SO CIRCULATION LA English DT Article DE echocardiography; mitral valve chordae; mitral valve regurgitation; myocardial infarction; regurgitation; remodeling ID 3-DIMENSIONAL ECHOCARDIOGRAPHIC RECONSTRUCTION; ACUTE MYOCARDIAL-INFARCTION; LEAFLET 2ND-ORDER CHORDAE; DOPPLER-ECHOCARDIOGRAPHY; VALVE ANNULOPLASTY; MECHANISM; SEVERITY; REVASCULARIZATION; RECOMMENDATIONS; MORTALITY AB Background-Undersized ring annuloplasty for ischemic mitral regurgitation (MR) is associated with variable results and > 30% MR recurrence. We tested whether subvalvular repair by severing second-order mitral chordae can improve annuloplasty by reducing papillary muscle tethering. Methods and Results-Posterolateral myocardial infarction known to produce chronic remodeling and MR was created in 28 sheep. At 3 months, sheep were randomized to sham surgery versus isolated undersized annuloplasty versus isolated bileaflet chordal cutting versus the combined therapy (n = 7 each). At baseline, chronic myocardial infarction (3 months), and euthanasia (6.6 months), we measured left ventricular (LV) volumes and ejection fraction, wall motion score index, MR regurgitation fraction and vena contracta, mitral annulus area, and posterior leaflet restriction angle (posterior leaflet to mitral annulus area) by 2-dimensional and 3-dimensional echocardiography. All groups were comparable at baseline and chronic myocardial infarction, with mild to moderate MR (MR vena contracta, 4.6 +/- 0.1 mm; MR regurgitation fraction, 24.2 +/- 2.9%) and mitral annulus dilatation (P < 0.01). At euthanasia, MR progressed to moderate to severe in controls but decreased to trace with ring plus chordal cutting versus trace to mild with chordal cutting alone versus mild to moderate with ring alone (MR vena contracta, 5.9 +/- 1.1 mm in controls, 0.5 +/- 0.08 with both, 1.0 +/- 0.3 with chordal cutting alone, 2.0 +/- 0.4 with ring alone; P < 0.01). In addition, LV end-systolic volume increased by 108% in controls versus 28% with ring plus chordal cutting, less than with each intervention alone (P < 0.01). In multivariate analysis, LV end-systolic volume and mitral annulus area most strongly predicted MR (r(2) = 0.82, P < 0.01). Conclusions-Comprehensive annular and subvalvular repair improves long- term reduction of both chronic ischemic MR and LV remodeling without decreasing global or segmental LV function at follow-up. (Circulation. 2012;126:2720-2727.) C1 [Messas, Emmanuel] Hop Europeen Georges Pompidou, INSERM, U633, PARCC,Dept Cardiovasc Med, F-75015 Paris, France. [Szymanski, Catherine; Bel, Alain; Cohen, Iris; Touchot, Bernard; Desnos, Michel; Carpentier, Alain; Menasche, Philippe; Hagege, Albert A.; Messas, Emmanuel] Univ Paris 05, Fac Med, Paris, France. [Szymanski, Catherine; Bel, Alain; Cohen, Iris; Touchot, Bernard; Desnos, Michel; Carpentier, Alain; Menasche, Philippe; Hagege, Albert A.; Messas, Emmanuel] Hop Europeen Georges Pompidou, AP HP, Dept Cardiol & Cardiovasc Surg, F-75015 Paris, France. [Handschumacher, Mark D.; Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. RP Messas, E (reprint author), Hop Europeen Georges Pompidou, INSERM, U633, PARCC,Dept Cardiovasc Med, 20 Rue Leblanc, F-75015 Paris, France. EM emmanuel.messas@egp.aphp.fr FU National Institutes of Health, Bethesda, MD [R01 HL38176, HL72265]; Fondation Leducq, Mitral Network of Excellence, Paris, France [07CVD04]; Federation Francaise de Cardiologie FX This study was supported in part by grants R01 HL38176 and HL72265 from the National Institutes of Health, Bethesda, MD, and by the Fondation Leducq, Mitral Network of Excellence, grant 07CVD04, Paris, France. Dr Catherine Szymanski was supported by a grant from the Federation Francaise de Cardiologie. NR 47 TC 18 Z9 18 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 4 PY 2012 VL 126 IS 23 BP 2720 EP 2727 DI 10.1161/CIRCULATIONAHA.111.033472 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048TY UT WOS:000311937200013 PM 23139296 ER PT J AU Khouri, MG Douglas, PS Mackey, JR Martin, M Scott, JM Scherrer-Crosbie, M Jones, LW AF Khouri, Michel G. Douglas, Pamela S. Mackey, John R. Martin, Miguel Scott, Jessica M. Scherrer-Crosbie, Marielle Jones, Lee W. TI Cancer Therapy-Induced Cardiac Toxicity in Early Breast Cancer Addressing the Unresolved Issues SO CIRCULATION LA English DT Review DE cardiomyopathies; chemotherapy; heart failure; women ID LEFT-VENTRICULAR DYSFUNCTION; HIGH-DOSE CHEMOTHERAPY; ANTHRACYCLINE-INDUCED CARDIOTOXICITY; TRASTUZUMAB-RELATED CARDIOTOXICITY; CONGESTIVE-HEART-FAILURE; DOXORUBICIN-INDUCED CARDIOMYOPATHY; DRUG-INDUCED CARDIOTOXICITY; ADJUVANT ENDOCRINE THERAPY; PROGENITOR-CELL FUNCTION; ASSOCIATION TASK-FORCE C1 [Khouri, Michel G.; Douglas, Pamela S.; Jones, Lee W.] Duke Univ, Med Ctr, Durham, NC USA. [Mackey, John R.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Martin, Miguel] Univ Complutense, Hosp Gen Univ Gregorio Maranon, E-28040 Madrid, Spain. [Scott, Jessica M.] NASA, Johnson Space Ctr, Houston, TX USA. [Scherrer-Crosbie, Marielle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Jones, LW (reprint author), Duke Canc Inst, Box 3085, Durham, NC 27710 USA. EM lee.w.jones@duke.edu OI MARTIN, MIGUEL/0000-0001-9237-3231 FU National Institutes of Health [CA143254, CA142566, CA138634, CA133895]; Susan G. Komen Investigator Initiated Grant FX Dr Jones is supported by National Institutes of Health grants CA143254, CA142566, CA138634, and CA133895 and funds from George and Susan Beischer. Dr Scherrer-Crosbie is supported by a Susan G. Komen Investigator Initiated Grant. NR 146 TC 58 Z9 59 U1 0 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 4 PY 2012 VL 126 IS 23 BP 2749 EP 2763 DI 10.1161/CIRCULATIONAHA.112.100560 PG 15 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048TY UT WOS:000311937200016 PM 23212997 ER PT J AU Bart, BA Goldsmith, SR Lee, KL Stevenson, LW O'Connor, CM Bull, DA Redfield, MM Deswal, A Rouleau, JL LeWinter, MM Ofili, EO Givertz, MM Semigran, MJ Felker, GM Chen, HH Hernandez, AF Anstrom, KJ McNulty, SE Velazquez, EJ Mascette, AM Braunwald, E AF Bart, Bradley A. Goldsmith, Steven R. Lee, Kerry L. Stevenson, Lynne W. O'Connor, Christopher M. Bull, David A. Redfield, Margaret M. Deswal, Anita Rouleau, Jean L. LeWinter, Martin M. Ofili, Elizabeth O. Givertz, Micheal M. Semigran, Marc J. Felker, G. M. Chen, Horng H. Hernandez, Adrian F. Anstrom, Kevin J. McNulty, Steven E. Velazquez, Eric J. Mascette, Alice M. Braunwald, Eugene TI Cardiorenal Rescue Study in Acute Decompensated Heart Failure: Results of CARRESS-HF, for the Heart Failure Clinical Research Network SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association CY NOV 03-07, 2012 CL Los Angeles, CA SP Amer Heart Assoc DE Acute heart failure; Diuretics; Renal function; Device C1 [Bart, Bradley A.; Goldsmith, Steven R.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Lee, Kerry L.; O'Connor, Christopher M.; Felker, G. M.; Hernandez, Adrian F.; Anstrom, Kevin J.; McNulty, Steven E.; Velazquez, Eric J.] Duke Univ, Durham, NC USA. [Stevenson, Lynne W.; Givertz, Micheal M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bull, David A.] Univ Utah, Salt Lake City, UT USA. [Redfield, Margaret M.; Chen, Horng H.] Mayo Clin, Rochester, MN USA. [Deswal, Anita] Baylor Coll Med, Houston, TX 77030 USA. [Deswal, Anita] VA Med Cntr, Houston, TX USA. [Rouleau, Jean L.] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [LeWinter, Martin M.] Univ Vermont, Berlington, VT USA. [Ofili, Elizabeth O.] Morehouse Sch Med, Atlanta, GA 30310 USA. [Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mascette, Alice M.] NHLBI, Bethesda, MD 20892 USA. [Braunwald, Eugene] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 4 PY 2012 VL 126 IS 23 BP 2786 EP 2786 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048TY UT WOS:000311937200046 ER PT J AU Semigran, M Bonderman, D Ghio, S Felix, SB Ghofrani, HA Michelakis, ED Mitrovic, V Oudiz, RJ Roessig, L Scalise, AV AF Semigran, Marc Bonderman, Diana Ghio, Stefano Felix, Stephan B. Ghofrani, Hossein A. Michelakis, Evangelos D. Mitrovic, Veselin Oudiz, Ronald J. Roessig, Lothar Scalise, Andrea V. TI Left Ventricular Systolic Dysfunction Associated With Pulmonary Hypertension Riociguat Trial (LEPHT) SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association CY NOV 03-07, 2012 CL Los Angeles, CA SP Amer Heart Assoc DE Heart failure; Pulmonary hypertension; Vasodilator agents C1 [Semigran, Marc] Massachusetts Gen Hosp, Heart Cntr, Boston, MA 02114 USA. [Bonderman, Diana] Med Univ Vienna, Vienna, Austria. [Ghio, Stefano] Fdn Policlin S Matteo, Pavia, Italy. [Felix, Stephan B.] Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany. [Ghofrani, Hossein A.] Univ Hosp Giessen & Marburg, Giessen, Germany. [Michelakis, Evangelos D.] Univ Alberta, Edmonton, AB, Canada. [Mitrovic, Veselin] Kerckhoff Heart Cntr, Bad Nauheim, Germany. [Oudiz, Ronald J.] Harbor UCLA Med Cntr, Los Angeles Biomed Rsch Inst, Torrance, CA USA. [Roessig, Lothar] Bayer Pharma AG, Berlin, Germany. [Scalise, Andrea V.] Bayer Hispania SL, Barcelona, Spain. NR 0 TC 2 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 4 PY 2012 VL 126 IS 23 BP 2789 EP 2790 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048TY UT WOS:000311937200053 ER PT J AU Desai, NR Kohli, P Giugliano, RP Kim, JB Mohanavelu, S Hoffman, E Liu, T Scott, R Wasserman, S Sabatine, MS AF Desai, Nihar R. Kohli, Payal Giugliano, Robert P. Kim, Jae B. Mohanavelu, Satishkumar Hoffman, Elaine Liu, Thomas Scott, Robert Wasserman, Scott Sabatine, Marc S. TI AMG 145, a Fully Human Monoclonal Antibody Against Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9), Facilitates Achievement of NCEP LDL-Cholesterol Goals in High-Risk Patients SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association CY NOV 03-07, 2012 CL Los Angeles, CA SP Amer Heart Assoc DE Lipids; Cholesterol-lowering drugs; Quality improvement C1 [Desai, Nihar R.; Kohli, Payal; Giugliano, Robert P.; Hoffman, Elaine; Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, Boston, MA 02115 USA. [Kim, Jae B.; Mohanavelu, Satishkumar; Liu, Thomas; Scott, Robert; Wasserman, Scott] Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 4 PY 2012 VL 126 IS 23 BP 2791 EP 2791 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048TY UT WOS:000311937200058 ER PT J AU Saxena, V Ramdas, S Ochoa, CR Wallace, D Bhide, P Kohane, I AF Saxena, Vishal Ramdas, Shweta Ochoa, Courtney Rothrock Wallace, David Bhide, Pradeep Kohane, Isaac TI Structural, Genetic, and Functional Signatures of Disordered Neuro-Immunological Development in Autism Spectrum Disorder SO PLOS ONE LA English DT Article ID SET ENRICHMENT ANALYSIS; EXPRESSION; ASSOCIATION; SUSCEPTIBILITY; CYTOKINE; PROTEINS; CHILDREN; BRAIN; IDENTIFICATION; SCHIZOPHRENIA AB Background: Numerous linkage studies have been performed in pedigrees of Autism Spectrum Disorders, and these studies point to diverse loci and etiologies of autism in different pedigrees. The underlying pattern may be identified by an integrative approach, especially since ASD is a complex disorder manifested through many loci. Method: Autism spectrum disorder (ASD) was studied through two different and independent genome-scale measurement modalities. We analyzed the results of copy number variation in autism and triangulated these with linkage studies. Results: Consistently across both genome-scale measurements, the same two molecular themes emerged: immune/chemokine pathways and developmental pathways. Conclusion: Linkage studies in aggregate do indeed share a thematic consistency, one which structural analyses recapitulate with high significance. These results also show for the first time that genomic profiling of pathways using a recombination distance metric can capture pathways that are consistent with those obtained from copy number variations (CNV). C1 [Saxena, Vishal; Bhide, Pradeep] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Saxena, Vishal] Massachusetts Gen Hosp, Dept Med, Charlestown, MA USA. [Saxena, Vishal; Kohane, Isaac] Harvard Univ, Sch Med, Boston, MA USA. [Saxena, Vishal; Wallace, David] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Ochoa, Courtney Rothrock] Univ S Alabama Coll, Ctr Lung Biol, Mobile, AL USA. [Saxena, Vishal; Kohane, Isaac] Childrens Hosp, Dept Endocrinol, Boston, MA 02115 USA. [Ramdas, Shweta] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. RP Saxena, V (reprint author), Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. EM vishal@mit.edu OI Bhide, Pradeep/0000-0003-4236-9415 FU Conte Center for Computational System Genomics of Neuropsychiatric Phenotypes(National Institutes of Health) [P50MH94267]; Nancy Lurie Marks Foundation FX The research was funded in part by Conte Center for Computational System Genomics of Neuropsychiatric Phenotypes(National Institutes of Health P50MH94267). ISK was supported in part by the Nancy Lurie Marks Foundation. No additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 8 Z9 8 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 DEC 4 PY 2012 VL 7 IS 12 AR e48835 DI 10.1371/journal.pone.0048835 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 051EQ UT WOS:000312108500002 PM 23239965 ER PT J AU Kim, DH Ghaffari, R Lu, NS Wang, SD Lee, SP Keum, H D'Angelo, R Klinker, L Su, YW Lu, CF Kim, YS Ameen, A Li, YH Zhang, YH de Graff, B Hsu, YY Liu, ZJ Ruskin, J Xu, LZ Lu, C Omenetto, FG Huang, YG Mansour, M Slepian, MJ Rogers, JA AF Kim, Dae-Hyeong Ghaffari, Roozbeh Lu, Nanshu Wang, Shuodao Lee, Stephen P. Keum, Hohyun D'Angelo, Robert Klinker, Lauren Su, Yewang Lu, Chaofeng Kim, Yun-Soung Ameen, Abid Li, Yuhang Zhang, Yihui de Graff, Bassel Hsu, Yung-Yu Liu, ZhuangJian Ruskin, Jeremy Xu, Lizhi Lu, Chi Omenetto, Fiorenzo G. Huang, Yonggang Mansour, Moussa Slepian, Marvin J. Rogers, John A. TI Electronic sensor and actuator webs for large-area complex geometry cardiac mapping and therapy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE flexible electronics; semiconductor nanomaterials; stretchable electronics; implantable biomedical devices; cardiac electrophysiology ID PERSISTENT ATRIAL-FIBRILLATION; CATHETER ABLATION; EPICARDIAL ACTIVATION; PULMONARY VEINS; SOCK ELECTRODE; IN-VIVO; ARRHYTHMIAS; HEART; ELECTROPHYSIOLOGY; ELECTROGONIOMETER AB Curved surfaces, complex geometries, and time-dynamic deformations of the heart create challenges in establishing intimate, non-constraining interfaces between cardiac structures and medical devices or surgical tools, particularly over large areas. We constructed large area designs for diagnostic and therapeutic stretchable sensor and actuator webs that conformally wrap the epicardium, establishing robust contact without sutures, mechanical fixtures, tapes, or surgical adhesives. These multifunctional web devices exploit open, mesh layouts and mount on thin, bio-resorbable sheets of silk to facilitate handling in a way that yields, after dissolution, exceptionally low mechanical moduli and thicknesses. In vivo studies in rabbit and pig animal models demonstrate the effectiveness of these device webs for measuring and spatially mapping temperature, electrophysiological signals, strain, and physical contact in sheet and balloon-based systems that also have the potential to deliver energy to perform localized tissue ablation. C1 [Keum, Hohyun; Kim, Yun-Soung; Ameen, Abid; Xu, Lizhi; Lu, Chi; Rogers, John A.] Univ Illinois, Dept Mat Sci & Engn, Urbana, IL 61801 USA. [Kim, Dae-Hyeong] Seoul Natl Univ, Sch Chem & Biol Engn, World Class Univ Program Chem Convergence Energy, Inst Basic Sci,Ctr Nanoparticle Res, Seoul 151742, South Korea. [Lu, Nanshu] Univ Texas Austin, Dept Aerosp Engn & Engn Mech, Austin, TX 78712 USA. [Ghaffari, Roozbeh; Lee, Stephen P.; D'Angelo, Robert; Klinker, Lauren; de Graff, Bassel; Hsu, Yung-Yu] MC10 Inc, Cambridge, MA 02140 USA. [Wang, Shuodao; Su, Yewang; Lu, Chaofeng; Li, Yuhang; Zhang, Yihui; Huang, Yonggang] Northwestern Univ, Dept Mech Engn, Evanston, IL 60208 USA. [Wang, Shuodao; Su, Yewang; Lu, Chaofeng; Li, Yuhang; Zhang, Yihui; Huang, Yonggang] Northwestern Univ, Dept Civil & Environm Engn, Evanston, IL 60208 USA. [Su, Yewang; Zhang, Yihui] Tsinghua Univ, Ctr Mech & Mat, Beijing 100084, Peoples R China. [Lu, Chaofeng] Zhejiang Univ, Soft Matter Res Ctr, Hangzhou 310058, Zhejiang, Peoples R China. [Lu, Chaofeng] Zhejiang Univ, Dept Civil Engn, Hangzhou 310058, Zhejiang, Peoples R China. [Li, Yuhang] Harbin Inst Technol, Sch Astronaut, Harbin 150001, Peoples R China. [Liu, ZhuangJian] ASTAR, Inst High Performance Comp, Singapore 138632, Singapore. [Ruskin, Jeremy; Mansour, Moussa] Massachusetts Gen Hosp, Cardiac Arrhythmia Unit, Boston, MA 02140 USA. [Omenetto, Fiorenzo G.] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. [Slepian, Marvin J.] Univ Arizona, Sarver Heart Ctr, Dept Med, Tucson, AZ 85724 USA. [Slepian, Marvin J.] Univ Arizona, Sarver Heart Ctr, Dept Biomed Engn, Tucson, AZ 85724 USA. RP Rogers, JA (reprint author), Univ Illinois, Dept Mat Sci & Engn, Urbana, IL 61801 USA. EM jrogers@illinois.edu RI Lu, Chaofeng/C-2162-2009; Huang, Yonggang/B-6998-2009; Xu, Lizhi/D-8143-2016; Wang, Shuodao/H-6014-2011; Rogers, John /L-2798-2016; OI Xu, Lizhi/0000-0001-6888-0524; Lee, Stephen/0000-0002-8521-8652 FU World Class University (WCU) program through the National Research Foundation of Korea; Ministry of Education, Science and Technology [R31-10013, 2012R1A1A1004925]; Basic Science Research Program through the Korea National Research Foundation; National Security Science and Engineering Faculty Fellowship; Cockrell School of Engineering at the University of Texas at Austin FX We thank Roja Nunna and Nishan Subedi for implementation and testing of the data acquisition system, and Behrooz Dehdashti and members of the Sarver Heart Center for help with in vivo animal studies. This material is based on work conducted at the Materials Research Laboratory and Center for Microanalysis of Materials (DE-FG02-07ER46453) at the University of Illinois at Urbana-Champaign. This work was supported by the World Class University (WCU) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (R31-10013) and the Basic Science Research Program through the Korea National Research Foundation funded by Ministry of Education, Science and Technology Grant 2012R1A1A1004925. J.A.R. has received a National Security Science and Engineering Faculty Fellowship. N.L. receives support from the startup fund from the Cockrell School of Engineering at the University of Texas at Austin. NR 55 TC 72 Z9 74 U1 15 U2 116 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 DEC 4 PY 2012 VL 109 IS 49 BP 19910 EP 19915 DI 10.1073/pnas.1205923109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054MF UT WOS:000312347200019 PM 23150574 ER PT J AU Lewis, LD Weiner, VS Mukamel, EA Donoghue, JA Eskandar, EN Madsen, JR Anderson, WS Hochberg, LR Cash, SS Brown, EN Purdon, PL AF Lewis, Laura D. Weiner, Veronica S. Mukamel, Eran A. Donoghue, Jacob A. Eskandar, Emad N. Madsen, Joseph R. Anderson, William S. Hochberg, Leigh R. Cash, Sydney S. Brown, Emery N. Purdon, Patrick L. TI Rapid fragmentation of neuronal networks at the onset of propofol-induced unconsciousness SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE electrophysiology; single units; GABA; cortical networks ID LESS-THAN-1 HZ OSCILLATION; INDUCED ALPHA-RHYTHM; GENERAL-ANESTHESIA; SLEEP ELECTROENCEPHALOGRAM; BURST-SUPPRESSION; POINT PROCESS; SLOW; CONSCIOUSNESS; BRAIN; EEG AB The neurophysiological mechanisms by which anesthetic drugs cause loss of consciousness are poorly understood. Anesthetic actions at the molecular, cellular, and systems levels have been studied in detail at steady states of deep general anesthesia. However, little is known about how anesthetics alter neural activity during the transition into unconsciousness. We recorded simultaneous multiscale neural activity from human cortex, including ensembles of single neurons, local field potentials, and intracranial electrocorticograms, during induction of general anesthesia. We analyzed local and global neuronal network changes that occurred simultaneously with loss of consciousness. We show that propofol-induced unconsciousness occurs within seconds of the abrupt onset of a slow (<1 Hz) oscillation in the local field potential. This oscillation marks a state in which cortical neurons maintain local patterns of network activity, but this activity is fragmented across both time and space. Local (<4 mm) neuronal populations maintain the millisecond-scale connectivity patterns observed in the awake state, and spike rates fluctuate and can reach baseline levels. However, neuronal spiking occurs only within a limited slow oscillation-phase window and is silent otherwise, fragmenting the time course of neural activity. Unexpectedly, we found that these slow oscillations occur asynchronously across cortex, disrupting functional connectivity between cortical areas. We conclude that the onset of slow oscillations is a neural correlate of propofol-induced loss of consciousness, marking a shift to cortical dynamics in which local neuronal networks remain intact but become functionally isolated in time and space. C1 [Brown, Emery N.; Purdon, Patrick L.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Hochberg, Leigh R.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Lewis, Laura D.; Weiner, Veronica S.; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Donoghue, Jacob A.; Brown, Emery N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Brown, Emery N.; Purdon, Patrick L.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Donoghue, Jacob A.; Cash, Sydney S.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Eskandar, Emad N.; Madsen, Joseph R.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Mukamel, Eran A.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Mukamel, Eran A.] Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA. [Madsen, Joseph R.] Boston Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Anderson, William S.] Johns Hopkins Univ Hosp, Sch Med, Dept Neurosurg, Baltimore, MD 21287 USA. [Hochberg, Leigh R.] Dept Vet Affairs, Rehabil Res & Dev Serv, Providence, RI 02908 USA. [Hochberg, Leigh R.] Brown Univ, Sch Engn, Inst Brain Sci, Providence, RI 02912 USA. RP Purdon, PL (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM patrickp@nmr.mgh.harvard.edu FU Center for Integration of Medicine and Innovative Technology; National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) [NS062092, K08NS066099-01A1]; National Eye Institute [EY017658]; National Institute on Drug Abuse [NS063249]; National Science Foundation [IOB 0645886]; Howard Hughes Medical Institute; Klingenstein Foundation; NIH [DP1OD003646, R01-MH071847, DP2-OD006454, K25-NS057580]; Department of Veterans Affairs Career Development Transition Award; Doris Duke Charitable Foundation-Clinical Scientist Development Award; Massachusetts General Hospital-Deane Institute for Integrated Research on Atrial Fibrillation and Stroke; NIH/National Institute on Deafness and Other Communications Disorders [R01DC009899]; Canadian Institute of Health Research Fellowship FX We thank A. Dykstra and A. Chan for help with electrode localization methods, A. Smith for sharing spike rate Bayesian estimation code, and D. Ba for assistance with GLM fitting code. This work was funded by a grant from the Center for Integration of Medicine and Innovative Technology and by National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) Grants NS062092 (to S. S. C.) and K08NS066099-01A1 (to W. S. A.); by National Eye Institute Grant EY017658, National Institute on Drug Abuse Grant NS063249, National Science Foundation Grant IOB 0645886, the Howard Hughes Medical Institute, and the Klingenstein Foundation (to E.N.E.); by NIH Director's Pioneer Award DP1OD003646 and Grant R01-MH071847 (to E.N.B.); by a Department of Veterans Affairs Career Development Transition Award, a Doris Duke Charitable Foundation-Clinical Scientist Development Award, Massachusetts General Hospital-Deane Institute for Integrated Research on Atrial Fibrillation and Stroke, and NIH/National Institute on Deafness and Other Communications Disorders Grant R01DC009899 (to L. R. H.); by a Canadian Institute of Health Research Fellowship (to L. D. L.); and by NIH New Innovator Award DP2-OD006454 and K-Award K25-NS057580 (to P.L.P.). NR 51 TC 95 Z9 96 U1 0 U2 20 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 DEC 4 PY 2012 VL 109 IS 49 BP E3377 EP E3386 DI 10.1073/pnas.1210907109 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054MF UT WOS:000312347200011 PM 23129622 ER PT J AU Peisley, A Jo, MH Lin, C Wu, B Orme-Johnson, M Walz, T Hohng, S Hur, S AF Peisley, Alys Jo, Myung Hyun Lin, Cecilie Wu, Bin Orme-Johnson, McGhee Walz, Thomas Hohng, Sungchul Hur, Sun TI Kinetic mechanism for viral dsRNA length discrimination by MDA5 filaments SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antiviral; innate immunity; filament dynamics; helicase; viral RNA ID DOUBLE-STRANDED-RNA; RECEPTOR RIG-I; INNATE IMMUNE-RESPONSE; SINGLE-MOLECULE; PATTERN-RECOGNITION; STRUCTURAL BASIS; ACTIVATION; DNA; HELICASE; FORMS AB The viral sensor MDA5 distinguishes between cellular and viral dsRNAs by length-dependent recognition in the range of similar to 0.5-7 kb. The ability to discriminate dsRNA length at this scale sets MDA5 apart from other dsRNA receptors of the immune system. We have shown previously that MDA5 forms filaments along dsRNA that disassemble upon ATP hydrolysis. Here, we demonstrate that filament formation alone is insufficient to explain its length specificity, because the intrinsic affinity of MDA5 for dsRNA depends only moderately on dsRNA length. Instead, MDA5 uses a combination of end disassembly and slow nucleation kinetics to "discard" short dsRNA rapidly and to suppress rebinding. In contrast, filaments on long dsRNA cycle between partial end disassembly and elongation, bypassing nucleation steps. MDA5 further uses this repetitive cycle of assembly and disassembly processes to repair filament discontinuities, which often are present because of multiple, internal nucleation events, and to generate longer, continuous filaments that more accurately reflect the length of the underlying dsRNA scaffold. Because the length of the continuous filament determines the stability of the MDA5-dsRNA interaction, the mechanism proposed here provides an explanation for how MDA5 uses filament assembly and disassembly dynamics to discriminate between self vs. nonself dsRNA. C1 [Peisley, Alys; Wu, Bin; Hur, Sun] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Lin, Cecilie; Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Walz, Thomas] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Peisley, Alys; Wu, Bin; Orme-Johnson, McGhee; Hur, Sun] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Jo, Myung Hyun; Hohng, Sungchul] Seoul Natl Univ, Dept Phys & Astron, Seoul 151747, South Korea. RP Hur, S (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM hur@idi.harvard.edu RI Wu, Bin/C-4715-2015 FU GlaxoSmithKline; Creative Research Initiatives (Physical Genetics Laboratory) [2009-0081562]; World Class University program of the National Research Foundation of Korea [R31-10032]; Massachusetts Life Sciences Center; Pew Scholarship FX We thank S. Harrison for rotavirus particles. A. P. and B. W. are recipients of postdoctoral fellowships from GlaxoSmithKline. T. W. is an Investigator in the Howard Hughes Medical Institute. S. Hohng is the recipient of Grants 2009-0081562 from the Creative Research Initiatives (Physical Genetics Laboratory) and R31-10032 from the World Class University program of the National Research Foundation of Korea. S. Hur is the recipient of a New Investigator Award from Massachusetts Life Sciences Center and a Pew Scholarship. NR 37 TC 42 Z9 42 U1 1 U2 11 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 DEC 4 PY 2012 VL 109 IS 49 BP E3340 EP E3349 DI 10.1073/pnas.1208618109 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054MF UT WOS:000312347200007 PM 23129641 ER PT J AU Leonardi, S Thomas, L Neely, ML Tricoci, P Lopes, RD White, HD Armstrong, PW Giugliano, RP Antman, EM Califf, RM Newby, LK Mahaffey, KW AF Leonardi, Sergio Thomas, Laine Neely, Megan L. Tricoci, Pierluigi Lopes, Renato D. White, Harvey D. Armstrong, Paul W. Giugliano, Robert P. Antman, Elliott M. Califf, Robert M. Newby, L. Kristin Mahaffey, Kenneth W. TI Comparison of the Prognosis of Spontaneous and Percutaneous Coronary Intervention-Related Myocardial Infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE angioplasty; cardiovascular; clinical trial; creatine kinase; diagnostic techniques; endpoint determination; myocardial infarction; surrogate endpoint ID ST-SEGMENT ELEVATION; COMPOSITE END-POINTS; UNIVERSAL DEFINITION; INVASIVE MANAGEMENT; MEDICAL-MANAGEMENT; ADVERSE OUTCOMES; CLINICAL-TRIALS; MORTALITY; RISK; EPTIFIBATIDE AB Objectives This study compared prognoses of myocardial infarction related to percutaneous coronary intervention (PCI, procedural MI) using increasing creatine kinase-myocardial band (CK-MB) thresholds with spontaneous MI. Background Procedural MI usually is defined by a CK-MB elevation of more than 3 times the upper limit of normal (ULN), but higher thresholds have been proposed. Methods Patients from the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndrome) study and the SYNERGY (Superior Yield of the New strategy of Enoxaparin, Revascularization and GIYcoprotein IIb/IIIa inhibitors) study treated with PCI were included. The primary end point was 1-year all-cause mortality from 24 h after PCI. To determine an enzymatic threshold for procedural MI with a prognosis similar to that of spontaneous MI, we redefined procedural MI using increasing CK-MB thresholds and compared corresponding hazard ratios with those of spontaneous MI (CK-MB more than twice the ULN). Hazard ratios for mortality for procedural and spontaneous MI were calculated using Cox proportional hazards regression and Global Registry of Acute Cardiac Events covariates for risk adjustment. Results Nine thousand eighty-seven patients who underwent PCI (46.8%) were included; 773 procedural MI and 239 spontaneous MI occurred within 30 days. Adjusted hazard ratios for 1-year death were 1.39 (95% confidence interval [CI]: 1.01 to 1.89) for procedural MI and 5.37 (95% CI: 3.90 to 7.38) for spontaneous MI. The CK-MB threshold for procedural MI that achieved the same prognosis as spontaneous MI was 27.7 times the ULN (95% CI: 13.9 to 58.4), but this differed between the SYNERGY study (57.9 times the ULN, 95% CI: 17.9 to 63.6) and the EARLY-ACS study (20.4 times the ULN, 95% CI: 5.16 to 24.2). Of all procedural MI, 49 (6%) had CK-MB elevations of 27.7 or more times the ULN. Conclusions The current enzymatic definition of procedural MI (CK-MB more than 3 times the ULN) used in clinical trials is less strongly associated with death than that of spontaneous MI. Procedural MI achieves similar prognosis for 1-year mortality when much higher CK-MB thresholds are applied. (J Am Coll Cardiol 2012;60:2296-304) (C) 2012 by the American College of Cardiology Foundation C1 [Leonardi, Sergio; Thomas, Laine; Neely, Megan L.; Tricoci, Pierluigi; Lopes, Renato D.; Newby, L. Kristin; Mahaffey, Kenneth W.] Duke Clin Res Inst, Durham, NC 27705 USA. [Leonardi, Sergio] Fdn IRCCS Policlin S Matteo, Pavia, Italy. [White, Harvey D.] Green Lane Cardiovasc Serv, Auckland, New Zealand. [Armstrong, Paul W.] Canadian VIGOUR Ctr, Edmonton, AB, Canada. [Giugliano, Robert P.; Antman, Elliott M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. [Califf, Robert M.] Duke Translat Med Inst, Durham, NC USA. RP Leonardi, S (reprint author), Duke Clin Res Inst, 2400 Pratt St,Room 0311, Durham, NC 27705 USA. EM sergio.leonardi@duke.edu OI Leonardi, Sergio/0000-0002-4800-6132 FU Schering-Plough; Sanofi-Aventis; Merck, Inc.; Bristol-Myers Squibb; Schering-Plough Research Institute; Eli Lilly Company; Daiichi Sankyo; Amylin; JJ-Scios; Merck/Schering Plough; Novartis; Bristol-Myers Squibb Foundation; AstraZeneca; diaDexus; Eli Lilly Co.; GlaxoSmithKline; Murdock Study; NHLBI; Regado Biosciences, Inc.; Roche; Abbott Vascular; Amgen Inc.; Amylin Inc.; Baxter; Edwards Lifesciences; Guidant Corp.; Ikaria; Johnson Johnson; KAI; Luitpold Pharmaceuticals; Medtronic; Portola Pharmaceuticals; POZEN Pharmaceuticals; Regado Biosciences; Roche Diagnostic; The Medicines Co. FX EARLY-ACS was funded by Schering-Plough, and SYNERGY was funded by Sanofi-Aventis. The current analyses were funded by Merck, Inc. Dr. Tricoci has served on an advisory board and has received research grants from Merck, Inc. Dr. Lopes received a research grant from Bristol-Myers Squibb. Dr. White has received research grants from Schering-Plough and Merck, Inc. Dr. Armstrong has received research grants from Schering-Plough Research Institute and Merck, Inc. Dr. Giugliano is a consultant to Beckman-Coulter; and received research grant support from Merck. Dr. Antman has received research grants from Eli Lilly & Company and Daiichi Sankyo. Dr. Califf has received research grants from Amylin, J&J-Scios, Merck/Schering Plough, Novartis, and the Bristol-Myers Squibb Foundation; is a consultant for J&J-Scios, Novartis, Bayer, Roche, Pfizer, and the Bristol-Myers Squibb Foundation; and has equity in NITROX LLC. Dr. Newby has received research grants from Amylin, AstraZeneca, Bristol-Myers Squibb, diaDexus, Eli Lilly & Co., GlaxoSmithKline, Merck, Inc., Murdock Study, NHLBI, Regado Biosciences, Inc., Roche, and Schering-Plough; and is a consultant for AstraZeneca, Daiichi-Sankyo, Eli Lilly & Co., Genentech, Johnson & Johnson, and Novartis. Dr. Mahaffey has received research grants from Abbott Vascular, Amgen Inc., Amylin Inc., AstraZeneca, Baxter, Bayer HealthCare, Boehringer Ingelheim, Brisol-Myers Squibb, Cordis, Daiichi Sankyo, Edwards Lifesciences, Eli Lilly & Co., GlaxoSmithKline, Guidant Corp., Ikaria, Johnson & Johnson, KAI, Luitpold Pharmaceuticals, Medtronic, Merck, Inc., Novartis, Portola Pharmaceuticals, POZEN Pharmaceuticals, Regado Biosciences, Roche Diagnostic, Schering-Plough, and The Medicines Co.; and is a consultant for Adolor, Amgen, AstraZeneca, Bayer HealthCare, Biotronik, Boehringer Ingelheim, Briston-Myers Squibb, Daiichi Sankyo, Eli Lilly & Co., Elsevier (AHJ), Exeter Group, Forest, Genentech, GlaxoSmithKline, Gilead Science, Haemonetics, Johnson & Johnson, Medtronic Inc., Merck & Co., Novartis, Orexigen, Orth/McNeill, Pfizer, Polymedix, Sanofi-Aventis, Schering-Plough, South East Area Health Education Center (SEAHEC), Springer Publishing, St. Jude Medical, Sun Pharma, and WebMD. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 28 TC 15 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 4 PY 2012 VL 60 IS 22 BP 2296 EP 2304 DI 10.1016/j.jacc.2012.09.005 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 045FN UT WOS:000311680500007 PM 23122801 ER PT J AU Robbins, GK Lester, W Johnson, KL Chang, YC Estey, G Surrao, D Zachary, K Lammert, SM Chueh, HC Meigs, JB Freedberg, KA AF Robbins, Gregory K. Lester, William Johnson, Kristin L. Chang, Yuchiao Estey, Gregory Surrao, Dominic Zachary, Kimon Lammert, Sara M. Chueh, Henry C. Meigs, James B. Freedberg, Kenneth A. TI Efficacy of a Clinical Decision-Support System in an HIV Practice A Randomized Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ELECTRONIC HEALTH RECORD; PHYSICIAN ORDER ENTRY; AMBULATORY-CARE; ANTIRETROVIRAL THERAPY; FOLLOW-UP; INFECTED PATIENTS; DELIVERY-SYSTEM; PATIENT SAFETY; ALERTS; INFORMATICS AB Background: Data to support improved patient outcomes from clinical decision-support systems (CDSSs) are lacking in HIV care. Objective: To test the efficacy of a CDSS in improving HIV outcomes in an outpatient clinic. Design: Randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00678600) Setting: Massachusetts General Hospital HIV Clinic. Participants: HIV care providers and their patients. Intervention: Computer alerts were generated for virologic failure (HIV RNA level >400 copies/mL after a previous HIV RNA level <= 400 copies/mL), evidence of suboptimal follow-up, and 11 abnormal laboratory test results. Providers received interactive computer alerts, facilitating appointment rescheduling and repeated laboratory testing, for half of their patients and static alerts for the other half. Measurements: The primary end point was change in CD4 cell count. Other end points included time to clinical event, 6-month suboptimal follow-up, and severe laboratory toxicity. Results: Thirty-three HIV care providers followed 1011 patients with HIV. In the intervention group, the mean increase in CD4 cell count was greater (0.0053 vs. 0.0032 x 10(9) cells/L per month; difference, 0.0021 x 10(9) cells/L per month [95% CI, 0.0001 to 0.004]; P = 0.040) and the rate of 6-month suboptimal follow-up was lower (20.6 vs. 30.1 events per 100 patient-years; P = 0.022) than those in the control group. Median time to next scheduled appointment was shorter in the intervention group than in the control group after a suboptimal follow-up alert (1.71 vs. 3.48 months; P < 0.001) and after a toxicity alert (2.79 vs. >6 months; P = 0.072). More than 90% of providers supported adopting the CDSS as part of standard care. Limitation: This was a 1-year informatics study conducted at a single hospital subspecialty clinic. Conclusion: A CDSS using interactive provider alerts improved CD4 cell counts and clinic follow-up for patients with HIV. Wider implementation of such systems can provide important clinical benefits. C1 [Robbins, Gregory K.] Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, Ctr AIDS Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Robbins, GK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, Ctr AIDS Res, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM grobbins@partners.org OI Lester, William/0000-0003-4086-9280 FU National Institute of Allergy and Infectious Diseases [K01AI062435, K24AI062476, P30AI42851, K24DK080140, R37AI42006]; Massachusetts General Hospital; National Institute of Allergy and Infectious Diseases FX By the National Institute of Allergy and Infectious Diseases (K01AI062435, K24AI062476, P30AI42851, K24DK080140, and R37AI42006) and the Massachusetts General Hospital Clinical Research Program.; National Institute of Allergy and Infectious Diseases. NR 56 TC 6 Z9 6 U1 8 U2 9 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 DEC 4 PY 2012 VL 157 IS 11 BP 757 EP + DI 10.7326/0003-4819-157-11-201212040-00003 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 049RC UT WOS:000312000100001 PM 23208165 ER PT J AU Shaheen, NJ Weinberg, DS Denberg, TD Chou, R Qaseem, A Shekelle, P AF Shaheen, Nicholas J. Weinberg, David S. Denberg, Thomas D. Chou, Roger Qaseem, Amir Shekelle, Paul CA Amer Coll Phys TI Upper Endoscopy for Gastroesophageal Reflux Disease: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ESOMEPRAZOLE 40 MG; SEVERE EROSIVE ESOPHAGITIS; OPEN-ACCESS ENDOSCOPY; QUALITY-OF-LIFE; BARRETTS-ESOPHAGUS; UNITED-STATES; GASTROINTESTINAL ENDOSCOPY; GASTRIC CARDIA; TIME TRENDS; SURVEILLANCE AB Background: Upper endoscopy is commonly used in the diagnosis and management of gastroesophageal reflux disease (GERD). Evidence demonstrates that it is indicated only in certain situations, and inappropriate use generates unnecessary costs and exposes patients to harms without improving outcomes. Methods: The Clinical Guidelines Committee of the American College of Physicians reviewed evidence regarding the indications for, and yield of, upper endoscopy in the setting of GERD, and to highlight how clinicians can increase the delivery of high-value health care. Best Practice Advice 1: Upper endoscopy is indicated in men and women with heartburn and alarm symptoms (dysphagia, bleeding, anemia, weight loss, and recurrent vomiting). Best Practice Advice 2: Upper endoscopy is indicated in men and women with: Typical GERD symptoms that persist despite a therapeutic trial of 4 to 8 weeks of twice-daily proton-pump inhibitor therapy. Severe erosive esophagitis after a 2-month course of proton-pump inhibitor therapy to assess healing and rule out Barrett esophagus. Recurrent endoscopy after this follow-up examination is not indicated in the absence of Barrett esophagus. History of esophageal stricture who have recurrent symptoms of dysphagia. Best Practice Advice 3: Upper endoscopy may be indicated: In men older than 50 years with chronic GERD symptoms (symptoms for more than 5 years) and additional risk factors (nocturnal reflux symptoms, hiatal hernia, elevated body mass index, tobacco use, and intra-abdominal distribution of fat) to detect esophageal adenocarcinoma and Barrett esophagus. For surveillance evaluation in men and women with a history of Barrett esophagus. In men and women with Barrett esophagus and no dysplasia, surveillance examinations should occur at intervals no more frequently than 3 to 5 years. More frequent intervals are indicated in patients with Barrett esophagus and dysplasia. Ann Intern Med. 2012; 157: 808-816. www.annals.org For author affiliations, see end of text. C1 [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19106 USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Harvard Vanguard Med Associates, Auburndale, MA 02466 USA. Oregon Hlth & Sci Univ, Portland, OR 97239 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Qaseem, A (reprint author), Amer Coll Physicians, 190 N Independence Mall W, Philadelphia, PA 19106 USA. RI Shaheen, Nicholas/A-1898-2013 FU National Cancer Institute [U54CA163060, U54CA156733] FX Financial support for the development of this best practice advice paper comes exclusively from the ACP's operating budget. Dr. Shaheen is supported by the National Cancer Institute (grant U54CA163060 and U54CA156733). NR 73 TC 49 Z9 51 U1 0 U2 8 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 DEC 4 PY 2012 VL 157 IS 11 BP 808 EP + DI 10.7326/0003-4819-157-11-201212040-00008 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 049RC UT WOS:000312000100006 PM 23208168 ER PT J AU D'Alcante, CC Diniz, JB Fossaluza, V Batistuzzo, MC Lopes, AC Shavitt, RG Deckersbach, T Malloy-Diniz, L Miguel, EC Hoexter, MQ AF D'Alcante, Carina C. Diniz, Juliana B. Fossaluza, Victor Batistuzzo, Marcelo C. Lopes, Antonio C. Shavitt, Roseli G. Deckersbach, Thilo Malloy-Diniz, Leandro Miguel, Euripedes C. Hoexter, Marcelo Q. TI Neuropsychological predictors of response to randomized treatment in obsessive-compulsive disorder SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Article DE Cognitive-behavioral therapy; Neuropsychology; Obsessive-compulsive disorder; Serotonin reuptake inhibitors; Treatment-naive ID SEROTONIN REUPTAKE INHIBITORS; COGNITIVE-BEHAVIORAL THERAPY; CLINICAL-TRIAL; PREFRONTAL CORTEX; NAIVE PATIENTS; IMPAIRMENT; PHARMACOTHERAPY; PERFORMANCE; DIMENSIONS; INVENTORY AB Objective: To identify neuropsychological predictors of treatment response to cognitive-behavioral therapy (CBT) and fluoxetine in treatment-naive adults with obsessive-compulsive disorder (OCD). Method: Thirty-eight adult outpatients with OCD underwent neuropsychological assessment, including tasks of intellectual function, executive functioning and visual and verbal memory, before randomization to a 12-week clinical trial of either CBT or fluoxetine. Neuropsychological measures were used to identify predictors of treatment response in OCD. Results: Neuropsychological measures that predicted a better treatment response to either CBT or fluoxetine were higher verbal IQ (Wechsler Abbreviated Scale of Intelligence) (p = 0.008); higher verbal memory on the California Verbal Learning Test (p = 0.710); shorter time to complete part D (Dots) (p<0.001), longer time to complete part W (Words) (p = 0.025) and less errors on part C (Colors) (p<0.001) in the Victoria Stroop Test (VST). Fewer perseverations on the California Verbal Learning Test, a measure of mental flexibility, predicted better response to CBT, but worse response to fluoxetine (p = 0.002). Conclusion: In general, OCD patients with better cognitive and executive abilities at baseline were more prone to respond to either CBT or fluoxetine. Our finding that neuropsychological measures of mental flexibility predicted response to treatment in opposite directions for CBT and fluoxetine suggests that OCD patients with different neuropsychological profiles may respond preferentially to one type of treatment versus the other. Further studies with larger samples of OCD patients are necessary to investigate the heuristic value of such findings in a clinical context. (C) 2012 Elsevier Inc. All rights reserved. C1 [D'Alcante, Carina C.; Diniz, Juliana B.; Fossaluza, Victor; Batistuzzo, Marcelo C.; Lopes, Antonio C.; Shavitt, Roseli G.; Miguel, Euripedes C.; Hoexter, Marcelo Q.] Univ Sao Paulo, Sch Med, Dept Psychiat, Obsess Compuls Disorder Spectrum Project Clin, BR-78505453 Sao Paulo, Brazil. [Fossaluza, Victor] Univ Sao Paulo, Inst Math & Stat, BR-78505453 Sao Paulo, Brazil. [Deckersbach, Thilo] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Malloy-Diniz, Leandro] Univ Fed Minas Gerais, Inst Biol Sci, Grad Program Neurosci, Belo Horizonte, MG, Brazil. [Hoexter, Marcelo Q.] Fed Univ Sao Paulo UNIFESP, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LiNC, Sao Paulo, Brazil. RP D'Alcante, CC (reprint author), Univ Sao Paulo, Med Sch Sao Paulo, Rua Dr Ovidio Pires de Campos, BR-78505453 Sao Paulo, Brazil. EM chaubetca@hcnet.usp.br RI Malloy-Diniz, Leandro/D-7829-2013; Miguel, Euripedes/B-2871-2008; Fossaluza, Victor/B-3377-2014; Hoexter, Marcelo/D-7620-2013; Batistuzzo, Marcelo/H-7790-2015 OI Malloy-Diniz, Leandro/0000-0002-6606-1354; Fossaluza, Victor/0000-0002-9328-0210; Hoexter, Marcelo/0000-0002-9302-4380; FU National Council for Scientific and Technological Development (CNPq: Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) [521369/96-7, 475919/2006-8, 481791/2004-3]; Foundation for the Support of Research in the State of Sao Paulo (FAPESP: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) [05/55628-08, 05/04206-6, 06/61459-7, 06/50273-0]; FAPESP [06/58286-3] FX This study received financial support in the form of grants provided by the following Brazilian governmental agencies: the National Council for Scientific and Technological Development (CNPq: Conselho Nacional de Desenvolvimento Cientifico e Tecnologico), grant numbers: 521369/96-7, 475919/2006-8 and 481791/2004-3; and the Foundation for the Support of Research in the State of Sao Paulo (FAPESP: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo), grant numbers: 05/55628-08, 05/04206-6,06/61459-7 and 06/50273-0). Dr. Carina received research support from FAPESP (06/58286-3). All other authors report no competing interests. NR 63 TC 20 Z9 21 U1 5 U2 41 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD DEC 3 PY 2012 VL 39 IS 2 BP 310 EP 317 DI 10.1016/j.pnpbp2012.07.002 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 035JU UT WOS:000310943500014 PM 22789662 ER PT J AU Britton, KA Pedley, A Massaro, JM Corsini, EM Murabito, JM Hoffmann, U Fox, CS AF Britton, Kathryn A. Pedley, Alison Massaro, Joseph M. Corsini, Erin M. Murabito, Joanne M. Hoffmann, Udo Fox, Caroline S. TI Prevalence, Distribution, and Risk Factor Correlates of High Thoracic Periaortic Fat in the Framingham Heart Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE body fat distribution; obesity; perivascular adipose tissue; risk factors; visceral adipose tissue ID PERIVASCULAR ADIPOSE-TISSUE; METABOLICALLY-OBESE; PHYSICAL-ACTIVITY; DISEASE; ASSOCIATION; NUTRITION; COHORT AB Background-Thoracic periaortic adipose tissue (TAT) is associated with atherosclerosis and cardiovascular disease (CVD) risk factors and may play a role in obesity-mediated vascular disease. We sought to determine the prevalence, distribution, and risk factor correlates of high TAT. Methods and Results-Participants from the Framingham Heart Study (n=3246, 48% women, mean age 51.1 years) underwent multidetector computed tomography; high TAT and visceral adipose tissue (VAT) were defined on the basis of sex-specific 90th percentiles in a healthy referent sample. The prevalence of high TAT was 38.1% in women and 35.7% in men. Among individuals without high VAT, 10.1% had high TAT. After adjustment for age and VAT, both women and men with high TAT in the absence of high VAT were older and had a higher prevalence of CVD (P<0.0001) compared with those without high TAT. In addition, men in this group were more likely to be smokers (P=0.02), whereas women were more likely to have low high-density lipoprotein cholesterol (P=0.005). Conclusions-Individuals in our community-based sample with high TAT in the absence of high VAT were characterized by an adverse cardiometabolic profile. This adipose tissue phenotype may identify a subset of individuals with distinct metabolic characteristics. C1 [Britton, Kathryn A.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Britton, Kathryn A.; Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Britton, Kathryn A.; Pedley, Alison; Murabito, Joanne M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Corsini, Erin M.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham, MA USA. [Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Hypertens, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBIs Framingham Heart Study, 75 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Murabito, Joanne/0000-0002-0192-7516; Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; National Heart, Lung, and Blood Institute [K12 HL083786] FX This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract N01-HC-25195). Dr. Britton was supported by a Research Career Development Award (K12 HL083786) from the National Heart, Lung, and Blood Institute. NR 26 TC 18 Z9 18 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 DEC PY 2012 VL 1 IS 6 AR UNSP e004200 DI 10.1161/JAHA.112.004200 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243RY UT WOS:000326335900007 PM 23316328 ER PT J AU Thanassoulis, G Massaro, JM Corsini, E Rogers, I Schlett, CL Meigs, JB Hoffmann, U O'Donnell, CJ Fox, CS AF Thanassoulis, George Massaro, Joseph M. Corsini, Erin Rogers, Ian Schlett, Christopher L. Meigs, James B. Hoffmann, Udo O'Donnell, Christopher J. Fox, Caroline S. TI Periaortic Adipose Tissue and Aortic Dimensions in the Framingham Heart Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE adipose tissue; aneurysm; aorta; peripheral vascular disease ID PERICARDIAL FAT; RISK-FACTORS; ANEURYSMS; DISEASE; HEALTH; COMMUNITY; DIAMETER; OBESITY; COHORT AB Background-Periaortic fat, because of its contiguity with the aorta, may promote vascular remodeling and aortic dilatation. However, the relations between perioartic fat depots and aortic dimensions have not been previously described. Methods and Results-A total of 3001 individuals (mean age 50 +/- 10 years, 49% women) from the Framingham Offspring and Third Generation cohorts underwent computed tomography for quantification of periaortic fat and aortic dimensions. We estimated the association between quantitative periaortic and visceral adipose tissue volumes (per standard deviation [SD] increment of volume) with aortic dimensions in both the thorax and abdomen. Thoracic periaortic fat was associated with higher thoracic aortic dimensions (beta coefficient per SD of fat volume 0.67 mm, 95% confidence interval 0.58 to 0.76 mm; P<0.001). The association persisted after adjustment for age, sex, and cardiovascular risk factors including body mass index and visceral adipose tissue volume. Results for the association of periaortic fat and abdominal aortic dimensions were similar. Further adjustment for adipokines (resistin and adiponectin) had no significant impact on these associations. Conclusions-Periaortic fat volume was associated with aortic dimensions in both the thorax and abdomen, supporting the notion that local fat depots may contribute to aortic remodeling. Further work to understand the mechanisms underlying this association is warranted. C1 [Thanassoulis, George; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, NIH, Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Corsini, Erin; Rogers, Ian; Schlett, Christopher L.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, NIH, Intramural Res, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), NHLBI, NIH, Framingham Heart Study, Framingham, MA USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Canadian Institute of Health Research; Fonds de Recherche en Sante du Quebec FX This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (contract N01-HC-25195). Dr Thanassoulis was supported by a Research Fellowship from the Canadian Institute of Health Research and the Fonds de Recherche en Sante du Quebec. NR 25 TC 18 Z9 18 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD DEC PY 2012 VL 1 IS 6 AR UNSP e000885 DI 10.1161/JAHA.112.000885 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243RY UT WOS:000326335900021 PM 23316310 ER PT J AU Dietrich, EA Gebhard, KH Fasching, CE Giacaman, RA Kappes, JC Ross, KF Herzberg, MC AF Dietrich, Elizabeth A. Gebhard, Kristin H. Fasching, Claudine E. Giacaman, Rodrigo A. Kappes, John C. Ross, Karen F. Herzberg, Mark C. TI Short Communication HIV Type 1 Escapes Inactivation by Saliva via Rapid Escape into Oral Epithelial Cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID PERMISSIVE CELLS; KERATINOCYTES; TRANSMISSION; INFECTION AB Saliva contains anti-HIV-1 factors, which show unclear efficacy in thwarting mucosal infection. When incubated in fresh, unfractionated whole saliva, infectious HIV-1 IIIb and BaL (X4- and R5-tropic, respectively) persisted from 4 to at least 30 min in a saliva concentration-dependent manner. In salivary supernatant for up to 6 h, both infectious HIV-1 strains "escaped" into immortalized oral epithelial cells; infectious BaL showed selectively enhanced escape in the presence of saliva. Fluorescently labeled HIV-1 virus-like particles entered oral epithelial cells within minutes of exposure. Using a previously unrecognized mechanism, therefore, strains of HIV-1 escape inactivation by saliva via rapid uptake into oral epithelial cells. C1 [Herzberg, Mark C.] Univ Minnesota, Sch Dent, Dept Diagnost & Biol Sci, Minneapolis, MN 55455 USA. [Dietrich, Elizabeth A.; Gebhard, Kristin H.; Fasching, Claudine E.; Giacaman, Rodrigo A.; Ross, Karen F.; Herzberg, Mark C.] Minneapolis VA Med Ctr, Mucosal & Vaccine Res Ctr, Minneapolis, MN USA. [Kappes, John C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Kappes, John C.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Kappes, John C.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Kappes, John C.] Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA. RP Herzberg, MC (reprint author), Univ Minnesota, Sch Dent, Dept Diagnost & Biol Sci, 17-164 Moos Tower,515 Delaware St SE, Minneapolis, MN 55455 USA. EM mcherzb@umn.edu RI Giacaman, Rodrigo/A-9811-2010 OI Giacaman, Rodrigo/0000-0003-3362-5173 FU NIH/ NIDCR [R01DE015503, R21DE015506]; Minneapolis VA Medical Center; UAB Center for AIDS Research Virology and Sequencing Cores [P30-AI-27767]; Genetically Defined Microbe and Expression Core of the UAB Mucosal HIV and Immunobiology Center [R24 DK-64400]; Veterans Affairs, Research Service FX The support of NIH/ NIDCR R01DE015503 (M. C. H.), R21DE015506 (K. F. R.), and funds from the Minneapolis VA Medical Center by J.C.K. and M. C. H. is greatly appreciated. Research in J.C.K.'s laboratory was supported by the UAB Center for AIDS Research Virology and Sequencing Cores (P30-AI-27767), the Genetically Defined Microbe and Expression Core of the UAB Mucosal HIV and Immunobiology Center (R24 DK-64400), and a Merit Review Award from the Veterans Affairs, Research Service. NR 16 TC 5 Z9 5 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC PY 2012 VL 28 IS 12 BP 1574 EP 1578 DI 10.1089/aid.2011.0069 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 047FW UT WOS:000311825000007 PM 22077822 ER PT J AU Cayabyab, MJ Macovei, L Campos-Neto, A AF Cayabyab, Mark J. Macovei, Lilia Campos-Neto, Antonio TI Current and novel approaches to vaccine development against tuberculosis SO FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY LA English DT Review DE tuberculosis; Mycobacterium tuberculosis; vaccine; antigen; adjuvant; recombinant protein; delivery system ID T-CELL RESPONSES; BACILLUS-CALMETTE-GUERIN; RECOMBINANT MYCOBACTERIUM-SMEGMATIS; MULTIDRUG-RESISTANT TUBERCULOSIS; MICROBIAL ENUMERATION TECHNIQUE; ACTIVE PULMONARY TUBERCULOSIS; HIV-ASSOCIATED TUBERCULOSIS; GUINEA-PIG MODEL; PROTECTIVE IMMUNITY; TUBERCLE-BACILLI AB Antibiotics and vaccines are the two most successful medical countermeasures that humans have created against a number of pathogens. However a select few e.g., Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) have evaded eradication by vaccines and therapeutic approaches. TB is a global public health problem that kills 1.4 million people per year. The past decade has seen significant progress in developing new vaccine candidates, but the most fundamental questions in understanding disease progression and protective host responses that are responsible for controlling Mtb infection still remain poorly resolved. Current TB treatment requires intense chemotherapy with several antimicrobials, while the only approved vaccine is the classical viable whole-cell based Bacille-Calmette-Guerin (BCG) that protects children from severe forms of TB, but fails to protect adults. Taken together, there is a growing need to conduct basic and applied research to develop novel vaccine strategies against TB. This review is focused on the discussion surrounding current strategies and innovations being explored to discover new protective antigens, adjuvants, and delivery systems in the hopes of creating an efficacious TB vaccine. C1 [Cayabyab, Mark J.; Macovei, Lilia; Campos-Neto, Antonio] Forsyth Inst, Cambridge, MA 02142 USA. [Cayabyab, Mark J.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Campos-Neto, A (reprint author), Forsyth Inst, Infect Dis Res Ctr, 245 1st St, Cambridge, MA 02142 USA. EM acampos@forsyth.org FU National Institutes of Health [R01 AI076425] FX Financial support: This work was supported by the following grants from the National Institutes of Health: R01 AI076425 to A. Campos-Neto. NR 168 TC 11 Z9 12 U1 1 U2 9 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 2235-2988 J9 FRONT CELL INFECT MI JI Front. Cell. Infect. Microbiol. PD DEC PY 2012 VL 2 AR UNSP 154 DI 10.3389/fcimb.2012.00154 PG 16 WC Immunology; Microbiology SC Immunology; Microbiology GA 221EC UT WOS:000324639400003 PM 23230563 ER PT J AU Utech, AE Tadros, EM Hayes, TG Garcia, JM AF Utech, Anne E. Tadros, Eiriny M. Hayes, Teresa G. Garcia, Jose M. TI Predicting survival in cancer patients: the role of cachexia and hormonal, nutritional and inflammatory markers SO JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE LA English DT Article DE Inflammation; Anorexia; Interleukin-6; TNF-alpha; Testosterone ID RESTING ENERGY-EXPENDITURE; TUMOR-BEARING RATS; CELL LUNG-CANCER; PROINFLAMMATORY CYTOKINES; SYMPTOM ASSESSMENT; TERMINAL CANCER; SERUM-LEVELS; WEIGHT-LOSS; FOOD-INTAKE; HYPOGONADISM AB Background Cancer can lead to weight loss, anorexia, and poor nutritional status, which are associated with decreased survival in cancer patients. Methods Male cancer patients (n=136) were followed for a mean time of 4.5 years. Variables were obtained at baseline: cancer stage, albumin, hemoglobin, tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, bioavailable testosterone, appetite questionnaire, and weight change from baseline to 18 months. Primary statistical tests included Kaplan-Meier survival analysis and Cox proportional hazard regression (PHREG). Results Univariate PHREG showed that cancer stage, albumin, hemoglobin, TNF-alpha, IL-6, and weight change were each significantly associated with mortality risk (P<0.05), but bioavailable testosterone was not. Multivariate PHREG analysis established that weight change and albumin were jointly statistically significant even after adjusting for stage. Conclusion In this sample of male oncology patients, cancer stage, serum albumin, and weight loss predicted survival. High levels of inflammatory markers and hemoglobin are associated with increased mortality, but do not significantly improve the ability to predict survival above and beyond cancer stage, albumin, and weight loss. C1 [Utech, Anne E.; Tadros, Eiriny M.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. [Hayes, Teresa G.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Div Hematol & Oncol, Houston, TX 77030 USA. [Garcia, Jose M.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Houston, TX 77030 USA. RP Garcia, JM (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Houston, TX 77030 USA. EM jgarcia1@bcm.edu FU Dept. of Veterans Affairs [BX000507, CX000174]; Abbott; Aeterna Zentaris; Helsinn Therapeutics FX This material is based upon work supported by the Dept. of Veterans Affairs (MREP, SCVAHNCDA, MERIT awards BX000507 and CX000174). Dr. Garcia receives research support from Abbott, Aeterna Zentaris, and Helsinn Therapeutics. The authors of this manuscript certify that they comply with the ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia, and Muscle [35]. NR 35 TC 25 Z9 25 U1 0 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 2190-5991 J9 J CACHEXIA SARCOPENI JI J. Caxhexia Sarcopenia Muscle PD DEC PY 2012 VL 3 IS 4 BP 245 EP 251 DI 10.1007/s13539-012-0075-5 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 218WV UT WOS:000324464200005 PM 22648739 ER PT J AU Ghobrial, IM AF Ghobrial, Irene M. TI Are you sure this is Waldenstrom macroglobulinemia? SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; LYMPHOPLASMACYTIC LYMPHOMA/WALDENSTROM MACROGLOBULINEMIA; IGM MONOCLONAL GAMMOPATHY; FREE LIGHT-CHAIN; PHASE-II TRIAL; UNDETERMINED SIGNIFICANCE; PROGNOSTIC-FACTORS; MULTIPLE-MYELOMA; FOLLOW-UP AB Waldenstrom macroglobulinemia (WM) is a rare lymphoproliferative disorder characterized by the presence of lymphoplasmacytic cells in the BM and IgM monoclonal protein in the serum. The origin of the malignant clone is thought to be a B cell arrested after somatic hypermutation in the germinal center and before terminal differentiation to plasma cells. In this review, recent advances in the genetic and epigenetic regulators of tumor progression are discussed. Risk factors include IgM-monoclonal gammopathy of undermined significance, familial disease, and immunological factors. The clinical manifestations of the disease include those related to clonal infiltration of the BM, lymph nodes, and, rarely, other sites such as pulmonary or CNS infiltration (Bing-Neel syndrome). Other manifestations are related to the IgM monoclonal protein, including hyperviscosity, cryoglobulinemia, protein-protein interactions, Ab-mediated disorders such as neuropathy, hemolytic anemia, and Schnitzler syndrome. IgM deposition in organs can lead to amyloidogenic manifestations in WM. The diagnostic workup for a patient with WM and rare presentations of WM are described herein. Prognosis of WM depends on 5 major factors in the International Staging System, including age, anemia, thrombocytopenia, beta-2 microglobulin, and IgM level. The differential diagnosis of WM includes IgM-multiple myeloma, marginal zone lymphoma, mantle cell lymphoma, and follicular lymphoma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,D1B30, Boston, MA 02115 USA. EM Irene_ghobrial@dfci.harvard.edu FU International Waldenstrom Macroglobulinemia Foundation [1R01F0003743]; Heje fellowship; Kirsch Laboratory for Waldenstrom at Dana-Farber Cancer Institute, Boston, MA FX This study was supported in part by the International Waldenstrom Macroglobulinemia Foundation (1R01F0003743), Heje fellowship, and Kirsch Laboratory for Waldenstrom at Dana-Farber Cancer Institute, Boston, MA. NR 58 TC 14 Z9 15 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2012 BP 586 EP 594 DI 10.1182/asheducation-2012.1.586 PG 9 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA 209KT UT WOS:000323755900087 ER PT J AU Corro, G Rocco, CA De Candia, C Catano, G Turk, G Mangano, A Aulicino, PC Bologna, R Sen, L AF Corro, Guillermo Rocco, Carlos A. De Candia, Cristian Catano, Gabriel Turk, Gabriela Mangano, Andrea Aulicino, Paula C. Bologna, Rosa Sen, Luisa TI Genetic and Functional Analysis of HIV Type 1 nef Gene Derived from Long-Term Nonprogressor Children: Association of Attenuated Variants with Slow Progression to Pediatric AIDS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DISEASE PROGRESSION; PERINATAL INFECTION; STRUCTURAL DEFECTS; REPEAT SEQUENCES; NATURAL-HISTORY; TRANSGENIC MICE; T-CELLS; TRANSMISSION; REPLICATION AB Among persons infected by HIV-1, the rate of progression to AIDS is multifactorial being affected by host and viral factors, including the HIV-encoded negative factor (Nef). Our aim was to define whether variations in the nef gene as well as its functions may be associated with slower HIV disease course in infected children. The proviral HIV-1 nef gene was cloned, sequenced, and compared in children with contrasting disease course: 10 long-term nonprogressors (LTNP) and six rapid progressor (RP). The CD4 and MHC-I down-modulation ability of nef alleles derived from LTNP and RP children was analyzed. We observed that only one of our 10 LTNP had a protective genetic background, and out of them, 40% had defective nef genes, carrying substitutions at the (AWLEAQ(56-61)) and the (Rxx(22-24)) domains, and that those alleles were unable of down-regulate CD4 and MHC-I. The emergence or presence of Nef L58V substitution was associated with viral attenuation, indicated by a reduction in HIV viral loads, a persistent preservation of CD4(+) T cell counts, and lack of AIDS-related symptoms. Our results demonstrate that HIV-1 perinatally infected children carrying functionally defective nef HIV-1 strains have prolonged asymptomatic phases without therapy, suggesting a relevant role of CD4 and MHC-I down-modulation Nef domains on in vivo HIV-1 pathogenesis and pediatric immunodeficiency outcome. C1 [Corro, Guillermo; Rocco, Carlos A.; Mangano, Andrea; Aulicino, Paula C.; Sen, Luisa] Hosp Pediat Prof Dr Juan P Garran, Lab Biol Celular & Retrovirus, Buenos Aires, DF, Argentina. [Corro, Guillermo; Mangano, Andrea; Aulicino, Paula C.; Sen, Luisa] Consejo Nacl Invest Cient & Tecn, Buenos Aires, DF, Argentina. [De Candia, Cristian; Turk, Gabriela] Univ Buenos Aires, Natl Reference Ctr AIDS, Buenos Aires, DF, Argentina. [Catano, Gabriel] S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV Infect 1, San Antonio, TX USA. [Catano, Gabriel] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Bologna, Rosa] Hosp Pediat Prof Dr Juan P Garrahan, Serv Infectol, Buenos Aires, DF, Argentina. RP Corro, G (reprint author), 1881 Combate Pozos St,C1245AAM, Buenos Aires, DF, Argentina. EM gcorro2@gmail.com NR 54 TC 6 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC PY 2012 VL 28 IS 12 BP 1617 EP 1626 DI 10.1089/aid.2012.0020 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 047FW UT WOS:000311825000013 PM 22583022 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI CLEAVING AN UNKNOWN WORLD: The Powell Expeditions and the Scientific Exploration of the Colorado Plateau SO JOURNAL OF THE WEST LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ABC-CLIO PI SANTA BARBARA PA 130 CREMONA DR, SANTA BARBARA, CA 93117 USA SN 0022-5169 J9 J WEST JI J. West PD WIN PY 2012 VL 51 IS 1 BP 86 EP 87 PG 2 WC History SC History GA 134FA UT WOS:000318194400014 ER PT J AU Sun, JZ Wang, GI Goyal, VK Varshney, LR AF Sun, John Z. Wang, Grace I. Goyal, Vivek K. Varshney, Lav R. TI A framework for Bayesian optimality of psychophysical laws SO JOURNAL OF MATHEMATICAL PSYCHOLOGY LA English DT Article DE Relative Error; Bayesian Quantization; Weber-Fechner; Psychophysical Scale ID WEBER-FECHNER LAW; INFORMATION; INTENSITY; DISCRIMINATION; COMPRESSION; MAGNITUDE; EQUATION; SYSTEM; CORTEX; BRAIN AB The Weber-Fechner law states that perceived intensity is proportional to physical stimuli on a logarithmic scale. In this work, we formulate a Bayesian framework for the scaling of perception and find logarithmic and related scalings are optimal under expected relative error fidelity. Therefore, the Weber-Fechner law arises as being information theoretically efficient under the constraint of limited representability. An even stronger connection is drawn between the Weber-Fechner law and a Bayesian framework when neural storage or communication is the dominant concern, such as for numerosity. Theoretical results and experimental verification for perception of sound intensity are both presented. (C) 2012 Elsevier Inc. All rights reserved. C1 [Sun, John Z.; Wang, Grace I.; Goyal, Vivek K.; Varshney, Lav R.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Wang, Grace I.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Varshney, Lav R.] IBM Thomas J Watson Res Ctr, Hawthorne, NY 10532 USA. RP Varshney, LR (reprint author), IBM Thomas J Watson Res Ctr, Hawthorne, NY 10532 USA. EM varshney@alum.mit.edu FU National Science Foundation [0643836, 1115159] FX This material is based upon work supported by the National Science Foundation under Grants 0643836 and 1115159. The authors thank the reviewers, the associate editor, Bo Wen, Dmitri B. Chklovskii, Barbara Shinn-Cunningham, Katherine Heller, and Jeff Beck for their insightful comments. NR 49 TC 14 Z9 15 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-2496 J9 J MATH PSYCHOL JI J. Math. Psychol. PD DEC PY 2012 VL 56 IS 6 BP 495 EP 501 DI 10.1016/j.jmp.2012.08.002 PG 7 WC Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods; Psychology, Mathematical SC Mathematics; Mathematical Methods In Social Sciences; Psychology GA 119IP UT WOS:000317091300009 ER PT J AU Vernochet, C Kahn, CR AF Vernochet, Cecile Kahn, C. Ronald TI Mitochondria, obesity and aging SO AGING-US LA English DT Editorial Material C1 [Vernochet, Cecile] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Vernochet, C (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK031036, R01 DK082659, R37 DK031036] NR 7 TC 9 Z9 10 U1 0 U2 4 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD DEC PY 2012 VL 4 IS 12 BP 859 EP 860 PG 2 WC Cell Biology SC Cell Biology GA 104HD UT WOS:000315981800003 PM 23363767 ER PT J AU Thesen, T McDonald, CR Carlson, C Doyle, W Cash, S Sherfey, J Felsovalyi, O Girard, H Barr, W Devinsky, O Kuzniecky, R Halgren, E AF Thesen, Thomas McDonald, Carrie R. Carlson, Chad Doyle, Werner Cash, Syd Sherfey, Jason Felsovalyi, Olga Girard, Holly Barr, William Devinsky, Orrin Kuzniecky, Ruben Halgren, Eric TI Sequential then interactive processing of letters and words in the left fusiform gyrus SO NATURE COMMUNICATIONS LA English DT Article ID ANTEROVENTRAL TEMPORAL-LOBE; DEPTH-RECORDED POTENTIALS; FORM AREA; SPATIOTEMPORAL DYNAMICS; OCCIPITOTEMPORAL CORTEX; BRAIN IMAGES; TIME-COURSE; FMRI; RECOGNITION; PERCEPTION AB Despite decades of cognitive, neuropsychological and neuroimaging studies, it is unclear if letters are identified before word-form encoding during reading, or if letters and their combinations are encoded simultaneously and interactively. Here using functional magnetic resonance imaging, we show that a 'letter-form' area (responding more to consonant strings than false fonts) can be distinguished from an immediately anterior 'visual word-form area' in ventral occipito-temporal cortex (responding more to words than consonant strings). Letter-selective magnetoencephalographic responses begin in the letter-form area similar to 60 ms earlier than word-selective responses in the word-form area. Local field potentials confirm the latency and location of letter-selective responses. This area shows increased high-gamma power for similar to 400 ms, and strong phase-locking with more anterior areas supporting lexico-semantic processing. These findings suggest that during reading, visual stimuli are first encoded as letters before their combinations are encoded as words. Activity then rapidly spreads anteriorly, and the entire network is engaged in sustained integrative processing. C1 [Thesen, Thomas; Carlson, Chad; Doyle, Werner; Barr, William; Devinsky, Orrin; Kuzniecky, Ruben] NYU, Dept Neurol, Comprehens Epilepsy Ctr, New York, NY 10016 USA. [Thesen, Thomas; McDonald, Carrie R.; Sherfey, Jason; Felsovalyi, Olga; Girard, Holly; Halgren, Eric] Univ Calif San Diego, Dept Radiol, Multimodal Imaging Lab, La Jolla, CA 92037 USA. [Thesen, Thomas; McDonald, Carrie R.; Sherfey, Jason; Felsovalyi, Olga; Girard, Holly; Halgren, Eric] Univ Calif San Diego, Dept Neurosci, Multimodal Imaging Lab, La Jolla, CA 92037 USA. [Cash, Syd] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Cambridge, MA 02114 USA. [Halgren, Eric] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92037 USA. [Halgren, Eric] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92037 USA. [Halgren, Eric] Univ Calif San Diego, Kavli Inst Mind & Brain, La Jolla, CA 92037 USA. RP Thesen, T (reprint author), NYU, Dept Neurol, Comprehens Epilepsy Ctr, New York, NY 10016 USA. EM thomas.thesen@med.nyu.edu OI Barr, William/0000-0001-7711-7758; Devinsky, Orrin/0000-0003-0044-4632 FU NIH [NS18741]; FACES FX We thank Anders Dale and Donald Hagler for analysis tools, and Mark Blumberg and Amy Trongnetrpunya for help with data collection. This research was supported by grants from NIH (NS18741) and FACES. NR 51 TC 33 Z9 33 U1 2 U2 17 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 DEC PY 2012 VL 3 AR 1284 DI 10.1038/ncomms2220 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 109HH UT WOS:000316356700051 PM 23250414 ER PT J AU Yu, WY Chory, EJ Wernimont, AK Tempel, W Scopton, A Federation, A Marineau, JJ Qi, J Barsyte-Lovejoy, D Yi, JN Marcellus, R Iacob, RE Engen, JR Griffin, C Aman, A Wienholds, E Li, FL Pineda, J Estiu, G Shatseva, T Hajian, T Al-awar, R Dick, JE Vedadi, M Brown, PJ Arrowsmith, CH Bradner, JE Schapira, M AF Yu, Wenyu Chory, Emma J. Wernimont, Amy K. Tempel, Wolfram Scopton, Alex Federation, Alexander Marineau, Jason J. Qi, Jun Barsyte-Lovejoy, Dalia Yi, Joanna Marcellus, Richard Iacob, Roxana E. Engen, John R. Griffin, Carly Aman, Ahmed Wienholds, Erno Li, Fengling Pineda, Javier Estiu, Guillermina Shatseva, Tatiana Hajian, Taraneh Al-awar, Rima Dick, John E. Vedadi, Masoud Brown, Peter J. Arrowsmith, Cheryl H. Bradner, James E. Schapira, Matthieu TI Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors SO NATURE COMMUNICATIONS LA English DT Article ID EXCHANGE MASS-SPECTROMETRY; MIXED-LINEAGE LEUKEMIA; H3K79 METHYLATION; PROTEIN METHYLTRANSFERASES; HISTONE METHYLTRANSFERASE; DRUG DISCOVERY; SET DOMAIN; CELLS AB Selective inhibition of protein methyltransferases is a promising new approach to drug discovery. An attractive strategy towards this goal is the development of compounds that selectively inhibit binding of the cofactor, S-adenosylmethionine, within specific protein methyltransferases. Here we report the three-dimensional structure of the protein methyltransferase DOT1L bound to EPZ004777, the first S-adenosylmethionine-competitive inhibitor of a protein methyltransferase with in vivo efficacy. This structure and those of four new analogues reveal remodelling of the catalytic site. EPZ004777 and a brominated analogue, SGC0946, inhibit DOT1L in vitro and selectively kill mixed lineage leukaemia cells, in which DOT1L is aberrantly localized via interaction with an oncogenic MLL fusion protein. These data provide important new insight into mechanisms of cell-active S-adenosylmethionine-competitive protein methyltransferase inhibitors, and establish a foundation for the further development of drug-like inhibitors of DOT1L for cancer therapy. C1 [Yu, Wenyu; Wernimont, Amy K.; Tempel, Wolfram; Scopton, Alex; Barsyte-Lovejoy, Dalia; Li, Fengling; Shatseva, Tatiana; Hajian, Taraneh; Vedadi, Masoud; Brown, Peter J.; Arrowsmith, Cheryl H.; Schapira, Matthieu] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada. [Chory, Emma J.; Federation, Alexander; Marineau, Jason J.; Qi, Jun; Yi, Joanna; Pineda, Javier; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chory, Emma J.; Iacob, Roxana E.; Engen, John R.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Yi, Joanna] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Marcellus, Richard; Griffin, Carly; Aman, Ahmed; Al-awar, Rima] Ontario Inst Canc Res, Toronto, ON M5G 1L7, Canada. [Wienholds, Erno; Dick, John E.] Univ Toronto, Campbell Family Inst, Ontario Canc Inst, Princess Margaret Canc Ctr,Univ Hlth Network, Toronto, ON M5G 1L7, Canada. [Wienholds, Erno; Dick, John E.] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1L7, Canada. [Pineda, Javier; Estiu, Guillermina] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. [Bradner, James E.] Harvard Univ, Dept Med, Sch Med, Boston, MA USA. [Schapira, Matthieu] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON M5S 1A8, Canada. RP Arrowsmith, CH (reprint author), Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada. EM carrow@uhnresearch.ca; james_bradner@dfci.harvard.edu; matthieu.schapira@utoronto.ca FU National Science Foundation [OCI-1053575]; National Cancer Institute [Y1-CO-1020]; National Institute of General Medical Sciences [Y1-GM-1104]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; Leukaemia and Lymphoma Society (SCOR); National Institutes of Health [R01 CA152314, K08CA128972]; American Society of Hematology; William Lawrence and Blanche Hughes Foundation; Steamboat Foundation Award; Northeastern University; Barnett Institute of Chemical and Biological Analysis; NIH [R01-GM086507]; Canadian Institutes of Health Research, Eli Lilly Canada; Genome Canada; GlaxoSmithKline; Ontario Ministry of Economic Development and Innovation; Novartis Research Foundation; Pfizer; AbbVie; Takeda; Wellcome Trust FX We wish to thank Dr Abdellah Allali-Hassani and Guillermo Senisterra for their expert advice on biochemical assays, and Dr Aled Edwards for critical comments on the manuscript. This work used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant number OCI-1053575. The computations were performed on Kraken at the National Institute for Computational Sciences (http://www.nics.tennessee.edu/). X-ray diffraction data were collected at the LRL Collaborative Access Team (LRL-CAT) beam line facilities at Sector 31 of the Advanced Photon Source operated by Eli Lilly and Company, GM/CA CAT that is funded in whole or in part with Federal funds from the National Cancer Institute (Y1-CO-1020) and the National Institute of General Medical Sciences (Y1-GM-1104); the Advanced Photon Source supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. J.E.B., J.Q. and J.J.M. are supported by the Leukaemia and Lymphoma Society (SCOR), the National Institutes of Health (R01 CA152314 and K08CA128972), the American Society of Hematology and the William Lawrence and Blanche Hughes Foundation. E.J.C. is supported by a Steamboat Foundation Award. We would like to acknowledge Northeastern University and the Barnett Institute of Chemical and Biological Analysis for financial support, partial funding from NIH R01-GM086507 and a research agreement with the Waters Corporation (J.R.E.). The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from Canadian Institutes of Health Research, Eli Lilly Canada, Genome Canada, GlaxoSmithKline, the Ontario Ministry of Economic Development and Innovation, the Novartis Research Foundation, Pfizer, AbbVie, Takeda and the Wellcome Trust. C.H.A. holds a Canada Research Chair in Structural Genomics. Funding for OICR is provided by the Ontario Ministry of Economic Development and Innovation. NR 28 TC 78 Z9 78 U1 7 U2 53 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 DEC PY 2012 VL 3 AR 1288 DI 10.1038/ncomms2304 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 109HH UT WOS:000316356700055 PM 23250418 ER PT J AU Srivastava, MK Dubinett, S Sharma, S AF Srivastava, Minu K. Dubinett, Steven Sharma, Sherven TI Targeting MDSCs enhance therapeutic vaccination responses against lung cancer SO ONCOIMMUNOLOGY LA English DT Editorial Material DE immune suppression; immunotherapy; lung cancer; myeloid-derived suppressor cells ID SUPPRESSOR-CELLS; BONE-MARROW AB Myeloid-derived suppressor cells (MDSCs) are important regulators of immune responses. These cells suppress the cytotoxic activities of natural killer (NK)-cell and T-cell effectors and promote tumor growth. We demonstrated that depleting MDSCs improve therapeutic responses to vaccination in a murine model of lung cancer. This approach may prove beneficial against tumors in which MDSC exert prominent immunosuppressive effects. C1 [Srivastava, Minu K.; Dubinett, Steven; Sharma, Sherven] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Lung Canc Res Program, Los Angeles, CA 90095 USA. [Dubinett, Steven; Sharma, Sherven] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Srivastava, Minu K.; Dubinett, Steven; Sharma, Sherven] Vet Affairs Greater Los Angeles Healthcare Syst, Mol Gene Med Lab, Los Angeles, CA USA. RP Sharma, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Lung Canc Res Program, Los Angeles, CA 90095 USA. EM ssharma@mednet.ucla.edu FU NCATS NIH HHS [UL1 TR000124] NR 8 TC 10 Z9 10 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 J9 ONCOIMMUNOLOGY JI OncoImmunology PD DEC PY 2012 VL 1 IS 9 BP 1650 EP 1651 DI 10.4161/onci.21970 PG 2 WC Oncology; Immunology SC Oncology; Immunology GA 108GY UT WOS:000316281700035 PM 23264925 ER PT J AU Uebel, M AF Uebel, Michael TI Psychoanalysis and the Question of Violence: From Masochism to Shame SO AMERICAN IMAGO LA English DT Article ID WORLD-WAR-II; TRAINING PSYCHOTHERAPISTS; MENTAL-HEALTH; GUILT; MIND; ZEN; EMBARRASSMENT; PERSPECTIVES; ATTRIBUTES; COMPASSION C1 US Dept Vet Affairs, Cent Texas Vet Hlth Care Syst, Washington, DC 20420 USA. RP Uebel, M (reprint author), US Dept Vet Affairs, Cent Texas Vet Hlth Care Syst, Washington, DC 20420 USA. NR 133 TC 0 Z9 0 U1 1 U2 3 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0065-860X J9 AM IMAGO JI Am. Imago PD WIN PY 2012 VL 69 IS 4 BP 473 EP 505 PG 33 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA 099YP UT WOS:000315662200003 ER PT J AU Cassuto, O Dufies, M Jacquel, A Robert, G Ginet, C Dubois, A Hamouda, A Puissant, A Luciano, F Karsenti, JM Legros, L Cassuto, JP Lenain, P Auberger, P AF Cassuto, Ophelie Dufies, Maeva Jacquel, Arnaud Robert, Guillaume Ginet, Clemence Dubois, Alix Hamouda, Amine Puissant, Alexandre Luciano, Frederic Karsenti, Jean-Michel Legros, Laurence Cassuto, Jill Patrice Lenain, Pascal Auberger, Patrick TI All tyrosine kinase inhibitor-resistant chronic myelogenous cells are highly sensitive to Ponatinib SO ONCOTARGET LA English DT Article DE CML; BCR ABL; TKI; Resistance; Ponatinib ID CHRONIC MYELOID-LEUKEMIA; BCR-ABL INHIBITORS; CML CELLS; IMATINIB; APOPTOSIS; AP24534; MUTANT; LYN; DIFFERENTIATION; OVEREXPRESSION AB The advent of tyrosine kinase inhibitor (TKI) therapy has considerably improved the survival of patients suffering chronic myelogenous leukemia (CML). Indeed, inhibition of BCR-ABL by imatinib, dasatinib or nilotinib triggers durable responses in most patients suffering from this disease. Moreover, resistance to imatinib due to kinase domain mutations can be generally circumvented using dasatinib or nilotinib, but the multi-resistant T315I mutation that is insensitive to these TKIs, remains to date a major clinical problem. In this line, ponatinib (AP24534) has emerged as a promising therapeutic option in patients with all kinds of BCR-ABL mutations, especially the T315I one. However and surprisingly, the effect of ponatinib has not been extensively studied on imatinib-resistant CML cell lines. Therefore, in the present study, we used several CML cell lines with different mechanisms of resistance to TKI to evaluate the effect of ponatinib on cell viability, apoptosis and signaling. Our results show that ponatinib is highly effective on both sensitive and resistant CML cell lines, whatever the mode of resistance and also on BaF3 murine B cells carrying native BCR-ABL or T315I mutation. We conclude that ponatinib could be effectively used for all types of TKI-resistant patients. C1 [Cassuto, Ophelie; Dufies, Maeva; Jacquel, Arnaud; Robert, Guillaume; Ginet, Clemence; Dubois, Alix; Hamouda, Amine; Puissant, Alexandre; Luciano, Frederic; Auberger, Patrick] Fac Med Nice, INSERM, Team Cell Death Differentiat Inflammat & Canc U10, C3M, F-06034 Nice, France. [Cassuto, Ophelie; Dufies, Maeva; Jacquel, Arnaud; Robert, Guillaume; Ginet, Clemence; Dubois, Alix; Hamouda, Amine; Puissant, Alexandre; Luciano, Frederic; Auberger, Patrick] Equipe Labellisee Ligue Natl Canc 2011 2013, Paris, France. [Cassuto, Ophelie; Karsenti, Jean-Michel; Legros, Laurence; Cassuto, Jill Patrice; Auberger, Patrick] CHU Nice, Serv Hematol Clin & Transplantat, Nice, France. [Cassuto, Ophelie; Lenain, Pascal] CLCC, Ctr Henri Becquerel, Rouen, France. [Puissant, Alexandre] Dana Farber Canc Inst, Pediat Oncol Dept, Boston, MA 02115 USA. RP Auberger, P (reprint author), Fac Med Nice, INSERM, Team Cell Death Differentiat Inflammat & Canc U10, C3M, U210, F-06034 Nice, France. EM auberger@unice.fr RI PUISSANT, ALEXANDRE/O-9575-2016; AUBERGER, Patrick/G-1491-2013 OI PUISSANT, ALEXANDRE/0000-0002-3997-9282; AUBERGER, Patrick/0000-0002-2481-8275 FU Ligue Nationale Contre le Cancer (LNCC, Equipe Labellisee); Association pour la Recherche contre le Cancer (ARC); Institut National de Canceropoles [INCA-PL-2010-219]; Fondation de France; Fondation pour la Recherche Medicale; Ligue Nationale Contre le Cancer FX This work was supported by The Ligue Nationale Contre le Cancer (LNCC, Equipe Labellisee 2011-2013), The Association pour la Recherche contre le Cancer (ARC), The Institut National de Canceropoles (INCA-PL-2010-219) and The Fondation de France. OC, GR and AJ A are fellowships from the Fondation pour la Recherche Medicale, the Fondation de France and the Ligue Nationale Contre le Cancer, respectively. NR 23 TC 16 Z9 19 U1 0 U2 7 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD DEC PY 2012 VL 3 IS 12 BP 1557 EP 1565 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 101UZ UT WOS:000315801200016 PM 23238683 ER PT J AU Herrmann, H Blatt, K Shi, JW Gleixner, KV Cerny-Reiterer, S Mullauer, L Vakoc, CR Sperr, WR Horny, HP Bradner, JE Zuber, J Valent, P AF Herrmann, Harald Blatt, Katharina Shi, Junwei Gleixner, Karoline V. Cerny-Reiterer, Sabine Muellauer, Leonhard Vakoc, Christopher R. Sperr, Wolfgang R. Horny, Hans-Peter Bradner, James E. Zuber, Johannes Valent, Peter TI Small-molecule inhibition of BRD4 as a new potent approach to eliminate leukemic stem-and progenitor cells in acute myeloid leukemia (AML) SO ONCOTARGET LA English DT Article DE AML; leukemic stem cells; BRD4; JQ1; targeted therapy ID ACUTE MYELOGENOUS LEUKEMIA; INITIATING CELLS; PROGNOSTIC MARKERS; THERAPEUTIC TARGET; TRANSPLANTATION; CLASSIFICATION; CANCER; MICE; HETEROGENEITY; EXPRESSION AB Acute myeloid leukemia (AML) is a life-threatening stem cell disease characterized by uncontrolled proliferation and accumulation of myeloblasts. Using an advanced RNAi screen-approach in an AML mouse model we have recently identified the epigenetic 'reader' BRD4 as a promising target in AML. In the current study, we asked whether inhibition of BRD4 by a small-molecule inhibitor, JQ1, leads to growth-inhibition and apoptosis in primary human AML stem-and progenitor cells. Primary cell samples were obtained from 37 patients with freshly diagnosed AML (n=23) or refractory AML (n=14). BRD4 was found to be expressed at the mRNA and protein level in unfractionated AML cells as well as in highly enriched CD34(+)/CD38(-) and CD34(+)/CD38(+) stem-and progenitor cells in all patients examined. In unfractionated leukemic cells, submicromolar concentrations of JQ1 induced major growth-inhibitory effects (IC50 0.05-0.5 mu M) in most samples, including cells derived from relapsed or refractory patients. In addition, JQ1 was found to induce apoptosis in CD34(+)/CD38(-) and CD34(+)/CD38(+) stem- and progenitor cells in all donors examined as evidenced by combined surface/Annexin-V staining. Moreover, we were able to show that JQ1 synergizes with ARA-C in inducing growth inhibition in AML cells. Together, the BRD4-targeting drug JQ1 exerts major anti-leukemic effects in a broad range of human AML subtypes, including relapsed and refractory patients and all relevant stem-and progenitor cell compartments, including CD34(+)/CD38(-) and CD34(+)/CD38(+) AML cells. These results characterize BRD4-inhibition as a promising new therapeutic approach in AML which should be further investigated in clinical trials. C1 [Herrmann, Harald; Cerny-Reiterer, Sabine; Sperr, Wolfgang R.; Valent, Peter] Ludwig Boltzmann Cluster Oncol, Vienna, Austria. [Blatt, Katharina; Gleixner, Karoline V.; Sperr, Wolfgang R.] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, Vienna, Austria. [Shi, Junwei; Vakoc, Christopher R.; Zuber, Johannes] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Muellauer, Leonhard] Med Univ Vienna, Dept Pathol, Vienna, Austria. [Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Horny, Hans-Peter] Univ Munich, Inst Pathol, D-80539 Munich, Germany. [Zuber, Johannes] Res Inst Mol Pathol IMP, Vienna, Austria. RP Valent, P (reprint author), Ludwig Boltzmann Cluster Oncol, Vienna, Austria. EM peter.valent@meduniwien.ac.at OI Vakoc, Christopher/0000-0002-1158-7180 FU Cancer Stem Cell Research Grant from the Medical University of Vienna; Burroughs-Wellcome Fund Career Award for Medical Scientists FX This study was supported by a Cancer Stem Cell Research Grant from the Medical University of Vienna. C.R.V. is supported by a Burroughs-Wellcome Fund Career Award for Medical Scientists. NR 51 TC 64 Z9 66 U1 1 U2 20 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD DEC PY 2012 VL 3 IS 12 BP 1588 EP 1599 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 101UZ UT WOS:000315801200019 PM 23249862 ER PT J AU Saunders, GH Chisolm, TH Wallhagen, MI AF Saunders, Gabrielle H. Chisolm, Theresa H. Wallhagen, Margaret I. TI Older Adults and Hearing Help-Seeking Behaviors SO AMERICAN JOURNAL OF AUDIOLOGY LA English DT Article DE adults; aging; amplification or hearing aids; auditory rehabilitation; hearing loss; outcomes ID QUALITY-OF-LIFE; NEGATIVE CONSEQUENCES; URINARY-INCONTINENCE; IMPAIRMENT; AID; POPULATION; PEOPLE; CARE; AGE; DETERMINANTS AB Purpose: To review the current literature on help seeking for hearing health care among older adults. Method: The authors conducted a literature review regarding help seeking for hearing-related communication difficulties as well as for other chronic medical conditions. Results: Untreated hearing loss can lead to numerous negative secondary consequences; uptake and use of hearing aids remain low, despite the fact that hearing aids provide an effective treatment option for older adults with hearing loss. The authors describe models relevant to understanding the help-seeking and decision-making behaviors of older adults with hearing loss and discuss recommendations for future research. Conclusion: Because of the considerable overlap in factors associated with help-seeking behaviors across chronic medical conditions and because help-seeking behaviors are complex, help seeking should be examined within the framework of a multifactorial model, such as the health belief model or the transtheoretical stages of change model. C1 [Saunders, Gabrielle H.] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR USA. [Chisolm, Theresa H.] Univ S Florida, Tampa, FL USA. [Wallhagen, Margaret I.] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. RP Saunders, GH (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR USA. EM Gabrielle.saunders@va.gov NR 48 TC 21 Z9 23 U1 3 U2 16 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1059-0889 J9 AM J AUDIOL JI Am. J. Audiol. PD DEC PY 2012 VL 21 IS 2 BP 331 EP 337 DI 10.1044/1059-0889(2012/12-0028) PG 7 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 083HY UT WOS:000314455400020 PM 23233518 ER PT J AU Eisner, BH Sheth, S Herrick, B Pais, VM Sawyer, M Miller, N Hurd, KJ Humphreys, MR AF Eisner, Brian H. Sheth, Sonali Herrick, Benjamin Pais, Vernon M., Jr. Sawyer, Mark Miller, Nicole Hurd, Kimberly J. Humphreys, Mitchell R. TI The effects of ambient temperature, humidity and season of year on urine composition in patients with nephrolithiasis SO BJU INTERNATIONAL LA English DT Article DE kidney stone; risk; urine; weather; temperature; humidity ID KIDNEY-STONES; RISK-FACTORS; CALCIUM; UROLITHIASIS; TIME AB OBJECTIVE To understand the effects of temperature, humidity and season of year on 24-h urine composition in patients with nephrolithiasis. PATIENTS AND METHOD A retrospective review was performed of patients evaluated at four metabolic stone clinics. Multivariate linear regression models examined the relationship between mean temperature, average humidity, season of year and 24-h urine composition. Multivariate models adjusted for known risk factors for stone disease. Mean temperature and average humidity data were obtained from http://www.weatherunderground.com based on patient-provided addresses. RESULTS A total of 599 patients were included in the study, comprising 239 women and 360 men with a mean age of 53.6 years (SD 15.0). Mean temperature was 16.9 degrees C (SD 4.8, range -21.1 to 38.3 degrees C) and average humidity was 58.1% (SD 23.5, range 11 -100%). On multivariate linear regression, increasing temperature was associated with increasing urine calcium (beta = 11.3, 95% CI 2.2-20.0), super-saturation of calcium oxalate (beta = 0.6, 95% CI 0.2-0.9), super-saturation of calcium phosphate (beta = 0.14, 95% CI 0.03-0.2), and decreasing urine sodium (beta = -5.2, 95% CI -10.3 to -0.1). As seasons become warmer (i.e. from winter to autumn to spring to summer), changes were increased urine volume (beta = 0.09, 95% CI 0.01-0.2) and decreased super-saturation of calcium phosphate (beta = -0.2, 95% CI -0.3 to -0.03). There were no associations between quintile of humidity and any 24-h urine constituents. CONCLUSIONS Increasing temperature may increase stone risk by increasing urine excretion of calcium, and the super-saturation of calcium oxalate and calcium phosphate. These findings were independent of humidity and of season of year. This appears to be related to a physiological impact of temperature itself, rather than to geographic location. C1 [Eisner, Brian H.; Sheth, Sonali] Massachusetts Gen Hosp Urol, Boston, MA USA. [Herrick, Benjamin; Pais, Vernon M., Jr.] Dartmouth Hitchcock Med Ctr Urol, Lebanon, NH USA. [Sawyer, Mark; Miller, Nicole] Vanderbilt Univ, Med Ctr Urol, Nashville, TN USA. [Hurd, Kimberly J.; Humphreys, Mitchell R.] Mayo Clin, Dept Urol, Phoenix, AZ USA. RP Eisner, BH (reprint author), Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 11 TC 10 Z9 10 U1 0 U2 38 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD DEC PY 2012 VL 110 IS 11C BP E1014 EP E1017 DI 10.1111/j.1464-410X.2012.11186.x PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 091DQ UT WOS:000315029700041 PM 22578009 ER PT J AU Sullivan, MP Cristofaro, V Radisavljevic, ZM Yalla, SV AF Sullivan, Maryrose P. Cristofaro, Vivian Radisavljevic, Ziv M. Yalla, Subbarao V. TI Regional distribution and molecular interaction of caveolins in bladder smooth muscle SO BJU INTERNATIONAL LA English DT Article DE bladder; smooth muscle; caveolin; caveolae ID URINARY-BLADDER; SIGNAL-TRANSDUCTION; CELLS; COLOCALIZATION; EXPRESSION; DETRUSOR; MOUSE; RAT AB OBJECTIVE To determine the regional expression profile of caveolin isoforms (integral membrane proteins abundant in caveolae), the spatial relationships among caveolin proteins within specific smooth muscle (SM) regions and the extent of their molecular interactions in bladder SM (BSM). MATERIALS AND METHODS Regional differences in the expression of caveolin family members were determined by quantitative reverse transcriptase-polymerase chain reaction and Western blot of RNA and protein extracted from the base, body and dome of rat bladders. To evaluate the distribution of caveolin-1 (Cav-1), Cav-2 and Cav-3 within the bladder, longitudinal tissue sections from the base to dome were processed for confocal microscopy and quantified for intensity of immunoreactivity (IR) and extent of co-localisation. Interactions among Cav-1, Cav-2 and Cav-3 were determined by co-immunoprecipitation. RESULTS Differential expression of Cav-1 and Cav-3 was detected among bladder regions, with lowest expression in the bladder base relative to the dome. Cav-1 was highly expressed in all regions, although an increase in IR from submucosa to serosa was detected in each region. The distribution of Cav-2 IR generally paralleled Cav-1, but progressively decreased from submucosa to serosa in each region. Cav-3 expression predominated in the medial region of BSM increasing progressively from base to dome, but was poorly expressed in the outer SM layer particularly in the dome. Cav-1 co-precipitated extensively with both Cav-2 and Cav-3. Co-precipitation between Cav-3 and Cav-2 was also detected. CONCLUSIONS The isoform-specific spatial distribution and distinct molecular interactions among caveolins in BSM may contribute to the contractile heterogeneity of BSM cells and facilitate differential modulation of responses to local stimuli. As BSM caveolae regulate key signalling processes involved in contraction, altered expression of caveolin proteins may generate a regional imbalance in contraction/relaxation responses, thus leading to bladder dysfunction. C1 [Sullivan, Maryrose P.; Cristofaro, Vivian; Radisavljevic, Ziv M.; Yalla, Subbarao V.] Harvard Univ, Brigham & Womens Hosp, Vet Affairs Boston Healthcare Syst, Div Urol,Dept Surg,Med Sch, Boston, MA 02115 USA. RP Sullivan, MP (reprint author), VA Boston Healthcare Syst, Div Urol, 1400 VFW Pkwy, Boston, MA 02132 USA. EM msullivan@rics.bwh.harvard.edu FU Medical Research service, Department of Veteran's Affairs, Washington, DC FX Supported by Medical Research service, Department of Veteran's Affairs, Washington, DC. NR 28 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD DEC PY 2012 VL 110 IS 11C BP E1163 EP E1172 DI 10.1111/j.1464-410X.2012.11410.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 091DQ UT WOS:000315029700066 PM 22897417 ER PT J AU Chopra, V Quinti, L Kim, J Vollor, L Narayanan, KL Edgerly, C Cipicchio, PM Lauver, MA Choi, SH Silverman, RB Ferrante, RJ Hersch, S Kazantsev, AG AF Chopra, Vanita Quinti, Luisa Kim, Jinho Vollor, Lorraine Narayanan, K. Lakshmi Edgerly, Christina Cipicchio, Patricia M. Lauver, Molly A. Choi, Soo Hyuk Silverman, Richard B. Ferrante, Robert J. Hersch, Steven Kazantsev, Aleksey G. TI The Sirtuin 2 Inhibitor AK-7 Is Neuroprotective in Huntington's Disease Mouse Models SO CELL REPORTS LA English DT Article ID DEACETYLASE; PROTEIN; MICE AB Inhibition of sirtuin 2 (SIRT2) deacetylase mediates protective effects in cell and invertebrate models of Parkinson's disease and Huntington's disease (HD). Here we report the in vivo efficacy of a brain-permeable SIRT2 inhibitor in two genetic mouse models of HD. Compound treatment resulted in improved motor function, extended survival, and reduced brain atrophy and is associated with marked reduction of aggregated mutant huntingtin, a hallmark of HD pathology. Our results provide preclinical validation of SIRT2 inhibition as a potential therapeutic target for HD and support the further development of SIRT2 inhibitors for testing in humans. C1 [Chopra, Vanita; Quinti, Luisa; Vollor, Lorraine; Narayanan, K. Lakshmi; Hersch, Steven; Kazantsev, Aleksey G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Kim, Jinho; Edgerly, Christina; Cipicchio, Patricia M.; Lauver, Molly A.; Ferrante, Robert J.] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15213 USA. [Kim, Jinho; Edgerly, Christina; Cipicchio, Patricia M.; Lauver, Molly A.; Ferrante, Robert J.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Kim, Jinho; Edgerly, Christina; Cipicchio, Patricia M.; Lauver, Molly A.; Ferrante, Robert J.] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15213 USA. [Kim, Jinho; Edgerly, Christina; Cipicchio, Patricia M.; Lauver, Molly A.; Ferrante, Robert J.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr GR H 00, Pittsburgh, PA 15206 USA. [Choi, Soo Hyuk; Silverman, Richard B.] Northwestern Univ, Ctr Mol Innovat & Drug Discovery, Chem Life Proc Inst, Dept Mol Biosci,Dept Chem, Evanston, IL 60208 USA. RP Kazantsev, AG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. EM akazantsev@partners.org FU NIH [1U01NS066912-01A1] FX This study was supported by NIH grant 1U01NS066912-01A1 to A.G.K., S.H., R.J.F., and R.B.S. A.G.K., S.H., V.C., R.J.F., and R.B.S. designed the research; V.C., L.Q., L.V., L.K., J.K., C.E., P.M.C., and S.H.C. performed research; V.C., L.Q., and R.J.F. analyzed data; and A.G.K., V.C., S.H., R.J.F., and R.B.S. wrote the paper. NR 25 TC 48 Z9 48 U1 1 U2 19 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 DEC PY 2012 VL 2 IS 6 BP 1492 EP 1497 DI 10.1016/j.celrep.2012.11.001 PG 6 WC Cell Biology SC Cell Biology GA 083JJ UT WOS:000314459200004 PM 23200855 ER PT J AU Hansson, J Rafiee, MR Reiland, S Polo, JM Gehring, J Okawa, S Huber, W Hochedlinger, K Krijgsveld, J AF Hansson, Jenny Rafiee, Mahmoud Reza Reiland, Sonja Polo, Jose M. Gehring, Julian Okawa, Satoshi Huber, Wolfgang Hochedlinger, Konrad Krijgsveld, Jeroen TI Highly Coordinated Proteome Dynamics during Reprogramming of Somatic Cells to Pluripotency SO CELL REPORTS LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; EMBRYONIC STEM-CELLS; INTERACTION NETWORK; DEFINED FACTORS; SELF-RENEWAL; IPS CELLS; COMPLEX; MOUSE; FIBROBLASTS; EXPRESSION AB Generation of induced pluripotent stem cells (iPSCs) is a process whose mechanistic underpinnings are only beginning to emerge. Here, we applied in-depth quantitative proteomics to monitor proteome changes during the course of reprogramming of fibroblasts to iPSCs. We uncover a two-step resetting of the proteome during the first and last 3 days of reprogramming, with multiple functionally related proteins changing in expression in a highly coordinated fashion. This comprised several biological processes, including changes in the stoichiometry of electron transport-chain complexes, repressed vesicle-mediated transport during the intermediate stage, and an EMT-like process in the late phase. In addition, we demonstrate that the nucleoporin Nup210 is essential for reprogramming by its permitting of rapid cellular proliferation and subsequent progression through MET. Along with the identification of proteins expressed in a stage-specific manner, this study provides a rich resource toward an enhanced mechanistic understanding of cellular reprogramming. C1 [Hansson, Jenny; Rafiee, Mahmoud Reza; Reiland, Sonja; Gehring, Julian; Okawa, Satoshi; Huber, Wolfgang; Krijgsveld, Jeroen] European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany. [Polo, Jose M.; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Polo, Jose M.; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Polo, Jose M.; Hochedlinger, Konrad] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Polo, Jose M.; Hochedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Hochedlinger, Konrad] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Hochedlinger, Konrad] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Krijgsveld, J (reprint author), European Mol Biol Lab, Genome Biol Unit, Meyerhofstr 1, D-69117 Heidelberg, Germany. EM jeroen.krijgsveld@embl.de RI Hansson, Jenny/J-5062-2014; Reiland, Sonja/O-9810-2014; OI Hansson, Jenny/0000-0001-9174-8089; Reiland, Sonja/0000-0003-1791-7504; Huber, Wolfgang/0000-0002-0474-2218; Gehring, Julian/0000-0003-0070-4975 FU Netherlands Organisation for Scientific Research (NWO) FX We gratefully acknowledge the EMBL Proteomics Core Facility for excellent technical support. We thank Bernd Fischer for advice in statistics, Ryan Walsh for secondary MEF cells, and Martin W. Hetzer for Nup210 shRNA. This work was supported by a Vidi grant from the Netherlands Organisation for Scientific Research (NWO). NR 72 TC 90 Z9 92 U1 5 U2 34 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 DEC PY 2012 VL 2 IS 6 BP 1579 EP 1592 DI 10.1016/j.celrep.2012.10.014 PG 14 WC Cell Biology SC Cell Biology GA 083JJ UT WOS:000314459200015 PM 23260666 ER PT J AU Manor, I Ben-Hayun, R Aharon-Peretz, J Salomy, D Weizman, A Daniely, Y Megiddo, D Newcorn, JH Biederman, J Adler, LA AF Manor, Iris Ben-Hayun, Rachel Aharon-Peretz, Judith Salomy, Dana Weizman, Abraham Daniely, Yaron Megiddo, Dalia Newcorn, Jeffrey H. Biederman, Joseph Adler, Lenard A. TI A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating the Efficacy, Safety, and Tolerability of Extended-Release Metadoxine in Adults With Attention-Deficit/Hyperactivity Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COMORBIDITY SURVEY REPLICATION; ADHD; PREVALENCE; PREDICTORS; PERSISTENT; SYMPTOMS; VALIDITY; TRIAL AB Objective: To evaluate the efficacy, safety, and tolerability of an oral extended-release (ER) formulation of the nonstimulant metadoxine in the treatment of adult attention-deficit/hyperactivity disorder (ADHD). Method:This was a 1:1 randomized, double-blind, placebo-controlled, parallel-design, phase 2 study of metadoxine ER 1,400 mg/d treatment for 6 weeks, following a 2-week baseline/screening period, involving 120 adults with DSM-IV defined ADHD. A follow-up assessment occurred 2 weeks after the trial was completed. Efficacy measures included changes in Conners'Adult ADHD Rating Scale-Investigator Rated (CAARS-INV) total ADHD symptoms score with adult ADHD prompts (primary measure), response rates (>= 25% or 40% improvement in CAARS-INV total ADHD symptom score),Test of Variables of Attention (TOVA) performance, and Adult ADHD Quality of Life (AAQoL) total score. The study was conducted from March 15, 2011, to August 21, 2011. Results: Intent-to-treat analysis revealed that subjects receiving metadoxine ER showed statistically significant improvement in CAARS-INV total ADHD symptoms score (P = .02), higher rate of response (>= 25% [P = .03] or >= 40% [P = .04] improvement) on the CAARS-INV total ADHD symptoms score, and improvement in TOVA score (P = .02) and AAQoL score (P = .01) compared with the placebo group. Improvements in ADHD symptoms (scored by CAARS-INV) were significantly different in subjects treated with metadoxine ER versus placebo as early as 2 weeks following treatment initiation. Metadoxine ER was generally well tolerated, with nausea (17% [10/58] vs 0% [0/59]), fatigue (31% [18/58] vs 27% [16/59]), and headaches (29% [17/58] vs 39% [23/59]) being the most frequently reported adverse effects for the metadoxine ER and placebo groups, respectively. Conclusions: Findings suggest that metadoxine ER is a well-tolerated and effective treatment for adults with ADHD. C1 [Manor, Iris; Salomy, Dana; Weizman, Abraham] Geha Mental Hlth Ctr, Petah Tiqwa, Israel. [Manor, Iris; Weizman, Abraham] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Ben-Hayun, Rachel; Aharon-Peretz, Judith] Rambam Hlth Care Campus, Haifa, Israel. [Daniely, Yaron; Megiddo, Dalia] Alcobra Ltd, Tel Aviv, Israel. [Newcorn, Jeffrey H.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Adler, Lenard A.] NYU, Med Ctr, Dept Psychiat, New York, NY 10016 USA. [Adler, Lenard A.] NYU, Med Ctr, Dept Child & Adolescent Psychiat, New York, NY 10016 USA. [Adler, Lenard A.] New York VA Harbor Healthcare Syst, Psychiat Serv, New York, NY USA. [Biederman, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Biederman, Joseph] Harvard Univ, Sch Med, Boston, MA USA. RP Adler, LA (reprint author), NYU Sch Med, 650 1st Ave,7th Floor, New York, NY 10016 USA. EM lenard.adler@nyumc.org OI Newcorn, Jeffrey /0000-0001-8993-9337; Adler, Len/0000-0002-9812-8234 FU Alcobra; ElMindA; Janssen; McNeil; Shire; Massachusetts General Hospital (MGH) Psychiatry Academy; Children's Hospital of Southwest Florida/Lee Memorial Health System; MGH Psychiatry Academy; National Institute on Drug Abuse; Chelsea Therapeutics; Theravance; Eli Lilly; Bristol-Myers Squibb; Alcobra Ltd, Tel Aviv, Israel FX Dr Manor has been a consultant to Enzymotec, Janssen-Cilag, Teva, and Novartis; has received research support from Alcobra; and has been on a speakers/advisory board for Janssen-Cilag. Dr Weizman has been a consultant to Eli Lilly, Sanofi-Aventis, Pfizer, Lundbeck, and Teva and has been on a speakers/advisory board for AstraZeneca, Eli Lilly, Pfizer, Teva, Lundbeck, and Sanofi-Aventis. Dr Daniely is an employee of Alcobra. Dr Megiddo is an employee of, consultant to, and stock shareholder in Alcobra. Dr Newcorn has been a consultant to Alcobra, Eli Lilly, Biobehavioral Diagnostics, Shire, Neos, and Otsuica and has received honoraria from and been on the advisory boards of Eli Lilly, Ortho-McNeil-Janssen, and Shire. Dr Biederman is currently receiving research support from ElMindA, Janssen, McNeil, and Shire; in 2012, he received an honorarium from the Massachusetts General Hospital (MGH) Psychiatry Academy and the Children's Hospital of Southwest Florida/Lee Memorial Health System for tuition-funded CME courses; in 2011, he gave a single unpaid talk for Juste Pharmaceutical Spain, received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course, received an honorarium for presenting at an international scientific conference on ADHD, received an honorarium from Cambridge University Press for a chapter publication, and received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Eli Lilly, Shire, and AstraZeneca; these royalties were paid to the Department of Psychiatry at MGH. Dr Adler has been a consultant to Alcobra, Otsuka, Shire, Theravance, National Football League, and Major League Baseball; has received grant/research support from National Institute on Drug Abuse, Shire, Chelsea Therapeutics, Theravance, Eli Lilly, and Bristol-Myers Squibb; has received an options grant from Alcobra; has received honoraria from Alcobra, Otsuka, Shire, Theravance, National Football League, and Major League Baseball; and has received royalty payments (as inventor) from New York University for license of adult ADHD scales and training materials since 2004. Drs Ben-Haynn, Aharon-Peretz, and Salomy report no potential conflict of interest.; This study was funded by Alcobra Ltd, Tel Aviv, Israel. NR 35 TC 7 Z9 7 U1 1 U2 15 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2012 VL 73 IS 12 BP 1517 EP 1523 DI 10.4088/JCP.12m07767 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 090SR UT WOS:000315000800003 PM 23290324 ER PT J AU Papakostas, GI Vitolo, OV IsHak, WW Rapaport, MH Zajecka, JM Kinrys, G Mischoulon, D Lipkin, SH Hails, KA Abrams, J Ward, SG Meisner, A Schoenfeld, DA Shelton, RC Winokur, A Okasha, MS Bari, MA Fava, M AF Papakostas, George I. Vitolo, Ottavio V. IsHak, Waguih W. Rapaport, Mark H. Zajecka, John M. Kinrys, Gustavo Mischoulon, David Lipkin, Samuel H. Hails, Katherine A. Abrams, Jonah Ward, Sean G. Meisner, Allison Schoenfeld, David A. Shelton, Richard C. Winokur, Andrew Okasha, Mahmoud S. Bari, Mohammed A. Fava, Maurizio TI A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Comparison Trial of Ziprasidone as Monotherapy for Major Depressive Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; MEDIAL PREFRONTAL CORTEX; ANTIPSYCHOTIC-DRUGS; CLINICAL-TRIALS; ACETYLCHOLINE-RELEASE; NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; EXTENDED-RELEASE; POOLED ANALYSIS; RAT-BRAIN AB Objective: To study ziprasidone monotherapy for major depressive disorder, defined according to the DSM-IV. Method: One hundred twenty outpatients were enrolled between June 2008 and September 2010 in a 12-week study that was divided into two 6-week periods according to the sequential parallel comparison design. Patients were randomized in a 2:3:3 fashion to receive ziprasidone for 12 weeks, placebo for 6 weeks followed by ziprasidone for 6 weeks, or placebo for 12 weeks. The main outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS-17), with the Quick Inventory of Depressive Symptomatology, Self-Rated (QIDS-SR), and Clinical Global Impressions-Severity of Illness scale (CGI-S) serving as the study secondary measures. Results: One hundred twenty patients (53 women [44.1%]) were randomized to treatment. The mean (SD) age of these patients was 43.7 (11.0) years. Mean (SD) baseline HDRS-17, CGI-S, and QIDS-SR scores were 19.9 (5.0), 4.3 (0.6), and 15.6 (3.0), respectively. There was no statistically significant difference in reduction of depressive symptoms, response rates, or remission rates between ziprasidone- or placebo-treated patients. This was true for both the study primary as well as secondary outcome scales. Conclusions: In conclusion, treatment with ziprasidone monotherapy was not associated with any statistically significant advantage in efficacy over placebo. Although studies involving larger sample size would be required to have adequate statistical power to detect treatment differences smaller than 2.5 points on the HDRS-17, such differences would be of questionable clinical relevance. C1 [Papakostas, George I.; Vitolo, Ottavio V.; Mischoulon, David; Lipkin, Samuel H.; Hails, Katherine A.; Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Ctr Treatment Resistant Depress, Depress Clin & Res Program,Med Sch, Boston, MA 02114 USA. [Kinrys, Gustavo] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, Boston, MA 02114 USA. [Schoenfeld, David A.] Harvard Univ, Massachusetts Gen Hosp, Ctr Biostat, Sch Med, Boston, MA 02114 USA. [Kinrys, Gustavo; Mischoulon, David; Abrams, Jonah; Ward, Sean G.; Fava, Maurizio] Massachusetts Gen Hosp, CTNI, Boston, MA 02114 USA. [Meisner, Allison] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. [IsHak, Waguih W.] Cedars Sinai Med Ctr, Dept Psychiat & Behav Neurosci, Los Angeles, CA 90048 USA. [IsHak, Waguih W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Bari, Mohammed A.] Synergy Res Ctr, San Diego, CA USA. [Rapaport, Mark H.] Emory Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Zajecka, John M.] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. [Shelton, Richard C.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. [Winokur, Andrew] Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06032 USA. [Okasha, Mahmoud S.] Comprehens Psychiat Care, Norwich, CT USA. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Treatment Resistant Depress, Depress Clin & Res Program,Med Sch, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013; IsHak, Waguih/C-1336-2011 OI Papakostas, George/0000-0002-2465-5103; IsHak, Waguih/0000-0003-1970-4756 FU Forest; National Institute of Mental Health (NIMH); Pamlab; Pfizer; Ridge Diagnostics; Sunovion; AstraZeneca; Cyberonics; Hoffman-LaRoche; NIMH; Novartis; Otsuka; Shire; Takeda; Bristol-Myers Squibb; Eli Lilly; Bowman Family Foundation; Cederroth; FisherWallace; Ganeden; Lichtwer Pharma; Nordic Naturals; Roche; CytRx; ISIS; Elan; Euthymics Bioscience; Janssen; Otsuka, Pamlab; Repligen; St. Jude Medical; Forest Research Institute; Takeda Global Research; Abbot Laboratories; Alkermes; Aspect Medical Systems; AstraZeneca,; BioResearch; BrainCells; CeNeRx BioPharma; Cephalon; Clinical Trials Solutions; Clintara; Covance; Covidien; ElMindA; EnVivo Pharmaceuticals; Forest Pharmaceuticals; Ganeden Biotech; GlaxoSmithKline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; National Alliance for Research on Schizophrenia Depression; National Center for Complementary and Alternative Medicine; NIDA; Novartis AG; Organon; Pharmavite; Photothera; RCT Logic; Sanofi-Aventis; Solvay; Synthelabo; Wyeth-Ayerst; Adamed; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; Belvoir Media Group; Boehringer Ingelheim GmbH; CME Institute/Physicians Postgraduate Press; Eli Lilly and Company; Imedex; Massachusetts General Hospital (MGH) Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; PharmaStar; United BioSource; Pfizer, Inc. FX Over the past 12 months, Dr Papakostas has served as an advisor/consultant for Brainsway Ltd, Eli Lilly, Pamlab, Takeda, Theracos, and Ridge Diagnostics; has received honoraria from AstraZeneca PLC, Hoffman-LaRoche AG, Lundbeck A/S, Otsuka, and Pfizer; and has received research support from Forest, National Institute of Mental Health (NIMH), Pamlab, Pfizer, Ridge Diagnostics, and Sunovion. Over the past 12 months, Dr IsHak has received research support from Pfizer. Over the past 12 months, Dr Rapaport has served as an advisor/consultant to the NIMH, the National Institute on Drug Abuse (NIDA), the National Center for Complimentary and Alternative Medicine, and PAX (unpaid). Over the past 12 months, Dr Zajecka has served as a consultant/advisor for Abbott, Pamlab, Shire, and Takeda and has received research support from AstraZeneca, Cyberonics, Hoffman-LaRoche, NIMH, Novartis, Otsuka, Pfizer, Shire, and Takeda. Although Dr Zajecka has served on the speaker's bureau for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Otsuka, and Pamlab during the past 12 months, he has divested himself of these relationships effective September 1, 2011. Over the past 12 months, Dr Kinrys has received research support from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest, and Pfizer and has also served as an advisor/consultant for AstraZeneca, Forest, and Pfizer. Over the past 12 months, Dr Mischoulon has received research support from the Bowman Family Foundation, Bristol-Myers Squibb, Cederroth, FisherWallace, Ganeden, Lichtwer Pharma, and Nordic Naturals; has received honoraria for consulting, speaking, and writing from Pamlab, Bristol-Myers Squibb, and Nordic Naturals; and has received royalties from Back Bay Scientific for PMS Escape, and from Lippincott Williams & Wilkins for his book, entitled Natural Medications for Psychiatric Disorders: Considering the Alternatives. Over the past 12 months, Dr Schoenfeld has served as a consultant/advisor for Averion, Gerson Lehrman Group, Guidepoint Global, Neuronova, Cytokinetics, GlaxoSmithKline, Merck, Aggennix, Pfizer, and Baker Botts and has received research support from AstraZeneca, Roche, CytRx, and ISIS. Over the past 12 months, Dr Shelton has served as a consultant for Eli Lilly, Cyberonics, Janssen, Medtronic, Pamlab, Pfizer, Ridge Diagnostics, and Takeda Pharmaceuticals and has received grant/research support from Bristol-Myers Squibb, Eli Lilly, Elan, Euthymics Bioscience, Forest, Janssen, Novartis, Otsuka, Pamlab, Pfizer, Repligen, Ridge Diagnostics, St. Jude Medical, and Takeda. Over the past 12 months, Dr Okasha has received research support from Bristol-Myers Squibb, Euthymics Bioscience, Forest Research Institute, Pfizer, and Takeda Global Research and has served as a guest speaker for Forest.; In his lifetime, Dr Fava has received research support from Abbot Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Clinical Trials Solutions, Clintara, Covance, Covidien, Eli Lilly, ElMindA, EnVivo Pharmaceuticals, Euthymics Bioscience, Forest Pharmaceuticals, Ganeden Biotech, GlaxoSmithKline, Icon Clinical Research, i3 Innovus/Ingenix, Johnson & Johnson Pharmaceutical Research & Development, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, National Alliance for Research on Schizophrenia & Depression, National Center for Complementary and Alternative Medicine, NIDA, NIMH, Novartis AG, Organon, Pamlab, Pfizer, Pharmavite, Photothera, Roche, RCT Logic, Sanofi-Aventis, Shire, Solvay, Synthelabo, and Wyeth-Ayerst; has been a consultant or advisor to Abbott, Affectis AG, Alkermes, Amarin Pharma, Aspect Medical Systems, AstraZeneca, Auspex, Bayer AG, Best Practice Project Management, BioMarin Pharmaceuticals, Biovall, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Clinical Trials Solutions, CNS Response, Compellis, Cypress, DiagnoSearch Life Sciences (P), Dainippon Sumitomo Pharma, Dov, Edgemont, Eisai, Eli Lilly, EnVivo, ePharmaSolutions, EPIX, Euthymics Bioscience, Fabre-Kramer, Forest, GenOmind, GlaxoSmithKline, Grunenthal GmbH, i3 Innovus/Ingenis, Janssen, Jazz, Johnson & Johnson Pharmaceutical Research & Development, Knoll, Labopharm, Lorex, Lundbeck, MedAvante, Merck, MSI Methylation Sciences, Naurex, Neuronetics, Next Wave Pharmaceuticals, Novartis AG, Nutrition 21, Orexigen Therapeutics, Organon, Otsuka, Pamlab, Pfizer, PharmaStar, Pharmavite, PharmoRx Therapeutics, Precision Human Biolaboratory, Prexa Pharmaceuticals, Puretech Ventures, PsychoGenics, Psylin Neurosciences, Rexahn, Ridge Diagnostics, Roche, RCT Logic, Sanofi-Aventis, Sepracor, Servier, Schering-Plough, Solvay, Somaxon, Somerset, Sunovion, Supernus, Synthelabo, Takeda, Tal Medical, Tetragenex, Trans Form, Transcept, and Vanda; has received speaking/publishing fees from Adamed, Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir Media Group, Boehringer Ingelheim GmbH, Bristol-Myers Squibb, Cephalon, CME Institute/Physicians Postgraduate Press, Eli Lilly and Company, Forest Pharmaceuticals, GlaxoSmithKline, Imedex, Massachusetts General Hospital (MGH) Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed Elsevier, Novartis AG, Organon, Pfizer, PharmaStar, United BioSource, and Wyeth-Ayerst; has equity holdings in Compel lis; receives copyright royalties for the MGH Cognitive & Physical Functioning Questionnaire, Sexual Functioning Inventory, Antidepressant Treatment Response Questionnaire, Discontinuation-Emergent Signs & Symptoms, and SAFER; and has a patent application for a combination of azapirones and bupropion in major depressive disorder. Dr Fava also has a patent for Sequential Parallel Comparison Design (SPCD) and a patent for research and licensing of SPCD with RCT Logic; Lippincott, Williams & Wilkins; Wolkers Kluwer; and World Scientific Publishing. Drs Vitolo, Winokur, and Bari; Mss Hails and Meisner; and Messrs Lipkin, Abrams, and Ward report no potential or other conflicts of interest.; This trial was funded by Pfizer, Inc. Massachusetts General Hospital assisted with the coordination of this study. NR 31 TC 14 Z9 14 U1 2 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2012 VL 73 IS 12 BP 1541 EP 1547 DI 10.4088/JCP.12m07670 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 090SR UT WOS:000315000800006 PM 23290327 ER PT J AU Mallery, RM Klein, JP Pless, ML AF Mallery, Robert M. Klein, Joshua P. Pless, Misha L. TI Isolated Sixth Nerve Palsy From Hemorrhage of a Pontine Cavernous Malformation SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Editorial Material ID NATURAL-HISTORY AB A 32-year-old woman who developed binocular horizontal diplopia was found to have an isolated fascicular sixth nerve palsy secondary to hemorrhage of a cavernous malformation within the left pontine tegmentum. There was sparing of the paramedian pontine reticular formation and absence of a horizontal gaze palsy. The natural history of cavernous malformations and a mechanism by which hemorrhage of these vascular lesions may produce minimal neurologic signs, including isolated ocular motor cranial nerve palsies, is discussed. Magnetic resonance imaging (MRI) that includes susceptibility-weighted sequences leads to their accurate diagnosis. Journal of Neuro-Ophthalmology 2012;32:335-337 doi: 10.1097/WNO.0b013e31825e42ca (c) 2012 by North American Neuro-Ophthalmology Society C1 [Mallery, Robert M.; Pless, Misha L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mallery, Robert M.; Klein, Joshua P.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Pless, ML (reprint author), 15 Parkman St,WACC Suite 835, Boston, MA 02114 USA. EM pless.misha@mgh.harvard.edu NR 5 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD DEC PY 2012 VL 32 IS 4 BP 335 EP 337 DI 10.1097/WNO.0b013e31825e42ca PG 3 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 048FI UT WOS:000311895300009 PM 22743823 ER PT J AU Verhulst, S Dau, T Shera, CA AF Verhulst, Sarah Dau, Torsten Shera, Christopher A. TI Nonlinear time-domain cochlear model for transient stimulation and human otoacoustic emission SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID BASILAR-MEMBRANE; COHERENT REFLECTION; CHINCHILLA; MECHANICS; RESPONSES; LEVEL; EARS AB This paper describes the implementation and performance of a nonlinear time-domain model of the cochlea for transient stimulation and human otoacoustic emission generation. The nonlinearity simulates compressive growth of measured basilar-membrane impulse responses. The model accounts for reflection and distortion-source otoacoustic emissions (OAEs) and simulates spontaneous OAEs through manipulation of the middle-ear reflectance. The model was calibrated using human psychoacoustical and otoacoustic tuning parameters. It can be used to investigate time-dependent properties of cochlear mechanics and the generator mechanisms of otoacoustic emissions. Furthermore, the model provides a suitable preprocessor for human auditory perception models where realistic cochlear excitation patterns are desired. (C) 2012 Acoustical Society of America. [http://dx.doi.org/10.1121/1.4763989] C1 [Verhulst, Sarah; Dau, Torsten] Tech Univ Denmark, Dept Elect Engn, Ctr Appl Hearing Res, DK-2800 Lyngby, Denmark. [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Verhulst, S (reprint author), Tech Univ Denmark, Dept Elect Engn, Ctr Appl Hearing Res, Orsteds Plads Bldg 352, DK-2800 Lyngby, Denmark. EM save@bu.edu FU DTU; Oticon Foundation; NIDCD, National Institutes of Health [R01 DC003687] FX The authors would like to thank Diek Duifhuis and Peter Van Hengel for providing the original source code of the FORTRAN models presented in van Netten and Duifhuis (1983), Duifhuis et al. (1985), van Hengel (1996), and Duifhuis (2012). The code of these models is available at http://extras.springer.com/2012/978-1-4419-6117-4. Bastian Epp is acknowledged for help in compiling the different FORTRAN files into an executable, and Peter L. Soendergaard is thanked for help in adjusting the model to read in.wav files and for future integration of the model into the Auditory Model Toolbox. Work supported by DTU, the Oticon Foundation, and Grant No. R01 DC003687 from the NIDCD, National Institutes of Health. NR 40 TC 23 Z9 23 U1 0 U2 12 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD DEC PY 2012 VL 132 IS 6 BP 3842 EP 3848 DI 10.1121/1.4763989 PG 7 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 090RB UT WOS:000314995600028 PM 23231114 ER PT J AU Ford, EC de Los Santos, LF Pawlicki, T Sutlief, S Dunscombe, P AF Ford, E. C. de Los Santos, L. Fong Pawlicki, T. Sutlief, S. Dunscombe, P. TI Consensus recommendations for incident learning database structures in radiation oncology SO MEDICAL PHYSICS LA English DT Article DE patient safety; radiation therapy; brachytherapy; incident learning ID IMPROVING PATIENT SAFETY; RADIOTHERAPY; THERAPY; ERRORS; SYSTEM; RISK AB Purpose: Incident learning plays a key role in improving quality and safety in a wide range of industries and medical disciplines. However, implementing an effective incident learning system is complex, especially in radiation oncology. One current barrier is the lack of technical standards to guide users or developers. This report, the product of an initiative by the Work Group on Prevention of Errors in Radiation Oncology of the American Association of Physicists in Medicine, provides technical recommendations for the content and structure of incident learning databases in radiation oncology. Methods: A panel of experts was assembled and tasked with developing consensus recommendations in five key areas: definitions, process maps, severity scales, causality taxonomy, and data elements. Experts included representatives from all major North American radiation oncology organizations as well as users and developers of public and in-house reporting systems with over two decades of collective experience. Recommendations were developed that take into account existing incident learning systems as well as the requirements of outside agencies. Results: Consensus recommendations are provided for the five major topic areas. In the process mapping task, 91 common steps were identified for external beam radiation therapy and 88 in brachytherapy. A novel feature of the process maps is the identification of "safety barriers," also known as critical control points, which are any process steps whose primary function is to prevent errors or mistakes from occurring or propagating through the radiotherapy workflow. Other recommendations include a ten-level medical severity scale designed to reflect the observed or estimated harm to a patient, a radiation oncology-specific root causes table to facilitate and regularize root-cause analyses, and recommendations for data elements and structures to aid in development of electronic databases. Also presented is a list of key functional requirements of any reporting system. Conclusions: Incident learning is recognized as an invaluable tool for improving the quality and safety of treatments. The consensus recommendations in this report are intended to facilitate the implementation of such systems within individual clinics as well as on broader national and international scales. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4764914] C1 [Ford, E. C.] Univ Washington, Med Ctr, Dept Radiat Oncol, Seattle, WA 98195 USA. [de Los Santos, L. Fong] Mayo Clin, Dept Radiat Oncol, Rochester, MN 55905 USA. [Pawlicki, T.] Univ Calif San Diego, Dept Radiat Med & Appl Sci, La Jolla, CA 92093 USA. [Sutlief, S.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Dunscombe, P.] Univ Calgary, Dept Oncol, Calgary, AB T2N 1N4, Canada. RP Ford, EC (reprint author), Univ Washington, Med Ctr, Dept Radiat Oncol, Box 356043,1959 NE Pacific St, Seattle, WA 98195 USA. EM eford@uw.edu FU American Association of Physicists in Medicine FX The American Association of Physicists in Medicine is acknowledged for funding the members and guests of the WGPE who attended the Workshop. The partnering organizations, mentioned above, are also acknowledged for their support of this endeavor by sponsoring their representatives. Corbi Foster and Noel Crisman-Fillhart, from AAPM Headquarters provided much of the logistical support of the Workshop. Finally all the participants are recognized for their active involvement and contributions to this effort. WGPE members and guests, fully sponsored by the AAPM, were: Peter Dunscombe, Luis Fong de Los Santos, Eric Ford, Anne Greener, Jennifer Johnson, Ajay Kapur, Janaki Krishnamoorthy, Sasa Mutic, Todd Pawlicki, Steven Sutlief, Stephanie Terezakis M.D., Bruce Thomadsen. Representatives of partnering organizations were: Jean-Pierre Bissonnette (COMP), Jim Deye (NIH), Rachel Hackett (AAMD), Sandra Hayden (ASRT), James Hevezi (ACR), Ola Holmberg (IAEA), Jatinder Palta (ASTRO/NROR), Emily Wilson (ASTRO). Dr. Barrett Caldwell served as a consultant to the Causal Taxonomies group. The authors also acknowledge valuable discussions with Peter Gabriel, M.D. and Edna Volz, MS of the University of Pennsylvania, and Howard Bergendahl, M.S., J.D. (Bergendahl Institute, LLC). This report has been reviewed and approved by the AAPM. References to AAPM Task Group-100 have been reviewed and approved by the TG-100 writing group and parent committees within AAPM. NR 30 TC 34 Z9 34 U1 0 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2012 VL 39 IS 12 BP 7272 EP 7290 DI 10.1118/1.4764914 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 049FJ UT WOS:000311967400011 PM 23231278 ER PT J AU Cloud, LJ Rosenblatt, A Margolis, RL Ross, CA Pillai, JA Corey-Bloom, J Tully, HM Bird, T Panegyres, PK Nichter, CA Higgins, DS Helmers, SL Factor, SA Jones, R Testa, CM AF Cloud, Leslie J. Rosenblatt, Adam Margolis, Russel L. Ross, Christopher A. Pillai, Jagan A. Corey-Bloom, Jody Tully, Hannah M. Bird, Thomas Panegyres, Peter K. Nichter, Charles A. Higgins, Donald S., Jr. Helmers, Sandra L. Factor, Stewart A. Jones, Randi Testa, Claudia M. TI Seizures in Juvenile Huntington's Disease: Frequency and Characterization in a Multicenter Cohort SO MOVEMENT DISORDERS LA English DT Article DE Huntington's disease; juvenile Huntington's disease; seizures ID EARLY-ONSET; AGE AB Little is known about the epilepsy that often occurs in the juvenile form of Huntington's disease (HD), but is absent from the adult-onset form. The primary aim of this study was to characterize the seizures in juvenile HD (JHD) subjects with regard to frequency, semiology, defining EEG characteristics, and response to antiepileptic agents. A multicenter, retrospective cohort was identified by database query and/or chart review. Data on age of HD onset, primary HD manifestations, number of CAG repeats, the presence or absence of seizures, seizure type(s), antiepileptic drugs used, subjects' response to antiepileptic drugs (AEDs), and EEG results were assembled, where available. Ninety subjects with genetically confirmed JHD were included. Seizures were present in 38% of subjects and were more likely to occur with younger ages of HD onset. Generalized tonic-clonic seizures were the most common seizure type, followed by tonic, myoclonic, and staring spells. Multiple seizure types commonly occurred within the same individual. Data on EEG findings and AED usage are presented. Seizure risk in JHD increases with younger age of HD onset. Our ability to draw firm conclusions about defining EEG characteristics and response to AEDs was limited by the retrospective nature of the study. Future prospective studies are required. (C) 2012 Movement Disorder Society C1 [Cloud, Leslie J.; Rosenblatt, Adam; Testa, Claudia M.] Virginia Commonwealth Univ, Dept Neurol, Richmond, VA 23298 USA. [Rosenblatt, Adam] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA. [Margolis, Russel L.; Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Div Neurobiol,Dept Neurol, Baltimore, MD 21205 USA. [Margolis, Russel L.; Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Program Cellular & Mol Med, Baltimore, MD USA. [Pillai, Jagan A.; Corey-Bloom, Jody] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Tully, Hannah M.; Bird, Thomas] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Tully, Hannah M.] Seattle Childrens Hosp, Seattle, WA USA. [Bird, Thomas] Univ Washington, Geriatr Res Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Panegyres, Peter K.] Neurodegenerat Disorders Res Pty Ltd, Subiaco, WA, Australia. [Nichter, Charles A.; Higgins, Donald S., Jr.] Albany Med Coll, Dept Neurol, Albany, NY 12208 USA. [Higgins, Donald S., Jr.] Samuel Stratton VA Med Ctr, Neurol Serv, Albany, NY USA. [Helmers, Sandra L.; Factor, Stewart A.; Jones, Randi] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. RP Cloud, LJ (reprint author), Virginia Commonwealth Univ, Dept Neurol, 1001 E Broad St,Suite 222,POB 980539, Richmond, VA 23298 USA. EM lcloud@vcu.edu RI Ross, Christopher/H-8395-2013 NR 10 TC 13 Z9 13 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD DEC PY 2012 VL 27 IS 14 BP 1797 EP 1800 DI 10.1002/mds.25237 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 089GN UT WOS:000314899000018 PM 23124580 ER PT J AU Mata, IF Checkoway, H Hutter, CM Samii, A Roberts, JW Kim, HM Agarwal, P Alvarez, V Ribacoba, R Pastor, P Lorenzo-Betancor, O Infante, J Sierra, M Gomez-Garre, P Mir, P Ritz, B Rhodes, SL Colcher, A Van Deerlin, V Chung, KA Quinn, JF Yearout, D Martinez, E Farin, FM Wan, JY Edwards, KL Zabetian, CP AF Mata, Ignacio F. Checkoway, Harvey Hutter, Carolyn M. Samii, Ali Roberts, John W. Kim, Hojoong M. Agarwal, Pinky Alvarez, Victoria Ribacoba, Renee Pastor, Pau Lorenzo-Betancor, Oswaldo Infante, Jon Sierra, Maria Gomez-Garre, Pilar Mir, Pablo Ritz, Beate Rhodes, Shannon L. Colcher, Amy Van Deerlin, Vivianna Chung, Kathryn A. Quinn, Joseph F. Yearout, Dora Martinez, Erica Farin, Federico M. Wan, Jia Y. Edwards, Karen L. Zabetian, Cyrus P. TI Common Variation in the LRRK2 Gene is a Risk Factor for Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; LRRK2; SNP ID GENOME-WIDE ASSOCIATION; EXONIC VARIANTS; METAANALYSIS; MUTATIONS; REGION; SNCA AB Background: Common variants in the LRRK2 gene influence the risk of Parkinson's disease (PD) in Asians, but whether the same is true in European-derived populations is less clear. Methods: We genotyped 66 LRRK2 tagging single-nucleotide polymorphisms (SNPs) in 575 PD patients and 689 controls from the northwestern United States (tier 1). PD-associated SNPs (P < .05) were then genotyped in an independent sample of 3617 cases and 2512 controls from the United States and Spain (tier 2). Logistic regression was used to model additive SNP genotype effects adjusted for age and sex among white individuals. Results: Two regions showed independent association with PD in tier 1, and SNPs in both regions were successfully replicated in tier 2 (rs10878226, combined odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.33; P = 6.3 x 10(-4); rs11176013, OR, 0.89; CI, 0.83-0.95; P = 4.6 x 10(-4)). Conclusions: Our data suggest that common variation within LRRK2 conveys susceptibility for PD in individuals of European ancestry. (C) 2012 Movement Disorder Society C1 [Mata, Ignacio F.; Samii, Ali; Kim, Hojoong M.; Yearout, Dora; Martinez, Erica; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Mata, Ignacio F.; Samii, Ali; Kim, Hojoong M.; Yearout, Dora; Martinez, Erica; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Checkoway, Harvey; Farin, Federico M.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Hutter, Carolyn M.; Wan, Jia Y.; Edwards, Karen L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Hutter, Carolyn M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, Seattle, WA 98104 USA. [Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Agarwal, Pinky] Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. [Alvarez, Victoria] Hosp Univ Cent Asturias, Inst Invest Nefrol IRSINFRIAT, Genet Mol Lab, Oviedo, Spain. [Ribacoba, Renee] Hosp Univ Cent Asturias, Dept Neurol, Oviedo, Spain. [Pastor, Pau; Lorenzo-Betancor, Oswaldo] Univ Navarra, Ctr Appl Med Res, Div Neurosci, Neurogenet Lab, E-31080 Pamplona, Spain. [Pastor, Pau; Lorenzo-Betancor, Oswaldo] Univ Navarra, Dept Neurol, Clin Univ Navarra, Sch Med, E-31080 Pamplona, Spain. [Pastor, Pau; Lorenzo-Betancor, Oswaldo; Infante, Jon; Gomez-Garre, Pilar; Mir, Pablo] Inst Salud Carlos III, CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain. [Infante, Jon; Sierra, Maria] Marques de Valdecilla Univ Hosp, Dept Neurol, Santander, Spain. [Gomez-Garre, Pilar; Mir, Pablo] Univ Seville, CSIC, Hosp Univ Virgen del Rocio,Inst Biomed Sevilla IB, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain. [Ritz, Beate; Rhodes, Shannon L.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Ritz, Beate] Univ Calif Los Angeles, Sch Publ Hlth, Dept Environm Hlth Sci, Los Angeles, CA 90024 USA. [Ritz, Beate] Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. [Colcher, Amy] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Van Deerlin, Vivianna] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Chung, Kathryn A.; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Chung, Kathryn A.; Quinn, Joseph F.] Portland VA Med Ctr, Portland, OR USA. RP Mata, IF (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S 182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM nachofm@u.washington.edu; zabetian@u.washington.edu RI Pastor, Pau/C-9834-2009; Ritz, Beate/E-3043-2015; IBIS, MOVIMIENTO/P-3309-2015; Mir, Pablo/C-8662-2013 OI Pastor, Pau/0000-0002-7493-8777; Mir, Pablo/0000-0003-1656-302X FU BLRD VA [I01 BX000531]; NIEHS NIH HHS [P01 ES016732, P30 ES007033, P42 ES004696, R01 ES010544, U54 ES012078]; NINDS NIH HHS [P50 NS038367, P50 NS053488, P50 NS062684, R01 NS065070] NR 20 TC 0 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD DEC PY 2012 VL 27 IS 14 BP 1822 EP 1825 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 089GN UT WOS:000314899000024 PM 23115130 ER PT J AU Lipshultz, SE Miller, TL Lipsitz, SR Neuberg, DS Dahlberg, SE Colan, SD Silverman, LB Henkel, JM Franco, VI Cushman, LL Asselin, BL Clavell, LA Athale, U Michon, B Laverdiere, C Schorin, MA Larsen, E Usmani, N Sallan, SE AF Lipshultz, Steven E. Miller, Tracie L. Lipsitz, Stuart R. Neuberg, Donna S. Dahlberg, Suzanne E. Colan, Steven D. Silverman, Lewis B. Henkel, Jacqueline M. Franco, Vivian I. Cushman, Laura L. Asselin, Barbara L. Clavell, Luis A. Athale, Uma Michon, Bruno Laverdiere, Caroline Schorin, Marshall A. Larsen, Eric Usmani, Naheed Sallan, Stephen E. CA Dana-Farber Canc Inst Acute TI Continuous Versus Bolus Infusion of Doxorubicin in Children With ALL: Long-term Cardiac Outcomes SO PEDIATRICS LA English DT Article DE anthracycline; cardiotoxicity; doxorubicin; leukemia; pediatrics ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CONTINUOUS INTRAVENOUS-INFUSION; CHILDHOOD-CANCER SURVIVOR; LATE CARDIOTOXICITY; PROSPECTIVE (PCHIV)-C-2-H-2; REDUCED CARDIOTOXICITY; 5-YEAR SURVIVORS; ADULT SURVIVORS; WEEKLY SCHEDULE; LATE MORTALITY AB BACKGROUND AND OBJECTIVES: Doxorubicin, effective against many malignancies, is limited by cardiotoxicity. Continuous-infusion doxorubicin, compared with bolus-infusion, reduces early cardiotoxicity in adults. Its effectiveness in reducing late cardiotoxicity in children remains uncertain. We determined continuous-infusion doxorubicin cardioprotective efficacy in long-term survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: The Dana-Farber Cancer Institute ALL Consortium Protocol 91-01 enrolled pediatric patients between 1991 and 1995. Newly diagnosed high-risk patients were randomly assigned to receive a total of 360 mg/m(2) of doxorubicin in 30 mg/m2 doses every 3 weeks, by either continuous (over 48 hours) or bolus-infusion (within 15 minutes). Echocardiograms at baseline, during, and after doxorubicin therapy were blindly remeasured centrally. Primary outcomes were late left ventricular (LV) structure and function. RESULTS: A total of 102 children were randomized to each treatment group. We analyzed 484 serial echocardiograms from 92 patients (n = 49 continuous; n = 43 bolus) with >= 1 echocardiogram >= 3 years after assignment. Both groups had similar demographics and normal baseline LV characteristics. Cardiac follow-up after randomization (median, 8 years) showed changes from baseline within the randomized groups (depressed systolic function, systolic dilation, reduced wall thickness, and reduced mass) at 3, 6, and 8 years; there were no statistically significant differences between randomized groups. Ten-year ALL event-free survival rates did not differ between the 2 groups (continuous-infusion, 83% versus bolus-infusion, 78%; P = .24). CONCLUSIONS: In survivors of childhood high-risk ALL, continuous-infusion doxorubicin, compared with bolus-infusion, provided no long-term cardioprotection or improvement in ALL event-free survival, hence provided no benefit over bolus-infusion. Pediatrics 2012;130:1003-1011 C1 [Lipshultz, Steven E.; Miller, Tracie L.; Henkel, Jacqueline M.; Franco, Vivian I.; Cushman, Laura L.] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33101 USA. [Lipshultz, Steven E.; Miller, Tracie L.] Univ Miami, Sylvester Comprehens Canc Ctr, Jackson Mem Med Ctr, Holtz Childrens Hosp, Miami, FL 33101 USA. [Lipsitz, Stuart R.] Brigham & Womens Hosp, Dept Gen Internal Med, Boston, MA 02115 USA. [Neuberg, Donna S.; Dahlberg, Suzanne E.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Silverman, Lewis B.; Sallan, Stephen E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Colan, Steven D.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Silverman, Lewis B.; Sallan, Stephen E.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Asselin, Barbara L.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Clavell, Luis A.] San Jorge Childrens Hosp, Santurce, PR USA. [Athale, Uma] McMaster Univ, Hamilton, ON, Canada. [Michon, Bruno] Ctr Hosp Univ Quebec, Quebec City, PQ, Canada. [Laverdiere, Caroline] Ctr Hosp St Justine, Montreal, PQ, Canada. [Schorin, Marshall A.] Inova Fairfax Hosp Children, Falls Church, VA USA. [Larsen, Eric] Maine Childrens Canc Program, Portland, ME USA. [Usmani, Naheed] Univ Massachusetts, Med Ctr, Worcester, MA USA. RP Lipshultz, SE (reprint author), Univ Miami, Miller Sch Med, Dept Pediat D820, POB 016820, Miami, FL 33101 USA. EM slipshultz@med.miami.edu FU National Institutes of Health [HL072705, HL078522, HL053392, CA127642, CA068484, HD052104, AI50274, HD052102, HL087708, HL079233, HL004537, HL087000, HL007188, HL094100, HL095127, HD80002]; Children's Cardiomyopathy Foundation; Women's Cancer Association; Lance Armstrong Foundation; STOP Children's Cancer Foundation; Scott Howard Fund; Michael Garil Fund; National Institutes of Health (NIH) FX This work was supported in part by grants from the National Institutes of Health (HL072705, HL078522, HL053392, CA127642, CA068484, HD052104, AI50274, CA068484, HD052102, HL087708, HL079233, HL004537, HL087000, HL007188, HL094100, HL095127, and HD80002); Children's Cardiomyopathy Foundation; Women's Cancer Association; Lance Armstrong Foundation; STOP Children's Cancer Foundation; Scott Howard Fund; and the Michael Garil Fund. Funded by the National Institutes of Health (NIH). NR 48 TC 27 Z9 28 U1 0 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2012 VL 130 IS 6 BP 1003 EP 1011 DI 10.1542/peds.2012-0727 PG 9 WC Pediatrics SC Pediatrics GA 087YZ UT WOS:000314802000048 PM 23166343 ER PT J AU Brown, SD Donelan, K Martins, Y Burmeister, K Buchmiller, TL Sayeed, SA Mitchell, C Ecker, JL AF Brown, Stephen D. Donelan, Karen Martins, Yolanda Burmeister, Kelly Buchmiller, Terry L. Sayeed, Sadath A. Mitchell, Christine Ecker, Jeffrey L. TI Differing Attitudes Toward Fetal Care by Pediatric and Maternal-Fetal Medicine Specialists SO PEDIATRICS LA English DT Article DE prenatal care; pediatrics; pregnancy complications; treatment refusal; attitudes ID OUTCOMES; PREGNANCY; DIAGNOSIS; CHILDRENS; EXPOSURE; IMPROVES; ALCOHOL; INFANTS; BRAIN AB OBJECTIVES: The expansion of pediatric-based fetal care raises questions regarding pediatric specialists' involvement in pregnancies when maternal conditions may affect pediatric outcomes. For several such conditions, we compared pediatric and obstetric specialists' attitudes regarding whether and when pediatrics consultation should be offered and their views about seeking court authorization to override maternal refusal of physician recommendations. METHODS: We used a mail survey of 434 maternal-fetal medicine specialists (MFMs) and fetal care pediatric specialists (FCPs) (response rate: MFM, 60.9%; FCP, 54.2%). RESULTS: FCPs were more likely than MFMs to indicate that pediatric counseling should occur before decisions regarding continuing or interrupting pregnancies complicated by maternal alcohol abuse (FCP versus MFM: 63% vs 36%), cocaine abuse (FCP versus MFM: 60% vs 32%), use of seizure medications (FCP versus MFM: 62% vs 33%), and diabetes (FCP versus MFM: 56% vs 27%) (all P < .001). For all conditions, MFMs were more than twice as likely as FCPs to think that no pediatric specialist consultation was ever necessary. FCPs were more likely to agree that seeking court interventions was appropriate for maternal refusal to enter a program to discontinue cocaine use (FCP versus MFM: 72% vs 33%), refusal of azidothymidine to prevent perinatal HIV transmission (80% vs 41%), and refusal of percutaneous transfusion for fetal anemia (62% vs 28%) (all P < .001). CONCLUSIONS: Pediatric and obstetric specialists differ considerably regarding pediatric specialists' role in prenatal care for maternal conditions, and regarding whether to seek judicial intervention for maternal refusal of recommended treatment. Pediatrics 2012;130:e1534-e1540 C1 [Brown, Stephen D.] Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Buchmiller, Terry L.] Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Martins, Yolanda; Burmeister, Kelly] Boston Childrens Hosp, Clin Res Ctr, Boston, MA 02115 USA. [Buchmiller, Terry L.] Boston Childrens Hosp, Adv Fetal Care Ctr, Boston, MA 02115 USA. [Sayeed, Sadath A.] Boston Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. [Mitchell, Christine] Boston Childrens Hosp, Off Eth, Boston, MA 02115 USA. [Donelan, Karen] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Ecker, Jeffrey L.] Massachusetts Gen Hosp, Maternal Fetal Med Div, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Martins, Yolanda] Dana Farber Canc Inst, Ctr Populat Sci, Boston, MA 02115 USA. [Sayeed, Sadath A.; Mitchell, Christine] Harvard Univ, Sch Med, Div Med Eth, Boston, MA USA. RP Brown, SD (reprint author), Boston Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM stephen.brown@childrens.harvard.edu OI Martins, Yolanda/0000-0002-3983-3531 FU Greenwall Foundation; Kornfeld Program in Bioethics and Patient Care; Harvard University Milton Fund; American Roentgen Ray Society Leonard Berlin Scholarship in Medical Professionalism; Faculty Career Development Award, Office of Faculty Development, Boston Children's Hospital FX Funding was provided by grants from the Greenwall Foundation, the Kornfeld Program in Bioethics and Patient Care, and the Harvard University Milton Fund. Dr Brown received salary support from the American Roentgen Ray Society Leonard Berlin Scholarship in Medical Professionalism, and a Faculty Career Development Award, Office of Faculty Development, Boston Children's Hospital. NR 41 TC 5 Z9 5 U1 2 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2012 VL 130 IS 6 BP E1534 EP E1540 DI 10.1542/peds.2012-1352 PG 7 WC Pediatrics SC Pediatrics GA 087YZ UT WOS:000314802000015 PM 23129074 ER PT J AU Nabi-Burza, E Regan, S Drehmer, J Ossip, D Rigotti, N Hipple, B Dempsey, J Hall, N Friebely, J Weiley, V Winickoff, JP AF Nabi-Burza, Emara Regan, Susan Drehmer, Jeremy Ossip, Deborah Rigotti, Nancy Hipple, Bethany Dempsey, Janelle Hall, Nicole Friebely, Joan Weiley, Victoria Winickoff, Jonathan P. TI Parents Smoking in Their Cars With Children Present SO PEDIATRICS LA English DT Article DE parents; pediatrics; secondhand smoke; smoking in car; tobacco control; tobacco smoke ID ENVIRONMENTAL TOBACCO-SMOKE; INFANT-DEATH-SYNDROME; SECONDHAND SMOKE; PASSIVE SMOKING; EXPOSURE; CHILDHOOD; HEALTH; POLLUTION; DISEASE; ASTHMA AB OBJECTIVE: To determine prevalence and factors associated with strictly enforced smoke-free car policies among smoking parents. METHODS: As part of a cluster, randomized controlled trial addressing parental smoking, exit interviews were conducted with parents whose children were seen in 10 control pediatric practices. Parents who smoked were asked about smoking behaviors in their car and receipt of smoke-free car advice at the visit. Parents were considered to have a "strictly enforced smoke-free car policy" if they reported having a smoke-free car policy and nobody had smoked in their car within the past 3 months. RESULTS: Of 981 smoking parents, 817 (83%) had a car; of these, 795 parents answered questions about their car smoking policy. Of these 795 parents, 29% reported having a smoke-free car policy, and 24% had a strictly enforced smoke-free car policy. Of the 562 parents without a smoke-free car policy, 48% reported that smoking occurred with children present. Few parents who smoke (12%) were advised to have a smoke-free car. Multivariable logistic regression controlling for parent age, gender, education, and race showed that having a younger child and smoking <= 10 cigarettes per day were associated with having a strictly enforced smoke-free car policy. CONCLUSIONS: The majority of smoking parents exposed their children to tobacco smoke in cars. Coupled with the finding of low rates of pediatricians addressing smoking in cars, this study highlights the need for improved pediatric interventions, public health campaigns, and policies regarding smoke-free car laws to protect children from tobacco smoke. Pediatrics 2012;130:e1471-e1478 C1 [Nabi-Burza, Emara; Hipple, Bethany; Dempsey, Janelle; Hall, Nicole; Friebely, Joan; Winickoff, Jonathan P.] Massachusetts Gen Hosp Children, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Nabi-Burza, Emara; Rigotti, Nancy; Hipple, Bethany; Dempsey, Janelle; Hall, Nicole; Friebely, Joan; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Regan, Susan; Rigotti, Nancy] Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA. [Drehmer, Jeremy; Weiley, Victoria] Amer Acad Pediat, Pediat Res Off Settings, Elk Grove Village, IL USA. [Winickoff, Jonathan P.] Amer Acad Pediat, AAP Richmond Ctr Excellence, Elk Grove Village, IL USA. [Ossip, Deborah] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. RP Winickoff, JP (reprint author), Massachusetts Gen Hosp Children, Ctr Child & Adolescent Hlth Res & Policy, 15 Floor,Suite 1542A,100 Cambridge St, Boston, MA 02114 USA. EM jwinickoff@partners.org OI Drehmer, Jeremy/0000-0002-5022-5836 FU National Institutes of Health National Cancer Institute [R01-CA127127]; National Institute on Drug Abuse; Agency for Healthcare Research and Quality; Flight Attendant Medical Research Institute; Health Resources and Services Administration's Maternal and Child Health Bureau [HRSA 5-UA6-10-001]; American Academy of Pediatrics; National Institutes of Health (NIH) FX Supported by the National Institutes of Health National Cancer Institute grant R01-CA127127 (to Dr Winickoff), the National Institute on Drug Abuse, and the Agency for Healthcare Research and Quality. This study was also partially supported by a grant from the Flight Attendant Medical Research Institute to the AAP Julius B. Richmond Center, and the Pediatric Research in Office Settings Network receives core funding from theHealth Resources and Services Administration's Maternal and Child Health Bureau (HRSA 5-UA6-10-001) and the American Academy of Pediatrics. The funders had no role in the design or conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript. Funded by the National Institutes of Health (NIH). NR 43 TC 14 Z9 14 U1 0 U2 11 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2012 VL 130 IS 6 BP E1471 EP E1478 DI 10.1542/peds.2012-0334 PG 8 WC Pediatrics SC Pediatrics GA 087YZ UT WOS:000314802000007 PM 23147972 ER PT J AU Healy, BC Degano, IR Schreck, A Rintell, D Weiner, H Chitnis, T Glanz, BI AF Healy, Brian C. Degano, Irene R. Schreck, Ana Rintell, David Weiner, Howard Chitnis, Tanuja Glanz, Bonnie I. TI The impact of a recent relapse on patient-reported outcomes in subjects with multiple sclerosis SO QUALITY OF LIFE RESEARCH LA English DT Article DE Clinical relapse; Depression; Fatigue; Health related quality of life; Multiple sclerosis ID QUALITY-OF-LIFE; DISEASE; PEOPLE AB Purpose In this study, we estimate the impact of a recent relapse on physical and mental health in subjects with relapsing-remitting multiple sclerosis (RRMS) using validated patient-reported outcome (PRO) measures. Methods Subjects enrolled in the Comprehensive Longitudinal Investigation of MS at the Brigham and Women's Hospital with RRMS were eligible for enrollment. Subjects with a clinical visit within 45 days of a relapse were identified and divided into groups based on whether the relapse occurred before (recent relapse) (n = 59) or after the visit (pre-relapse) (n = 31). A group of subjects with no relapses was also identified (remission) (n = 336). PRO measures in these three groups were compared. All outcomes were compared using a t test and linear regression controlling for age, disease duration, sex, and EDSS. Results Subjects with a recent relapse had significantly worse functioning on several physical and mental health scales compared to subjects in remission even after adjusting for potential confounders. Subjects with a recent relapse also showed significant deterioration on PRO measures over 1 year compared to subjects in remission (P < 0.05 for each comparison). Subjects in the pre-relapse group were not significantly different than subjects in remission. Conclusions Clinical relapses have a measurable effect on PRO in subjects with RRMS. C1 [Healy, Brian C.; Degano, Irene R.; Schreck, Ana; Rintell, David; Weiner, Howard; Chitnis, Tanuja; Glanz, Bonnie I.] Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Brookline, MA 02445 USA. [Healy, Brian C.; Rintell, David; Weiner, Howard; Chitnis, Tanuja; Glanz, Bonnie I.] Harvard Univ, Sch Med, Dept Neurol, Brookline, MA USA. [Healy, Brian C.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. RP Healy, BC (reprint author), Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, 6th Floor,1 Brookline Pl, Brookline, MA 02445 USA. EM bchealy@partners.org RI Roman Degano, Irene/C-1826-2012 FU Nancy Davis Foundation; Merck Serono FX The CLIMB study is funded in part by the Nancy Davis Foundation and Merck Serono. NR 24 TC 9 Z9 9 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD DEC PY 2012 VL 21 IS 10 BP 1677 EP 1684 DI 10.1007/s11136-011-0108-0 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 089MT UT WOS:000314915400001 PM 22237991 ER PT J AU Stillman, MJ Chinnery, PF Kleindorfer, D Pittock, SJ Sahin, M Selcen, D Traynor, B Cash, SS Titulaer, M AF Stillman, Michael J. Chinnery, Patrick F. Kleindorfer, Dawn Pittock, Sean J. Sahin, Mustafa Selcen, Duygu Traynor, Brian Cash, Sydney S. Titulaer, Maarten TI What Do New ANA Members Think of the Future of Academic Neurology? SO ANNALS OF NEUROLOGY LA English DT Editorial Material C1 [Chinnery, Patrick F.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Kleindorfer, Dawn] Univ Cincinnati, Cincinnati, OH 45221 USA. [Pittock, Sean J.; Selcen, Duygu] Mayo Clin, Rochester, MN USA. [Sahin, Mustafa] Childrens Hosp Boston, Boston, MA USA. [Traynor, Brian] NIA, NIH, Bethesda, MD 20892 USA. [Cash, Sydney S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Titulaer, Maarten] IDIBAPS Univ Barcelona, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2012 VL 72 IS 6 BP A8 EP A9 DI 10.1002/ana.23826 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 086CH UT WOS:000314660100003 PM 23280853 ER PT J AU Galarce, EM Viswanath, K AF Galarce, Ezequiel M. Viswanath, K. TI Crisis Communication: An Inequalities Perspective on the 2010 Boston Water Crisis SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Article DE crisis communication; communication inequalities; behavioral compliance; social determinants ID RISK COMMUNICATION; DRINKING-WATER; OUTBREAK; INFORMATION; MODEL AB Objective: Although the field of crisis risk communication has generated substantial research, the interaction between social determinants, communication processes, and behavioral compliance has been less well studied. With the goal of better understanding these interactions, this report examines how social determinants influenced communications and behavioral compliance during the 2010 Boston, Massachusetts, water crisis. Methods: An online survey was conducted to assess Boston residents' knowledge, beliefs, attitudes, mass and interpersonal communication, and preventive behaviors on emergency preparedness topics dealing with the water crisis. Of a total sample of 726 respondents, approximately one-third (n=267) reported having been affected by the water crisis. Only data from affected participants were analyzed. Results: Following an order to boil water, 87.5% of respondents refrained from drinking unboiled tap water. These behaviors and other cognitive and attitudinal factors, however, were not uniform across population subgroups. All communication and behavioral compliance variables varied across sociodemographic factors. Conclusions: Crisis communication, in conjunction with other public health preparedness fields, is central to reducing the negative impact of sudden hazards. Emergency scenarios such as the Boston water crisis serve as unique opportunities to understand how effectively crisis messages are conveyed to and received by different segments of the population. (Disaster Med Public Health Preparedness. 2012; 6:349-356) C1 [Galarce, Ezequiel M.; Viswanath, K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Viswanath, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Galarce, EM (reprint author), Univ Calif San Francisco, Robert Wood Johnson Fdn, Hlth & Soc Scholars Program, Ctr Community Hlth, 3333 Calif St,St 465, San Francisco, CA 94118 USA. EM galarcee@chc.ucsf.edu FU Centers for Disease Control and Prevention [1P01TP000307] FX This research was supported by Centers for Disease Control and Prevention grant 1P01TP000307 (Dr Viswanath). NR 33 TC 7 Z9 7 U1 3 U2 24 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD DEC PY 2012 VL 6 IS 4 BP 349 EP 356 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 083WY UT WOS:000314497800007 PM 23241465 ER PT J AU Coleman, CN Hrdina, C Casagrande, R Cliffer, KD Mansoura, MK Nystrom, S Hatchett, R Caro, JJ Knebel, AR Wallace, KS Adams, SA AF Coleman, C. Norman Hrdina, Chad Casagrande, Rocco Cliffer, Kenneth D. Mansoura, Monique K. Nystrom, Scott Hatchett, Richard Caro, J. Jaime Knebel, Ann R. Wallace, Katherine S. Adams, Steven A. TI User-Managed Inventory: An Approach to Forward-Deployment of Urgently Needed Medical Countermeasures for Mass-Casualty and Terrorism Incidents SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Article DE medical countermeasures; user-managed inventory; nuclear ID NUCLEAR DETONATION; SCARCE RESOURCES; SURGE CAPACITY; HEALTH; ALLOCATION AB The user-managed inventory (UMI) is an emerging idea for enhancing the current distribution and maintenance system for emergency medical countermeasures (MCMs). It increases current capabilities for the dispensing and distribution of MCMs and enhances local/regional preparedness and resilience. In the UMI, critical MCMs, especially those in routine medical use ("dual utility") and those that must be administered soon after an incident before outside supplies can arrive, are stored at multiple medical facilities (including medical supply or distribution networks) across the United States. The medical facilities store a sufficient cache to meet part of the surge needs but not so much that the resources expire before they would be used in the normal course of business. In an emergency, these extra supplies can be used locally to treat casualties, including evacuees from incidents in other localities. This system, which is at the interface of local/regional and federal response, provides response capacity before the arrival of supplies from the Strategic National Stockpile (SNS) and thus enhances the local/regional medical responders' ability to provide life-saving MCMs that otherwise would be delayed. The UMI can be more cost-effective than stockpiling by avoiding costs due to drug expiration, disposal of expired stockpiled supplies, and repurchase for replacement. (Disaster Med Public Health Preparedness. 2012; 6:408-414) C1 [Coleman, C. Norman; Hrdina, Chad; Cliffer, Kenneth D.; Mansoura, Monique K.; Nystrom, Scott; Hatchett, Richard; Knebel, Ann R.] US Dept HHS, Off Assistant Secretary Preparedness & Response, Washington, DC 20201 USA. [Coleman, C. Norman] NCI, Radiat Res Program, NIH, Bethesda, MD 20892 USA. [Casagrande, Rocco] Gryphon Sci, Takoma Pk, MD USA. [Caro, J. Jaime] UnitedBiosource Corp, Lexington, MA USA. [Caro, J. Jaime] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. [Caro, J. Jaime] McGill Univ, Div Gen Internal Med, Montreal, PQ, Canada. [Wallace, Katherine S.] US Dept Vet Affairs, Off Operat Secur & Preparedness, Washington, DC USA. [Adams, Steven A.] Ctr Dis Control & Prevent, Div Strateg Natl Stockpile, Off Publ Hlth Preparedness & Response, Atlanta, GA USA. RP Coleman, CN (reprint author), 6130 Execut Blvd, Rockville, MD 20852 USA. EM Norman.Coleman@nih.gov NR 16 TC 4 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD DEC PY 2012 VL 6 IS 4 BP 408 EP 414 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 083WY UT WOS:000314497800015 PM 23241473 ER PT J AU Easler, JJ Zureikat, A Papachristou, GI AF Easler, Jeffrey J. Zureikat, Amer Papachristou, Georgios I. TI An update on minimally invasive therapies for pancreatic necrosis SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE acute pancreatitis; endoscopic necrosectomy; infected pancreatic necrosis; minimally invasive techniques; necrosectomy; necrosis; pancreas; pancreatic fluid collections; pancreatic necrosis; walled-off pancreatic necrosis ID INFECTED NECROTIZING PANCREATITIS; STANDARD PERCUTANEOUS DRAINAGE; ACUTE BILIARY PANCREATITIS; DUAL MODALITY DRAINAGE; ENDOSCOPIC NECROSECTOMY; RETROPERITONEAL APPROACH; RADIOLOGICAL PROCEDURES; SURGICAL-MANAGEMENT; CATHETER DRAINAGE; REDUCES LENGTH AB Pancreatic necrosis is a local complication of severe acute pancreatitis associated with multiple organ dysfunction, infection and increased mortality. While surgery is the mainstay for invasive management, studies have demonstrated that delaying necrosectomy translates to improved patient outcomes. Minimally invasive therapies have been described both for early and late management of necrotic pancreatic collections and fall into three broad categories: endoscopic, radiology assisted percutaneous drainage and laparoscopic or retroperitoneal surgical techniques. Such interventions may serve as temporizing measures delaying necrosectomy, but more importantly, as best demonstrated in recent randomized controlled trials, can serve as alternative approaches resulting in improved patient outcomes. Access to these techniques is based on their availability at expert centers. Minimally invasive therapies have increased in popularity, with a general consensus among experts being that reduced complications and mortality rates are realized by approaches other than open necrosectomy. However, additional well-designed, randomized trials are needed. C1 [Easler, Jeffrey J.; Papachristou, Georgios I.] Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Zureikat, Amer] Univ Pittsburgh Med, Div Gastrointestinal Surg, Pittsburgh, PA USA. [Papachristou, Georgios I.] Vet Affairs Pittsburgh Hlth Syst, Div Gastroenterol, Pittsburgh, PA USA. RP Papachristou, GI (reprint author), Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. EM papachri@pitt.edu NR 44 TC 4 Z9 4 U1 0 U2 12 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4124 J9 EXPERT REV GASTROENT JI Expert Rev. Gastroenterol. Hepatol. PD DEC PY 2012 VL 6 IS 6 BP 745 EP 753 DI 10.1586/EGH.12.48 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 083JZ UT WOS:000314460900016 PM 23237259 ER PT J AU Unglert, CI Warger, WC Hostens, J Namati, E Birngruber, R Bouma, BE Tearney, GJ AF Unglert, Carolin I. Warger, William C., II Hostens, Jeroen Namati, Eman Birngruber, Reginald Bouma, Brett E. Tearney, Guillermo J. TI Validation of two-dimensional and three-dimensional measurements of subpleural alveolar size parameters by optical coherence tomography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE alveolar structure; alveolar volume; ray-tracing; optical coherence tomography ID REFRACTIVE-INDEX; TISSUE AB Optical coherence tomography (OCT) has been increasingly used for imaging pulmonary alveoli. Only a few studies, however, have quantified individual alveolar areas, and the validity of alveolar volumes represented within OCT images has not been shown. To validate quantitative measurements of alveoli from OCT images, we compared the cross-sectional area, perimeter, volume, and surface area of matched subpleural alveoli from microcomputed tomography (micro-CT) and OCT images of fixed air-filled swine samples. The relative change in size between different alveoli was extremely well correlated (r > 0.9, P < 0.0001), but OCT images underestimated absolute sizes compared to micro-CT by 27% (area), 7% (perimeter), 46% (volume), and 25% (surface area) on average. We hypothesized that the differences resulted from refraction at the tissue-air interfaces and developed a ray-tracing model that approximates the reconstructed alveolar size within OCT images. Using this model and OCT measurements of the refractive index for lung tissue (1.41 for fresh, 1.53 for fixed), we derived equations to obtain absolute size measurements of superellipse and circular alveoli with the use of predictive correction factors. These methods and results should enable the quantification of alveolar sizes from OCT images in vivo. (c) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.12.126015] C1 [Unglert, Carolin I.; Warger, William C., II; Namati, Eman; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Unglert, Carolin I.; Warger, William C., II; Namati, Eman; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Unglert, Carolin I.] Air Liquide Ctr Rech Claude Delorme, Med Gases Grp, Les Loges En Josas, France. [Hostens, Jeroen] Bruker MicroCT, B-2550 Kontich, Belgium. [Birngruber, Reginald] Med Univ Lubeck, Inst Biomed Opt, D-23562 Lubeck, Germany. [Bouma, Brett E.; Tearney, Guillermo J.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Unglert, CI (reprint author), Wellman Ctr Photomed, 40 Parkman St,RSL 160, Boston, MA 02114 USA. EM cunglert@mgh.harvard.edu RI Birngruber, Reginald/Q-2342-2016 FU Air Liquide R&D, Medical Gases, Les-Loges-en-Josas, France; Center for Biomedical OCT Research and Translation [P41EB015903]; National Center for Research Resources; National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health FX The authors thank Elkan Halpern from the MGH Institute for Technology Assessment and Benoit Piednoir from Air Liquide for expert statistical advice, as well as Hao Wang and Veronica Delaney for help with the tissue paste preparation and with the index measurement. This work has been supported by Air Liquide R&D, Medical Gases, Les-Loges-en-Josas, France. Additional funds were provided by the Center for Biomedical OCT Research and Translation through grant number P41EB015903, awarded by the National Center for Research Resources and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health. NR 23 TC 6 Z9 6 U1 0 U2 8 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD DEC PY 2012 VL 17 IS 12 AR 126015 DI 10.1117/1.JBO.17.12.126015 PG 11 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 083ZB UT WOS:000314504400023 PM 23235834 ER PT J AU Chang, BH Stein, NR Trevino, K Stewart, M Hendricks, A Skarf, LM AF Chang, Bei-Hung Stein, Nathan R. Trevino, Kelly Stewart, Max Hendricks, Ann Skarf, Lara M. TI End-of-life spiritual care at a VA medical center: Chaplains' perspectives SO PALLIATIVE & SUPPORTIVE CARE LA English DT Article DE End of life; Spiritual care; Chaplains; Veterans ID QUALITY AB Objective: Spiritual care is an essential component of quality palliative care. Recognizing the importance, the Department of Veterans Affairs (VA) mandates the inclusion of chaplains in a palliative care consult team (PCCT). The purpose of this study is to explain the process and content of spiritual care provided in a VA Medical Center from chaplains' perspectives. Method: Five Christian chaplains who provide care to patients at end of life were interviewed. Each interview was recorded and transcribed. Analysis based on the grounded theory was used to identify themes from each interview question. Results: The PCCT in this study appeared to have a strong referral and communication system in which every palliative care patient was seen by a chaplain and the care plan was discussed with an interdisciplinary team. Chaplains reported providing a range of services, which addressed religious, spiritual, emotional, family, and illness concerns. Chaplains were aware of the unique spiritual needs of veterans, including working through guilt for killing in war and requiring forgiveness. Chaplains' ideas for improvement of spiritual care services included increasing time to provide care, providing bereavement care and support to families, and adding chaplains with different religious backgrounds. Chaplains reported how their own spirituality influenced the care they provided. Significance of results: Spiritual care in the VA can include a range of services and should consider the unique needs of the veteran population. Future studies can build upon our findings from chaplains to learn about the perspectives of patients, family, and other healthcare providers of spiritual care. This information would allow identification of strengths of current spiritual care practices and areas for care improvement, and ultimately could improve the wellbeing of patients at the end of life. C1 [Chang, Bei-Hung; Stein, Nathan R.; Stewart, Max; Hendricks, Ann; Skarf, Lara M.] VA Boston Healthcare Syst, Boston, MA USA. [Chang, Bei-Hung] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Trevino, Kelly] Dana Farber Canc Inst, Boston, MA 02115 USA. [Trevino, Kelly] Harvard Univ, Sch Med, Boston, MA USA. RP Chang, BH (reprint author), 150 S Huntington Ave,152H, Boston, MA 02130 USA. EM bhchang@bu.edu NR 12 TC 5 Z9 5 U1 0 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1478-9515 J9 PALLIAT SUPPORT CARE JI Palliat. Support Care PD DEC PY 2012 VL 10 IS 4 BP 273 EP 278 DI 10.1017/S1478951511001003 PG 6 WC Health Policy & Services SC Health Care Sciences & Services GA 083KF UT WOS:000314461700006 PM 22612863 ER PT J AU Sanders, MA Shirk, SD Burgin, CJ Martin, LL AF Sanders, Matthew A. Shirk, Steve D. Burgin, Chris J. Martin, Leonard L. TI The Gargle Effect: Rinsing the Mouth With Glucose Enhances Self-Control SO PSYCHOLOGICAL SCIENCE LA English DT Article ID ANTERIOR CINGULATE CORTEX; EGO DEPLETION; PERFORMANCE C1 [Sanders, Matthew A.; Martin, Leonard L.] Univ Georgia, Dept Psychol, Athens, GA 30602 USA. [Shirk, Steve D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Burgin, Chris J.] Tennessee Technol Univ, Dept Counseling & Psychol, Cookeville, TN USA. RP Sanders, MA (reprint author), Univ Georgia, Dept Psychol, Athens, GA 30602 USA. EM sandersm@uga.edu NR 15 TC 33 Z9 33 U1 1 U2 22 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD DEC PY 2012 VL 23 IS 12 BP 1470 EP 1472 DI 10.1177/0956797612450034 PG 3 WC Psychology, Multidisciplinary SC Psychology GA 083YL UT WOS:000314502600006 PM 23090756 ER PT J AU Stanford, RH Buikema, AR Riedel, AA Camargo, CA Rey, GG Chapman, KR AF Stanford, Richard H. Buikema, Ami R. Riedel, Aylin A. Camargo, Carlos A., Jr. Rey, Gabriel Gomez Chapman, Kenneth R. TI Asthma controller delay and recurrence risk after an emergency department visit or hospitalization SO RESPIRATORY MEDICINE LA English DT Article DE Managed care; Emergency hospital service; Emergency care; Hospitalization; Anti-asthmatic agents ID EXACERBATIONS; ADULTS; MEDICATIONS; DISCHARGE; TRIAL AB Background: Patients who have asthma-related emergency department (ED) visits or hospitalizations are at risk for recurrent exacerbation events. Our objectives were to assess whether receiving a controller medication at discharge affects risk of recurrence and whether delaying controller initiation alters this risk. Methods: Asthma patients with an ED visit or inpatient (IP) stay who received a controller dispensing within 6 months were identified from healthcare claims. Cox proportional hazards of the time to first recurrence of an asthma-related ED or IP visit in the 6-month period following the initial event were constructed, with time following discharge without controller medication as the primary predictor. Results: A total of 6139 patients met inclusion criteria, 78% with an ED visit and 22% with an IP visit; 15% had a recurrence within 6 months. The adjusted hazard ratio (HR) associated with not having controller medication at discharge was 1.79 (95% confidence interval [CI], 1.42 -2.25). The controller-by-time interaction was significant (P<0.001), with hazard rising as time-to-controller initiation increased. Delaying initiation by 1 day approximately tripled the risk (HR 2.95; 95%Cl 1.48-5.88). Sensitivity analyses, including accounting for controller fills prior to the index event, did not substantially alter these results. Conclusions: This observational study shows that the risk of a recurrent asthma-related ED visit or IP stay increased as the time to initiate a controller increased. Our findings support the importance of early controller initiation following an asthma-related ED or IP visit in reducing risk of recurrence. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Stanford, Richard H.] GlaxoSmithKline, US Hlth Outcomes, Res Triangle Pk, NC 27709 USA. [Buikema, Ami R.; Riedel, Aylin A.; Rey, Gabriel Gomez] Optumlnsight, Eden Prairie, MN 55344 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chapman, Kenneth R.] Univ Hlth Network, Asthma & Airway Ctr, Toronto, ON M5T 2S8, Canada. RP Stanford, RH (reprint author), GlaxoSmithKline, US Hlth Outcomes, 5 Moore Dr, Res Triangle Pk, NC 27709 USA. EM richard.h.stanford@gsk.com OI Buikema, Ami/0000-0002-2481-4872; Chapman, Kenneth/0000-0002-2498-9859 FU Boehringer-Ingelheim; GlaxoSmithKline; Grifols; Nyconned (Takeda); Family Physicians Airways Group of Canada; Canadian Network for Respiratory Care; Talecris; Research Triangle Park; North Carolina FX RHS is employed by GlaxoSnnithKline. ARB, AAR, and GGR are employed by OptumInsight, which was contracted by GlaxoSmithKline to conduct the study. CAC has served as a consultant to AstraZeneca, Dey, Genentech, GlaxSmithKline, Merck, Novartis, Pfizer, and sanofi-aventis. KRC holds the GSK-CIHR Research Chair in Respiratory Healthcare Delivery at the University Health Network, has served as a consultant to CSL Behring, GlaxoSmithKline, Novartis, Nycomed (Takeda), and Talecris (Grifols), and has received payment for lectures or service on speakers bureaus from Boehringer-Ingelheim, GlaxoSmithKline, Grifols, Nyconned (Takeda), Family Physicians Airways Group of Canada, Canadian Network for Respiratory Care, and Talecris.; This study was funded by GlaxoSmithKline, Research Triangle Park, North Carolina. The study sponsor was not involved in the study design, collection, analysis, or interpretation of data, the writing of the manuscript, or the decision to submit the manuscript for publication beyond the role of RHS as a study author. NR 18 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD DEC PY 2012 VL 106 IS 12 BP 1631 EP 1638 DI 10.1016/j.rmed.2012.08.017 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 088TM UT WOS:000314860000002 PM 22990041 ER PT J AU Hunter, RC Klepac-Ceraj, V Lorenzi, MM Grotzinger, H Martin, TR Newman, DK AF Hunter, Ryan C. Klepac-Ceraj, Vanja Lorenzi, Magen M. Grotzinger, Hannah Martin, Thomas R. Newman, Dianne K. TI Phenazine Content in the Cystic Fibrosis Respiratory Tract Negatively Correlates with Lung Function and Microbial Complexity SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE phenazine; cystic fibrosis; Pseudomonas aeruginosa; biofilm; microbiome ID PSEUDOMONAS-AERUGINOSA PYOCYANIN; AIRWAY EPITHELIAL-CELLS; BACTERIAL DIVERSITY; ANTIBIOTICS; INFECTIONS; SPUTUM; GENE; PATHOGENESIS; ACQUISITION; MECHANISMS AB Although much is known about how virulence factors affect pathogens and host tissues in vitro, far less is understood about their dynamics in vivo. As a step toward characterizing the chemistry of infected environments, we measured phenazine abundance in the lungs of patients with cystic fibrosis (CF). Phenazines are redox-active small molecules produced by Pseudomonas aeruginosa that damage host epithelia, curb the growth of competing organisms, and play physiologically important roles in the cells that produce them. Here, we quantify phenazines within expectorated sputum, characterize the P. aeruginosa populations responsible for phenazine production, and assess their relationship to CF lung microflora. Chemical analyses of expectorated sputum showed that the concentrations of two phenazines, namely, pyocyanin (PYO) and phenazine-1-carboxylic acid (PCA), were negatively correlated (rho = -0.68 and -0.57, respectively) with lung function. Furthermore, the highest phenazine concentrations were found in patients whose pulmonary function showed the greatest rates of decline. The constituent P. aeruginosa populations within each patient showed diverse capacities for phenazine production. Early during infection, individual isolates produced more PYO than later during infection. However, total PYO concentrations in sputum at any given stage correlated well with the average production by the total P. aeruginosa population. Finally, bacterial community complexity was negatively correlated with phenazine concentrations and declines in lung function, suggesting a link to the refinement of the overall microbial population. Together, these data demonstrate that phenazines negatively correlate with CF disease states in ways that were previously unknown, and underscore the importance of defining in vivo environmental parameters to better predict clinical outcomes of infections. C1 [Hunter, Ryan C.; Grotzinger, Hannah; Newman, Dianne K.] CALTECH, Div Biol Sci, Pasadena, CA 91125 USA. [Newman, Dianne K.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA. [Hunter, Ryan C.; Newman, Dianne K.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA. [Klepac-Ceraj, Vanja] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Lorenzi, Magen M.; Martin, Thomas R.] Childrens Hosp Boston, Dept Pediat, Boston, MA USA. RP Newman, DK (reprint author), CALTECH, Div Biol, 147-75,1200 E Calif Blvd, Pasadena, CA 91125 USA. EM dkn@caltech.edu OI Klepac-Ceraj, Vanja/0000-0001-5387-5706; Hunter, Ryan/0000-0003-3841-1676 FU Howard Hughes Medical Institute; Canadian Cystic Fibrosis Foundation; Cystic Fibrosis Foundation Center FX This work was supported by the Howard Hughes Medical Institute (D.K.N.); by the Canadian Cystic Fibrosis Foundation (R.C.H); and by a grant from the Cystic Fibrosis Foundation Center to Children's Hospital Boston for the sequencing of samples. NR 71 TC 70 Z9 73 U1 7 U2 46 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2012 VL 47 IS 6 BP 738 EP 745 DI 10.1165/rcmb.2012-0088OC PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 082QH UT WOS:000314406800003 PM 22865623 ER PT J AU Stolley, JM Gong, DP Farley, K Zhao, PC Cooley, J Crouch, EC Benarafa, C Remold-O'Donnell, E AF Stolley, J. Michael Gong, Dapeng Farley, Kalamo Zhao, Picheng Cooley, Jessica Crouch, Erika C. Benarafa, Charaf Remold-O'Donnell, Eileen TI Increased Surfactant Protein D Fails to Improve Bacterial Clearance and Inflammation in serpinB1(-/-) Mice SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE surfactant protein D; lung infection; inflammation; serpinB1; proteolysis ID PULMONARY SURFACTANT; CYSTIC-FIBROSIS; LUNG INJURY; NEUTROPHIL ELASTASE; IN-VITRO; INFECTION; COLLECTINS; GENE; EXPRESSION; BINDING AB Previously, we described the protective role of the neutrophil serine protease inhibitor serpinB1 in preventing early mortality of Pseudomonas aeruginosa lung infection by fostering bacterial clearance and limiting inflammatory cytokines and proteolytic damage. Surfactant protein D(SP-D), which maintains the antiinflammatory pulmonary environment and mediates bacterial removal, was degraded in infected serpinB1-deficient mice. Based on the hypothesis that increased SP-D would rescue or mitigate the pathological effects of serpinB1 deletion, we generated two serpinB1(-/-) lines overexpressing lung-specific rat SP-D and inoculated the mice with P. aeruginosa. Contrary to predictions, bacterial counts in the lungs of SP-D-low serpinB1(-/-) and SP-D-high serpinB1(-/-) mice were 4 logs higher than wild-type and not different from serpinB1(-/-) mice. SP-D overexpression also failed to mitigate inflammation (TNF-alpha), lung injury (free protein, albumin), or excess neutrophil death (free myeloperoxidase, elastase). These pathological markers were higher for infected SP-D-high serpinB1(-/-) mice than for serpinB1(-/-) mice, although the differences were not significant after controlling for multiple comparisons. The failure of transgenic SP-D to rescue antibacterial defense of serpin-B1-deficient mice occurred despite 5-fold or 20-fold increased expression levels, largely normal structure, and dose-dependent bacteria-aggregating activity. SP-D of infected wild-type mice was intact in 43-kD monomers by reducing SDS-PAGE. By contrast, proteolytic fragments of 35, 17, and 8 kD were found in infected SP-D-low serpinB1(-/-), SP-D-high serpinB1(-/-) mice, and serpinB1(-/-) mice. Thus, although therapies to increase lung concentration of SP-D may have beneficial applications, the findings suggest that therapy with SP-D may not be beneficial for lung inflammation or infection if the underlying clinical condition includes excess proteolysis. C1 [Stolley, J. Michael; Gong, Dapeng; Farley, Kalamo; Zhao, Picheng; Cooley, Jessica; Remold-O'Donnell, Eileen] Boston Childrens Hosp, Immune Dis Inst, Boston, MA USA. [Stolley, J. Michael; Gong, Dapeng; Farley, Kalamo; Zhao, Picheng; Cooley, Jessica; Remold-O'Donnell, Eileen] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Remold-O'Donnell, Eileen] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Gong, Dapeng; Farley, Kalamo; Zhao, Picheng; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Crouch, Erika C.] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. [Crouch, Erika C.] Washington Univ, Sch Med, Dept Immunol, St Louis, MO USA. [Benarafa, Charaf] Univ Bern, Theodor Kocher Inst, CH-3012 Bern, Switzerland. RP Remold-O'Donnell, E (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 3 Blackfan Circle, Boston, MA 02115 USA. EM remold@idi.harvard.edu RI ZHAO, PICHENG/G-3737-2014; OI Benarafa, Charaf/0000-0002-2049-7769 FU National Institutes of Health [HL-066548]; Parker B. Francis Fellowship in Pulmonary Research FX This work was supported by National Institutes of Health grant HL-066548 (E.R-O'D.) and by a Parker B. Francis Fellowship in Pulmonary Research (C.B.). NR 46 TC 3 Z9 3 U1 2 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2012 VL 47 IS 6 BP 792 EP 799 DI 10.1165/rcmb.2012-0145OC PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 082QH UT WOS:000314406800009 PM 23024061 ER PT J AU Kim, JK Vinarsky, V Wain, J Zhao, R Jung, K Choi, J Lam, A Pardo-Saganta, A Breton, S Rajagopal, J Yun, SH AF Kim, Jun Ki Vinarsky, Vladimir Wain, John Zhao, Rui Jung, Keehoon Choi, Jinwoo Lam, Adam Pardo-Saganta, Ana Breton, Sylvie Rajagopal, Jayaraj Yun, Seok Hyun TI In Vivo Imaging of Tracheal Epithelial Cells in Mice during Airway Regeneration SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE in vivo fluorescence microscopy; mouse imaging; epithelial regeneration ID STEM-CELLS; LUNG; EXPRESSION; PROMOTER AB Many human lung diseases, such as asthma, chronic obstructive pulmonary disease, bronchiolitis obliterans, and cystic fibrosis, are characterized by changes in the cellular composition and architecture of the airway epithelium. Intravital fluorescence microscopy has emerged as a powerful approach in mechanistic studies of diseases, but it has been difficult to apply this tool for in vivo respiratory cell biology in animals in a minimally invasive manner. Here, we describe a novel miniature side-view confocal probe capable of visualizing the epithelium in the mouse trachea in vivo at a single-cell resolution. We performed serial real-time endotracheal fluorescence microscopy in live transgenic reporter mice to view the three major cell types of the large airways, namely, basal cells, Clara cells, and ciliated cells. As a proof-of-concept demonstration, we monitored the regeneration of Clara cells over 18 days after a sulfur dioxide injury. Our results show that in vivo tracheal microscopy offers a new approach in the study of altered, regenerating, or metaplastic airways in animal models of lung diseases. C1 [Kim, Jun Ki; Jung, Keehoon; Choi, Jinwoo; Yun, Seok Hyun] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Jun Ki; Jung, Keehoon; Choi, Jinwoo; Yun, Seok Hyun] Wellman Ctr Photomed, Boston, MA USA. [Vinarsky, Vladimir; Wain, John; Zhao, Rui; Lam, Adam; Pardo-Saganta, Ana; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Kim, Jun Ki; Yun, Seok Hyun] Korea Adv Inst Sci & Technol, WCU Grad Sch Nanosci & Technol, Taejon 305701, South Korea. [Breton, Sylvie] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Div Nephrol, Boston, MA 02114 USA. [Rajagopal, Jayaraj] Harvard Stem Cell Inst, Holyoke Ctr, Cambridge, MA USA. [Yun, Seok Hyun] Harvard Massachusetts Inst Technol Hlth Sci & Tec, Cambridge, MA USA. RP Yun, SH (reprint author), 65 Lansdowne St,UP-5, Cambridge, MA 02139 USA. EM syun@hms.harvard.edu RI Zhao, Rui/J-7110-2014 FU National Institutes of Health [RC2DK088661, U54CA143837, R01AI081734, P41EB015903, P30HL101287, HD040793, DK085715, T32HL007874]; National Research Foundation of Korea [R31-2008-000-10071-0, 2009-352-C00042]; Harvard Stem Cell Institute FX This work was supported by National Institutes of Health grants RC2DK088661, U54CA143837, R01AI081734, P41EB015903, P30HL101287, HD040793, DK085715, and T32HL007874, National Research Foundation of Korea grants R31-2008-000-10071-0 and 2009-352-C00042, and by the Harvard Stem Cell Institute. NR 17 TC 10 Z9 10 U1 0 U2 12 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2012 VL 47 IS 6 BP 864 EP 868 DI 10.1165/rcmb.2012-0164OC PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 082QH UT WOS:000314406800017 PM 22984086 ER PT J AU Fried-Oken, M Rowland, C Daniels, D Dixon, M Fuller, B Mills, C Noethe, G Small, J Still, K Oken, B AF Fried-Oken, Melanie Rowland, Charity Daniels, Darlene Dixon, Mayling Fuller, Bret Mills, Carolyn Noethe, Glory Small, Jeon Still, Kevin Oken, Barry TI AAC to Support Conversation in Persons with Moderate Alzheimer's Disease SO AUGMENTATIVE AND ALTERNATIVE COMMUNICATION LA English DT Article DE AAC; Alzheimer's disease; Dementia; Aided conversation ID MEMORY AIDS; DEMENTIA; ADULTS; PREVALENCE; DIAGNOSIS; STATE AB Even though we know that external memory aids support communication in Alzheimer's disease, the components of the communication aids for individuals with Alzheimer's disease have not been studied systematically. The goal of these two pilot experiments was to examine differences in conversational performance of adults with Alzheimer's disease related to the presence and absence of an aid, the type of symbol embedded in the aid, and the presence or absence of voice output. In Experiment 1, 30 adults with moderate-to-severe Alzheimer's disease participated in 10-min conversations with and without personalized AAC boards. There was no effect of AAC, regardless of symbol type, and a deleterious effect of voice output. In Experiment 2, modified spaced-retrieval training preceded conversations, standardized prompts were presented, and semantically-based dependent variables were examined. For the 11 participants in the second experiment, there was a significant effect of AAC, showing that the presence of AAC was associated with greater use of targeted words during personal conversations. We discuss new information about the contribution of AAC for persons with Alzheimer's disease, and demonstrate how the applied research process evolves over the course of a long-term commitment to a scientific investigation. C1 [Fried-Oken, Melanie; Rowland, Charity; Daniels, Darlene; Dixon, Mayling; Mills, Carolyn; Noethe, Glory; Still, Kevin; Oken, Barry] Oregon Hlth & Sci Univ, Portland, OR 97207 USA. [Fuller, Bret] Portland VA Med Ctr, Portland, OR USA. [Small, Jeon] Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Fried-Oken, M (reprint author), Oregon Hlth & Sci Univ, POB 574, Portland, OR 97207 USA. EM friedm@ohsu.edu FU U.S. Department of Health and Human Services, National Institutes of Health [R21 HD47754, P30 AG008017]; U.S. Department of Education, National Institute on Disability and Rehabilitation Research [H133G040176]; Oregon Tax Check-Off Alzheimer's Research Grant FX We acknowledge support from the U.S. Department of Health and Human Services, National Institutes of Health grant R21 HD47754 and P30 AG008017; the U.S. Department of Education, National Institute on Disability and Rehabilitation Research grant H133G040176; and the 2004 Oregon Tax Check-Off Alzheimer's Research Grant. We thank the participants and their caregivers for inviting us into their homes and permitting us to document their conversations. NR 47 TC 5 Z9 5 U1 3 U2 26 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0743-4618 EI 1477-3848 J9 AUGMENT ALTERN COMM JI Augment. Altern. Commun. PD DEC PY 2012 VL 28 IS 4 BP 219 EP 231 DI 10.3109/07434618.2012.732610 PG 13 WC Audiology & Speech-Language Pathology; Rehabilitation SC Audiology & Speech-Language Pathology; Rehabilitation GA 077DO UT WOS:000314008300003 PM 23256854 ER PT J AU Chen, H Manning, AK Dupuis, J AF Chen, Han Manning, Alisa K. Dupuis, Josee TI A Method of Moments Estimator for Random Effect Multivariate Meta-Analysis SO BIOMETRICS LA English DT Article DE Between-study covariance matrix; Heterogeneity; Method of moments estimator; Multivariate meta-analysis; Random effect model ID REGRESSION; OUTCOMES AB Meta-analysis is a powerful approach to combine evidence from multiple studies to make inference about one or more parameters of interest, such as regression coefficients. The validity of the fixed effect model meta-analysis depends on the underlying assumption that all studies in the meta-analysis share the same effect size. In the presence of heterogeneity, the fixed effect model incorrectly ignores the between-study variance and may yield false positive results. The random effect model takes into account both within-study and between-study variances. It is more conservative than the fixed effect model and should be favored in the presence of heterogeneity. In this paper, we develop a noniterative method of moments estimator for the between-study covariance matrix in the random effect model multivariate meta-analysis. To our knowledge, it is the first such method of moments estimator in the matrix form. We show that our estimator is a multivariate extension of DerSimonian and Laird's univariate method of moments estimator, and it is invariant to linear transformations. In the simulation study, our method performs well when compared to existing random effect model multivariate meta-analysis approaches. We also apply our method in the analysis of a real data example. C1 [Chen, Han; Manning, Alisa K.; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Manning, Alisa K.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Manning, Alisa K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Manning, Alisa K.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Chen, H (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave, Boston, MA 02118 USA. EM hanchen@bu.edu OI Dupuis, Josee/0000-0003-2871-3603; Chen, Han/0000-0002-9510-4923 FU NIH [R01 DK078616, U01 DK85526]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center FX This research was partially supported by NIH awards R01 DK078616 and U01 DK85526. A portion of this research was conducted using the Linux Clusters for Genetic Analysis (LinGA) computing resource funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center and contributions from individual investigators. NR 15 TC 73 Z9 73 U1 1 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2012 VL 68 IS 4 BP 1278 EP 1284 DI 10.1111/j.1541-0420.2012.01761.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 080IX UT WOS:000314236200029 PM 22551393 ER PT J AU Kieran, MW Kalluri, R Cho, YJ AF Kieran, Mark W. Kalluri, Raghu Cho, Yoon-Jae TI The VEGF Pathway in Cancer and Disease: Responses, Resistance, and the Path Forward SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID ENDOTHELIAL-GROWTH-FACTOR; RENAL-CELL CARCINOMA; PHASE-II TRIAL; TYROSINE KINASE INHIBITOR; ACUTE MYELOID-LEUKEMIA; ADVANCED SOLID TUMORS; METASTATIC BREAST-CANCER; ANTI-ANGIOGENIC THERAPY; BEVACIZUMAB PLUS IRINOTECAN; ANTIANGIOGENIC AGENT SU5416 AB Antiangiogenesis was proposed as a novel target for the treatment of cancer 40 years ago. Since the original hypothesis put forward by Judah Folkman in 1971, factors that mediate angiogenesis, their cellular targets, many of the pathways they signal, and inhibitors of the cytokines and receptors have been identified. Vascular endothelial growth factor (VEGF) is the most prominent among the angiogenic cytokines and is believed to play a central role in the process of neovascularization, both in cancer as well as other inflammatory diseases. This article reviews the biology of VEGF and its receptors, the use of anti-VEGF approaches in clinical disease, the toxicity of these therapies, and the resistance mechanisms that have limited the activity of these agents when used as monotherapy. C1 [Kieran, Mark W.] Dana Farber Canc Inst, Dept Pediat Med Neurooncol, Boston, MA 02115 USA. [Kieran, Mark W.] Childrens Hosp, Div Pediat Oncol, Boston, MA 02115 USA. [Kalluri, Raghu] Beth Israel Deaconess Med Ctr, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Cho, Yoon-Jae] Stanford Univ, Dept Neurol & Neurosurg, Stanford, CA 94305 USA. [Cho, Yoon-Jae] Lucile Packard Childrens Hosp, Stanford, CA 94305 USA. RP Kieran, MW (reprint author), Dana Farber Canc Inst, Dept Pediat Med Neurooncol, Boston, MA 02115 USA. EM mark_kieran@dfci.harvard.edu RI Kalluri, Raghu/E-2677-2015; OI Kalluri, Raghu/0000-0002-2190-547X; Kieran, Mark/0000-0003-2184-7692 NR 195 TC 55 Z9 56 U1 1 U2 13 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD DEC PY 2012 VL 2 IS 12 AR a006593 DI 10.1101/cshperspect.a006593 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 080ZD UT WOS:000314282700007 PM 23209176 ER PT J AU Nienhuis, AW Nathan, DG AF Nienhuis, Arthur W. Nathan, David G. TI Pathophysiology and Clinical Manifestations of the beta-Thalassemias SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID HEMOGLOBIN-STABILIZING PROTEIN; TRANSFERRIN-BOUND IRON; LABILE PLASMA IRON; SICKLE-CELL-ANEMIA; FETAL-HEMOGLOBIN; MAGNETIC-RESONANCE; CHELATION-THERAPY; CARDIAC IRON; GLOBIN GENE; INEFFECTIVE ERYTHROPOIESIS AB The beta-thalassemia syndromes reflect deficient or absent beta-globin synthesis usually owing to a mutation in the beta-globin locus. The relative excess of alpha-globin results in the formation of insoluble aggregates leading to ineffective erythropoiesis and shortened red cell survival. A relatively high capacity for fetal hemoglobin synthesis is a major genetic modifier of disease severity, with polymorphisms in other genes also having a significant role. Iron overload secondary to enhanced absorption and red cell transfusions causes an increase in liver iron and in various other tissues, leading to endocrine and cardiac dysfunction. Modern chelation regimens are effective in removing iron and preserving or restoring organ function. C1 [Nienhuis, Arthur W.] St Jude Childrens Res Hosp, Dept Hematol, Memphis, TN 38105 USA. [Nathan, David G.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Nathan, David G.] Childrens Hosp, Div Hematol & Oncol, Boston, MA 02215 USA. RP Nienhuis, AW (reprint author), St Jude Childrens Res Hosp, Dept Hematol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM arthur.nienhuis@stjude.org NR 105 TC 25 Z9 26 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 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD DEC PY 2012 VL 2 IS 12 AR a011726 DI 10.1101/cshperspect.a011726 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 080ZD UT WOS:000314282700004 PM 23209183 ER PT J AU Pace, CA Lioznov, D Cheng, DM Wakeman, SE Raj, A Walley, AY Coleman, SM Bridden, C Krupitsky, E Samet, JH AF Pace, C. A. Lioznov, D. Cheng, D. M. Wakeman, S. E. Raj, A. Walley, A. Y. Coleman, S. M. Bridden, C. Krupitsky, E. Samet, J. H. TI Sexually transmitted infections among HIV-infected heavy drinkers in St Petersburg, Russia SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE sexually transmitted infection; HIV; AIDS; STIs; risk behaviour; alcohol drinking; Russia ID TRANSMISSION RISKS; UNITED-STATES; SEX WORK; SYPHILIS; PREVALENCE; MEN; FEDERATION; CHLAMYDIA; GONORRHEA; DIAGNOSIS AB The objective of this study was to estimate the prevalence and identify correlates of four sexually transmitted infections (STIs) among HIV-infected Russians reporting heavy alcohol use and recent unprotected sex, we conducted a cross-sectional analysis of baseline data from the HERMITAGE study. The primary outcome was any current STI, based on urine tests for Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis and serological testing for infection with Treponema pallidum. Data on potential demographic and behavioural predictors of STI were obtained from surveys administered at study entry. Of 682 participants, 12.8% (95% confidence interval [CI] 10.3, 15.3) tested positive for at least one STI. In a multivariable model adjusted for gender, age and marital status, only sex trade involvement over the last three months was significantly associated with an increased odds of STI (adjusted odds ratio [AOR] 2.00, 95% CI 1.13, 3.55). Given that STIs were common in this HIV-infected cohort, and that few patient characteristics predicted STI, the current practice of screening HIV-infected Russians for syphilis alone merits re-evaluation. C1 [Pace, C. A.; Cheng, D. M.; Walley, A. Y.; Bridden, C.; Samet, J. H.] Boston Univ, Sch Med, Clin Addict Res & Educ CARE Unit, Dept Med,Sect Gen Internal Med,Boston Med Ctr, Boston, MA 02118 USA. [Lioznov, D.] Pavlov State Med Univ, Dept Infect Dis & Epidemiol, St Petersburg, Russia. [Cheng, D. M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Wakeman, S. E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Raj, A.] Univ Calif San Diego, Dept Med, Div Global Publ Hlth, San Diego, CA 92103 USA. [Coleman, S. M.] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA. [Krupitsky, E.] Pavlov State Med Univ, St Petersburg Sci Res Ctr Addict & Psychopharmaco, St Petersburg, Russia. [Samet, J. H.] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA 02118 USA. RP Pace, CA (reprint author), Boston Univ, Sch Med, Clin Addict Res & Educ CARE Unit, Dept Med,Sect Gen Internal Med,Boston Med Ctr, 801 Massachusetts Ave,2nd Floor, Boston, MA 02118 USA. EM Christine.pace@bmc.org RI Lioznov, Dmitry/J-2539-2013; OI Lioznov, Dmitry/0000-0003-3643-7354; Samet, Jeffrey/0000-0002-0897-3400; Bridden, Carly/0000-0002-7208-7235; Walley, Alexander/0000-0002-8158-4882 FU National Institute of Alcohol Abuse and Alcoholism (NIAAA) [R01AA016059, K24-AA015674]; National Institute of Drug Abuse (NIDA) [R25DA13582]; National Institute of Allergy and Infectious Diseases (NIAID) [T32 AI052074-06A2] FX CAP, DL, SEW, AYW, AR, EK and JHS conceived the research question and designed the analysis. JHS obtained funding for the parent HERMITAGE study. DMC and SMC conducted the statistical analysis. All authors participated in interpretation of data. All authors participated in preparation of the manuscript and have approved the final draft for submission. The authors wish to acknowledge the participants in the HERMITAGE study, as well as the clinical and administrative study staff, particularly Elena Blokhina, Victoria Churchill and the Data Coordinating Center at Boston University. In addition, we are grateful to Aseem Mehta for assistance with the literature review, and Guillermo Madico for advice on STI laboratory testing. Support for this work came from the National Institute of Alcohol Abuse and Alcoholism (NIAAA; R01AA016059 and K24-AA015674), the National Institute of Drug Abuse (NIDA; R25DA13582) and the National Institute of Allergy and Infectious Diseases (NIAID; T32 AI052074-06A2). NR 31 TC 7 Z9 8 U1 0 U2 10 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD DEC PY 2012 VL 23 IS 12 BP 853 EP 858 DI 10.1258/ijsa.2012.012004 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 069WJ UT WOS:000313467500004 PM 23258823 ER PT J AU von Lutzau, P Otto, M Hechler, T Metzing, S Wolfe, J Zernikow, B AF von Luetzau, Pia Otto, Michael Hechler, Tanja Metzing, Sabine Wolfe, Joanne Zernikow, Boris TI Children Dying from Cancer: Parents' perspectives on symptoms, quality of life, characteristics of death, and end-of-life decisions SO JOURNAL OF PALLIATIVE CARE LA English DT Article DE end-of-life care period; children; cancer; end-of-life decision ID RESEARCH PARTICIPATION; PEDIATRIC ONCOLOGY; PALLIATIVE CARE; EXPERIENCES; PERCEPTIONS; FATIGUE; PEOPLE; HOME; PAIN AB In this study, we investigated the experience of children who died of cancer, as perceived by their parents. All the pediatric oncology departments in one German federal state were contacted and asked to invite parents who had lost a child to cancer in the period 2005-2006 to participate. Those parents who accepted were interviewed by means of a semi-structured questionnaire. In the participating 16 departments, 158 children died in 2005-2006. Parents of 48 children (38.3 percent) agreed to participate and were interviewed. Nearly all of the children had suffered from at least one distressing symptom. Pain and fatigue occurred most frequently. Symptoms were successfully treated over 65 percent of the time. In all, 64 percent of the children received home care services; 50 percent died at home, and only 10 percent in the ICU. Results suggest that some progress has been made in pediatric palliative care. To further improve end-of-life care for children with cancer, it is also necessary to evaluate parents' perspectives on structures for pediatric palliative care delivery. C1 [von Luetzau, Pia; Otto, Michael; Hechler, Tanja; Zernikow, Boris] Childrens & Adolescents Hosp, Pediat Palliat Care Ctr, Datteln, Germany. [von Luetzau, Pia; Otto, Michael; Hechler, Tanja; Zernikow, Boris] Childrens & Adolescents Hosp, German Pediat Pain Ctr, Datteln, Germany. [von Luetzau, Pia; Otto, Michael; Hechler, Tanja; Zernikow, Boris] Univ Witten Herdecke, Fac Hlth, Sch Med, Dept Childrens Pain Therapy & Paediat Palliat Car, D-45711 Datteln, Germany. [Metzing, Sabine] Univ Witten Herdecke, Fac Hlth, Sch Nursing Sci, Witten, Germany. [Wolfe, Joanne] Harvard Univ, Sch Med, Boston, MA USA. [Wolfe, Joanne] Boston Childrens Hosp, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA USA. RP von Lutzau, P (reprint author), Childrens & Adolescents Hosp, Pediat Palliat Care Ctr, Datteln, Germany. EM p.vonluetzau@kinderklinik-datteln.de FU German Children's Cancer Fund FX We would like to thank the study participants, the interviewers (E. Baum, D. Behnen, R. Bruggemann, M. Czech, M. Fortkord, C. Hansen, A. Menke, and D. Wunnenberg), and the German Children's Cancer Fund, which supported the survey. In addition, we thank all of the departments that participated in the research and that helped us to contact the parents who shared their perspectives with us: the Department of Pediatric and Adolescent Medicine, University Hospital Aachen (clinical director, Prof. Dr. N. Wagner); the Department of Pediatric Oncology, Gilead Hospital, Bielefeld (clinical director, Dr. N. Jorch); the Department of Hematology and Oncology, University Clinic for Children, Bonn (clinical director, Prof. Dr. D. Dilloo); the Department of Hematology and Oncology, Children's and Adolescents' Hospital, Datteln, Witten/Herdecke University (clinical director, Prof. Dr. M. Paulussen); the Department of Pediatric Medicine, Klinikunn Lippe (clinical director, Dr. T. Brune); the Department of Pediatric Oncology, Dortmund Children's Hospital (clinical director, Prof. Dr. D. Schneider); the Clinic for Pediatrics III, University Clinic of Essen (clinical director, Prof. Dr. A. Eggert); the Department of Pediatric Medicine, Children's Hospital, Herdecke (clinical director, PD Dr. A. Langler); the Department of Pediatric Oncology, Children's Clinic, University Hospital of Koln (clinical director, Prof. Dr. F. Berthold); the Department of Pediatric Oncology, Children's Hospital Amsterdamer Strasse, Koln (clinical director, Dr. A. Prokop); the Department of Pediatric Oncology, HELIOS Klinikum Krefeld (clinical director, Prof. Dr. T. Niehues); the Department of Pediatric Medicine, Klinikum Minden (clinical director, Prof. Dr. B. Erdlenbruch); the Department of Hematology and Oncology, University Clinic for Children, Munster (clinical director, Prof. Dr. H. Jurgens); the Department of Pediatric Oncology, Children's Red Cross Hospital, Siegen (clinical director, Prof. Dr. R. Burghard); the Department of Pediatric Medicine, Asklepiop Klinik St. Augustin (clinical director, Prof. Dr. G. Horneff); and the Department of Pediatric Medicine, HELIOS Klinikum Wuppertal (clinical director, Prof. Dr. S. Wirth). NR 44 TC 16 Z9 17 U1 4 U2 29 PU CENTRE RECHERCHE INSTITUT UNIV GERIATRIE MONTREAL PI MONTREAL PA 4565 CHEMIN QUEEN MARY, MONTREAL, QUEBEC H3W 1W5, CANADA SN 0825-8597 J9 J PALLIAT CARE JI J. Palliative Care PD WIN PY 2012 VL 28 IS 4 BP 274 EP 281 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 082IQ UT WOS:000314385900006 PM 23413763 ER PT J AU Neveu, G Cassonnet, P Vidalain, PO Rolloy, C Mendoza, J Jones, L Tangy, F Muller, M Demeret, C Tafforeau, L Lotteau, V Rabourdin-Combe, C Trave, G Dricot, A Hill, DE Vidal, M Favre, M Jacob, Y AF Neveu, Gregory Cassonnet, Patricia Vidalain, Pierre-Olivier Rolloy, Caroline Mendoza, Jose Jones, Louis Tangy, Frederic Muller, Mandy Demeret, Caroline Tafforeau, Lionel Lotteau, Vincent Rabourdin-Combe, Chantal Trave, Gilles Dricot, Amelie Hill, David E. Vidal, Marc Favre, Michel Jacob, Yves TI Comparative analysis of virus-host interactomes with a mammalian high-throughput protein complementation assay based on Gaussia princeps luciferase SO METHODS LA English DT Article DE Comparative interactomics; HPV; E6; E7; Interactome; Complementation assay ID HUMAN-PAPILLOMAVIRUS E6; RETINOBLASTOMA TUMOR-SUPPRESSOR; E7 ONCOPROTEIN; E6-AP; P53; UBIQUITINATION; ASSOCIATION; COMPLEXES; MECHANISM; DATABASE AB Comparative interactomics is a strategy for inferring potential interactions among orthologous proteins or "interologs". Herein we focus, in contrast to standard homology-based inference, on the divergence of protein interaction profiles among closely related organisms, showing that the approach can correlate specific traits to phenotypic differences. As a model, this new comparative interactomic approach was applied at a large scale to human papillomaviruses (HPVs) proteins. The oncogenic potential of HPVs is mainly determined by the E6 and E7 early proteins. We have mapped and overlapped the virus-host protein interaction networks of E6 and E7 proteins from 11 distinct HPV genotypes, selected for their different tropisms and pathologies. We generated robust and comprehensive datasets by combining two orthogonal protein interaction assays: yeast two-hybrid (Y2H), and our recently described "high-throughput Gaussia princeps protein complementation assay" (HT-GPCA). HT-GPCA detects protein interaction by measuring the interaction-mediated reconstitution of activity of a split G. princeps luciferase. Hierarchical clustering of interaction profiles recapitulated HPV phylogeny and was used to correlate specific virus-host interaction profiles with pathological traits, reflecting the distinct carcinogenic potentials of different HPVs. This comparative interactomics constitutes a reliable and powerful strategy to decipher molecular relationships in virtually any combination of microorganism-host interactions. (c) 2012 Elsevier Inc. All rights reserved. C1 [Neveu, Gregory; Cassonnet, Patricia; Rolloy, Caroline; Mendoza, Jose; Muller, Mandy; Demeret, Caroline; Favre, Michel; Jacob, Yves] Inst Pasteur, Unite Genet Papillomavirus & Canc Humain GPCH, F-75015 Paris, France. [Vidalain, Pierre-Olivier; Tangy, Frederic] Inst Pasteur, Unite Genom Virale & Vaccinat G2V, F-75015 Paris, France. [Jones, Louis] Inst Pasteur, Grp Logiciels & Banques Donnees, F-75015 Paris, France. [Tafforeau, Lionel; Lotteau, Vincent; Rabourdin-Combe, Chantal] IFR 128 BioSci, IMAP Team, F-69007 Lyon, France. [Trave, Gilles] ESBS, CNRS, UMR 7175, Equipe Oncoprot, F-67412 Illkirch Graffenstaden, France. [Dricot, Amelie; Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02215 USA. [Dricot, Amelie; Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Dricot, Amelie; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Jacob, Y (reprint author), Inst Pasteur, Unite Genet Papillomavirus & Canc Humain GPCH, 25 Rue Docteur Roux, F-75015 Paris, France. EM yves.jacob@pasteur.fr RI Hill, David/B-6617-2011; lotteau, vincent/M-8143-2014; TRAVE, Gilles/P-8577-2016; OI Tafforeau, Lionel/0000-0002-8468-7422; Neveu, Gregory/0000-0002-2363-6031 FU Institut Pasteur; Ligue nationale contre le Cancer [R05/75-129, RS07/75-75]; Association pour la Recherche sur le Cancer [3731XA0531F, 4867]; Agence Nationale de la Recherche (EPI-HPV-3D program); Center of Excellence in Genomic Science (CEGS) [P50-HG004233, R01-H6001715]; National Human Genome Research Institute (NHGRI); Conseil General de la Vienne; Pasteur Weizmann foundation; Ministere de l'education nationale, de la recherche et de la technologie (MENRT) fellowship FX We thank Richard Paul, Katherine Kean and Michael Cusick for critical reading of the manuscript. This work was supported in part by funding from the Institut Pasteur, and by grants from the Ligue nationale contre le Cancer (grants R05/75-129 and RS07/75-75), the Association pour la Recherche sur le Cancer (grants 3731XA0531F and 4867), and the Agence Nationale de la Recherche (EPI-HPV-3D program) and by Center of Excellence in Genomic Science (CEGS) grants P50-HG004233 and R01-H6001715 from the National Human Genome Research Institute (NHGRI) (M. V, DE.H). G.N. was a recipient of the Conseil General de la Vienne and Pasteur Weizmann foundation. C.R. was a recipient of a Ministere de l'education nationale, de la recherche et de la technologie (MENRT) fellowship. NR 35 TC 20 Z9 20 U1 0 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD DEC PY 2012 VL 58 IS 4 BP 349 EP 359 DI 10.1016/j.ymeth.2012.07.029 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 082FS UT WOS:000314378300006 PM 22898364 ER PT J AU Tusset, C Noel, SD Trarbach, EB Silveira, LFG Jorge, AAL Brito, VN Cukier, P Seminara, SB de Mendonca, BB Kaiser, UB Latronico, AC AF Tusset, Cintia Noel, Sekoni D. Trarbach, Ericka B. Silveira, Leticia F. G. Jorge, Alexander A. L. Brito, Vinicius N. Cukier, Priscila Seminara, Stephanie B. de Mendonca, Berenice B. Kaiser, Ursula B. Latronico, Ana Claudia TI Mutational analysis of TAC3 and TACR3 genes in patients with idiopathic central pubertal disorders SO ARQUIVOS BRASILEIROS DE ENDOCRINOLOGIA E METABOLOGIA LA English DT Article DE Neurokinin B; neurokinin B receptor; central precocious puberty; normosmic isolated hypogonadotropic hypogonadism; constitutional delay of growth and puberty ID GONADOTROPIN-RELEASING-HORMONE; HYPOGONADOTROPIC HYPOGONADISM; NEUROKININ-B; TACHYKININ RECEPTORS; CONSTITUTIONAL DELAY; PROPEPTIDE MUTATION; ARCUATE NUCLEUS; REPRODUCTION; INHERITANCE; PATTERNS AB Objective: To investigate the presence of variants in the TAC3 and TACR3 genes, which encode NKB and its receptor (NK3R), respectively, in a large cohort of patients with idiopathic central pubertal disorders. Subjects and methods: Two hundred and thirty seven patients were studied: 114 with central precocious puberty (CPP), 73 with normosmic isolated hypogonadotropic hypogonadism (IHH), and 50 with constitutional delay of growth and puberty (CDGP). The control group consisted of 150 Brazilian individuals with normal pubertal development. Genomic DNA was extracted from peripheral blood and the entire coding region of both TAC3 and TACR3 genes were amplified and automatically sequenced. Results: We identified one variant (p.A63P) in NKB and four variants, p.G18D, p.L58L (c.172C > T), p.W275* and p.A449S in NK3R, which were absent in the control group. The p.A63P variant was identified in a girl with CPP, and p.A449S in a girl with CDGP. The known p.G18D, p.L58L, and p.W275* variants were identified in three unrelated males with normosmic IHH. Conclusion: Rare variants in the TAC3 and TACR3 genes were identified in patients with central pubertal disorders. Loss-of-function variants of TACR3 were associated with the normosmic IHH phenotype. Arq Bras Endocrinol Metab. 2012; 56(9):646-52 C1 [Tusset, Cintia; Trarbach, Ericka B.; Silveira, Leticia F. G.; Jorge, Alexander A. L.; Brito, Vinicius N.; Cukier, Priscila; de Mendonca, Berenice B.; Latronico, Ana Claudia] Univ Sao Paulo, Fac Med, Lab Hormonios & Genet Mol LIM42, Unidade Endocrinol Desenvolvimento,Hosp Clin, Sao Paulo, Brazil. [Noel, Sekoni D.; Kaiser, Ursula B.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Noel, Sekoni D.; Kaiser, Ursula B.] Brigham & Womens Hosp, Harvard Ctr Reprod Sci, Boston, MA 02115 USA. [Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Seminara, Stephanie B.] Massachusetts Gen Hosp, Harvard Ctr Reprod Sci, Boston, MA 02114 USA. RP Latronico, AC (reprint author), Av Dr Eneas de Carvalho Aguiar 155,2 Andar,Bloco, BR-05403900 Sao Paulo, Brazil. EM cintiatusset@yahoo.com.br; anacl@usp.br RI BRITO, VINICIUS/B-3776-2013; Silveira, Leticia/D-3975-2014; Jorge, Alexander/C-7697-2012; Trarbach, Ericka/I-5395-2012 OI BRITO, VINICIUS/0000-0003-4140-6296; Jorge, Alexander/0000-0003-2567-7360; FU Fapesp [05/04726]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [302825/2011-8, 305743/2011-8]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH) [U54 HD28138] FX this study was supported by Fapesp grants 05/04726 and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) grants 302825/2011-8 (to A.C.L.), by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) grants 305743/2011-8 (to B.B.M.), and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), by means of the cooperative agreement U54 HD28138 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research (to U.B.K.). NR 34 TC 13 Z9 15 U1 0 U2 3 PU SBEM-SOC BRASIL ENDOCRINOLOGIA & METABOLOGIA PI RIO DE JANEIRO, RJ PA RUA HUMAITA, 85 CJ 501, RIO DE JANEIRO, RJ, 22261-000, BRAZIL SN 0004-2730 J9 ARQ BRAS ENDOCRINOL JI Arq. Bras. Endocrinol. Metabol. PD DEC PY 2012 VL 56 IS 9 BP 646 EP 652 PG 7 GA 072XL UT WOS:000313706900008 PM 23329188 ER PT J AU Babu, K Hu, ZT Chien, SC Garriga, G Kaplan, JM AF Babu, Kavita Hu, Zhitao Chien, Shih-Chieh Garriga, Gian Kaplan, Joshua M. TI Using C. elegans to understand the function and regulation of cell adhesion molecules SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Meeting Abstract CT 19th Biennial Meeting of the International-Society-for-Developmental-Neuroscience (ISDN) CY JAN 11-14, 2012 CL Mumbai, INDIA SP Int Soc Dev Neurosci (ISDN) C1 [Babu, Kavita; Hu, Zhitao; Kaplan, Joshua M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Chien, Shih-Chieh; Garriga, Gian] Univ Calif Berkeley, Dept Mol Cell Biol, Berkeley, CA 94720 USA. [Babu, Kavita] Indian Inst Sci Educ & Res, Mohali 140306, Punjab, India. EM kavitababu@iisermohali.ac.in NR 1 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2012 VL 30 IS 8 BP 665 EP 665 DI 10.1016/j.ijdevneu.2012.03.314 PG 1 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 077EE UT WOS:000314009900129 ER PT J AU Schroy, PC Emmons, KM Peters, E Glick, JT Robinson, PA Lydotes, MA Mylvaganam, SR Coe, AM Chen, CA Chaisson, CE Pignone, MP Prout, MN Davidson, PK Heeren, TC AF Schroy, Paul C., III Emmons, Karen M. Peters, Ellen Glick, Julie T. Robinson, Patricia A. Lydotes, Maria A. Mylvaganam, Shamini R. Coe, Alison M. Chen, Clara A. Chaisson, Christine E. Pignone, Michael P. Prout, Marianne N. Davidson, Peter K. Heeren, Timothy C. TI Aid-Assisted Decision Making and Colorectal Cancer Screening A Randomized Controlled Trial SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID SERVICES TASK-FORCE; PATIENT PREFERENCES; UPDATE; IMPACT; RECOMMENDATION; INTERVENTIONS; SURVEILLANCE; PERCEPTIONS; GUIDELINES; RATIONALE AB Background: Shared decision making (SDM) is a widely recommended yet unproven strategy for increasing colorectal cancer (CRC) screening uptake. Previous trials of decision aids to increase SDM and CRC screening uptake have yielded mixed results. Purpose: To assess the impact of decision aid-assisted SDM on CRC screening uptake. Design: RCT. Setting/participants: The study was conducted at an urban, academic safety-net hospital and community health center between 2005 and 2010. Participants were asymptomatic, average-risk patients aged 50-75 years due for CRC screening. Intervention: Study participants (n = 825) were randomized to one of two intervention arms (decision aid plus personalized risk assessment or decision aid alone) or control arm. The interventions took place just prior to a routine office visit with their primary care providers. Main outcome measures: The primary outcome was completion of a CRC screening test within 12 months of the study visit. Logistic regression was used to identify predictors of test completion and mediators of the intervention effect. Analysis was completed in 2011. Results: Patients in the decision-aid group were more likely to complete a screening test than control patients (43.1% vs 34.8%, p = 0.046) within 12 months of the study visit; conversely, test uptake for the decision aid and decision aid plus personalized risk assessment arms was similar (43.1% vs 37.1%, p = 0.15). Assignment to the decision-aid arm (AOR = 1.48, 95% CI = 1.04, 2.10), black race (AOR = 1.52, 95% CI = 1.12, 2.06) and a preference for a patient-dominant decision-making approach (AOR = 1.55, 95% CI = 1.02, 2.35) were independent determinants of test completion. Activation of the screening discussion and enhanced screening intentions mediated the intervention effect. Conclusions: Decision aid-assisted SDM has a modest impact on CRC screening uptake. A decision aid plus personalized risk assessment tool is no more effective than a decision aid alone. C1 [Schroy, Paul C., III; Glick, Julie T.; Robinson, Patricia A.; Lydotes, Maria A.; Mylvaganam, Shamini R.; Coe, Alison M.; Davidson, Peter K.] Boston Univ, Dept Med, Boston, MA 02215 USA. [Chen, Clara A.; Chaisson, Christine E.] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA. [Prout, Marianne N.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Heeren, Timothy C.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Peters, Ellen] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Pignone, Michael P.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. RP Schroy, PC (reprint author), Boston Med Ctr, 85 E Concord St,Suite 7715, Boston, MA 02118 USA. EM paul.schroy@bmc.org OI Prout, Marianne/0000-0001-8747-6199; Pignone, Michael/0000-0002-6657-7342; Heeren, Timothy/0000-0001-5643-3559; Chaisson, Christine/0000-0002-3207-9257 FU Agency for Healthcare Research and Quality [RO1HS013912]; National Cancer Institute [K05CA 129166]; National Science Foundation [SES-1047757, SES-0517770] FX The study was supported by grant RO1HS013912 from the Agency for Healthcare Research and Quality (PI, Paul C. Schroy III). Dr. Pignone's effort was supported by a National Cancer Institute Established Investigator Award K05CA 129166. Dr. Peters's effort was supported in part by the National Science Foundation (SES-1047757 and SES-0517770). NR 48 TC 23 Z9 23 U1 8 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD DEC PY 2012 VL 43 IS 6 BP 573 EP 583 DI 10.1016/j.amepre.2012.08.018 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 071FR UT WOS:000313574800002 PM 23159252 ER PT J AU Kuznetsov, HS Marsh, T Markens, BA Castano, Z Greene-Colozzi, A Hay, SA Brown, VE Richardson, AL Signoretti, S Battinelli, EM McAllister, SS AF Kuznetsov, Hanna S. Marsh, Timothy Markens, Beth A. Castano, Zafira Greene-Colozzi, April Hay, Samantha A. Brown, Victoria E. Richardson, Andrea L. Signoretti, Sabina Battinelli, Elisabeth M. McAllister, Sandra S. TI Identification of Luminal Breast Cancers That Establish a Tumor-Supportive Macroenvironment Defined by Proangiogenic Platelets and Bone Marrow-Derived Cells SO CANCER DISCOVERY LA English DT Article ID ANTI-ANGIOGENESIS THERAPY; ALPHA-GRANULES; ASPIRIN; METASTASIS; EXPRESSION; GROWTH; CD24; TRANSFORMATION; NEPHRECTOMY; CARCINOMA AB Breast cancer recurrence rates vary following treatment, suggesting that tumor cells disseminate early from primary sites but remain indolent indefinitely before progressing to symptomatic disease. The reasons why some indolent disseminated tumors erupt into overt disease are unknown. We discovered a novel process by which certain luminal breast cancer (LBC) cells and patient tumor specimens (LBC "instigators") establish a systemic macroenvironment that supports outgrowth of otherwise-indolent disseminated tumors ("responders"). Instigating LBCs secrete cytokines that are absorbed by platelets, which are recruited to responding tumor sites where they aid vessel formation. Instigator-activated bone marrow cells enrich responding tumor cell expression of CD24, an adhesion molecule for platelets, and provide a source of VEGF receptor 2(+) tumor vessel cells. This cascade results in growth of responder adenocarcinomas and is abolished when platelet activation is inhibited by aspirin. These findings highlight the macroenvironment as an important component of disease progression that can be exploited therapeutically. SIGNIFICANCE: Currently, processes that mediate progression of otherwise indolent tumors are not well understood, making it difficult to accurately predict which cancer patients are likely to relapse. Our findings highlight the macroenvironment as an important component of disease progression that can be exploited to more accurately identify patients who would benefit from adjuvant therapy. Cancer Discov; 2(12); 1150-65. (C) 2012 AACR. C1 [McAllister, Sandra S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Brown, Victoria E.; Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Castano, Zafira; Signoretti, Sabina; Battinelli, Elisabeth M.; McAllister, Sandra S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Greene-Colozzi, April; Richardson, Andrea L.; Signoretti, Sabina] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [McAllister, Sandra S.] Harvard Stem Cell Inst, Boston, MA USA. [McAllister, Sandra S.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP McAllister, SS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, 1 Blackfan Circle,Karp 5-214, Boston, MA 02115 USA. EM smcallister1@partners.org RI McAllister, Sandra/J-7373-2012; Silva, Mariana/B-9530-2012 FU Dana-Farber/Harvard Breast Cancer SPORE NCI [2 P50 CA89393-06]; Dana Farber/Harvard Cancer Center Kidney Cancer SPORE [P50 CA101942]; NIH NHLBI [K08HL097070]; Malcolm Hecht Jr. Hematology Research Endowment; Dana Farber/Harvard Cancer Center Breast Cancer SPORE NCI [5 P30 CA006516-46-2010-01-NN-02]; Harvard Stem Cell Institute; BWH Biomedical Research Institute FX This work was supported in part by funds from the Dana-Farber/Harvard Breast Cancer SPORE NCI, 2 P50 CA89393-06 (A.L. Richardson); the Dana Farber/Harvard Cancer Center Kidney Cancer SPORE P50 CA101942 (S. Signoretti); NIH NHLBI K08HL097070 and the Malcolm Hecht Jr. Hematology Research Endowment (EMB); the Dana Farber/Harvard Cancer Center Breast Cancer SPORE NCI 5 P30 CA006516-46-2010-01-NN-02, Harvard Stem Cell Institute, and BWH Biomedical Research Institute (S.S. McAllister). S.A. Hay is an American Cancer Society Fuller Research Fellow. NR 47 TC 34 Z9 34 U1 1 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD DEC PY 2012 VL 2 IS 12 BP 1150 EP 1165 DI 10.1158/2159-8290.CD-12-0216 PG 16 WC Oncology SC Oncology GA 072AZ UT WOS:000313641700026 PM 22896036 ER PT J AU Losordo, DW Kibbe, MR Mendelsohn, F Marston, W Driver, VR Sharafuddin, M Teodorescu, V Wiechmann, BN Thompson, C Kraiss, L Carman, T Dohad, S Huang, P Junge, CE Story, K Weistroffer, T Thorne, TM Millay, M Runyon, JP Schainfeld, R AF Losordo, Douglas W. Kibbe, Melina R. Mendelsohn, Farrell Marston, William Driver, Vickie R. Sharafuddin, Melhem Teodorescu, Victoria Wiechmann, Bret N. Thompson, Charles Kraiss, Larry Carman, Teresa Dohad, Suhail Huang, Paul Junge, Candice E. Story, Kenneth Weistroffer, Tara Thorne, Tina M. Millay, Meredith Runyon, John Paul Schainfeld, Robert CA Autologous CD34 Cell Therapy Criti TI A Randomized, Controlled Pilot Study of Autologous CD34+ Cell Therapy for Critical Limb Ischemia SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE peripheral vascular disease; revascularization; reperfusion; randomized trial; stem cells ID PERIPHERAL ARTERIAL-DISEASE; GROWTH-FACTOR PLASMID; DOUBLE-BLIND; CONTROLLED-TRIAL; INTRAMUSCULAR INJECTION; PARENTERAL THERAPY; 6-MONTH OUTCOMES; LIPO-ECRAPROST; GENE-THERAPY; ANGIOGENESIS AB Background-Critical limb ischemia portends a risk of major amputation of 25% to 35% within 1 year of diagnosis. Preclinical studies provide evidence that intramuscular injection of autologous CD34+ cells improves limb perfusion and reduces amputation risk. In this randomized, double-blind, placebo-controlled pilot study, we evaluated the safety and efficacy of intramuscular injections of autologous CD34+ cells in subjects with moderate or high-risk critical limb ischemia, who were poor or noncandidates for surgical or percutaneous revascularization (ACT34-CLI). Methods and Results-Twenty-eight critical limb ischemia subjects were randomized and treated: 7 to 1x10(5) (low-dose) and 9 to 1x10(6) (high-dose) autologous CD34+ cells/kg; and 12 to placebo (control). Intramuscular injections were distributed into 8 sites within the ischemic lower extremity. At 6 months postinjection, 67% of control subjects experienced a major or minor amputation versus 43% of low-dose and 22% of high-dose cell-treated subjects (P=0.137). This trend continued at 12 months, with 75% of control subjects experiencing any amputation versus 43% of low-dose and 22% of high-dose cell-treated subjects (P=0.058). Amputation incidence was lower in the combined cell-treated groups compared with control group (6 months: P=0.125; 12 months: P=0.054), with the low-dose and high-dose groups individually showing trends toward improved amputation-free survival at 6 months and 12 months. No adverse safety signal was associated with cell administration. Conclusions-This study provides evidence that intramuscular administration of autologous CD34+ cells was safe in this patient population. Favorable trends toward reduced amputation rates in cell-treated versus control subjects were observed. These findings warrant further exploration in later-phase clinical trials. C1 [Losordo, Douglas W.; Weistroffer, Tara; Thorne, Tina M.; Millay, Meredith] Northwestern Univ, NW Mem Hosp, Div Cardiovasc Med, Chicago, IL 60611 USA. [Losordo, Douglas W.; Weistroffer, Tara; Thorne, Tina M.; Millay, Meredith] Northwestern Univ, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA. [Kibbe, Melina R.] Northwestern Univ, NW Mem Hosp, Div Cardiol, Chicago, IL 60611 USA. [Kibbe, Melina R.] Northwestern Univ, NW Mem Hosp, Div Vasc Surg, Chicago, IL 60611 USA. [Mendelsohn, Farrell] Ctr Therapeut Angiogenesis, Birmingham, AL USA. [Marston, William] Univ N Carolina, Div Vasc Surg, Chapel Hill, NC USA. [Driver, Vickie R.] Boston Med Ctr, Dept Surg, Boston, MA USA. [Driver, Vickie R.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Sharafuddin, Melhem] Univ Iowa, Dept Surg, Iowa City, IA 52242 USA. [Teodorescu, Victoria] Mt Sinai Sch Med, Div Vasc Surg, New York, NY USA. [Wiechmann, Bret N.] Vasc & Intervent Phys, Gainesville, FL USA. [Thompson, Charles] Orlando Reg Med Ctr Vasc Specialist Cent FL, Orlando, FL USA. [Kraiss, Larry] Univ Utah, Div Vasc Surg, Salt Lake City, UT USA. [Carman, Teresa] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Dohad, Suhail] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Huang, Paul] Swedish Med Ctr, Seattle, WA USA. [Losordo, Douglas W.; Junge, Candice E.; Story, Kenneth] Baxter Healthcare Corp, Deerfield, IL 60015 USA. [Runyon, John Paul] Christ Hosp, Cincinnati, OH 45219 USA. [Schainfeld, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Losordo, DW (reprint author), Baxter Healthcare Corp, 1 Baxter Pkwy, Deerfield, IL 60015 USA. EM douglas_losordo@baxter.com OI Huang, Paul/0000-0003-0563-921X FU NIH [HL-53354, HL-77428, HL-63414, HL-80137, HL95874, HLPO1-108795, HL-57516] FX Baxter Healthcare Corporation. This study was supported in part by grants from the NIH (HL-53354, HL-77428, HL-63414, HL-80137, HL95874, HLPO1-108795, HL-57516). NR 24 TC 50 Z9 55 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD DEC PY 2012 VL 5 IS 6 BP 821 EP 830 DI 10.1161/CIRCINTERVENTIONS.112.968321 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071GA UT WOS:000313576500021 PM 23192920 ER PT J AU Pham, PCT Pham, PMT Pham, PTT AF Pham, Phuong-Chi T. Pham, Phuong-Mai T. Pham, Phuong-Thu T. TI Patients with diabetes mellitus Type 2 and hypomagnesemia may have enhanced glomerular filtration via hypocalcemia SO CLINICAL NEPHROLOGY LA English DT Article DE hypomagnesemia; diabetes mellitus; glomerular hyperfiltration; hypocalcemia ID HUMAN MAGNESIUM-DEFICIENCY; LOWER SERUM MAGNESIUM; PARATHYROID-HORMONE; CALCIUM; VASOCONSTRICTION; HYPERFILTRATION; RESISTANCE; INSULIN; KIDNEY AB Introduction: Hypomagnesemia and glomerular hyperfiltration are commonly observed in patients with diabetes mellitus Type 2 (DM2). In the current study, we examined the relationship between hypomagnesemia and glomerular filtration rates in DM2 patients. Materials and methods: Data were obtained for DM2 patients without documented kidney disease seen at UCLA-Olive View Medical Center during January through March 2001. Data for hemoglobin, hemoglobin A1C (HbA1C), routine electrolytes, lipid profiles, urinalyses, history of hypertension, and pharmacy profiles were retrieved. Estimation of glomerular filtration rate (eGFR) was based on the CKD-epi formula. Multivariate analyses were performed to determine the correlations between eGFR and clinical factors including age, gender, history of hypertension, the use of diuretics, renin angiotensin system (RAS) inhibitors, acetylsalicylic acid, and statins, serum calcium, magnesium, hemoglobin, HbA1C, lipid profile, and degree of proteinuria. Results: 550 patients (54% females) with mean age 57.5 +/- 11.0 years and eGFR 95.7 +/- 14.8 ml/min/1.73 m(2) were included. Multivariate analysis revealed negative correlations with eGFR for age (Pearson-correlation-coefficient: -0.7, p < 0.0001), hypertension (-0.32, p < 0.0001), magnesium (-0.21, p < 0.0001), calcium (-0.13, p = 0.009), proteinuria (-0.17, p < 0.0001), and the use of RAS inhibitors (-0.21, p < 0.0001), and diuretics (-0.24, p < 0.0001) and a positive correlation for HbA1C (0.28, p < 0.0001). Further analysis of the interaction between serum magnesium and calcium, defined as magnesium x calcium (Mg x Ca), revealed a more significant correlation with eGFR than either cation alone (-0.24, p < 0.0001). Conclusions: Serum magnesium, calcium, and (Mg x Ca) all had significant negative correlations with eGFR. In particular, (Mg x Ca) had the strongest correlation with eGFR. C1 [Pham, Phuong-Chi T.] Olive View UCLA Med Ctr, Div Nephrol & Hypertens, Sylmar, CA 91342 USA. [Pham, Phuong-Mai T.] VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Dept Internal Med, North Hills, CA USA. [Pham, Phuong-Thu T.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Pham, PCT (reprint author), Olive View UCLA Med Ctr, Div Nephrol & Hypertens, 14445 Olive View Dr,2B-182, Sylmar, CA 91342 USA. EM pham.pchi@ucla.edu NR 28 TC 3 Z9 3 U1 0 U2 3 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD DEC PY 2012 VL 78 IS 6 BP 442 EP 448 DI 10.5414/CN107525 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 068YF UT WOS:000313401400003 PM 23073059 ER PT J AU Sabuncu, MR Van Leemput, K AF Sabuncu, Mert R. Van Leemput, Koen CA Alzheimers Dis Neuroimaging TI The Relevance Voxel Machine (RVoxM): A Self-Tuning Bayesian Model for Informative Image-Based Prediction SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Image classification; pattern recognition ID DEFORMATION-BASED MORPHOMETRY; FEATURE-SELECTION TECHNIQUES; SUPPORT VECTOR MACHINE; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; CORTICAL SURFACE; PATTERN-CLASSIFICATION; VARIABLE SELECTION; COORDINATE SYSTEM AB This paper presents the relevance voxel machine (RVoxM), a dedicated Bayesian model for making predictions based on medical imaging data. In contrast to the generic machine learning algorithms that have often been used for this purpose, the method is designed to utilize a small number of spatially clustered sets of voxels that are particularly suited for clinical interpretation. RVoxM automatically tunes all its free parameters during the training phase, and offers the additional advantage of producing probabilistic prediction outcomes. We demonstrate RVoxM as a regression model by predicting age from volumetric gray matter segmentations, and as a classification model by distinguishing patients with Alzheimer's disease from healthy controls using surface-based cortical thickness data. Our results indicate that RVoxM yields biologically meaningful models, while providing state-of-the-art predictive accuracy. C1 [Sabuncu, Mert R.; Van Leemput, Koen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sabuncu, Mert R.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Van Leemput, Koen] Tech Univ Denmark, Dept Informat & Math Modeling, DK-2800 Lyngby, Denmark. [Van Leemput, Koen] Aalto Univ, Dept Informat & Comp Sci, FI-00076 Aalto, Finland. [Van Leemput, Koen] Aalto Univ, Dept Biomed Engn & Computat Sci, FI-00076 Aalto, Finland. RP Sabuncu, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RI Van Leemput, Koen/A-9197-2009 OI Van Leemput, Koen/0000-0001-6466-5309 FU NIH NCRR [P41-RR14075]; NIBIB [R01EB006758, R01EB013565, 1K25EB013649-01]; NINDS [R01NS052585]; Academy of Finland [133611]; Finnish Funding Agency for Technology and Innovation (ComBrain); Harvard Catalyst, Harvard Clinical and Translational Science Center (NIH) [1KL2RR025757-01]; NIH K25 grant [1K25EB013649-01]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; National Institutes of Health [P30 AG010129, K01 AG030514] FX This work was supported by the NIH NCRR (P41-RR14075), the NIBIB (R01EB006758, R01EB013565, 1K25EB013649-01), the NINDS (R01NS052585), the Academy of Finland (133611), the Finnish Funding Agency for Technology and Innovation (ComBrain), and the Harvard Catalyst, Harvard Clinical and Translational Science Center (NIH grant 1KL2RR025757-01 and financial contributions from Harvard and its affiliations) and an NIH K25 grant (1K25EB013649-01, NIH NIBIB). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health Rev March 26, 2012. The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This work was also supported by the National Institutes of Health under Grant P30 AG010129 and Grant K01 AG030514. NR 88 TC 17 Z9 17 U1 0 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD DEC PY 2012 VL 31 IS 12 BP 2290 EP 2306 DI 10.1109/TMI.2012.2216543 PG 17 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 072RT UT WOS:000313690600011 PM 23008245 ER PT J AU Parast, L Cheng, SC Cai, TX AF Parast, Layla Cheng, Su-Chun Cai, Tianxi TI Landmark Prediction of Long-Term Survival Incorporating Short-Term Event Time Information SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Risk prediction; Survival time; Varying-coefficient model ID VARYING-COEFFICIENT MODELS; STAGE RENAL-DISEASE; SUDDEN CARDIAC DEATH; RISK-PREDICTION; BREAST-CANCER; DIALYSIS PATIENTS; MULTISTATE MODEL; COMPETING RISKS; REGRESSION; PERFORMANCE AB In recent years, a wide range of markers have become available as potential tools to predict risk or progression of disease. In addition to such biological and genetic markers, short-term outcome information may be useful in predicting long-term disease outcomes. When such information is available, it would be desirable to combine this along with predictive markers to improve the prediction of long-term survival. Most existing methods for incorporating censored short-term event information in predicting long-term survival focus on modeling the disease process and are derived under restrictive parametric models in a multistate survival setting. When such model assumptions fail to hold, the resulting prediction of long-term outcomes may be invalid or inaccurate. When there is only a single discrete baseline covariate, a fully nonparametric estimation procedure to incorporate short-term event time information has been previously proposed. However, such an approach is not feasible for settings with one or more continuous covariates due to the curse of dimensionality. In this article, we propose to incorporate short-term event time information along with multiple covariates collected up to a landmark point via a flexible varying-coefficient model. To evaluate and compare the prediction performance of the resulting landmark prediction rule, we use robust nonparametric procedures that do not require the correct specification of the proposed varying-coefficient model. Simulation studies suggest that the proposed procedures perform well in finite samples. We illustrate them here using a dataset of postdialysis patients with end-stage renal disease. C1 [Parast, Layla] RAND Corp, Santa Monica, CA 90401 USA. [Cheng, Su-Chun] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Parast, L (reprint author), RAND Corp, Santa Monica, CA 90401 USA. EM Layla_Parast@rand.org; scheng@jimmy.harvard.edu; tcai@hsph.harvard.edu FU National Institutes of Health [T32GM074897, R01AI052817, R01-GM079330, U54LM008748] FX Layla Parast is Associate Statistician, RAND Corporation, Santa Monica, CA 90401 (E-mail: Layla_Parast@rand.org). This work was completed while Parast was a Ph.D. candidate in biostatistics at Harvard University. Su-Chun Cheng is Senior Research Scientist, Dana-Farber Cancer Institute, Boston, MA 02115 (E-mail: scheng@jimmy.harvard.edu). Tianxi Cai is Professor, Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115 (E-mail: tcai@hsph.harvard.edu). The data reported here have been supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U.S. government. The authors are grateful to the editor, an associate editor, and the reviewers for their insightful comments on the article. Support for this research was provided by National Institutes of Health grants T32GM074897 (Parast), R01AI052817 (Parast), R01-GM079330 (Cai), and U54LM008748 (Cai). NR 60 TC 5 Z9 5 U1 1 U2 8 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 2012 VL 107 IS 500 BP 1492 EP 1501 DI 10.1080/01621459.2012.721281 PG 10 WC Statistics & Probability SC Mathematics GA 068VP UT WOS:000313394600018 PM 23293405 ER PT J AU Hsieh, DT Pfeifer, HH Thiele, EA AF Hsieh, David T. Pfeifer, Heidi H. Thiele, Elizabeth A. TI Dietary Management of Epilepsy SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material ID GLYCEMIC-INDEX TREATMENT; MODIFIED ATKINS DIET; KETOGENIC DIET; CHILDHOOD EPILEPSY; EFFICACY C1 [Hsieh, David T.; Pfeifer, Heidi H.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hsieh, DT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM david.hsieh@us.af.mil NR 11 TC 2 Z9 2 U1 0 U2 4 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD DEC 1 PY 2012 VL 86 IS 11 BP 1000 EP + PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 047YL UT WOS:000311877300006 PM 23198664 ER PT J AU Atlas, SJ Ashburner, JM Chang, YC Lester, WT Barry, MJ Grant, RW AF Atlas, Steven J. Ashburner, Jeffrey M. Chang, Yuchiao Lester, William T. Barry, Michael J. Grant, Richard W. TI Population-Based Breast Cancer Screening in a Primary Care Network SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID INCREASE RECOMMENDATION; COLORECTAL CANCERS; PATIENT REMINDERS; MAMMOGRAPHY; INTERVENTIONS; PROVIDERS; QUALITY; MODEL; COMMUNICATION; METAANALYSIS AB Objectives:To assess the ability of a health information technology system to facilitate population-based breast cancer screening. Study Design: Cohort study with 2-year follow-up after a 1-year cluster randomized trial. Methods: Study population was women 42 to 69 years old receiving care within a 12-practice primary care network. The management informatics system (1) identified women overdue for mammograms, (2) connected them to primary care providers using a web-based tool, (3) created automatically generated outreach letters for patients specified by providers, (4) monitored for subsequent mammography scheduling and completion, and (5) provided practice delegates with a list of women remaining unscreened for reminder phone calls. Eligible women overdue for a mammogram during a 1-year study period included those overdue at study start (prevalent cohort) and those who became overdue during follow-up (incident cohort).The main outcome measure was mammography completion rates over 3 years. Results: Among 32,688 eligible women, 9795 (30%) were overdue for screening (4487 intervention, 5308 control). Intervention patients were somewhat younger, more likely to be non-Hispanic white, and more likely to have health insurance compared with control patients. Adjusted completion rates in the prevalent cohort In = 6697) were significantly higher among intervention patients after 3 years (51.7% vs 45.8%; P = .0021. For patients in the incident cohort (n = 3098), adjusted completion rates after 2 years were 53.8% versus 48.7%, respectively (P = .052). Conclusions: Population-based informatics systems can enable sustained increases in mammography screening rates beyond rates seen with office-based visit reminders. (Am J Manag Care. 2012;18(12):821-829) C1 [Atlas, Steven J.; Ashburner, Jeffrey M.; Chang, Yuchiao; Barry, Michael J.; Grant, Richard W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Div,Med Serv, Boston, MA 02114 USA. [Lester, William T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Comp Sci Lab, Boston, MA 02114 USA. RP Atlas, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Div,Med Serv, 50 Staniford St, Boston, MA 02114 USA. EM satlas@partners.org OI Lester, William/0000-0003-4086-9280; Grant, Richard/0000-0002-6164-8025 FU National Cancer Institute [NCI 1 R21 CA121908]; Agency for Healthcare Research and Quality [AHRQ R18 HS018161] FX Grant funding was provided by the National Cancer Institute (NCI 1 R21 CA121908) and by institutional support through the Massachusetts General Hospital Primary Care Operations Improvement program.; Drs Atlas and Grant are supported by a grant from the Agency for Healthcare Research and Quality (AHRQ R18 HS018161). The other authors. (JMA, YC, WTL, MJB) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article. NR 26 TC 6 Z9 6 U1 0 U2 4 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 DEC PY 2012 VL 18 IS 12 BP 821 EP 829 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 062JO UT WOS:000312916300005 PM 23286611 ER PT J AU Unni, US Raj, T Sambashivaiah, S Kuriyan, R Uthappa, S Vaz, M Regan, MM Kurpad, AV AF Unni, Uma S. Raj, Tony Sambashivaiah, Sucharita Kuriyan, Rebecca Uthappa, Sheila Vaz, Mario Regan, Meredith M. Kurpad, Anura V. TI The effect of a controlled 8-week metabolic ward based lysine supplementation on muscle function, insulin sensitivity and leucine kinetics in young men SO CLINICAL NUTRITION LA English DT Article DE Indian adults; Lysine requirement; Skeletal muscle; Muscle strength; Insulin sensitivity ID AMINO-ACID OXIDATION; ASIAN INDIAN MEN; BODY-COMPOSITION; PROTEIN-SYNTHESIS; BALANCE TECHNIQUE; ELDERLY-MEN; MASS; RESISTANCE; GLUCOSE; REQUIREMENTS AB Background & aims: The 2007 FAO/WHO/UNU lysine requirement is 30 mg kg(-1) d(-1). Developing country populations may be at risk of lysine deficiency, with effects on muscle and its function. The effect of an 8 wk lysine supplementation diet on muscle mass and function was assessed. Methods: Healthy, under and well-nourished men were studied before and after 8 wk, during which low (n = 20) and high (n = 20) lysine diets were consumed. The low lysine diets (similar to 25 and similar to 40 mg kg(-1) d(-1) for under and well-nourished respectively) were based on the subjects' habitual lysine intake, while the high lysine diet supplied 80 mg kg(-1) d(-1) Anthropometry, muscle function, insulin sensitivity (IS) and leucine kinetics were measured before and after the experimental period. Results: The high lysine diet had a small positive effect (about +7.5%) on muscle strength, but no effect on other parameters. Over the 8 wk period in the whole group, the change in muscle strength correlated with the change in muscle mass (r = 0.5, P = 0.001), while the change in muscle mass correlated with the change in IS (r = 0.3, P = 0.04), but there were no intake specific differences. Conclusion: Over an 8 wk controlled feeding period, an intake of 80 mg lysine kg(-1) d(-1) had a small positive effect on muscle strength, but no other effects. (C) 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. C1 [Unni, Uma S.; Raj, Tony; Sambashivaiah, Sucharita; Kuriyan, Rebecca; Vaz, Mario; Kurpad, Anura V.] St Johns Natl Acad Hlth Sci, St Johns Res Inst, Div Nutr, Bangalore 560034, Karnataka, India. [Unni, Uma S.; Uthappa, Sheila] St Johns Med Coll, Dept Biochem, Bangalore 560034, Karnataka, India. [Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Kurpad, AV (reprint author), St Johns Natl Acad Hlth Sci, St Johns Res Inst, Div Nutr, Bangalore 560034, Karnataka, India. EM uma@sjri.res.in; tonyraj@sjri.res.in; sucharita.dr@gmail.com; rebecca@sjri.res.in; sheilauthappa@hotmail.com; mariovaz@sjri.res.in; mregan@jimmy.harvard.edu; a.kurpad@sjri.res.in FU Ajinomoto Amino Acid Research Program FX Authors acknowledge the financial support provided by Ajinomoto Amino Acid Research Program, which had no role in study design, in the collection, analysis and interpretation of data. The authors acknowledge the assistance of Dr. G. Ramakrishnan, Dr. S. Shastry and Mr. Vincent in the conduct of these studies. NR 30 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0261-5614 J9 CLIN NUTR JI Clin. Nutr. PD DEC PY 2012 VL 31 IS 6 BP 903 EP 910 DI 10.1016/j.clnu.2012.03.008 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 067NH UT WOS:000313301100013 PM 22524975 ER PT J AU Anderson, E Siegel, E White, D Barrett, LF AF Anderson, Eric Siegel, Erika White, Dominique Barrett, Lisa Feldman TI Out of Sight but Not Out of Mind: Unseen Affective Faces Influence Evaluations and Social Impressions SO EMOTION LA English DT Article DE affect; continuous flash suppression; consciousness; person perception ID MEDIAL PREFRONTAL CORTEX; TOP-DOWN FACILITATION; RHESUS-MONKEY; ORBITOFRONTAL CORTEX; BINOCULAR-RIVALRY; VISUAL AWARENESS; FEARFUL FACES; CONNECTIONS; PERCEPTION; EMOTION AB Using Continuous Flash Suppression (CFS), we demonstrated in four experiments that affective information extracted from unseen faces influences both affective and personality judgments of neutral faces. In four experiments, participants judged neutral faces as more pleasant or unpleasant (Studies 1 and 2) or as more or less trustworthy, likable, and attractive (Study 3) or as more or less competent or interpersonally warm (Study 4) when paired with unseen smiling or scowling faces compared to when paired with unseen neutral faces. These findings suggest that affective influences are a normal part of everyday experience and provide evidence for the affective foundations consciousness. Affective misattribution arises even when affective changes occur after a neutral stimulus is presented, demonstrating that these affective influences cannot be explained as a simple semantic priming effect. These findings have implications for understanding the constructive nature of experience, as well as the role of affect in social impressions. C1 [Anderson, Eric; Siegel, Erika; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [White, Dominique] Boston Coll, Dept Psychol, Chestnut Hill, MA 02167 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. RP Barrett, LF (reprint author), Northeastern Univ, Dept Psychol, 125 Nightingale Hall,360 Huntington Ave, Boston, MA 02115 USA. EM l.barrett@neu.edu OI Anderson, Eric/0000-0002-4215-6308 FU NIH HHS [DP1 OD003312, DP1OD003312] NR 64 TC 16 Z9 16 U1 6 U2 33 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD DEC PY 2012 VL 12 IS 6 BP 1210 EP 1221 DI 10.1037/a0027514 PG 12 WC Psychology, Experimental SC Psychology GA 047YZ UT WOS:000311878700007 PM 22506501 ER PT J AU Maurovich-Horvat, P Schlett, CL Alkadhi, H Nakano, M Otsuka, F Stolzmann, P Scheffel, H Ferencik, M Kriegel, MF Seifarth, H Virmani, R Hoffmann, U AF Maurovich-Horvat, Pal Schlett, Christopher L. Alkadhi, Hatem Nakano, Masataka Otsuka, Fumiyuki Stolzmann, Paul Scheffel, Hans Ferencik, Maros Kriegel, Matthias F. Seifarth, Harald Virmani, Renu Hoffmann, Udo TI The Napkin-Ring Sign Indicates Advanced Atherosclerotic Lesions in Coronary CT Angiography SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE computed tomography; coronary artery disease; histopathology; napkin-ring sign; plaque attenuation pattern; vulnerable coronary plaque ID MULTISLICE COMPUTED-TOMOGRAPHY; INCREMENTAL PROGNOSTIC VALUE; RISK-ASSESSMENT STRATEGIES; MULTIDETECTOR-ROW CT; INTRAVASCULAR ULTRASOUND; NONINVASIVE ASSESSMENT; VULNERABLE PLAQUE; ARTERY-DISEASE; STABLE ANGINA; CULPRIT AB OBJECTIVES This study sought to determine the accuracy of plaque pattern assessment by coronary computed tomography angiography (CCTA) to differentiate between early and advanced atherosclerotic lesions as defined by histology. BACKGROUND A ringlike attenuation pattern of coronary atherosclerotic plaques termed as napkin-ring sign (NRS) was described in CCTA of patients who had acute coronary syndrome. METHODS All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local ethics committees was obtained. We investigated 21 coronary arteries of 7 donor hearts. Overall, 611 histological sections were obtained and coregistered with CCTA images. The CCTA cross sections were read in random order for conventional plaque categories (noncalcified [NCP], mixed [MP], calcified [CP]) and plaque patterns (homogenous, heterogeneous with no napkin-ring sign [non-NRS], and heterogeneous with NRS). RESULTS No plaque was detected in 134 (21.9%), NCP in 254 (41.6%), MP in 191 (31.3%), and CP in 32 (5.2%) CCTA cross sections. The NCP and MP were further classified into homogenous plaques (n = 207, 46.5%), non-NRS plaques (n = 200, 44.9%), and NRS plaques (n = 38, 8.6%). The specificities of NCP and MP to identify advanced lesions were moderate (57.9%, 95% confidence interval [CI]: 50.1% to 65.6%, and 72.1%, 95% CI: 64.7% to 79.4%, respectively), which were similar to the homogenous and heterogeneous plaques (62.6%, 95% CI: 54.8% to 70.3%, and 67.3%, 95% CI: 58.6% to 76.1%, respectively). In contrast, the specificity of the NRS to identify advanced lesions was excellent (98.9%, 95% CI: 97.6% to 100%). The diagnostic performance of the pattern-based scheme to identify advanced lesions was significantly better than that of the conventional plaque scheme (area under the curve: 0.761 vs. 0.678, respectively; p = 0.001). CONCLUSIONS The assessment of the plaque pattern improves diagnostic accuracy of CCTA to identify advanced atherosclerotic lesions. The CCTA finding of NRS has a high specificity and high positive predictive value for the presence of advanced lesions. (J Am Coll Cardiol Img 2012; 5: 1243-52) (C) 2012 by the American College of Cardiology Foundation C1 [Maurovich-Horvat, Pal; Schlett, Christopher L.; Alkadhi, Hatem; Stolzmann, Paul; Scheffel, Hans; Ferencik, Maros; Kriegel, Matthias F.; Seifarth, Harald; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, Boston, MA 02114 USA. [Maurovich-Horvat, Pal; Schlett, Christopher L.; Alkadhi, Hatem; Stolzmann, Paul; Scheffel, Hans; Ferencik, Maros; Kriegel, Matthias F.; Seifarth, Harald; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Maurovich-Horvat, Pal] Semmelweis Univ, Ctr Heart, Budapest, Hungary. [Nakano, Masataka; Otsuka, Fumiyuki; Virmani, Renu] CV Path Inst Inc, Gaithersburg, MD USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org OI Maurovich-Horvat, Pal/0000-0003-0885-736X FU GE Healthcare; Deutsche Forschungsgemeinschaft [DFG Se 2029/1-1]; Terumo Corporation; [TAMOP-4.2.1/B-09/1/KMR-2010-0001] FX From the *Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; dagger Heart Center, Semmelweis University, Budapest, Hungary; and the double dagger CV Path Institute Inc., Gaithersburg, Maryland. This work was supported by an unrestricted grant from GE Healthcare. Dr. Maurovich-Horvat received support from grant no. TAMOP-4.2.1/B-09/1/KMR-2010-0001. Dr. Seifarth was supported by a grant from Deutsche Forschungsgemeinschaft (grant no. DFG Se 2029/1-1). Dr. Virmani has been a consultant to Terumo Corporation, from whom he has received research grant support. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 45 TC 37 Z9 39 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD DEC PY 2012 VL 5 IS 12 BP 1243 EP 1252 DI 10.1016/j.jcmg.2012.03.019 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 066WF UT WOS:000313251400009 PM 23236975 ER PT J AU Simmons-Stern, NR Deason, RG Brandler, BJ Frustace, BS O'Connor, MK Ally, BA Budson, AE AF Simmons-Stern, Nicholas R. Deason, Rebecca G. Brandler, Brian J. Frustace, Bruno S. O'Connor, Maureen K. Ally, Brandon A. Budson, Andrew E. TI Music-based memory enhancement in Alzheimer's Disease: Promise and limitations SO NEUROPSYCHOLOGIA LA English DT Article DE Alzheimer's disease; Recognition memory; Music; Mnemonics; Familiarity; Recollection ID MILD COGNITIVE IMPAIRMENT; FALSE RECOGNITION; OLDER-ADULTS; NEURAL BASIS; DEMENTIA; FAMILIARITY; RECOLLECTION; DIAGNOSIS; PICTURES; FLUENCY AB In a previous study (Simmons-Stern, Budson & Ally, 2010), we found that patients with Alzheimer's disease (AD) better recognized visually presented lyrics when the lyrics were also sung rather than spoken at encoding. The present study sought to further investigate the effects of music on memory in patients with AD by making the content of the song lyrics relevant for the daily life of an older adult and by examining how musical encoding alters several different aspects of episodic memory. Patients with AD and healthy older adults studied visually presented novel song lyrics related to instrumental activities of daily living (IADL) that were accompanied by either a sung or a spoken recording. Overall, participants performed better on a memory test of general lyric content for lyrics that were studied sung as compared to spoken. However, on a memory test of specific lyric content, participants performed equally well for sung and spoken lyrics. We interpret these results in terms of a dual-process model of recognition memory such that the general content questions represent a familiarity-based representation that is preferentially sensitive to enhancement via music, while the specific content questions represent a recollection-based representation unaided by musical encoding. Additionally, in a test of basic recognition memory for the audio stimuli, patients with AD demonstrated equal discrimination for sung and spoken stimuli. We propose that the perceptual distinctiveness of musical stimuli enhanced metamemorial awareness in AD patients via a non-selective distinctiveness heuristic, thereby reducing false recognition while at the same time reducing true recognition and eliminating the mnemonic benefit of music. These results are discussed in the context of potential music-based memory enhancement interventions for the care of patients with AD. Published by Elsevier Ltd. C1 [Simmons-Stern, Nicholas R.; Deason, Rebecca G.; Brandler, Brian J.; Frustace, Bruno S.; O'Connor, Maureen K.; Budson, Andrew E.] VA Boston Healthcare Syst, Ctr Translat Cognit Neurosci, Boston, MA 02130 USA. [Simmons-Stern, Nicholas R.; Deason, Rebecca G.; Brandler, Brian J.; Frustace, Bruno S.; O'Connor, Maureen K.; Budson, Andrew E.] Boston Univ, Sch Med, Dept Neurol, Alzheimers Dis Ctr, Boston, MA 02118 USA. [O'Connor, Maureen K.] Bedford Vet Adm Hosp, Dept Psychol, Bedford, MA USA. [Ally, Brandon A.] Vanderbilt Univ, Dept Neurol, Nashville, TN USA. [Ally, Brandon A.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. [Ally, Brandon A.] Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. RP Deason, RG (reprint author), VA Boston Healthcare Syst, Ctr Translat Cognit Neurosci, 150 S Huntington Ave,Mailstop 151-C, Boston, MA 02130 USA. EM rdeason@bu.edu OI Ally, Brandon/0000-0002-6034-7968 FU National Institute on Aging [R01 AG025815, K23 AG031925, P30 AG13846]; Department of Veterans Affairs, Veterans Health Administration FX This research was supported by National Institute on Aging grants R01 AG025815 (AEB), K23 AG031925 (BAA), P30 AG13846 (AEB), and a Department of Veterans Affairs, Veterans Health Administration, VISN 1 Early Career Development Award to RGD. This material is also the result of work supported with resources and the use of facilities at the VA Boston Healthcare System, Boston, MA We would additionally like to thank our vocalist Anna Miller, and Levi Miller for his help with data processing. NR 50 TC 14 Z9 15 U1 2 U2 83 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD DEC PY 2012 VL 50 IS 14 BP 3295 EP 3303 DI 10.1016/j.neuropsychologia.2012.09.019 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 065IT UT WOS:000313142700015 PM 23000133 ER PT J AU Wang, H Jurado, KA Wu, XL Shun, MC Li, X Ferris, AL Smith, SJ Patel, PA Fuchs, JR Cherepanov, P Kvaratskhelia, M Hughes, SH Engelman, A AF Wang, Hao Jurado, Kellie A. Wu, Xiaolin Shun, Ming-Chieh Li, Xiang Ferris, Andrea L. Smith, Steven J. Patel, Pratiq A. Fuchs, James R. Cherepanov, Peter Kvaratskhelia, Mamuka Hughes, Stephen H. Engelman, Alan TI HRP2 determines the efficiency and specificity of HIV-1 integration in LEDGF/p75 knockout cells but does not contribute to the antiviral activity of a potent LEDGF/p75-binding site integrase inhibitor SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PREINTEGRATION COMPLEX-FORMATION; RETROVIRAL DNA INTEGRATION; SMALL-MOLECULE INHIBITORS; TYPE-1 REPLICATION; CHROMATIN-BINDING; COACTIVATOR P75; HUMAN GENOME; IN-VITRO; DOMAIN AB The binding of integrase (IN) to lens epithelium-derived growth factor (LEDGF)/p75 in large part determines the efficiency and specificity of HIV-1 integration. However, a significant residual preference for integration into active genes persists in Psip1 (the gene that encodes for LEDGF/p75) knockout (KO) cells. One other cellular protein, HRP2, harbors both the PWWP and IN-binding domains that are important for LEDGF/p75 co-factor function. To assess the role of HRP2 in HIV-1 integration, cells generated from Hdgfrp2 (the gene that encodes for HRP2) and Psip1/Hdgfrp2 KO mice were infected alongside matched control cells. HRP2 depleted cells supported normal infection, while disruption of Hdgfrp2 in Psip1 KO cells yielded additional defects in the efficiency and specificity of integration. These deficits were largely restored by ectopic expression of either LEDGF/p75 or HRP2. The double-KO cells nevertheless supported residual integration into genes, indicating that IN and/or other host factors contribute to integration specificity in the absence of LEDGF/p75 and HRP2. Psip1 KO significantly increased the potency of an allosteric inhibitor that binds the LEDGF/p75 binding site on IN, a result that was not significantly altered by Hdgfrp2 disruption. These findings help to rule out the host factor-IN interactions as the primary antiviral targets of LEDGF/p75-binding site IN inhibitors. C1 [Wang, Hao; Jurado, Kellie A.; Shun, Ming-Chieh; Li, Xiang; Engelman, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Wang, Hao; Jurado, Kellie A.; Shun, Ming-Chieh; Li, Xiang; Engelman, Alan] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Wu, Xiaolin] SAIC Frederick Inc, Lab Mol Technol, Frederick, MD 21702 USA. [Ferris, Andrea L.; Smith, Steven J.; Hughes, Stephen H.] Frederick Natl Lab Canc Res, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Patel, Pratiq A.; Fuchs, James R.] Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. [Cherepanov, Peter] Canc Res UK, London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England. [Kvaratskhelia, Mamuka] Ohio State Univ, Coll Pharm, Ctr Retrovirus Res, Columbus, OH 43210 USA. [Kvaratskhelia, Mamuka] Ohio State Univ, Coll Pharm, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Engelman, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. EM alan_engelman@dfci.harvard.edu RI wang, hao/O-6217-2014; Cherepanov, Peter/F-6859-2010 OI Cherepanov, Peter/0000-0002-0634-538X FU US National Institutes of Health (NIH) [AI039394, AI081581, AI097044]; National Cancer Institute's Intramural Center for Cancer Research; UK Medical Research Council [G1000917] FX US National Institutes of Health (NIH) [AI039394 to A. E., AI081581 to M. K., AI097044 to J.R.F.]; National Cancer Institute's Intramural Center for Cancer Research, which supports the HIV Drug Resistance Program [to S. H. H.]; UK Medical Research Council [G1000917 to P. C.]. Funding for open access charge: US NIH [AI039394]. NR 70 TC 34 Z9 34 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC PY 2012 VL 40 IS 22 BP 11518 EP 11530 DI 10.1093/nar/gks913 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 069DG UT WOS:000313414800036 PM 23042676 ER PT J AU Canolty, RT Ganguly, K Carmena, JM AF Canolty, Ryan T. Ganguly, Karunesh Carmena, Jose M. TI Task-Dependent Changes in Cross-Level Coupling between Single Neurons and Oscillatory Activity in Multiscale Networks SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID FIELD POTENTIAL OSCILLATIONS; PRIMATE MOTOR CORTEX; SENSORIMOTOR CORTEX; PARIETAL CORTEX; CELL ASSEMBLIES; ORIENTATION SELECTIVITY; GAMMA OSCILLATIONS; PREFRONTAL CORTEX; BETA-OSCILLATIONS; WORKING-MEMORY AB Understanding the principles governing the dynamic coordination of functional brain networks remains an important unmet goal within neuroscience. How do distributed ensembles of neurons transiently coordinate their activity across a variety of spatial and temporal scales? While a complete mechanistic account of this process remains elusive, evidence suggests that neuronal oscillations may play a key role in this process, with different rhythms influencing both local computation and long-range communication. To investigate this question, we recorded multiple single unit and local field potential (LFP) activity from microelectrode arrays implanted bilaterally in macaque motor areas. Monkeys performed a delayed center-out reach task either manually using their natural arm (Manual Control, MC) or under direct neural control through a brain-machine interface (Brain Control, BC). In accord with prior work, we found that the spiking activity of individual neurons is coupled to multiple aspects of the ongoing motor beta rhythm (10-45 Hz) during both MC and BC, with neurons exhibiting a diversity of coupling preferences. However, here we show that for identified single neurons, this beta-to-rate mapping can change in a reversible and task-dependent way. For example, as beta power increases, a given neuron may increase spiking during MC but decrease spiking during BC, or exhibit a reversible shift in the preferred phase of firing. The within-task stability of coupling, combined with the reversible cross-task changes in coupling, suggest that task-dependent changes in the beta-to-rate mapping play a role in the transient functional reorganization of neural ensembles. We characterize the range of task-dependent changes in the mapping from beta amplitude, phase, and inter-hemispheric phase differences to the spike rates of an ensemble of simultaneously-recorded neurons, and discuss the potential implications that dynamic remapping from oscillatory activity to spike rate and timing may hold for models of computation and communication in distributed functional brain networks. C1 [Canolty, Ryan T.; Carmena, Jose M.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Ganguly, Karunesh] San Francisco VA Med Ctr, San Francisco, CA USA. [Ganguly, Karunesh] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Carmena, Jose M.] Univ Calif Berkeley, UCB UCSF Joint Grad Grp Bioengn, Berkeley, CA 94720 USA. RP Canolty, RT (reprint author), Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. EM carmena@eecs.berkeley.edu FU NIH NINDS [1K99NS070627-01A1]; NSF [CBET-0954243]; DARPA [N66001-10-C-2008] FX This work was supported by grants from the NIH NINDS (1K99NS070627-01A1 to RTC), NSF (CBET-0954243 to JMC), and a DARPA Contract N66001-10-C-2008 to JMC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 80 TC 15 Z9 15 U1 0 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD DEC PY 2012 VL 8 IS 12 AR e1002809 DI 10.1371/journal.pcbi.1002809 PG 23 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 062EI UT WOS:000312901500016 PM 23284276 ER PT J AU Sze, JA Goodkind, MS Gyurak, A Levenson, RW AF Sze, Jocelyn A. Goodkind, Madeleine S. Gyurak, Anett Levenson, Robert W. TI Aging and Emotion Recognition: Not Just a Losing Matter SO PSYCHOLOGY AND AGING LA English DT Article DE aging; emotion recognition; empathic accuracy; social interaction ID AGE-RELATED DIFFERENCES; ADULT LIFE-SPAN; EMPATHIC ACCURACY; FACIAL EXPRESSIONS; SOCIOEMOTIONAL SELECTIVITY; PHYSIOLOGICAL LINKAGE; MARITAL INTERACTION; GENDER-DIFFERENCES; SOCIAL COGNITION; SEX-DIFFERENCES AB Past studies on emotion recognition and aging have found evidence of age-related decline when emotion recognition was assessed by having participants detect single emotions depicted in static images of full or partial (e.g., eye region) faces. These tests afford good experimental control but do not capture the dynamic nature of real-world emotion recognition, which is often characterized by continuous emotional judgments and dynamic multimodal stimuli. Research suggests that older adults often perform better under conditions that better mimic real-world social contexts. We assessed emotion recognition in young, middle-aged, and older adults using two traditional methods (single emotion judgments of static images of faces and eyes) and an additional method in which participants made continuous emotion judgments of dynamic, multimodal stimuli (videotaped interactions between young, middle-aged, and older couples). Results revealed an Age x Test interaction. Largely consistent with prior research, we found some evidence that older adults performed worse than young adults when judging single emotions from images of faces (for sad and disgust faces only) and eyes (for older eyes only), with middle-aged adults falling in between. In contrast, older adults did better than young adults on the test involving continuous emotion judgments of dyadic interactions, with middle-aged adults falling in between. In tests in which target stimuli differed in age, emotion recognition was not facilitated by an age match between participant and target. These findings are discussed in terms of theoretical and methodological implications for the study of aging and emotional processing. C1 [Sze, Jocelyn A.] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA USA. [Goodkind, Madeleine S.] VA Palo Alto Hlth Care Syst, Sierra Pacific Mental Illness Res Educ & Clin Ctr, Palo Alto, CA USA. [Goodkind, Madeleine S.; Gyurak, Anett] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Gyurak, Anett] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Levenson, Robert W.] Univ Calif Berkeley, Inst Personal & Social Res, Dept Psychol, Berkeley, CA 94720 USA. RP Levenson, RW (reprint author), Univ Calif Berkeley, Inst Personal & Social Res, Dept Psychol, 4143 Tolman Hall MC 5050, Berkeley, CA 94720 USA. EM boblev@socrates.berkeley.edu FU NIA NIH HHS [R01 AG041762, R37 AG017766, R37-AG017766] NR 82 TC 14 Z9 14 U1 2 U2 39 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD DEC PY 2012 VL 27 IS 4 BP 940 EP 950 DI 10.1037/a0029367 PG 11 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA 067PB UT WOS:000313306500020 PM 22823183 ER PT J AU Gilman, SE AF Gilman, Stephen E. TI The successes and challenges of life course epidemiology: A commentary on Gibb, Fergusson and Horwood (2012) SO SOCIAL SCIENCE & MEDICINE LA English DT Editorial Material DE Life course epidemiology; Mental health; Social inequality; Income ID SOCIOECONOMIC-STATUS; ADULT HEALTH; UNNECESSARY ADJUSTMENT; DEVELOPMENTAL ORIGINS; SENSITIVITY-ANALYSIS; FAMILY DISRUPTION; MAJOR DEPRESSION; COHORT PROFILE; HEART-DISEASE; RISK C1 [Gilman, Stephen E.] Harvard Univ, Dept Soc Human Dev & Hlth, Sch Publ Hlth, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA. [Gilman, Stephen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Gilman, SE (reprint author), Harvard Univ, Dept Soc Human Dev & Hlth, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM sgilman@hsph.harvard.edu RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 FU NIMH NIH HHS [MH087544] NR 56 TC 4 Z9 4 U1 0 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 2012 VL 75 IS 12 BP 2124 EP 2128 DI 10.1016/j.socscimed.2012.08.007 PG 5 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 060DX UT WOS:000312757800009 PM 22959838 ER PT J AU Caspi, CE Kawachi, I Subramanian, SV Adamkiewicz, G Sorensen, G AF Caspi, Caitlin E. Kawachi, Ichiro Subramanian, S. V. Adamkiewicz, Gary Sorensen, Glorian TI The relationship between diet and perceived and objective access to supermarkets among low-income housing residents (vol 75, pg 1254, 2012) SO SOCIAL SCIENCE & MEDICINE LA English DT Correction C1 [Caspi, Caitlin E.; Kawachi, Ichiro; Subramanian, S. V.; Adamkiewicz, Gary; Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02114 USA. [Adamkiewicz, Gary; Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Caspi, CE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Kresge 7th Floor,677 Huntingon Ave, Boston, MA 02114 USA. EM caitlincaspi@gmail.com NR 1 TC 0 Z9 0 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 2012 VL 75 IS 12 BP 2540 EP 2540 DI 10.1016/j.socscimed.2012.09.002 PG 1 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 060DX UT WOS:000312757800061 ER PT J AU Gordon, JA AF Gordon, James A. TI Reflections on the Consensus Process: A Leadership Role for Emergency Medicine in Educational Scholarship and Practice Across Health Care SO ACADEMIC EMERGENCY MEDICINE LA English DT Editorial Material ID SIMULATION AB In just a few decades, emergency medicine (EM) has assumed a leadership role in medical education across many academic medical centers. This rapid evolution suggests medical education as a natural priority area for EM scholarship. This year's Academic Emergency Medicine consensus conference provides an ideal forum to focus on educational research as a core element of the specialty's academic portfolio. C1 [Gordon, James A.] Massachusetts Gen Hosp, MGH Learning Lab, Boston, MA 02114 USA. [Gordon, James A.] Massachusetts Gen Hosp, Div Med Simulat, Dept Emergency Med, Boston, MA 02114 USA. [Gordon, James A.] Harvard Univ, Sch Med, Gilbert Program Med Simulat, Boston, MA USA. RP Gordon, JA (reprint author), Massachusetts Gen Hosp, MGH Learning Lab, Boston, MA 02114 USA. EM jgordon3@partners.org NR 11 TC 2 Z9 2 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD DEC PY 2012 VL 19 IS 12 SI SI BP 1333 EP 1335 DI 10.1111/acem.12020 PG 3 WC Emergency Medicine SC Emergency Medicine GA 059XX UT WOS:000312740100004 PM 23216790 ER PT J AU Choo, EK Fernandez, R Hayden, EM Schneider, JI Clyne, B Ginsburg, S Gruppen, LD AF Choo, Esther K. Fernandez, Rosemarie Hayden, Emily M. Schneider, Jeffrey I. Clyne, Brian Ginsburg, Shiphra Gruppen, Larry D. TI An Agenda for Increasing Grant Funding of Emergency Medicine Education Research SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID SCHOOL-OF-MEDICINE; RESEARCH PRODUCTIVITY; FACULTY-DEVELOPMENT; CRITICAL-APPRAISAL; PROGRAM; PUBLICATIONS; OPPORTUNITY; OUTCOMES; QUALITY; GUIDE AB Funding is a perennial challenge for medical education researchers. Through a consensus process, the authors developed a multifaceted agenda for increasing funding of education research in emergency medicine (EM). Priority agenda items include developing resources to increase the competitiveness of medical education research faculty in grant applications, identifying means by which departments may bolster their faculty's grant writing success, taking long-term steps to increase the number of grants available to education researchers in the field, and encouraging a shift in cultural attitudes toward education research. C1 [Choo, Esther K.; Clyne, Brian] Brown Univ, Dept Emergency Med, Warren Alpert Med Sch, Providence, RI 02912 USA. [Fernandez, Rosemarie] Univ Washington, Div Emergency Med, Seattle, WA 98195 USA. [Hayden, Emily M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Schneider, Jeffrey I.] Boston Univ, Sch Med, Dept Emergency Med, Boston Med Ctr, Boston, MA 02118 USA. [Ginsburg, Shiphra] Univ Toronto, Dept Med, Wilson Ctr Res Educ, Fac Med, Toronto, ON, Canada. [Gruppen, Larry D.] Univ Michigan, Sch Med, Dept Med Educ, Ann Arbor, MI USA. RP Choo, EK (reprint author), Brown Univ, Dept Emergency Med, Warren Alpert Med Sch, Providence, RI 02912 USA. EM esther_choo@brown.edu RI Ginsburg, Shiphra/C-1695-2008; OI Ginsburg, Shiphra/0000-0002-4595-6650; Schneider, Jeffrey/0000-0002-7861-2854; Choo, Esther/0000-0001-8847-5745; Gruppen, Larry/0000-0002-2107-0126 NR 39 TC 1 Z9 1 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD DEC PY 2012 VL 19 IS 12 SI SI BP 1434 EP 1441 DI 10.1111/acem.12041 PG 8 WC Emergency Medicine SC Emergency Medicine GA 059XX UT WOS:000312740100018 PM 23252424 ER PT J AU Shiwaku, Y Anada, T Yamazaki, H Honda, Y Morimoto, S Sasaki, K Suzuki, O AF Shiwaku, Y. Anada, T. Yamazaki, H. Honda, Y. Morimoto, S. Sasaki, K. Suzuki, O. TI Structural, morphological and surface characteristics of two types of octacalcium phosphate-derived fluoride-containing apatitic calcium phosphates SO ACTA BIOMATERIALIA LA English DT Article DE Octacalcium phosphate; Fluoride; Hydrolysis; Fluoride-containing hydroxyapatite; Scaffold materials ID IN-VITRO; HYDROXYAPATITE COATINGS; THERMODYNAMIC ANALYSIS; BIOLOGICAL RESPONSES; SPRAYED COATINGS; BONE-FORMATION; ENAMEL; HYDROLYSIS; CELLS; SOLUBILITY AB Octacalcium phosphate (OCP) has been reported to stimulate bone regeneration during hydrolysis into hydroxyapatite (HA). The present study was designed to characterize structural, morphological and surface properties of fluoride-containing apatitic calcium phosphates (CaP) obtained through OCP hydrolysis or direct precipitation of OCP in the presence of 12-230 ppm of fluoride (F). The products were characterized by chemical analysis, X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and Fourier transform infrared spectroscopy (FTIR) as well as measurements of surface area, solubility, osteoblastic activities and bovine serum albumin (BSA) adsorption. XRD analysis re-confirmed that both preparations yielded more apatitic CaP with a higher concentration of F. However, the co-precipitated products (CF-CaP) maintained the properties of OCP, in particular the solubility, whereas the hydrolysis products (HF-CaP) had the characteristics of fluoridated apatite. The crystals of plate-like OCP were changed to the crystals of rod-like CF-CaP and small irregular HF-CaP with the advance of the hydrolysis. The SAED analysis detected both OCP and apatite crystals even in the most hydrolyzed CF-CaP. Mouse bone marrow stromal ST-2 cells grew better on CF-CaP compared with HF-CaP. BSA adsorption was inhibited on HF-CaP more than on CF-CaP. These results show that OCP produces physicochemically distinct apatitic fluoridated CaP during hydrolysis, regarding the structure, the crystal morphology and the protein adsorption, depending on the fluoride introduction route, which provides biologically interesting material. (c) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Shiwaku, Y.; Anada, T.; Honda, Y.; Morimoto, S.; Suzuki, O.] Tohoku Univ, Grad Sch Dent, Div Craniofacial Funct Engn, Aoba Ku, Sendai, Miyagi 9808575, Japan. [Shiwaku, Y.; Sasaki, K.] Tohoku Univ, Grad Sch Dent, Div Adv Prosthet Dent, Aoba Ku, Sendai, Miyagi 9808575, Japan. [Yamazaki, H.] Forsyth Inst, Dept Biomineralizat, Cambridge, MA 02142 USA. RP Suzuki, O (reprint author), Tohoku Univ, Grad Sch Dent, Div Craniofacial Funct Engn, Aoba Ku, 4-1 Sehyo Machi, Sendai, Miyagi 9808575, Japan. EM suzuki-o@m.tohoku.ac.jp FU Ministry of Education, Science, Sports and Culture of Japan [23390450, 23659909, 23106010]; Iketani Science and Technology Foundation FX This study was supported in part by Grants-in-aid (23390450, 23659909 and 23106010) from the Ministry of Education, Science, Sports and Culture of Japan and Iketani Science and Technology Foundation. The authors thank Professor Hiroshi Masumoto at The Center for Interdisciplinary Research (CIR), Tohoku University, for his direction in observing the present materials by FE-SEM. NR 56 TC 17 Z9 17 U1 2 U2 46 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 J9 ACTA BIOMATER JI Acta Biomater. PD DEC PY 2012 VL 8 IS 12 BP 4417 EP 4425 DI 10.1016/j.actbio.2012.07.041 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 060GR UT WOS:000312765000027 PM 22868193 ER PT J AU Jain, RK AF Jain, Rakesh K. TI Delivery of molecular and cellular medicine to solid tumors SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE Tumor microcirculation; Angiogenesis; Blood flow; Vascular permeability; Diffusion and convection; Receptor-ligand binding; Interstitial pressure; Lymphatics; Cell adhesion and deformation; Cancer detection and treatment ID INTERSTITIAL FLUID PRESSURE; ENDOTHELIAL GROWTH-FACTOR; NATURAL-KILLER-CELLS; VASCULAR-PERMEABILITY FACTOR; COLON ADENOCARCINOMA XENOGRAFT; POSITRON-EMISSION-TOMOGRAPHY; ENZYME-CONJUGATED ANTIBODIES; INDUCED LEUKOCYTE ADHESION; HUMAN-MELANOMA XENOGRAFTS; NECROSIS-FACTOR-ALPHA AB To reach cancer cells in a tumor, a blood-borne therapeutic molecule or cell must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium, and finally migrate through the interstitium. Unfortunately, tumors often develop in ways that hinder each of these steps. Our research goals are to analyze each of these steps experimentally and theoretically, and then integrate the resulting information in a unified theoretical framework. This paradigm of analysis and synthesis has allowed us to obtain a better understanding of physiological barriers in solid tumors, and to develop novel strategies to exploit and/or to overcome these barriers for improved cancer detection and treatment. (C) 2012 Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu FU National Cancer Institute; National Science Foundation; American Cancer Society FX I thank Carol Lyons, Larry Baxter and Stuart Friedrich for their help with the references, Lance Munn for his help with Figures 1-3, Fan Yuan with Figures 4 and 7, Gabriel Helmlinger with Figure 6, David Berk with Figure 8, Marc Dellian with Figure 9, Larry Baxter with Figure 10, Paolo Netti with Figure 11, and Yves Boucher with Table 2. Research described here was primarily supported by grants from the National Cancer Institute, the National Science Foundation and the American Cancer Society. NR 150 TC 40 Z9 41 U1 2 U2 65 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X EI 1872-8294 J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD DEC PY 2012 VL 64 SU S BP 353 EP 365 DI 10.1016/j.addr.2012.09.011 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 058EK UT WOS:000312616700031 PM 24511174 ER PT J AU Thomas, B Mimiaga, MJ Mayer, KH Closson, EE Johnson, CV Menon, S Mani, J Vijaylakshmi, R Dilip, M Betancourt, T Safren, SA AF Thomas, Beena Mimiaga, Matthew J. Mayer, Kenneth H. Closson, Elizabeth E. Johnson, Carey V. Menon, Sunil Mani, Jamuna Vijaylakshmi, R. Dilip, Meenalochini Betancourt, Theresa Safren, Steven A. TI ENSURING IT WORKS: A COMMUNITY-BASED APPROACH TO HIV PREVENTION INTERVENTION DEVELOPMENT FOR MEN WHO HAVE SEX WITH MEN IN CHENNAL INDIA SO AIDS EDUCATION AND PREVENTION LA English DT Article ID IDENTIFIED MEN; RISK; PREVALENCE; BEHAVIOR; MUMBAI; MSM; INFECTION; VIOLENCE; STIGMA; SAMPLE AB Men who have sex with men (MSM) in India have an HIV seroprevalence 22 times greater than the country's general population and face unique challenges that may hinder the effectiveness of current HIV prevention efforts. To obtain an understanding of the logistical and sociocultural barriers MSM experience while accessing HIV prevention services, focus groups and key informant interviews were conducted with 55 MSM in Chennai, India. Qualitative data were analyzed using descriptive qualitative content analysis. Sixty-five percent of participants identified as kothi (receptive partners), 9% as panthi (insertive partners), 22% as double decker (receptive and insertive), and 4% did not disclose. Themes included: (a) fatigue with current HIV risk reduction messages; (b) increased need for non-judgmental and confidential services; and (c) inclusion of content that acknowledges individual and structural-level determinants of risk such as low self-esteem, depression, and social discrimination. MSM interventions may benefit from approaches that address multilevel psychosocial factors, including skills building and strategies to foster self-acceptance and increased social support. C1 [Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Behav Med Serv,Dept Psychiat, Boston, MA 02114 USA. [Thomas, Beena; Mani, Jamuna; Vijaylakshmi, R.; Dilip, Meenalochini] Indian Council Med Res, TB Res Ctr, Madras, Tamil Nadu, India. [Mimiaga, Matthew J.; Mayer, Kenneth H.; Closson, Elizabeth E.; Johnson, Carey V.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. [Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Infect Dis, Boston, MA 02114 USA. [Menon, Sunil] Sahodaran, Madras, Tamil Nadu, India. [Betancourt, Theresa] Harvard Univ, Sch Publ Hlth, Francois Xavier Bagnoud Ctr Hlth & Human Rights, Boston, MA 02114 USA. RP Mimiaga, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Behav Med Serv,Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM mmimiaga@partners.org FU NIMH NIH HHS [R21 MH085314, R21 MH085314-01] NR 43 TC 10 Z9 10 U1 3 U2 10 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0899-9546 J9 AIDS EDUC PREV JI Aids Educ. Prev. PD DEC PY 2012 VL 24 IS 6 BP 483 EP 499 PG 17 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 058IV UT WOS:000312628200001 PM 23206199 ER PT J AU Psaros, C Barinas, J Robbins, GK Bedoya, CA Safren, SA Park, ER AF Psaros, Christina Barinas, Jennifer Robbins, Gregory K. Bedoya, C. Andres Safren, Steven A. Park, Elyse R. TI Intimacy and Sexual Decision Making: Exploring the Perspective of HIV Positive Women Over 50 SO AIDS PATIENT CARE AND STDS LA English DT Article ID OLDER WOMEN; CLINICAL-TRIAL; BODY-IMAGE; HIV/AIDS; AGE; LIPODYSTROPHY; KNOWLEDGE; ATTITUDES; BEHAVIOR; ADULTS AB Due to advances made in HIV treatment, the population of individuals with HIV over the age of 50 is growing. Aging women face many developmental challenges and some of these challenges, including having or maintaining intimate partner relationships, may be particularly pronounced for aging women living with HIV. However, research exploring the psychosocial needs of aging women with HIV is limited. Thus, the aim of this study was to explore factors that impact intimate partner relationships for older women with HIV. Nineteen women (mean age = 56.79, SD = 4.63 years) referred from Boston-area community organizations and hospitals completed in-depth individual interviews. Forty-seven percent of participants identified themselves as Black/African American, and 37% as White/Caucasian. Average time since diagnosis was 16.32 years (SD = 5.70). Interviews continued until saturation of content was reached. Inclusion criteria included: biologically born female; aged 50 years or older; diagnosis of HIV/AIDS; and English speaking. Qualitative interviews were coded by two raters and content analyses were conducted using NVivo 9 software. The findings are described across the following three main themes: (1) stigma; (2) body image concerns; and (3) the disclosure dilemma. The themes and issues identified by this study may help guide sexual health-related interventions for older HIV-infected women. C1 [Psaros, Christina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Behav Med Serv,Dept Psychiat, Boston, MA 02114 USA. [Robbins, Gregory K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Infect Dis, Boston, MA 02114 USA. RP Psaros, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Behav Med Serv,Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM cpsaros@partners.org FU Harvard University Center for AIDS Research (CFAR); NIH [P30 AI060354]; NIAID; NCI; NICHD; NHLBI; NIDA; NIMH; NIA; NCCAM; FIC; OAR FX Dr. Psaros' time was supported by the Harvard University Center for AIDS Research (CFAR), an NIH funded program (P30 AI060354) which is supported by the following NIH Co-Funding and Participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, NCCAM, FIC, and OAR. Additional author time was supported by K01 AI062435 (Robbins), and K24 MH094214 (Safren). NR 38 TC 7 Z9 7 U1 0 U2 17 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD DEC PY 2012 VL 26 IS 12 BP 755 EP 760 DI 10.1089/apc.2012.0256 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 048CB UT WOS:000311886700007 PM 23199193 ER PT J AU O'Neil, CK Hanlon, JT Marcum, ZA AF O'Neil, Christine K. Hanlon, Joseph T. Marcum, Zachary A. TI Adverse Effects of Analgesics Commonly Used by Older Adults With Osteoarthritis: Focus on Non-Opioid and Opioid Analgesics SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY LA English DT Review DE adverse drug events; aged; analgesics; osteoarthritis ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; EMERGENCY-DEPARTMENT VISITS; ELDERLY-PATIENTS; KNEE OSTEOARTHRITIS; UNITED-STATES; CYCLO-OXYGENASE-2 INHIBITORS; PHARMACOLOGICAL MANAGEMENT; ACETAMINOPHEN ABSORPTION; MYOCARDIAL-INFARCTION; OARSI RECOMMENDATIONS AB Background: Osteoarthritis (OA) is the most common cause of disability in older adults, and although analgesic use can be helpful, it can also result in adverse drug events. Objective: To review the recent literature to describe potential adverse drug events associated with analgesics commonly used by older adults with OA. Methods: To identify articles for this review, a systematic search of the English-language literature from January 2001 to June 2012 was conducted using PubMed, MEDLINE, EBSCO, and the Cochrane Database of Systematic Reviews for publications related to the medical management of OA. Search terms used were "analgesics," "acetaminophen," "nonsteroidal anti-inflammatory drugs" (NSAIDs), "opioids," "pharmacokinetics," "pharmacodynamics," and "adverse drug events." The search was restricted to those articles that concerned humans aged >= 65 years. A manual search of the reference lists from identified articles and the authors' article files, book chapters, and recent reviews was conducted to identify additional articles. From these, the authors identified those studies that examined analgesic use in older adults. Results: There are limited data to suggest that non-frail elders are more likely than their younger counterparts to develop acetaminophen-induced hepatotoxicity. However, decreased hepatic phase II metabolism in frail elders may result in increased risk of hepatotoxicity. It is now well established that older adults are at higher risk of NSAID-induced gastrointestinal toxicity and renal insufficiency. Insofar as opioids, the data that suggest an increased risk of falls, fractures, or delirium need to be tempered by the potential risk of inadequately treating severe chronic OA-related pain. Conclusions: Acetaminophen is the mainstay frontline analgesic for treating OA-related pain in older adults. NSAIDs should be limited to short-term use only, and for moderate to severe OA-related pain, opioids may be preferable in individuals without substance abuse or dependence issues. (Am J Geriatr Pharmacother. 2012;10: 331-342)(C) 2012 Elsevier HS Journals, Inc. All rights reserved. C1 [O'Neil, Christine K.] Duquesne Univ, Dept Pharm Practice, Sch Pharm, Pittsburgh, PA 15219 USA. [Hanlon, Joseph T.; Marcum, Zachary A.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Marcum, Zachary A.] Univ Pittsburgh, Geriatr Pharmaceut Outcomes & Geroinformat Res &, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hanlon, Joseph T.; Marcum, Zachary A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Marcum, ZA (reprint author), Univ Pittsburgh, Sch Med Geriatr, 3471 5th Ave,Ste 500, Pittsburgh, PA 15213 USA. EM zam12@pitt.edu FU National Institute on Aging [R56AG 027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056, R01AG028050]; National Institute of Nursing Research grant [R01 NR010135]; Agency for Healthcare Research and Quality grants [R01 HS017695, K12 HS019461, R01HS018721]; VA Health Services Research grant [IIR-06-062] FX Supported in part by National Institute on Aging grants and contracts (R56AG 027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056, and R01AG028050), a National Institute of Nursing Research grant (R01 NR010135), Agency for Healthcare Research and Quality grants (R01 HS017695, K12 HS019461, and R01HS018721), and a VA Health Services Research grant (IIR-06-062). Dr. O'Neil helped with the literature search, study design, data collection, data interpretation, and writing of the manuscript. Dr. Marcum helped with the literature search, table creation, study design, data collection, data interpretation, and writing of the manuscript. Dr. Hanlon helped with the study design, data collection, data interpretation, and writing of the manuscript. NR 67 TC 49 Z9 53 U1 3 U2 27 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 1543-5946 J9 AM J GERIATR PHARMAC JI Am. J. Geriatr. Pharmacother. PD DEC PY 2012 VL 10 IS 6 BP 331 EP 342 DI 10.1016/j.amjopharm.2012.09.004 PG 12 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 064NT UT WOS:000313083000001 PM 23036838 ER PT J AU Egan, CA Marakovitz, SE O'Rourke, JA Osiecki, L Illmann, C Barton, L McLaughlin, E Proujansky, R Royal, J Cowley, H Rangel-Lugo, M Pauls, DL Scharf, JM Mathews, CA AF Egan, Crystelle A. Marakovitz, Susan E. O'Rourke, Julia A. Osiecki, Lisa Illmann, Cornelia Barton, Lauren McLaughlin, Elizabeth Proujansky, Rachel Royal, Justin Cowley, Heather Rangel-Lugo, Martha Pauls, David L. Scharf, Jeremiah M. Mathews, Carol A. CA Tourette Syndrome Assoc Int TI Effectiveness of a Web-Based Protocol for the Screening and Phenotyping of Individuals With Tourette Syndrome for Genetic Studies SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE rapid phenotyping; genome wide association study (GWAS); Internet; recruitment; neuropsychiatric disorder ID GENOME-WIDE ASSOCIATION; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE SYMPTOMS; MAJOR DEPRESSIVE DISORDER; PSYCHOMETRIC PROPERTIES; SELF-REPORT; INTERNET; POPULATION; RELIABILITY; FEASIBILITY AB Genome-wide association studies (GWAS) and other emerging technologies offer great promise for the identification of genetic risk factors for complex psychiatric disorders, yet such studies are constrained by the need for large sample sizes. Web-based collection offers a relatively untapped resource for increasing participant recruitment. Therefore, we developed and implemented a novel web-based screening and phenotyping protocol for genetic studies of Tourette syndrome (TS), a childhood-onset neuropsychiatric disorder characterized by motor and vocal tics. Participants were recruited over a 13-month period through the membership of the Tourette Syndrome Association (TSA; n = 28,878). Of the TSA members contacted, 4.3% (1,242) initiated the questionnaire, and 79.5% (987) of these were enrollment eligible. 63.9% (631) of enrolled participants completed the study by submitting phenotypic data and blood specimens. Age was the only variable that predicted study completion; children and young adults were significantly less likely to be study completers than adults 26 and older. Compared to a clinic-based study conducted over the same time period, the web-based method yielded a 60% larger sample. Web-based participants were older and more often female; otherwise, the sample characteristics did not differ significantly. TS diagnoses based on the web-screen demonstrated 100% accuracy compared to those derived from in-depth clinical interviews. Our results suggest that a web-based approach is effective for increasing the sample size for genetic studies of a relatively rare disorder and that our web-based screen is valid for diagnosing TS. Findings from this study should aid in the development of web-based protocols for other disorders. (C) 2012 Wiley Periodicals, Inc. C1 [Egan, Crystelle A.; Rangel-Lugo, Martha; Mathews, Carol A.] Univ Calif San Francisco, Dept Psychiat, Langley Porter Psychiat Inst, San Francisco, CA 94143 USA. [Marakovitz, Susan E.] Integrated Ctr Child Dev, Newton, MA USA. [O'Rourke, Julia A.] Massachusetts Gen Hosp, Dept Pediat, Lurie Ctr Autism, Boston, MA 02114 USA. [O'Rourke, Julia A.] Massachusetts Gen Hosp, Dept Med, Comp Sci Lab, Boston, MA 02114 USA. [Osiecki, Lisa; Illmann, Cornelia; Barton, Lauren; McLaughlin, Elizabeth; Proujansky, Rachel; Royal, Justin; Pauls, David L.; Scharf, Jeremiah M.] Massachusetts Gen Hosp, Psychiat Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Illmann, Cornelia; Barton, Lauren; McLaughlin, Elizabeth; Proujansky, Rachel; Royal, Justin; Pauls, David L.; Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Cowley, Heather] Tourette Syndrome Assoc, Bayside, NY USA. [Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Scharf, Jeremiah M.] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA. RP Egan, CA (reprint author), Univ Calif San Francisco, Dept Psychiat, Langley Porter Psychiat Inst, 401 Parnassus Ave,Box F-0984, San Francisco, CA 94143 USA. EM caegan@my.uri.edu FU National Institute for Neurological Disorders and Stroke (NINDS) [U01 NS40024-S1, U01 NS40024, MH085057]; Tourette Syndrome Association (TSA) FX Grant sponsor: National Institute for Neurological Disorders and Stroke (NINDS); Grant numbers: U01 NS40024-S1, U01 NS40024, MH085057; Grant sponsor: Tourette Syndrome Association (TSA). NR 51 TC 3 Z9 3 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD DEC PY 2012 VL 159B IS 8 BP 987 EP 996 DI 10.1002/ajmg.b.32107 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 059SI UT WOS:000312725200011 PM 23090870 ER PT J AU Brown, A Hirsch, R Laor, T Hannon, MJ Levesque, MC Starz, T Francis, K Kwoh, CK AF Brown, Amanda Hirsch, Raphael Laor, Tal Hannon, Michael J. Levesque, Marc C. Starz, Terence Francis, Kimberly Kwoh, C. Kent TI Do patients with juvenile idiopathic arthritis in clinical remission have evidence of persistent inflammation on 3T magnetic resonance imaging? SO ARTHRITIS CARE & RESEARCH LA English DT Article ID EARLY RHEUMATOID-ARTHRITIS; AMERICAN-COLLEGE; SELECT CATEGORIES; FOLLOW-UP; RHEUMATOLOGY/EUROPEAN LEAGUE; DISEASE; CHILDREN; CRITERIA; THERAPY; CLASSIFICATION AB Objective Up to 90% of adults with rheumatoid arthritis (RA) in clinical remission have persistent synovitis and/or bone marrow lesions (BMLs) on magnetic resonance imaging (MRI). MRI findings in patients with juvenile idiopathic arthritis (JIA) in clinical remission have not been described. We utilized 3T MRI with contrast enhancement to examine JIA patients with hand and/or wrist involvement who were in clinical remission and compared them with a cohort of adult RA patients. Methods In total, 11 JIA patients and 10 RA patients with arthritis involving the hands and/or wrists were identified by their primary rheumatologist as being in physician-defined clinical remission, having no signs or symptoms of active arthritis and no medication changes for at least 6 months. A study rheumatologist performed a joint evaluation for tenderness, swelling, and limitation of motion, and study participants self-reported tender joint counts. The participants underwent MRI with intravenous contrast enhancement of 1 hand and wrist with a history of prior symptoms. A pediatric musculoskeletal radiologist blinded to the clinical data scored the MRIs for synovitis, tenosynovitis, and/or BMLs. Results Sixty-three percent of the JIA cohort and 70% of the RA cohort had MRI findings of synovitis, BMLs, and/or tenosynovitis. All pediatric patients with MRI abnormalities had normal physician tender and swollen joint counts. The patients' self-report of painful joint counts did not predict MRI abnormalities. Conclusion Over one-half of the patients in clinical remission had MRI evidence of persistent inflammation, defined as the presence of synovitis, tenosynovitis, or BMLs. A substantial portion of patients with JIA may have subclinical disease despite clinical remission. C1 [Brown, Amanda] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Hirsch, Raphael; Francis, Kimberly] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Hirsch, Raphael; Hannon, Michael J.; Levesque, Marc C.; Starz, Terence; Francis, Kimberly; Kwoh, C. Kent] Univ Pittsburgh, Pittsburgh, PA USA. [Laor, Tal] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Laor, Tal] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare, Pittsburgh, PA USA. RP Kwoh, CK (reprint author), S702 BSTWR,200 Lothrop St, Pittsburgh, PA 15206 USA. EM kwoh@pitt.edu FU Children's Hospital of Pittsburgh; NIH [R21-AR-056690, T32-AR-052282, P60-AR-054731] FX Supported in part by the Children's Hospital of Pittsburgh. Dr. Hirsch's work was supported by the NIH (grants R21-AR-056690 and T32-AR-052282). Dr. Kwoh's work was supported by the NIH (grant P60-AR-054731). NR 45 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD DEC PY 2012 VL 64 IS 12 BP 1846 EP 1854 DI 10.1002/acr.21774 PG 9 WC Rheumatology SC Rheumatology GA 045NZ UT WOS:000311704800008 PM 22740386 ER PT J AU Richards, JS Cannon, GW Hayden, CL Amdur, RL Lazaro, D Mikuls, TR Reimold, AM Caplan, L Johnson, DS Schwab, P Cherascu, BN Kerr, GS AF Richards, J. Steuart Cannon, Grant W. Hayden, Candace L. Amdur, Richard L. Lazaro, Deana Mikuls, Ted R. Reimold, Andreas M. Caplan, Liron Johnson, Dannette S. Schwab, Pascale Cherascu, Bogdan N. Kerr, Gail S. TI Adherence with bisphosphonate therapy in US veterans with rheumatoid arthritis SO ARTHRITIS CARE & RESEARCH LA English DT Article ID HEALTH-ASSESSMENT QUESTIONNAIRE; HIP FRACTURE; DISEASE-ACTIVITY; MEDICATION ADHERENCE; OSTEOPOROTIC WOMEN; RISK; PERSISTENCE; ALENDRONATE; DATABASES; RATES AB Objective Pharmacy Benefits Management program data for patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were linked with clinical data to determine bisphosphonate adherence and persistence among US veterans with rheumatoid arthritis (RA) and to determine factors associated with adherence. Methods The primary outcome measures were the duration of bisphosphonate therapy and the medication possession ratio (MPR). Patients with an MPR <0.80 were classified as nonadherent. Potential covariates considered in the analysis included patient demographics, RA disease activity and severity parameters, and factors associated with osteoporosis risk. Associations of patient factors with duration of therapy and adherence were examined using multivariable regression modeling. Results Bisphosphonates were prescribed to 573 (41.5%) of 1,382 VARA subjects. The mean +/- SD duration of therapy for bisphosphonates was 39.2 +/- 31.4 months. A longer duration of therapy correlated with older age, more years of education, and dual x-ray absorptiometry testing. The mean +/- SD MPR of VARA subjects for bisphosphonate therapy was 0.69 +/- 0.28; 302 (52.7%) were nonadherent. In multivariate analyses, nonadherence with bisphosphonate therapy was associated with a longer duration of RA disease (odds ratio [OR] 1.02, 95% confidence interval [95% CI] 1.001.04) and duration of bisphosphonate therapy >32 months (OR 1.63, 95% CI 1.042.57). Whites were less likely to have a low MPR compared with nonwhites (OR 0.52, 95% CI 0.300.88). Conclusion Nonadherence with bisphosphonates was common in this cohort of RA patients and was associated with nonwhite ethnicity, a longer duration of RA disease, and a greater duration of bisphosphonate therapy. C1 [Richards, J. Steuart; Amdur, Richard L.] VA Med Ctr, Washington, DC USA. [Richards, J. Steuart; Amdur, Richard L.] Georgetown Univ, Washington, DC USA. [Cannon, Grant W.; Hayden, Candace L.] George E Whalen VA Med Ctr, Salt Lake City, UT USA. [Cannon, Grant W.; Hayden, Candace L.] Univ Utah, Salt Lake City, UT USA. [Lazaro, Deana] Brooklyn VA, New York, NY USA. [Mikuls, Ted R.] Omaha VA Med Ctr, Omaha, NE USA. [Mikuls, Ted R.] Univ Nebraska Med Ctr, Omaha, NE USA. [Reimold, Andreas M.] VA Med Ctr, Dallas, TX USA. [Reimold, Andreas M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Caplan, Liron] Denver VA Med Ctr, Denver, CO USA. [Caplan, Liron] Univ Colorado, Aurora, CO USA. [Johnson, Dannette S.] DO GV Sonny Montgomery VA Med Ctr, Jackson, MS USA. [Johnson, Dannette S.] Univ Mississippi, Jackson, MS USA. [Schwab, Pascale] Portland VA, Portland, OR USA. [Cherascu, Bogdan N.] Iowa City VA, Iowa City, IA USA. [Kerr, Gail S.] Howard Univ, Washington, DC 20059 USA. [Kerr, Gail S.] Georgetown Univ, VA Med Ctr, Washington, DC USA. RP Richards, JS (reprint author), DC VA Med Ctr, 50 Irving St NW, Washington, DC 20422 USA. EM john.richards1@va.gov FU VA Health Services Research and Development grant [SHP 08-172] FX Supported by a VA Health Services Research and Development grant (SHP 08-172). NR 31 TC 7 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD DEC PY 2012 VL 64 IS 12 BP 1864 EP 1870 DI 10.1002/acr.21777 PG 7 WC Rheumatology SC Rheumatology GA 045NZ UT WOS:000311704800010 PM 22740421 ER PT J AU Wright, EA Katz, JN Baron, JA Wright, RJ Malchau, H Mahomed, N Prokopetz, JJZ Losina, E AF Wright, Elizabeth A. Katz, Jeffrey N. Baron, John A. Wright, R. John Malchau, Henrik Mahomed, Nizar Prokopetz, Julian J. Z. Losina, Elena TI Risk factors for revision of primary total hip replacement: Results from a national case-control study SO ARTHRITIS CARE & RESEARCH LA English DT Article ID ARTHROPLASTY REGISTER; JOINT REPLACEMENT; IMPLANT FAILURE; SURVIVAL; INFECTION; OUTCOMES; INDEX AB Objective To study the risk factors for revision of primary total hip replacement (THR) in a US population-based sample. Methods Using Medicare claims, we identified beneficiaries from 29 US states who underwent primary THR between July 1, 1995 and June 30, 1996, with followup through December 31, 2008. Potential cases had International Classification of Diseases, Ninth Revision, Clinical Modification codes indicating a revision THR. Each case was matched by state with 1 control THR recipient who was alive and unrevised when the case had a revision THR. We abstracted hospital records to document potential risk factors. We examined the associations between preoperative factors and revision risk using multivariate conditional logistic regression. Results The analysis data set contained 719 of 836 casecontrol pairs with complete data for analysis variables. The factors associated with higher revision odds in multivariate models were age =75 years at primary surgery (odds ratio [OR] 1.52 [95% confidence interval (95% CI) 1.201.92]), height in the highest tertile (OR 1.40 [95% CI 1.061.85]), weight in the highest tertile (OR 1.66 [95% CI 1.242.22]), cemented femoral component (OR 1.44 [95% CI 1.101.87]), prior contralateral primary THR (OR 1.36 [95% CI 1.051.76]), other prior orthopedic surgery (OR 1.45 [95% CI 1.131.84]), and living with others (versus alone; OR 1.26 [95% CI 0.991.61]). Conclusion This first US population-based casecontrol study of risk factors for revision of primary THR showed that younger, taller, and heavier patients and those receiving a cemented femoral component had a greater likelihood of undergoing a revision THR over a 12-year followup period. Effects of age and body size on revision risk should be addressed by clinicians with patients considering primary THR. C1 [Wright, Elizabeth A.] Brigham & Womens Hosp, Orthoped & Arthrit Ctr Outcomes Res, Boston, MA 02115 USA. [Katz, Jeffrey N.; Losina, Elena] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Baron, John A.] Univ N Carolina, Chapel Hill, NC USA. [Malchau, Henrik] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wright, Elizabeth A.; Wright, R. John; Malchau, Henrik] Harvard Univ, Sch Med, Boston, MA USA. [Mahomed, Nizar] Toronto Western Hosp, Univ Hlth Network, Toronto, ON M5T 2S8, Canada. [Losina, Elena] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Wright, EA (reprint author), Brigham & Womens Hosp, Orthoped & Arthrit Ctr Outcomes Res, 75 Francis St,OBC-4, Boston, MA 02115 USA. EM wright@hsph.harvard.edu OI Malchau, Henrik/0000-0002-4291-2441 FU NIH [P60-AR-47782, K24-AR-057827] FX Supported by the NIH (grants P60-AR-47782 and K24-AR-057827). NR 29 TC 6 Z9 7 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD DEC PY 2012 VL 64 IS 12 BP 1879 EP 1885 DI 10.1002/acr.21760 PG 7 WC Rheumatology SC Rheumatology GA 045NZ UT WOS:000311704800012 PM 23193090 ER PT J AU Guo, J Song, LG Liu, ML Mahon, MJ AF Guo, Jun Song, Lige Liu, Minlin Mahon, Matthew J. TI Fluorescent ligand-directed co-localization of the parathyroid hormone 1 receptor with the brush-border scaffold complex of the proximal tubule reveals hormone-dependent changes in ezrin immunoreactivity consistent with inactivation SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Parathyroid hormone; Parathyroid hormone receptor; Ezrin; NHERF1; NHERF2; Megalin ID OPOSSUM KIDNEY-CELLS; REGULATORY FACTOR-I; EZRIN/RADIXIN/MOESIN ERM PROTEINS; KINASE ANCHORING PROTEIN; COTRANSPORTER NAPI-IIA; PHOSPHATE-TRANSPORT; MEMBRANE MICRODOMAINS; LLC-PK1 CELLS; RAT-KIDNEY; CYCLIC-AMP AB Through binding to parathyroid hormone (PTH), PTH1R interacts with kidney-specific scaffold proteins, including the sodium hydrogen exchanger regulatory factors 1 and 2 (NHERFs), and ezrin. To facilitate in vivo localization, tetramethylrhodamine-labeled PTH (PTH-TMR) was used as a fluorescent probe. In mice, PTH-TMR localizes to luminal surfaces of tubular Si segments that overlap PTH1R immunostaining, but does not directly overlap with megalin-specific antibodies. FTH-TMR staining directly overlaps with Npt2a in nascent, endocytic vesicles, marking the location of transporter regulation. PICA substrate antibodies display marked staining increases in segments labeled with PTH-TMR, demonstrating a functional effect. In the presence of secondary hyperparathyroidism, PTH-TMR staining is markedly reduced and shifts to co-localizing with megalin. At 15 min post-injection, PTH-TMR-labeled vesicles do not co-localize with either NHERF or ezrin, suggesting PTH1R dissociation from the scaffold complex. At the 5 min time point, FTH-TMR stains the base of microvilli where it localizes with both NHERF2 and ezrin, and only partially with NHERF1. Strikingly, the bulk of ezrin protein becomes undetectable with the polyclonal, CS3145 antibody, revealing a PTH-induced conformational change in the scaffold. A second ezrin antibody (3C12) is capable of detecting the altered ezrin protein. The CS3145 antibody only binds to the active form of ezrin and fails to recognize the inactive form, while the 3C12 reagent can detect either active or inactive ezrin. Here we show that the PTH1R is part of the ezrin scaffold complex and that acute actions of PTH suggest a rapid inactivation of ezrin in a spatially defined manner. (C) 2012 Elsevier B.V. All rights reserved. C1 [Mahon, Matthew J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Mahon, MJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St Their 10, Boston, MA 02114 USA. EM mahon@helix.mgh.harvard.edu FU NIH [P01 DK073911] FX This study was funded by a program project grant from the NIH (P01 DK073911) to Dr. John Potts. Thanks to Drs. Tom Gardella, Dennis Brown, Daniel C. Biemesderfer, Chris Yun and Jurg Biber for providing invaluable reagents. NR 50 TC 6 Z9 6 U1 0 U2 36 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD DEC PY 2012 VL 1823 IS 12 BP 2243 EP 2253 DI 10.1016/j.bbamcr.2012.09.010 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 058JF UT WOS:000312629200016 PM 23036889 ER PT J AU Crane, PK Carle, A Gibbons, LE Insel, P Mackin, RS Gross, A Jones, RN Mukherjee, S Curtis, SM Harvey, D Weiner, M Mungas, D AF Crane, Paul K. Carle, Adam Gibbons, Laura E. Insel, Philip Mackin, R. Scott Gross, Alden Jones, Richard N. Mukherjee, Shubhabrata Curtis, S. McKay Harvey, Danielle Weiner, Michael Mungas, Dan CA Alzheimer's Dis Neuroimaging TI Development and assessment of a composite score for memory in the Alzheimer's Disease Neuroimaging Initiative (ADNI) SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Memory; psychometrics; longitudinal analysis; cognition; hippocampus ID ITEM RESPONSE THEORY; MILD COGNITIVE IMPAIRMENT; DIAGNOSIS; DEMENTIA; NETWORK; DECLINE; MODEL AB We sought to develop and evaluate a composite memory score from the neuropsychological battery used in the Alzheimer's Disease (AD) Neuroimaging Initiative (ADNI). We used modern psychometric approaches to analyze longitudinal Rey Auditory Verbal Learning Test (RAVLT, 2 versions), AD Assessment Schedule - Cognition (ADAS-Cog, 3 versions), Mini-Mental State Examination (MMSE), and Logical Memory data to develop ADNI-Mem, a composite memory score. We compared RAVLT and ADAS-Cog versions, and compared ADNI-Mem to RAVLT recall sum scores, four ADAS-Cog-derived scores, the MMSE, and the Clinical Dementia Rating Sum of Boxes. We evaluated rates of decline in normal cognition, mild cognitive impairment (MCI), and AD, ability to predict conversion from MCI to AD, strength of association with selected imaging parameters, and ability to differentiate rates of decline between participants with and without AD cerebrospinal fluid (CSF) signatures. The second version of the RAVLT was harder than the first. The ADAS-Cog versions were of similar difficulty. ADNI-Mem was slightly better at detecting change than total RAVLT recall scores. It was as good as or better than all of the other scores at predicting conversion from MCI to AD. It was associated with all our selected imaging parameters for people with MCI and AD. Participants with MCI with an AD CSF signature had somewhat more rapid decline than did those without. This paper illustrates appropriate methods for addressing the different versions of word lists, and demonstrates the additional power to be gleaned with a psychometrically sound composite memory score. C1 [Crane, Paul K.; Gibbons, Laura E.; Mukherjee, Shubhabrata; Curtis, S. McKay] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Carle, Adam] Univ Cincinnati, Sch Med, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Carle, Adam] Univ Cincinnati, Coll Arts & Sci, Cincinnati, OH 45229 USA. [Insel, Philip; Mackin, R. Scott; Weiner, Michael] San Francisco VA Med Ctr, CIND, San Francisco, CA 94121 USA. [Gross, Alden; Jones, Richard N.] Hebrew Senior Life, Inst Aging Res, Dept Psychiat, Boston, MA 02131 USA. [Harvey, Danielle] Univ Calif Davis, Dept Publ Hlth Sci, Div Biostat, Davis, CA 95616 USA. [Mungas, Dan] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. RP Crane, PK (reprint author), Univ Washington, Harborview Med Ctr, Box 359780,325 9th Ave, Seattle, WA 98104 USA. EM pcrane@u.washington.edu; gibbonsl@u.washington.edu RI Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Saykin, Andrew/A-1318-2007; Crane, Paul/C-8623-2014; Jones, Richard/J-3488-2013; OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438; Saykin, Andrew/0000-0002-1376-8532; Jones, Richard/0000-0002-1049-218X; Crane, Paul/0000-0003-4278-7465; Mukherjee, Shubhabrata/0000-0003-2522-2884 FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering; NIH [P30 AG010129, K01 AG030514, R01 AG029672, P50 AG05136, R13 AG030995]; Dana Foundation. Data management FX Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory of Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. Data management and the specific analyses reported here wer\e supported by NIH grant R01 AG029672 (Paul Crane, PI), P50 AG05136 (Murray Raskind, PI), and R13 AG030995 (Dan Mungas, PI). NR 25 TC 63 Z9 64 U1 1 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2012 VL 6 IS 4 BP 502 EP 516 DI 10.1007/s11682-012-9186-z PG 15 WC Neuroimaging SC Neurosciences & Neurology GA 061VL UT WOS:000312878200003 PM 22782295 ER PT J AU Gibbons, LE Carle, AC Mackin, RS Harvey, D Mukherjee, S Insel, P Curtis, SM Mungas, D Crane, PK AF Gibbons, Laura E. Carle, Adam C. Mackin, R. Scott Harvey, Danielle Mukherjee, Shubhabrata Insel, Philip Curtis, S. McKay Mungas, Dan Crane, Paul K. CA Alzheimer's Dis Neuroimaging TI A composite score for executive functioning, validated in Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with baseline mild cognitive impairment SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Executive function; Mild cognitive impairment; Item response theory; Composite scores ID EPISODIC MEMORY; BIOMARKER SIGNATURE; CONVERSION; DEMENTIA; MCI; HETEROGENEITY; DECLINE AB The Alzheimer's Disease Neuroimaging Initiative (ADNI) measures abilities broadly related to executive function (EF), including WAIS-R Digit Symbol Substitution, Digit Span Backwards, Trails A and B, Category Fluency, and Clock Drawing. This study investigates whether a composite executive function measure based on these multiple indicators has better psychometric characteristics than the widely used individual components. We applied item response theory methods to 800 ADNI participants to derive an EF composite score (ADNI-EF) from the above measures. We then compared ADNI-EF with component measures in 390 longitudinally-followed participants with mild cognitive impairment (MCI) with respect to: (1) Ability to detect change over time; (2) Ability to predict conversion to dementia; (3) Strength of cross-sectional association with MRI-derived measures of structures involved in frontal systems, and (4) Strength of baseline association with cerebrospinal fluid (CSF) levels of amyloid beta(1-42), total tau, and phosphorylated tau(181P). ADNI-EF showed the greatest change over time, followed closely by Category Fluency. ADNI-EF needed a 40 % smaller sample size to detect change. ADNI-EF was the strongest predictor of AD conversion. ADNI-EF was the only measure significantly associated with all the MRI regions, though other measures were more strongly associated in a few of the regions. ADNI-EF was associated with all the CSF measures. ADNI-EF appears to be a useful composite measure of EF in MCI, as good as or better than any of its composite parts. This study demonstrates an approach to developing a psychometrically sophisticated composite score from commonly-used tests. C1 [Gibbons, Laura E.; Mukherjee, Shubhabrata; Curtis, S. McKay; Crane, Paul K.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Carle, Adam C.] Univ Cincinnati, Sch Med, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Carle, Adam C.] Univ Cincinnati, Coll Arts & Sci, Cincinnati, OH 45229 USA. [Mackin, R. Scott; Insel, Philip] San Francisco VA Med Ctr, CIND, San Francisco, CA 94121 USA. [Harvey, Danielle] Univ Calif Davis, Dept Publ Hlth Sci, Div Biostat, Davis, CA 95616 USA. [Mungas, Dan] UC Davis Med Ctr, Dept Neurol3, Sacramento, CA 95817 USA. RP Gibbons, LE (reprint author), Univ Washington, Harborview Med Ctr, Box 359780,325 9th Ave, Seattle, WA 98104 USA. EM gibbonsl@washington.edu RI Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Saykin, Andrew/A-1318-2007; Crane, Paul/C-8623-2014; OI Mukherjee, Shubhabrata/0000-0003-2522-2884; Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438; Saykin, Andrew/0000-0002-1376-8532; Crane, Paul/0000-0003-4278-7465 FU National Institute on Aging [R01 AG 029672, P50 AG05136, R13 AG030995]; National Institute of Mental Health [K08MH081065]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; NIH [P30 AG010129, K01 AG030514]; Dana Foundation FX Supported by grants R01 AG 029672 (P Crane), P50 AG05136 (Raskind), and R13 AG030995 (Mungas) from the National Institute on Aging, and K08MH081065 (Mackin) from the National Institute of Mental Health.; Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory of Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. NR 45 TC 56 Z9 56 U1 4 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2012 VL 6 IS 4 BP 517 EP 527 DI 10.1007/s11682-012-9176-1 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA 061VL UT WOS:000312878200004 PM 22644789 ER PT J AU Park, LQ Gross, AL McLaren, DG Pa, J Johnson, JK Mitchell, M Manly, JJ AF Park, Lovingly Quitania Gross, Alden L. McLaren, Donald G. Pa, Judy Johnson, Julene K. Mitchell, Meghan Manly, Jennifer J. CA Alzheimer's Dis Neuroimaging TI Confirmatory factor analysis of the ADNI neuropsychological battery SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE ADNI; Neuropsychology; Cognition; Cognitive change; Confirmatory factor analysis ID MILD COGNITIVE IMPAIRMENT; ITEM RESPONSE THEORY; ALZHEIMERS-DISEASE; MEASUREMENT INVARIANCE; MEMORY DECLINE; DEMENTIA; VALIDITY; MODEL; RELIABILITY; BIOMARKERS AB The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a large multi-center study designed to develop optimized methods for acquiring longitudinal neuroimaging, cognitive, and biomarker measures of AD progression in a large cohort of patients with Alzheimer's disease (AD), patients with Mild Cognitive Impairment, and healthy controls. Detailed neuropsychological testing was conducted on all participants. We examined the factor structure of the ADNI Neuropsychological Battery across older adults with differing levels of clinical AD severity based on the Clinical Dementia Rating Scale (CDR). Confirmatory factor analysis (CFA) of 23 variables from 10 neuropsychological tests resulted in five factors (memory, language, visuospatial functioning, attention, and executive function/processing speed) that were invariant across levels of cognitive impairment. Thus, these five factors can be used as indicators of cognitive function in older adults who are participants in ADNI. C1 [Park, Lovingly Quitania] Univ Calif Davis, UCDMC Dept Neurol, Alzheimers Dis Ctr, Sacramento, CA 95817 USA. [Gross, Alden L.] Harvard Univ, Sch Med, Inst Aging Res, Boston, MA USA. [Gross, Alden L.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [Pa, Judy; Johnson, Julene K.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [McLaren, Donald G.; Mitchell, Meghan] ENRM Vet Hosp, Geriatr Res Educ & Clin Ctr, Bedford, MA USA. [McLaren, Donald G.; Mitchell, Meghan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [McLaren, Donald G.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Johnson, Julene K.] Univ Calif San Francisco, Dept Social & Behav Sci, Inst Hlth & Aging, San Francisco, CA USA. [Manly, Jennifer J.] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, Dept Neurol, New York, NY USA. RP Park, LQ (reprint author), Univ Calif Davis, UCDMC Dept Neurol, Alzheimers Dis Ctr, 4860 Y St,Suite 3900, Sacramento, CA 95817 USA. EM lovingly.quitania@ucdmc.ucdavis.edu RI Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Saykin, Andrew/A-1318-2007; OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438; Saykin, Andrew/0000-0002-1376-8532; McLaren, Donald/0000-0002-0566-4610 FU National Institute on Aging [R13AG030995, P01 AG031720, AG036694, AG027171, K01 AG034175, R01 AG031252, AG022538, AG028786, AG037212]; National Institutes of Health [T32 AG023480]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; NIH [P30 AG010129, K01 AG030514]; Dana Foundation FX We gratefully acknowledge a conference grant from the National Institute on Aging (R13AG030995, PI: Dan Mungas) that facilitated data analysis for this project.; Dr. Park was supported by a grant from the National Institute of Aging (R01 AG031252 PI: Sarah Farias). Dr. Gross was supported by a National Institutes of Health Translational Research in Aging fellowship (T32 AG023480, PI: Lewis Lipsitz) and a grant from the National Institute on Aging (P01 AG031720 PI: Sharon Inouye). Dr. McLaren was supported by National Institute on Aging grants AG036694 (PI: Reisa Sperling) and AG027171 (PI: Alireza Atri). Dr. Pa was supported by the National Institute on Aging (K01 AG034175, PI: Dr. Pa). Dr. Johnson was supported by a grant from the National Institute of Aging grant AG022538 (PI: Johnson). Dr. Manly was supported by National Institute on Aging grants AG028786 (PI: Manly) and AG037212 (PI: Mayeux).; Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. NR 57 TC 8 Z9 9 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2012 VL 6 IS 4 BP 528 EP 539 DI 10.1007/s11682-012-9190-3 PG 12 WC Neuroimaging SC Neurosciences & Neurology GA 061VL UT WOS:000312878200005 PM 22777078 ER PT J AU Johnson, JK Gross, AL Pa, J McLaren, DG Park, LQ Manly, JJ AF Johnson, Julene K. Gross, Alden L. Pa, Judy McLaren, Donald G. Park, Lovingly Quitania Manly, Jennifer J. TI Longitudinal change in neuropsychological performance using latent growth models: a study of mild cognitive impairment SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE ADNI; Neuropsychology; Cognition; Mild cognitive impairment; Cognitive change; Executive function ID ALZHEIMERS-DISEASE; OLDER PERSONS; INDIVIDUAL-DIFFERENCES; DEFICITS; DECLINE; HETEROGENEITY; CONVERSION; ATTENTION; DEMENTIA; MEMORY AB The goal of the current study was to examine cognitive change in both healthy controls (n = 229) and individuals with mild cognitive impairment (MCI) (n = 397) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We applied latent growth modeling to examine baseline and longitudinal change over 36 months in five cognitive factors derived from the ADNI neuropsychological test battery (memory, executive function/processing speed, language, attention and visuospatial). At baseline, MCI patients demonstrated lower performance on all of the five cognitive factors when compared to controls. Both controls and MCI patients declined on memory over 36 months; however, the MCI patients declined at a significantly faster rate than controls. The MCI patients also declined over 36 months on the remaining four cognitive factors. In contrast, the controls did not exhibit significant change over 36 months on the non-memory cognitive factors. Within the MCI group, executive function declined faster than memory, while the other factor scores changed slower than memory over time. These findings suggest different patterns of cognitive change in healthy older adults and MCI patients. The findings also suggest that, when compared with memory, executive function declines faster than other cognitive factors in patients with MCI. Thus, decline in non-memory domains may be an important feature for distinguishing healthy older adults and persons with MCI. C1 [Johnson, Julene K.] Univ Calif San Francisco, Inst Hlth & Aging, Dept Social & Behav Sci, San Francisco, CA 94118 USA. [Johnson, Julene K.; Pa, Judy] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94118 USA. [Gross, Alden L.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [Gross, Alden L.] Harvard Univ, Sch Med, Inst Aging Res, Boston, MA USA. [McLaren, Donald G.] ENRM Vet Hosp, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [McLaren, Donald G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [McLaren, Donald G.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Park, Lovingly Quitania] Univ Calif Davis, Dept Neurol, Alzheimers Dis Ctr, Davis, CA 95616 USA. [Manly, Jennifer J.] Columbia Univ, Med Ctr, Dept Neurol, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. RP Johnson, JK (reprint author), Univ Calif San Francisco, Inst Hlth & Aging, Dept Social & Behav Sci, 3333 Calif St,Suite 340, San Francisco, CA 94118 USA. EM julene.johnson@ucsf.edu RI Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Saykin, Andrew/A-1318-2007 OI McLaren, Donald/0000-0002-0566-4610; Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438; Saykin, Andrew/0000-0002-1376-8532 FU National Institute on Aging (NIA) [R13 AG030995, R01 AG022538, P01 AG031720, P01 AG036694, K23 AG027171, K01 AG034175, R01 AG031252, R01 AG028786, R01 AG037212]; National Institutes of Health [T32AG023480-07, P30 AG010129, K01 AG030514]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; Dana Foundation FX We gratefully acknowledge a conference grant from the National Institute on Aging (NIA) (R13 AG030995, PI: Mungas) that facilitated data analysis for this project.; Dr. Johnson was supported by NIA grant R01 AG022538 (PI: Johnson). Dr. Gross was supported by a National Institutes of Health Translational Research in Aging fellowship (T32AG023480-07) and NIA grant P01 AG031720 (PI: Inouye). Dr. McLaren was supported by NIA grants P01 AG036694 (PI: Sperling) and K23 AG027171 (PI: Atri). Dr. Pa was supported by NIA grant K01 AG034175 (PI: Pa). Dr. Park was supported by NIA grant R01 AG031252 (PI: Farias). Dr. Manly was supported by NIA grants R01 AG028786 (PI: Manly) and R01 AG037212 (PI: Mayeux).; Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. NR 56 TC 17 Z9 17 U1 1 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2012 VL 6 IS 4 BP 540 EP 550 DI 10.1007/s11682-012-9161-8 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA 061VL UT WOS:000312878200006 PM 22562439 ER PT J AU Gross, AL Manly, JJ Pa, J Johnson, JK Park, LQ Mitchell, MB Melrose, RJ Inouye, SK McLaren, DG AF Gross, Alden L. Manly, Jennifer J. Pa, Judy Johnson, Julene K. Park, Lovingly Quitania Mitchell, Meghan B. Melrose, Rebecca J. Inouye, Sharon K. McLaren, Donald G. CA Alzheimer's Dis Neuroimaging TI Cortical signatures of cognition and their relationship to Alzheimer's disease SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE MRI; Freesurfer; Cortical thickness; ADNI; Cognition; Brain mapping ID MAGNETIC-RESONANCE IMAGES; SURFACE-BASED ANALYSIS; MINI-MENTAL-STATE; MILD AD DEMENTIA; COORDINATE SYSTEM; EPISODIC MEMORY; BRAIN ATROPHY; IMPAIRMENT; MRI; PREDICTION AB Recent changes in diagnostic criteria for Alzheimer's disease (AD) state that biomarkers can enhance certainty in a diagnosis of AD. In the present study, we combined cognitive function and brain morphology, a potential imaging biomarker, to predict conversion from mild cognitive impairment to AD. We identified four biomarkers, or cortical signatures of cognition (CSC), from regressions of cortical thickness on neuropsychological factors representing memory, executive function/processing speed, language, and visuospatial function among participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Neuropsychological factor scores were created from a previously validated multidimensional factor structure of the neuropsychological battery in ADNI. Mean thickness of each CSC at the baseline study visit was used to evaluate risk of conversion to clinical AD among participants with mild cognitive impairment (MCI) and rate of decline on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score. Of 307 MCI participants, 119 converted to AD. For all domain-specific CSC, a one standard deviation thinner cortical thickness was associated with an approximately 50 % higher hazard of conversion and an increase of approximately 0.30 points annually on the CDR-SB. In combined models with a domain-specific CSC and neuropsychological factor score, both CSC and factor scores predicted conversion to AD and increasing clinical severity. The present study indicated that factor scores and CSCs for memory and language both significantly predicted risk of conversion to AD and accelerated deterioration in dementia severity. We conclude that predictive models are best when they utilize both neuropsychological measures and imaging biomarkers. C1 [Gross, Alden L.; Inouye, Sharon K.] Harvard Univ, Sch Med, Inst Aging Res, Hebrew SeniorLife, Boston, MA 02115 USA. [Gross, Alden L.; Inouye, Sharon K.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [Manly, Jennifer J.] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. [Pa, Judy; Johnson, Julene K.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Johnson, Julene K.] Univ Calif San Francisco, Dept Social & Behav Sci, Inst Hlth & Aging, San Francisco, CA USA. [Park, Lovingly Quitania] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. [Mitchell, Meghan B.; McLaren, Donald G.] Edith Nourse Rogers Mem Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, Bedford, MA 01730 USA. [Mitchell, Meghan B.; McLaren, Donald G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Melrose, Rebecca J.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Melrose, Rebecca J.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [McLaren, Donald G.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Gross, AL (reprint author), Harvard Univ, Sch Med, Inst Aging Res, Hebrew SeniorLife, 1200 Ctr St,Rm 634, Boston, MA 02115 USA. EM aldengross@hsl.harvard.edu; jjm71@columbia.edu; judy.pa@ucsf.edu; Julene.Johnson@ucsf.edu; lovingly.quitania@ucdmc.ucdavis.edu; Meghan.Mitchell@va.gov; rjmelrose@ucla.edu; sharoninouye@hsl.harvard.edu; mclaren@nmr.mgh.harvard.edu RI Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Saykin, Andrew/A-1318-2007; OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438; Saykin, Andrew/0000-0002-1376-8532; McLaren, Donald/0000-0002-0566-4610 FU National Institute on Aging [R13AG030995]; NIH [T32AG023480-07, P30 AG010129, K01 AG030514]; NIA [P01AG031720, RO1 AG036694, K23 AG027171, R01 AG022538, K01 AG034175, R01 AG031252]; VA Career Development Award & UCLA Semel Scholar Award; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; Dana Foundation FX We gratefully acknowledge a conference grant from the National Institute on Aging (R13AG030995, PI: Mungas) that facilitated data analysis for this project. Dr. Gross was supported by an NIH Translational Research in Aging fellowship (T32AG023480-07, PI: Lipsitz) and the NIA (P01AG031720, PI: Inouye). Dr. McLaren was supported by NIA grant RO1 AG036694 (PI: Sperling) and K23 AG027171 (PI: Atri). Dr. Bruce Rosen (MGH-Harvard-MIT Martinos Center for Biomedical Imaging) provided guidance, space, and resources for this research. Dr. Johnson was supported by the NIA (R01 AG022538, PI: Johnson). Dr. Melrose was supported by a VA Career Development Award & UCLA Semel Scholar Award. Dr. Pa was supported by the NIA Career Development Award (K01 AG034175, PI: Pa). Dr. Park was supported by a grant from the National Institute of Aging (R01 AG031252 PI: Farias). Dr. Inouye holds the Milton and Shirley F. Levy Family Chair in Alzheimer's Disease.; Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. NR 75 TC 6 Z9 6 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2012 VL 6 IS 4 BP 584 EP 598 DI 10.1007/s11682-012-9180-5 PG 15 WC Neuroimaging SC Neurosciences & Neurology GA 061VL UT WOS:000312878200009 PM 22718430 ER PT J AU Stricker, NH Dodge, HH Dowling, NM Han, SD Erosheva, EA Jagust, WJ AF Stricker, Nikki H. Dodge, Hiroko H. Dowling, N. Maritza Han, S. Duke Erosheva, Elena A. Jagust, William J. CA Alzheimer's Dis Neuroimaging TI CSF biomarker associations with change in hippocampal volume and precuneus thickness: implications for the Alzheimer's pathological cascade SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Biomarkers; Beta amyloid; Phosphorylated tau; MRI; Alzheimer's disease; Hippocampus; Precuneus ID MILD COGNITIVE IMPAIRMENT; NEUROIMAGING INITIATIVE SUBJECTS; PHOSPHORYLATED TAU-PROTEIN; CEREBROSPINAL-FLUID TAU; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; BETA-AMYLOID BURDEN; DEFAULT NETWORK; MRI BIOMARKERS; DISEASE AB Neurofibrillary tangles (NFT) and amyloid plaques are hallmark neuropathological features of Alzheimer's disease (AD). There is some debate as to which neuropathological feature comes first in the disease process, with early autopsy studies suggesting that NFT develop first, and more recent neuroimaging studies supporting the early role of amyloid beta (A beta) deposition. Cerebrospinal fluid (CSF) biomarkers of A beta(42) and hyperphosphorylated tau (p-tau) have been shown to serve as in vivo proxy measures of amyloid plaques and NFT, respectively. The aim of this study was to examine the association between CSF biomarkers and rate of atrophy in the precuneus and hippocampus. These regions were selected because the precuneus appears to be affected early and severely by A beta deposition, and the hippocampus similarly by NFT pathology. We predicted (1) baseline A beta(42) would be related to accelerated rate of cortical thinning in the precuneus and volume loss in the hippocampus, with the latter relationship expected to be weaker, (2) baseline p-tau(181p) would be related to accelerated rate of hippocampal atrophy and cortical thinning in the precuneus, with the latter relationship expected to be weaker. Using all ADNI cohorts, we fitted separate linear mixed-effects models for changes in hippocampus and precuneus longitudinal outcome measures with baseline CSF biomarkers modeled as predictors. Results partially supported our hypotheses: Both baseline p-tau(181p) and A beta(42) were associated with hippocampal atrophy over time. Neither p-tau(181p) nor A beta(42) were significantly related to cortical thinning in the precuneus over time. However, follow-up analyses demonstrated that having abnormal levels of both A beta(42) and p-tau(181p) was associated with an accelerated rate of atrophy in both the hippocampus and precuneus. Results support early effects of A beta in the Alzheimer's disease process, which are less apparent than and perhaps dependent on p-tau effects as the disease progresses. However, amyloid deposition alone may be insufficient for emergence of significant morphometric changes and clinical symptoms. C1 [Stricker, Nikki H.] VA Boston Med Ctr 116B, Boston, MA 02130 USA. [Stricker, Nikki H.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Stricker, Nikki H.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Dodge, Hiroko H.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Dowling, N. Maritza] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Han, S. Duke] Rush Univ, Med Ctr, Dept Behav Sci, Chicago, IL 60612 USA. [Erosheva, Elena A.] Univ Washington, Dept Stat, Seattle, WA 98195 USA. [Erosheva, Elena A.] Univ Washington, Sch Social Work, Seattle, WA 98195 USA. [Jagust, William J.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Jagust, William J.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA. RP Stricker, NH (reprint author), VA Boston Med Ctr 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM stricker@bu.edu RI Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Saykin, Andrew/A-1318-2007 OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438; Saykin, Andrew/0000-0002-1376-8532 FU National Institute on Aging [R13 AG030995]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health); National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; NIH [P30 AG010129, K01 AG030514, P30 AG008017, R01 AG029672-01A1]; Dana Foundation FX This manuscript was a collaborative effort from the 2011 Friday Harbor Advanced Psychometrics Workshop, funded by the National Institute on Aging R13 AG030995. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-LaRoche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, P30 AG008017, R01 AG029672-01A1 and the Dana Foundation. NR 60 TC 17 Z9 17 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2012 VL 6 IS 4 BP 599 EP 609 DI 10.1007/s11682-012-9171-6 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA 061VL UT WOS:000312878200010 PM 22614327 ER PT J AU Han, SD Gruhl, J Beckett, L Dodge, HH Stricker, NH Farias, S Mungas, D AF Han, S. Duke Gruhl, Jonathan Beckett, Laurel Dodge, Hiroko H. Stricker, Nikki H. Farias, Sarah Mungas, Dan CA Alzheimer's Dis Neuroimaging TI Beta amyloid, tau, neuroimaging, and cognition: sequence modeling of biomarkers for Alzheimer's Disease SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Beta amyloid; Tau; Memory; Executive Functions; Neuroimaging ID SURFACE-BASED ANALYSIS; CSF BIOMARKERS; OLDER PERSONS; A-BETA; DECLINE; BRAIN; NEUROPATHOLOGY; SEGMENTATION; DEMENTIA; POPULATION AB Alzheimer's disease (AD) is associated with a cascade of pathological events involving formation of amyloid-based neuritic plaques and tau-based neurofibrillary tangles, changes in brain structure and function, and eventually, cognitive impairment and functional disability. The precise sequence of when each of these disease markers becomes abnormal is not yet clearly understood. The present study systematically tested the relationship between classes of biomarkers according to a proposed model of temporal sequence by Jack et al. (Lancet Neurology 9:119-128, 2010). We examined temporal relations among four classes of biomarkers: CSF A beta, CSF tau, neuroimaging variables (hippocampal volume, ventricular volume, FDG PET), and cognitive variables (memory and executive function). Random effects modeling of longitudinal data obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) was used to test hypotheses that putative earlier markers of AD predicted change in later markers, and that intervening markers reduced effects of earlier on later markers. Specifically, we hypothesized that CSF tau would explain CSF A beta's relation to neuroimaging and cognitive variables, and neuroimaging variables would explain tau's relation to cognitive variables. Consistent with hypotheses, results indicated that CSF A beta effects on cognition change were substantially attenuated by CSF tau and measures of brain structure and function, and CSF tau effects on cognitive change were attenuated by neuroimaging variables. Contrary to hypotheses, CSF A beta and CSF tau were observed to have independent effects on neuroimaging and CSF tau had a direct effect on baseline cognition independent of brain structure and function. These results have implications for clarifying the temporal sequence of AD changes and corresponding biomarkers. C1 [Han, S. Duke] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Han, S. Duke] Rush Univ, Med Ctr, Dept Behav Sci, Chicago, IL 60612 USA. [Gruhl, Jonathan] Univ Washington, Dept Stat, Seattle, WA 98195 USA. [Beckett, Laurel] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Dodge, Hiroko H.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Stricker, Nikki H.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Stricker, Nikki H.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Farias, Sarah; Mungas, Dan] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. RP Han, SD (reprint author), Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, 600 S Paulina St,1022, Chicago, IL 60612 USA. EM Duke_Han@rush.edu RI Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Saykin, Andrew/A-1318-2007; Finger, Elizabeth/B-6453-2015; OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438; Saykin, Andrew/0000-0002-1376-8532; Beckett, Laurel/0000-0002-2418-9843 FU ADNI (National Institutes of Health) [U01 AG024904]; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; NIH [P30 AG010129, K01 AG030514]; Dana Foundation FX This manuscript was a collaborative effort from the 2011 Friday Harbor Advanced Psychometrics Workshop (R13 AG030995), and used with gracious permission data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) downloaded on 6/1/11. Data collection and sharing for this project was funded by ADNI (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. NR 39 TC 16 Z9 16 U1 2 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2012 VL 6 IS 4 BP 610 EP 620 DI 10.1007/s11682-012-9177-0 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA 061VL UT WOS:000312878200011 PM 22648764 ER PT J AU Ramanan, VK Kim, S Holohan, K Shen, L Nho, K Risacher, SL Foroud, TM Mukherjee, S Crane, PK Aisen, PS Petersen, RC Weiner, MW Saykin, AJ AF Ramanan, Vijay K. Kim, Sungeun Holohan, Kelly Shen, Li Nho, Kwangsik Risacher, Shannon L. Foroud, Tatiana M. Mukherjee, Shubhabrata Crane, Paul K. Aisen, Paul S. Petersen, Ronald C. Weiner, Michael W. Saykin, Andrew J. CA ADNI TI Genome-wide pathway analysis of memory impairment in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort implicates gene candidates, canonical pathways, and networks SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Memory; Psychometrics; Alzheimer's disease; Mild cognitive impairment; Pathway analysis; Genome-wide association study ID MILD COGNITIVE IMPAIRMENT; MINI-MENTAL STATE; STATISTICAL-METHODS; MULTIPLE-SCLEROSIS; QUANTITATIVE TRAIT; APOLIPOPROTEIN-E; SET ENRICHMENT; TYPE-4 ALLELE; AXON GUIDANCE; OLDER-ADULTS AB Memory deficits are prominent features of mild cognitive impairment (MCI) and Alzheimer's disease (AD). The genetic architecture underlying these memory deficits likely involves the combined effects of multiple genetic variants operative within numerous biological pathways. In order to identify functional pathways associated with memory impairment, we performed a pathway enrichment analysis on genome-wide association data from 742 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. A composite measure of memory was generated as the phenotype for this analysis by applying modern psychometric theory to item-level data from the ADNI neuropsychological test battery. Using the GSA-SNP software tool, we identified 27 canonical, expertly-curated pathways with enrichment (FDR-corrected p-value < 0.05) against this composite memory score. Processes classically understood to be involved in memory consolidation, such as neurotransmitter receptor-mediated calcium signaling and long-term potentiation, were highly represented among the enriched pathways. In addition, pathways related to cell adhesion, neuronal differentiation and guided outgrowth, and glucose- and inflammation-related signaling were also enriched. Among genes that were highly-represented in these enriched pathways, we found indications of coordinated relationships, including one large gene set that is subject to regulation by the SP1 transcription factor, and another set that displays co-localized expression in normal brain tissue along with known AD risk genes. These results 1) demonstrate that psychometrically-derived composite memory scores are an effective phenotype for genetic investigations of memory impairment and 2) highlight the promise of pathway analysis in elucidating key mechanistic targets for future studies and for therapeutic interventions. C1 [Ramanan, Vijay K.; Kim, Sungeun; Holohan, Kelly; Shen, Li; Nho, Kwangsik; Risacher, Shannon L.; Saykin, Andrew J.] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Ctr Neuroimaging, Indianapolis, IN USA. [Ramanan, Vijay K.; Holohan, Kelly; Foroud, Tatiana M.; Saykin, Andrew J.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA. [Ramanan, Vijay K.] Indiana Univ Sch Med, Med Scientist Training Program, Indianapolis, IN USA. [Kim, Sungeun; Shen, Li; Nho, Kwangsik; Foroud, Tatiana M.; Saykin, Andrew J.] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN USA. [Mukherjee, Shubhabrata; Crane, Paul K.] Univ Washington, Dept Med, Seattle, WA USA. [Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Petersen, Ronald C.] Mayo Clin Minnesota, Dept Neurol, Rochester, MN USA. [Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Saykin, AJ (reprint author), Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Ctr Neuroimaging, Indianapolis, IN USA. EM asaykin@iupui.edu RI Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Saykin, Andrew/A-1318-2007; Crane, Paul/C-8623-2014; OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438; Saykin, Andrew/0000-0002-1376-8532; Mukherjee, Shubhabrata/0000-0003-2522-2884; Shen, Li/0000-0002-5443-0503; Crane, Paul/0000-0003-4278-7465 FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; NIH [P30 AG010129, K01 AG030514]; Dana Foundation; NSF [IIS-1117335]; NIA [R13 AG030995, R01 AG19771, P30 AG10133, R01 AG029672] FX Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research provides funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. Data management and the specific analyses reported here were supported by NSF IIS-1117335 (Shen), NIA R13 AG030995 (Mungas), NIA R01 AG19771 (Saykin), P30 AG10133 (Saykin/Ghetti), and R01 AG029672 (Crane). The authors declare that they have no conflict of interest. NR 79 TC 25 Z9 25 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2012 VL 6 IS 4 BP 634 EP 648 DI 10.1007/s11682-012-9196-x PG 15 WC Neuroimaging SC Neurosciences & Neurology GA 061VL UT WOS:000312878200013 PM 22865056 ER PT J AU Mukherjee, S Trittschuh, E Gibbons, LE Mackin, RS Saykin, A Crane, PK AF Mukherjee, Shubhabrata Trittschuh, Emily Gibbons, Laura E. Mackin, R. Scott Saykin, Andrew Crane, Paul K. CA Alzheimer's Dis Neuroimaging TI Dysexecutive and amnesic AD subtypes defined by single indicator and modern psychometric approaches: relationships with SNPs in ADNI SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Memory; Executive functioning; Alzheimer's disease; Phenotype; Genetic analyses; Psychometrics ID GENOME-WIDE ASSOCIATION; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; DYSFUNCTION; CONSORTIUM; BIOMARKERS; PHENOTYPES; DIAGNOSIS; PATTERNS; PROGRESS AB Previous investigators have suggested the existence of distinct cognitive phenotypes of Alzheimer's disease (AD): a dysexecutive subgroup with executive functioning worse than memory and an amnesic subgroup with memory worse than executive functioning. We evaluated data from the AD Neuroimaging Initiative. We assigned people with AD to dysexecutive and amnesic subgroups using single indicators, and analogously using the ADNI-Mem and ADNI-EF composite scores developed using modern psychometric approaches. We evaluated associations between subgroup membership, APOE genotype, and single nucleotide polymorphisms (SNPs) are associated with AD, and brain vascular disease defined as white matter hyperintensities (WMH) and MRI-identified infarcts. We hypothesized that APOE epsilon 4 and alleles associated with higher risk for AD would predict amnesic subgroup membership; alleles associated with higher WMH or infarct burden would predict dysexecutive subgroup membership. Classification agreement between the two approaches was only fair (kappa = 0.23). There was no relationship between APOE alleles and the dysexecutive or amnesic phenotypes defined by either categorization approach. There were 58 AD-related and 25 WMH- or infarct-related SNPs for which odds ratios were > 1.5 or < 0.67 for dysexecutive vs. amnesic subgroup defined by either categorization approach. Higher proportions of SNPs had odds ratios in the hypothesized direction for the subgroups defined by the modern psychometric approach for AD-related (58 % vs. 38 %, p-value < 0.001) and brain vascular disease-related SNPs (48 vs. 32 %, p-value = 0.01). Genetic variation may underlie differential performance in memory and executive functioning among people with AD. Modern psychometric composite scores produced group assignments with more SNP associations in the hypothesized direction. C1 [Mukherjee, Shubhabrata; Gibbons, Laura E.; Crane, Paul K.] Univ Washington, Dept Med, Seattle, WA USA. [Trittschuh, Emily] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Trittschuh, Emily] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Mackin, R. Scott] San Francisco VA Med Ctr, CIND, San Francisco, CA USA. [Saykin, Andrew] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Ctr Neuroimaging, Indianapolis, IN USA. RP Mukherjee, S (reprint author), Box 359780,325 9th Ave, Seattle, WA 98104 USA. EM smukherj@u.washington.edu RI Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Saykin, Andrew/A-1318-2007; Crane, Paul/C-8623-2014; OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438; Saykin, Andrew/0000-0002-1376-8532; Crane, Paul/0000-0003-4278-7465; Mukherjee, Shubhabrata/0000-0003-2522-2884 FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; NIH [P30 AG010129, K01 AG030514, R01 AG029672, R13 AG030995]; NIA [P50 AG05136] FX Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514. Data management and the specific analyses reported here were supported by NIH grant R01 AG029672 (Paul Crane, PI), R13 AG030995 (Mungas), and P50 AG05136 (Raskind), from the NIA. NR 37 TC 5 Z9 5 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2012 VL 6 IS 4 BP 649 EP 660 DI 10.1007/s11682-012-9207-y PG 12 WC Neuroimaging SC Neurosciences & Neurology GA 061VL UT WOS:000312878200014 PM 23161456 ER PT J AU Gertow, K Sennblad, B Strawbridge, RJ Ohrvik, J Zabaneh, D Shah, S Veglia, F Fava, C Kavousi, M McLachlan, S Kivimaki, M Bolton, JL Folkersen, L Gigante, B Leander, K Vikstrom, M Larsson, M Silveira, A Deanfield, J Voight, BF Fontanillas, P Sabater-Lleal, M Colombo, GI Kumari, M Langenberg, C Wareham, NJ Uitterlinden, AG Gabrielsen, A Hedin, U Franco-Cereceda, A Nyyssonen, K Rauramaa, R Tuomainen, TP Savonen, K Smit, AJ Giral, P Mannarino, E Robertson, CM Talmud, PJ Hedblad, B Hofman, A Erdmann, J Reilly, MP O'Donnell, CJ Farrall, M Clarke, R Franzosi, MG Seedorf, U Syvanen, AC Hansson, GK Eriksson, P Samani, NJ Watkins, H Price, JF Hingorani, AD Melander, O Witteman, JCM Baldassarre, D Tremoli, E de Faire, U Humphries, SE Hamsten, A AF Gertow, Karl Sennblad, Bengt Strawbridge, Rona J. Oehrvik, John Zabaneh, Delilah Shah, Sonia Veglia, Fabrizio Fava, Cristiano Kavousi, Maryam McLachlan, Stela Kivimaeki, Mika Bolton, Jennifer L. Folkersen, Lasse Gigante, Bruna Leander, Karin Vikstrom, Max Larsson, Malin Silveira, Angela Deanfield, John Voight, Benjamin F. Fontanillas, Pierre Sabater-Lleal, Maria Colombo, Gualtiero I. Kumari, Meena Langenberg, Claudia Wareham, Nick J. Uitterlinden, Andre G. Gabrielsen, Anders Hedin, Ulf Franco-Cereceda, Anders Nyyssonen, Kristiina Rauramaa, Rainer Tuomainen, Tomi-Pekka Savonen, Kai Smit, Andries J. Giral, Philippe Mannarino, Elmo Robertson, Christine M. Talmud, Philippa J. Hedblad, Bo Hofman, Albert Erdmann, Jeanette Reilly, Muredach P. O'Donnell, Christopher J. Farrall, Martin Clarke, Robert Franzosi, Maria Grazia Seedorf, Udo Syvanen, Ann-Christine Hansson, Goran K. Eriksson, Per Samani, Nilesh J. Watkins, Hugh Price, Jacqueline F. Hingorani, Aroon D. Melander, Olle Witteman, Jacqueline C. M. Baldassarre, Damiano Tremoli, Elena de Faire, Ulf Humphries, Steve E. Hamsten, Anders TI Identification of the BCAR1-CFDP1-TMEM170A Locus as a Determinant of Carotid Intima-Media Thickness and Coronary Artery Disease Risk SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE atherosclerosis; carotid intima-media thickness; coronary artery disease; genetics ID GENOME-WIDE ASSOCIATION; VASCULAR SMOOTH-MUSCLE; CARDIOVASCULAR RISK; MYOCARDIAL-INFARCTION; WHITEHALL-II; ATHEROSCLEROSIS; SUSCEPTIBILITY; METAANALYSIS; ROTTERDAM; CALCIFICATION AB Background-Carotid intima-media thickness (cIMT) is a widely accepted marker of subclinical atherosclerosis. To date, large-scale investigations of genetic determinants of cIMT are sparse. Methods and Results-To identify cIMT-associated genes and genetic variants, a discovery analysis using the Illumina 200K CardioMetabochip was conducted in 3430 subjects with detailed ultrasonographic determinations of cIMT from the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population) study. Segment-specific IMT measurements of common carotid, bifurcation, and internal carotid arteries, and composite IMT variables considering the whole carotid tree (IMTmean, IMTmax, and IMTmean-max), were analyzed. A replication stage investigating 42 single-nucleotide polymorphisms for association with common carotid IMT was undertaken in 5 independent European cohorts (total n=11 590). A locus on chromosome 16 (lead single-nucleotide polymorphism rs4888378, intronic in CFDP1) was associated with cIMT at significance levels passing multiple testing correction at both stages (array-wide significant discovery P=6.75x10(-7) for IMTmax; replication P=7.24x10(-6) for common cIMT; adjustments for sex, age, and population substructure where applicable; minor allele frequency 0.43 and 0.41, respectively). The protective minor allele was associated with lower carotid plaque score in a replication cohort (P=0.04, n=2120) and lower coronary artery disease risk in 2 case-control studies of subjects with European ancestry (odds ratio [95% confidence interval] 0.83 [0.77-0.90], P=6.53x10(-6), n=13 591; and 0.95 [0.92-0.98], P=1.83x10(-4), n= 82 297, respectively). Queries of human biobank data sets revealed associations of rs4888378 with nearby gene expression in vascular tissues (n=126-138). Conclusions-This study identified rs4888378 in the BCAR1-CFDP1-TMEM170A locus as a novel genetic determinant of cIMT and coronary artery disease risk in individuals of European descent. (Circ Cardiovasc Genet. 2012;5:656-665.) C1 [Gertow, Karl; Sennblad, Bengt; Strawbridge, Rona J.; Oehrvik, John; Folkersen, Lasse; Larsson, Malin; Silveira, Angela; Sabater-Lleal, Maria; Eriksson, Per; Hamsten, Anders] Karolinska Univ Hosp Solna, Ctr Mol Med, Atherosclerosis Res Unit, Dept Med,Karolinska Inst, S-17176 Stockholm, Sweden. [Folkersen, Lasse; Uitterlinden, Andre G.; Hansson, Goran K.] Karolinska Univ Hosp Solna, Ctr Mol Med, Expt Cardiovasc Res Unit, Dept Med,Karolinska Inst, S-17176 Stockholm, Sweden. [Zabaneh, Delilah; Shah, Sonia] UCL, Genet Inst, London, England. [Kivimaeki, Mika; Kumari, Meena; Langenberg, Claudia; Hingorani, Aroon D.] UCL, Genet Epidemiol Grp, Dept Epidemiol & Publ Hlth, London, England. [Talmud, Philippa J.; Humphries, Steve E.] UCL, BHF Labs, Dept Med, Ctr Clin Pharmacol, London, England. [Veglia, Fabrizio; Colombo, Gualtiero I.; Baldassarre, Damiano; Tremoli, Elena] IRCCS, Ctr Cardiol Monzino, Milan, Italy. [Fava, Cristiano; Hedblad, Bo; Melander, Olle] Lund Univ, Skane Univ Hosp, Dept Clin Sci, Clin Res Ctr, Lund, Sweden. [Fava, Cristiano] Univ Verona, Hosp Policlin GB Rossi, Dept Med, Div Internal Med C, Verona, Italy. [Kavousi, Maryam; Uitterlinden, Andre G.; Hofman, Albert; Witteman, Jacqueline C. M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Kavousi, Maryam; Uitterlinden, Andre G.; Hofman, Albert; Witteman, Jacqueline C. M.] Sponsored Netherlands Consortium Healthy Ageing, Netherlands Genom Initiat, Rotterdam, Netherlands. [McLachlan, Stela; Bolton, Jennifer L.; Robertson, Christine M.; Price, Jacqueline F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Gigante, Bruna; Leander, Karin; Vikstrom, Max; de Faire, Ulf] Karolinska Inst, Div Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden. [Hedin, Ulf; Franco-Cereceda, Anders] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Deanfield, John] Great Ormond St Hosp Sick Children, Cardiothorac Unit, London, England. [Voight, Benjamin F.; Fontanillas, Pierre] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Voight, Benjamin F.; Fontanillas, Pierre] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Voight, Benjamin F.; Fontanillas, Pierre] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Langenberg, Claudia; Wareham, Nick J.] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 2QQ, England. [Nyyssonen, Kristiina; Tuomainen, Tomi-Pekka] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland. [Rauramaa, Rainer; Savonen, Kai] Fdn Res Hlth Exercise & Nutr, Kuopio Res Inst Exercise Med, Kuopio, Finland. [Rauramaa, Rainer; Savonen, Kai] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland. [Smit, Andries J.] Univ Groningen, Univ Med Ctr Groningen, Dept Med, NL-9713 AV Groningen, Netherlands. [Giral, Philippe] Grp Hop Pitie Salpetriere, AP HP, Serv Endocrinol Metab, Unites Prevent Cardiovasc, Paris, France. [Mannarino, Elmo] Univ Perugia, Dept Clin & Expt Med, I-06100 Perugia, Italy. [Erdmann, Jeanette] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany. [Reilly, Muredach P.] Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA. [Farrall, Martin; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Oxford, England. [Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Farrall, Martin; Watkins, Hugh] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England. [Franzosi, Maria Grazia] Inst Mario Negri, Dept Cardiovasc Res, Milan, Italy. [Seedorf, Udo] Univ Munster, LIFA, Gesell Arterioskleroseforsch eV, Munster, Germany. [Syvanen, Ann-Christine] Uppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, Uppsala, Sweden. [Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Samani, Nilesh J.] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England. [Baldassarre, Damiano; Tremoli, Elena] Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy. RP Gertow, K (reprint author), Karolinska Univ Hosp Solna, Ctr Mol Med, Atherosclerosis Res Unit, Dept Med,Karolinska Inst, Bldg L8 03, S-17176 Stockholm, Sweden. EM karl.gertow@ki.se RI Sabater-Lleal, Maria/I-5832-2013; Shah, Sonia/N-7547-2013; Colombo, Gualtiero/B-4737-2010; Strawbridge, Rona/H-5422-2012; Veglia, Fabrizio/K-1958-2016; Leander, Karin/C-7261-2017; Baldassarre, Damiano/J-3295-2016; Erdmann, Jeanette/P-7513-2014; OI Shah, Sonia/0000-0001-5860-4526; Colombo, Gualtiero/0000-0002-7348-1939; Strawbridge, Rona/0000-0001-8506-3585; Veglia, Fabrizio/0000-0002-9378-8874; Leander, Karin/0000-0002-1404-9222; TREMOLI, ELENA/0000-0002-0929-6106; Baldassarre, Damiano/0000-0002-2766-8882; mannarino, elmo/0000-0002-9771-8056; Kivimaki, Mika/0000-0002-4699-5627; Talmud, Philippa/0000-0002-5560-1933; Seedorf, Udo/0000-0003-4652-5358; Erdmann, Jeanette/0000-0002-4486-6231; Gigante, Bruna/0000-0003-4508-7990; Folkersen, Lasse/0000-0003-0708-9530; Humphries, Stephen E/0000-0002-8221-6547; Kumari, Meena/0000-0001-9716-1035; Watkins, Hugh/0000-0002-5287-9016; Hedin, Ulf/0000-0001-9212-3945; Sabater Lleal, Maria/0000-0002-0128-379X FU Medical Research Council-GlaxoSmithKline pilot program grant [ID 85374]; European Commission [QLG1-CT-2002-00896, Health F2 2008 200647, FP7-HEALTH- 2007-A-201668]; Swedish Heart-Lung Foundation [20090541]; Swedish Research Council [8691, 0593, 12660]; Knut and Alice Wallenberg Foundation; Torsten and Ragnar Sderberg Foundation; Swedish Foundation for Strategic Research; Stockholm County Council [562183]; Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet; Stockholm County Council, Academy of Finland [110413]; Ministry of Education and Culture of Finland; City of Kuopio; British Heart Foundation (BHF) [RG2008/014, RG2008/08, RG005/014, PG1041133124260, RG1081008]; Italian Ministry of Health (Ricerca Corrente); University College London Genetics Institute; Erasmus Medical Center; Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly [014-93-015; RIDE2]; Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; Netherlands Organization of Scientific Research (De Nederlandse Organisatie voor Wetenschappelijk Onderzoek) [175.010.2005.011, 911-03-012]; Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging [050-060-810]; Netherlands Organization of Scientific Research [918-76-619]; Medical Research Council; National Institutes of Health [R01HL36310, AG13196]; European Research Council [ERC-StG-282255]; Chief Scientist Office of the Scottish Executive Health Department; AFA Insurance Foundation; European Community Sixth Framework Program [LSHM-CT-2007-037273]; AstraZeneca; Wellcome Trust [090532/Z/09/Z]; Strategic Cardiovascular Program of Karolinska Institutet; Foundation for Strategic Research; BHF Center of Research Excellence; Marie Curie Intra European Fellowship within the seventh Framework Program of the European Union [PIEF-GA-2009-252361]; National Heart, Lung and Blood Institute [R01HL36310]; Medical Research Foundation; National Heart, Blood and Lung Institute [HL36310]; Academy of Finland [110413]; French Health Ministry; European Commission 6th Framework Program; European Commission Seventh Framework Program on Diabetes FX The authors fully acknowledge the thousands of study participants who volunteered their time to help advance science and the scores of research staff and scientists who have made this research possible. The Edinburgh Artery Study would particularly like to acknowledge all staff and participants. The authors representing the Rotterdam Study are grateful to the participants and staff, the participating general practitioners, and the pharmacists. Whitehall-II genotyping was, in part, supported by a Medical Research Council-GlaxoSmithKline pilot program grant (ID 85374). David Altshuler, Sekar Kathiresan, and " The Pfizer Broad-Massachusetts General Hospital-Broad Genetics Collaboration" are acknowledged for supporting the genotyping in the MDC study. Members, sources of funding, and disclosures of the CARDIOGRAM consortium are listed in onlineonly Data Supplement Section S7. Members of the PROCARDIS consortium are listed in online-only Data Supplement Section S8. Members of the writing group and affiliations by participating study are listed in online-only Data Supplement Section S9.; The IMPROVE study was supported by the European Commission (Contract No. QLG1-CT-2002-00896), the Swedish Heart-Lung Foundation, the Swedish Research Council (projects 8691 and 0593), the Knut and Alice Wallenberg Foundation, the Torsten and Ragnar Sderberg Foundation, the Swedish Foundation for Strategic Research, the Stockholm County Council (project 562183), the Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet and Stockholm County Council, Academy of Finland (Grant 110413), the Ministry of Education and Culture of Finland, the City of Kuopio, the British Heart Foundation (BHF) (RG2008/014), and the Italian Ministry of Health (Ricerca Corrente). The University College London Genetics Institute supported Dr Zabaneh and S. Shah, and Dr Humphries was supported by the BHF (RG2008/08). The Rotterdam Study was funded by the Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The Rotterdam Genome-Wide Association study was funded by the Netherlands Organization of Scientific Research (De Nederlandse Organisatie voor Wetenschappelijk Onderzoek) Investments (number 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2) and the Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging (project 050-060-810). The present work was further supported by a Netherlands Organization of Scientific Research grant (vici, 918-76-619). The Whitehall-II study was supported by the Medical Research Council, the BHF, and the National Institutes of Health (R01HL36310). Drs Humphries and Talmud were supported by BHF RG005/014. The Malm Diet and Cancer Study was supported by the Swedish Research Council, the Swedish Heart-Lung Foundation, and the European Research Council (ERC-StG-282255). The Edinburgh Artery Study was financed by the BHF and the Chief Scientist Office of the Scottish Executive Health Department. The Advanced Study of Aortic Pathology Study was supported by the Swedish Research Council (12660), the Swedish Heart-Lung Foundation (20090541), the European Commission (FAD, Health F2 2008 200647), and a donation from Fredrik Lundberg. The Biobank of Karolinska Endarterectomies Study was funded by the Swedish Heart-Lung Foundation, the Swedish Research Council, the European Commission (AtheroRemo; FP7-HEALTH- 2007-A-201668), the AFA Insurance Foundation, and the Torsten and Ragnar Sderberg Foundation. PROCARDIS was supported by the European Community Sixth Framework Program (LSHM-CT-2007-037273), AstraZeneca, the BHF, the Wellcome Trust (Contract No. 090532/Z/09/Z), the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung Foundation, the Torsten and Ragnar Sderberg Foundation, the Strategic Cardiovascular Program of Karolinska Institutet and Stockholm County Council, the Foundation for Strategic Research and the Stockholm County Council. M. Farall and H. Watkins are supported by the BHF Center of Research Excellence. Dr SabaterLleal is a recipient of a Marie Curie Intra European Fellowship within the seventh Framework Program of the European Union (PIEF-GA-2009-252361).; Dr McLachlan reports stock ownership interest in Pfizer. Dr Kivim ki reports receiving research grant support from the National Heart, Lung and Blood Institute (R01HL36310; principal investigator). Dr Deanfield reports receiving research grant support from the BHF and Medical Research Foundation and honoraria payment and payment for speakers' bureau appointments (Novartis, Roche, Merck, Danone, Pfizer). Dr Voight reports receiving research grant support from the National Institutes of Health (A Genome-Wide Association Study for Early Onset MI; postdoc) and an industry grant (Toward Therapeutical Markers for MI in a T2D Background; postdoc). Dr Kumari reports receiving research grant support from the BHF (PG1041133124260, RG1081008), the National Institutes of Health (AG13196), the Medical Research Council, and the National Heart, Blood and Lung Institute (HL36310). Dr Gabrielsen was employed by Bayer after completion of the study. Dr Hedin reports consultant relationship with Cardoz AB. Dr Nyyssnen reports receiving research grant support from the Academy of Finland for the IMPROVE study (Grant 110413). Dr Giral reports receiving Hospital Clinical Research Program research grant support, awarded by the French Health Ministry. Dr Clarke reports receiving research grant support from the BHF. Dr Franzosi reports receiving research grant support from the European Commission 6th Framework Program as collaborator in the PROCARDIS project. Dr Hingorani reports receiving research grant support from the BHF. Dr Baldassarre reports receiving research grant support from the European Commission (Contract No. QLG1-CT-2002-00896) for the IMPROVE study. Dr Tremoli reports receiving research grant support from the European Commission (Contract No. QLG1-CT-2002-00896) for the IMPROVE study. Dr Humphries reports receiving research grant support from the BHF (RG2008/08, program and project grants on cardiovascular genetics) and the European Commission Seventh Framework Program on Diabetes, and discloses speakers' bureau appointment payment (Genzyme meeting on FH, Amsterdam, November 2011) and 1 consultant/advisory board relationship (Store Gene, a Coronary Heart Disease risk genetic testing University College London spin-off company). NR 33 TC 13 Z9 13 U1 0 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD DEC PY 2012 VL 5 IS 6 BP 656 EP 665 DI 10.1161/CIRCGENETICS.112.963660 PG 10 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 060JY UT WOS:000312774800014 PM 23152477 ER PT J AU Matar, AJ Crepeau, RL Pathiraja, V Robson, S Fishman, JA Spitzer, TR Sachs, DH Huang, CA Duran-Struuck, R AF Matar, Abraham J. Crepeau, Rebecca L. Pathiraja, Vimukthi Robson, Simon Fishman, Jay A. Spitzer, Thomas R. Sachs, David H. Huang, Christene A. Duran-Struuck, Raimon TI Effects of Mobilization Regimens in Donors on Outcomes of Hematopoietic Cell Transplantation in Miniature Swine SO COMPARATIVE MEDICINE LA English DT Article ID BONE-MARROW-TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; VERSUS-HOST-DISEASE; HEALTHY-INDIVIDUALS; CHIMERISM; PIGS; COMPLICATIONS; COAGULATION; IMMUNOTOXIN; ENGRAFTMENT AB Toxicities and complications associated with hematopoietic cell transplantation currently limit this potentially curative therapy for malignant and nonmalignant blood disorders. Miniature swine provide a clinically relevant model for studies to improve posttransplantation outcomes. Miniature swine recipients of high-dose haploidentical hepatopoietic cell transplantation after reduced-intensity conditioning consisting of low-dose (100 cGy) total-body irradiation, partial T-cell depletion by using a CD3 immunotoxin, and a 45-d course of cyclosporine A typically successfully engraft without graft-versus-host disease. We recently observed broad variability in engraftment outcomes that correlates with the occurrence of adverse reactions in donors after cytokine treatment to mobilize hematopoietic progenitor cells from the bone marrow to the peripheral blood for collection. Haploidentical recipients (n = 16) of cells from donors remaining healthy during cytokine treatment engrafted with multilineage chimerism, did not develop graft-versus-host disease, and did not require any blood products. In comparison, identically conditioned recipients of cells from donors that had severe reactions during cytokine treatment had adverse outcomes, including the development of clinically significant thrombocytopenia requiring blood product support in 8 of 11 swine. Furthermore, all 11 recipients lost peripheral blood myeloid chimerism (indicating lack of engraftment of donor stem cells). These data suggest that posttransplantation complications in swine are influenced by the health status of the donor before and during the collection of hematopoietic cells by leukapheresis. C1 [Matar, Abraham J.; Crepeau, Rebecca L.; Pathiraja, Vimukthi; Sachs, David H.; Huang, Christene A.; Duran-Struuck, Raimon] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Spitzer, Thomas R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Fishman, Jay A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Robson, Simon] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Duran-Struuck, R (reprint author), Columbia Univ, Columbia Ctr Translat Immunol, New York, NY 10027 USA. EM Rd2605@columbia.edu FU NIAID NIH HHS [P01 AI045897, R01 AI084657] NR 24 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD DEC PY 2012 VL 62 IS 6 BP 487 EP 494 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 059DJ UT WOS:000312684300005 PM 23561882 ER PT J AU Nield, M Hoo, GWS AF Nield, Margaret Hoo, Guy W. Soo TI Real-Time Telehealth for COPD Self-Management Using Skype (TM) SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE Social support; Dyspnea; Breathing strategy; Telecommunication ID OBSTRUCTIVE PULMONARY-DISEASE; SOCIAL SUPPORT; HOME TELEHEALTH; DYSPNEA; HEALTH; STATEMENT; OUTCOMES AB The utility of real-time interactive voice and video telehealth for teaching pursed-lips breathing (PLB) in chronic obstructive pulmonary disease (COPD) is unknown. This was a pilot study to determine its feasibility and efficacy on the key variables of social support and dyspnea. A randomized control study design with repeated measures (baseline, 4 and 12 weeks) was used. All participants in the control and intervention groups received PLB instruction at baseline, but only the intervention group received one weekly PLB reinforcement session for 4 weeks via home computer and Skype (TM) software. Outcome measures were Medical Outcomes Study Social Support Survey and dyspnea assessment (visual analogue scales for intensity and distress, modified Borg after six-minute walk distance, and Shortness of Breath Questionnaire for activity-associated dyspnea). A total of 22 participants with COPD (mean FEV1 % predicted = 56) were randomized; 16 (9 telehealth, 7 control) completed the protocol. Intent-to-treat analysis at week 4, but not week 12, demonstrated significantly improved total social support (P = 0.02) and emotional/informational subscale (P = 0.03) scores. Dyspnea intensity decreased (P = 0.08) for the intervention group with a minimal clinical important difference of 10.4 units. Analysis of only participants who completed the protocol demonstrated a significant decrease in dyspnea intensity (P = <0.01) for the intervention group at both week 4 and 12. Real-time telehealth is a feasible, innovative approach for PLB instruction in the home with outcomes of improved social support and decreased dyspnea. C1 [Nield, Margaret] VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, Los Angeles, CA 90073 USA. [Hoo, Guy W. Soo] Univ Calif Los Angeles, W Los Angeles VA Healthcare Ctr, Pulm & Crit Care Sect, Los Angeles, CA USA. [Hoo, Guy W. Soo] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RP Nield, M (reprint author), VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, 11301 Wilshire Blvd,111Q, Los Angeles, CA 90073 USA. EM pegnield@gmail.com FU Breathe California of Los Angeles County; National Institutes of Health [P20 NR010671-01] FX Margaret Nield has no conflict of interest to disclose. Guy W. Soo Hoo is a member of the board of Breathe California of Los Angeles County. The funding sources (Breathe California of Los Angeles County and in part by National Institutes of Health [Grant P20 NR010671-01]) 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. The authors are responsible for the content and the writing of this paper. NR 37 TC 13 Z9 13 U1 2 U2 25 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1541-2555 J9 COPD JI COPD-J. Chronic Obstr. Pulm. Dis. PD DEC PY 2012 VL 9 IS 6 BP 611 EP 619 DI 10.3109/15412555.2012.708067 PG 9 WC Respiratory System SC Respiratory System GA 056PO UT WOS:000312503400006 PM 22946768 ER PT J AU Li, N Zhang, ST Hou, JB Jang, IKK Yu, B AF Li, Ning Zhang, Shaotao Hou, Jingbo Jang, I. K. -Kyung Yu, Bo TI Assessment of Pulmonary Artery Morphology by Optical Coherence Tomography SO HEART LUNG AND CIRCULATION LA English DT Article DE Pulmonary artery; Optical coherence tomography; Histology; Imaging ID HYPERTENSION AB Since its invention, optical coherence tomography (OCT) has been primarily used for the diagnosis of coronary artery disease. A few feasibility studies of OCT to visualise the pulmonary arteries were reported. However, OCT findings in the pulmonary arteries have not been validated using histology as the gold standard. To validate OCT findings for pulmonary arterial imaging, we selected 27 pulmonary arteries from 11 cadavers (6 males, 5 females, mean age 39.6 +/- 21.3 years). Comparison of OCT images and histology was performed. Each histological sample was examined using three types of stains, and the quantified results were analysed by statistics. In conclusion, there was a strong correlation between histology and OCT measurements of the pulmonary arterial wall thickness, the pulmonary arterial wall has a single-layered structure with an average thickness of 0.162 mm. We propose that OCT is probably a useful tool of diagnosing pulmonary artery hypertension and may provide a means to study the pulmonary remodelling process. (Heart, Lung and Circulation 2012;21:778-781) (C) 2012 Published by Elsevier Inc on behalf of Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). C1 [Li, Ning; Zhang, Shaotao; Hou, Jingbo; Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin 150086, Heilongjiang, Peoples R China. [Li, Ning; Zhang, Shaotao; Hou, Jingbo; Yu, Bo] Chinese Minist Educ, Key Lab Myocardial Ischemia, Harbin, Heilongjiang, Peoples R China. [Jang, I. K. -Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Yu, B (reprint author), Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin 150086, Heilongjiang, Peoples R China. EM yubodr@163.com NR 10 TC 7 Z9 7 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1443-9506 J9 HEART LUNG CIRC JI Heart Lung Circ. PD DEC PY 2012 VL 21 IS 12 BP 778 EP 781 DI 10.1016/j.hlc.2012.07.014 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 059FB UT WOS:000312688700002 PM 22884790 ER PT J AU Yonekawa, Y AF Yonekawa, Yoshihiro TI Epidemiology and Management of Uveal Melanoma SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Uveal melanoma; Choroidal melanoma; Proton beam irradiation; Brachytherapy; Enucleation ID COMS RANDOMIZED-TRIAL; COLLABORATIVE OCULAR MELANOMA; PROTON-BEAM IRRADIATION; INTRAARTERIAL HEPATIC FOTEMUSTINE; CHOROIDAL MELANOMA; MALIGNANT-MELANOMA; PLAQUE RADIOTHERAPY; RISK-FACTORS; IODINE-125 BRACHYTHERAPY; RADIATION RETINOPATHY AB Uveal melanoma is the most common primary intraocular malignancy in adults. The annual incidence is approximately 5 per million in the United States. Risk factors include white race, fair skin, light iris color, ancestry from northern latitudes, and ocular/oculodermal melanocytosis. Historically, enucleation was the definitive treatment for uveal melanoma, but brachytherapy and proton beam irradiation are now the most commonly employed treatments. However, there are no effective therapies against metastatic uveal melanoma. Recent studies suggest that the pathogenesis of uveal melanoma includes activation of the MAPK pathway via GNAQ/11, and that metastatic potential may be modulated by mechanisms involving BAP1. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA 02114 USA. RP Yonekawa, Y (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM ivana_kim@meei.harvard.edu NR 103 TC 16 Z9 16 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 2012 VL 26 IS 6 BP 1169 EP + DI 10.1016/j.hoc.2012.08.004 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA 058IJ UT WOS:000312627000004 PM 23116575 ER PT J AU Cascio, EW Riley, KJ McCormack, J Flanagan, R AF Cascio, Ethan W. Riley, Kent J. McCormack, Joe Flanagan, Rob TI Single Event Effects in Power MOSFETs Due to the Secondary Neutron Environment in a Proton Therapy Center SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT IEEE Radiation Effects Data Workshop (REDW) is Part of the Nuclear and Space Radiation Effects Conference (NSREC) CY JUL 16-20, 2012 CL Miami, FL SP IEEE Nucl & Plasma Sci Soc, Inst Elect & Elect Engineers Inc (IEEE) DE Neutron radiation effects; power MOSFETs; protons; single event burnout ID BURNOUT AB Secondary neutron induced single event burnouts (SEB) in power MOSFETs to be installed in an X-ray generator located in a proton therapy treatment vault are characterized. This is done using both accelerated and in situ testing. Experimental techniques and schematics are presented that allow non-destructive testing of multiple MOSFETs in parallel for in situ real time measurements. C1 [Cascio, Ethan W.; Riley, Kent J.; McCormack, Joe] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Flanagan, Rob] MPI Software Inc, Wayland, MA 01778 USA. RP Cascio, EW (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. FU U.S. National Institutes of Health National Cancer Institute [6-PO1 CA21239] FX This work was supported by the U.S. National Institutes of Health National Cancer Institute under Grant 6-PO1 CA21239. NR 14 TC 1 Z9 1 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9499 EI 1558-1578 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD DEC PY 2012 VL 59 IS 6 BP 3154 EP 3159 DI 10.1109/TNS.2012.2221741 PN 1 PG 6 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 056JX UT WOS:000312486000073 ER PT J AU Springelkamp, H Lee, K Ramdas, WD Vingerling, JR Hofman, A Klaver, CCW Sonka, M Abramoff, MD Jansonius, NM AF Springelkamp, Henriet Lee, Kyungmoo Ramdas, Wishal D. Vingerling, Johannes R. Hofman, Albert Klaver, Caroline C. W. Sonka, Milan Abramoff, Michael D. Jansonius, Nomdo M. TI Optimizing the Information Yield of 3-D OCT in Glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; FIBER LAYER THICKNESS; SPECTRAL-DOMAIN OCT; OPEN-ANGLE GLAUCOMA; CIRRUS HD-OCT; NERVE HEAD; STRATUS OCT; REPRODUCIBILITY; EYES; REPEATABILITY AB PURPOSE. To determine, first, which regions of 3-D optical coherence tomography (OCT) volumes can be segmented completely in the majority of subjects and, second, the relationship between analyzed area and thickness measurement test-retest variability. METHODS. Three-dimensional OCT volumes (6X6 mm) centered around the fovea and optic nerve head (ONH) of 925 Rotterdam Study participants were analyzed; 44 participants were scanned twice. Volumes were segmented into 10 layers, and we determined the area where all layers could be identified in at least 95% (macula) or 90% (ONH) of subjects. Macular volumes were divided in 2 x 2, 4 x 4, 6 x 6, 8 x 8, or 68 blocks. We placed two circles around the ONH; the ONH had to fit into the smaller circle, and the larger circle had to fit into the segmentable part of the volume. The area between the circles was divided in 3 to 12 segments. We determined the test-retest variability (coefficient of repeatability) of the retinal nerve fiber layer (RNFL) and ganglion cell layer (RGCL) thickness measurements as a function of size of blocks/segments. RESULTS. Eighty-two percent of the macular volume could be segmented in at least 95% of subjects; for the ONH, this was 65% in at least 90%. The radii of the circles were 1.03 and 1.84 mm. Depending on the analyzed area, median test-retest variability ranged from 8% to 15% for macular RNFL, 11% to 22% for macular RGCL, 5% to 11% for the two together, and 18% to 22% for ONH RNFL. CONCLUSIONS. Test-retest variability hampers a detailed analysis of 3-D OCT data. Combined macular RNFL and RGCL thickness averaged over larger areas had the best test-retest variability. (Invest Ophthalmol Vis Sci. 2012; 53: 8162-8171) DOI:10.1167/iovs.12-10551 C1 [Springelkamp, Henriet; Ramdas, Wishal D.; Vingerling, Johannes R.; Klaver, Caroline C. W.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands. [Springelkamp, Henriet; Ramdas, Wishal D.; Vingerling, Johannes R.; Hofman, Albert; Klaver, Caroline C. W.; Jansonius, Nomdo M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Lee, Kyungmoo; Sonka, Milan; Abramoff, Michael D.] Univ Iowa, Dept Elect & Comp Engn, Iowa City, IA 52242 USA. [Abramoff, Michael D.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA. [Abramoff, Michael D.] Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA. [Abramoff, Michael D.] US Dept Vet Affairs, Iowa City, IA USA. [Jansonius, Nomdo M.] Univ Groningen, Univ Med Ctr Groningen, Dept Ophthalmol, Groningen, Netherlands. RP Abramoff, MD (reprint author), Univ Iowa Hosp & Clin, Dept Ophthalmol & Visual Sci PFP 11205, Iowa City, IA 52242 USA. EM michael-abramoff@uiowa.edu RI Klaver, Caroline/A-2013-2016 FU Rotterdam: Stichting Lijf en Leven, Krimpen aan de Lek, The Netherlands; MD Fonds, Utrecht, The Netherlands; Rotterdamse Vereniging Blindenbelangen, Rotterdam, The Netherlands; Stichting Oogfonds Nederland, Utrecht, The Netherlands; Blindenpenning, Amsterdam, The Netherlands; Blindenhulp, The Hague, The Netherlands; Algemene Nederlandse Vereniging ter Voorkoming van Blindheid (ANVVB), Doorn, The Netherlands; Landelijke Stichting voor Blinden en Slechtzienden, Utrecht, The Netherlands; Swart van Essen, Rotterdam, The Netherlands; Stichting Winckel-Sweep, Utrecht, The Netherlands; Henkes Stichting, Rotterdam, The Netherlands; Lameris Ootech BV, Nieuwegein, The Netherlands; Medical Workshop, de Meern, The Netherlands; Topcon Europe BV, Capelle aan de IJssel, The Netherlands; Heidelberg Engineering, Dossenheim, Germany; Iowa: National Institute of Health [EY019112] FX Supported by Rotterdam: Stichting Lijf en Leven, Krimpen aan de Lek; MD Fonds, Utrecht; Rotterdamse Vereniging Blindenbelangen, Rotterdam; Stichting Oogfonds Nederland, Utrecht; Blindenpenning, Amsterdam; Blindenhulp, The Hague; Algemene Nederlandse Vereniging ter Voorkoming van Blindheid (ANVVB), Doorn; Landelijke Stichting voor Blinden en Slechtzienden, Utrecht; Swart van Essen, Rotterdam; Stichting Winckel-Sweep, Utrecht; Henkes Stichting, Rotterdam; Lameris Ootech BV, Nieuwegein; Medical Workshop, de Meern; Topcon Europe BV, Capelle aan de IJssel; all in The Netherlands; and Heidelberg Engineering, Dossenheim, Germany; Iowa: National Institute of Health Grant EY019112. The authors alone are responsible for the content and writing of the paper. NR 40 TC 3 Z9 3 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2012 VL 53 IS 13 BP 8162 EP 8171 DI 10.1167/iovs.12-10551 PG 10 WC Ophthalmology SC Ophthalmology GA 064EX UT WOS:000313056000034 PM 23154462 ER PT J AU Mima, A Qi, W Hiraoka-Yamomoto, J Park, K Matsumoto, M Kitada, M Li, Q Mizutani, K Yu, E Shimada, T Lee, J Shoelson, SE Jobin, C Rask-Madsen, C King, GL AF Mima, Akira Qi, Weier Hiraoka-Yamomoto, Junko Park, Kyoungmin Matsumoto, Motonobu Kitada, Munehiro Li, Qian Mizutani, Koji Yu, Edward Shimada, Takeshi Lee, Jongsoon Shoelson, Steven E. Jobin, Christian Rask-Madsen, Christian King, George L. TI Retinal Not Systemic Oxidative and Inflammatory Stress Correlated with VEGF Expression in Rodent Models of Insulin Resistance and Diabetes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; IMPAIRED GLUCOSE-TOLERANCE; NF-KAPPA-B; MACULAR EDEMA; IN-VIVO; RETINOPATHY; ACTIVATION; PERICYTES; NEOVASCULARIZATION; PERMEABILITY AB PURPOSE. To correlate changes between VEGF expression with systemic and retinal oxidative stress and inflammation in rodent models of obesity induced insulin resistance and diabetes. METHODS. Retinal VEGF mRNA and protein levels were assessed by RT-PCR and VEGF ELISA, respectively. Urinary 8-hydroxydeoxyguanosine (8-OHdG), blood levels of C-reactive protein (CRP), malondialdehyde (MDA), and CD11b/c positive cell ratio were used as systemic inflammatory markers. Retinal expression of Nox2, Nox4, and p47phox mRNA levels were measured as oxidative stress markers. TNF-alpha, inter-cellular adhesion molecule-1 (ICAM-1), IL1 beta, and activation of nuclear factor kappa B (NF-kappa B) were used as retinal inflammatory markers. RESULTS. Retinal VEGF mRNA and protein expression increased in Zucker diabetic fatty (ZDF(fa/fa)) rats and streptozotosin (STZ) induced diabetic Sprague-Dawley rats, after two months of disease, but not in Zucker fatty (ZF) rats. Systemic markers of oxidative stress and inflammation were elevated in insulin resistant and diabetic rats. Some oxidative stress and inflammatory markers (TNF-alpha, IL-6, ICAM-1, and IL1-beta) were upregulated in the retina of ZDF(fa/fa) and STZ diabetic rats after 4 months of disease. In contrast, activation of NF-kappa B in the retina was observed in high fat fed nondiabetic and diabetic cis-NF-kappa B-EGFP mice, ZF, ZDF(fa/fa), and STZ-induced diabetic rats. CONCLUSIONS. Only persistent hyperglycemia and diabetes increased retinal VEGF expression. Some markers of inflammation and oxidative stress were elevated in the retina and systemic circulation of obese and insulin resistant rodents with and without diabetes. Induction of VEGF and its associated retinal pathologies by diabetes requires chronic hyperglycemia and factors in addition to inflammation and oxidative stress. (Invest Ophthalmol Vis Sci. 2012; 53: 8424-8432) DOI: 10.1167/iovs.12-10207 C1 [King, George L.] Harvard Univ, Dianne Nunnally Hoppes Lab Diabet Complicat, Div Res, Joslin Diabet Ctr,Med Sch, Boston, MA 02215 USA. [Jobin, Christian] Univ N Carolina, Dept Med, Chapel Hill, NC USA. RP King, GL (reprint author), Harvard Univ, Dianne Nunnally Hoppes Lab Diabet Complicat, Div Res, Joslin Diabet Ctr,Med Sch, 1 Joslin Pl, Boston, MA 02215 USA. EM George.king@joslin.harvard.edu FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [DK053105, R01EY016150]; National Institutes of Health [EY018677]; Manpei Suzuki Diabetes Foundation; Kanzawa Medical Research Foundation; NOVARTIS Foundation, Japan; Diabetes Endocrinology Research Center [P30DK036836]; Juvenile Diabetes Research Foundation FX Supported by Grants DK053105 and R01EY016150 from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (GLK) and EY018677 from the National Institutes of Health (CRM), a Research Fellowship (Manpei Suzuki Diabetes Foundation, Kanzawa Medical Research Foundation, NOVARTIS Foundation, Japan [AM]), Diabetes Endocrinology Research Center (P30DK036836), and a Juvenile Diabetes Research Foundation Postdoctoral Fellowship (WQ). NR 40 TC 12 Z9 14 U1 1 U2 11 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2012 VL 53 IS 13 BP 8424 EP 8432 DI 10.1167/iovs.12-10207 PG 9 WC Ophthalmology SC Ophthalmology GA 064EX UT WOS:000313056000066 PM 23197686 ER PT J AU Perry, LP Jakobiec, FA Zakka, FR Walton, DS AF Perry, Lynn P. Jakobiec, Frederick A. Zakka, Fouad R. Walton, David S. TI Newborn primary congenital glaucoma: Histopathologic features of the anterior chamber filtration angle SO JOURNAL OF AAPOS LA English DT Article ID UPDATE AB We present histopathologic findings that have not been previously reported as associated with abnormalities of the anterior chamber angle underlying newborn primary congenital glaucoma as a distinct entity. The major histopathologic findings were partial absence and retrodisplacement of Schlemm's canal, hypoplasia of the trabecular meshwork, broad attachment of ciliary muscle to the meshwork, and anterior insertion of hypoplastic iris with the formation of a pseudomembrane. These profound anatomic derangements explain why goniosurgery is frequently unsuccessful in cases of newborn glaucoma. C1 [Jakobiec, Frederick A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Perry, Lynn P.; Jakobiec, Frederick A.; Zakka, Fouad R.; Walton, David S.] Harvard Univ, Dept Ophthalmol, Sch Med, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu FU Heed Foundation FX Supported in part by the Heed Foundation (LPP). NR 6 TC 6 Z9 6 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD DEC PY 2012 VL 16 IS 6 BP 565 EP 568 DI 10.1016/j.jaapos.2012.06.012 PG 4 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 059AM UT WOS:000312676800015 PM 23158552 ER PT J AU Lin, F Vance, DE Gleason, CE Heidrich, SM AF Lin, Feng Vance, David E. Gleason, Carey E. Heidrich, Susan M. TI Caring for Older Adults with Mild Cognitive Impairment An Update for Nurses SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Article ID MINI-MENTAL-STATE; OF-THE-LITERATURE; ALZHEIMERS-DISEASE; INSTRUMENTAL ACTIVITIES; NEUROPSYCHIATRIC SYMPTOMS; SIGNIFICANT OTHERS; PHYSICAL-ACTIVITY; GROUP-THERAPY; RATING-SCALE; DEMENTIA AB Mild cognitive impairment (MCI) is a mild decline in single or multiple cognitive domains, while global cognition and basic activities of daily living remain intact. Nurses play an important role in early detection of MCI and providing care to maintain maximum independence for individuals with MCI. This article seeks to provide nurses with a review of the most recent research regarding the etiology and diagnosis of MCI, related risk and protective factors, patient and family experiences, and current interventions. This update provides research evidence to inform nursing practice of MCI care. C1 [Lin, Feng] Univ Rochester, Med Ctr, Sch Nursing, Rochester, NY 14642 USA. [Vance, David E.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. [Gleason, Carey E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Heidrich, Susan M.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Lin, F (reprint author), Univ Rochester, Med Ctr, Sch Nursing, HWH 2W128,601 Elmwood Ave, Rochester, NY 14642 USA. EM vankee_lin@urmc.rochester.edu OI Vance, David/0000-0002-0498-6263 FU NIA NIH HHS [P50 AG033514] NR 107 TC 1 Z9 1 U1 3 U2 13 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD DEC PY 2012 VL 38 IS 12 BP 22 EP 37 DI 10.3928/00989134-20121112-99 PG 19 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 064AQ UT WOS:000313043700006 PM 23189995 ER PT J AU Turiano, NA Hill, PL Roberts, BW Spiro, A Mroczek, DK AF Turiano, Nicholas A. Hill, Patrick L. Roberts, Brent W. Spiro, Avron, III Mroczek, Daniel K. TI Smoking mediates the effect of conscientiousness on mortality: The Veterans Affairs Normative Aging Study SO JOURNAL OF RESEARCH IN PERSONALITY LA English DT Article DE Personality; Conscientiousness; Mortality; Longevity; Smoking; Mediation ID ALL-CAUSE MORTALITY; PERSONALITY-TRAITS; SOCIOECONOMIC-STATUS; PROSPECTIVE COHORT; OLDER MEN; LIFE-SPAN; HEALTH; LONGEVITY; PREDICTORS; MECHANISMS AB This study examined the relationship between conscientiousness and mortality over 18 years and whether smoking behavior mediated this relationship. We utilized data from the Veterans Affairs Normative Aging Study on 1349 men who completed the Goldberg (1992) adjectival markers of the Big Five. Over the 18-year follow-up, 547 (41%) participants died. Through proportional hazards modeling in a structural equation modeling framework, we found that higher levels of conscientiousness significantly predicted longer life, and that this effect was mediated by current smoking status at baseline. Methodologically, we also demonstrate the effectiveness of using a structural equation modeling framework to evaluate mediation when using a censored outcome such as mortality. (C) 2012 Elsevier Inc. All rights reserved. C1 [Turiano, Nicholas A.] Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY 14642 USA. [Turiano, Nicholas A.; Mroczek, Daniel K.] Ctr Aging & Life Course, W Lafayette, IN USA. [Hill, Patrick L.; Roberts, Brent W.] Univ Illinois, Dept Psychol, Champaign, IL USA. [Spiro, Avron, III] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Med, Boston, MA 02118 USA. [Spiro, Avron, III] Boston Univ, Sch Dent Med, Boston, MA 02118 USA. [Mroczek, Daniel K.] Purdue Univ, Dept Human Dev & Family Studies, W Lafayette, IN 47907 USA. RP Turiano, NA (reprint author), 300 Crittenden Blvd,Box Psych, Rochester, NY 14642 USA. EM nicholas_turiano@urmc.rochester.edu; phill1@illinois.edu; broberts@cyrus.psych.illinois.edu; aspiro3@bu.edu; dmroczek@purdue.edu FU NIA NIH HHS [T32 AG025671, R01 AG018436, R01 AG021178]; NIMH NIH HHS [T32 MH018911] NR 48 TC 8 Z9 8 U1 3 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0092-6566 J9 J RES PERS JI J. Res. Pers. PD DEC PY 2012 VL 46 IS 6 BP 719 EP 724 DI 10.1016/j.jrp.2012.08.009 PG 6 WC Psychology, Social SC Psychology GA 058IA UT WOS:000312626100010 PM 23504043 ER PT J AU Van der Wilden, G Albers, C Haefeli, P Zimmerman, H Exadaktylos, A Levy, P Birkham, O Michailidou, M Sideris, A Velmahos, G Alam, H King, D Fagenholz, P Yeh, D de Moya, MA Inaba, K AF Van der Wilden, Gwen Albers, Christof Haefeli, Peter Zimmerman, Heinz Exadaktylos, Aris Levy, Phillip Birkham, Oscar Michailidou, Maria Sideris, Antonios Velmahos, George Alam, Hasan King, David Fagenholz, Peter Yeh, Dante de Moya, Marc A. Inaba, Kenji TI Using micropower impulse radar technology to screen for pneumothorax: An international bi-institutional study SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Western-Trauma-Association CY FEB 26-MAR 03, 2012 CL Vail, CO SP Western Trauma Assoc DE Pneumothorax; micropower impulse radar; trauma ID BLUNT CHEST TRAUMA; COMPUTED-TOMOGRAPHY; THORACIC ULTRASOUND; BEDSIDE ULTRASOUND; RADIOGRAPHY; ULTRASONOGRAPHY; SENSITIVITY; DIAGNOSIS AB BACKGROUND: Pneumothoraces (PTXs) are a common entity in thoracic trauma. Micropower impulse radar (MIR) has been able to detect PTXs in surgical patients. However, this technology has not been tested previously on trauma patients. The purpose of this study was to determine the sensitivity and specificity of MIR to detect clinically significant PTXs. We hypothesized that MIR technology can effectively screen trauma patients for clinically significant PTXs. METHODS: This was a prospective observational study in Level I trauma centers in Boston, Massachusetts, and Bern, Switzerland. All trauma patients undergoing a chest computed tomographic (CT) scan were eligible for the study. Consent was obtained, and readings were performed within 30 minutes before or after the CT scan. The patients had eight lung fields tested (four on each side). The qualitative and quantitative MIR results were blinded and stored on the device. We then compared the results of the MIR to the CT scan and the need for chest tube drainage. We defined PTXs as clinically significant if they required a chest tube. RESULTS: Seventy-five patients were enrolled, with a mean age of 46 +/- 16 years. Eighty-four percent were male. The screening test took approximately 1 minute. All but two patients had blunt chest trauma. Six true-positives, 6 false-positives, 63 true-negatives, and 0 false-negatives resulted in an overall sensitivity of 100%. CONCLUSION: MIR is an easy to use handheld technology that effectively screened patients for clinically significant PTXs, with a sensitivity and negative predictive value of 100%. MIR may be used for rapid, repeatable, and ongoing surveillance of trauma patients. (J Trauma Acute Care Surg. 2012;73: 1418-1422. Copyright (C) 2012 by Lippincott Williams & Wilkins) C1 [Van der Wilden, Gwen; Birkham, Oscar; Michailidou, Maria; Sideris, Antonios; Velmahos, George; Alam, Hasan; King, David; Fagenholz, Peter; Yeh, Dante; de Moya, Marc A.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Van der Wilden, Gwen; Birkham, Oscar; Michailidou, Maria; Sideris, Antonios; Velmahos, George; Alam, Hasan; King, David; Fagenholz, Peter; Yeh, Dante; de Moya, Marc A.] Harvard Univ, Sch Med, Boston, MA USA. [Albers, Christof; Haefeli, Peter; Zimmerman, Heinz; Exadaktylos, Aris] Univ Hosp Bern, Dept Emergency Med, CH-3010 Bern, Switzerland. [Albers, Christof; Haefeli, Peter; Zimmerman, Heinz; Exadaktylos, Aris] Univ Bern, Bern, Switzerland. [Inaba, Kenji] Univ So Calif, Div Trauma & Crit Care, Los Angeles, CA USA. RP de Moya, MA (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM mdemoya@partners.org RI Albers, Christoph/B-3529-2013; OI King, David/0000-0003-1028-1478 NR 22 TC 1 Z9 1 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD DEC PY 2012 VL 73 IS 6 BP 1418 EP 1422 DI 10.1097/TA.0b013e318270bbe4 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 058FV UT WOS:000312620400010 PM 23188233 ER PT J AU Jin, G Duggan, M Imam, A deMoya, MA Sillesen, M Hwabejire, J Jepsen, CH Liu, BL Mejaddam, AY Lu, J Smith, WM Velmahos, GC Socrate, S Alam, HB AF Jin, Guang Duggan, Michael Imam, Ayesha deMoya, Marc A. Sillesen, Martin Hwabejire, John Jepsen, Cecilie H. Liu, Baoling Mejaddam, Ali Y. Lu, Jennifer Smith, William Michael Velmahos, George C. Socrate, Simona Alam, Hasan B. TI Pharmacologic resuscitation for hemorrhagic shock combined with traumatic brain injury SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Western-Trauma-Association CY FEB 26-MAR 03, 2012 CL Vail, CO SP Western Trauma Assoc DE Brain; trauma; resuscitation; valproic acid; swine ID FOCAL CEREBRAL-ISCHEMIA; HISTONE DEACETYLASE INHIBITION; INDUCED NEURONAL APOPTOSIS; VALPROIC ACID; HEAD-INJURY; FLUID RESUSCITATION; INTRACRANIAL-PRESSURE; ADHESION MOLECULES; MODEL; ACTIVATION AB BACKGROUND: We have previously demonstrated that valproic acid (VPA), a histone deacetylase inhibitor, can improve survival after hemorrhagic shock (HS), protect neurons from hypoxia-induced apoptosis, and attenuate the inflammatory response. We have also shown that administration of 6% hetastarch (Hextend [Hex]) after traumatic brain injury (TBI) decreases brain swelling, without affecting size of the lesion. This study was performed to determine whether addition of VPA to flex would decrease the lesion size in a clinically relevant large animal model of TBI + HS. METHODS: Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. A custom-designed, computer-controlled cortical impact device was used to create a TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4-m/s velocity, 100-millisecond dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was started (40% blood volume) concurrent with the TBI. After 2 hours of shock, animals were randomized to one of three resuscitation groups (n = 7 per group) as follows: (1) isotonic sodium chloride solution; (2) 6% hetastarch, Hex; and (3) Hex and VPA 300 mg/kg (Hex + VPA). Volumes of Hex matched the shed blood, whereas that of the isotonic sodium chloride solution was three times the volume. VPA treatment was started after an hour of shock. After 6 hours of postresuscitation monitoring, brains were sectioned into 5-mm slices and stained with 2, 3, 5-Triphenyltetrazolium chloride to quantify the lesion size (mm(3)) and brain swelling (percent change compared with uninjured side). Levels of acetylated histone H3 were determined to quantify acetylation, and myeloperoxidase and interleuldne-1 beta (IL-1 beta) levels were measured as markers of brain inflammation. RESULTS:. Combination of 40% blood loss with cortical impact and a period of shock (2 hours) and resuscitation resulted in a highly reproducible brain injury. Lesion size and brain swelling in the Hex + VPA group (1,989 [156.8] mm(3), and 19% [1.6%], respectively) were significantly smaller than the isotonic sodium chloride solution group (3,335 [287.9] mm(3) and 36% [2.2%], respectively). Hex alone treatment significantly decreased the swelling (27% [1.6%]) without reducing the lesion size. The number of CD11b-positive cells as well as myeloperoxidase and IL-1 levels in the brains were significantly reduced by the VPA treatment. CONCLUSION: In a combined HS and TBI model, treatment with artificial colloid (Hex) improves hemodynamic parameters and reduces swelling, without affecting the actual size of the brain lesion. Addition of VPA effectively reduces both the size of brain lesion and associated swelling by attenuating the inflammatory response. (J Trauma Acute Care Surg. 2012;73: 1461-1470. Copyright (C) 2012 by Lippincott Williams & Wilkins) C1 [Alam, Hasan B.] Univ Michigan Hosp, Taubman Ctr 2920, Dept Surg, Ann Arbor, MI 48109 USA. [Jin, Guang; Duggan, Michael; Imam, Ayesha; deMoya, Marc A.; Hwabejire, John; Jepsen, Cecilie H.; Liu, Baoling; Mejaddam, Ali Y.; Lu, Jennifer; Smith, William Michael; Velmahos, George C.; Alam, Hasan B.] Harvard Univ, Sch Med, Dept Surg,Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02115 USA. [Socrate, Simona] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Alam, HB (reprint author), Univ Michigan Hosp, Taubman Ctr 2920, Dept Surg, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu NR 53 TC 24 Z9 24 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD DEC PY 2012 VL 73 IS 6 BP 1461 EP 1470 DI 10.1097/TA.0b013e3182782641 PG 10 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 058FV UT WOS:000312620400017 PM 23188239 ER PT J AU Schneider, JC Gerrard, P Goldstein, R DiVita, MA Niewczyk, P Ryan, CM Tan, WH Kowalske, K Zafonte, R AF Schneider, Jeffrey C. Gerrard, Paul Goldstein, Richard DiVita, Margaret A. Niewczyk, Paulette Ryan, Colleen M. Tan, Wei-Han Kowalske, Karen Zafonte, Ross TI Predictors of transfer from rehabilitation to acute care in burn injuries SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Burn injury; rehabilitation; risk factors; complications; outcomes ID RISK-FACTORS; HOSPITAL READMISSION; INPATIENT REHABILITATION; STROKE REHABILITATION; 30-DAY READMISSION; ADULT PATIENTS; HEART-FAILURE; DEATH; MORTALITY; OUTCOMES AB BACKGROUND: Transfer to acute care from rehabilitation represents an interruption in a patient's recovery and a potential deficiency in quality of care. The objective of this study was to examine predictors of transfer to acute care in the inpatient burn rehabilitation population. METHODS: Data are obtained from Uniform Data System for Medical Rehabilitation from 2002 to 2010 for patients with a primary diagnosis of burn injury. Predictor variables include demographic, medical, and facility data. Descriptive statistics are calculated for acute and nonacute transfer patients. Logistic regression analysis is used to determine significant predictors of acute transfer within the first 3 days. A scoring system is developed to determine the risk of acute transfer. RESULTS: There were 78 acute transfers in the first 3 days of a total of 4,572 burn admissions. Functional level at admission, age, and admission classification are significant predictors of transfer to acute care (p < 0.05). Total body surface area burned and medical comorbidities were not significantly associated with acute transfer risk. A 12-point acute transfer risk scoring system was developed, which demonstrates validity. CONCLUSION: Efforts to reduce readmissions to acute care should include greater scrutiny of older, lower-functioning patients with burn injury who are evaluated for admission to inpatient rehabilitation. This acute transfer scoring system may be useful to clinicians, health care institutions, and policymakers to help predict those patients at highest risk for early transfer to the acute hospital from rehabilitation. (J Trauma Acute Care Surg. 2012;73: 1596-1601. Copyright (c) 2012 by Lippincott Williams & Wilkins) C1 [Schneider, Jeffrey C.; Gerrard, Paul; Goldstein, Richard; Tan, Wei-Han; Zafonte, Ross] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Ryan, Colleen M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv,Sumner Redstone Burn Ctr, Boston, MA USA. [Ryan, Colleen M.] Shriners Hosp Children, Boston, MA USA. [DiVita, Margaret A.; Niewczyk, Paulette] Daemen Coll, Uniform Data Syst Med Rehabil, Amherst, NY USA. [Niewczyk, Paulette] Daemen Coll, Dept Hlth Care Studies, Amherst, NY USA. [Kowalske, Karen] Univ Texas SW Med Ctr Dallas, Dept Phys Med & Rehabil, Dallas, TX 75390 USA. RP Schneider, JC (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. EM jcschneider@partners.org OI Gerrard, Paul/0000-0003-0654-5354; DiVita, Margaret/0000-0002-4878-2959 NR 30 TC 17 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD DEC PY 2012 VL 73 IS 6 BP 1596 EP 1601 DI 10.1097/TA.0b013e318270d73d PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 058FV UT WOS:000312620400037 PM 23188249 ER PT J AU Orman, JA Geyer, D Jones, J Schneider, EB Grafman, J Pugh, MJ DuBose, J AF Orman, Jean A. Geyer, Dennis Jones, John Schneider, Eric B. Grafman, Jordan Pugh, Mary Jo DuBose, Joseph TI Epidemiology of moderate-to-severe penetrating versus closed traumatic brain injury in the Iraq and Afghanistan wars SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Traumatic and penetrating brain injury; military; epidemiology; Operation Enduring Freedom/Iraqi Freedom; Operation New Dawn ID COMBAT WOUNDS; FREEDOM; HOSPITALIZATIONS; BATTLEFIELD AB BACKGROUND: US combat operations in Iraq and Afghanistan have resulted in a greater proportion of service members with head and neck wounds caused by explosions compared with that of previous wars. Although penetrating traumatic brain injury (TBI) is frequently associated with these wounds, the epidemiology of penetrating TBI from these conflicts has not been well described. METHODS: The Joint Theater Trauma Registry was queried for January 2003 through December 2010 to identify all patients with moderate-to-severe brain injury with a maximum Abbreviated Injury Scale (AIS) score of the head of 3 or greater and a diagnosis of penetrating or closed TBI in accordance with the Department of Defense Traumatic Brain Injury Surveillance definition. The epidemiology of these injuries was examined, including demographics, TBI severity, overall injury severity, and surgical interventions provided. RESULTS: A total of 1,255 TBI patients (774 penetrating, 481 closed) meeting criteria were identified. Penetrating brain injuries were more severe, more likely to be battle related, and less likely to be isolated injuries than a group of moderate-to-severe closed TBIs within the same range of anatomic injury severity. During the 5-year period of the Iraq war with the largest numbers of TBIs (2004-2008), the numbers of penetrating TBIs exceeded closed TBIs by a ratio of 2:1. During the 3-year period of the Afghanistan war with the greatest numbers of TBIs (2008-2010), the ratio of penetrating to closed TBIs was substantially lower, approximately 1.3:1. CONCLUSION: This study represents the first comprehensive report on the epidemiology of moderate-to-severe penetrating and closed TBIs resulting from the wars in Iraq and Afghanistan using Joint Theater Trauma Registry data. With the maturing theater of conflicts, penetrating TBIs were substantially less predominant compared with closed TBIs. While this finding may reflect changes in the use of protective measures and tactics or improvements in diagnosis of closed TBIs, additional research is needed to identify the reason for this shift and the subsequent effect on outcome after combat-related TBIs. (J Trauma Acute Care Surg. 2012;73: S496-S502. Copyright (C) 2012 by Lippincott Williams & Wilkins) C1 [Orman, Jean A.] USA, Inst Surg Res, ATTN MCMR SRR, Ft Sam Houston, TX 78234 USA. [Orman, Jean A.; Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Geyer, Dennis] San Antonio Mil Med Ctr, Dept Surg, Neurosurg Serv, San Antonio, TX USA. [Pugh, Mary Jo] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Schneider, Eric B.] Johns Hopkins Sch Med, Ctr Surg Trials & Outcomes Res, Baltimore, MD USA. [DuBose, Joseph] Univ Maryland Med Syst, R Adams Cowley Shock Trauma Ctr, Baltimore, MD USA. [Jones, John] Northwestern Univ, Rehabil Inst Chicago, Chicago, IL 60611 USA. [Grafman, Jordan] Northwestern Univ, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. RP Orman, JA (reprint author), USA, Inst Surg Res, ATTN MCMR SRR, 3698 Chambers Pass, Ft Sam Houston, TX 78234 USA. EM Jean.A.Orman@amedd.army.mil OI Grafman, Jordan H./0000-0001-8645-4457; Pugh, Mary Jo/0000-0003-4196-7763 FU South Texas Veterans Healthcare System FX We acknowledge JTTR for providing data for this study and Ms. Susan West and Ms. Celina Garcia of the JTTR staff for their invaluable assistance in preparing the data set. Some work for this study was supported by resources of the South Texas Veterans Healthcare System. NR 38 TC 8 Z9 9 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD DEC PY 2012 VL 73 SU 5 BP S496 EP S502 DI 10.1097/TA.0b013e318275473c PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 056QT UT WOS:000312506900020 PM 23192076 ER PT J AU Tsai, J Rosenheck, RA Decker, SE Desai, RA Harpaz-Rotem, I AF Tsai, Jack Rosenheck, Robert A. Decker, Suzanne E. Desai, Rani A. Harpaz-Rotem, Ilan TI Trauma Experience Among Homeless Female Veterans: Correlates and Impact on Housing, Clinical, and Psychosocial Outcomes SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MILITARY SEXUAL TRAUMA; WOMEN VETERANS; COOCCURRING DISORDERS; SUBSTANCE-ABUSE; MENTAL-HEALTH; RISK-FACTORS; VICTIMIZATION; ASSOCIATION; THERAPY AB This study examined lifetime exposure to traumatic events as reported by 581 homeless female veterans enrolled in a Homeless Women Veterans Program across 11 sites to characterize the types of trauma they experienced; their correlation with baseline characteristics; and their association with housing, clinical outcomes, and psychosocial functioning over a 1-year treatment period. Almost all participants endorsed multiple types and episodes of traumatic events. Among the most common were having someone close experience a serious or life-threatening illness (82%) and rape (67%). Exploratory factor analysis revealed 6 potential trauma categories: being robbed, experiencing accident or disasters, illness or death of others, combat, sexual assault, and physical assault. At baseline, trauma from sexual assault was associated with more days homeless (beta = .18, p < .001), trauma from accidents or disasters was associated with poorer physical health (beta = -.23, p < .001), and trauma from being robbed was related to greater use of drugs (beta = .22, p < .001). Trauma reported at baseline, however, was not predictive of 1-year outcomes, suggesting type and frequency of trauma does not negatively affect the housing gains homeless women veterans can achieve through homeless services. C1 [Tsai, Jack; Rosenheck, Robert A.; Decker, Suzanne E.; Harpaz-Rotem, Ilan] Vet Affairs New England Mental Illness, Res Educ & Clin Ctr, West Haven, CT USA. [Tsai, Jack; Rosenheck, Robert A.; Decker, Suzanne E.; Desai, Rani A.; Harpaz-Rotem, Ilan] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Rosenheck, Robert A.; Desai, Rani A.] Yale Univ, Sch Epidemiol & Publ Hlth, New Haven, CT USA. [Desai, Rani A.] US Dept Vet Affairs, NE Program Evaluat Ctr, West Haven, CT USA. [Harpaz-Rotem, Ilan] VA Connecticut Healthcare Syst, Clin Neurosci Div, Natl Ctr Posttraumat Stress Disorder, West Haven, CT USA. RP Tsai, J (reprint author), VACT, 950 Campbell Ave,151D, West Haven, CT 06516 USA. EM Jack.Tsai@yale.edu RI Tsai, Jack/D-3889-2013; OI Tsai, Jack/0000-0002-0329-648X NR 37 TC 4 Z9 4 U1 3 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2012 VL 25 IS 6 BP 624 EP 632 DI 10.1002/jts.21750 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 051TW UT WOS:000312151400003 PM 23225030 ER PT J AU Haak, CS Farinelli, WA Tam, J Doukas, AG Anderson, RR Haedersdal, M AF Haak, Christina S. Farinelli, William A. Tam, Joshua Doukas, Apostolos G. Anderson, R. Rox Haedersdal, Merete TI Fractional laser-assisted delivery of methyl aminolevulinate: Impact of laser channel depth and incubation time SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE drug delivery; fractional CO2 laser; photosensitizer ID BASAL-CELL CARCINOMA; NONMELANOMA SKIN-CANCER; PHOTODYNAMIC THERAPY; ENDOGENOUS PROTOPORPHYRIN; PROSPECTIVE TRIAL; GUIDELINES; PHOTOTHERMOLYSIS; MULTICENTER; SURGERY; UPDATE AB Background and Objectives Pretreatment of skin with ablative fractional lasers (AFXL) enhances the uptake of topical photosensitizers used in photodynamic therapy (PDT). Distribution of photosensitizer into skin layers may depend on depth of laser channels and incubation time. This study evaluates whether depth of intradermal laser channels and incubation time may affect AFXL-assisted delivery of methyl aminolevulinate (MAL). Materials and Methods Yorkshire swine were treated with CO2 AFXL at energy levels of 37, 190, and 380?mJ/laser channel and subsequent application of MAL cream (Metvix (R)) for 30, 60, 120, and 180?minutes incubation time. Fluorescence photography and fluorescence microscopy quantified MAL-induced porphyrin fluorescence (PpIX) at the skin surface and at five specific skin depths (120, 500, 1,000, 1,500, and 1,800?mu m). Results Laser channels penetrated into superficial (similar to 300?mu m), mid (similar to 1,400?mu m), and deep dermis/upper subcutaneous fat layer (similar to 2,100?mu m). Similar fluorescence intensities were induced at the skin surface and throughout skin layers independent of laser channel depth (180?minutes; P?-/- mice, George Washington and the COBRE Animal Pathobiology Core, as well as Margaret H. Romano and the Core Histology Laboratory at MUSC for their technical assistance. NR 43 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-8823 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD DEC PY 2012 VL 99 IS 3-4 BP 124 EP 130 DI 10.1016/j.prostaglandins.2012.08.003 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 056SN UT WOS:000312511800008 PM 22940715 ER PT J AU Schouten, R AF Schouten, Ronald TI Psychiatric Consultation in Problem Employee Situations SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Occupational psychiatry; Americans with Disabilities Act; Violence risk assessment; Fitness for duty evaluations; Workplace violence; Disability discrimination ID EXPERT WITNESS; CLINICIAN; VIOLENCE AB This article focuses on psychiatric consultation in "problem employee situations," a broad term that refers to any situation in which there is conflict between an employee and the employer or coworkers. It summarizes key principles and observations that are common to psychiatric consultations in the workplace and then offers case examples that are representative of such consultations and highlights those principles. Although the focus is on psychiatric consultation to employers, an employee may seek consultation himself or herself, especially when prospects for adversarial proceedings arise. The principles described here apply in both sets of circumstances. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Law & Psychiat Serv, Boston, MA 02114 USA. RP Schouten, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Law & Psychiat Serv, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM rschouten@partners.org NR 13 TC 0 Z9 0 U1 1 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 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2012 VL 35 IS 4 BP 901 EP + DI 10.1016/j.psc.2012.08.010 PG 15 WC Psychiatry SC Psychiatry GA 058FE UT WOS:000312618700009 PM 23107569 ER PT J AU Simpson, TL Stappenbeck, CA Varra, AA Moore, SA Kaysen, D AF Simpson, Tracy L. Stappenbeck, Cynthia A. Varra, Alethea A. Moore, Sally A. Kaysen, Debra TI Symptoms of Posttraumatic Stress Predict Craving Among Alcohol Treatment Seekers: Results of a Daily Monitoring Study SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE alcohol craving; PTSD; daily monitoring; self-medication hypothesis ID ECOLOGICAL MOMENTARY ASSESSMENT; SUBSTANCE USE DISORDERS; TIMELINE FOLLOW BACK; PTSD CHECKLIST; CUE REACTIVITY; PSYCHOMETRIC PROPERTIES; DRINKING PATTERNS; FEMALE VETERANS; NEGATIVE AFFECT; SEXUAL ASSAULT AB Alcohol use disorders (AUDs) and Posttraumatic Stress Disorder (PTSD) commonly co-occur. Craving for alcohol is a common aspect of AUD, with and without PTSD, and is one of the key predictors of continued problematic alcohol use among treatment seekers. The present study sought to investigate the self-medication hypothesis using daily Interactive Voice Response (IVR) reports to examine the relationships between PTSD symptomatology and both same-day and next-day alcohol craving. Twenty-nine individuals with an AUD (26 of whom screened positive for PTSD) entering AUD treatment provided daily IVR data for up to 28 days regarding their alcohol use, craving, and 7 symptoms of PTSD. Given the nested nature of daily data, generalized estimating equations using a negative binomial distribution and a log link function were used to test hypotheses. Results suggest that days with greater overall PTSD severity are associated with greater alcohol craving, and greater reports of startle and anger/irritability were particularly associated with same-day craving. The next-day results suggest that the combination of the 7 PTSD symptoms did not predict next-day craving. However, greater distress from nightmares the previous night, emotional numbing, and hypervigilance predicted greater next-day craving, while greater anger/irritability predicted lower next-day craving. These findings highlight the importance of assessing the relationship between specific symptoms of PTSD and alcohol cravings in order to increase our understanding of the functional interplay among them for theory building. Additionally, clinicians may be better able to refine treatment decisions to more efficiently break the cycle between PTSD-related distress and AUD symptoms. C1 [Simpson, Tracy L.; Stappenbeck, Cynthia A.; Varra, Alethea A.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Simpson, Tracy L.; Varra, Alethea A.; Moore, Sally A.; Kaysen, Debra] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Moore, Sally A.] Evidence Based Treatment Ctr Seattle PLLC, Seattle, WA USA. RP Simpson, TL (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Tracy.Simpson@va.gov NR 70 TC 22 Z9 22 U1 4 U2 16 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X EI 1939-1501 J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD DEC PY 2012 VL 26 IS 4 BP 724 EP 733 DI 10.1037/a0027169 PG 10 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 059CM UT WOS:000312682000005 PM 22369221 ER PT J AU Berbeco, RI Korideck, H Ngwa, W Kumar, R Patel, J Sridhar, S Johnson, S Price, BD Kimmelman, A Makrigiorgos, GM AF Berbeco, Ross I. Korideck, Houari Ngwa, Wilfred Kumar, Rajiv Patel, Janki Sridhar, Srinivas Johnson, Sarah Price, Brendan D. Kimmelman, Alec Makrigiorgos, G. Mike TI DNA Damage Enhancement from Gold Nanoparticles for Clinical MV Photon Beams SO RADIATION RESEARCH LA English DT Article ID TARGETED DRUG-DELIVERY; DOSE ENHANCEMENT; RADIATION-THERAPY; PLATFORM AB Berbeco, R. I., Korideck, H., Ngwa, W., Kumar, R., Patel, J., Sridhar, S., Johnson, S., Price, B. D., Kimmelman, A. and Makrigiorgos, G. M. DNA Damage Enhancement from Gold Nanoparticles for Clinical MV Photon Beams. Radiat. Res. 178, 604-608 (2012). In this study, we quantify the relative damage enhancement due to the presence of gold nanoparticles (GNP) in vitro in a clinical 6 MV beam for various delivery parameters and depths. It is expected that depths and delivery modes that produce a larger proportions of low-energy photons will have a larger effect on the cell samples containing GNP. HeLa cells with and without 50 nm GNP were irradiated at depths of 1.5, 5, 10, 15 and 20 cm. Conventional beams with square aperture sizes 5, 10 and 15 cm at isocenter, and flattening filter free (FFF) beams were used. Relative DNA damage enhancement with GNP was evaluated by gamma-H2AX staining. Statistically significant increases in DNA damage with GNP, compared to the absence of GNP, were observed for all depths and delivery modes. Relative to the shallowest depth, damage enhancement was observed to increase as a function of increasing depth for all deliveries. For the conventional (open field) delivery, DNA damage enhancement with GNP was seen to increase as a function of field size. For FFF delivery, a substantial increase in enhancement was found relative to the conventional field delivery. The measured relative DNA damage enhancement validates the theoretically predicted trends as a function of depth and delivery mode for clinical MV photon beams. The results of this study open new possibilities for the clinical development of gold nanoparticle-aided radiation therapy. (c) 2012 by Radiation Research Society C1 [Berbeco, Ross I.; Korideck, Houari; Ngwa, Wilfred; Kimmelman, Alec; Makrigiorgos, G. Mike] Brigham & Womens Hosp, Dept Radiat Oncol, Div Med Phys & Biophys, Dana Farber Canc Inst, Boston, MA 02115 USA. [Berbeco, Ross I.; Korideck, Houari; Ngwa, Wilfred; Johnson, Sarah; Price, Brendan D.; Kimmelman, Alec; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Boston, MA USA. [Kumar, Rajiv; Patel, Janki; Sridhar, Srinivas] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Johnson, Sarah; Price, Brendan D.] Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Instabil & DNA Repair, Boston, MA 02115 USA. RP Berbeco, RI (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Div Med Phys & Biophys, Dana Farber Canc Inst, 75 Francis St,ASBI-L2, Boston, MA 02115 USA. EM rberbeco@lroc.harvard.edu FU BWH Biomedical Research Institute; NTH grant [CA93602] FX The authors would like to thank Buford J. Maddox and Cliff Miner for assistance with the flattening filter free delivery on the clinical linear accelerator. This project was supported, in part, by a grant from the BWH Biomedical Research Institute and by NTH grant CA93602 to BDP. NR 26 TC 26 Z9 28 U1 0 U2 20 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2012 VL 178 IS 6 BP 604 EP 608 DI 10.1667/RR3001.1 PG 5 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 060AV UT WOS:000312748900011 PM 23148509 ER PT J AU Shuja, F Kwolek, CJ AF Shuja, Fahad Kwolek, Christopher J. TI Treating the Paravisceral Aorta with Parallel Endografts (Chimneys and Snorkels) SO SEMINARS IN VASCULAR SURGERY LA English DT Article ID ENDOVASCULAR ANEURYSM REPAIR; BRANCH VESSELS; GRAFT; PATHOLOGIES; EXPERIENCE; OUTCOMES; PATENCY; COMPLEX; STENTS; TRIAL AB While excellent results can be achieved with the open repair of juxtarenal and suprarenal aortic aneurysms in good-risk patients, the outcomes in high-risk patients are less favorable. The use of standard infrarenal endografts to treat these patients has been limited due to the absence of a suitable proximal landing zone. Using infrarenal endografts outside the instructions for use has been shown to lead to poorer outcomes with a higher incidence of type I endoleaks and graft migration. Fenestrated and branched endografts are viable options, but until recently have not been commercially available within the United States. In addition, they require meticulous preoperative planning and 4 to 6 weeks to manufacture. This makes them unsuitable for use in the urgent setting. Others have looked at the use of parallel covered stents placed alongside the main endograft body, the "chimney" or "snorkel" graft technique, to allow for continued perfusion to visceral/renal vessels. This technique allows for proximal placement of the landing zone of the main body, while maintaining blood flow to critical branches. The purpose of this article is to review the current literature on chimney grafts, their efficacy, and associated morbidity and mortality. Semin Vase Surg 25:200-202 (C) 2012 Published by Elsevier Inc. C1 [Shuja, Fahad; Kwolek, Christopher J.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Kwolek, CJ (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,WAC 442, Boston, MA 02114 USA. EM ckwolek@partners.org RI caicedo valdes, diego/I-1145-2012 NR 24 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0895-7967 J9 SEMIN VASC SURG JI Semin. Vasc. Surg. PD DEC PY 2012 VL 25 IS 4 BP 200 EP 202 DI 10.1053/j.semvascsurg.2012.09.005 PG 3 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 056RX UT WOS:000312510200005 PM 23206566 ER PT J AU Kushida, CA Nichols, DA Holmes, TH Quan, SF Walsh, JK Gottlieb, DJ Simon, RD Guilleminault, C White, DP Goodwin, JL Schweitzer, PK Leary, EB Hyde, PR Hirshkowitz, M Green, S McEvoy, LK Chan, C Gevins, A Kay, GG Bloch, DA Crabtree, T Dement, WC AF Kushida, Clete A. Nichols, Deborah A. Holmes, Tyson H. Quan, Stuart F. Walsh, James K. Gottlieb, Daniel J. Simon, Richard D., Jr. Guilleminault, Christian White, David P. Goodwin, James L. Schweitzer, Paula K. Leary, Eileen B. Hyde, Pamela R. Hirshkowitz, Max Green, Sylvan McEvoy, Linda K. Chan, Cynthia Gevins, Alan Kay, Gary G. Bloch, Daniel A. Crabtree, Tami Dement, William C. TI Effects of Continuous Positive Airway Pressure on Neurocognitive Function in Obstructive Sleep Apnea Patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) SO SLEEP LA English DT Article DE Obstructive sleep apnea; continuous positive airway pressure; neurocognitive function; randomized controlled trial; sleepiness ID PRINCIPAL COMPONENT ANALYSIS; NEUROPSYCHOLOGICAL DEFICITS; CLINICAL-TRIALS; APNEA/HYPOPNEA SYNDROME; BREATHING DISORDERS; COGNITIVE FUNCTION; PROPENSITY SCORE; CPAP THERAPY; PERFORMANCE; SELECTION AB Study Objective: To determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA). Design, Setting, and Participants: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S. university, hospital, or private practices. Of 1,516 participants enrolled, 1,105 were randomized, and 1,098 participants diagnosed with OSA contributed to the analysis of the primary outcome measures. Intervention: Active or sham CPAP Measurements: Three neurocognitive variables, each representing a neurocognitive domain: Pathfinder Number Test-Total Time (attention and psychomotor function [A/P]), Buschke Selective Reminding Test-Sum Recall (learning and memory [L/M]), and Sustained Working Memory Test-Overall Mid-Day Score (executive and frontal-lobe function [E/F]) Results: The primary neurocognitive analyses showed a difference between groups for only the E/F variable at the 2 month CPAP visit, but no difference at the 6 month CPAP visit or for the A/P or L/M variables at either the 2 or 6 month visits. When stratified by measures of OSA severity (AHI or oxygen saturation parameters), the primary E/F variable and one secondary E/F neurocognitive variable revealed transient differences between study arms for those with the most severe OSA. Participants in the active CPAP group had a significantly greater ability to remain awake whether measured subjectively by the Epworth Sleepiness Scale or objectively by the maintenance of wakefulness test. Conclusions: CPAP treatment improved both subjectively and objectively measured sleepiness, especially in individuals with severe OSA (AHI > 30). CPAP use resulted in mild, transient improvement in the most sensitive measures of executive and frontal-lobe function for those with severe disease, which suggests the existence of a complex OSA-neurocognitive relationship. C1 [Kushida, Clete A.; Nichols, Deborah A.; Holmes, Tyson H.; Guilleminault, Christian; Leary, Eileen B.; Hyde, Pamela R.; Bloch, Daniel A.; Dement, William C.] Stanford Univ, Stanford, CA 94305 USA. [Quan, Stuart F.; Goodwin, James L.; Green, Sylvan] Univ Arizona, Tucson, AZ USA. [Walsh, James K.; Schweitzer, Paula K.] St Lukes Hosp, Chesterfield, MO USA. [Gottlieb, Daniel J.] VA Boston Healthcare Syst, Boston, MA USA. [Quan, Stuart F.; Gottlieb, Daniel J.; White, David P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Simon, Richard D., Jr.] Providence St Mary Med Ctr, Walla Walla, WA USA. [Hirshkowitz, Max] VAMC Sleep Ctr, Houston, TX USA. [McEvoy, Linda K.] Univ Calif San Diego, San Diego, CA 92103 USA. [Chan, Cynthia; Gevins, Alan] SAM Technol Inc, San Francisco, CA USA. [Chan, Cynthia; Gevins, Alan] San Francisco Brain Res Inst, San Francisco, CA USA. [Kay, Gary G.] Georgetown Univ, Sch Med, Washington, DC USA. RP Kushida, CA (reprint author), Stanford Sleep Med Ctr, 450 Broadway St,MC 5704,Pavill C,2nd Floor, Redwood City, CA 94063 USA. EM clete@stanford.edu FU Respironics, Inc.; ResMed; Pacific Medico Co., Ltd.; Merck Co.; Cephalon; Ventus Medical; Jazz Pharmaceuticals; Respironics; Pfizer; Somnus; Vanda Pharmaceuticals; Neurogen; Sanofi-Aventis; Apnex; World Class CME; Apnex Medical; Merck Sharpe Dohme FX This study was funded by Respironics, Inc. Dr. Kushida received research support through Stanford University from ResMed, Pacific Medico Co., Ltd., Merck & Co., Cephalon, Ventus Medical, Jazz Pharmaceuticals, and Respironics. Dr. Walsh receives research support from Pfizer, Merck & Co., Somnus, Vanda Pharmaceuticals, Neurogen, Sanofi-Aventis, Ventus Medical, Respironics, Apnex, and Jazz Pharmaceuticals. He has consulted for Sanofi-Aventis, Respironics, Transcept, Neurogen, Glaxo-SmithKline, Eli Lilly, Merck & Co., Kingsdown, Vanda Pharmaceuticals, Ventus Medical, Vivus Inc., and Somnus Therapeutics, Inc. Dr. Simon has consulted for Asante Communications and has received sponsorship fees from World Class CME. Dr. White is the chief medical officer for Philips Respironics. Dr. Schweitzer has received research support from Apnex Medical, Merck Sharpe & Dohme, Vanda Pharmaceuticals, and Ventus Medical. She also serves on the speaker bureau for Somaxon Pharmaceuticals. Dr. Hirshkowitz serves on the speaker bureau for Cephalon and Somaxon Pharmaceuticals. Dr. Gevins is employed by Technology, Inc. Dr. Kay is the president of a contract research organization; clients in the last 12 months: Allergan, Arena, Factor Nutrition, Helicon, Merck & Co., Pfizer, Shire, Vivus Inc., and Watson. The other authors have indicated no financial conflicts of interest. NR 71 TC 80 Z9 81 U1 3 U2 16 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD DEC 1 PY 2012 VL 35 IS 12 BP 1593 EP U40 DI 10.5665/sleep.2226 PG 30 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063LO UT WOS:000313000600005 PM 23204602 ER PT J AU Jonker, MA Sauerhammer, TM Faucher, LD Schurr, MJ Kudsk, KA AF Jonker, Mark A. Sauerhammer, Tina M. Faucher, Lee D. Schurr, Michael J. Kudsk, Kenneth A. TI Bilateral versus Unilateral Bronchoalveolar Lavage for the Diagnosis of Ventilator-Associated Pneumonia SO SURGICAL INFECTIONS LA English DT Article ID NOSOCOMIAL PNEUMONIA; QUANTITATIVE CULTURES; RANDOMIZED-TRIAL; TRAUMA PATIENTS; RISK-FACTORS; BLIND; EFFICACY; BRONCHOSCOPY; MANAGEMENT; ACCURACY AB Background: Ventilator-associated pneumonia (VAP) complicates the clinical course of critically injured intubated patients. Bronchoscopic bronchoalveolar lavage (BAL) represents an invasive and accurate means of VAP diagnosis. Unilateral and blinded techniques offer less invasive alternatives to bronchoscopic BAL. This study evaluated clinical criteria as well as unilateral directed versus bilateral BAL for VAP diagnosis. Methods: A retrospective chart review of 113 consecutive intubated trauma patients with clinically suspected VAP undergoing unilateral versus bilateral BAL was performed with comparison of positive culture results (>10(4) colony-forming units [CFU]/mL). Culture results were compared with chest radiograph (CXR) infiltrates and white blood cell (WBC) count elevation. Results: Bilateral BAL was more likely to be positive than unilateral BAL (50.4% vs. 25.5%). In 37.1% of bilateral BALs, there was discordance between the sides of positivity or the bacteria isolated. A CXR infiltrate and WBC count elevation did not predict positive BAL. Conclusions: Clinical indicators of VAP are inaccurate, and bilateral bronchoscopic BAL is more likely than unilateral BAL to provide a positive sample in intubated trauma patients. Techniques that do not sample both lungs reliably should be avoided for diagnosis in this patient population. C1 [Jonker, Mark A.; Sauerhammer, Tina M.; Faucher, Lee D.; Schurr, Michael J.; Kudsk, Kenneth A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI USA. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Kudsk, KA (reprint author), 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu FU National Institute of Health (NIH) [R01 GM53439]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service FX This research is supported by National Institute of Health (NIH) Grant R01 GM53439.; This material is also based on work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service. The contents of this article do not represent the views of the Dept. of Veterans Affairs or the United States Government. NR 32 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-2964 J9 SURG INFECT JI Surg. Infect. PD DEC PY 2012 VL 13 IS 6 BP 391 EP 395 DI 10.1089/sur.2011.081 PG 5 WC Infectious Diseases; Surgery SC Infectious Diseases; Surgery GA 061GF UT WOS:000312835800008 PM 23240724 ER PT J AU Rodrigues, FSLM Yang, XY Nikaido, M Liu, QS Kelsh, RN AF Rodrigues, Frederico S. L. M. Yang, Xueyan Nikaido, Masataka Liu, Qingsong Kelsh, Robert N. TI A Simple, Highly Visual in Vivo Screen for Anaplastic Lymphoma Kinase Inhibitors SO ACS CHEMICAL BIOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; NON-HODGKINS-LYMPHOMA; CELL LUNG-CANCER; ALK KINASE; ACTIVATING MUTATIONS; C-MET; NEUROBLASTOMA; ZEBRAFISH; GENE; IDENTIFICATION AB Anaplastic lymphoma kinase (ALK) is an important drug target in many cancers, including lymphoma, neuroblastoma, and lung cancer. Here, we demonstrate proof-of-principle for a novel and inexpensive assay for ALK inhibitor activity and identification in zebrafish. We demonstrate that the human oncogenic ALK fusion, NPM-ALK, drives overproduction of iridophores, a highly visible, shiny pigment cell-type in zebrafish. Treatment with the potent ALK inhibitor, TAE684, fully inhibits production of ALK-dependent iridophores. Using our assay, we test multiple properties of TAE684 in vivo, including efficacy, specificity, and toxicity. We note that TAE684 also inhibits the closely related leukocyte tyrosine kinase (Ltk) that is required for endogenous iridophore development. Similar effects are observed with an independent inhibitor, Crizotinib. Our assay can thus be utilized to identify ALK or LTK inhibitors. Importantly, the natural reflectivity of iridophores lends itself to automation for high throughput assessment of ALK and LTK inhibitor compounds in vivo. C1 [Rodrigues, Frederico S. L. M.; Yang, Xueyan; Nikaido, Masataka; Kelsh, Robert N.] Univ Bath, Dept Biol & Biochem, Ctr Regenerat Med, Bath BA2 7AY, Avon, England. [Liu, Qingsong] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Liu, Qingsong] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kelsh, RN (reprint author), Univ Bath, Dept Biol & Biochem, Ctr Regenerat Med, Bath BA2 7AY, Avon, England. EM bssrnk@bath.ac.uk RI Kelsh, Robert/B-6445-2008; OI Kelsh, Robert/0000-0002-9381-0066; liu, qing song/0000-0002-7829-2547 FU MRC [G0400806]; Wellcome Trust [066326, 077454]; Fundacao para a Ciencia e Tecnologia (FCT) FX We wish to thank S. Elworthy for the original suggestion to use the NPM-ALK assay as a kinase inhibitor screen, R. Jager for the NPM-ALK clone, C. Chien for IRES-eGFP fragment, and N. Gray, P. Janne, and C. Miduturu for providing kinase profiling data. We thank C. de Paiva for technical assistance with some Vatalanib experiments. We are grateful to C. Anastasaki for the schematic figures and to M. Morais for the chemical structure figures. We thank E. Patton for comments on versions of this manuscript. We gratefully acknowledge the support of the MRC (grant G0400806 to R.N.K.), the Wellcome Trust (grants 066326 and 077454), and Fundacao para a Ciencia e Tecnologia (FCT; to F.S.L.M.R.) for funding this work. NR 34 TC 5 Z9 6 U1 0 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD DEC PY 2012 VL 7 IS 12 BP 1968 EP 1974 DI 10.1021/cb300361a PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 057LE UT WOS:000312564000005 PM 22985331 ER PT J AU Mader, BJ Pivtoraiko, VN Flippo, HM Klocke, BJ Roth, KA Mangieri, LR Shacka, JJ AF Mader, Burton J. Pivtoraiko, Violetta N. Flippo, Hilary M. Klocke, Barbara J. Roth, Kevin A. Mangieri, Leandra R. Shacka, John J. TI Rotenone Inhibits Autophagic Flux Prior to Inducing Cell Death SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Rotenone; autophagy; lysosome; cell death; Parkinson's disease; SH-SY5Y ID LYSOSOMAL DEGRADATION PATHWAY; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; MEMBRANE PERMEABILIZATION; DOPAMINERGIC-NEURONS; SH-SY5Y CELLS; DYSFUNCTION; APOPTOSIS; MODELS; CLEARANCE AB Rotenone, which selectively inhibits mitochondrial complex I, induces oxidative stress, alpha-synuclein accumulation, and dopaminergic neuron death, principal pathological features of Parkinson's disease. The autophagy-lysosome pathway degrades damaged proteins and organelles for the intracellular maintenance of nutrient and energy balance. While it is known that rotenone causes autophagic vacuole accumulation, the mechanism by which this effect occurs has not been thoroughly investigated. Treatment of differentiated SH-SY5Y cells with rotenone (10 mu M) induced the accumulation of autophagic vacuoles at 6 h and 24 h as indicated by Western blot analysis for microtubule associated protein-light chain 3-II (MAP-LC3-II). Assessment of autophagic flux at these time points indicated that autophagic vacuole accumulation resulted from a decrease in their effective lysosomal degradation, which was substantiated by increased levels of autophagy substrates p62 and alpha-synuclein. Inhibition of lysosomal degradation may be explained by the observed decrease in cellular ATP levels, which in turn may have caused the observed concomitant increase in acidic vesicle pH. The early (6 h) effects of rotenone on cellular energetics and autophagy-lysosome pathway function preceded the induction of cell death and apoptosis. These findings indicate that the classical mitochondrial toxin rotenone has a pronounced effect on macroautophagy completion that may contribute to its neurotoxic potential. C1 [Shacka, John J.] Univ Alabama Birmingham, Dept Pathol, Div Neuropathol, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Shacka, JJ (reprint author), Univ Alabama Birmingham, Dept Pathol, Div Neuropathol, SC 930G4,1530 3rd Ave S, Birmingham, AL 35294 USA. EM shacka@uab.edu RI di Ronza, Alberto/H-7674-2016; OI di Ronza, Alberto/0000-0002-9813-5143; Mangieri, Leandra/0000-0001-8981-0103; Roth, Kevin/0000-0002-0643-995X FU VA Merit Award [1 101 BX000957-01]; NIH R01s (National) [NS35107, NS41962, CA134773] FX J.J.S. is supported by a VA Merit Award 1 101 BX000957-01. K.A.R. is supported by NIH R01s (National NS35107, NS41962, and CA134773. We also thank the UAB Neuroscience Core facilities (NS047466 and NS057098) for technical assistance. NR 41 TC 25 Z9 25 U1 2 U2 20 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 DEC PY 2012 VL 3 IS 12 BP 1063 EP 1072 DI 10.1021/cn300145z PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA 057LH UT WOS:000312564400010 PM 23259041 ER PT J AU Blevins, JE Moralejo, DH Wolden-Hanson, TH Thatcher, BS Ho, JM Kaiyala, KJ Matsumoto, K AF Blevins, James E. Moralejo, Daniel H. Wolden-Hanson, Tami H. Thatcher, Brendan S. Ho, Jacqueline M. Kaiyala, Karl J. Matsumoto, Kozo TI Alterations in activity and energy expenditure contribute to lean phenotype in Fischer 344 rats lacking the cholecystokinin-1 receptor gene SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE satiety; meal size; cholecystokinin; CCK1 receptors ID DEPENDENT DIABETES-MELLITUS; C-FOS EXPRESSION; TOKUSHIMA FATTY RAT; QUANTITATIVE-TRAIT LOCUS; INDUCED OBESE RATS; BRAIN-STEM NUCLEI; FOOD-INTAKE; BODY-WEIGHT; MICE LACKING; A RECEPTORS AB Blevins JE, Moralejo DH, Wolden-Hanson TH, Thatcher BS, Ho JM, Kaiyala KJ, Matsumoto K. Alterations in activity and energy expenditure contribute to lean phenotype in Fischer 344 rats lacking the cholecystokinin-1 receptor gene. Am J Physiol Regul Integr Comp Physiol 303: R1231-R1240, 2012. First published October 31, 2012; doi:10.1152/ajpregu.00393.2012.-CCK is hypothesized to inhibit meal size by acting at CCK1 receptors (CCK1R) on vagal afferent neurons that innervate the gastrointestinal tract and project to the hindbrain. Earlier studies have shown that obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which carry a spontaneous null mutation of the CCK1R, are hyperphagic and obese. Recent findings show that rats with CCK1R-null gene on a Fischer 344 background (Cck1r(-/-)) are lean and normophagic. In this study, the metabolic phenotype of this rat strain was further characterized. As expected, the CCK1R antagonist, devazepide, failed to stimulate food intake in the Cck1r(-/-) rats. Both Cck1r(+/+) and Cck1r(-/-) rats became diet-induced obese (DIO) when maintained on a high-fat diet relative to chow-fed controls. Cck1r(-/-) rats consumed larger meals than controls during the dark cycle and smaller meals during the light cycle. These effects were accompanied by increased food intake, total spontaneous activity, and energy expenditure during the dark cycle and an apparent reduction in respiratory quotient during the light cycle. To assess whether enhanced responsiveness to anorexigenic factors may contribute to the lean phenotype, we examined the effects of melanotan II (MTII) on food intake and body weight. We found an enhanced effect of MTII in Cck1r(-/-) rats to suppress food intake and body weight following both central and peripheral administration. These results suggest that the lean phenotype is potentially driven by increases in total spontaneous activity and energy expenditure. C1 [Moralejo, Daniel H.] Univ Texas MD Anderson Canc Ctr, Dept Vet Sci, Bastrop, TX USA. [Blevins, James E.; Wolden-Hanson, Tami H.; Thatcher, Brendan S.; Ho, Jacqueline M.] VA Puget Sound Hlth Care Syst, Off Res & Dev, Med Res Serv, Dept Vet Affairs Med Ctr, Seattle, WA USA. [Blevins, James E.; Ho, Jacqueline M.] Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Kaiyala, Karl J.] Univ Washington, Dept Dent Publ Hlth Sci, Seattle, WA 98195 USA. [Matsumoto, Kozo] Kyoto Sangyo Univ, Fac Life Sci, Dept Anim Med Sci, Kyoto 603, Japan. RP Moralejo, DH (reprint author), UT MD Anderson Canc Ctr, Dept Vet Sci, Michale E Keeling Ctr Comparat Med & Res, 650 Cool Water Dr, Bastrop, TX 78602 USA. EM moralejo@uw.edu FU Office of Research and Development, Medical Research Service, Department of Veterans Affairs (VA); VA Puget Sound Health Care System Rodent Metabolic and Behavioral Phenotyping Core; biomedical research core program of the National Institutes of Health (NIH) Diabetes Research Center at the University of Washington; American Diabetes Association [1-05-JF-32]; Department of VA Merit Review Research Program, NIH [DK-17047, RO1DK-61516, P30DK017047-31, P30KD017047-31689] FX This material is based upon work supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs (VA), the VA Puget Sound Health Care System Rodent Metabolic and Behavioral Phenotyping Core, the biomedical research core program of the National Institutes of Health (NIH) Diabetes Research Center at the University of Washington, and the American Diabetes Association. The research in our laboratory has been supported by the Department of VA Merit Review Research Program, NIH Grants DK-17047, RO1DK-61516, P30DK017047-31, and P30KD017047-31689, and by the Junior Faculty Award 1-05-JF-32 by the American Diabetes Association. NR 56 TC 4 Z9 4 U1 1 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD DEC PY 2012 VL 303 IS 12 BP R1231 EP R1240 DI 10.1152/ajpregu.00393.2012 PG 10 WC Physiology SC Physiology GA 057SQ UT WOS:000312584700003 PM 23115121 ER PT J AU Kim, KS Kim, MJ Kononen, E Lounatmaa, K Summanen, P Finegold, SM AF Kim, Keun-Sung Kim, Min-Ju Kononen, Eija Lounatmaa, Kari Summanen, Paula Finegold, Sydney M. TI Single nucleotide polymorphisms are randomly dispersed and mostly synonymous in partial rpoB and cpn60 genes of Campylobacter showae human isolates SO ANAEROBE LA English DT Article DE Campylobacter showae; 16S rRNA gene; rpoB gene; cpn60 gene; SNPs AB The partial 16S rRNA, rpoB, and cpn60 genes congruently allow this study to identify all the eight isolates as the species Campylobacter showae. To our knowledge, this is the first report to reveal the interspecies and intraspecies sequence variations present in the three genes of the C. showae isolates. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Kim, Keun-Sung; Kim, Min-Ju] Chung Ang Univ, Dept Food Sci & Technol, Ansung 456756, Kyungki Do, South Korea. [Kononen, Eija] Natl Inst Hlth & Welf, Bacteriol Unit, Helsinki, Finland. [Kononen, Eija] Univ Turku, Inst Dent, Turku, Finland. [Lounatmaa, Kari] Oy Lounatmaa Ltd, Helsinki, Finland. [Summanen, Paula] W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. [Finegold, Sydney M.] W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect, Los Angeles, CA 90073 USA. [Finegold, Sydney M.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Finegold, Sydney M.] Univ Calif Los Angeles, Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA. RP Kim, KS (reprint author), Chung Ang Univ, Dept Food Sci & Technol, Ansung 456756, Kyungki Do, South Korea. EM keunsung@cau.ac.kr FU DOD [W81XWH-0510134]; VA Merit Review funds FX This work has been supported, in part, by DOD Grant # W81XWH-0510134 and by VA Merit Review funds. NR 5 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1075-9964 J9 ANAEROBE JI Anaerobe PD DEC PY 2012 VL 18 IS 6 BP 626 EP 629 DI 10.1016/j.anaerobe.2012.09.006 PG 4 WC Microbiology SC Microbiology GA 056FK UT WOS:000312473600012 PM 23022203 ER PT J AU Jung, D Bhattacharyya, N AF Jung, David Bhattacharyya, Neil TI Association of Hearing Loss With Decreased Employment and Income Among Adults in the United States SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE employment; hearing loss; income; wage ID EXPENDITURE; PREVALENCE AB Objectives: We evaluated the association of hearing loss with employment and income in adults. Methods: Patients with a coded diagnosis of hearing loss were identified from the 2006 and 2008 Medical Expenditure Panel Survey linked household and medical conditions files and compared to patients without hearing loss. Differences in employment, wage income, and Supplemental Security Income were evaluated with multivariate regression models after adjustment for several demographic and Charlson comorbidity variables. Results: An estimated 933,921 88,474 adults were identified with hearing loss (54.7% of whom were male; mean age for all, 51.0 years). Patients with hearing loss were more likely to be unemployed or partly unemployed than those without hearing loss (adjusted odds ratio, 2.2; p < 0.001). Similarly, adults with hearing loss were less likely to have any wage income than those without hearing loss (adjusted odds ratio, 2.5; p < 0.001). The population with hearing loss earned a mean wage of $23,481 +/- $3,366, versus $31,272 +/- $517 for the population without hearing loss (difference in wages, $7,791; p < 0.001). The association between hearing loss and receiving Supplemental Security Income was not significant (p = 0.109). Conclusions: Adults with hearing loss are more likely to be unemployed and on average earn significantly less wage income than adults without hearing loss. Further work is needed to determine the potential impact of treatment on these differences. C1 [Jung, David] Massachusetts Eye & Ear Infirm, Harvard Otolaryngol Training Program, Boston, MA 02114 USA. [Jung, David; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol, Boston, MA 02115 USA. RP Jung, D (reprint author), Massachusetts Eye & Ear Infirm, Harvard Otolaryngol Training Program, 243 Charles St, Boston, MA 02114 USA. NR 14 TC 12 Z9 13 U1 2 U2 6 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD DEC PY 2012 VL 121 IS 12 BP 771 EP 775 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 056CX UT WOS:000312467100001 PM 23342548 ER PT J AU Nierenberg, AA Bentley, KH Farabaugh, AH Fava, M Deckersbach, T AF Nierenberg, Andrew A. Bentley, Kate H. Farabaugh, Amy H. Fava, Maurizio Deckersbach, Thilo TI The absence of depressive symptoms is not the presence of wellness: Validation of the Clinical Positive Affect Scale SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Article DE Clinical positive affect scale; self-report questionnaire; validation ID NEGATIVE AFFECT SCHEDULE; ABUSE SCREENING-TEST; DSM-IV ANXIETY; PSYCHOMETRIC PROPERTIES; RESIDUAL SYMPTOMS; BECK DEPRESSION; POPULATION; DISORDERS; INVENTORY; MOOD AB Objective: Many patients with depression respond or remit with current treatments, but often experience persistent distress, in part because they perceive that they have not returned to their normal or premorbid state. Some continue to have a lack of subjective psychological well-being and positive affect following treatment. It would be useful to measure these deficits and explore whether interventions can improve them. Currently, no clinically useful scale has been developed to measure positive affect. To fill this gap, we developed the Clinical Positive Affect Scale (CPAS). Method: The purpose of this study is to describe the development and validation of the CPAS, a 16-item self-report measurement of self-perceived affective and cognitive correlates of positive affect, in a sample of 300 college students. Results: A principal component analysis with varimax rotation showed one major factor of positive affect, with all items revealing high loadings (>= 0.65) on the single factor. The CPAS also demonstrated good internal consistency (alpha=0.97) and strong part-whole correlations. Finally, the CPAS revealed some degree of divergent validity through moderately strong negative correlations with validated measures of depression, anxiety and drug abuse. Conclusions: This study supports the validity of the CPAS, which may help clinicians and researchers to assess patients' current self-perceived levels of hedonic capacity and enthusiasm for life. C1 [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin, Boston, MA 02114 USA. [Bentley, Kate H.] Boston Univ, Boston, MA 02215 USA. [Farabaugh, Amy H.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Nierenberg, Andrew A.; Deckersbach, Thilo] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM anierenberg@partners.org FU MGH from Cephalon; MGH from NIMH; MGH from PamLabs; MGH from Pfizer Pharmaceuticals; MGH from Shire; Astra Zeneca; Eli Lilly; Janssen Pharmaceuticals; Bristol-Myers Squibb; NARSAD; HMS; NIMH; Abbott Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells, Inc.; Cephalon, Inc.; Clinical Trials Solutions LLC; Clintara LLC; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Icon Clinical Research; Johnson & Johnson Pharmaceutical Research Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NCCAM; NIDA; Novartis AG; Organon Pharmaceuticals; PamLab LLC; Pfizer, Inc.; Pharmavite(R) LLC; Roche; RCT Logic LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories; TSA; OCF; MGH Psychiatry Academy; Systems Research and Applications Corporation; Boston University; Catalan Agency for Health Technology Assessment and Research; National Association of Social Workers Massachusetts; Massachusetts Medical Society; Oxford University Press; NIH; NIA; Forest Research Institute; Shire Development, Inc.; Medtronic; Cyberonics; Northstar FX AAN has received grant/research support through MGH from: Cephalon, NIMH, PamLabs, Pfizer Pharmaceuticals, and Shire. He has received honoraria from: American Society for Clinical Psychopharmacology, APSARD, Belvoir Publishing, Hillside Hospital, IMEDEX, ISBD, MBL Publishing, and Physicians Postgraduate Press.; AAN is a presenter for the Massachusetts General Hospital Psychiatry Academy (MGHPA). The education programs conducted by the MGHPA were supported through Independent Medical Education (IME) grants from the following pharmaceutical companies in 2008: Astra Zeneca, Eli Lilly, and Janssen Pharmaceuticals; in 2009: Astra Zeneca, Bristol-Myers Squibb, and Eli Lilly.; AHF's research has been funded by NARSAD, HMS, and NIMH. She has received honoraria from the MGH Psychiatry Academy. She has equity holdings in Pfizer, GlaxoSmithKlein, and Wyeth.; MF has received research support from the following: Abbott Laboratories, Alkermes, Inc., Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, Inc., Bristol-Myers Squibb, Cephalon, Inc., Clinical Trials Solutions LLC, Clintara LLC, Covidien, Eli Lilly and Company, EnVivo Pharmaceuticals, Inc., Forest Pharmaceuticals, Inc., Ganeden Biotech, Inc., GlaxoSmithKline, Icon Clinical Research, Johnson & Johnson Pharmaceutical Research & Development, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, NCCAM, NIDA, NIMH, Novartis AG, Organon Pharmaceuticals, PamLab LLC, Pfizer, Inc., Pharmavite (R) LLC, Roche, RCT Logic LLC, Sanofi-Aventis US LLC, Shire, Solvay Pharmaceuticals, Inc., Synthelabo, and Wyeth-Ayerst Laboratories.; TD's research has been funded by NIMH, NARSAD, TSA, and OCF. He has received honoraria, consultation fees and/or royalties from the MGH Psychiatry Academy, BrainCells, Inc., Systems Research and Applications Corporation, Boston University, the Catalan Agency for Health Technology Assessment and Research, the National Association of Social Workers Massachusetts, Massachusetts Medical Society and Oxford University Press. He has also participated in research funded by NIH, NIA, Janssen Pharmaceuticals, The Forest Research Institute, Shire Development, Inc., Medtronic, Cyberonics, and Northstar. NR 37 TC 8 Z9 8 U1 1 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD DEC PY 2012 VL 46 IS 12 BP 1165 EP 1172 DI 10.1177/0004867412459810 PG 8 WC Psychiatry SC Psychiatry GA 048BI UT WOS:000311884800008 PM 22990434 ER PT J AU Stone, RM AF Stone, Richard M. TI Is it time to revisit standard post-remission therapy? SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE acute myeloid leukemia (AML); maintenance; post-remission; risk-adapted; standard therapy; transplant ID ACUTE MYELOID-LEUKEMIA; HIGH-DOSE CYTARABINE; STEM-CELL TRANSPLANTATION; TRANS-RETINOIC ACID; AGE 60 YEARS; GROUP-B; ELDERLY-PATIENTS; CANCER; INTENSIFICATION; CHEMOTHERAPY AB There are several strategies for improving post-remission therapy in acute myeloid leukemia (AML). One is a risk-adapted strategy for younger adults in which patients with non-favorable characteristics based on cytogenetics and genetics are allocated to allogeneic stem cell transplantation and others receive intensive high-dose ara-C-based therapies. Additional genetic data and/or minimal residual disease level may prove useful in post-remission therapeutic choice. Future approaches, badly needed in older AML patients, may include the addition of new agents to currently used therapies or maintenance with DNA methyltransferase inhibitors. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Stone, Richard M.] Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02115 USA. [Stone, Richard M.] Harvard Univ, Sch Med, Boston, MA USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, Adult Leukemia Program, 450 Brookline Ave,MIB 17, Boston, MA 02115 USA. EM rstone@partners.org FU Genzyme Corporation; Infinity; Ariad; Agios FX Consulting fees: Genzyme Corporation; Infinity; Ariad; Agios. NR 22 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD DEC PY 2012 VL 25 IS 4 BP 437 EP 441 DI 10.1016/j.beha.2012.10.006 PG 5 WC Hematology SC Hematology GA 057PD UT WOS:000312574600006 PM 23200540 ER PT J AU Steensma, DR AF Steensma, David R. TI Can hypomethylating agents provide a platform for curative therapy in myelodysplastic syndromes? SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE azacitidine; decitabine; hypomethylating agent; myelodysplastic syndrome (MDS) ID ACUTE MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; RANDOMIZED PHASE-III; LOW-DOSE AZACITIDINE; REGULATORY T-CELLS; DNA METHYLATION; GROUP-B; MAINTENANCE THERAPY; EPIGENETIC CHANGES; ELDERLY-PATIENTS AB The hypomethylating agents (HMAs) azacitidine and decitabine have changed the treatment landscape of myelodysplastic syndromes (MDS) since their approval by the United States Food and Drug Administration (US FDA) in 2004 and 2006, respectively. However, neither agent is able to cure patients with MDS, and when patients fail to respond to treatment with these agents, their prognosis is poor. For this reason, investigators are currently testing combination regimens with an HMA as a backbone and altering the dose, schedule, and method of delivery of HMAs. Additionally, more than 30 new molecules are currently being tested in interventional studies for which patients with MDS are eligible to enroll. These efforts may further improve outcomes for patients with MDS. For the time being, allogeneic stem cell transplantation (ASCT) remains patients' only real opportunity for cure and should be performed whenever possible in patients with higher-risk disease. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Steensma, David R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Steensma, David R.] Harvard Univ, Sch Med, Boston, MA USA. RP Steensma, DR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Suite D1B30 Mayer 1B21, Boston, MA 02215 USA. EM david_steensma@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284 NR 65 TC 9 Z9 10 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD DEC PY 2012 VL 25 IS 4 BP 443 EP 451 DI 10.1016/j.beha.2012.10.007 PG 9 WC Hematology SC Hematology GA 057PD UT WOS:000312574600007 PM 23200541 ER PT J AU Walovitch, RC Chokron, P Agarwal, S AF Walovitch, Richard C. Chokron, Patrick Agarwal, Sheela TI US FDA draft Guidance Standard for Clinical Trial Imaging Endpoints: more than just imaging? SO BIOMARKERS IN MEDICINE LA English DT Review DE adjudication; BICR; blinded review; DMIHP; DMIP; FDA guidance document; imaging; imaging contract research organization; independent review committee; subjective assessment ID GASTROINTESTINAL STROMAL TUMORS; POSITRON-EMISSION-TOMOGRAPHY; PROGRESSION-FREE SURVIVAL; IMATINIB MESYLATE; THERMAL ABLATION; EARLY PREDICTION; THERAPY; CRITERIA; ONCOLOGY; EFFICACY AB The current cost of developing a successful drug is typically over a billion dollars, with the registration trial(s) determining the success or failure of the entire development program. Often the primary endpoint of these trials is a subjective assessment. For registration trials with subjective endpoints, a regulatory agency may require a blinded independent central review (BICR) of the trial data. The BICR is a mechanism to reduce bias in open-labeled trials and to potentially increase accuracy and precision. A decision tree algorithm has been developed that can be used to determine when and what type of a BICR is needed. The US FDA draft Guidance Standard for Clinical Trial Imaging Endpoints can be used as an effective process map in exploring the value and use of BICRs in imaging, and in any hard to interpret variable subjective assessment in general. C1 [Walovitch, Richard C.; Chokron, Patrick] Worldcare Clin LLC, Boston, MA 02114 USA. [Agarwal, Sheela] Massachusetts Gen Hosp, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. RP Walovitch, RC (reprint author), Worldcare Clin LLC, 7 Bulfinch Pl, Boston, MA 02114 USA. EM rwalovitch@wcclinical.com NR 39 TC 0 Z9 0 U1 1 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD DEC PY 2012 VL 6 IS 6 BP 839 EP 847 DI 10.2217/BMM.12.74 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 055LA UT WOS:000312416600024 PM 23227850 ER PT J AU Fang, QQ Kaeli, DR AF Fang, Qianqian Kaeli, David R. TI Accelerating mesh-based Monte Carlo method on modern CPU architectures SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID COMPLEX HETEROGENEOUS TISSUES; OPTICAL-SIMULATION; PHOTON MIGRATION; LIGHT TRANSPORT; MOUSE; BODY; CODE AB In this report, we discuss the use of contemporary ray-tracing techniques to accelerate 3D mesh-based Monte Carlo photon transport simulations. Single Instruction Multiple Data (SIMD) based computation and branch-less design are exploited to accelerate ray-tetrahedron intersection tests and yield a 2-fold speed-up for ray-tracing calculations on a multi-core CPU. As part of this work, we have also studied SIMD-accelerated random number generators and math functions. The combination of these techniques achieved an overall improvement of 22% in simulation speed as compared to using a non-SIMD implementation. We applied this new method to analyze a complex numerical phantom and both the phantom data and the improved code are available as open-source software at http://mcx.sourceforge.net/mmc/. (C) 2012 Optical Society of America C1 [Fang, Qianqian] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Kaeli, David R.] Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. RP Fang, QQ (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM fangq@nmr.mgh.harvard.edu FU Bill & Melinda Gates Foundation [OPP1035992] FX QF wishes to thank the funding support from the Bill & Melinda Gates Foundation (#OPP1035992). NR 23 TC 0 Z9 0 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD DEC 1 PY 2012 VL 3 IS 12 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 059ML UT WOS:000312709500016 ER PT J AU Mai, CT Riehle-Colarusso, T O'Halloran, A Cragan, JD Olney, RS Lin, A Feldkamp, M Botto, LD Rickard, R Anderka, M Ethen, M Stanton, C Ehrhardt, J Canfield, M AF Mai, Cara T. Riehle-Colarusso, Tiffany O'Halloran, Alissa Cragan, Janet D. Olney, Richard S. Lin, Angela Feldkamp, Marcia Botto, Lorenzo D. Rickard, Russel Anderka, Marlene Ethen, Mary Stanton, Carol Ehrhardt, Joan Canfield, Mark CA Natl Birth Defects Prevention Netw TI Selected birth defects data from population-based birth defects surveillance programs in the United States, 2005-2009: Featuring critical congenital heart defects targeted for pulse oximetry screening SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article ID PREVALENCE; DISEASE C1 [Mai, Cara T.; Riehle-Colarusso, Tiffany; Cragan, Janet D.; Olney, Richard S.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. [O'Halloran, Alissa] Carter Consulting, Atlanta, GA USA. [Lin, Angela] MassGen Hosp Children, Genet Unit, Boston, MA USA. [Lin, Angela; Anderka, Marlene] Massachusetts Dept Publ Hlth, Massachusetts Ctr Birth Defects Res & Prevent, Boston, MA USA. [Feldkamp, Marcia; Botto, Lorenzo D.] Univ Utah, Dept Pediat, Div Med Genet, Hlth Sci Ctr, Salt Lake City, UT USA. [Feldkamp, Marcia; Botto, Lorenzo D.] Utah Dept Hlth, Utah Birth Defect Network, Salt Lake City, UT 84116 USA. [Rickard, Russel; Stanton, Carol] Colorado Dept Publ Hlth & Environm, Denver, CO USA. [Ethen, Mary; Canfield, Mark] Texas Dept State Hlth Serv, Birth Defects Epidemiol & Surveillance Branch, Austin, TX USA. [Ehrhardt, Joan] Michigan Dept Community Hlth, Lansing, MI USA. RP Mai, CT (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, 1600 Clifton Rd, Atlanta, GA 30333 USA. EM cmai@cdc.gov FU Intramural CDC HHS [CC999999] NR 9 TC 9 Z9 9 U1 0 U2 8 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 DEC PY 2012 VL 94 IS 12 SI SI BP 970 EP 983 DI 10.1002/bdra.23098 PG 14 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 056YH UT WOS:000312527100003 PM 24083317 ER PT J AU Luquetti, DV Saltzman, BS Vivaldi, D Pimenta, LA Hing, AV Cassell, CH Starr, JR Heike, CL AF Luquetti, Daniela V. Saltzman, Babette S. Vivaldi, Daniela Pimenta, Luiz A. Hing, Anne V. Cassell, Cynthia H. Starr, Jacqueline R. Heike, Carrie L. TI Evaluation of ICD-9-CM codes for craniofacial microsomia SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE craniofacial microsomia; hemifacial microsomia; oculo-auriculo-vertebral spectrum; microtia; Goldenhar; birth defects surveillance; ICD-9-CM ID HEMIFACIAL MICROSOMIA; MICROTIA; SPECTRUM AB BACKGROUND Craniofacial microsomia (CFM) is a congenital condition characterized by microtia and mandibular underdevelopment. Healthcare databases and birth defects surveillance programs could be used to improve knowledge of CFM. However, no specific International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code exists for this condition, which makes standardized data collection challenging. Our aim was to evaluate the validity of existing ICD-9-CM codes to identify individuals with CFM. METHODS Study sample eligibility criteria were developed by an expert panel and matched to 11 ICD-9-CM codes. We queried hospital discharge data from two craniofacial centers and identified a total of 12,254 individuals who had =1 potentially CFM-related code(s). We reviewed all (n = 799) medical records identified at the University of North Carolina (UNC) and 500 randomly selected records at Seattle Children's Hospital (SCH). Individuals were classified as a CFM case or non-case. RESULTS Thirty-two individuals (6%) at SCH and 93 (12%) at UNC met the CFM eligibility criteria. At both centers, 59% of cases and 95% of non-cases had only one code assigned. At both centers, the most frequent codes were 744.23 (microtia), 754.0 and 756.0 (nonspecific codes), and the code 744.23 had a positive predictive value (PPV) >80% and sensitivity >70%. The code 754.0 had a sensitivity of 3% (PPV <1%) at SCH and 36% (PPV = 5%) at UNC, whereas 756.0 had a sensitivity of 38% (PPV = 5%) at SCH and 18% (PPV = 26%) at UNC. CONCLUSIONS These findings suggest the need for a specific CFM code to facilitate CFM surveillance and research. Birth Defects Research (Part A), 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Luquetti, Daniela V.; Saltzman, Babette S.; Hing, Anne V.; Heike, Carrie L.] Seattle Childrens Hosp, Craniofacial Ctr, Seattle, WA USA. [Luquetti, Daniela V.; Hing, Anne V.; Heike, Carrie L.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Vivaldi, Daniela; Pimenta, Luiz A.] Univ N Carolina, Sch Dent, Craniofacial Ctr, Chapel Hill, NC USA. [Vivaldi, Daniela; Pimenta, Luiz A.] Univ N Carolina, Sch Dent, Dept Dent Ecol, Chapel Hill, NC 27599 USA. [Cassell, Cynthia H.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. [Starr, Jacqueline R.] Forsyth Inst, Cambridge, MA USA. [Starr, Jacqueline R.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Luquetti, Daniela V.; Saltzman, Babette S.; Vivaldi, Daniela; Pimenta, Luiz A.; Hing, Anne V.; Starr, Jacqueline R.; Heike, Carrie L.] FACIAL, Seattle, WA USA. RP Luquetti, DV (reprint author), 1900 9th Ave,Room 520,C9S-5, Seattle, WA 98101 USA. EM daniela.luquetti@seattlechildrens.org OI Starr, Jacqueline/0000-0002-3039-2311 FU National Institute of Dental and Craniofacial Research in the National Institutes of Health [RC1 DE 020270] FX Supported by a grant from the National Institute of Dental and Craniofacial Research in the National Institutes of Health (grant number RC1 DE 020270). NR 15 TC 1 Z9 1 U1 1 U2 4 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 DEC PY 2012 VL 94 IS 12 SI SI BP 990 EP 995 DI 10.1002/bdra.23059 PG 6 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 056YH UT WOS:000312527100005 PM 22903955 ER PT J AU Ten Berg, P Ring, D AF Ten Berg, Paul Ring, David TI Quantitative 3D-CT Anatomy of Hamate Osteoarticular Autograft for Reconstruction of the Middle Phalanx Base SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PROXIMAL INTERPHALANGEAL JOINT; FRACTURE-DISLOCATIONS; ARTHROPLASTY AB Background Hamate osteoarticular autografts are difficult to obtain and it is unclear to what degree the graft matches the joint surface to be replaced and whether a direct ulnar approach might provide a more reliable graft than the standard proximal to distal approach. Purpose We modeled hemihamate osteotomies using quantitative three-dimensional CT (3D-CT) to measure the amount of hamate articular surface used and the match with the native volar base of the middle phalanx. Methods In virtual hemihamate osteotomies (standard and direct ulnar) on CTs of 20 patients (11 men and nine women), we measured the percentage of hamate articular surface used for each finger, the match of the articular contour, and the percentage of hamate articular surface removed. Results The autograft in the standard approach used an average of 26% of the hamate articular surface and had an average 75% match of the articular contour with the volar half of the middle phalanx base. A direct ulnar approach removed an additional small margin of dorsal ulnar hamate with an average maximum width of 2.5 mm and volume of 27 mm 3. Conclusions An osteoarticular allograft from the hamate to replace the volar half of the middle phalanx base uses less than 1/3 of the hamate articular surface even if the dorsal ulnar margin of the hamate is taken with the graft. Clinical Relevance These data suggest that it might be feasible to make the deep cut from a direct ulnar approach. C1 [Ten Berg, Paul; Ring, David] Harvard Univ, Orthopaed Hand & Upper Extrem Serv, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ten Berg, Paul] Acad Med Ctr, Amsterdam, Netherlands. RP Ring, D (reprint author), Harvard Univ, Orthopaed Hand & Upper Extrem Serv, Sch Med, Massachusetts Gen Hosp, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 11 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2012 VL 470 IS 12 BP 3492 EP 3498 DI 10.1007/s11999-012-2372-x PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 054UO UT WOS:000312370200031 PM 22538961 ER PT J AU Kramer, JR Bayless, ML Lorenzi, GM Ziegler, GK Larkin, ME Lackaye, ME Harth, J Diminick, LJ Anderson, KL Braffett, BH Cleary, PA AF Kramer, John R. Bayless, Margaret L. Lorenzi, Gayle M. Ziegler, Georgia K. Larkin, Mary E. Lackaye, Mary E. Harth, Judith Diminick, Lisa J. Anderson, Karen L. Braffett, Barbara H. Cleary, Patricia A. CA DCCT-EDIC Study Grp TI Participant characteristics and study features associated with high retention rates in a longitudinal investigation of type 1 diabetes mellitus SO CLINICAL TRIALS LA English DT Article; Proceedings Paper CT University-of-Pennsylvania Annual Conference on Statistical Issues in Clinical Trials CY APR 13-13, 2011 CL Philadelphia, PA ID CLINICAL-TRIAL; ACCORD AB Background The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study has sustained an extraordinarily high level of participant involvement for over two decades. Purpose In order to identify specific characteristics of EDIC that contributed most strongly to retention, study-designed questionnaires were distributed to 1334 participants. Methods Confidential questionnaires were completed during EDIC Years 15-17. Participants were classified as Completely Adherent (completed all visits), Partly Adherent (missed >1 visit or major portion of a visit), or Inactive (did not participate for >5 years). Questionnaire items addressed specific aspects of clinic visits, evaluation procedures, staff-participant relationships, and medical/health-care support provided by EDIC. Results The most commonly cited reasons for continuing participation were Cutting Edge Tests to assess diabetes complications (79.3%), Annual Evaluations (67.7%), a desire to Help Others (65.2%), and Better Care for Diabetes (61.6%). Women chose Cutting Edge Tests as their first or second most important reason significantly more often than men, whereas men chose Better Care for Diabetes more frequently. Individuals with at least three diabetes-related complications were more likely than those with fewer complications to choose Annual Evaluations as their first or second reason for continued involvement. Limitations The small proportion of individuals who discontinued participation restricted our ability to identify factors associated with suspended involvement. In addition, our analysis is limited to a cohort with type 1 diabetes followed in an observational study after an average participation time of 6.5 years in a randomized trial. Conclusions The primary reasons identified by respondents for their long-term commitment are consistent with shorter-term studies and underscore the importance of expert medical care, supportive staff-participant relationships, and involvement with clinically and scientifically meaningful research. Clinical Trials 2012; 9: 798-805. http://ctj.sagepub.com C1 [Kramer, John R.] Univ Iowa, Carver Coll Med, Dept Psychiat, MEB, Iowa City, IA 52242 USA. [Bayless, Margaret L.] Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. [Lorenzi, Gayle M.] Univ Calif San Diego, Sch Med, Dept Med, San Diego, CA 92103 USA. [Ziegler, Georgia K.] Mayo Clin, Rochester, MN USA. [Larkin, Mary E.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. [Lackaye, Mary E.] Weill Cornell Med Coll, Dept Endocrinol, New York, NY USA. [Harth, Judith] Univ Western Ontario, Schulich Sch Med & Dent, Dept Med, London, ON, Canada. [Diminick, Lisa J.; Anderson, Karen L.; Braffett, Barbara H.; Cleary, Patricia A.] George Washington Univ, Off Vice President Res, Res Facil A, Ctr Biostat, Rockville, MD USA. RP Kramer, JR (reprint author), Univ Iowa, Carver Coll Med, Dept Psychiat, MEB, Iowa City, IA 52242 USA. EM john-kramer@uiowa.edu FU Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease; National Eye Institute; National Institute of Neurologic Disorders and Stroke; Genetic Clinical Research Centers Program; Clinical Translational Science Center Program, Bethesda, Maryland, USA FX The DCCT/EDIC has been supported by U01 Cooperative Agreement grants (1983-93) and contracts (1994-present) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease, and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the Genetic Clinical Research Centers Program (1993-2007), and Clinical Translational Science Center Program (2006-present), Bethesda, Maryland, USA. NR 16 TC 5 Z9 5 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PD DEC PY 2012 VL 9 IS 6 BP 798 EP 805 DI 10.1177/1740774512458986 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 055XZ UT WOS:000312452600019 PM 23027646 ER PT J AU IsHak, WW Bolton, MA Bensoussan, JC Dous, G Nguyen, TT Powell-Hicks, AL Gardner, JE Ponton, KM AF IsHak, Waguih William Bolton, Michael A. Bensoussan, Jean-Charles Dous, GeorgeV. Nguyen, Trang T. Powell-Hicks, Allycin L. Gardner, Jennifer E. Ponton, Kimberly M. TI Quality of life in body dysmorphic disorder SO CNS SPECTRUMS LA English DT Review DE Body dysmorphic disorder; body image; dysmorphophobia; quality of life ID COMPULSIVE DISORDER; SOCIAL PHOBIA; INDIVIDUALS; COMORBIDITY; POPULATION; PREVALENCE AB Body dysmorphic disorder (BDD) has a significant impact on the patients' quality of life (QOL). This is an initial literature review of QOL in patients with BDD, examining the extent of QOL impairments, the impact of psychiatric comorbidity on QOL, and the effect of treatment on QOL in BDD. Studies were identified through PubMed, MEDLINE, and PsycINFO searches from 1960-2011 using the keywords: "quality of life," "body dysmorphic disorder," "dysmorphophobia," and "body image." Studies included in this review were selected using specific criteria by two authors reaching consensus. Most BDD research studies have used symptom severity measures mainly to study BDD and its treatments. BBD with or without comorbidities is significantly associated with poor QOL and functioning. Studies show that treatment of BDD, either by psychopharmacological treatments such as selective serotonin reuptake inhibitors (SSRIs) or cognitive behavior therapy, might have positive effects on QOL, although these results need to be replicated in larger studies. In conclusion, QOL could add significant value to the assessment of BDD if used as one of the primary measures in research and clinical work in BDD, by providing more information and clearer understanding on the impact of the illness on satisfaction with activities of daily life and overall sense of wellbeing before and after treatment. Received 10 March 2012; Accepted 16 July 2012 C1 [IsHak, Waguih William] Univ Calif Los Angeles, David Geffen Sch Med, Psychiat Residency Training Program, Los Angeles, CA 90048 USA. [IsHak, Waguih William; Bensoussan, Jean-Charles; Dous, GeorgeV.; Powell-Hicks, Allycin L.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Bolton, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gardner, Jennifer E.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. RP IsHak, WW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Psychiat Residency Training Program, 8730 Alden Dr,Thalians W-157, Los Angeles, CA 90048 USA. EM Waguih.Ishak@cshs.org RI IsHak, Waguih/C-1336-2011 OI IsHak, Waguih/0000-0003-1970-4756 FU NARSAD; Pfizer FX Waguih William IsHak, MD, has received research support from NARSAD (quality of life in major depression) and Pfizer (ziprasidone monotherapy for major depression). The remaining authors have nothing to disclose. NR 28 TC 5 Z9 5 U1 3 U2 25 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD DEC PY 2012 VL 17 IS 4 BP 167 EP 175 DI 10.1017/S1092852912000624 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 056XZ UT WOS:000312526000002 PM 22939280 ER PT J AU Barbash, I Kabraji, S Han, M Kohn, R Thompson, R AF Barbash, Ian Kabraji, Sheheryar Han, Maria Kohn, Rachel Thompson, Ryan TI A CROSS-SECTIONAL STUDY OF DISCREPANCIES IN CODE STATUS DOCUMENTATION FOR HOSPITALIZED PATIENTS SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Barbash, Ian] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 718 BP U196 EP U196 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045700678 ER PT J AU Cummings, B Cowl, A El Saleeby, C Yager, P Shank, E Noviski, N AF Cummings, Brian Cowl, Allison El Saleeby, Chadi Yager, Phoebe Shank, Eric Noviski, Natan TI CARDIOVASCULAR EFFECTS OF DEXMEDETOMIDINE INFUSION WITHOUT A LOADING DOSE IN CRITICALLY ILL CHILDREN SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Cummings, Brian; El Saleeby, Chadi; Yager, Phoebe; Shank, Eric; Noviski, Natan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cowl, Allison] Univ Connecticut, Storrs, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 959 BP U261 EP U261 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045701228 ER PT J AU Cummings, B Ahmed, F Noviski, N AF Cummings, Brian Ahmed, Faheem Noviski, Natan TI REDUCTION OF REPETITIVE IMAGING ON PEDIATRIC PATIENTS REFERRED TO A PICU: A QUALITY INITIATIVE SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Ahmed, Faheem] Kings Coll London, Sch Med, London, England. [Cummings, Brian; Noviski, Natan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 139 BP U45 EP U45 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045700104 ER PT J AU Elmer, J Hou, P Schreiber, H Duran-Mendicuti, MA Pallin, DJ Wilcox, SR Chang, Y Okechukwu, I Pontes-Neto, O Bajwa, E Hess, DR Avery, L Camargo, CA Greenberg, SM Rosand, J Goldstein, J AF Elmer, Jonathan Hou, Peter Schreiber, Hannah Duran-Mendicuti, Maria Alejandra Pallin, Daniel J. Wilcox, Susan R. Chang, Yuchiao Okechukwu, Ikenna Pontes-Neto, Octavio Bajwa, Ednan Hess, Dean R. Avery, Laura Camargo, Carlos A., Jr. Greenberg, Steven M. Rosand, Jonathan Goldstein, Joshua TI ACUTE RESPIRATORY DISTRESS SYNDROME AFTER SPONTANEOUS INTRACEREBRAL HEMORRHAGE SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Elmer, Jonathan] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. [Hou, Peter; Schreiber, Hannah; Duran-Mendicuti, Maria Alejandra; Pallin, Daniel J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wilcox, Susan R.; Chang, Yuchiao; Okechukwu, Ikenna; Pontes-Neto, Octavio; Bajwa, Ednan; Hess, Dean R.; Avery, Laura; Camargo, Carlos A., Jr.; Greenberg, Steven M.; Rosand, Jonathan; Goldstein, Joshua] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Pallin, Daniel/H-6382-2013; Pontes-Neto, Octavio/G-4294-2012 OI Pallin, Daniel/0000-0002-8517-9702; Pontes-Neto, Octavio/0000-0003-0317-843X NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 388 BP U111 EP U111 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045700351 ER PT J AU Glisic, E Riker, R Kelner, A Perrey, H Fraser, G AF Glisic, Elizabeth Riker, Richard Kelner, Andrew Perrey, Hilary Fraser, Gilles TI TRANSITIONING PATIENTS TREATED WITH DEXMEDETOMIDINE TO ENTERAL CLONIDINE: A RETROSPECTIVE STUDY SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Glisic, Elizabeth; Riker, Richard; Kelner, Andrew; Fraser, Gilles] Maine Med Ctr, Portland, ME USA. [Perrey, Hilary] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 1110 BP U300 EP U300 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045701376 ER PT J AU Hobai, I Morse, J Abbasi, W Chen, E Siwik, D Colucci, W AF Hobai, Ion Morse, Justin Abbasi, Wafaa Chen, Estela Siwik, Deborah Colucci, Wilson TI PROLONGED EXPOSURE TO BACTERIAL LIPOPOLYSACCHARIDE AND INFLAMMATORY CYTOKINES INHIBITS EXCITATION CONTRACTION COUPLING IN ADULT RAT CARDIOMYOCYTES. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Hobai, Ion] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hobai, Ion; Siwik, Deborah; Colucci, Wilson] Boston Univ, Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 168 BP U53 EP U53 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045700133 ER PT J AU Hwang, D Yagoda, D Perrey, H Tehan, T Guanci, M Ananian, L Currier, P Cobb, JP Rosand, J AF Hwang, David Yagoda, Daniel Perrey, Hilary Tehan, Tara Guanci, Mary Ananian, Lillian Currier, Paul Cobb, J. Perren Rosand, Jonathan TI CONSISTENCY OF COMMUNICATION AMONG INTENSIVE CARE UNIT STAFF AS PERCEIVED BY FAMILY MEMBERS OF PATIENTS SURVIVING TO DISCHARGE SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Hwang, David] Yale New Haven Med Ctr, New Haven, CT USA. [Yagoda, Daniel; Perrey, Hilary; Tehan, Tara; Guanci, Mary; Ananian, Lillian; Currier, Paul; Cobb, J. Perren; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 890 BP U243 EP U243 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045701159 ER PT J AU Mehta, N Pichoff, D McAdam, A Paster, B Priebe, G AF Mehta, Nilesh Pichoff, Darla McAdam, Alexander Paster, Bruce Priebe, Gregory TI MICROBIOME IDENTIFICATION USING CULTURE-INDEPENDENT MOLECULAR TECHNIQUE IN MECHANICALLY VENTILATED CHILDREN - NEW INSIGHTS SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Mehta, Nilesh; Pichoff, Darla; McAdam, Alexander; Priebe, Gregory] Boston Childrens Hosp, Boston, MA USA. [Paster, Bruce] Forsyth Inst, Cambridge, MA 02142 USA. RI Mehta, Nilesh/G-7073-2016 NR 0 TC 0 Z9 0 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 177 BP U55 EP U55 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045700142 ER PT J AU Moromizato, T Mendu, M McKane, C Gibbons, F Christopher, K AF Moromizato, Takuhiro Mendu, Mallika McKane, Caitlin Gibbons, Fiona Christopher, Kenneth TI ERYTHROCYTE TRANSFUSION AND ACUTE KIDNEY INJURY IN THE CRITICALLY ILL SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Moromizato, Takuhiro; Mendu, Mallika; McKane, Caitlin; Christopher, Kenneth] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gibbons, Fiona] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 636 BP U175 EP U175 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045700597 ER PT J AU Moromizato, T Marmarelis, M Mendu, M McKane, C Gibbons, F Christopher, K AF Moromizato, Takuhiro Marmarelis, Melina Mendu, Mallika McKane, Caitlin Gibbons, Fiona Christopher, Kenneth TI DIABETES MELLITUS AND COMMUNITY BLOODSTREAM INFECTION IN THE CRITICALLY ILL SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Moromizato, Takuhiro; Mendu, Mallika; McKane, Caitlin; Christopher, Kenneth] Brigham & Womens Hosp, Boston, MA 02115 USA. [Marmarelis, Melina] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gibbons, Fiona] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 361 BP U103 EP U104 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045700324 ER PT J AU Moromizato, T Litonjua, A Braun, A Gibbons, F Giovannucci, E Christopher, K AF Moromizato, Takuhiro Litonjua, Augusto Braun, Andrea Gibbons, Fiona Giovannucci, Edward Christopher, Kenneth TI PRE-HOSPITAL SERUM VITAMIN D LEVELS AND MORTALITY FOLLOWING CORONARY ARTERY BYPASS GRAFTING SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Moromizato, Takuhiro; Litonjua, Augusto; Christopher, Kenneth] Brigham & Womens Hosp, Boston, MA 02115 USA. [Braun, Andrea; Gibbons, Fiona] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 38 BP U28 EP U28 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045700039 ER PT J AU Moromizato, T Litonjua, A Braun, A Gibbons, F Giovannucci, E Christopher, K AF Moromizato, Takuhiro Litonjua, Augusto Braun, Andrea Gibbons, Fiona Giovannucci, Edward Christopher, Kenneth TI PRE-HOSPITAL VITAMIN D DEFICIENCY AND SEPSIS IN THE CRITICALLY ILL SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Moromizato, Takuhiro; Litonjua, Augusto; Christopher, Kenneth] Brigham & Womens Hosp, Boston, MA 02115 USA. [Braun, Andrea; Gibbons, Fiona] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 24 BP U24 EP U24 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045700025 ER PT J AU Sheridan, R Stoddard, F Kazis, L Lee, A Meyer, W Kagan, R Palmieri, T Herndon, D Tompkins, R AF Sheridan, Robert Stoddard, Fredrick Kazis, Lewis Lee, Austin Meyer, Walter Kagan, Richard Palmieri, Tina Herndon, David Tompkins, Ronald TI LONG-TERM POST-TRAUMATIC STRESS SYMPTOMS VARY INVERSELY WITH EARLY OPIATE DOSING IN CHILDREN RECOVERING FROM SERIOUS BURNS-EFFECTS DURABLE AT FOUR YEARS SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Sheridan, Robert; Stoddard, Fredrick; Kazis, Lewis; Lee, Austin; Meyer, Walter; Kagan, Richard; Palmieri, Tina; Herndon, David] Massachusetts Gen Hosp, Shriners Hosp Children, Boston, MA 02114 USA. [Sheridan, Robert] Boston VA Healthcare Syst, Boston, MA USA. [Kazis, Lewis; Lee, Austin] Boston Univ, Boston, MA 02215 USA. [Meyer, Walter; Herndon, David] Univ Texas Med Branch, Galveston, TX USA. [Kagan, Richard] Univ Cincinnati, Cincinnati, OH 45221 USA. [Palmieri, Tina] Univ Calif Davis, Davis, CA USA. [Tompkins, Ronald] Harvard Univ, Sch Med, Shriners Hosp Children, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 129 BP U42 EP U43 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045700094 ER PT J AU Thoma, B Pizzi, L McDaniel, C Li, J Mearns, E Wordell, C Cavarocchi, N AF Thoma, Brandi Pizzi, Laura McDaniel, Cara Li, Julius Mearns, Elizabeth Wordell, Cindy Cavarocchi, Nicholas TI DEXMEDETOMIDINE VERSUS PROPOFOL AND MIDAZOLAM IN PATIENTS UNDERGOING CORONARY ARTERY BYPASS GRAFTING SURGERY SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Thoma, Brandi; McDaniel, Cara; Wordell, Cindy] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Pizzi, Laura; Mearns, Elizabeth] Thomas Jefferson Univ, Sch Pharm, Philadelphia, PA USA. [Li, Julius] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 1120 BP U302 EP U302 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045701386 ER PT J AU Voscopoulos, C Freeman, J Brayanov, J Ladd, D Lalli, M MacNabb, CM Eikermann, M AF Voscopoulos, Christopher Freeman, Jenny Brayanov, Jordan Ladd, Diane Lalli, Michael MacNabb, C. Marshall Eikermann, Matthias TI EVALUATION OF A NON-INVASIVE RESPIRATORY VOLUME MONITOR DURING OBSTRUCTED BREATHING SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Voscopoulos, Christopher] Brigham & Womens Hosp, Boston, MA 02115 USA. [Freeman, Jenny; Lalli, Michael; MacNabb, C. Marshall] Resp Mot Inc, Waltham, MA USA. [Brayanov, Jordan] Harvard Univ, Cambridge, MA 02138 USA. [Ladd, Diane] W Virginia Univ, Morgantown, WV 26506 USA. [Eikermann, Matthias] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 103 BP U35 EP U36 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045700068 ER PT J AU Yager, P Dapul, H Murphy, S Clark, M Zheng, H Noviski, N AF Yager, Phoebe Dapul, Heda Murphy, Sarah Clark, Maureen Zheng, Hui Noviski, Natan TI COMPARISON OF FACE-TO-FACE VERSUS TELEMEDICINE PATIENT ASSESSMENT IN A PEDIATRIC INTENSIVE CARE UNIT SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 42nd Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 19-23, 2013 CL San Juan, PR SP Soc Crit Care Medi C1 [Yager, Phoebe; Dapul, Heda; Murphy, Sarah; Clark, Maureen; Zheng, Hui; Noviski, Natan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 SU S MA 253 BP U75 EP U75 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 050HZ UT WOS:000312045700216 ER PT J AU Tanner, JM Friedlander, AH Chang, TI AF Tanner, J. M. Friedlander, A. H. Chang, T. I. TI Bilateral bifid mandibular condyles diagnosed with three-dimensional reconstruction SO DENTOMAXILLOFACIAL RADIOLOGY LA English DT Article DE bifid mandibular condyle ID BEAM COMPUTED-TOMOGRAPHY; TEMPOROMANDIBULAR-JOINT; POPULATION AB Bifid mandibular condyles (BMCs) are rare anomalies. The overwhelming majority of prior reports described their predominantly unilateral occurrence diagnosed by panoramic radiography. We present an even rarer case of bilateral BMC initially identified by panoramic radiography and confirmed with colour-enhanced three-dimensional CT. These images substantiate the theory that the secondary condyles arise from the neck of the mandible (Lopez-Lopez et al. Bifid condyle: review of the literature of the last 10 years and report of two cases. Cianio 2010; 28: 136-140). Dentomaxillofacial Radiology (2012) 41, 691-695. doi: 10.1259/dmfr/15030240 C1 [Tanner, J. M.; Chang, T. I.] VA Greater Los Angeles Healthcare Syst, Oral & Maxillofacial Surg Sect, Los Angeles, CA 90073 USA. RP Chang, TI (reprint author), VA Greater Los Angeles Healthcare Syst, Oral & Maxillofacial Surg Sect, 11301 Wilshire Blvd W160, Los Angeles, CA 90073 USA. EM Tina.Chang2@va.gov NR 16 TC 0 Z9 0 U1 0 U2 1 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0250-832X J9 DENTOMAXILLOFAC RAD JI Dentomaxillofac. Radiol. PD DEC PY 2012 VL 41 IS 8 BP 691 EP 695 DI 10.1259/dmfr/15030240 PG 5 WC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging SC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging GA 056TM UT WOS:000312514300012 PM 22241877 ER PT J AU Ning, MM Lopez, M Cao, J Buonanno, FS Lo, EH AF Ning, MingMing Lopez, Mary Cao, Jing Buonanno, Ferdinando S. Lo, Eng H. TI Application of proteomics to cerebrovascular disease SO ELECTROPHORESIS LA English DT Review DE Biomarker; Cerebrovascular disease; Cerebrospinal fluid (CSF); Mass spectrometry; Pharmaco-proteomics; Stroke ID FOCAL CEREBRAL-ISCHEMIA; BLOOD-BRAIN-BARRIER; MATRIX-METALLOPROTEINASE EXPRESSION; TISSUE-PLASMINOGEN ACTIVATOR; STROKE-PRONE RATS; SELDI-TOF-MS; SUBARACHNOID HEMORRHAGE; CEREBROSPINAL-FLUID; SYSTEMS BIOLOGY; INTRACEREBRAL HEMORRHAGE AB While neurovascular diseases such as ischemic and hemorrhagic stroke are the leading causes of disability in the world, the repertoire of therapeutic interventions has remained remarkably limited. There is a dire need to develop new diagnostic, prognostic, and therapeutic options. The study of proteomics is particularly enticing for cerebrovascular diseases such as stroke, which most likely involve multiple gene interactions resulting in a wide range of clinical phenotypes. Currently, rapidly progressing neuroproteomic techniques have been employed in clinical and translational research to help identify biologically relevant pathways, to understand cerebrovascular pathophysiology, and to develop novel therapeutics and diagnostics. Future integration of proteomic with genomic, transcriptomic, and metabolomic studies will add new perspectives to better understand the complexities of neurovascular injury. Here, we review cerebrovascular proteomics research in both preclinical (animal, cell culture) and clinical (blood, urine, cerebrospinal fluid, microdialyates, tissue) studies. We will also discuss the rewards, challenges, and future directions for the application of proteomics technology to the study of various disease phenotypes. To capture the dynamic range of cerebrovascular injury and repair with a translational targeted and discovery approach, we emphasize the importance of complementing innovative proteomic technology with existing molecular biology models in preclinical studies, and the need to advance pharmacoproteomics to directly probe clinical physiology and gauge therapeutic efficacy at the bedside. C1 [Ning, MingMing; Cao, Jing; Buonanno, Ferdinando S.; Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Clin Prote Res Ctr, Boston, MA 02114 USA. [Ning, MingMing; Cao, Jing; Buonanno, Ferdinando S.; Lo, Eng H.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ning, MingMing; Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol & Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Lopez, Mary] Thermo Fisher BRIMS, Cambridge, MA USA. RP Ning, MM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Clin Prote Res Ctr, 15 Parkman St,ACC-739C, Boston, MA 02114 USA. EM ning@hms.harvard.edu FU NIH/NINDS [R01 NS067139, P01-NS55104] FX This work was supported by the NIH/NINDS: R01 NS067139 (Ning) and P01-NS55104 (Lo). NR 145 TC 3 Z9 3 U1 3 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD DEC PY 2012 VL 33 IS 24 SI SI BP 3582 EP 3597 DI 10.1002/elps.201200481 PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 057FT UT WOS:000312548900002 PM 23161401 ER PT J AU Kamnaksh, A Kwon, SK Kovesdi, E Ahmed, F Barry, ES Grunberg, NE Long, J Agoston, D AF Kamnaksh, Alaa Kwon, Sook-Kyung Kovesdi, Erzsebet Ahmed, Farid Barry, Erin S. Grunberg, Neil E. Long, Joseph Agoston, Denes TI Neurobehavioral, cellular, and molecular consequences of single and multiple mild blast exposure SO ELECTROPHORESIS LA English DT Article DE Blast; Cumulative effect; Neurobehavior; Protein biomarkers; Traumatic brain injury ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; HIPPOCAMPAL SLICE CULTURES; ENDOTHELIAL GROWTH-FACTOR; ISCHEMIA/REPERFUSION INJURY; ADULT HIPPOCAMPUS; COMBAT VETERANS; IRAQI FREEDOM; NEUROGENESIS; PTSD AB Mild traumatic brain injury, caused by the exposure to single or repeated blast overpressure, is a principal concern due to its pathological complexity and neurobehavioral similarities with posttraumatic stress disorder. In this study, we exposed rats to a single or multiple (five total; administered on consecutive days) mild blasts, assessed their behavior at 1 and 16 days postinjury) and performed histological and protein analyses of brains and plasma at an early (2 h) and a late (22 days) termination time point. One day postinjury, multiple-injured (MI) rats showed the least general locomotion and the most depression- and anxiety-related behaviors among the experimental groups; there were no such differences at 16 days. However, at the later time point, both injured groups displayed elevated levels of select protein biomarkers. Histology showed significantly increased numbers of TUNEL+ (terminal-deoxy-transferase-mediated dUTP nick-end labeling)-positive cells in the dorsal and ventral hippocampus (DHC and VHC) of both injured groups as early as 2 h after injury. At 22 days, the increase was limited to the VHC of MI animals. Our findings suggest that the exposure to mild blast overpressure triggers early hippocampal cell death as well as neuronal, glial, and vascular damage that likely contribute to significant, albeit transient increases in depression- and anxiety-related behaviors. However, the severity of the observed pathological changes in MI rats failed to support the hypothesized cumulative effect of repeated injury. We infer that at this blast frequency, a potential conditioning phenomenon counteracts with and reduces the extent of subsequent damage in MI rats. C1 [Agoston, Denes] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Sch Med, Bethesda, MD 20814 USA. [Kamnaksh, Alaa; Kwon, Sook-Kyung; Ahmed, Farid; Barry, Erin S.; Grunberg, Neil E.; Agoston, Denes] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Kovesdi, Erzsebet] US Dept Vet Affairs, Vet Affairs Cent Off, Washington, DC USA. [Barry, Erin S.; Grunberg, Neil E.] Walter Reed Army Inst Res, Dept Med & Clin Psychol, Silver Spring, MD USA. [Long, Joseph] Walter Reed Army Inst Res, Blast Induced Neurotrauma Branch, Ctr Mil Psychiat & Neurosci, Silver Spring, MD USA. RP Agoston, D (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Sch Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM vagoston@usuhs.edu FU Center for Neuroscience and Regenerative Medicine [G1703F] FX We thank the Neurotrauma Team at the Walter Reed Army Institute of Research for their technical help during the exposures. This work was supported by the Center for Neuroscience and Regenerative Medicine grant number G1703F. The views, opinions, and/or findings contained herein are those of the authors and should not be construed as an official position, policy, or decision of the Department of the Army or the Department of Defense. Animal handling and treatments were conducted in compliance with the Animal Welfare Act and other Federal statutes and regulations related to animals and experiments involving animals, and adhered to principles stated in the Guide to the Care and Use of Laboratory Animals, National Research Council. The facilities are fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International. NR 68 TC 18 Z9 19 U1 1 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD DEC PY 2012 VL 33 IS 24 SI SI BP 3680 EP 3692 DI 10.1002/elps.201200319 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 057FT UT WOS:000312548900011 PM 23161523 ER PT J AU De Calisto, J Villablanca, EJ Mora, JR AF De Calisto, Jaime Villablanca, Eduardo J. Mora, J. Rodrigo TI Fc gamma RI (CD64): An identity card for intestinal macrophages SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Editorial Material DE Gut mucosal interface; Immune tolerance; Inflammation; Intestinal immune homeostasis; Macrophages ID CD103(+) DENDRITIC CELLS; HIGH-AFFINITY RECEPTOR; HUMAN NEUTROPHILS; RESPONSES; EXPRESSION; INFLAMMATION; HOMEOSTASIS; MONOCYTES; IMMUNITY; SUBSET AB Macrophages are becoming increasingly recognized as key cellular players in intestinal immune homeostasis. However, differentiating between macrophages and dendritic cells (DCs) is often difficult, and finding a specific phenotypic signature for intestinal macrophage identification has remained elusive. In this issue of the European Journal of Immunology, Tamoutounour et al. [Eur. J. Immunol. 2012. 42: 3150-3166] identify CD64 as a specific macrophage marker that can be used to discriminate DCs from macrophages in the murine small and large intestine, under both steady-state and inflammatory conditions. The authors also propose a sequential monocyte-waterfall model for intestinal macrophage differentiation, with implications for immune tolerance and inflammation at the gut mucosal interface. This Commentary will discuss the advantages and potential limitations of CD64 as a marker for intestinal macrophages. C1 [De Calisto, Jaime; Villablanca, Eduardo J.; Mora, J. Rodrigo] Harvard Univ, Gastrointestinal Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Mora, JR (reprint author), Harvard Univ, Gastrointestinal Unit, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,GRJ 815, Boston, MA 02114 USA. EM j_rodrigo_mora@hms.harvard.edu RI Villablanca, Eduardo/E-1380-2016 OI Villablanca, Eduardo/0000-0001-9522-9729 FU NCCDPHP CDC HHS [DP2 2009A054301]; NIAID NIH HHS [P30 AI060354]; NIH HHS [DP2 OD006512] NR 31 TC 4 Z9 4 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 2012 VL 42 IS 12 BP 3136 EP 3140 DI 10.1002/eji.201243061 PG 5 WC Immunology SC Immunology GA 057FJ UT WOS:000312547800009 PM 23255010 ER PT J AU Aleksic, M Liddy, N Molloy, PE Pumphrey, N Vuidepot, A Chang, KM Jakobsen, BK AF Aleksic, Milos Liddy, Nathaniel Molloy, Peter E. Pumphrey, Nick Vuidepot, Annelise Chang, Kyong-Mi Jakobsen, Bent K. TI Different affinity windows for virus and cancer-specific T-cell receptors: Implications for therapeutic strategies SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Immunotherapy; T-cell; Thymic selection; Tumor immunology ID MEDULLARY EPITHELIAL-CELLS; GENE-EXPRESSION; HUMAN THYMUS; ANTIGEN; PEPTIDES; SINGLE; CRYSTALLIZATION; RECOGNITION; LYMPHOCYTES; VACCINATION AB T-cell destiny during thymic selection depends on the affinity of the TCR for autologous peptide ligands presented in the context of MHC molecules. This is a delicately balanced process; robust binding leads to negative selection, yet some affinity for the antigen complex is required for positive selection. All TCRs of the resulting repertoire thus have some intrinsic affinity for an MHC type presenting an assortment of peptides. Generally, TCR affinities of peripheral T cells will be low toward self-derived peptides, as these would have been presented during thymic selection, whereas, by serendipity, binding to pathogen-derived peptides that are encountered de novo could be stronger. A crucial question in assessing immunotherapeutic strategies for cancer is whether natural TCR repertoires have the capacity for efficiently recognizing tumor-associated peptide antigens. Here, we report a comprehensive comparison of TCR affinities to a range of HLA-A2 presented antigens. TCRs that bind viral antigens fall within a strikingly higher affinity range than those that bind cancer-related antigens. This difference may be one of the key explanations for tumor immune escape and for the deficiencies of T-cell vaccines against cancer. C1 [Aleksic, Milos; Liddy, Nathaniel; Molloy, Peter E.; Pumphrey, Nick; Vuidepot, Annelise; Jakobsen, Bent K.] Immunocore Ltd, Abingdon OX14 4RX, Oxon, England. [Chang, Kyong-Mi] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Chang, Kyong-Mi] Univ Penn, Philadelphia, PA 19104 USA. RP Jakobsen, BK (reprint author), Immunocore Ltd, 57C Milton Pk, Abingdon OX14 4RX, Oxon, England. EM bent.jakobsen@immunocore.com FU Immunocore Ltd., Abingdon, United Kingdom; NIH [AI047519]; Abramson Cancer Center FACS facility; Philadelphia VA Medical Research FX We would like to thank Peter Bader, Debbie Baker, Giovanna Bossi, Scott Burrows, Enzo Cerundolo, Sophie Conchon, Linda Hibbert, Erik Hooijberg John Miles, Yasuharu Nishimura, Samantha Paston, Jim Riley, Andrew Sewell, Robert Thimme, and Cassian Yee for providing T-cell clones; Hyosun Cho for work on the HCV-specific T cell lines; Conor Hayes, Qin Su, and Arsen Volkov for isolating TCR chains by RACE-PCR; Brian Cameron, Emma Gostick, Nikolai Lissin, Tara Mahon, and Alex Powlesland for protein production and SPR measurements; and Joanne Oates and Karen Pulford for assistance in manuscript preparation. This work was funded by Immunocore Ltd., Abingdon, United Kingdom. K.C. is also supported in part by: NIH AI047519, Abramson Cancer Center FACS facility and Philadelphia VA Medical Research. The contents of the publications/presentations do not represent the views of the VA or the US government. NR 36 TC 55 Z9 55 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 2012 VL 42 IS 12 BP 3174 EP 3179 DI 10.1002/eji.201242606 PG 6 WC Immunology SC Immunology GA 057FJ UT WOS:000312547800014 PM 22949370 ER PT J AU Baker, ML Seeley, ES Pai, R Suriawinata, AA Mino-Kenudson, M Zamboni, G Kloppel, G Longnecker, DS AF Baker, Michael L. Seeley, E. Scott Pai, Reetesh Suriawinata, Arief A. Mino-Kenudson, Mari Zamboni, Giuseppe Kloeppel, Gunter Longnecker, Daniel S. TI Invasive mucinous cystic neoplasms of the pancreas SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article DE Mucinous cystic neoplasm; Intraductal papillary mucinous neoplasm; Mucinous cystadenoma; Mucinous cystadenocarcinoma; Colloid carcinoma; MUC2; CDX2; Pancreas ID CYSTADENOCARCINOMA; FEATURES; CARCINOMA; STROMA; TUMORS; PROGNOSIS; BEHAVIOR AB Mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPMN) of the pancreas both appear to have been included and intermixed in some early reports of pancreatic cystic neoplasms. Recognition of their distinguishing features evolved during the last decade of the twentieth century. One legacy of the early period is the statement that mucinous cystic neoplasms sometimes progress to invasive colloid carcinoma. It is now recognized that colloid carcinomas characteristically arise from IPMN. We set out to see if we could find MCN that invaded as colloid carcinomas and found no examples in MCN collected in two academic medical centers. We then sought to expand the number of MCN by evaluating series from additional centers. This yielded no examples of colloid carcinomas associated with 291 MCN, however one MCN exhibited a minor component with colloid (non-cystic mucinous) growth pattern within the fibrous wall of the neoplasm. The expression of CDX2, a marker of intestinal differentiation that is found in colloid carcinomas was examined by immunostaining in the original MCN series and in the MCN with the intratumoral colloid growth pattern. Focal expression of CDX2 was found in 22 of 43 MCN including the MCN that exhibited the intratumoral colloid growth pattern. Overall, the data suggest that MCN rarely, if ever, invade as colloid carcinoma but the expression of CDX2 by some MCN and the observation of intratumoral colloid growth pattern in one MCN seems to leave open the possibility that MCN might rarely invade as colloid carcinoma. The majority of malignant MCN invade with a tubular (ductal) pattern, and rarely the invasive component was anaplastic. (C) 2012 Elsevier Inc. All rights reserved. C1 [Baker, Michael L.; Suriawinata, Arief A.; Longnecker, Daniel S.] Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03756 USA. [Baker, Michael L.; Suriawinata, Arief A.; Longnecker, Daniel S.] Dartmouth Med Sch, Lebanon, NH 03756 USA. [Seeley, E. Scott; Pai, Reetesh] Stanford Hosp & Clin, Dept Pathol, Stanford, CA USA. [Seeley, E. Scott; Pai, Reetesh] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Harvard Univ, Sch Med, Boston, MA USA. [Zamboni, Giuseppe] Osped S Cuore Don Calabria, Dept Pathol, Calabria, Italy. [Zamboni, Giuseppe] Univ Verona, I-37100 Verona, Italy. [Kloeppel, Gunter] Tech Univ Munich, Dept Pathol, D-8000 Munich, Germany. [Kloeppel, Gunter] Univ Kiel, Dept Pathol, D-24098 Kiel, Germany. RP Baker, ML (reprint author), Texas Childrens Hosp, Dept Pathol, 6621 Fannin St,Suite AB1195, Houston, TX 77030 USA. EM bakerm10@lsus.edu RI Giuseppe, Zamboni/A-5991-2016 OI Giuseppe, Zamboni/0000-0001-7428-4673 NR 28 TC 12 Z9 13 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD DEC PY 2012 VL 93 IS 3 SI SI BP 345 EP 349 DI 10.1016/j.yexmp.2012.07.005 PG 5 WC Pathology SC Pathology GA 056CN UT WOS:000312466100012 PM 22902940 ER PT J AU Ji, JY Miles, WO Korenjak, M Zheng, YN Dyson, NJ AF Ji, Jun-Yuan Miles, Wayne O. Korenjak, Michael Zheng, Yani Dyson, Nicholas J. TI In Vivo Regulation of E2F1 by Polycomb Group Genes in Drosophila SO G3-GENES GENOMES GENETICS LA English DT Article DE cell proliferation; E2F1; Su(z)2; PcG; Drosophila ID GROUP PROTEIN COMPLEXES; POSTERIOR SEX COMBS; CELL-CYCLE; HISTONE H3; TRANSCRIPTION FACTOR; ECTOPIC EXPRESSION; TUMOR SUPPRESSION; RNA INTERFERENCE; S-PHASE; MELANOGASTER AB The E2F transcription factors are important regulators of the cell cycle whose function is commonly misregulated in cancer. To identify novel regulators of E2F1 activity in vivo, we used Drosophila to conduct genetic screens. For this, we generated transgenic lines that allow the tissue-specific depletion of dE2F1 by RNAi. Expression of these transgenes using Gal4 drivers in the eyes and wings generated reliable and modifiable phenotypes. We then conducted genetic screens testing the capacity of Exelixis deficiencies to modify these E2F1-RNAi phenotypes. From these screens, we identified mutant alleles of Suppressor of zeste 2 [Su(z)2] and multiple Polycomb group genes as strong suppressors of the E2F1-RNA interference phenotypes. In validation of our genetic data, we find that depleting Su(z)2 in cultured Drosophila cells restores the cell-proliferation defects caused by reduction of dE2F1 by elevating the level of dE2f1. Furthermore, analyses of methylation status of histone H3 lysine 27 (H3K27me) from the published modENCODE data sets suggest that the genomic regions harboring dE2f1 gene and certain dE2f1 target genes display H3K27me during development and in several Drosophila cell lines. These in vivo observations suggest that the Polycomb group may regulate cell proliferation by repressing the transcription of dE2f1 and certain dE2F1 target genes. This mechanism may play an important role in coordinating cellular differentiation and proliferation during Drosophila development. C1 [Ji, Jun-Yuan; Zheng, Yani] Texas A&M Hlth Sci Ctr, Dept Mol & Cellular Med, Coll Med, College Stn, TX 77843 USA. [Ji, Jun-Yuan; Miles, Wayne O.; Korenjak, Michael; Dyson, Nicholas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Lab Mol Oncol, Charlestown, MA 02129 USA. [Ji, Jun-Yuan; Miles, Wayne O.; Korenjak, Michael; Dyson, Nicholas J.] Harvard Univ, Dept Pathol, Sch Med, Charlestown, MA 02129 USA. RP Ji, JY (reprint author), Texas A&M Hlth Sci Ctr, Dept Mol & Cellular Med, Coll Med, College Stn, TX 77843 USA. EM ji@medicine.tamhsc.edu FU Fund for Medical Discovery Postdoctoral Fellowship from Massachusetts General Hospital; Texas A&M Health Science Center; American Heart Association; National Institutes of Health [R01GM053203] FX We thank Richard Carthew and Andre Bernard for sharing the pWIZ vector, Fajun Yang for his advice in generating pWIZ-dE2f1 constructs, Doug Renee at the MGH Drosophila transgene core facility for his help in making transgenic flies, Bill Fowle at the Northeastern University for his expertise with scanning electron microscopy, and Rebecca Wang for technical assistant. We appreciate Keith Maggert as well as the anonymous reviewers for critical reading of the manuscript and constructive comments. We are grateful to Richard Carthew, Robert Duronio, Richard Emmons, Antonio Garcia-Bellido, Vincenzo Pirrotta, Chao-Ting Wu, and the Bloomington Drosophila Stock Center for mutant stocks and reagents used in this work. This work is supported in part by a Fund for Medical Discovery Postdoctoral Fellowship from Massachusetts General Hospital, a startup fund from Texas A&M Health Science Center and a grant from the American Heart Association to J.-Y.J., and National Institutes of Health grant (R01GM053203) to N.J.D., the James and Shirley Curvey MGH Research Scholar. The first author would like to dedicate this paper to the memory of Professor Gerold Schubiger for his many years of inspiration and support. NR 63 TC 7 Z9 7 U1 1 U2 4 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD DEC 1 PY 2012 VL 2 IS 12 BP 1651 EP 1660 DI 10.1534/g3.112.004333 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 055ZZ UT WOS:000312458000016 PM 23275887 ER PT J AU Newhouse, JP Price, M Huang, J McWilliams, JM Hsu, J AF Newhouse, Joseph P. Price, Mary Huang, Jie McWilliams, J. Michael Hsu, John TI Steps To Reduce Favorable Risk Selection In Medicare Advantage Largely Succeeded, Boding Well For Health Insurance Exchanges SO HEALTH AFFAIRS LA English DT Article ID ADVERSE SELECTION; ADJUSTMENT; MODEL AB Within Medicare, the Medicare Advantage program has historically attracted better risks-healthier, lower-cost patients-than has traditional Medicare. The disproportionate enrollment of lower-cost patients and avoidance of higher-cost ones during the 1990s-known as favorable selection-resulted in Medicare's spending more per beneficiary who enrolled in Medicare Advantage than if the enrollee had remained in traditional Medicare. We looked at two measures that can indicate whether favorable selection is taking place-predicted spending on beneficiaries and mortality-and studied whether policies that Medicare implemented in the past decade succeeded in reducing favorable selection in Medicare Advantage. We found that these policies-an improved risk adjustment formula and a prohibition on monthly disenrollment by beneficiaries-largely succeeded. Differences in predicted spending between those switching from traditional Medicare to Medicare Advantage relative to those who remained in traditional Medicare markedly narrowed, as did adjusted mortality rates. Because insurance exchanges set up under the Affordable Care Act will employ similar policies to combat risk selection, our results give reason for optimism about managing competition among health plans. C1 [Newhouse, Joseph P.] Harvard Univ, Div Hlth Policy Res & Educ, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Interfac Initiat Hlth Policy, Boston, MA 02115 USA. [Price, Mary; Huang, Jie] Kaiser Permanente No Calif Div Res, Oakland, CA USA. [McWilliams, J. Michael] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA USA. [Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Program Clin Econ & Policy Anal, Boston, MA 02114 USA. [Newhouse, Joseph P.] Harvard Univ, Comm Higher Degrees Hlth Policy, Boston, MA 02115 USA. RP Newhouse, JP (reprint author), Harvard Univ, Div Hlth Policy Res & Educ, Boston, MA 02115 USA. EM newhouse@hcp.med.harvard.edu FU National Institute on Aging [P01-032952] FX Earlier versions of this article were presented at the International Health Economics Association meeting, in Toronto, Ontario, July 2011, and the American Society of Health Economists meeting, in Minneapolis, Minnesota, July 2012. The authors acknowledge support from the National Institute on Aging, Grant No. P01-032952. Joseph Newhouse is a director of, and holds equity in, Aetna, which sells Medicare Advantage products. The authors thank Thomas G. McGuire and three reviewers for comments. NR 25 TC 26 Z9 26 U1 0 U2 14 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD DEC PY 2012 VL 31 IS 12 BP 2618 EP 2628 DI 10.1377/hlthaff.2012.0345 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 057ZA UT WOS:000312602100004 PM 23213145 ER PT J AU McWilliams, JM Hsu, J Newhouse, JP AF McWilliams, J. Michael Hsu, John Newhouse, Joseph P. TI New Risk-Adjustment System Was Associated With Reduced Favorable Selection In Medicare Advantage SO HEALTH AFFAIRS LA English DT Article ID BIASED SELECTION; HMOS AB Health plans participating in the Medicare managed care program, called Medicare Advantage since 2003, have historically attracted healthier enrollees than has the traditional fee-for-service program. Medicare Advantage plans have gained financially from this favorable risk selection since their payments have traditionally been adjusted only minimally for clinical characteristics of enrollees, causing overpayment for healthier enrollees and underpayment for sicker ones. As a result, a new risk-adjustment system was phased in from 2004 to 2007, and a lock-in provision instituted to limit midyear disenrollment by enrollees experiencing health declines whose exodus could benefit plans financially. To determine whether these reforms were associated with intended reductions in risk selection, we compared differences in self-reported health care use and health between Medicare Advantage and traditional Medicare beneficiaries before versus after these reforms were implemented. We similarly compared differences between those who switched into or out of Medicare Advantage and nonswitchers. Most differences in 2001-03 were substantially narrowed by 2006-07, suggesting reduced selection. Similar risk-adjustment methods may help reduce incentives for plans competing in health insurance exchanges and accountable care organizations to select patients with favorable clinical risks. C1 [McWilliams, J. Michael; Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [McWilliams, J. Michael] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Program Clin Econ & Policy Anal, Boston, MA 02114 USA. [Newhouse, Joseph P.] Harvard Univ, Div Hlth Policy Res & Educ, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Comm Higher Degrees Hlth Policy, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Interfac Initiat Hlth Policy, Boston, MA 02115 USA. RP McWilliams, JM (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. EM mcwilliams@hcp.med.harvard.edu FU National Institute on Aging [K08 AG038354, P01 AG032952]; American Federation for Aging Research FX Findings were previously reported at the Society of General Internal Medicine Annual Meeting, Orlando, Florida, May 2012; and at the AcademyHealth Annual Research Meeting, Orlando, Florida, June 2012. This study was supported by grants from the Beeson Career Development Award Program (National Institute on Aging Grant No. K08 AG038354 and American Federation for Aging Research) and from the National Institute on Aging (Grant No. P01 AG032952). Joseph Newhouse is a director of and holds equity in Aetna, which sells Medicare Advantage plans. Michael McWilliams and John Hsu have no conflicts of interest to disclose. The authors are grateful to Pasha Hamed and Mary Price for statistical programming, to Austin Frakt and Jeff Souza for sharing statistical code, and to Thomas G. McGuire and John Z. Ayanian for helpful comments on an earlier draft. NR 20 TC 19 Z9 19 U1 0 U2 8 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD DEC PY 2012 VL 31 IS 12 BP 2630 EP 2640 DI 10.1377/hlthaff.2011.1344 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 057ZA UT WOS:000312602100006 PM 23213147 ER PT J AU Reed, ME Graetz, I Fung, V Newhouse, JP Hsu, J AF Reed, Mary E. Graetz, Ilana Fung, Vicki Newhouse, Joseph P. Hsu, John TI In Consumer-Directed Health Plans, A Majority Of Patients Were Unaware Of Free Or Low-Cost Preventive Care SO HEALTH AFFAIRS LA English DT Article ID EXPENDITURES; EMPLOYER; SERVICES; COVERAGE AB Consumer-directed health plans are plans with high deductibles that typically require patients to bear no out-of-pocket costs for preventive care, such as annual physicals or screening tests, in order to ease financial barriers and encourage patients to seek such care. We surveyed people in California who had a consumer-directed health plan and found that fewer than one in five understood that their plan exempted preventive office visits, medical tests, and screenings from their deductible, meaning that this care was free or had a modest copayment. Roughly one in five said that they had delayed or avoided a preventive office visit, test, or screening because of cost. Those who were confused about the exemption were significantly more likely to report avoiding preventive visits because of cost concerns. Special efforts to educate consumers about preventive care cost-sharing exemptions may be necessary as more health plans, including Medicare, adopt this model. C1 [Reed, Mary E.; Graetz, Ilana] Kaiser Permanente, No Calif Div Res, Oakland, CA 94612 USA. [Graetz, Ilana] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Fung, Vicki] MidAtlantic Permanente Med Grp, Midatlantic Permanente Res Inst, Rockville, MD USA. [Newhouse, Joseph P.] Harvard Univ, Div Hlth Policy Res & Educ, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Comm Higher Degrees Hlth Policy, Boston, MA 02115 USA. [Hsu, John] Massachusetts Gen Hosp, Program Clin Econ & Policy Anal, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Hsu, John] Harvard Univ, Sch Med, Boston, MA USA. RP Reed, ME (reprint author), Kaiser Permanente, No Calif Div Res, Oakland, CA 94612 USA. EM mary.e.reed@kp.org RI Graetz, Ilana/N-1189-2016 OI Graetz, Ilana/0000-0003-3664-5815 FU Kaiser Foundation Research Institute FX Findings included in this article were presented at the AcademyHealth Annual Research Meeting, June 2010, in Boston, Massachusetts. This study was funded by the Kaiser Foundation Research Institute. Joseph Newhouse is a director of and holds equity in Aetna, which sells consumer-directed health plans. NR 20 TC 15 Z9 15 U1 1 U2 5 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD DEC PY 2012 VL 31 IS 12 BP 2641 EP 2648 DI 10.1377/hlthaff.2012.0059 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 057ZA UT WOS:000312602100007 PM 23213148 ER PT J AU Kind, AJH Jensen, L Barczi, S Bridges, A Kordahl, R Smith, MA Asthana, S AF Kind, Amy J. H. Jensen, Laury Barczi, Steve Bridges, Alan Kordahl, Rebecca Smith, Maureen A. Asthana, Sanjay TI Low-Cost Transitional Care With Nurse Managers Making Mostly Phone Contact With Patients Cut Rehospitalization At A VA Hospital SO HEALTH AFFAIRS LA English DT Article ID CONTROLLED-TRIAL; HEART-FAILURE; VETERANS; DEMENTIA; INTERVENTION; VALIDATION; MEDICARE; PROGRAM; QUALITY AB The Coordinated-Transitional Care (C-TraC) Program was designed to improve care coordination and outcomes among veterans with high-risk conditions discharged to community settings from the William S. Middleton Memorial Veterans Hospital, in Madison, Wisconsin. Under the program, patients work with nurse case managers on care and health issues, including medication reconciliation, before and after hospital discharge, with all contacts made by phone once the patient is at home. Patients who received the C-TraC protocol experienced one-third fewer rehospitalizations than those in a baseline comparison group, producing an estimated savings of $1,225 per patient net of programmatic costs. This model requires a relatively small amount of resources to operate and may represent a viable alternative for hospitals seeking to offer improved transitional care as encouraged by the Affordable Care Act. In particular, the model may be attractive for providers in rural areas or other care settings challenged by wide geographic dispersion of patients or by constrained resources. C1 [Kind, Amy J. H.] William S Middleton Mem Vet Adm Med Ctr, Coordinated Transit Care Program C TraC, GRECC, Madison, WI USA. [Kind, Amy J. H.; Barczi, Steve; Asthana, Sanjay] Univ Wisconsin, Sch Med & Publ Hlth, Div Geriatr & Gerontol, Madison, WI 53706 USA. [Asthana, Sanjay] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53706 USA. [Kordahl, Rebecca] William S Middleton Mem Vet Adm Med Ctr, Patient Care Serv, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Hlth Innovat Program, Madison, WI 53706 USA. RP Kind, AJH (reprint author), William S Middleton Mem Vet Adm Med Ctr, Coordinated Transit Care Program C TraC, GRECC, Madison, WI USA. EM ajk@medicine.wisc.edu FU VA Transformation-21 Grant, "Patient-Centric Alternatives to Institutional Extended Care"; Madison VA Geriatrics Research, Education, and Clinical Center (GRECC) [2012-08]; National Institute on Aging [K23AG034551]; National Institute on Aging, in partnership with the American Federation for Aging Research; John A. Hartford Foundation; Atlantic Philanthropies; Starr Foundation; University of Wisconsin School of Medicine and Public Health's Health Innovation Program; Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research; Clinical and Translational Science Award program of the National Center for Research Resources, National Institutes of Health [1UL1RR025011]; VA Office of Geriatrics and Extended Care in the VA Central Office; Veterans Integrated Service Network 12; William S. Middleton Memorial Veterans Hospital FX Some of the information in this article was presented as a poster at the annual meeting of the American Geriatrics Society, Seattle, Washington, May 3, 2012. The design, implementation, and assessment of the C-TraC Program and the writing of this article were supported by a VA Transformation-21 Grant, "Patient-Centric Alternatives to Institutional Extended Care," and the Madison VA Geriatrics Research, Education, and Clinical Center (GRECC-Manuscript No. 2012-08); and were funded through the National Institute on Aging Paul B. Beeson Patient-Oriented Research Career Development Award (K23AG034551 [PI Kind], National Institute on Aging, in partnership with the American Federation for Aging Research, the John A. Hartford Foundation, the Atlantic Philanthropies, and the Starr Foundation). Additional support was provided by the University of Wisconsin School of Medicine and Public Health's Health Innovation Program; the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research; and the Clinical and Translational Science Award program of the National Center for Research Resources, National Institutes of Health (Grant No. 1UL1RR025011). No funding source had a 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. The authors acknowledge Ken Shay, Barbara Hyduke, and Karen Massey in the VA Office of Geriatrics and Extended Care in the VA Central Office and the leadership of both the Veterans Integrated Service Network 12 and the William S. Middleton Memorial Veterans Hospital for their support of the C-TraC Program; Peggy Munson for Institutional Review Board assistance; Sheila Kelly and Megan Carey for data abstraction; and Colleen Brown, Andrea Gilmore, Melissa Hovanes, Brock Polnaszek, and Joanna Wong for manuscript formatting and graphics. NR 27 TC 23 Z9 24 U1 1 U2 18 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD DEC PY 2012 VL 31 IS 12 BP 2659 EP 2668 DI 10.1377/hlthaff.2012.0366 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 057ZA UT WOS:000312602100009 PM 23213150 ER PT J AU Das, J Holla, A Das, V Mohanan, M Tabak, D Chan, B AF Das, Jishnu Holla, Alaka Das, Veena Mohanan, Manoj Tabak, Diana Chan, Brian TI In Urban And Rural India, A Standardized Patient Study Showed Low Levels Of Provider Training And Huge Quality Gaps SO HEALTH AFFAIRS LA English DT Article ID LOW-INCOME COUNTRIES; MEDICAL-EDUCATION; CARE; PERFORMANCE; SERVICES; DOCTORS; IMPACT; DELHI AB This article reports on the quality of care delivered by private and public providers of primary health care services in rural and urban India. To measure quality, the study used standardized patients recruited from the local community and trained to present consistent cases of illness to providers. We found low overall levels of medical training among health care providers; in rural Madhya Pradesh, for example, 67 percent of health care providers who were sampled reported no medical qualifications at all. What's more, we found only small differences between trained and untrained doctors in such areas as adherence to clinical checklists. Correct diagnoses were rare, incorrect treatments were widely prescribed, and adherence to clinical checklists was higher in private than in public clinics. Our results suggest an urgent need to measure the quality of health care services systematically and to improve the quality of medical education and continuing education programs, among other policy changes. C1 [Holla, Alaka] World Bank, Human Dev Network, Chief Economists Off, Washington, DC 20433 USA. [Das, Veena] Johns Hopkins Univ, Baltimore, MD USA. [Mohanan, Manoj] Duke Univ, Sanford Sch Publ Policy, Durham, NC USA. [Tabak, Diana] Univ Toronto, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada. [Tabak, Diana] Univ Toronto, Standardized Patient Program, Toronto, ON M5S 1A1, Canada. [Chan, Brian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chan, Brian] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Das, J (reprint author), Ctr Policy Res, New Delhi, India. EM jdas1@worldbank.org FU Global Health Program of the Bill & Melinda Gates Foundation [50728] FX This study was funded by the Global Health Program of the Bill & Melinda Gates Foundation through Grant No. 50728, which was made to Innovations for Poverty Action, in New Haven, Connecticut. The authors thank Purshottam, Rajan Singh, Devender, Charu Nanda, Simi Bajaj, Geeta, the standardized patients, and all of the other members of the Institute for Socioeconomic Research on Democracy and Development in Delhi for conducting the fieldwork. Monisha Ashok, Anvesha Khandelwal, Carl Liebersohn, Suzanne Plant, and especially Aakash Mohpal provided invaluable research assistance. The authors thank Michael Kremer, Karthik Muralidharan, Sreela Dasgupta, and the staff of the Center for Policy Research, New Delhi, for many helpful discussions and comments. The findings, interpretations, and conclusions expressed in this article are those of the authors and do not necessarily represent the views of the World Bank, its executive directors, or the governments they represent. NR 33 TC 66 Z9 66 U1 0 U2 9 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD DEC PY 2012 VL 31 IS 12 BP 2774 EP 2784 DI 10.1377/hlthaff.2011.1356 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 057ZA UT WOS:000312602100021 PM 23213162 ER PT J AU Park, JD Metlay, J Asch, JM Asch, DA AF Park, James D. Metlay, Jessica Asch, Jeremy M. Asch, David A. TI The New York Times Readers' Opinions About Paying People to Take Their Medicine SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE chronic disease management; health policy; health promotion; media; qualitative methods ID FINANCIAL INCENTIVES; HEALTH; ACCEPTABILITY; SMOKING AB Background. There has been considerable interest in using financial incentives to help people improve their health. However, paying people to improve their health touches on strongly held views about personal responsibility. Method. The New York Times printed two articles in June 2010 about patient financial incentives, which resulted in 394 comments from their online audience. The authors systematically analyzed those online responses to news media in order to understand the range of themes that were expressed regarding the use of financial incentives to improve health. Results. The New York Times online readers revealed a broad range of attitudes about paying individuals to be healthy. Many comments reflected disdain for financial incentives, describing them as "absurd" or "silly." Other comments reflected the notion that financial incentives reward individuals for being irresponsible toward their health. Many individuals communicated concerns that paying individuals for healthy behaviors may weaken their internal drive to be healthy. A smaller set of comments conveyed support for financial incentives, recognizing it as a small sum to pay to prevent or offset higher costs related to chronic diseases. Conclusions. Although a measurable group of individuals supported financial incentives, most readers revealed negative perceptions of these approaches and an appeal for greater personal responsibility for individual health. Despite experimental success of financial incentives, negative perceptions may limit their public acceptability and uptake. C1 [Park, James D.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Metlay, Jessica] Vassar Coll, Poughkeepsie, NY 12601 USA. [Asch, Jeremy M.] Brandeis Univ, Waltham, MA USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Park, JD (reprint author), Univ Penn, Div Gen Internal Med, 1005 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jdpark@mail.med.upenn.edu OI Asch, David/0000-0002-7970-286X FU PHS HHS [T32-HP-10026] NR 26 TC 3 Z9 3 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD DEC PY 2012 VL 39 IS 6 BP 725 EP 731 DI 10.1177/1090198111428645 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 057JM UT WOS:000312559300010 PM 22467634 ER PT J AU Akiyoshi, T Hirohashi, T Alessandrini, A Chase, CM Farkash, EA Smith, RN Madsen, JC Russell, PS Colvin, RB AF Akiyoshi, Takurin Hirohashi, Tsutomu Alessandrini, Alessandro Chase, Catherine M. Farkash, Evan A. Smith, R. Neal Madsen, Joren C. Russell, Paul S. Colvin, Robert B. TI Role of complement and NK cells in antibody mediated rejection SO HUMAN IMMUNOLOGY LA English DT Article ID RENAL-ALLOGRAFT REJECTION; TRANSPLANTED MOUSE HEARTS; IFN-GAMMA PRODUCTION; INTERFERON-GAMMA; KIDNEY-TRANSPLANTATION; C4D DEPOSITION; HYPERACUTE REJECTION; HUMORAL ANTIBODIES; ENDOTHELIAL-CELLS; CORONARY ARTERIOSCLEROSIS AB Despite extensive research on T cells and potent immunosuppressive regimens that target cellular mediated rejection, few regimens have been proved to be effective on antibody-mediated rejection (AMR), particularly in the chronic setting. C4d deposition in the graft has been proved to be a useful marker for AMR; however, there is an imperfect association between C4d and AMR. While complement has been considered as the main player in acute AMR, the effector mechanisms in chronic AMR are still debated. Recent studies support the role of NK cells and direct effects of antibody on endothelium cells in a mechanism suggesting the presence of a complement-independent pathway. Here, we review the history, currently available systems and progress in experimental animal research. Although there are consistent findings from human and animal research, transposing the experimental results from rodent to human has been hampered by the differences in endothelial functions between species. We briefly describe the findings from patients and compare them with results from animals, to propose a combined perspective. (C) 2012 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics. C1 [Akiyoshi, Takurin; Farkash, Evan A.; Smith, R. Neal; Colvin, Robert B.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirohashi, Tsutomu; Alessandrini, Alessandro; Chase, Catherine M.; Madsen, Joren C.; Russell, Paul S.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Colvin, RB (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Thier 831, Boston, MA 02114 USA. EM colvin@helix.mgh.harvard.edu FU National Institutes of Health; Roche Organ Transplantation Research Foundation; American Society of Transplantation FX The authors acknowledge grant support from the National Institutes of Health, the Roche Organ Transplantation Research Foundation, and the American Society of Transplantation. NR 85 TC 25 Z9 25 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD DEC PY 2012 VL 73 IS 12 SI SI BP 1226 EP 1232 DI 10.1016/j.humimm.2012.07.330 PG 7 WC Immunology SC Immunology GA 047WN UT WOS:000311872300004 PM 22850181 ER PT J AU Mahida, S Ellinor, PT AF Mahida, Saagar Ellinor, Patrick T. TI New Advances in the Genetic Basis of Atrial Fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; genetics; inherited arrhythmias; molecular biology; heart rate ID GENOME-WIDE ASSOCIATION; CA2+-ACTIVATED K+ CHANNELS; OF-FUNCTION MUTATION; CHROMOSOME 4Q25; SMALL-CONDUCTANCE; EUROPEAN ANCESTRY; PACEMAKER CHANNEL; ISCHEMIC-STROKE; HEART-FAILURE; HOMEOBOX GENE AB New Genetic Loci for Atrial Fibrillation. Over the past decade, compelling evidence has emerged from population-based studies to suggest that AF is a heritable disease. More recently, we have begun to elucidate the genetic substrate underlying AF. Genome-wide association studies (GWAS) have led to the identification of multiple risk loci that confer increased susceptibility to the arrhythmia. These loci harbor intriguing candidate genes including those encoding ion channels, transcription factors, and signaling molecules. Current efforts are ongoing to functionally validate the role of these genes in disease pathogenesis. In the future, novel genotyping technologies such as exome sequencing and whole-genome sequencing promise to uncover a greater proportion of the heritability underlying AF. In this article we review recent advances in AF genetics research and discuss future developments in the field. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1400-1407, December 2012) C1 [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Mahida, Saagar; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. EM pellinor@partners.org FU NIH [1RO1HL092577, 5R21DA027021, 1RO1HL104156, 1K24HL105780] FX Dr. Ellinor is supported by NIH grants 1RO1HL092577, 5R21DA027021, 1RO1HL104156, and 1K24HL105780. NR 72 TC 16 Z9 17 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD DEC PY 2012 VL 23 IS 12 BP 1400 EP 1406 DI 10.1111/j.1540-8167.2012.02445.x PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 057CC UT WOS:000312538500025 PM 23066792 ER PT J AU Huynh, TN Weigt, SS Sugar, CA Shapiro, S Kleerup, EC AF Huynh, Thanh N. Weigt, S. Sam Sugar, Catherine A. Shapiro, Shelley Kleerup, Eric C. TI Prognostic factors and outcomes of patients with pulmonary hypertension admitted to the intensive care unit SO JOURNAL OF CRITICAL CARE LA English DT Article DE Pulmonary hypertension; Intensive care unit; Pulmonary artery catheterization ID CRITICALLY-ILL PATIENTS; RIGHT HEART-FAILURE; ARTERIAL-HYPERTENSION; PROSTACYCLIN; MANAGEMENT; DISEASE; CATHETER; INFUSION; THERAPY AB Purpose: Patients with pulmonary hypertension (PH) can decompensate to the point where they require care in the intensive care unit (ICU). Our objective is to examine the outcomes and characteristics of patients with PH admitted to the ICU. Methods: This is a retrospective study of 99 patients with PH who were admitted to the medical ICU of a single tertiary care center. Baseline characteristics, interventions during ICU admission, and ICU and 6-month outcome were documented. Univariate and multivariate logistic regressions were used to evaluate association of patient characteristics with mortality. Results: Intensive care unit mortality was 30%, and 6-month mortality was 40%. Acute Physiology and Chronic Health Evaluation II score, World Health Organization Group 3 PH, and preexisting treatment with a prostacyclin at time of ICU admission were associated with worse outcome. Patients who received cardiopulmonary resuscitation had 100% mortality. The requirement for mechanical ventilation and dialysis was also associated with increased mortality. Pulmonary artery catheter placement was associated with reduced mortality, specifically if it was placed early during ICU admission and if associated with a change in the present management. Conclusions: Mortality is high in critically ill patients with PH. The identification of prognostic baseline characteristics and interventions in the ICU is important and warrants further investigation. (C) 2012 Elsevier Inc. All rights reserved. C1 [Huynh, Thanh N.; Weigt, S. Sam; Kleerup, Eric C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Shapiro, Shelley] Univ Calif Los Angeles, Dept Cardiol, VA Greater Healthcare Syst, Los Angeles, CA 90095 USA. RP Huynh, TN (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, BOX 951690,37-131 CHS, Los Angeles, CA 90095 USA. EM thuynh@mednet.ucla.edu FU NCRR NIH HHS [L30 RR033215] NR 23 TC 5 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 0883-9441 J9 J CRIT CARE JI J. Crit. Care PD DEC PY 2012 VL 27 IS 6 AR 739.e7 DI 10.1016/j.jcrc.2012.08.006 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 057YF UT WOS:000312599800034 PM 23089677 ER PT J AU Carter, SC Konijeti, R Hu, J AF Carter, Stacey C. Konijeti, Ramdev Hu, Jim TI Selective Suture Ligation of the Dorsal Vein Complex During Robot-Assisted Laparoscopic Radical Prostatectomy SO JOURNAL OF ENDOUROLOGY LA English DT Article AB Technique for apical dissection and control of the dorsal vein complex (DVC) during robot-assisted laparoscopic radical prostatectomy (RALP) affects blood loss, apical positive margins, and recovery of urinary control. Over the past 7 years, our technique for apical dissection has been spurred by the overarching goal of minimizing injury to the rhabdosphincter to improve urinary continence, evolving from stapling to suture ligation of the DVC before bladder neck dissection to an athermal DVC division followed by selective suture ligation (DVC-SSL) before RALP anastomosis. Assessment of patient-reported quality of life outcomes demonstrates earlier recovery of continence with DVC-SSL. C1 [Carter, Stacey C.; Hu, Jim] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90024 USA. [Konijeti, Ramdev] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Hu, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, 924 Westwood Blvd,Ste 1000, Los Angeles, CA 90024 USA. EM JCHu@mednet.ucla.edu NR 1 TC 4 Z9 5 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD DEC PY 2012 VL 26 IS 12 BP 1576 EP 1577 DI 10.1089/end.2012.0415 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 054XQ UT WOS:000312379200009 PM 23146080 ER PT J AU Velmurugan, K Bouchard, R Mahaffey, G Pugazhenthi, S AF Velmurugan, Kalpana Bouchard, Ron Mahaffey, Gregory Pugazhenthi, Subbiah TI Neuroprotective actions of Glucagon-like peptide-1 in differentiated human neuroprogenitor cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; apoptosis; CREB; glucagon-like peptide-1; human neuroprogenitor cells; signal transduction ID ELEMENT-BINDING PROTEIN; NEURAL STEM-CELLS; TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; HIPPOCAMPAL-NEURONS; PROMOTES NEUROGENESIS; DIABETES-MELLITUS; DOWN-REGULATION; BCL-2 PROMOTER; CREB AB Glucagon-like peptide-1 (GLP-1)-based therapies are currently available for the treatment of type 2 diabetes, based on their actions on pancreatic beta cells. GLP-1 is also known to exert neuroprotective actions. To determine its mechanism of action, we developed a neuron-rich cell culture system by differentiating human neuroprogenitor cells in the presence of a combination of neurotrophins and retinoic acid. The neuronal nature of these cells was characterized by neurogenesis pathway-specific array. GLP-1 receptor expression was seen mainly in the neuronal population. Culture of neurons in the presence of A beta oligomers resulted in the induction of apoptosis as shown by the activation of caspase-3 and caspase-6. Exendin-4, a long-acting analog of GLP-1, protected the neurons from apoptosis induced by A beta oligomers. Exendin-4 stimulated cyclic AMP response element binding protein phosphorylation, a regulatory step in its activation. A transient transfection assay showed induction of a reporter linked to CRE site-containing human brain-derived neurotrophic factor promoter IV, by the growth factor through multiple signaling pathways. The anti-apoptotic action of exendin-4 was lost following down-regulation of cAMP response element binding protein. Withdrawal of neurotrophins resulted in the loss of neuronal phenotype of differentiated neuroprogenitor cells, which was prevented by incubation in the presence of exendin-4. Diabetes is a risk factor in the pathogenesis of Alzheimer's disease. Our findings suggest that GLP-1-based therapies can decrease the incidence of Alzheimer's disease among aging diabetic population. C1 [Velmurugan, Kalpana; Bouchard, Ron; Pugazhenthi, Subbiah] Vet Affairs Med Ctr, Endocrinol Sect, Denver, CO USA. [Velmurugan, Kalpana; Bouchard, Ron; Mahaffey, Gregory; Pugazhenthi, Subbiah] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA. RP Pugazhenthi, S (reprint author), Univ Colorado Denver, Denver VA Med Ctr, Mail Stop 8106,12801 E 17th Ave, Aurora, CO 80045 USA. EM subbiah.pugazhenthi@ucdenver.edu FU Veterans Administration [NEUD-004-07F] FX This work was carried out with the use of resources and facilities at Denver VA Medical Center. This study was supported by Merit Review grant NEUD-004-07F from the Veterans Administration (to S. P.). RT-PCR analysis was performed at the University of Colorado Cancer Center Core Facility. Digital deconvolution microscopy was carried out at the VA Microscopy Core Facility. Authors declare that there is no conflict of interest associated with this manuscript. NR 48 TC 18 Z9 18 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2012 VL 123 IS 6 BP 919 EP 931 DI 10.1111/jnc.12036 PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 051WK UT WOS:000312158500004 PM 23020846 ER PT J AU Wang, GI Delgutte, B AF Wang, Grace I. Delgutte, Bertrand TI Sensitivity of cochlear nucleus neurons to spatio-temporal changes in auditory nerve activity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE coincidence detection; spatio-temporal pattern; cochlear nucleus; auditory nerve; anesthetized cat ID LATERAL SUPERIOR OLIVE; MASKING PERIOD PATTERNS; SPHERICAL BUSHY CELLS; LOW-FREQUENCY NEURONS; SOUND PRESSURE LEVEL; INFERIOR COLLICULUS; DISCHARGE PATTERNS; OCTOPUS CELLS; ONSET NEURONS; GLYCINERGIC INHIBITION AB Wang GI, Delgutte B. Sensitivity of cochlear nucleus neurons to spatio-temporal changes in auditory nerve activity. J Neurophysiol 108: 3172-3195, 2012. First published September 12, 2012; doi:10.1152/jn.00160.2012.-The spatio-temporal pattern of auditory nerve (AN) activity, representing the relative timing of spikes across the tonotopic axis, contains cues to perceptual features of sounds such as pitch, loudness, timbre, and spatial location. These spatio-temporal cues may be extracted by neurons in the cochlear nucleus (CN) that are sensitive to relative timing of inputs from AN fibers innervating different cochlear regions. One possible mechanism for this extraction is "cross-frequency" coincidence detection (CD), in which a central neuron converts the degree of coincidence across the tonotopic axis into a rate code by preferentially firing when its AN inputs discharge in synchrony. We used Huffman stimuli (Carney LH. J Neurophysiol 64: 437-456, 1990), which have a flat power spectrum but differ in their phase spectra, to systematically manipulate relative timing of spikes across tonotopically neighboring AN fibers without changing overall firing rates. We compared responses of CN units to Huffman stimuli with responses of model CD cells operating on spatio-temporal patterns of AN activity derived from measured responses of AN fibers with the principle of cochlear scaling invariance. We used the maximum likelihood method to determine the CD model cell parameters most likely to produce the measured CN unit responses, and thereby could distinguish units behaving like cross-frequency CD cells from those consistent with same-frequency CD (in which all inputs would originate from the same tonotopic location). We find that certain CN unit types, especially those associated with globular bushy cells, have responses consistent with cross-frequency CD cells. A possible functional role of a cross-frequency CD mechanism in these CN units is to increase the dynamic range of binaural neurons that process cues for sound localization. C1 [Wang, Grace I.; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Wang, Grace I.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Wang, Grace I.; Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Delgutte, Bertrand] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Delgutte, B (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM bertrand_delgutte@meei.harvard.edu OI , /0000-0003-1349-9608 FU National Institute on Deafness and Other Communication Disorders [R01 DC-002258, P30 DC-005209] FX This work was supported by National Institute on Deafness and Other Communication Disorders Grants R01 DC-002258 and P30 DC-005209. NR 89 TC 4 Z9 4 U1 0 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2012 VL 108 IS 12 BP 3172 EP 3195 DI 10.1152/jn.00160.2012 PG 24 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 057UI UT WOS:000312589100002 PM 22972956 ER PT J AU Cao, KX Rosenberg, AE Hakim, J Masiakos, PT AF Cao, Kevin Xi Rosenberg, Andrew E. Hakim, Joseph Masiakos, Peter T. TI Axillary calcifying fibrous tumor (CFT) in an 8 year old girl SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Calcifying fibrous tumor; Calcifying fibrous pseudotumor; Inflammatory myofibroblastic tumor; Childhood fibrous tumors with psammoma bodies ID INFLAMMATORY MYOFIBROBLASTIC TUMOR; ADRENAL-GLAND; PSEUDOTUMOR; PLEURA; FEATURES; LESION; NECK AB Calcifying fibrous tumors (CFTs) are benign soft tissue masses that can occur at many sites. This case report outlines the diagnostic workup for this rare, fast-growing, solitary mass in an otherwise healthy 8year old patient. We also describe the radiographic and pathological characteristics unique to this lesion. (C) 2012 Elsevier Inc. All rights reserved. C1 [Cao, Kevin Xi; Masiakos, Peter T.] Massachusetts Gen Hosp, Div Pediat Surg, Boston, MA 02114 USA. [Rosenberg, Andrew E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hakim, Joseph] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Masiakos, PT (reprint author), Massachusetts Gen Hosp, Div Pediat Surg, Boston, MA 02114 USA. EM pmasiakos@partners.org NR 37 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD DEC PY 2012 VL 47 IS 12 BP 2341 EP 2344 DI 10.1016/j.jpedsurg.2012.10.008 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 050SD UT WOS:000312073400048 PM 23217902 ER PT J AU Keung, EZ Liu, XX Nuzhad, A Rabinowits, G Patel, V AF Keung, Emily Z. Liu, Xiaoxia Nuzhad, Afrin Rabinowits, Guilherme Patel, Vihas TI In-Hospital and Long-Term Outcomes after Percutaneous Endoscopic Gastrostomy in Patients with Malignancy SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID CLINICAL PALLIATIVE CARE; PEG-TUBE PLACEMENT; NECK-CANCER; ADVANCED HEAD; COMPLICATIONS; SURGEONS; THERAPY; CHEMORADIOTHERAPY; MORTALITY; DEMENTIA AB BACKGROUND: Although percutaneous endoscopic gastrostomy (PEG) is widely performed for nutrition or palliation, PEG-associated outcomes in cancer patients remain poorly described. We examined the safety and benefits of PEG placement in this population at our institution. STUDY DESIGN: A 5-year retrospective review of patients with malignancy (excluding head/neck and thoracic malignancy) who underwent PEG at our institution was performed. RESULTS: One hundred and eighty-nine patients with malignancy underwent PEG; 33.9% had hematologic malignancy, 66.1% had nonhematologic malignancy, and 44.4% had metastatic disease. Indications for PEG were enteral access (73%) and gastric decompression/ management of obstructive symptoms (27%). Few patients achieved independence from total parenteral nutrition (22%) or diet advancement (24.6%). Overall rates of major complications (eg, aspiration, tube dislodgement/leakage, bleeding, visceral injury, respiratory failure after procedure, and cardiac arrest) and minor complications (eg, superficial infection and ileus) were 10.2% and 11.3%, respectively. All-cause in-hospital mortality was high (19.6%) and was associated with ICU admission (p = 0.018), earlier bone marrow transplantation (p = 0.022), steroid treatment (p = 0.024), and lower preoperative albumin (p = 0.003). Code status was changed after PEG in 44 patients from full code to DNR/do no intubate or comfort measures only. CONCLUSIONS: Percutaneous endoscopic gastrostomy placement in this study population was associated with major procedure-related complications. The majority of patients failed to achieve total parenteral nutrition independence or advancement of diet. Nearly 25% of patients declined aggressive resuscitation strategies after undergoing surgery for PEG. This study cautions to carefully weigh the risks and benefits of PEG placement in this patient population. Prospective studies are needed to uncover factors affecting the decision process and patient selection. (J Am Coll Surg 2012; 215: 777-786. (c) 2012 by the American College of Surgeons) C1 [Keung, Emily Z.; Nuzhad, Afrin; Patel, Vihas] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Liu, Xiaoxia] Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. [Rabinowits, Guilherme] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Patel, V (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM vpatel3@partners.org NR 45 TC 16 Z9 16 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD DEC PY 2012 VL 215 IS 6 BP 777 EP 786 DI 10.1016/j.jamcollsurg.2012.08.013 PG 10 WC Surgery SC Surgery GA 057WU UT WOS:000312595800004 PM 22999329 ER PT J AU Kousoulis, AA Economopoulos, KP Hatzinger, M Eshraghian, A Tsiodras, S AF Kousoulis, Antonis A. Economopoulos, Konstantinos P. Hatzinger, Martin Eshraghian, Ahad Tsiodras, Sotirios TI The Fatal Disease of Emperor Galerius SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Editorial Material ID FOURNIERS-GANGRENE; INFECTIONS; MANAGEMENT; SECONDARY; DIAGNOSIS C1 [Kousoulis, Antonis A.] Univ Athens, Hist Med Dept, Athens 18344, Greece. [Kousoulis, Antonis A.; Economopoulos, Konstantinos P.] Soc Jr Doctors, Athens, Greece. [Tsiodras, Sotirios] Univ Athens, Sch Med, Attikon Univ Hosp, Acad Dept Internal Med & Infect Dis 4, Athens 18344, Greece. [Economopoulos, Konstantinos P.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hatzinger, Martin] Markushospital, Dept Urol, Frankfurt, Germany. [Eshraghian, Ahad] Shiraz Univ Med Sci, Dept Internal Med, Gastroenterohepatol Res Ctr, Shiraz, Iran. RP Kousoulis, AA (reprint author), Univ Athens, Hist Med Dept, 131 Lambrou Katsoni St, Athens 18344, Greece. EM antonis.kousoulis@sni.gr RI Kousoulis, Antonis/D-5540-2011; OI Kousoulis, Antonis/0000-0002-8763-3358; Tsiodras, Sotirios/0000-0002-0463-4321; Economopoulos, Konstantinos/0000-0003-4856-0405 NR 28 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 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD DEC PY 2012 VL 215 IS 6 BP 890 EP 893 DI 10.1016/j.jamcollsurg.2012.05.039 PG 4 WC Surgery SC Surgery GA 057WU UT WOS:000312595800015 PM 22863796 ER PT J AU O'Hare, AM Walker, R Haneuse, S Crane, PK McCormick, WC Bowen, JD Larson, EB AF O'Hare, Ann M. Walker, Rod Haneuse, Sebastian Crane, Paul K. McCormick, Wayne C. Bowen, James D. Larson, Eric B. TI Relationship Between Longitudinal Measures of Renal Function and Onset of Dementia in a Community Cohort of Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE dementia; renal function; eGFR; variability; trajectory ID CHRONIC KIDNEY-DISEASE; COGNITIVE FUNCTION; IMPAIRMENT; ALBUMINURIA; HEALTH; DECLINE; RISK; MICROALBUMINURIA; ASSOCIATION; POPULATION AB Objectives To evaluate the association between dynamic measures of renal function ascertained over time and onset of dementia. Design Prospective community cohort study. Setting Group Health, Seattle, Washington. Participants Two thousand nine hundred sixty-eight adults aged 65 and older followed for the development of dementia over a median of 6.0 years (interquartile range 3.110.1 years). Measurements Time-varying measures of renal function were constructed based on 49,340 serum creatinine measurements and included average estimated glomerular filtration rate (eGFR), eGFR trajectory, and variability in eGFR around this trajectory over 5-year exposure windows. The association between these three eGFR exposure measures and risk of dementia was estimated using a Cox regression model adjusted for other participant characteristics. Time-varying measures of urine protein by dipstick were also adjusted for in sensitivity analyses. Results Participants with a lower eGFR had a higher incidence of dementia, but this did not reach statistical significance in adjusted analyses (omnibus P = .14). There were trends toward a higher adjusted incidence of dementia in participants with positive eGFR trajectories (omnibus P = .07) and greater variability in eGFR (omnibus P = .04) over time. The results of sensitivity analyses, including those in which time-varying measures of proteinuria were included, were consistent with those of the primary analysis. Conclusion In a community cohort of older adults followed for a median of 6 years, strong associations were not found between measures of kidney disease severity and progression and incident dementia. J Am Geriatr Soc 60:2215-2222, 2012. C1 [O'Hare, Ann M.] VA Puget Sound Healthcare Syst, Dept Med, Seattle, WA 98119 USA. [O'Hare, Ann M.; Crane, Paul K.; McCormick, Wayne C.; Larson, Eric B.] Univ Washington, Dept Med, Seattle, WA USA. [Haneuse, Sebastian] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bowen, James D.] Swedish Med Ctr, Swedish Neurosci Inst, Seattle, WA USA. RP O'Hare, AM (reprint author), VA Puget Sound Healthcare Syst, Dept Med, 1160 S Columbian Way, Seattle, WA 98119 USA. EM Ann.OHare@va.gov RI Crane, Paul/C-8623-2014; OI Crane, Paul/0000-0003-4278-7465 FU National Institutes of Health [U01 AG006781, 1K23AG28980] FX This work was supported by National Institutes of Health Grants U01 AG006781 (PI: Larson) and 1K23AG28980 (PI: O'Hare). NR 32 TC 7 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2012 VL 60 IS 12 BP 2215 EP 2222 DI 10.1111/j.1532-5415.2012.04238.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 056AY UT WOS:000312460500003 PM 23231548 ER PT J AU Pierluissi, E Mehta, KM Kirby, KA Boscardin, WJ Fortinsky, RH Palmer, RM Landefeld, CS AF Pierluissi, Edgar Mehta, Kala M. Kirby, Katharine A. Boscardin, W. John Fortinsky, Richard H. Palmer, Robert M. Landefeld, C. Seth TI Depressive Symptoms After Hospitalization in Older Adults: Function and Mortality Outcomes SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE depression symptoms; hospitalized older adults; elderly; function; mortality ID CONGESTIVE-HEART-FAILURE; RANDOMIZED-CONTROLLED-TRIAL; ELDERLY MEDICAL INPATIENTS; ACUTE CORONARY SYNDROME; MYOCARDIAL-INFARCTION; MAJOR DEPRESSION; HEALTH; CARE; DISEASE; ILLNESS AB Objectives To determine the relationship between depressive symptoms after hospitalization and survival and functional outcomes. Design Secondary analysis of a prospective cohort study. Setting General medical service of two urban, teaching hospitals in Ohio. Participants Hospitalized individuals aged 70 and older. Measurements Ten depressive symptoms, instrumental activities of daily living (IADLs), and basic activities of daily living (ADLs) were measured at hospital discharge and 1, 3, 6, and 12 months later. Participant-specific changes in depressive symptoms (slopes) were determined using all data points. Four groups were also defined according to number of depressive symptoms (=3 symptoms, low; 410 symptoms, high) at discharge and follow-up: lowlow, lowhigh, highlow, and highhigh. Mortality was measured 3, 6, and 12 months after hospital discharge. Results Participant-specific discharge depressive symptoms and change in depressive symptoms over time (slopes) were associated (P < .05) with functional and mortality outcomes. At 1 year, more participants in the lowlow depressive symptom group (49%) were alive and independent in IADLs and ADLs than in the lowhigh group (37%, P = .02), and more participants in the highlow group (39%) were alive and independent in IADLs and ADLs than in the highhigh group (19%, P < .001). Conclusion Number of depressive symptoms and change in number of depressive symptoms during the year after discharge were associated with functional and mortality outcomes in hospitalized older adults. Fewer participants with persistently high or increasing depressive symptoms after hospitalization were alive and functionally independent 1 year later than participants with decreasing or persistently low symptoms, respectively. J Am Geriatr Soc 60:2254-2262, 2012. C1 [Pierluissi, Edgar; Mehta, Kala M.; Kirby, Katharine A.; Boscardin, W. John] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94110 USA. [Mehta, Kala M.; Boscardin, W. John] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94110 USA. [Fortinsky, Richard H.] Univ Connecticut, Ctr Aging, Farmington, CT USA. [Palmer, Robert M.] Univ Pittsburgh, Div Geriatr Med & Gerontol, Pittsburgh, PA USA. [Landefeld, C. Seth] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. RP Pierluissi, E (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, 1001 Potrero Ave,Room 5H17, San Francisco, CA 94110 USA. EM epierluissi@medsfgh.ucsf.edu FU National Institute on Aging (NIA) [RO1 AG029233]; S.D. Bechtel, Jr. Foundation; NIA [RO1 AG029233, K-01AG025444, AG-10418-03]; NIA, National Institute of Nursing Research, and the National Center for Minority Health and Health Disparities [P30 AG 15272 350]; John A. Hartford Foundation [88277-3G, 2006-0108]; Summa Health System Foundation FX This work was supported by National Institute on Aging (NIA) Grant RO1 AG029233 and a grant from the S.D. Bechtel, Jr. Foundation (Principal Investigator, Dr. Landefeld). Dr. Mehta was supported by a Research Career Scientist Award from the NIA (K-01AG025444). She was an affiliate of the Center for Aging in Diverse Communities at the University of California at San Francisco, a part of the P30 AG 15272 350 Resource Centers for Minority Aging Research Program (NIA, National Institute of Nursing Research, and the National Center for Minority Health and Health Disparities). Dr. Pierluissi was supported by an administrative supplement to NIA Grant RO1 AG029233. The Acute Care for Elders studies were supported by grants from the John A. Hartford Foundation (88277-3G and 2006-0108), the NIA (AG-10418-03), and the Summa Health System Foundation. NR 46 TC 9 Z9 9 U1 5 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2012 VL 60 IS 12 BP 2254 EP 2262 DI 10.1111/jgs.12008 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 056AY UT WOS:000312460500008 PM 23176725 ER PT J AU Adams, K Bayliss, E Blumenthal, D Boyd, C Guralnik, J Krist, AH LaCroix, A Naylor, MD Patrick, DL Reuben, D Tinetti, M Wallace, RB Ware, JE Wolff, JL Hadley, E Salive, ME AF Adams, Karen Bayliss, Elizabeth Blumenthal, David Boyd, Cynthia Guralnik, Jack Krist, Alexander H. LaCroix, Andrea Naylor, Mary D. Patrick, Donald L. Reuben, David Tinetti, Mary Wallace, Robert B. Ware, John E., Jr. Wolff, Jennifer L. Hadley, Evan Salive, Marcel E. CA Working Grp Hlth Outcomes Older Pe TI Universal Health Outcome Measures for Older Persons with Multiple Chronic Conditions SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE geriatrics; chronic disease; comorbidity; outcome assessment; quality measurement ID QUALITY-OF-LIFE; GENERALIZED ANXIETY DISORDER; INFORMATION-SYSTEM PROMIS; PHYSICAL FUNCTION; FAMILY CAREGIVERS; INSTRUMENTS; PERFORMANCE; ADULTS; ACCURACY; VALIDITY AB Older adults with multiple chronic conditions (MCCs) require considerable health services and complex care. Because the persistence and progression of diseases and courses of treatments affect health status in multiple dimensions, well-validated universal outcome measures across diseases are needed for research, clinical care, and administrative purposes. An expert panel meeting held by the National Institute on Aging in September 2011 recommends that older persons with MCCs complete a brief initial composite measure that includes general health; pain; fatigue; and physical health, mental health, and social role function, along with gait speed measurement. Suitable composite measures include the Medical Outcomes Study 8 (SF-8) and 36 (SF-36) -item Short-Form Survey and the Patient Reported Outcomes Measurement Information System 29-item Health Profile. Based on responses to items in the initial measure, short follow-on measures should be selectively targeted to symptom burden, depression, anxiety, and daily activities. Persons unable to walk a short distance to assess gait speed should be assessed using a physical function scale. Remaining gaps to be considered for measure development include disease burden, cognitive function, and caregiver burden. Routine outcome assessment of individuals with MCCs could facilitate system-based care improvement and clinical effectiveness research. J Am Geriatr Soc 60: 2333-2341, 2012. C1 [Salive, Marcel E.] NIA, Geriatr Branch, Div Geriatr & Clin Gerontol, NIH, Bethesda, MD 20892 USA. [Bayliss, Elizabeth] Kaiser Permanente, Inst Hlth Res, Oakland, CA USA. [Blumenthal, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wolff, Jennifer L.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Guralnik, Jack] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Krist, Alexander H.] Virginia Commonwealth Univ, Med Ctr, Richmond, VA 23284 USA. [LaCroix, Andrea] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Naylor, Mary D.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Patrick, Donald L.] Univ Washington, Seattle, WA 98195 USA. [Reuben, David] UCLA Sch Med, Los Angeles, CA USA. [Tinetti, Mary] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Wallace, Robert B.] Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA. [Ware, John E., Jr.] Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. RP Salive, ME (reprint author), NIA, Geriatr Branch, Div Geriatr & Clin Gerontol, NIH, 7201 Wisconsin Ave,Suite 3C307, Bethesda, MD 20892 USA. EM saliveme@nia.nih.gov FU National Institute of Mental Health [K01MH082885]; NIH; NIA; Agency for Healthcare Research and Quality FX Jennifer Wolff was supported by National Institute of Mental Health Grant K01MH082885.; John E. Ware, Jr., PhD, is Chief Science Officer and Founder, John Ware Research Group (JWRG), Inc., a for-profit business funded by NIH SBIR grants and unrestricted gifts or industry grants to develop and integrate generic and disease-specific patient-reported outcome measures for use in research and improving healthcare outcomes. He has received grants from NIH, NIA, and the Agency for Healthcare Research and Quality and various honoraria from academic institutions (<$5,000 annually). He is a consultant to the medical products industry on measurement issues and clinical trial results and interpretations (< 10,000 annually), is the principal shareholder of JWRG, Inc., and has provided expert testimony in Food and Drug Administration review panel hearings (3 in past 5 years). He is the primary or co-inventor for numerous patents, all sold with the sale of Quality Metric, Inc. in March 2010. NR 46 TC 28 Z9 28 U1 8 U2 36 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 DEC PY 2012 VL 60 IS 12 BP 2333 EP 2341 DI 10.1111/j.1532-5415.2012.04240.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 056AY UT WOS:000312460500020 ER PT J AU Kirkman, MS Briscoe, VJ Clark, N Florez, H Haas, LB Halter, JB Huang, ES Korytkowski, MT Munshi, MN Odegard, PS Pratley, RE Swift, CS AF Kirkman, M. Sue Briscoe, Vanessa Jones Clark, Nathaniel Florez, Hermes Haas, Linda B. Halter, Jeffrey B. Huang, Elbert S. Korytkowski, Mary T. Munshi, Medha N. Odegard, Peggy Soule Pratley, Richard E. Swift, Carrie S. TI Diabetes in Older Adults: A Consensus Report SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; NUTRITION EXAMINATION SURVEY; INTENSIVE GLUCOSE CONTROL; LIFE-STYLE INTERVENTION; QUALITY-OF-LIFE; HOC EPIDEMIOLOGIC ANALYSIS; BASE-LINE CHARACTERISTICS; NURSING-HOME RESIDENTS; BLOOD-PRESSURE CONTROL; 10-YEAR FOLLOW-UP C1 [Halter, Jeffrey B.] Univ Michigan, Div Geriatr Med, Ann Arbor, MI 48109 USA. [Kirkman, M. Sue] Amer Diabet Assoc, Alexandria, VA USA. [Briscoe, Vanessa Jones] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Clark, Nathaniel] Diabet Ctr Cape Cod, Hyannis, MA USA. [Florez, Hermes] Univ Miami, Ctr Geriatr Res Educ & Clin, Miami Vet Affairs Healthcare Syst, Miami, FL USA. [Haas, Linda B.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Huang, Elbert S.] Univ Chicago, Gen Internal Med Sect, Chicago, IL 60637 USA. [Korytkowski, Mary T.] Univ Pittsburgh, Div Endocrinol, Pittsburgh, PA USA. [Munshi, Medha N.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Munshi, Medha N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Odegard, Peggy Soule] Univ Washington, Dept Pharm, Seattle, WA 98195 USA. [Pratley, Richard E.] Florida Hosp Diabet Inst, Orlando, FL USA. [Swift, Carrie S.] Kadlec Med Ctr, Richland, WA USA. RP Halter, JB (reprint author), Univ Michigan, Div Geriatr Med, Ann Arbor, MI 48109 USA. EM jhalter@med.umich.edu FU Association of Subspecialty Professors through the John A. Hartford Foundation; Lilly USA, LLC; Novo Nordisk; Medco Foundation; sanofi-aventis; Department of Veterans Affairs Geriatric Research, Education and Clinical Centers program; National Institutes of Health/U.S. Department of Health Human Services [1R18AE000049-01]; National Institute on Aging Claude D. Pepper Older Americans Independence Center [P30 AG024824]; National Institute of Diabetes and Digestive and Kidney Diseases, Diabetes Research and Training Center [P60 DK20595]; National Institute of Diabetes and Digestive and Kidney Diseases, Chicago Center for Diabetes Translational Research [P30 DK092949]; National Institute of Diabetes and Digestive and Kidney Diseases [RO1 DK081796] FX The authors thank Bobbie Alexander, Monique Lindsy, and Earnestine Walker for their assistance with the consensus development conference. The consensus development conference was supported by a planning grant from the Association of Subspecialty Professors (through a grant from the John A. Hartford Foundation), by educational grants from Lilly USA, LLC and Novo Nordisk, and sponsorships from the Medco Foundation and sanofi-aventis. Sponsors had no influence on the selection of speakers or writing group members, topics and content presented at the conference, or the content of this report. M.S.K.'s opinions in this work are her own and do not represent official position of the ADA.; H.F.'s work is partially supported by the Department of Veterans Affairs Geriatric Research, Education and Clinical Centers program and the National Institutes of Health/U.S. Department of Health & Human Services grant 1R18AE000049-01. J.B.H.'s work is supported in part by the National Institute on Aging Claude D. Pepper Older Americans Independence Center (P30 AG024824). E.S.H.'s work is supported in part through the following National Institute of Diabetes and Digestive and Kidney Diseases support: Diabetes Research and Training Center (P60 DK20595), Chicago Center for Diabetes Translational Research (P30 DK092949), and a project grant (RO1 DK081796). NR 131 TC 85 Z9 88 U1 2 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2012 VL 60 IS 12 BP 2342 EP 2356 DI 10.1111/jgs.12035 PG 15 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 056AY UT WOS:000312460500021 PM 23106132 ER PT J AU Friedlander, AH AF Friedlander, Arthur H. TI Poor Dental Health and Dementia SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; MANAGEMENT; LIFE; NUN C1 [Friedlander, Arthur H.] VA Greater Los Angeles, Grad Medicat Educ, Los Angeles, CA 90095 USA. [Friedlander, Arthur H.] Ronald Reagan UCLA Med Ctr, Hosp Dent Serv, Los Angeles, CA USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles, Grad Medicat Educ, Los Angeles, CA 90095 USA. NR 7 TC 0 Z9 0 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2012 VL 60 IS 12 BP 2382 EP 2383 DI 10.1111/jgs.12017 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 056AY UT WOS:000312460500039 PM 23231568 ER PT J AU Chang, H Yanachkov, IB Dix, EJ Li, YF Barnard, MR Wright, GE Michelson, AD Frelinger, AL AF Chang, H. Yanachkov, I. B. Dix, E. J. Li, Y. F. Barnard, M. R. Wright, G. E. Michelson, A. D. Frelinger, A. L., III TI Modified diadenosine tetraphosphates with dual specificity for P2Y1 and P2Y12 are potent antagonists of ADP-induced platelet activation SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE diadenosine; platelet; receptor ID P2Y(1) RECEPTOR ANTAGONISTS; DINUCLEOSIDE POLYPHOSPHATES; BIOLOGICAL-ACTIVITY; P2X(1) RECEPTORS; AGGREGATION; ANALOGS; INHIBITION; IDENTIFICATION; NUCLEOTIDES; DERIVATIVES AB Chang H, Yanachkov IB, Dix EJ, Li YF, Barnard MR, Wright GE, Michelson AD, Frelinger AL 3rd. Modified diadenosine tetraphosphates with dual specificity for P2Y1 and P2Y12 are potent antagonists of ADP-induced platelet activation. J Thromb Haemost 2012; 10: 257380. Summary. Background: Diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A), a natural compound stored in platelet dense granules, inhibits ADP-induced platelet aggregation. Ap4A inhibits the platelet ADP receptors P2Y1 and P2Y12, is a partial agonist of P2Y12, and is a full agonist of the platelet ATP-gated ion channel P2X1. Modification of the Ap4A tetraphosphate backbone enhances inhibition of ADP-induced platelet aggregation. However, the effects of these Ap4A analogs on human platelet P2Y1, P2Y12 and P2X1 are unclear. Objective: To determine the agonist and antagonist activities of diadenosine tetraphosphate analogs towards P2Y1, P2Y12, and P2X1. Methods: We synthesized the following Ap4A analogs: P1,P4-dithiotetraphosphate; P2,P3-chloromethylenetetraphosphate; P1-thio-P2,P3-chloromethylenetetraphosphate; and P1,P4-dithio-P2,P3-chloromethylenetetraphosphate. We then measured the effects of these analogs on: (i) ADP-induced platelet aggregation; (ii) P2Y1-mediated changes in cytosolic Ca2+; (iii) P2Y12-mediated changes in vasodilator-stimulated phosphoprotein phosphorylation; and (iv) P2X1-mediated entry of extracellular Ca2+.Results: Ap4A analogs with modifications in the phosphate backbone inhibited both P2Y1 and P2Y12, and showed no agonist activity towards these receptors. The dithio modification increased inhibition of P2Y1, P2Y12, and platelet aggregation, whereas the chloromethylene modification increased inhibition of P2Y12 and platelet aggregation, but decreased P2Y1 inhibition. Combining the dithio and chloromethylene modifications increased P2Y1 and P2Y12 inhibition. As compared with Ap4A, each modification decreased agonist activity towards P2X1, and the dual modification completely eliminated P2X1 agonist activity. Conclusions: As compared with Ap4A, tetraphosphate backbone analogs of Ap4A have diminished activity towards P2X1 but inhibit both P2Y1 and P2Y12 and, with greater potency, inhibit ADP-induced platelet aggregation. Thus, diadenosine tetraphosphate analogs with dual receptor selectivity may have potential as antiplatelet drugs. C1 [Barnard, M. R.; Michelson, A. D.; Frelinger, A. L., III] Harvard Univ, Boston Childrens Hosp, Sch Med,Div Hematol Oncol, Ctr Platelet Res Studies,Dana Farber Canc Inst, Boston, MA 02115 USA. [Chang, H.; Li, Y. F.; Barnard, M. R.; Michelson, A. D.; Frelinger, A. L., III] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. [Chang, H.] Chang Gung Univ, Chang Gung Mem Hosp, Div Hematol, Taipei, Taiwan. [Yanachkov, I. B.; Dix, E. J.; Wright, G. E.] GLSynthesis Inc, Worcester, MA USA. RP Frelinger, AL (reprint author), Harvard Univ, Boston Childrens Hosp, Sch Med,Div Hematol Oncol, Ctr Platelet Res Studies,Dana Farber Canc Inst, 300 Longwood Ave,Karp 07212, Boston, MA 02115 USA. EM andrew.frelinger@childrens.harvard.edu FU SBIR from the National Heart, Lung and Blood Institute [HL081992, HL088828]; GLSynthesis; Eli Lilly; Lilly FX This work was supported in part by SBIR grants HL081992 and HL088828 (to I. B. Yanachkov) from the National Heart, Lung and Blood Institute. A. L. Frelinger and A. D. Michelson have been investigators on research grants to Boston Children's Hospital from GLSynthesis and Eli Lilly. A. D. Michelson has been a member of the Data Monitoring Committee of a clinical trial sponsored by Lilly. I. B. Yanachkov and G. E. Wright are employees of GLSynthesis, Inc. E. J. Dix has been a consultant to GLSynthesis, Inc. The other authors state that they have no conflict of interest. NR 38 TC 8 Z9 8 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD DEC PY 2012 VL 10 IS 12 BP 2573 EP 2580 DI 10.1111/jth.12035 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 057CN UT WOS:000312539600019 PM 23083103 ER PT J AU Hartnick, CJ AF Hartnick, Christopher J. TI Management of complex pediatric voice disorders SO LARYNGOSCOPE LA English DT Article DE Pediatric; voice; dysphonia C1 Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. EM christopher_hartnick@meei.harvard.edu NR 2 TC 1 Z9 1 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2012 VL 122 SU 4 BP S87 EP S88 DI 10.1002/lary.23813 PG 2 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 056ZY UT WOS:000312532500017 PM 23254616 ER PT J AU Zhang, X Inukai, T Hirose, K Akahane, K Kuroda, I Honna-Oshiro, H Kagami, K Goi, K Nakamura, K Kobayashi, M Endo, M Yagita, H Kurosawa, H Look, AT Honda, H Inaba, T Nakazawa, S Sugita, K AF Zhang, X. Inukai, T. Hirose, K. Akahane, K. Kuroda, I. Honna-Oshiro, H. Kagami, K. Goi, K. Nakamura, K. Kobayashi, M. Endo, M. Yagita, H. Kurosawa, H. Look, A. Thomas Honda, H. Inaba, T. Nakazawa, S. Sugita, K. TI Oncogenic fusion E2A-HLF sensitizes t(17;19)-positive acute lymphoblastic leukemia to TRAIL-mediated apoptosis by upregulating the expression of death receptors SO LEUKEMIA LA English DT Article DE graft-versus-leukemia effect; acute lymphoblastic leukemia; TNF-related apoptosis-inducing ligand; E2A-HLF ID NF-KAPPA-B; CHIMERIC TRANSCRIPTION FACTOR; LIGAND TRAIL; DNA-BINDING; MYELOID-LEUKEMIA; TUMOR-METASTASIS; E2A GENE; CELLS; CASPASE-8; PATHWAYS AB t(17;19)-acute lymphoblastic leukemia (ALL) shows extremely poor prognosis. E2A-HLF derived from t(17;19) blocks apoptosis induced by the intrinsic mitochondrial pathway and has a central role in leukemogenesis and chemoresistance. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is expressed on cytotoxic T cells and natural killer cells and binds with death receptors (DR4/DR5), inducing apoptosis by dual activation of intrinsic and extrinsic pathways, and TRAIL mediates the graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT). We found that cell lines and patients' samples of t(17;19)ALL expressed death receptors for TRAIL, and recombinant soluble TRAIL immediately induced apoptosis into t(17;19)-ALL cell lines. E2A-HLF induced gene expression of DR4/DR5, which was dependent on the DNA-binding and transactivation activities of E2A-HLF through the 50 upstream region of the start site at least in the DR4 gene. Introduction of E2A-HLF into non-t(17;19)-ALL cell line upregulated DR4 and DR5 expression, and sensitized to proapoptotic activity of recombinant soluble TRAIL. Finally, a newly diagnosed t(17;19)-ALL patient underwent allo-SCT immediately after induction of first complete remission, and the patient has survived without relapse for over 3-1/2 years after allo-SCT. These findings suggest that E2A-HLF sensitizes t(17;19)-ALL to the GVL effect by upregulating death receptors for TRAIL. Leukemia (2012) 26, 2483-2493; doi:10.1038/leu.2012.139 C1 [Zhang, X.; Inukai, T.; Hirose, K.; Akahane, K.; Kuroda, I.; Honna-Oshiro, H.; Kagami, K.; Goi, K.; Nakazawa, S.; Sugita, K.] Univ Yamanashi, Sch Med, Dept Pediat, Yamanashi 4093898, Japan. [Nakamura, K.; Kobayashi, M.] Hiroshima Univ, Grad Sch Biomed Sci, Dept Pediat, Hiroshima, Japan. [Endo, M.] Iwate Med Univ, Sch Med, Dept Pediat, Morioka, Iwate 020, Japan. [Yagita, H.] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan. [Kurosawa, H.] Dokkyo Med Univ, Sch Med, Dept Pediat, Mibu, Tochigi, Japan. [Look, A. Thomas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Honda, H.] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Dis Model, Hiroshima, Japan. [Inaba, T.] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Mol Oncol, Hiroshima, Japan. RP Inukai, T (reprint author), Univ Yamanashi, Sch Med, Dept Pediat, 1110 Shimokatou, Yamanashi 4093898, Japan. EM tinukai@yamanashi.ac.jp FU Ministry of Education, Science and Culture in Japan FX We thank H Goto (Department of Pediatrics, Yokohama City University, Japan) for YCUB-2 cell line, F Rauscher III (Wister Institute, PA) for the pMT-CB6+ expression vector and T Sakai (Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Japan) for the vectors for DR5 reporter assay. This work was supported in part by research grants from the Ministry of Education, Science and Culture in Japan. NR 50 TC 3 Z9 3 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD DEC PY 2012 VL 26 IS 12 BP 2483 EP 2493 DI 10.1038/leu.2012.139 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 052GP UT WOS:000312186000006 PM 22743623 ER PT J AU Vesole, DH Oken, MM Heckler, C Greipp, PR Katz, MS Jacobus, S Morrow, GR AF Vesole, D. H. Oken, M. M. Heckler, C. Greipp, P. R. Katz, M. S. Jacobus, S. Morrow, G. R. CA Univ Rochester Canc Ctr Eastern Cooperative Oncology Grp TI Oral antibiotic prophylaxis of early infection in multiple myeloma: a URCC/ECOG randomized phase III study SO LEUKEMIA LA English DT Article DE antibiotics; multiple myeloma; infections ID RISK AB Multiple myeloma (MM) is a malignancy of clonal plasma cells, resulting in an increased production of ineffective immunoglobulins with suppression of non-involved immunoglobulins. Patients with MM are at increased risk of infectious complications, particularly streptococcal and staphylococcal infections. This study evaluated the impact of prophylactic antibiotics on the incidence of serious bacterial infections (SBIs) during the first 2 months of treatment in patients with newly diagnosed MM. Patients with MM receiving initial chemotherapy were randomized on a 1: 1: 1 basis to daily ciprofloxacin (C; 500mg twice daily), trimethoprim-sulfamethoxazole (T; DS twice daily) or observation (O) and evaluated for SBI (Eastern Cooperative Oncology Group >= grade 3) for the first 2 months of treatment. From July 1998 to January 2008, 212 MM patients were randomized to C (n = 69), T (n = 76) or O (n 67). The incidence of SBI was comparable among groups: C = 12.5%, T = 6.8% and O = 15.9%; P = 0.218. Further, any infection during the first 2 months was also comparable (20% vs 23% vs 22%, respectively, P = 0.954). We demonstrate that prophylactic antibiotics did not decrease the incidence of SBI (>= grade 3) within the first 2 months of treatment. We conclude that routine use of prophylactic antibiotics should not be mandated for patients receiving induction chemotherapy. Leukemia (2012) 26, 2517-2520; doi:10.1038/leu.2012.124 C1 [Vesole, D. H.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ 07601 USA. [Oken, M. M.] Northwestern Hosp, Minneapolis, MN USA. [Heckler, C.; Morrow, G. R.] Univ Rochester, Rochester, NY USA. [Greipp, P. R.] Mayo Clin, Div Hematol, Rochester, MN USA. [Katz, M. S.] Eastern Cooperat Oncol Grp, Boston, MA USA. [Jacobus, S.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Vesole, DH (reprint author), Hackensack Univ, Med Ctr, John Theurer Canc Ctr, 92 2nd St, Hackensack, NJ 07601 USA. EM dvesole@humed.com FU ECOG [CA13650, CA21115, CA23318] FX We thank the members and staff of URCC and ECOG and the patients and their families. This work was supported in part by ECOG Grant numbers CA13650, CA21115 and CA23318. NR 15 TC 16 Z9 16 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 2012 VL 26 IS 12 BP 2517 EP 2520 DI 10.1038/leu.2012.124 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 052GP UT WOS:000312186000010 PM 22678167 ER PT J AU Mangos, S Amaral, AP Faul, C Juppner, H Reiser, J Wolf, M AF Mangos, Steve Amaral, Ansel P. Faul, Christian Jueppner, Harald Reiser, Jochen Wolf, Myles TI Expression of fgf23 and aklotho in developing embryonic tissues and adult kidney of the zebrafish, Danio rerio SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE corpuscles of Stannius; FGF23; kidney; klotho; pronephros; zebrafish ID VITAMIN-D METABOLISM; KLOTHO; STANNIOCALCIN; HOMEOSTASIS; REGULATOR; PHOSPHATE; PROTEIN; CHANNEL; FAMILY; TUBULE AB Fibroblast growth factor 23 (FGF23) is an endocrine hormone that is secreted by bone and acts on the kidney and parathyroid glands to regulate phosphate homeostasis. The effects of FGF23 on phosphate homeostasis are mediated by binding to FGF receptors and their coreceptor, klotho, which are abundantly expressed in the kidney and parathyroid glands. However, the mechanisms of how FGF23 regulates phosphate handling in the proximal tubule are unclear because klotho is primarily expressed in the distal nephron in humans and rodents. The purpose of this study was to gain additional insight into the FGF23-klotho system by investigating the spatial and temporal aspects of the expression of fgf23 and klotho in the zebrafish, Danio rerio. Here, we report that zebrafish fgf23 begins to be expressed after organogenesis and is continually expressed into adulthood in the corpuscles of Stannius, which are endocrine glands that lie in close proximity to the nephron and are thought to contribute to calcium and phosphate homeostasis in fish. Zebrafish klotho expression can be detected by 24-h postfertilization in the brain, pancreas and the distal pronephros, and by 56-h postfertilization in liver. Expression in the distal pronephros persists throughout development, and by Day 5, there is also strong expression in the proximal pronephros. klotho continues to be expressed in the tubules of the metanephros of the adult kidney. These data indicate conservation of the FGF23-klotho system across species and suggest a likely role for klotho in the proximal and distal tubules. C1 [Mangos, Steve; Amaral, Ansel P.; Faul, Christian; Reiser, Jochen; Wolf, Myles] Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, Miami, FL 33136 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Dept Med, Endocrine Unit,Massachusetts Gen Hosp, Boston, MA USA. RP Wolf, M (reprint author), Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, Miami, FL 33136 USA. EM mwolf2@med.miami.edu FU National Institutes of Health [R01DK076116, R01DK081374] FX M.W. was supported by grants R01DK076116 and R01DK081374 from the National Institutes of Health. NR 32 TC 5 Z9 5 U1 0 U2 33 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD DEC PY 2012 VL 27 IS 12 BP 4314 EP 4322 DI 10.1093/ndt/gfs335 PG 9 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 058PK UT WOS:000312645800013 PM 22885518 ER PT J AU De Cosmo, S Prudente, S Lamacchia, O Lucchesi, D Shah, H Mendonca, C Pucci, L Mercuri, L Gervino, EV Hauser, TH Bailetti, D Penno, G Cignarelli, M Doria, A Trischitta, V AF De Cosmo, Salvatore Prudente, Sabrina Lamacchia, Olga Lucchesi, Daniela Shah, Hetal Mendonca, Christine Pucci, Laura Mercuri, Luana Gervino, Ernest V. Hauser, Thomas H. Bailetti, Diego Penno, Giuseppe Cignarelli, Mauro Doria, Alessandro Trischitta, Vincenzo TI The 9p21 coronary artery disease locus and kidney dysfunction in patients with Type 2 diabetes mellitus SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE albuminuria; coronary artery disease; gene polymorphism; glomerular filtration rate ID HEART-DISEASE; MYOCARDIAL-INFARCTION; ASSOCIATION; RISK; HERITABILITY; NEPHROPATHY; FAMILIES AB We investigated whether the coronary artery disease (CAD) locus on chromosome 9p21 (as represented by single nucleotide polymorphism rs2383206) is associated with low estimated glomerular filtration rate (eGFR) or increased urinary albumin excretion in patients with Type 2 diabetes mellitus (T2DM). Four samples, including a total of 3167 patients, were studied. The presence of low eGFR (60 mL/min/1.73m(2)) was estimated from serum creatinine by means of the Modification of Diet in Renal Disease Study equation. Increased urinary albumin excretion was defined as an albumincreatinine ratio (ACR) epsilon 2.5 mg/mmol in men and epsilon 3.5 mg/mmol in women. No association was found between rs2383206 and low eGFR or increased ACR in each sample as well as in a pooled analysis (overall odds ratio 1.07, 95 confidence interval 0.941.22, P 0.31 and overall odds ratio 1.00, 95 confidence interval 0.901.12, P 0.95, respectively). No interaction was observed between rs2383206 and poor glycemic control [HbA1c was above the median in the pooled sample (7.7) in modulating eGFR or ACR (P for interaction 0.42 and 0.90, respectively)]. Variability at the 9p21 CAD locus is unlikely to play a role in modulating susceptibility to kidney dysfunction in patients with T2DM. C1 [De Cosmo, Salvatore] IRCSS Casa Sollievo Sofferenza, Clin Unit Endocrinol, Dept Med Sci, San Giovanni Rotondo, Italy. [Prudente, Sabrina; Mercuri, Luana; Bailetti, Diego; Trischitta, Vincenzo] IRCSS Casa Sollievo Sofferenza, Mendel Lab, San Giovanni Rotondo, Italy. [Lamacchia, Olga; Cignarelli, Mauro] Univ Foggia, Dept Med Sci, Foggia, Italy. [Lucchesi, Daniela; Pucci, Laura; Penno, Giuseppe] Univ Pisa, Dept Endocrinol & Metab, Pisa, Italy. [Shah, Hetal; Mendonca, Christine; Doria, Alessandro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Shah, Hetal; Gervino, Ernest V.; Hauser, Thomas H.; Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gervino, Ernest V.; Hauser, Thomas H.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. [Trischitta, Vincenzo] IRCSS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. [Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy. RP De Cosmo, S (reprint author), IRCSS Casa Sollievo Sofferenza, Clin Unit Endocrinol, Dept Med Sci, San Giovanni Rotondo, Italy. EM sdecosm@tin.it RI Prudente, Sabrina/H-2886-2016; De Cosmo, Salvatore/J-7420-2016; Trischitta, Vincenzo/K-1487-2016; OI Prudente, Sabrina/0000-0001-9220-8981; De Cosmo, Salvatore/0000-0001-8787-8286; Trischitta, Vincenzo/0000-0003-1174-127X; PUCCI, LAURA/0000-0002-8162-4039 FU Italian Ministry of Health [RF2009, RC2011, RC2012, RC2010]; Fondazione Roma "Sostegno alla ricerca scientifica biomedica"; Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PST FX This work was supported by Italian Ministry of Health Grants: RF2009 (S.D.C.), RC2011 and RC2012 (S.P.), RC2010 (V.T.); Fondazione Roma "Sostegno alla ricerca scientifica biomedica 2008" (V.T.); Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PST 2006. NR 13 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD DEC PY 2012 VL 27 IS 12 BP 4411 EP 4413 DI 10.1093/ndt/gfs148 PG 3 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 058PK UT WOS:000312645800028 PM 22622453 ER PT J AU Canellos, GP AF Canellos, George P. TI Treatment for Favorable Localized Hodgkin Lymphoma: the Final Answer Is Awaited SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID LONG-TERM; RADIATION-THERAPY; DISEASE; CHEMOTHERAPY; RADIOTHERAPY; DOXORUBICIN; MORTALITY; SURVIVORS; TRIAL C1 [Canellos, George P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Canellos, George P.] Harvard Univ, Sch Med, Boston, MA USA. RP Canellos, GP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 22 TC 0 Z9 0 U1 1 U2 3 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2012 VL 26 IS 12 BP 1199 EP + PG 3 WC Oncology SC Oncology GA 058AA UT WOS:000312605000012 PM 23413601 ER PT J AU McKay, RR Kantof, P AF McKay, Rana R. Kantof, Philip TI Prostate Cancer 2012: Where Do We Stand and Where Are We Heading? SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID ABIRATERONE C1 [McKay, Rana R.; Kantof, Philip] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP McKay, RR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [T32 CA009172] NR 9 TC 0 Z9 0 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2012 VL 26 IS 12 BP 1222 EP 1224 PG 2 WC Oncology SC Oncology GA 058AA UT WOS:000312605000018 PM 23413607 ER PT J AU Wang, SX Song, L Tan, YH Ma, YX Tian, YH Jin, X Lim, G Zhang, SZ Chen, L Mao, JR AF Wang, Shuxing Song, Li Tan, Yonghui Ma, Yuxin Tian, Yinghong Jin, Xu Lim, Grewo Zhang, Shuzhuo Chen, Lucy Mao, Jianren TI A Functional Relationship Between Trigeminal Astroglial Activation and NR1 Expression in a Rat Model of Temporomandibular Joint Inflammation SO PAIN MEDICINE LA English DT Article DE Trigeminal Pain; NMDA Receptor; NR1; Astroglia; GFAP; Sp5C ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; PERIPHERAL-NERVE INJURY; NEUROPATHIC PAIN; INTRACEREBROVENTRICULAR INJECTION; THERMAL HYPERALGESIA; PERSISTENT PAIN; NITRIC-OXIDE; NEUROIMMUNE ACTIVATION; CUTANEOUS HYPERALGESIA; SUBNUCLEUS CAUDALIS AB Objective To examine the hypothesis that glial activation would regulate the expression of the N-methyl-D-aspartate receptor subunit 1 (NR1) in the trigeminal subnucleus caudalis (Sp5C) after temporomandibular joint (TMJ) inflammation. Methods Inflammation of TMJ was produced in rats by injecting 50?mu L complete Freund's adjuvant (CFA) into unilateral TMJ space. Sham control rats received incomplete Freund's adjuvant injection. Mechanical nociception in the affected and non-affected TMJ site was tested by using a digital algometer. Fractalkine, fluorocitrate, and/or MK801 were intracisternally administrated to examine the relationship between astroglial activation and NR1 upregulation. Results CFA TMJ injection resulted in persistent ipsilateral mechanical hyperalgesia 1, 3, and 5 days after CFA injection. The inflammation also induced significant upregulation of CX3C chemokine receptor 1 and glial fibrillary acidic protein (GFAP) beginning on day 1 and of NR1 beginning on day 3 within the ipsilateral Sp5C. Intracisternal administration of fluorocitrate for 5 days blocked the development of mechanical hyperalgesia as well as the upregulation of GFAP and NR1 in the Sp5C. Conversely, intracisternal injection of fractalkine for 5 days exacerbated the expression of NR1 in Sp5C and mechanical hyperalgesia induced by TMJ inflammation. Moreover, once daily intracisternal fractalkine administration for 5 days in naive rats induced the upregulation of NR1 and mechanical hyperalgesia. Conclusions These results suggest that astroglial activation contributes to the mechanism of TMJ pain through the regulation of NR1 expression in Sp5C. C1 [Wang, Shuxing; Song, Li; Tan, Yonghui; Ma, Yuxin; Tian, Yinghong; Jin, Xu; Lim, Grewo; Zhang, Shuzhuo; Chen, Lucy; Mao, Jianren] Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, MGH Ctr Translat Pain Res,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Song, Li] Sichuan Univ, W China Hosp, Dept Anesthesia, Chengdu 610064, Sichuan, Peoples R China. [Tan, Yonghui] Peking Univ, Sch & Hosp Stomatol, Ctr TMD & Orofacial Pain, Beijing 100871, Peoples R China. [Zhang, Shuzhuo] Beijing Inst Pharmacol & Toxicol, Beijing, Peoples R China. RP Mao, JR (reprint author), Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, MGH Ctr Translat Pain Res,Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jmao@partners.org FU NIH [R01DE18214, R01DE18538, P20DA26002] FX This study is supported by NIH RO1 grants NIH grants R01DE18214, R01DE18538, and P20DA26002. There is no conflict of interest in this project. NR 41 TC 4 Z9 4 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD DEC PY 2012 VL 13 IS 12 BP 1590 EP 1600 DI 10.1111/j.1526-4637.2012.01511.x PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 058QW UT WOS:000312649700009 PM 23110394 ER PT J AU Varraso, R Camargo, CA AF Varraso, Raphaelle Camargo, Carlos A., Jr. TI Can dietary interventions improve asthma control? SO PRIMARY CARE RESPIRATORY JOURNAL LA English DT Editorial Material ID SOY; ASSOCIATION; ISOFLAVONES; PREVALENCE; NUTRITION; ADULTS; HEALTH; WOMEN; FOOD C1 [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Varraso, Raphaelle] INSERM, CESP Ctr Res Epidemiol & Populat Hlth, U1018, Resp & Environm Epidemiol Team, Villejuif, France. [Varraso, Raphaelle] Univ Paris 11, UMRS 1018, Villejuif, France. RP Camargo, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org RI Varraso, Raphaelle/R-8740-2016 OI Varraso, Raphaelle/0000-0002-3338-7825 NR 15 TC 1 Z9 1 U1 0 U2 1 PU PRIMARY CARE RESPIRATORY SOC-PCRS UK PI WATERBECK PA EDITORIAL OFFICE, SMITHY HOUSE, WATERBECK, LOCKERBIE DG11 3EY, SCOTLAND SN 1471-4418 J9 PRIM CARE RESP J JI Prim. Care Respir. J. PD DEC PY 2012 VL 21 IS 4 BP 367 EP 368 DI 10.4104/pcrj.2012.00095 PG 2 WC Primary Health Care; Respiratory System SC General & Internal Medicine; Respiratory System GA 056WW UT WOS:000312523100005 PM 23138842 ER PT J AU Han, H Ahn, DH Song, J Hwang, TY Roh, S AF Han, Hyeree Ahn, Dong Hyun Song, Jinhee Hwang, Tae Yeon Roh, Sungwon TI Development of Mental Health Indicators in Korea SO PSYCHIATRY INVESTIGATION LA English DT Article DE Mental health; Mental health indicator; Development AB Objective Promoting mental health and preventing mental health problems are important tasks for international organizations and nations. Such goals entail the establishment of active information networks and effective systems and indicators to assess the mental health of populations. This being said, there is a need in Korea develop ways to measure the state of mental health in Korea. Methods This paper reviews the mental health indicator development policies and practices of seven organizations, countries, and regions: WHO, OECD, EU, United States, Australia, UK, and Scotland. Using Delphi method, we conducted two surveys of mental health indicators for experts in the field of mental health. The survey questionnaire included 5 domains: mental health status, mental health factor, mental health system, mental health service, and quality of mental health services. We considered 124 potential mental health indicators out of more than 600 from indicators of international organizations and foreign countries. Results We obtained the top 30 mental health indicators from the surveys. Among them, 10 indicators belong to the mental health system. The most important five mental health indicators are suicide rate, rate of increase in mental disorder treatment, burden caused by mental disorders, adequacy of identifying problems of mental health projects and deriving solutions, and annual prevalence of mental disorders. Conclusion Our study provides information about the process for indicator development and the use of survey results to measure the mental health status of the Korean population. The aim of mental health indicator development is to improve the mental health system by better grasping the current situation. We suggest these mental health indicators can monitor progress in efforts to implement reform policies, provide community services, and involve users, families and other stakeholders in mental health promotion, prevention, care and rehabilitation. Psychiatry Investig 2012;9:311-318 C1 [Han, Hyeree; Song, Jinhee; Roh, Sungwon] Seoul Natl Hosp, Minist Hlth & Welf, Dept Mental Hlth Res, Seoul 143711, South Korea. [Ahn, Dong Hyun] Hanyang Univ, Coll Med, Dept Psychiat, Seoul 133791, South Korea. [Song, Jinhee] Catholic Univ Korea, Dept Social Welf, Puchon, South Korea. [Hwang, Tae Yeon] Yongin Mental Hosp, WHO Collaborating Ctr PSR & CMH, Yongin, South Korea. [Roh, Sungwon] Harvard Univ, Sch Med, Dept Psychiat, Ctr Addict Med,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Roh, S (reprint author), Seoul Natl Hosp, Minist Hlth & Welf, Dept Mental Hlth Res, 398 Neungdong Ro, Seoul 143711, South Korea. EM swroh@korea.kr FU Lee Si-Hyung Social Psychiatry Research Fund of the Korean Foundation of Neuropsychiatric Research; National Center for Mental Health Research and Education of Seoul National Hospital FX This study was conducted with the support of Lee Si-Hyung Social Psychiatry Research Fund of the Korean Foundation of Neuropsychiatric Research (DHA and SR) and the National Center for Mental Health Research and Education of Seoul National Hospital (HH). The authors would also like to acknowledge the contributions of the participating experts: Jeongyee Bae, RN, PhD, Inje University; Yong-Mae Baek, PhD, Catholic University of Daegu; An Kee Chang, MD, Seoul National Hospital; Duk Hee Chun, PhD, Tongwon College; Duck-Gyu Kang, PhD, Haein Mental Health Center; Donghyeon Kim, MD, Choongmoosarang Hospital; Sun Ah Kim, RN, PhD, Yonsei University; Yoon Kim, MD, PhD, Seoul National University; Jong-Eun Lee, RN, PhD, Inha University; Jonggook Lee, MD, Yong-In Mental Hospital; Woo Kyeong Lee, PhD, Yong-In Mental Hospital; Yu Jin Lee, MD, PhD, Gachon University; Kyoung A Nam, RN, PhD, Ajou University; Jong-Woo Paik, MD, PhD, Kyung Hee University; Yongjin Seo, MD, Yong-In Mental Hospital; Jun Mo Sung, PhD, Korea Nazarene University; Hae-Joo Yoon, MA, Seoul National Hospital. NR 14 TC 1 Z9 1 U1 14 U2 22 PU KOREAN NEUROPSYCHIATRIC ASSOC PI SEOUL PA RN 522, G-FIVE CENTRAL PLAZA 1685-8 SEOCHO 4-DONG, SEOCHO-GU, SEOUL, 137-882, SOUTH KOREA SN 1738-3684 J9 PSYCHIAT INVEST JI Psychiatry Investig. PD DEC PY 2012 VL 9 IS 4 BP 311 EP 318 DI 10.4306/pi.2012.9.4.311 PG 8 WC Psychiatry SC Psychiatry GA 056VI UT WOS:000312519100001 PM 23251193 ER PT J AU Najafzadeh, M Marra, CA Lynd, LD Wiseman, SM AF Najafzadeh, Mehdi Marra, Carlo A. Lynd, Larry D. Wiseman, Sam M. TI Cost-Effectiveness of Using a Molecular Diagnostic Test to Improve Preoperative Diagnosis of Thyroid Cancer SO VALUE IN HEALTH LA English DT Article DE cost-effectiveness; gene expression; molecular diagnostic test; thyroid cancer; fine needle aspiration biopsy; The Bethesta System for Reporting Thyroid Cytopathology (TBSRTC) ID FINE-NEEDLE-ASPIRATION; RECOMBINANT HUMAN THYROTROPIN; RADIOIODINE ABLATION; UNITED-STATES; NODULES; CARCINOMA; CYTOLOGY; BIOPSY; SIMULATION; MANAGEMENT AB Objective: Fine-needle aspiration biopsy (FNAB) is a safe and inexpensive diagnostic procedure for evaluating thyroid nodules. Up to 25% of the results from an FNAB, however, may not be diagnostic or may be indeterminate, leading to a subsequent diagnostic thyroid surgery. A new molecularly based diagnostic test could potentially reduce indeterminate cytological results and, with high accuracy, provide a definitive diagnosis for cancer in thyroid nodules. The aim of the study was to estimate the cost-effectiveness of utilizing a molecular diagnostic (DX) test as an adjunct to FNAB, compared with NoDX, to improve the preoperative diagnosis of thyroid nodules. Methods: We constructed a patient-level simulation model to estimate the clinical and economic outcomes of using a DX test compared with current practice (NoDX) for the diagnosis of thyroid nodules. By using a cost-effectiveness framework, we measured incremental clinical benefits in terms of quality-adjusted life-years and incremental costs over a 10-year time horizon. Results: Assuming 95% sensitivity and specificity of the Dx test when used as an adjunct to FNAB, the utilization of the DX test resulted in a gain of 0.046 quality-adjusted life-years (95% confidence interval 0.019-0.078) and a saving of $1087 (95% confidence interval $691-$1533) in direct costs per patient. If the cost of the Dx test is less than $1087 per test, we expect to save quality-adjusted life-years and reduce costs when it is utilized. Sensitivity of the DX test, compared with specificity, had a larger influence on the overall outcomes. C1 [Wiseman, Sam M.] Univ British Columbia, Dept Surg, Vancouver, BC V6Z 1Y63, Canada. [Wiseman, Sam M.] Univ British Columbia, Dept Surg, St Pauls Hosp, Vancouver, BC V6Z 1Y63, Canada. [Najafzadeh, Mehdi] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Harvard MGH Ctr Genom Vulnerable Populat & Hlth D, Boston, MA 02114 USA. [Marra, Carlo A.; Lynd, Larry D.] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC V6Z 1Y63, Canada. [Marra, Carlo A.; Lynd, Larry D.] St Pauls Hosp, Ctr Hlth Evaluat & Outcome Sci, Vancouver, BC V6Z 1Y6, Canada. RP Wiseman, SM (reprint author), Univ British Columbia, Dept Surg, St Pauls Hosp, C303-1081 Burrard St, Vancouver, BC V6Z 1Y63, Canada. EM smwiseman@providencehealth.bc.ca FU National Research Council; Canadian Institute for Health Research Canada (CIHR) FX Source of financial support: This study was supported by the National Research Council Industrial Assistance Program (to Dr. Lesley Esford). Dr. Mehdi Najafzadeh was supported by a Canadian Institute for Health Research Canada (CIHR) Graduate Scholarship during the course of this study. NR 30 TC 10 Z9 10 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD DEC PY 2012 VL 15 IS 8 BP 1005 EP 1013 DI 10.1016/j.jval.2012.06.017 PG 9 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 055RT UT WOS:000312435300003 PM 23244801 ER PT J AU Anaya, HD Chan, K Karmarkar, U Asch, SM Goetz, MB AF Anaya, Henry D. Chan, Kee Karmarkar, Uday Asch, Steven M. Goetz, Matthew Bidwell TI Budget Impact Analysis of HIV Testing in the VA Healthcare System SO VALUE IN HEALTH LA English DT Article; Proceedings Paper CT International-Association-of-Physicians in AIDS Care (IAPAC) CY 2009 CL New Orleans, LA SP Int Assoc Phys AIDS Care (IAPAC) DE budget impact analysis; cost-effectiveness; facility costs; HIV testing ID REVISED RECOMMENDATIONS; COST-EFFECTIVENESS; UNITED-STATES; SETTINGS; VETERANS; ERA AB Objectives: The long-term cost effectiveness of routine HIV testing is favorable relative to other medical interventions. Facility-specific costs of expanded HIV testing and care for newly identified patients, however, are less well defined. To aid in resource allocation decisions, we developed a spreadsheet-based budget-impact tool populated with estimates of facility-specific HIV testing and care costs incurred with an expanded testing program. Methods: We modeled intervention effects on quarterly costs of antiretroviral therapy (ART), outpatient resource utilization, and staff expenditures in the Department of Veterans Affairs over a 2-year period of increasing HIV testing rates. We used HIV prevalence estimates, screening rates, counseling, positive tests, Veterans Affairs treatment, and published sources as inputs. We evaluated a single-facility cohort of 20,000 patients and at baseline assumed a serodiagnostic rate of 0.45%. Results: Expanding testing from 2% to 15% annually identified 21 additional HIV-positive patients over 2 years at a cost of approximately $290,000, more than 60% of which was due to providing ART to newly diagnosed patients. While quarterly testing costs decreased longitudinally as fewer persons required testing, quarterly ART costs increased from $10,000 to more than $60,000 over 2 years as more infected patients were identified and started on ART. In sensitivity analyses, serodiagnostic and annual HIV testing rates had the greatest cost impact. Conclusions: Expanded HIV testing costs are greatest during initial implementation and predominantly due to ART for new patients. Cost determinations of expanded HIV testing provide an important tool for managers charged with allocating resources within integrated systems providing both HIV testing and care. C1 [Anaya, Henry D.; Asch, Steven M.; Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, VA Greater Los Angeles Hlth Serv, Res & Dev Ctr Excellence, Los Angeles, CA 90073 USA. [Anaya, Henry D.; Asch, Steven M.; Goetz, Matthew Bidwell] Vet Affairs Qual Enhancement Res Initiat HIV Hepa, Los Angeles, CA 90073 USA. [Anaya, Henry D.; Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res GIM & HSR, Los Angeles, CA 90095 USA. [Chan, Kee] Boston Univ, Dept Hlth Sci, Sargent Coll Hlth & Rehabil Sci, Boston, MA 02215 USA. [Chan, Kee] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Karmarkar, Uday] UCLA Anderson Sch Business, Los Angeles, CA USA. [Asch, Steven M.] RAND Hlth, Santa Monica, CA USA. [Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Dept Med, Sect Infect Dis, Los Angeles, CA 90073 USA. RP Anaya, HD (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, VA Greater Los Angeles Hlth Serv, Res & Dev Ctr Excellence, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM hemy.anaya@va.gov OI Goetz, Matthew/0000-0003-4542-992X NR 17 TC 5 Z9 5 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD DEC PY 2012 VL 15 IS 8 BP 1022 EP 1028 DI 10.1016/j.jval.2012.08.2205 PG 7 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 055RT UT WOS:000312435300005 PM 23244803 ER PT J AU Glanz, BI Degano, IR Rintell, DJ Chitnis, T Weiner, HL Healy, BC AF Glanz, Bonnie I. Degano, Irene R. Rintell, David J. Chitnis, Tanuja Weiner, Howard L. Healy, Brian C. TI Work Productivity in Relapsing Multiple Sclerosis: Associations with Disability, Depression, Fatigue, Anxiety, Cognition, and Health-Related Quality of Life SO VALUE IN HEALTH LA English DT Article DE depression; fatigue; multiple sclerosis; quality of life; work productivity ID ACTIVITY IMPAIRMENT QUESTIONNAIRE; EMPLOYMENT STATUS; VALIDITY; IMPACT; UNEMPLOYMENT; ARTHRITIS; DISEASE; PRESENTEEISM; INDIVIDUALS; INSTRUMENTS AB Objectives: To characterize work productivity in relapsing multiple sclerosis (MS) by using a work productivity scale and to identify associations between work productivity and disability, depression, fatigue, anxiety, cognition, and health-related quality of life. Methods: Three hundred seventy-seven subjects with a clinically isolated syndrome or relapsing remitting MS participated in the study. Subjects underwent neurological examinations and completed patient-reported outcome and cognitive measures. Subjects also completed the Work Productivity and Activity Impairment Questionnaire: General Health to quantify absenteeism (missing work because of health problems), presenteeism (impairment while working), overall work impairment, and daily activity impairment attributable to health problems. Univariate correlations and multivariate models were used to determine the associations between each work productivity variable and clinical, patient-reported outcome, and cognitive measures. Results: Seventy-six percent of subjects were employed. Fourteen percent of working subjects reported absenteeism, and 47% reported presenteeism. The mean work time lost because of absenteeism was 4%, and the mean work time lost because of presenteeism was 12%. Absenteeism was not significantly associated with disease or patient-reported outcome measures. Statistically significant correlations (0.32-0.53) were found between presenteeism and increasing disability, fatigue, depression, anxiety, and reduced quality of life. No associations were observed between presenteeism and disease duration or cognitive function. Conclusions: Subjects with clinically isolated syndrome/relapsing remitting MS reported substantial work productivity losses due to presenteesim. Presenteeism was associated with increasing fatigue, depression, anxiety, and reduced quality of life. It is possible that the early identification and treatment of fatigue and mental health symptoms may improve productivity while working and extend employment for individuals with MS. C1 [Glanz, Bonnie I.; Degano, Irene R.; Rintell, David J.; Chitnis, Tanuja; Weiner, Howard L.; Healy, Brian C.] Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Brookline, MA 02445 USA. [Glanz, Bonnie I.; Degano, Irene R.; Rintell, David J.; Chitnis, Tanuja; Weiner, Howard L.; Healy, Brian C.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Healy, Brian C.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. RP Glanz, BI (reprint author), Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, 1 Brookline Pl,Suite 227, Brookline, MA 02445 USA. EM bglanz@partners.org RI Roman Degano, Irene/C-1826-2012 FU Nancy Davis Foundation; Merck Serono S.A. FX Source of financial support: This research was funded in part by the Nancy Davis Foundation and Merck Serono S.A. NR 50 TC 18 Z9 19 U1 2 U2 42 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 DEC PY 2012 VL 15 IS 8 BP 1029 EP 1035 DI 10.1016/j.jval.2012.07.010 PG 7 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 055RT UT WOS:000312435300006 PM 23244804 ER PT J AU Faraone, SV Biederman, J Wozniak, J AF Faraone, Stephen V. Biederman, Joseph Wozniak, Janet TI Examining the Comorbidity Between Attention Deficit Hyperactivity Disorder and Bipolar I Disorder: A Meta-Analysis of Family Genetic Studies SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID EMOTIONAL SELF-REGULATION; DEFICIT/HYPERACTIVITY DISORDER; CO-MORBIDITY; HIGH-RISK; PSYCHIATRIC-DISORDERS; CLINICAL-TRIALS; ONSET MANIA; CHILDREN; PARENTS; ADHD AB Objective: The existence of comorbidity between attention deficit hyperactivity disorder (ADHD) and bipolar I disorder has been documented in clinical and epidemiological studies, in studies of children and adults, and in diagnosed ADHD and bipolar I patient samples. Yet questions remain about the validity of diagnosing bipolar I disorder in ADHD youth. The authors aim to clarify these issues by reviewing family genetic studies of ADHD and bipolar I disorder. Method: The authors applied random-effects meta-analysis to family genetic studies of ADHD and bipolar I disorder. Twenty bipolar proband studies provided 37 estimates of the prevalence of ADHD in 4,301 relatives of bipolar probands and 1,937 relatives of comparison probands. Seven ADHD proband studies provided 12 estimates of the prevalence of bipolar I disorder in 1,877 relatives of ADHD probands and 1,601 relatives of comparison probands. Results: These studies found a significantly higher prevalence of ADHD among relatives of bipolar probands and a significantly higher prevalence of bipolar I disorder among relatives of ADHD probands. These results could not be accounted for by publication biases, unusual results from any one observation, sample characteristics, or study design features. The authors found no evidence of heterogeneity in the ADHD or bipolar family studies. Conclusions: The results suggest that ADHD plus bipolar comorbidity cannot be accounted for by misdiagnoses, but additional research is needed to rule out artifactual sources of comorbidity. More research is also needed to determine whether comorbidity of ADHD and bipolar I disorder constitutes a familial subtype distinct from its constituent disorders, which if confirmed would have implications for diagnostic nosology and genetic studies. (Am J Psychiatry 2012; 169:1256-1266) C1 [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Neurosci, New York, NY USA. SUNY Upstate Med Univ, Dept Physiol, New York, NY USA. Massachusetts Gen Hosp, Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat & Neurosci, New York, NY USA. EM sfaraone@childpsychresearch.org OI Faraone, Stephen/0000-0002-9217-3982 FU Alcobra; Shire; NIH; Eli Lilly; Janssen; McNeil; Novartis; Pfizer; Elminda; Fundacion Areces; Medice Pharmaceuticals; Spanish Child Psychiatry Association; Abbott; Alza; AstraZeneca; Bristol-Myers Squibb; Celltech; Cephalon; Esai; Forest; GlaxoSmithKline; Gliatech; Merck; NARSAD; National Institute on Drug Abuse; New River; National Institute of Child Health and Human Development; NIMH; Noven; Neurosearch; Organon; Otsuka; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma; Wyeth; Primedia/Massachusetts General Hospital Psychiatry Academy; Boehringer-Ingelheim; Sepracor; UCB (Schwarz) Pharma FX Dr. Faraone has received consulting fees and support from Alcobra and Shire and support from NIH; has received consulting or advisory board fees or participated in continuing medical education programs sponsored by Eli Lilly, Janssen, McNeil, Novartis, Pfizer, and Shire; and has received royalties from Guilford Press and Oxford University Press. Dr. Biederman has received support from Elminda, Janssen, McNeil, and Shire; has received speakers fees from Fundacion Areces, Medice Pharmaceuticals, and the Spanish Child Psychiatry Association; has received research support, consultation fees, or speakers fees from Abbott, Alza, AstraZeneca, Bristol-Myers Squibb, Celltech, Cephalon, Eli Lilly, Esai, Forest, GlaxoSmithKline, Gliatech, Janssen, McNeil, Merck, NARSAD, National Institute on Drug Abuse, New River, National Institute of Child Health and Human Development, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, the Prechter Foundation, Shire, the Stanley Foundation, UCB Pharma, and Wyeth. Dr. Wozniak has received speaking fees from McNeil, Primedia/Massachusetts General Hospital Psychiatry Academy; has served on advisory boards for Pfizer and Shire; and has received research support from Eli Lilly, McNeil, NIMH, and Shire. Dr. Wozniak's spouse has served on speakers bureaus for Boehringer-Ingelheim, Cephalon, GlaxoSmithKline, King, Sanofi-Aventis, Sepracor, Takeda; has served on advisory boards for Axon Labs, Boehringer-Ingelheim, GlaxoSmithKline, Jazz Pharmaceuticals, Neurogen, Novartis, Novadel Pharma, Pfizer, Sepracor, Takeda, and UCB (Schwarz) Pharma; and has received research support from Boehringer-Ingelheim, GlaxoSmithKline, Sepracor, and UCB (Schwarz) Pharma. NR 78 TC 29 Z9 29 U1 5 U2 17 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2012 VL 169 IS 12 BP 1256 EP 1266 DI 10.1176/appi.ajp.2012.12010087 PG 11 WC Psychiatry SC Psychiatry GA 052EC UT WOS:000312179500008 PM 23212057 ER PT J AU Papakostas, GI Shelton, RC Zajecka, JM Etemad, B Rickels, K Clain, A Baer, L Dalton, ED Sacco, GR Schoenfeld, D Pencina, M Meisner, A Bottiglieri, T Nelson, E Mischoulon, D Alpert, JE Barbee, JG Zisook, S Fava, M AF Papakostas, George I. Shelton, Richard C. Zajecka, John M. Etemad, Bijan Rickels, Karl Clain, Alisabet Baer, Lee Dalton, Elizabeth D. Sacco, Garret R. Schoenfeld, David Pencina, Michael Meisner, Allison Bottiglieri, Teodoro Nelson, Erik Mischoulon, David Alpert, Jonathan E. Barbee, James G. Zisook, Sidney Fava, Maurizio TI L-Methylfolate as Adjunctive Therapy for SSRI-Resistant Major Depression: Results of Two Randomized, Double-Blind, Parallel-Sequential Trials SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; PSYCHIATRIC CLINICAL-TRIALS; SERUM FOLATE; FOLIC-ACID; PLACEBO-RESPONSE; DISORDER; ANTIDEPRESSANT; HOMOCYSTEINE; DEFICIENCY; AUGMENTATION AB Objective: The authors conducted two multicenter sequential parallel comparison design trials to investigate the effect of L-methylfolate augmentation in the treatment of major depressive disorder in patients who had a partial response or no response to selective serotonin reuptake inhibitors (SSRIs). Method: In the first trial, 148 outpatients with SSRI-resistant major depressive disorder were enrolled in a 60-day study divided into two 30-day periods. Patients were randomly assigned, in a 2:3:3 ratio, to receive L-methylfolate for 60 days (7.5 mg/day for 30 days followed by 15 mg/day for 30 days), placebo for 30 days followed by L-methylfolate (7.5 mg/day) for 30 days, or placebo for 60 days. SSRI dosages were kept constant throughout the study. In the second trial, with 75 patients, the design was identical to the first, except that the L-methylfolate dosage was 15 mg/day during both 30-day periods. Results: In the first trial, no significant difference was observed in outcomes between the treatment groups. In the second trial, adjunctive L-methylfolate at 15 mg/day showed significantly greater efficacy compared with continued SSRI therapy plus placebo on both primary outcome measures (response rate and degree of change in depression symptom score) and two secondary outcome measures of symptom severity. The number needed to treat for response was approximately six in favor of adjunctive L-methylfolate at 15 mg/day. L-Methylfolate was well tolerated, with rates of adverse events no different from those reported with placebo. Conclusions: Adjunctive L-methylfolate at 15 mg/day may constitute an effective, safe, and relatively well tolerated treatment strategy for patients with major depressive disorder who have a partial response or no response to SSRls. (Am J Psychiatry 2012; 169:1267-1274) C1 [Papakostas, George I.] Massachusetts Gen Hosp, Ctr Treatment Resistant Depress, Depress Clin & Res Program, Ctr Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Trials Network & Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Clin Res Inst, Boston, MA USA. Boston Univ, Dept Biostat, Boston, MA 02215 USA. Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Baylor Res Inst, Inst Metab Dis, Dallas, TX USA. Univ Cincinnati, Acad Hlth Ctr, Dept Psychiat, Cincinnati, OH USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. San Diego VA Healthcare Serv, San Diego, CA USA. RP Papakostas, GI (reprint author), Massachusetts Gen Hosp, Ctr Treatment Resistant Depress, Depress Clin & Res Program, Ctr Biostat, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU Abbott; AstraZeneca; Brainsway; Bristol-Myers Squibb; Cephalon; Dey Pharma; Eli Lilly; Forest; GlaxoSmithKline; Lundbeck; NIMH; Otsuka; Pamlab; Ridge Diagnostics; Roche; Takeda; Theracos; Sunovion; Cyberonics; Elan; Euthymics Bioscience; Janssen Pharmaceutica; Medtronic; Novartis; Pfizer; Repligen; Takeda Pharmaceuticals; St. Jude Medical; Boehringer-Ingelheim; Hoffman-LaRoche; McNeil; Shire; National Heart, Lung and Blood Institute; Harvard School of Public Health; Bowman Family Foundation; Cederroth; FisherWallace; Ganeden; Lichtwer Pharma; Nordic Naturals; Alkermes; APA; Lorex; Aspect Medical Systems; J & J Pharmaceuticals; MGH Psychiatry Academy/Reed Medical Education; MGH Psychiatry Academy/Primedia; Organon; Pharmavite; Sanofi/Synthelabo; Solvay; Wyeth-Ayerst; Xian-Janssen; Belvoir Publishing; Dey Pharmaceuticals; Sheppard Pratt Health System; BioResearch; BrainCells; Bio-Pharma; Clinical Trials Solutions; Clintara; Covidien; EnVivo Pharmaceuticals; Ganeden Biotech; Icon Clinical Research; i3 Innovus; Johnson & Johnson Pharmaceutical Research and Development; Lorex Pharmaceuticals; NARSAD; National Center for Complementary and Alternative Medicine; National Institute on Drug Abuse; Photothera; RCT Logic; Sanofi-Aventis; Synthelabo FX Dr. Papakostas has received research support from, served as a consultant or speaker for, or received honoraria for CME activities for Abbott, AstraZeneca, Brainsway, Bristol-Myers Squibb, Cephalon, Dey Pharma, Eli Lilly, Forest, GlaxoSmithKline, Lundbeck, NIMH, Otsuka, Pamlab, Ridge Diagnostics, Roche, Takeda, Theracos, and Sunovion. Dr. Shelton has received research support or served as a consultant for Bristol-Myers Squibb, Eli Lilly, Cyberonics, Elan, Euthymics Bioscience, Forest, Janssen Pharmaceutica, Medtronic, Novartis, Otsuka, Pamlab, Pfizer, Repligen, Ridge Diagnostics, Takeda Pharmaceuticals, and St. Jude Medical. Dr. Zajecka has received research support from or served as a consultant, adviser, or speaker for Abbott, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Forest, GlaxoSmithKline, Hoffman-LaRoche, McNeil, Novartis, Otsuka, Pamlab, Pfizer, Shire, and Takeda. Dr. Schoenfeld is a patent holder for the sequential parallel design used in this study; the patent is owned by his employer, Massachusetts General Hospital. Dr. Pencina has served as a consultant for Pamlab and RCT Logic. Ms. Meisner has served as a consultant for Massachusetts General Hospital and Pamlab, has received a grant from the National Heart, Lung and Blood Institute, and has received funds from grants at the Harvard School of Public Health. Dr. Bottiglieri has received research support from and has served as a consultant for Pamlab, has served as the chairman of the advisory board for Methylation Sciences, and holds stock options in Methylation Sciences. Dr. Nelson has received research support from AstraZeneca, Eli Lilly, GlaxoSmithKline, and Pamlab. Dr. Mischoulon has received research support or honoraria for, consulting, speaking, and writing from the Bowman Family Foundation, Bristol-Myers Squibb, Cederroth, FisherWallace, Ganeden, Lichtwer Pharma, Nordic Naturals, and Pamlab and has received royalties from Back Bay Scientific and Lippincott Williams & Wilkins. Dr. Alpert has received research support from or served as an adviser, consultant, or speaker for Abbott, Alkermes, APA, Lichtwer Pharma, Lorex, Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb, Cephalon, Cyberonics, Eli Lilly, Forest, GlaxoSmithkline, J & J Pharmaceuticals, MGH Psychiatry Academy/Reed Medical Education, MGH Psychiatry Academy/Primedia, Novartis, Organon, Pamlab, Pfizer, Pharmavite, Roche, Sanofi/Synthelabo, Solvay, Wyeth-Ayerst, and Xian-Janssen and has received editorial fees from Belvoir Publishing. Dr. Barbee has received research support from or served as a speaker for AstraZeneca, Bristol-Myers Squibb, Dey Pharmaceuticals, Eli Lilly, Forest, Merck, Pfizer, and Sheppard Pratt Health System and has done forensic consulting work for various attorneys. Dr. Zisook has received research support from Pamlab. Dr.; Fava has received research support from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, Bristol-Myers Squibb, Cephalon, Bio-Pharma, Clinical Trials Solutions, Clintara, Covidien, Eli Lilly, EnVivo Pharmaceuticals, Euthymics Bioscience, Forest, Ganeden Biotech, GlaxoSmithKline, Icon Clinical Research, i3 Innovus, Johnson & Johnson Pharmaceutical Research and Development, Lichtwer Pharma, Lorex Pharmaceuticals, NARSAD, National Center for Complementary and Alternative Medicine, National Institute on Drug Abuse, NIMH, Novartis, Organon, Pamlab, Pfizer, Pharmavite, Photothera, Roche, RCT Logic, Sanofi-Aventis, Shire, Solvay, Synthelabo, and Wyeth-Ayerst; he has served as an adviser or consultant (unpaid except as otherwise noted) for Abbott Laboratories, Affectis Pharmaceuticals, Alkermes, Amarin Pharma, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer, Best Practice Project Management, BioMarin Pharmaceuticals, Biovail, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Clinical Trials Solutions, CNS Response, Compellis Pharmaceuticals, Cypress Pharmaceutical, DiagnoSearch Life Sciences, Dinippon Sumitomo Pharma, Dov Pharmaceuticals, Edgemont Pharmaceuticals, Eisai, Eli Lilly, ePharmaSolutions, EPIX Pharmaceuticals, Euthymics Bioscience, Fabre-Kramer, Forest, GenOmind, GlaxoSmithKline, Grunenthal, i3 Innovus, Janssen Pharmaceutica, Jazz Pharmaceuticals, Johnson SE Johnson Pharmaceutical Research and Development (remunerated), Knoll Pharmaceuticals, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante, Merck, MSI Methylation Sciences, Naurex, Neuronetics, Novartis, Nutrition 21, Orexigen Therapeutics, Organon, Otsuka, Pamlab, Pfizer, PharmaStar, Pharmavite, PharmoRx Therapeutics, Precision Human Biolaboratory, Prexa Pharmaceuticals, Puretech Ventures, PsychoGenics, Psylin Neurosciences, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche, RCT Logic, Sanofi-Aventis, Sepracor, Servier Laboratories, Schering-Plough, Solvay, Somaxon, Somerset Pharmaceuticals, Sunovion, Synthelabo, Takeda, Tetragenex, Trans-Form Pharmaceuticals, Transcept Pharmaceuticals, and Vanda Pharmaceuticals; he has provided speaking/publishing (unpaid except as otherwise noted) for Adamed, Advanced Meeting Partners, APA, American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir Media Group (remunerated), Boehringer Ingelheim, Bristol-Myers Squibb, Cephalon, CME Institute/Physicians Postgraduate Press (remunerated), Eli Lilly, Forest, GlaxoSmithKline, Imedex, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed Elsevier (remunerated), Novartis, Organon, Pfizer, PharrnaStar, United BioSource, and Wyeth-Ayerst; he has equity holdings in Compellis; he is a patent holder for the sequential parallel design used in this study (the patent is owned by Massachusetts General Hospital) and has a patent application for a combination of ketamine and scopolamine in major depression; and he receives royalties from Lippincott Williams & Wilkins. The other authors report no financial relationships with commercial interests. NR 35 TC 77 Z9 79 U1 4 U2 31 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2012 VL 169 IS 12 BP 1267 EP 1274 DI 10.1176/appi.ajp.2012.11071114 PG 8 WC Psychiatry SC Psychiatry GA 052EC UT WOS:000312179500009 PM 23212058 ER PT J AU Fanous, AH Zhou, BY Aggen, SH Bergen, SE Amdur, RL Duan, JB Sanders, AR Shi, JX Mowry, BJ Olincy, A Amin, F Cloninger, CR Silverman, JM Buccola, NG Byerley, WF Black, DW Freedman, R Dudbridge, F Holmans, PA Ripke, S Gejman, PV Kendler, KS Levinson, DF AF Fanous, Ayman H. Zhou, Baiyu Aggen, Steven H. Bergen, Sarah E. Amdur, Richard L. Duan, Jubao Sanders, Alan R. Shi, Jianxin Mowry, Bryan J. Olincy, Ann Amin, Farooq Cloninger, C. Robert Silverman, Jeremy M. Buccola, Nancy G. Byerley, William F. Black, Donald W. Freedman, Robert Dudbridge, Frank Holmans, Peter A. Ripke, Stephan Gejman, Pablo V. Kendler, Kenneth S. Levinson, Douglas F. CA Schizophrenia Psychiat Genome-Wide TI Genome-Wide Association Study of Clinical Dimensions of Schizophrenia: Polygenic Effect on Disorganized Symptoms SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MENTAL-RETARDATION; COMMON VARIANTS; DELTA-CATENIN; PSYCHOSIS; GENES; RISK; CLASSIFICATION; PHENOTYPES; MUTATIONS; HAPLOTYPE AB Objective: Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia. Method: Based on the Lifetime Dimensions of Psychosis Scale ratings of 2,454 case subjects of European ancestry from the Molecular Genetics of Schizophrenia (MGS) sample, three symptom factors (positive, negative/disorganized, and mood) were identified with exploratory factor analysis. Quantitative scores for each factor from a confirmatory factor analysis were analyzed for association with 696,491 single-nucleotide polymorphisms (SNPs) using linear regression, with correction for age, sex, clinical site, and ancestry. Polygenic score analysis was carried out to determine whether case and comparison subjects in 16 Psychiatric GWAS Consortium (PGC) schizophrenia samples (excluding MGS samples) differed in scores computed by weighting their genotypes by MGS association test results for each symptom factor. Results: No genome-wide significant associations were observed between SNPs and factor scores. Most of the SNPs producing the strongest evidence for association were in or near genes involved in neurodevelopment, neuroprotection, or neurotransmission, including genes playing a role in Mendelian CNS diseases, but no statistically significant effect was observed for any defined gene pathway. Finally, polygenic scores based on MGS GWAS results for the negative/disorganized factor were significantly different between case and comparison subjects in the PGC data set; for MGS subjects, negative/disorganized factor scores were correlated with polygenic scores generated using case-control GWAS results from the other PGC samples. Conclusions: The polygenic signal that has been observed in cross-sample analyses of schizophrenia GWAS data sets could be in part related to genetic effects on negative and disorganized symptoms (i.e., core features of chronic schizophrenia). (Am J Psychiatry 2012; 169:1309-1317) C1 [Fanous, Ayman H.] Mental Hlth Serv Line, Washington, DC USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. NorthShore Univ HealthSyst Res Inst, Ctr Psychiat Genet, Evanston, IL USA. Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia. Univ Colorado Denver, Dept Psychiat, Aurora, CO USA. Atlanta Vet Affairs Med Ctr, Dept Psychiat & Behav Sci, Atlanta, GA USA. Emory Univ, Atlanta, GA 30322 USA. Washington Univ, Dept Psychiat, St Louis, MO USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Louisiana State Univ, Hlth Sci Ctr, Sch Nursing, New Orleans, LA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Iowa, Carver Coll Med, Mental Hlth Clin Res Ctr, Iowa City, IA USA. Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. Inst Publ Hlth, Med Res Council Biostat Unit, Cambridge, England. MRC Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol, Sch Med, Cardiff, S Glam, Wales. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Broad Inst Harvard, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. RP Fanous, AH (reprint author), Mental Hlth Serv Line, Washington, DC USA. RI Hansen, Thomas/O-5965-2014; Holmans, Peter/F-4518-2015; OI Hansen, Thomas/0000-0001-6703-7762; Holmans, Peter/0000-0003-0870-9412; Bergen, Sarah/0000-0002-5888-0034; Buccola, Nancy/0000-0003-1378-4636 FU AstraZeneca; NIH R01 [MH-67257, MH-59588, MH-59571, MH-59565, MH-59587, MH-60870, MH-59566, MH-59586, MH-61675, MH-60879, MH-81800]; NIH U01 [MH-46276, MH-46289, MH-46318, MH-79469, MH-79470]; VA grant [1101CX000278]; NARSAD Young Investigator Awards; Genetic Association Information Network (GAIN); Paul Michael Donovan Charitable Foundation; National Center for Research Resources [U54 RR020278] FX Dr. Black has received research support from AstraZeneca. All other authors report no financial relationships with commercial interests.; Data collection, genotyping, and analysis were supported by NIH R01 grants (MH-67257 to Dr. Buccola, MH-59588 to Dr. Mowry, MH-59571 to Dr. Gejman, MH-59565 to Dr. Freedman, MH-59587 to Dr. Amin, MH-60870 to Dr. Byerley, MH-59566 to Dr. Black, MH-59586 to Dr. Silverman, MH-61675 to Dr. Levinson, MH-60879 to Dr. Cloninger, and MH-81800 to Dr. Gejman), NIH U01 grants (MH-46276 to Dr. Cloninger, MH-46289 to Dr. Charles Kaufmann, MH-46318 to Dr. Ming T. Tsuang, MH-79469 to Dr. Gejman, and MH-79470 to Dr. Levinson), VA grant 1101CX000278 (to Dr. Fanous), NARSAD Young Investigator Awards (to Drs. Duan and Saunders), the Genetic Association Information Network (GAIN), and the Paul Michael Donovan Charitable Foundation. Genotyping was carried out by the Broad Institute Center for Genotyping and Analysis at MIT and Harvard (by S. Gabriel and D.B. Mirel), with support from grant U54 RR020278 from the National Center for Research Resources. Genotyping of half of the European ancestry sample and almost all the African American sample was carried out with support from GAIN. NR 38 TC 38 Z9 38 U1 2 U2 23 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2012 VL 169 IS 12 BP 1309 EP 1317 DI 10.1176/appi.ajp.2012.12020218 PG 9 WC Psychiatry SC Psychiatry GA 052EC UT WOS:000312179500014 PM 23212062 ER PT J AU Lawson, EH Louie, R Zingmond, DS Brook, RH Hall, BL Han, L Rapp, M Ko, CY AF Lawson, Elise H. Louie, Rachel Zingmond, David S. Brook, Robert H. Hall, Bruce L. Han, Lein Rapp, Michael Ko, Clifford Y. TI A Comparison of Clinical Registry Versus Administrative Claims Data for Reporting of 30-Day Surgical Complications SO ANNALS OF SURGERY LA English DT Article DE Administrative claims; clinical registry; complications; postoperative; quality measurement; surgery ID QUALITY IMPROVEMENT PROGRAM; POSTOPERATIVE ADVERSE EVENTS; NSQIP AB Objectives: To compare the recording of 30-day postoperative complications between a national clinical registry and Medicare inpatient claims data and to determine whether the addition of outpatient claims data improves concordance with the clinical registry. Background: Policymakers are increasingly discussing use of postoperative complication rates for value-based purchasing. There is debate regarding the optimal data source for such measures. Methods: Patient records (2005-2008) from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) were linked to Medicare inpatient and outpatient claims data sets. We assessed the ability of (1) Medicare inpatient claims and (2) Medicare inpatient and outpatient claims to detect a core set of ACS-NSQIP 30-day postoperative complications: superficial surgical site infection (SSI), deep/organ-space SSI, any SSI (superficial and/or deep/organ-space), urinary tract infection, pneumonia, sepsis, deep venous thrombosis (DVT), pulmonary embolism, venous thromboembolism (DVT and/or pulmonary embolism), and myocardial infarction. Agreement of patient-level complications by ACS-NSQIP versus Medicare was assessed by. statistics. Results: A total of 117,752 patients from more than 200 hospitals were studied. The sensitivity of inpatient claims data for detecting ACS-NSQIP complications ranged from 0.27 to 0.78; the percentage of false-positives ranged from 48% to 84%. Addition of outpatient claims data improved sensitivity slightly but also greatly increased the percentage of false-positives. Agreement was routinely poor between clinical and claims data for patient-level complications. Conclusions: This analysis demonstrates important differences between ACS-NSQIP and Medicare claims data sets for measuring surgical complications. Poor accuracy potentially makes claims data suboptimal for evaluating surgical complications. These findings have meaningful implications for performance measures currently being considered. C1 [Lawson, Elise H.; Louie, Rachel; Zingmond, David S.; Brook, Robert H.; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Brook, Robert H.] RAND Corp, Santa Monica, CA USA. [Brook, Robert H.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. [Hall, Bruce L.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Hall, Bruce L.] Washington Univ, Sch Med, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Barnes Jewish Hosp, St Louis Vet Affairs Med Ctr, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Olin Business Sch, St Louis, MO USA. [Han, Lein; Rapp, Michael] Ctr Medicare Serv, Baltimore, MD USA. [Han, Lein; Rapp, Michael] Ctr Medicaid Serv, Baltimore, MD USA. [Rapp, Michael] George Washington Univ, Sch Med & Hlth Sci, Dept Emergency Med, Washington, DC 20052 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Lawson, EH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 10833 Le Conte Ave,72-215 CHS, Los Angeles, CA 90095 USA. EM elawson@mednet.ucla.edu FU VA Health Services Research and Development program [RWJ 65-020]; American College of Surgeons through the Robert Wood Johnson Foundation Clinical Scholars Program; Centers for Medicare & Medicaid Services (CMS) FX E.H.L.'s time was supported by the VA Health Services Research and Development program (RWJ 65-020) and the American College of Surgeons through the Robert Wood Johnson Foundation Clinical Scholars Program. This study was funded by a contract from the Centers for Medicare & Medicaid Services (CMS). None of the remaining authors had any conflicts of interests to declare. The views expressed in this article represent the authors' views and do not necessarily represent official policy or opinions of the Department of Health and Human Services, the Centers for Medicare & Medicaid Services. NR 15 TC 106 Z9 106 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD DEC PY 2012 VL 256 IS 6 BP 973 EP 981 DI 10.1097/SLA.0b013e31826b4c4f PG 9 WC Surgery SC Surgery GA 053HC UT WOS:000312261000022 PM 23095667 ER PT J AU Fitzgibbons, SC Chen, J Jagsi, R Weinstein, D AF Fitzgibbons, Shimae C. Chen, Jie Jagsi, Reshma Weinstein, Debra TI Long-Term Follow-Up on the Educational Impact of ACGME Duty Hour Limits A Pre-Post Survey Study SO ANNALS OF SURGERY LA English DT Article DE acreditation council for graduate medical education; duty hour limits; graduate medical education; resident fatigue; resident well-being; work hours ID ORTHOPEDIC-SURGERY RESIDENTS; ACCREDITATION-COUNCIL; ATTENDING SURGEONS; 80-HOUR WORKWEEK; PATIENT SAFETY; RESTRICTIONS; REFORM; ATTITUDES; PERSPECTIVES; PREPAREDNESS AB Objective: To evaluate the long-term impact of the 2003 Accreditation Council for Graduate Medical Education (ACGME) duty hour limits on residents' perception of education. Background: Eight years after the introduction of the ACGME duty hour limits, graduate medical education programs implemented a revised set of standards. Currently, limited data exist related to the long-term impact of the 2003 standards on resident education. Methods: A yearly survey from 2003 to 2009 was administered to orthopedic residents in a multi-institutional program, inquiring about several aspects of the resident's educational experience, work hours, amount of sleep, fatigue and its impact, and preparedness for practice. Results: A total of 216 responses (69%) were obtained from surveyed orthopedic residents between 2003 and 2009. There was no significant change in the average reported hours of sleep (34.6 hours per week in 2003 vs 33.7 hours per week between 2004 and 2009) despite a decrease in the mean reported number of work hours (74.5 hours in 2003 vs 66.2 hours in 2009; P = 0.046). However, a decrease in perceived fatigue and its negative impact on patient safety and quality of care was noted. The perceived sufficiency of direct clinical experience, the number of hours spent performing major procedures, and the overall satisfaction with education also decreased. Finally, the residents' sense of clinical preparedness diminished after the work hour limits were in place. Conclusions: After the implementation of the 2003 duty hour limits, residents' perceptions of fatigue improved without any increase in the reported amount of sleep. In addition, decreased resident satisfaction with their education and a diminished sense of clinical preparedness were noted. Additional studies are needed to better understand the influence of work hours and fatigue on the outcomes of education, resident well-being, and patient care to guide the optimal design and delivery of graduate medical education. C1 [Weinstein, Debra] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Fitzgibbons, Shimae C.] Lahey Clin Med Ctr, Dept Gen Surg, Burlington, MA 01803 USA. [Chen, Jie] Univ Massachusetts, Off Grad Studies, Boston, MA 02125 USA. [Jagsi, Reshma] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. RP Weinstein, D (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Bulfinch 230, Boston, MA 02114 USA. EM dweinstein@partners.org OI Jagsi, Reshma/0000-0001-6562-1228 NR 34 TC 29 Z9 30 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD DEC PY 2012 VL 256 IS 6 BP 1108 EP 1112 DI 10.1097/SLA.0b013e31825ffb33 PG 5 WC Surgery SC Surgery GA 053HC UT WOS:000312261000044 PM 23069864 ER PT J AU Garone, C Rubio, JC Calvo, SE Naini, A Tanji, K DiMauro, S Mootha, VK Hirano, M AF Garone, Caterina Carlos Rubio, Juan Calvo, Sarah E. Naini, Ali Tanji, Kurenai DiMauro, Salvatore Mootha, Vamsi K. Hirano, Michio TI MPV17 Mutations Causing Adult-Onset Multisystemic Disorder With Multiple Mitochondrial DNA Deletions SO ARCHIVES OF NEUROLOGY LA English DT Article ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; DEPLETION SYNDROME; POLG MUTATIONS; NAVAJO NEUROHEPATOPATHY; GENE; PROTEIN; PARKINSONISM; DISEASE AB Objective: To identify the cause of an adult-onset multisystemic disease with multiple deletions of mitochondrial DNA (mtDNA). Design: Case report. Setting: University hospitals. Patient: A 65-year-old man with axonal sensorimotor peripheral neuropathy, ptosis, ophthalmoparesis, diabetes mellitus, exercise intolerance, steatohepatopathy, depression, parkinsonism, and gastrointestinal dysmotility. Results: Skeletal muscle biopsy revealed ragged-red and cytochrome-c oxidase-deficient fibers, and Southern blot analysis showed multiple mtDNA deletions. No deletions were detected in fibroblasts, and the results of quantitative polymerase chain reaction showed that the amount of mtDNA was normal in both muscle and fibroblasts. Exome sequencing using a mitochondrial library revealed compound heterozygous MPV17 mutations (p.LysMet88-89MetLeu and p.Leu143*), a novel cause of mtDNA multiple deletions. Conclusions: In addition to causing juvenile-onset disorders with mtDNA depletion, MPV17 mutations can cause adult-onset multisystemic disease with multiple mtDNA deletions. Arch Neurol. 2012; 69(12): 1648-1651. Published online September 10, 2012. doi:10.1001/archneurol.2012.405 C1 [Garone, Caterina; Carlos Rubio, Juan; Naini, Ali; DiMauro, Salvatore; Hirano, Michio] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA. [Tanji, Kurenai] Columbia Univ, Med Ctr, Dept Pathol, New York, NY 10032 USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Calvo, Sarah E.; Mootha, Vamsi K.] MIT, Cambridge, MA 02139 USA. [Garone, Caterina] Univ Turin, Joint PhD Program, I-10124 Turin, Italy. [Garone, Caterina] Univ Bologna, Joint PhD Program, I-40126 Bologna, Italy. [Carlos Rubio, Juan] Hosp 12 Octubre, Unidad Genom, Ctr Invest, E-28041 Madrid, Spain. RP Hirano, M (reprint author), Columbia Univ, Med Ctr, Dept Neurol, 630 W 168th St,P&S 4-423, New York, NY 10032 USA. EM mh29@columbia.edu OI Garone, Caterina/0000-0003-4928-1037 FU Associazione Malattie Metaboliche Congenite ereditarie; National Institutes of Health [R01HD056103, 1R01HD057543, U54NS078059]; Muscular Dystrophy Association; Marriott Mitochondrial Disorder Clinical Research Fund FX Dr Garone is supported by the Associazione Malattie Metaboliche Congenite ereditarie. Dr Hirano is supported by National Institutes of Health grants R01HD056103, 1R01HD057543, and U54NS078059, by a Muscular Dystrophy Association grant, and by the Marriott Mitochondrial Disorder Clinical Research Fund. NR 21 TC 22 Z9 22 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 2012 VL 69 IS 12 BP 1648 EP 1651 DI 10.1001/archneurol.2012.405 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 052KI UT WOS:000312196100018 PM 22964873 ER PT J AU Mukkamala, SK Costa, RA Fung, A Sarraf, D Gallego-Pinazo, R Freund, KB AF Mukkamala, Sri Krishna Costa, Rogerio A. Fung, Adrian Sarraf, David Gallego-Pinazo, Roberto Freund, K. Bailey TI Optical Coherence Tomographic Imaging of Sub-Retinal Pigment Epithelium Lipid SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OCCULT CHOROIDAL NEOVASCULARIZATION; AGE-RELATED MACULOPATHY; DIABETIC-MACULAR-EDEMA; HYPERREFLECTIVE FOCI; APOLIPOPROTEIN-B; BASAL DEPOSITS; DEGENERATION; DRUSEN; CHOLESTEROL; DETACHMENT AB Objective: To describe an optical coherence tomographic finding of layered hyperreflective bands beneath the retinal pigment epithelium (RPE), the so-called onion sign believed to represent lipid within a vascularized pigment epithelial detachment. Methods: This retrospective observational case series involved reviewing clinical histories of patients with the onion sign. Imaging studies analyzed included spectral-domain optical coherence tomography, color and red-free photographs, near infrared reflectance, fundus autofluorescence, and blue-light fundus autofluorescence. Results: A total of 22 eyes of 20 patients with sub-RPE hyperreflective bands were identified. There were 15 women and 5 men with a mean patient age of 76 years (range, 60-92 years). Snellen best-corrected visual acuities ranged from 20/25 to counting fingers, with a median of 20/80. Two patients had bilateral involvement, and 3 of 17 eyes had multifocal onion signs in the same eye. All eyes had neovascular age-related macular degeneration, with type 1 (sub-RPE) neovascularization. In all patients, the onion sign correlated with areas of yellow-gray exudates seen clinically that appeared bright on red-free and near infrared reflectance imaging. No specific fundus autofluorescence or blue-light fundus autofluorescence pattern was identified. Conclusions: The onion sign refers to layered hyperreflective bands in the sub-RPE space usually associated with chronic exudation from type 1 neovascularization in patients with age-related macular degeneration. With an associated bright near infrared reflectance, these bands may correspond to lipid, collagen, or fibrin. Because the onion sign colocalizes to areas of exudation that are known to consist of lipoprotein, we propose that this finding may represent layers of precipitated lipid in the sub-RPE space. To our knowledge, this is the first report of lipid detected in the sub-RPE space on clinical examination. Arch Ophthalmol. 2012;130(12):1547-1553. Published online August 13, 2012. doi:10.1001/archophthalmol.2012.2491 C1 [Mukkamala, Sri Krishna; Fung, Adrian; Freund, K. Bailey] Vitreous Retina Macula Consultants New York, New York, NY 10022 USA. [Mukkamala, Sri Krishna; Fung, Adrian; Freund, K. Bailey] LuEsther T Mertz Retinal Res Ctr, New York, NY USA. [Mukkamala, Sri Krishna; Freund, K. Bailey] NYU, Dept Ophthalmol, New York, NY 10016 USA. [Mukkamala, Sri Krishna; Freund, K. Bailey] Columbia Univ, Edward S Harkness Eye Inst, New York, NY USA. [Costa, Rogerio A.] Ctr Brasileiro Ciencias Visuais, Belo Horizonte, MG, Brazil. [Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90024 USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Gallego-Pinazo, Roberto] Univ & Polytech Hosp, Dept Ophthalmol, Valencia, Spain. RP Freund, KB (reprint author), Vitreous Retina Macula Consultants New York, 460 Pk Ave,5th Fl, New York, NY 10022 USA. EM kbfnyf@aol.com RI Costa, Rogerio/E-6930-2013; OI Costa, Rogerio/0000-0002-0800-2233; Freund, K. Bailey/0000-0002-7888-9773 FU LuEsther T. Mertz Retinal Research Center; Manhattan Eye, Ear, and Throat Institute; Macula Foundation Inc; Karl Kirchgessner Foundation FX This study was supported by funding from the LuEsther T. Mertz Retinal Research Center; the Manhattan Eye, Ear, and Throat Institute; the Macula Foundation Inc; and the Karl Kirchgessner Foundation Ophthalmology Endowment Fund to Dr Sarraf. NR 37 TC 7 Z9 7 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 2012 VL 130 IS 12 BP 1547 EP 1553 DI 10.1001/archophthalmol.2012.2491 PG 7 WC Ophthalmology SC Ophthalmology GA 052KA UT WOS:000312195300007 PM 22892986 ER PT J AU Menda, SA Chen, M Naseri, A AF Menda, Shivali A. Chen, Michael Naseri, Ayman TI Technique for Shortening a Long Clear Corneal Incision SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CATARACT-SURGERY AB An optimal clear corneal incision creates a self-sealing intrastomal tunnel. Variability in incision length may pose surgical difficulties for subsequent phacoemulsification. An incision that is too long may lead to challenges including decreased instrument mobility, decreased visibility due to corneal striae, stromal hydration, and a difficult angle of approach to the cataract. These sequelae may lead to surgical complications or abandonment of the original incision. We describe a technique for shortening a long clear corneal incision with the intentional creation of a flap of corneal tissue at the posterior internal wound edge. This technique is a simple and quick modification that may avoid the pitfalls of an incision that is too long. Arch Ophthalmol. 2012;130(12):1589-1590 C1 [Naseri, Ayman] San Francisco VA Med Ctr, Dept Ophthalmol, San Francisco, CA 94121 USA. [Menda, Shivali A.; Chen, Michael; Naseri, Ayman] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA USA. RP Naseri, A (reprint author), San Francisco VA Med Ctr, Dept Ophthalmol, 4150 Clement St, San Francisco, CA 94121 USA. EM ayman.naseri@va.gov NR 5 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 2012 VL 130 IS 12 BP 1589 EP 1590 PG 2 WC Ophthalmology SC Ophthalmology GA 052KA UT WOS:000312195300015 PM 23229702 ER PT J AU Skondra, D Chang, GC Farber, HW Eliott, D AF Skondra, Dimitra Chang, Grace C. Farber, Harrison W. Eliott, Dean TI Ophthalmologic Diagnosis of Exacerbation of Idiopathic Pulmonary Arterial Hypertension SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID OPEN-ANGLE GLAUCOMA C1 [Skondra, Dimitra; Chang, Grace C.; Eliott, Dean] Harvard Univ, Sch Med, Retina Serv, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Farber, Harrison W.] Boston Univ, Sch Med, Pulm Hypertens Ctr, Boston Med Ctr, Boston, MA 02118 USA. RP Eliott, D (reprint author), Harvard Univ, Sch Med, Retina Serv, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM dean_eliott@meei.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 2012 VL 130 IS 12 BP 1619 EP 1621 PG 4 WC Ophthalmology SC Ophthalmology GA 052KA UT WOS:000312195300029 PM 23229713 ER PT J AU Hariri, LP Mino-Kenudson, M Mark, EJ Suter, MJ AF Hariri, Lida P. Mino-Kenudson, Mari Mark, Eugene J. Suter, Melissa J. TI In Vivo Optical Coherence Tomography The Role of the Pathologist SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT Houston Lung Symposium / Spring Seminar of the Houston-Society-of-Clinical-Pathologists / Advances in Lung Cancer Seminar of the Department-of-Pathology-and-Genomic-Medicine-of-the-Methodist-Hospital CY APR 28-29, 2012 CL Houston, TX SP Methodist Hosp, Dept Pathol & Genom Medi, Houston Soc Clin Pathologists (HSCP) ID CORONARY-ARTERY-DISEASE; HIGH-GRADE DYSPLASIA; CELL LUNG-CANCER; BARRETTS-ESOPHAGUS; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUES; INTESTINAL METAPLASIA; COMPUTED-TOMOGRAPHY; VULNERABLE PLAQUE; BRONCHIAL LESIONS AB Optical coherence tomography (OCT) is a nondestructive, high-resolution imaging modality, providing cross-sectional, architectural images at near histologic resolutions, with penetration depths up to a few millimeters. Optical frequency domain imaging is a second-generation OCT technology that has equally high resolution with significantly increased image acquisition speeds and allows for large area, high-resolution tissue assessments. These features make OCT and optical frequency domain imaging ideal imaging techniques for surface and endoscopic imaging, specifically when tissue is unsafe to obtain and/or suffers from biopsy sampling error. This review focuses on the clinical impact of OCT in coronary, esophageal, and pulmonary imaging and the role of the pathologist in interpreting high-resolution OCT images as a complement to standard tissue pathology. (Arch Pathol Lab Med. 2012; 136: 1492-1501; doi: 10.5858/arpa.2012-0252-SA) C1 [Hariri, Lida P.; Mino-Kenudson, Mari; Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Suter, Melissa J.] Massachusetts Gen Hosp, Dept Pulm, Boston, MA 02114 USA. [Suter, Melissa J.] Massachusetts Gen Hosp, Crit Care Unit, Boston, MA 02114 USA. [Hariri, Lida P.; Suter, Melissa J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hariri, Lida P.; Mino-Kenudson, Mari; Mark, Eugene J.; Suter, Melissa J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hariri, LP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren Bldg 219, Boston, MA 02114 USA. EM lhariri@partners.org NR 81 TC 9 Z9 9 U1 0 U2 4 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 2012 VL 136 IS 12 BP 1492 EP 1501 DI 10.5858/arpa.2012-0252-SA PG 10 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 053HO UT WOS:000312262300006 PM 23194041 ER PT J AU Kradin, RL AF Kradin, Richard L. TI Guiding the Pulmonologist's Hand: What They Need to Know About Lung Pathology and What is Lost in Translation SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID USUAL INTERSTITIAL PNEUMONIA; IDIOPATHIC PULMONARY-FIBROSIS; RESPIRATORY-DISTRESS-SYNDROME; TRANSBRONCHIAL BIOPSY; ORGANIZING PNEUMONIA; DISEASE; HYPERSENSITIVITY; PATHOGENESIS; DIAGNOSIS; FEATURES AB Increasing subspecialization in the practice of medicine has led to certain discrepancies in how pathologists and pulmonologists imagine lung disease. This article, written by a pathologist who also practices pulmonology at a large, academic hospital, highlights his perspective on the important role of the pathologist in guiding the hand of the pulmonary clinician. (Arch Pathol Lab Med. 2012; 136: 1528-1532; doi: 10.5858/arpa.2012-0273-SA) C1 [Kradin, Richard L.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 55 Fruit St,Warren 253, Boston, MA 02114 USA. EM rkradin@partners.org NR 28 TC 1 Z9 1 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 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 2012 VL 136 IS 12 BP 1528 EP 1532 DI 10.5858/arpa.2012-0273-SA PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 053HO UT WOS:000312262300011 PM 23194046 ER PT J AU Chen, RC Zhang, YY Chen, MH McMahon, E Loffredo, M McPherson, CP Nguyen, AU Nguyen, PL D'Amico, AV AF Chen, Ronald C. Zhang, Yuanye Chen, Ming-Hui McMahon, Elizabeth Loffredo, Marian McPherson, Carol P. Nguyen, Angela U. Nguyen, Paul L. D'Amico, Anthony V. TI Patient-reported quality of life during radiation treatment for localized prostate cancer: results from a prospective phase II trial SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; radiation therapy; quality of life; clinical trial ID INTENSITY-MODULATED RADIOTHERAPY; RADICAL PROSTATECTOMY; INTRARECTAL BALLOON; ENDORECTAL BALLOON; GLAND LOCALIZATION; CLINICAL-TRIALS; THERAPY; OUTCOMES; IMMOBILIZATION; GENITOURINARY AB OBJECTIVE To evaluate data collected from a phase II trial to describe the time course and trajectory of patient-reported acute urinary and bowel symptom development during radiation therapy (RT) for prostate cancer. PATIENTS AND METHODS In all, 100 patients with intermediate- or high-risk prostate cancer received 72 Gy of RT to the prostate and seminal vesicles, with 6 months of concurrent androgen deprivation therapy; a rectal balloon was used for prostate immobilization. Patients completed the validated Prostate Cancer Symptom Indices questionnaire every 12 weeks, reporting urinary and bowel symptoms on a four- or five-point Likert scale. A score of =3 in a symptom is associated with clinically meaningful distress. Cumulative incidence of each symptom is reported. Bonferroni corrections of P values were used to adjust for multiple comparisons. RESULTS Urinary symptoms were frequent at baseline and worsened during treatment. By the end of RT, 2850% of patients developed clinically meaningful obstructive and irritative urinary symptoms. Acute bowel symptoms were less frequent. Each bowel symptom increased in frequency by 926% from baseline to end of RT. Urinary incontinence was rare. Overall, symptom burden at the end of treatment was modest. CONCLUSIONS Urinary symptoms were common during RT, and bowel symptoms were less frequent. These results inform patients and physicians during the decision-making process about potential patient quality of life experiences during RT, and also provide a benchmark for comparative effectiveness studies against newer treatments and technologies. C1 [Chen, Ronald C.; McPherson, Carol P.] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. [Chen, Ronald C.] Univ N Carolina, Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA. [Zhang, Yuanye; Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [McMahon, Elizabeth; Loffredo, Marian; Nguyen, Angela U.; Nguyen, Paul L.; D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [McMahon, Elizabeth; Loffredo, Marian; Nguyen, Angela U.; Nguyen, Paul L.; D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chen, RC (reprint author), Univ N Carolina, Dept Radiat Oncol, CB 7512,101 Manning Dr, Chapel Hill, NC 27599 USA. EM ronald_chen@med.unc.edu RI zhang, yuanye/H-6315-2013 FU Varian Medical Systems FX Paul Nguyen received a research grant from Varian Medical Systems. NR 26 TC 7 Z9 7 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD DEC PY 2012 VL 110 IS 11 BP 1690 EP 1695 DI 10.1111/j.1464-410X.2012.11117.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 053BY UT WOS:000312245900027 PM 22502770 ER PT J AU Nakabayashi, M Werner, L Courtney, KD Buckle, G Oh, WK Bubley, GJ Hayes, JH Weckstein, D Elfiky, A Sims, DM Kantoff, PW Taplin, ME AF Nakabayashi, Mari Werner, Lilian Courtney, Kevin D. Buckle, Geoffrey Oh, William K. Bubley, Glen J. Hayes, Julia H. Weckstein, Douglas Elfiky, Aymen Sims, Danny M. Kantoff, Philip W. Taplin, Mary-Ellen TI Phase II trial of RAD001 and bicalutamide for castration-resistant prostate cancer SO BJU INTERNATIONAL LA English DT Article DE bicalutamide; castration-resistant prostate cancer; everolimus; mTOR; RAD001 ID RENAL-CELL CARCINOMA; ANDROGEN RECEPTOR MUTATIONS; MAMMALIAN TARGET; HORMONAL-THERAPY; SOLID TUMORS; MTOR; PATHWAY; INHIBITION; PTEN; RAPAMYCIN AB OBJECTIVES To determine best overall response and duration of response of RAD001, a selective inhibitor of mammalian target of rapamycin, in combination with bicalutamide in castration-resistant prostate cancer (CRPC). To characterize the toxicity profile of RAD001 in combination with bicalutamide in patients with CRPC. PATIENTS AND METHODS A phase II study was conducted to explore the efficacy and tolerability of RAD001 (10 mg daily) in combination with bicalutamide (50 mg daily) in men with progressive CRPC. The primary endpoint was a composite of prostate-specific antigen (PSA) level and measurable disease response by standard criteria. This single-stage trial with a sample size of 38 eligible patients provided 90% power to differentiate a response rate of =40% from a response rate of =20%, as expected for bicalutamide alone (a= 0.10, power = 0.90). RESULTS In total, 36 men were enrolled, with a median (range) age of 68 (6072) years and median (range) baseline PSA level of 22.2 (8.4121.3) ng/mL, and 89% had metastatic disease. There were 31 (86%) patients had previously used bicalutamide for a median duration of 7.4 months. There were two patients with a confirmed PSA level decline =50%. The median (interquartile range) time to progression was 8.7 (7.915.9) weeks. The most common toxicity was grade 1/2 mucositis, which was observed in 20 (56%) patients. CONCLUSION The combination of RAD001 and bicalutamide in men with CRPC was well tolerated but had low activity and failed to achieve the primary endpoint of improved response compared to the results previously achieved for bicalutamide alone in this population. C1 [Nakabayashi, Mari; Courtney, Kevin D.; Buckle, Geoffrey; Hayes, Julia H.; Elfiky, Aymen; Kantoff, Philip W.; Taplin, Mary-Ellen] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02215 USA. [Werner, Lilian] Dana Farber Canc Inst, Dept Med, Div Med Oncol, Boston, MA 02215 USA. [Werner, Lilian] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. [Bubley, Glen J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Oh, William K.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Weckstein, Douglas; Sims, Danny M.] New Hampshire Oncol Hematol, Hooksett, NH USA. RP Taplin, ME (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM mary_taplin@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 52 TC 42 Z9 42 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD DEC PY 2012 VL 110 IS 11 BP 1729 EP 1735 DI 10.1111/j.1464-410X.2012.11456.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 053BY UT WOS:000312245900034 PM 22928480 ER PT J AU Fung, C Chen, X Grandis, JR Duvvuri, U AF Fung, Christopher Chen, Xing Grandis, Jennifer R. Duvvuri, Umamaheswar TI EGFR tyrosine kinase inhibition induces autophagy in cancer cells SO CANCER BIOLOGY & THERAPY LA English DT Article DE EGFR; erlotinib; gefitinib; epidermal; autophagy; TKI; rapamycin ID LUNG-CANCER; CARCINOMA; INDUCTION; HEAD; NECK; RESISTANCE; ERLOTINIB; LINES; APOPTOSIS; SURVIVAL AB The epidermal growth factor receptor (EGFR) signaling pathway is frequently dysregulated in a variety of human malignancies. As a result, agents have been developed to selectively inhibit the tyrosine kinase function of EGFR (EGFR-TKI) for cancer therapy. However, the clinical efficacy of these drugs to date has been limited by both acquired and intrinsic resistance. Macroautophagy, a process of intracellular proteolysis, has been shown to be activated in response to EGFR targeted therapy. However, the specific role of the induction of autophagy remains controversial. Here we show that autophagy is induced in a dose-dependent manner by in vitro treatment of multiple cancer cell lines with EGFR-TKI. Additionally, we find that in cells highly resistant to EGFR-TKI, autophagy is not robustly activated and that co-treatment of these cells with rapamycin, a known inducer of autophagy, can partially restore sensitivity to EGFR-TKI. Finally, we demonstrate that, in resistant cell lines, EGFR-TKI sensitivity can be further inhibited by siRNA-mediated depletion of the critical autophagy protein ATG7. Thus, our data suggests that defective autophagy may be an EGFR-TKI resistance mechanism and that activation of autophagy may be a viable strategy to augment the cytotoxic effect of EGFR-TKIs. C1 [Fung, Christopher; Chen, Xing; Grandis, Jennifer R.; Duvvuri, Umamaheswar] Univ Pittsburgh, Sch Med, Dept Otolaryngol, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Grandis, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. [Fung, Christopher] Howard Hughes Med Inst, Med Fellows Program, Chevy Chase, MD USA. RP Duvvuri, U (reprint author), Univ Pittsburgh, Sch Med, Dept Otolaryngol, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. EM duvvuriu@upmc.edu FU Howard Hughes Medical Institute [57006715]; National Institutes of Health [5P50CA097190, 2R01CA098372]; American Cancer Society [CRP-08-229-01]; United States Department of Veteran's Affairs [CDA-2-057-10S] FX These studies were supported by grants 57006715 (C.F.) from the Howard Hughes Medical Institute, 5P50CA097190 and 2R01CA098372 (J.G.) from the National Institutes of Health, CRP-08-229-01 (J.G.) from the American Cancer Society, and CDA-2-057-10S (U.D.) from the United States Department of Veteran's Affairs. The ideas in this article do not represent the views of the Department of Veteran's Affairs. NR 29 TC 25 Z9 27 U1 2 U2 16 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD DEC PY 2012 VL 13 IS 14 BP 1417 EP 1424 DI 10.4161/cbt.22002 PG 8 WC Oncology SC Oncology GA 052QD UT WOS:000312212200009 PM 22954701 ER PT J AU Joh, HK Cho, E Choueiri, TK AF Joh, Hee-Kyung Cho, Eunyoung Choueiri, Toni K. TI ABO blood group and risk of renal cell cancer SO CANCER EPIDEMIOLOGY LA English DT Article DE ABO blood-group system; Blood group antigens; Carcinoma; Renal cell; Kidney neoplasms ID PANCREATIC-CANCER; GROUP ANTIGENS; GROUP ALLELES; CARCINOMA; DISEASE; TRIALS; COHORT AB Background: The genetic determinants of sporadic renal cell cancer (RCC) are largely unknown. Previous studies have suggested associations between ABO blood group and risk of various cancers. However, its relationship to RCC remains unclear and no prospective data are available. Methods: We prospectively followed up 77,242 women in the Nurses' Health Study and 30,071 men in the Health Professionals Follow-Up Study from 1996 to 2008. The information on the ABO blood group was collected from participants' self-reports in 1996. Incidence of pathology-confirmed RCC was compared using hazard ratios (HRs) and 95% confidence intervals (CIs) derived from Cox proportional hazards models. Results: During 12 years of follow-up, 163 cases of incident RCC were documented in women and 88 cases in men. The multivariate HRs between non-O blood group (combined group of A, AB, and B) vs. blood group O were 1.51 (95% CI 1.09-2.09) in women, 1.08 (95% CI 0.70-1.66) in men, and 1.32 (95% CI 0.95-1.82) in the pooled cohorts. The associations between ABO blood group and RCC were consistent across strata of known risk factors for RCC including age, obesity, smoking, and history of hypertension (Pinteraction >= 0.32). Conclusions: We found a suggestive non-significant association between non-O blood group and increased risk of RCC in the pooled cohorts of men and women, and this association was significant in women. Our findings need to be replicated by other prospective studies. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02215 USA. [Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Joh, Hee-Kyung] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02215 USA. [Joh, Hee-Kyung; Cho, Eunyoung] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. [Joh, Hee-Kyung] Seoul Natl Univ, Coll Med, Dept Med, Seoul, South Korea. [Cho, Eunyoung] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Choueiri, TK (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Kidney Canc Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM hjoh@hsph.harvard.edu; eunyoung.cho@channing.harvard.edu; Toni_Choueiri@dfci.harvard.edu RI Joh, Hee Kyung/J-5674-2012 FU National Institutes of Health, Dana-Farber/Harvard Cancer Center Kidney Cancer Specialized Programs of Research Excellence (SPORE) [CA137764, CA87969, CA55075]; Trust Family Fund for Kidney Cancer Research FX This study was supported by research grant CA137764, CA87969, and CA55075 from the National Institutes of Health, Dana-Farber/Harvard Cancer Center Kidney Cancer Specialized Programs of Research Excellence (SPORE), and the Trust Family Fund for Kidney Cancer Research. NR 29 TC 13 Z9 15 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD DEC PY 2012 VL 36 IS 6 BP 528 EP 532 DI 10.1016/j.canep.2012.07.001 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 053HB UT WOS:000312260900016 PM 22841339 ER PT J AU Hawkins, BM Drachman, DE AF Hawkins, Beau M. Drachman, Douglas E. TI Transradial access for carotid stenting: Exceptional outcomes in experienced hands... will the results be generalizable? SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID LEARNING-CURVE C1 [Drachman, Douglas E.] Massachusetts Gen Hosp, Cardiovasc Fellowship Program, Div Cardiol, Vasc Med Sect, Boston, MA 02114 USA. RP Drachman, DE (reprint author), Massachusetts Gen Hosp, Cardiovasc Fellowship Program, Div Cardiol, Vasc Med Sect, 55 Fruit St,Gray Bigelow 800, Boston, MA 02114 USA. EM ddrachman@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD DEC 1 PY 2012 VL 80 IS 7 BP 1088 EP 1089 DI 10.1002/ccd.24730 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 051RO UT WOS:000312144900007 PM 23225649 ER PT J AU Grosu, HB Lee, YI Lee, J Eden, E Eikermann, M Rose, KM AF Grosu, Horiana B. Lee, Young Im Lee, Jarone Eden, Edward Eikermann, Matthias Rose, Keith M. TI Diaphragm Muscle Thinning in Patients Who Are Mechanically Ventilated SO CHEST LA English DT Article ID DYSFUNCTION; THICKNESS; VARIABILITY; AREA AB Background: Approximately 40% of patients in medical ICUs require mechanical ventilation (MV). Approximately 20% to 25% of these patients will encounter difficulties in discontinuing MV. Multiple studies have suggested that MV has an unloading effect on the respiratory muscles that leads to diaphragmatic atrophy and dysfunction, a process called ventilator-induced diaphragmatic dysfunction (VIDD). VIDD may be an important factor affecting when and if MV can be discontinued. A sensitive and specific diagnostic test for VIDD could provide the physician with valuable information that might influence decisions regarding extubation or tracheostomy. The purpose of this study was to quantify, using daily sonographic assessments, the rate and degree of diaphragm thinning during MV. Methods: Seven intubated patients receiving MV during acute care were included. Using sonography, diaphragm muscle thickness was measured daily from the day of intubation until the patient underwent extubation or tracheostomy or died. We analyzed our data using standard descriptive statistics, linear regression, and mixed-model effects. Results: The overall rate of decrease in the diaphragm thickness of all seven patients over time averaged 6% per day of MV, which differed significantly from zero. Similarly, the diaphragm thickness decreased for each patient over time. Conclusion: Sonographic assessment of the diaphragm provides noninvasive measurement of diaphragmatic thickness and the degree of diaphragm thinning in patients receiving MV. Our data show that diaphragm muscle thinning starts within 48 h after initiation of MV. However, it is unclear if diaphragmatic thinning correlates with diaphragmatic atrophy or pulmonary function. The relationship between diaphragm thinning and diaphragm strength remains to be elucidated. CHEST 2012; 142(6):1455-1460 C1 [Grosu, Horiana B.; Lee, Young Im; Eden, Edward; Rose, Keith M.] Columbia Univ, Coll Phys & Surg, St Lukes & Roosevelt Hosp, Div Pulm Crit Care & Sleep Med, New York, NY USA. [Lee, Jarone; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Rose, KM (reprint author), St Lukes Roosevelt Hosp, Div Pulm & Crit Care, 1000 10th Ave, New York, NY 10019 USA. EM KRose@chpnet.org NR 16 TC 45 Z9 47 U1 1 U2 5 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2012 VL 142 IS 6 BP 1455 EP 1460 DI 10.1378/chest.11-1638 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 053PA UT WOS:000312283800019 PM 23364680 ER PT J AU Donington, J Ferguson, M Mazzone, P Handy, J Schuchert, M Fernando, H Loo, B Lanuti, M de Hoyos, A Detterbeck, F Pennathur, A Howington, J Landreneau, R Silvestri, G AF Donington, Jessica Ferguson, Mark Mazzone, Peter Handy, John, Jr. Schuchert, Matthew Fernando, Hiran Loo, Billy, Jr. Lanuti, Michael de Hoyos, Alberto Detterbeck, Frank Pennathur, Arjun Howington, John Landreneau, Rodney Silvestri, Gerard CA Soc Thoracic Surg TI American College of Chest Physicians and Society of Thoracic Surgeons Consensus Statement for Evaluation and Management for High-Risk Patients With Stage I Non-small Cell Lung Cancer SO CHEST LA English DT Article ID BODY RADIATION-THERAPY; PERCUTANEOUS RADIOFREQUENCY ABLATION; QUALITY-OF-LIFE; IDIOPATHIC PULMONARY-FIBROSIS; PROSPECTIVE PHASE-II; AIR-FLOW LIMITATION; SUBLOBAR RESECTION; STEREOTACTIC RADIOTHERAPY; SEGMENTAL RESECTION; EXERCISE CAPACITY AB Background: The standard treatment of stage I non-small cell lung cancer (NSCLC) is lobectomy with systematic mediastinal lymph node evaluation. Unfortunately, up to 25% of patients with stage I NSCLC are not candidates for lobectomy because of severe medical comorbidity. Methods: A panel of experts was convened through the Thoracic Oncology Network of the American College of Chest Physicians and the Workforce on Evidence-Based Surgery of the Society of Thoracic Surgeons. Following a literature review, the panel developed 13 suggestions for evaluation and treatment through iterative discussion and debate until unanimous agreement was achieved. Results: Pretreatment evaluation should focus primarily on measures of cardiopulmonary physiology, as respiratory failure represents the greatest interventional risk. Alternative treatment options to lobectomy for high-risk patients include sublobar resection with or without brachytherapy, stereotactic body radiation therapy, and radiofrequency ablation. Each is associated with decreased procedural morbidity and mortality but increased risk for involved lobe and regional recurrence compared with lobectomy, but direct comparisons between modalities are lacking. Conclusions: Therapeutic options for the treatment of high-risk patients are evolving quickly. Improved radiographic staging and the diagnosis of smaller and more indolent tumors push the risk-benefit decision toward parenchymal-sparing or nonoperative therapies in high-risk patients. Unbiased assessment of treatment options requires uniform reporting of treatment populations and outcomes in clinical series, which has been lacking to date. CHEST 2012; 142(6):1620-1635 C1 [Donington, Jessica] NYU, Sch Med, Dept Cardiothorac Surg, New York, NY 10016 USA. [Ferguson, Mark] Univ Chicago, Dept Surg, Chicago, IL 60637 USA. [Mazzone, Peter] Cleveland Clin Fdn, Dept Pulm Allergy & Crit Care Med, Cleveland, OH 44195 USA. [Handy, John, Jr.] Providence Canc Ctr, Portland, OR USA. [Schuchert, Matthew; Pennathur, Arjun; Landreneau, Rodney] Univ Pittsburgh, Med Ctr, Dept Cardiothorac Surg, Pittsburgh, PA USA. [Fernando, Hiran] Boston Med Ctr, Dept Cardiothorac Surg, Boston, MA USA. [Loo, Billy, Jr.] Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. [Lanuti, Michael] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [de Hoyos, Alberto] NW Mem Hosp, Dept Cardiothorac Surg, Chicago, IL 60611 USA. [Detterbeck, Frank] Yale Univ, Sch Med, Dept Thorac Surg, New Haven, CT USA. [Howington, John] Northshore Univ Hlth Syst, Dept Surg, Evanston, IL USA. [Silvestri, Gerard] Med Univ S Carolina, Div Pulm Med & Crit Care, Charleston, SC USA. RP Donington, J (reprint author), NYU, Sch Med, Dept Cardiothorac Surg, 530 1st Ave,Ste 9V, New York, NY 10016 USA. EM Jessica.donington@nyumc.org OI Fernando, Hiran/0000-0002-5330-7036 FU Department of Defense; National Institutes of Health; University of Texas South-western; Varian Medical Systems, Inc.; Intuitive Surgical, Inc. FX The authors have reported to CHEST the following conflicts of interest: Dr Loo receives lung cancer research funding from the Department of Defense, the National Institutes of Health, and Varian Medical Systems, Inc. He also receives funding from the University of Texas South-western for clinical trials patient enrollment. He has received speaking honoraria from General Electric Company; Gerson Lehrman Group, Inc; Varian Medical Systems, Inc; and Siemens AG. Dr Ferguson receives educational research support from Intuitive Surgical, Inc. Drs Donington, Mtizzone, Handy, Schuchert, Fernando, Lanuti, de Hoyos, Detterbeck, Pennathur, Howington, Landreneau, and Silvestri have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 116 TC 52 Z9 53 U1 0 U2 8 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2012 VL 142 IS 6 BP 1620 EP 1635 DI 10.1378/chest.12-0790 PG 16 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 053PA UT WOS:000312283800041 PM 23208335 ER PT J AU Hall, AL Bowden, MG Kautz, SA Neptune, RR AF Hall, A. L. Bowden, M. G. Kautz, S. A. Neptune, R. R. TI Biomechanical variables related to walking performance 6-months following post-stroke rehabilitation SO CLINICAL BIOMECHANICS LA English DT Article DE Hemiparesis; Body-weight supported treadmill training; Gait; Follow-up; Walking speed ID BODY-WEIGHT SUPPORT; CHRONIC STROKE; GAIT SPEED; TREADMILL; RECOVERY; CLASSIFICATION; LOCOMOTOR; SURVIVORS; STEPS AB Background: Body-weight supported treadmill training has been shown to be effective in improving walking speed in post-stroke hemiparetic subjects, and those that have shown improvements generally maintain them after the completion of rehabilitation. However, currently no biomechanical variables are known to be related to those who will either continue to improve or regress in their self-selected walking speed during the 6-month period following rehabilitation. The objective of this study was to identify those biomechanical variables that are associated with subjects who continue (or did not continue) to improve their self-selected walking speed following the completion of rehabilitation. Methods: Experimental kinematic and kinetic data were recorded from 18 hemiparetic subjects who participated in a 6-month follow-up study after completing a 12-week locomotor training program that included stepping on a treadmill with partial body weight support and manual assistance. Pearson correlation coefficients were used to determine which biomechanical variables evaluated during the post-training session were related to changes in self-selected walking speed from post-training to a 6-month follow-up session. Findings: Following the completion of rehabilitation, the majority of subjects increased or retained (i.e., did not change) their self-selected walking speed from post-training to the follow-up session. Post-training step length symmetry and daily step activity were positively related to walking speed improvements. Interpretation: Motor control deficits that lead to persistent step length asymmetry and low daily step activity at the end of rehabilitation are associated with poorer outcomes six months after completion of the program. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Hall, A. L.; Neptune, R. R.] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. [Bowden, M. G.; Kautz, S. A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Bowden, M. G.; Kautz, S. A.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Bowden, M. G.; Kautz, S. A.] Med Univ S Carolina, Div Phys Therapy, Charleston, SC 29425 USA. RP Neptune, RR (reprint author), Univ Texas Austin, Dept Mech Engn, 1 Univ Stn C2200, Austin, TX 78712 USA. EM rneptune@mail.utexas.edu RI Kinney, Allison/J-5814-2013; OI Kinney, Allison/0000-0003-3553-0733; Kautz, Steven/0000-0003-3151-8235 FU NIH [RO1 NS055380]; Rehabilitation Research & Development Service of the VA FX The authors would like to thank Helen Emery, Erin Carr, Dr. Bhavana Raja, Dr. Cameron Nott, Dr. Chitra Balasubramanian, Kelly Rooney and Ryan Knight for help with the data collection and processing and the members of the Neuromuscular Biomechanics Lab at The University of Texas at Austin for their insightful comments on the manuscript. This work was funded by NIH grant RO1 NS055380 and the Rehabilitation Research & Development Service of the VA. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NINDS or VA. NR 32 TC 13 Z9 13 U1 1 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD DEC PY 2012 VL 27 IS 10 BP 1017 EP 1022 DI 10.1016/j.clinbiomech.2012.07.006 PG 6 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 055MO UT WOS:000312420900007 PM 22917626 ER PT J AU Raja, B Neptune, RR Kautz, SA AF Raja, Bhavana Neptune, Richard R. Kautz, Steven A. TI Coordination of the non-paretic leg during hemiparetic gait: Expected and novel compensatory patterns SO CLINICAL BIOMECHANICS LA English DT Article DE Electromyography; Stroke; Walking; Muscle ID RECTUS FEMORIS TRANSFER; GROUND REACTION FORCES; STIFF-KNEE GAIT; POSTSTROKE HEMIPARESIS; STROKE PATIENTS; WALKING; FLEXION; SPEED; SUPPORT; POWER AB Background: Post-stroke hemiparesis is usually considered a unilateral motor control deficit of the paretic leg, while the non-paretic leg is assumed to compensate for paretic leg impairments and have minimal to no deficits. While the non-paretic leg electromyography (EMG) patterns are clearly altered, how the non-paretic leg acts to compensate remains to be established. Methods: Kinesiological data were recorded from sixty individuals with chronic hemiparesis (age: 60.9, SD=12.6 years, 21 females, 28 right hemiparetic, time since stroke: 4.5 years, SD 3.9 years), divided into three speed-based groups, and twenty similarly aged healthy individuals (age: 65.1, SD=10.4 years, 15 females). All walked on an instrumented split-belt treadmill at their self-selected speed and control subjects also walked at slower speeds matching those of the persons with hemiparesis. We determined the differences in magnitude and timing of non-paretic EMG activity relative to healthy control subjects in four pre-defined regions of stance phase of the gait cycle. Findings: Integrated EMG activity and EMG timing in the non-paretic leg were different in many muscles. Multiple compensatory patterns identified included: increased EMG output when the muscle was typically active in controls and novel compensatory EMG patterns that appeared to provide greater propulsion or support with little evidence of impaired motor performance. Interpretation: Most novel compensations were made possible by altered kinematics of the paretic and non-paretic leg (i.e., early stance plantarflexor activity provided propulsion due to the decreased advancement of the non-paretic foot) while others (late single limb stance knee extensor and late stance hamstring activity) appeared to be available mechanisms for increasing propulsion. Published by Elsevier Ltd. C1 [Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Neptune, Richard R.] Univ Texas Austin, Austin, TX 78712 USA. [Raja, Bhavana] Univ Florida, Rehabil Sci Doctoral Program, Gainesville, FL USA. [Kautz, Steven A.] Malcom Randall VA Med Ctr, Brain Rehabil Res Ctr, Gainesville, FL USA. [Kautz, Steven A.] Med Univ S Carolina, Coll Hlth Profess, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Kautz, Steven A.] Med Univ S Carolina, Coll Hlth Profess, Div Phys Therapy, Charleston, SC 29425 USA. RP Kautz, SA (reprint author), 77 President St,MSC 700, Charleston, SC 29425 USA. EM kautz@musc.edu OI Kautz, Steven/0000-0003-3151-8235 FU NIH [RO1 HD46820]; Rehabilitation Research & Development Service of the VA FX The authors would like to thank Helen Emery, Dr. Mark Bowden, Kelly Rooney, Francis Bergschneider, Dr. Cameron Nott and Ryan Knight for help with the data collection and processing. This work was funded by NIH grant RO1 HD46820 and the Rehabilitation Research & Development Service of the VA The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NICHD, VA or the United States Government. NR 25 TC 12 Z9 13 U1 2 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD DEC PY 2012 VL 27 IS 10 BP 1023 EP 1030 DI 10.1016/j.clinbiomech.2012.08.005 PG 8 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 055MO UT WOS:000312420900008 PM 22981679 ER PT J AU Kohli, P Cannon, CP AF Kohli, Payal Cannon, Christopher P. TI The Importance of Matching Language to Type of Evidence: Avoiding the Pitfalls of Reporting Outcomes Data SO CLINICAL CARDIOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; DRUG-ELUTING STENTS; BARE-METAL STENTS; FOLLOW-UP; POSTMENOPAUSAL ESTROGEN; MYOCARDIAL-INFARCTION; UPDATED GUIDELINES; 11-YEAR MORTALITY; LDL CHOLESTEROL; RISK AB Results from different types of clinical research studies provide different types of evidence for evaluating the effects of a new drug or intervention. For this reason, it is important to recognize this phenomenon during reporting and to choose appropriate language to match the type of study that was done, because this can become critical to the interpretation and application of the results in clinical practice. In this article, we aim to highlight this issue through a series of examples and provide some guidance on what the appropriate language for different types of studies should be. This editorial review was cowritten and developed as an expanded background piece to accompany the statement by the HEART Group journal editors, which is being published simultaneously with this article. The authors have no funding, financial relationships, or conflicts of interest to disclose. C1 [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Kohli, Payal] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM cpcannon@partners.org NR 18 TC 26 Z9 27 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD DEC PY 2012 VL 35 IS 12 BP 714 EP 717 DI 10.1002/clc.22066 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 053CW UT WOS:000312248700005 PM 23192955 ER PT J AU Udell, JA Scirica, BM Braunwald, E Raz, I Steg, PG Davidson, J Hirshberg, B Bhatt, DL AF Udell, Jacob A. Scirica, Benjamin M. Braunwald, Eugene Raz, Itamar Steg, Ph. Gabriel Davidson, Jaime Hirshberg, Boaz Bhatt, Deepak L. TI Statin and Aspirin Therapy for the Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus SO CLINICAL CARDIOLOGY LA English DT Review ID AMERICAN-HEART-ASSOCIATION; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; OF-CARDIOLOGY FOUNDATION; SECONDARY PREVENTION; COLLABORATIVE METAANALYSIS; MYOCARDIAL-INFARCTION; SCIENTIFIC STATEMENT; DISEASE PREVENTION; VASCULAR OUTCOMES AB Patients with type 2 diabetes mellitus are at 2 to 4 times increased risk of cardiovascular events compared with those without diabetes, both among patients with multiple risk factors only and those with established atherothrombosis. In this review, we provide recommendations for the use of statins and aspirin for the prevention of cardiovascular events in high-risk patients with diabetes mellitus. C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Dept Med, Boston, MA 02132 USA. [Udell, Jacob A.; Scirica, Benjamin M.; Braunwald, Eugene; Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Raz, Itamar] Hadassah Hebrew Univ, Sch Med, Dept Med, Diabet Unit, Jerusalem, Israel. [Steg, Ph. Gabriel] INSERM, U698, Paris, France. [Steg, Ph. Gabriel] Univ Paris Diderot, Paris, France. [Steg, Ph. Gabriel] Hop Bichat Claude Bernard, AP HP, Dept Cardiol, F-75877 Paris, France. [Davidson, Jaime] Univ Texas SW Med Sch, Dept Med, Div Endocrinol, Dallas, TX USA. [Hirshberg, Boaz] AstraZeneca, Res & Dev, Wilmington, DE USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, Dept Med, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu FU AstraZeneca; Bristol-Myers Squibb; Canadian Institutes for Health Research (CIHR); Canadian Foundation for Women's Health; Merck; Johnson Johnson; Bayer Healthcare; Gilead Sciences; Lexicon; Arena Pharmaceuticals; Servier; Amarin; Eisai; Ethicon; Medtronic; Sanofi Aventis; The Medicines Company FX The SAVOR-TIMI 53 trial is sponsored by AstraZeneca and Bristol-Myers Squibb. Dr. Udell is a recipient of a Postdoctoral Research Fellowship from the Canadian Institutes for Health Research (CIHR) and Canadian Foundation for Women's Health. Dr. Scirica receives research grants from AstraZeneca, Bristol-Myers Squibb, Merck, Johnson & Johnson, Bayer Healthcare, and Gilead Sciences and consultancy fees from Gilead Sciences, Lexicon, and Arena Pharmaceuticals. Dr. Braunwald receives research grants from AstraZeneca and Bristol-Myers Squibb. Dr. Raz has received honoraria/expenses for advisory board participation from AstraZeneca, Bristol-Myers Squibb, Novo Nordisk, Merck, Sharp & Dohme, and Eli Lilly; has served as a consultant for Andromea, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, HealOr, Insuline, Teva, and TransPharma; and has participated in speakers bureaus for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Novo Nordisk, Johnson & Johnson, and Roche. Dr. Steg receives research grants from Servier. Dr. Davidson participated on advisory panels for AstraZeneca, Bristol-Myers Squibb, Merck, Johnson & Johnson, Boehringer Ingelheim, Eli Lilly, Generex Biotechnology, Novo Nordisk A/S, Roche Diagnostics, and Takeda Pharmaceutical Company and participated in speaker's bureaus for Eli Lilly and Takeda Pharmaceutical Company. Dr. Hirshberg is an employee of and holds stock in AstraZeneca. Dr. Bhatt discloses the following relationships-Advisory Board: Medscape Cardiology; Board of Directors: Boston VA Research Institute, Society of Chest Pain Centers; Chair: American Heart Association Get With The Guidelines Science Subcommittee; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research: FlowCo, PLx Pharma, Takeda. The design and conduct of the SAVOR-TIMI 53 study are being done by the academic executive committee in collaboration with the sponsors. NR 46 TC 8 Z9 8 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD DEC PY 2012 VL 35 IS 12 BP 722 EP 729 DI 10.1002/clc.22032 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 053CW UT WOS:000312248700006 PM 22760763 ER PT J AU Acharya, D Robertson, P Kay, GN Jackson, L Warnock, DG Plumb, VJ Tallaj, JA AF Acharya, Deepak Robertson, Peter Kay, G. Neal Jackson, Leslie Warnock, David G. Plumb, Vance J. Tallaj, Jose A. TI Arrhythmias in Fabry Cardiomyopathy SO CLINICAL CARDIOLOGY LA English DT Article ID ENZYME REPLACEMENT THERAPY; LEFT-VENTRICULAR HYPERTROPHY; HUMAN ALPHA-GALACTOSIDASE; CARDIAC MANIFESTATIONS; DISEASE; INVOLVEMENT; IMPROVEMENT; PREVALENCE; TRIAL AB Background: Prior studies suggest that the incidence of ventricular arrhythmias is high in patients with Fabry cardiomyopathy. This study evaluated the incidence of significant arrhythmias in a series of patients with Fabry cardiomyopathy. Hypothesis: Arrhythmias are important causes of morbidity and mortality in Fabry Cardiomyopathy. Methods: This study was a retrospective chart review of 19 patients with known Fabry cardiomyopathy. Device interrogation reports were reviewed for those who had implantable devices. Electrocardiogram, Holter monitor, and event monitors were reviewed in those who did not have implantable devices. Results: Eighteen of nineteen patients were on enzyme replacement therapy (ERT). Nine (47%) out of 19 patients had implantable devices. Implant indications included symptomatic bradycardia, nonsustained ventricular tachycardia, conduction abnormalities, palpitations, and syncope. Mean follow-up in the patients with devices was 50 +/- 23 months. Two patients received implantable cardioverter-defibrillator (ICD) shocks, 1 of which was inappropriate for atrial fibrillation. Patients were paced in the atrium 71% +/- 37% of the time and paced in the ventricle 49% +/- 52% of the time. Four patients with devices were paced more than 95% of the time. Patients with an ICD had lower heart rates prior to ICD implant than the group that did not have devices (60 +/- 10 vs 78 +/- 16, P = 0.03). Of the patients without devices, only 1 had sudden cardiac death. Patients with implanted devices had higher left ventricular (LV) mass indices compared to patients without implanted devices (136 +/- 40 g/m2 vs 93 +/- 19 g/m2, P = 0.008). Conclusions: Significant ventricular arrhythmias are uncommon in patients with Fabry cardiomyopathy on ERT, but utilization of pacing is high. Sudden cardiac death in Fabry cardiomyopathy may be related to bradycardia. The authors have no funding, financial relationships, or conflicts of interest to disclose. C1 [Acharya, Deepak; Robertson, Peter; Kay, G. Neal; Plumb, Vance J.; Tallaj, Jose A.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Jackson, Leslie; Warnock, David G.] Univ Alabama Birmingham, Div Nephrol, Birmingham, AL USA. [Tallaj, Jose A.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL USA. RP Acharya, D (reprint author), THT 321,1900 Univ Blvd, Birmingham, AL 35226 USA. EM dacharya@cardiology.uab.edu NR 26 TC 9 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD DEC PY 2012 VL 35 IS 12 BP 738 EP 740 DI 10.1002/clc.22047 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 053CW UT WOS:000312248700008 PM 22886820 ER PT J AU Park, MY Altman, RK Orencole, M Kumar, P Parks, KA Heist, KE Singh, JP Picard, MH AF Park, Mi Young Altman, Robert K. Orencole, Mary Kumar, Prabhat Parks, Kimberly A. Heist, Kevin E. Singh, Jagmeet P. Picard, Michael H. TI Characteristics of Responders to Cardiac Resynchronization Therapy: The Impact of Echocardiographic Left Ventricular Volume SO CLINICAL CARDIOLOGY LA English DT Article ID DEFIBRILLATOR IMPLANTATION TRIAL; SPECKLE TRACKING; MADIT-CRT; PREDICTORS; DYSSYNCHRONY; GENDER; STRAIN; SIZE AB Background: One-third of patients who receive cardiac resynchronization therapy (CRT) are classified as nonresponders. Characteristics of responders to CRT have been studied in multiple clinical trials. Hypothesis: Independent predictors of CRT response may be identified by studying a series of patients in routine clinical practice. Method: One hundred twenty-five patients were examined retrospectively from a multidisciplinary CRT clinic program. Echocardiographic CRT response was defined as a decrease in left ventricular (LV) end-systolic volume of =15% and/or absolute increase of 5% in LV ejection fraction at the 6-month visit. Results: There were 81 responders and 44 nonresponders. By univariate analyses, female sex, nonischemic cardiomyopathy etiology, baseline QRS duration, the presence of left bundle branch block (LBBB), and left ventricular end-diastolic volume (LVEDV) index predicted CRT response. However, multivariate analysis demonstrated that only QRS duration, LBBB, and LVEDV index were independent predictors (QRS width, odds ratio [OR]: 1.027, 95% confidence interval [CI]: 1.0041.050, P = 0.023; LBBB, OR: 3.568, 95% CI: 1.2849.910, P = 0.015; LVEDV index, OR: 0.970, 95% CI: 0.9530.987, P = 0.001). Although female sex and nonischemic etiology were associated with an improved CRT response on univariate analyses, after adjusting for LV volumes they were not independent predictors. Conclusions: QRS width, LBBB, and LVEDV index are independent predictors for echocardiographic CRT response. Previously reported differences in CRT response for sex and cardiomyopathy etiology are associated with differences in baseline LV volumes in our clinical practice. Dr. Heist has received research grants (modest) from Biotronik, Boston Scientific, and St. Jude Medical; honoraria (modest) from Biotronik, Boston Scientific, Medtronic, Sorin, and St. Jude Medical; and consultant/advisory board positions (modest) from Boston Scientific, Sorin and St. Jude Medical. Dr. Singh has received research grants (significant) from Biotronik, Boston Scientific, Medtronic, and St. Jude Medical; and consultant/advisory board positions (modest) from Biosense Webster, Biotronik, Boston Scientific, CardioInsight, Medtronic, Sorin, St. Jude Medical, and Thoratec Inc. The statistical analysis 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 RR 025758, and financial contributions from Harvard University and its affiliated academic healthcare centers). The authors have no other funding, financial relationships, or conflicts of interest to disclose. C1 [Park, Mi Young; Altman, Robert K.; Orencole, Mary; Kumar, Prabhat; Parks, Kimberly A.; Heist, Kevin E.; Singh, Jagmeet P.; Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Heart, Boston, MA 02114 USA. RP Picard, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Heart, Yawkey 5E,55 Fruit St, Boston, MA 02114 USA. EM mhpicard@partners.org OI Altman, Robert/0000-0002-1612-3561; Picard, Michael/0000-0002-9264-3243 FU Biotronik; Boston Scientific; St. Jude Medical; Medtronic; Harvard University; National Center for Advancing Translational Sciences, National Institutes of Health [UL1 RR 025758] FX Dr. Heist has received research grants (modest) from Biotronik, Boston Scientific, and St. Jude Medical; honoraria (modest) from Biotronik, Boston Scientific, Medtronic, Sorin, and St. Jude Medical; and consultant/advisory board positions (modest) from Boston Scientific, Sorin and St. Jude Medical. Dr. Singh has received research grants (significant) from Biotronik, Boston Scientific, Medtronic, and St. Jude Medical; and consultant/advisory board positions (modest) from Biosense Webster, Biotronik, Boston Scientific, CardioInsight, Medtronic, Sorin, St. Jude Medical, and Thoratec Inc.; The statistical analysis 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 RR 025758, and financial contributions from Harvard University and its affiliated academic healthcare centers). NR 15 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD DEC PY 2012 VL 35 IS 12 DI 10.1002/clc.22043 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 053CW UT WOS:000312248700014 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Effects of Birth Cohort on Long-Term Trends in Mortality From Colorectal Cancer SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Colonoscopy Screening; Cohort Study; Epidemiology; Helicobacter pylori ID HELICOBACTER-PYLORI INFECTION; PEPTIC-ULCER; RISK; RATES; METAANALYSIS; POLYPECTOMY; PREVENTION; ENDOSCOPY; VETERANS; AUTOPSY AB BACKGROUND & AIMS: The decrease in mortality from colorectal cancer might have begun before widespread use of screening colonoscopy and sigmoidoscopy examinations. We examined long-term time trends in colorectal cancer mortality in 6 European countries to determine when the reduction began. METHODS: We analyzed mortality data from the national statistical offices of the United Kingdom (England and Wales), France, Italy, The Netherlands, Sweden, and Switzerland during the past 66 to 107 years. The data were made available by the national statistical offices of the 6 countries. Age-specific rates of death were plotted against the period of death, as period-age contours, and against the period of birth, as cohort-age contours. RESULTS: Long-term time trends in mortality from cancers of the rectum and colon each increased among generations born from 1800 to 1880, and then decreased among all subsequent generations, in all 6 countries analyzed. Similar temporal patterns also were observed when data from men and women were analyzed separately. The birth cohort patterns of colorectal cancer mortality resemble those of gastric cancer and peptic ulcer. CONCLUSIONS: Time trends of mortality from colorectal cancer, in 6 European countries, are associated with birth cohort patterns: colorectal cancer mortality decreased among all generations since 1880. These patterns indicate that in addition to the use of screening colonoscopy, other factors, such as changes in Helicobacter pylori infection, may have affected mortality. C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol, P3-GI,3710 SW US,Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 27 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 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2012 VL 10 IS 12 BP 1389 EP 1394 DI 10.1016/j.cgh.2012.09.008 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 053IW UT WOS:000312265900017 PM 22982097 ER PT J AU Khan, AM Chirinos, JA Litt, H Yang, W Rosas, SE AF Khan, Abigail May Chirinos, Julio A. Litt, Harold Yang, Wei Rosas, Sylvia E. TI FGF-23 and the Progression of Coronary Arterial Calcification in Patients New to Dialysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; GROWTH-FACTOR 23; LEFT-VENTRICULAR HYPERTROPHY; RENAL-TRANSPLANT RECIPIENTS; CARDIOVASCULAR-DISEASE; HEMODIALYSIS-PATIENTS; COMPUTED-TOMOGRAPHY; SERUM PHOSPHORUS; CALCIUM; MORTALITY AB Background and objective Fibroblast growth factor 23 (FGF-23), a regulator of phosphorus metabolism, is a risk marker in CKD. FGF-23 has been associated with coronary arterial calcification (CAC), but it is not known whether FGF-23 predicts CAC progression in CKD. The aim of this study was to evaluate the association of FGF-23 with CAC progression in advanced CKD. Design, setting, participants, & measurements FGF-23 levels and CAC were measured by electrocardiography-triggered multislice computed tomography in 99 individuals initiating dialysis. Patients were enrolled in the study from April 2008 to July 2010. CAC was calculated using Agatston and calcium volume score. Sixty-seven study participants had repeat CAC measures at 1 year. Linear regression was used to assess the association of FGF-23 with CAC. Results The mean age of study participants was 50 years; 33% were women, and 64% were black. The median FGF-23 level was 1238 relative units (RU)/ml (interquartile range, 515-2218 RU/ml). According to Agatston score, FGF-23 was not associated with baseline CAC (P=0.14) but was significantly associated with CAC progression. There was a 192.3-Agatston unit change in CAC score per 1-SD change in FGF-23 (P=0.008) in models adjusting for known risk factors for CAC and serum phosphate. This association persisted after adjustment for high-sensitivity C-reactive protein, 25-OH vitamin D levels, and the use of phosphorus binders. Results were similar when change in calcium volume score was used. Conclusions In individuals with advanced CKD, serum FGF-23 is strongly associated with CAC progression. FGF-23 may be a marker of cardiovascular risk in CKD. Clin J Am Soc Nephrol 7: 2017-2022, 2012. doi:10.2215/CJN.02160212 C1 [Khan, Abigail May; Chirinos, Julio A.] Hosp Univ Penn, Div Cardiovasc, Philadelphia, PA 19104 USA. [Chirinos, Julio A.; Rosas, Sylvia E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Litt, Harold] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Yang, Wei] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Rosas, Sylvia E.] Univ Penn, Renal Electrolyte & Hypertens Div, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Rosas, SE (reprint author), 3400 Spruce St,1 Founders Bldg, Philadelphia, PA 19010 USA. EM Sylvia.rosas@uphs.upenn.edu FU National Institutes of Health grant [R21 HL 086971]; American Recovery and Reinvestment Act supplement; National Center for Research Resources [UL1RR024134] FX This work was supported by National Institutes of Health grant R21 HL 086971 and an American Recovery and Reinvestment Act supplement. Salary support was also provided by the Veterans Health Administration and R01 DK 080033 (S.E.R). The project described was supported by grant UL1RR024134 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Funding sources had no involvement in study design, data collection, analysis, and interpretation, writing of the report, or decision to submit the paper for publication. NR 32 TC 24 Z9 26 U1 0 U2 32 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD DEC PY 2012 VL 7 IS 12 BP 2017 EP 2022 DI 10.2215/CJN.02160212 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 051FK UT WOS:000312111400016 PM 22997345 ER PT J AU Young, BA Chan, C Blagg, C Lockridge, R Golper, T Finkelstein, F Shaffer, R Mehrotra, R AF Young, Bessie A. Chan, Christopher Blagg, Christopher Lockridge, Robert Golper, Thomas Finkelstein, Fred Shaffer, Rachel Mehrotra, Rajnish CA ASN Dialysis Advisory Grp TI How to Overcome Barriers and Establish a Successful Home HD Program SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; QUALITY-OF-LIFE; IN-CENTER HEMODIALYSIS; PERITONEAL-DIALYSIS PATIENTS; SELF-CARE DIALYSIS; RANDOMIZED CONTROLLED-TRIAL; CHRONIC KIDNEY-DISEASE; NOCTURNAL HEMODIALYSIS; CONVENTIONAL HEMODIALYSIS; UNITED-STATES AB Home hemodialysis (HD) is an underused dialysis modality in the United States, even though it provides an efficient and probably cost-effective way to provide more frequent or longer dialysis. With the advent of newer home HD systems that are easier for patients to learn, use, and maintain, patient and provider interest in home HD is increasing. Although barriers for providers are similar to those for peritoneal dialysis, home HD requires more extensive patient training, nursing education, and infrastructure support in order to maintain a successful program. In addition, because many physicians and patients do not have experience with home HD, reluctance to start home HD programs is widespread. This in-depth review describes barriers to home HD, focusing on patients, individual physicians and practices, and dialysis facilities, and offers suggestions for how to overcome these barriers and establish a successful home HD program. Clin J Am Soc Nephrol 7: 2023-2032, 2012. doi:10.2215/CJN.07080712 C1 [Young, Bessie A.] Univ Washington, Div Nephrol, Kidney Res Inst, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Chan, Christopher] Univ Toronto, Toronto, ON, Canada. [Blagg, Christopher] NW Kidney Ctr, Seattle, WA USA. [Lockridge, Robert] Univ Virginia, Dept Med, Div Nephrol, Lynchburg, VA USA. [Golper, Thomas] Vanderbilt Univ, Nashville, TN USA. [Finkelstein, Fred] St Raphaels Med Ctr, New Haven, CT USA. [Shaffer, Rachel] Amer Soc Nephrol, Washington, DC USA. [Mehrotra, Rajnish] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. RP Young, BA (reprint author), Vet Affairs Puget Sound Hlth Care Syst 152 E, 1660 S Columbian Way, Seattle, WA 98108 USA. EM youngb@u.washington.edu OI Saggi, Subodh/0000-0001-9126-7226 FU Veterans Affairs Puget Sound Health Care System; Baxter Healthcare; DaVita; Mitsubishi; Shire; Takeda; Vifor FX This material is the result of work supported by resources from the Veterans Affairs Puget Sound Health Care System.; C.C. serves as a member of the scientific advisory board for Baxter Healthcare. C.B. is a consultant to DEKA Research and Development Corporation. R.L. serves as a member of the scientific advisory board for Fresenius Medical Care. T.G. conducts consultant activity for Baxter, Fresenius, DaVita, Takeda-Affymax, and Q Source. F.F. serves as a member of the scientific advisory board for NxStage and conducts consultant activity for Baxter Healthcare. R.S. is an employee of the American Society of Nephrology. R.M. has received grant support and/or honoraria from Baxter Healthcare, DaVita, Mitsubishi, Shire, Takeda, and Vifor. NR 97 TC 24 Z9 24 U1 2 U2 15 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD DEC PY 2012 VL 7 IS 12 BP 2023 EP 2032 DI 10.2215/CJN.07080712 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 051FK UT WOS:000312111400017 PM 23037981 ER PT J AU Riegel, B Glaser, D Richards, K Sayers, SL Marzolf, A Weintraub, WS Goldberg, LR AF Riegel, Barbara Glaser, Dale Richards, Kathy Sayers, Steven L. Marzolf, Amy Weintraub, William S. Goldberg, Lee R. TI Modifiable factors associated with sleep dysfunction in adults with heart failure SO EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING LA English DT Article DE Heart failure; sleep; sleep dysfunction; self-rated health; medications; sleep hygiene; depression ID QUALITY-OF-LIFE; GLOBAL PERCEIVED HEALTH; PRIMARY-CARE PATIENTS; SELF-RATED HEALTH; OLDER-ADULTS; DAYTIME SLEEPINESS; BLOOD-PRESSURE; POOR HEALTH; INSOMNIA; POPULATION AB Background: Sleep dysfunction contributes to poor quality of life in adults with heart failure (HF). The purpose of this study was to identify factors associated with sleep dysfunction that may be modifiable. Methods: Data were collected from 266 subjects enrolled from three sites in the U. S. Sleep dysfunction was measured over the past month with the Pittsburgh Sleep Quality Index, using a score > 10 to indicate sleep dysfunction. Potentially modifiable clinical, behavioral, and psychological factors thought to be associated with sleep dysfunction were analyzed with hierarchical logistic regression analysis. Results: When covariates of age, gender, race, data collection site, and New York Heart Association (NYHA) functional class were entered on the first step, only NYHA was a significant correlate of sleep dysfunction. When the clinical, behavioral, and psychological factors were entered, correlates of sleep dysfunction were the number of drugs known to cause daytime somnolence (OR = 2.08), depression (OR = 1.83), worse overall perceived health (OR = 1.64), and better sleep hygiene (OR = 1.40). Although most (54%) subjects had sleep disordered breathing (SDB), SDB was not a significant predictor of sleep dysfunction. Discussion: Factors associated with sleep dysfunction in HF include medications with sleepiness as a side-effect, depression, poorer health perceptions, and better sleep hygiene. Sleep dysfunction may motivate HF patients to address sleep hygiene. Eliminating medications with sleepiness as a side-effect, treating depression and perceptions of poor health may improve sleep quality in HF patients. C1 [Riegel, Barbara] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Glaser, Dale] Glaser Consulting, San Diego, CA USA. [Glaser, Dale] Univ San Diego, Sch Nursing, San Diego, CA 92110 USA. [Richards, Kathy] George Mason Univ, Fairfax, VA 22030 USA. [Sayers, Steven L.; Goldberg, Lee R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Sayers, Steven L.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Marzolf, Amy] Univ Penn, Heart Failure & Transplant Ctr, Philadelphia, PA 19104 USA. [Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. RP Riegel, B (reprint author), Univ Penn, Sch Nursing, 418 Curie Blvd, Philadelphia, PA 19104 USA. EM briegel@nursing.upenn.edu OI Goldberg, Lee/0000-0002-7906-9638 FU National Heart, Lung & Blood Institute [RO1 HL084394-01A1]; Philadelphia Veterans Affairs Medical Center; VISN 4 Mental Illness Research, Education, and Clinical Center (MIREC) FX This work was funded by a grant from the National Heart, Lung & Blood Institute (RO1 HL084394-01A1) and by the Philadelphia Veterans Affairs Medical Center, VISN 4 Mental Illness Research, Education, and Clinical Center (MIREC). NR 60 TC 7 Z9 7 U1 1 U2 13 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1474-5151 J9 EUR J CARDIOVASC NUR JI Eur. J. Cardiovasc. Nurs. PD DEC PY 2012 VL 11 IS 4 BP 402 EP 409 DI 10.1016/j.ejcnurse.2011.02.001 PG 8 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 054MS UT WOS:000312348500006 PM 21353642 ER PT J AU Jensen, RJ AF Jensen, Ralph J. TI Blocking GABA(C) receptors increases light responsiveness of retinal ganglion cells in a rat model of retinitis pigmentosa SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE retinal degeneration; retinal ganglion cell; light responsiveness; GABA(C) receptor antagonist; retinitis pigmentosa ID TIGER SALAMANDER RETINA; ROD BIPOLAR CELLS; SYNAPTIC-TRANSMISSION; TRANSGENIC RAT; RHO-SUBUNITS; MOUSE RETINA; INHIBITION; TERMINALS; DEGENERATION; SYSTEM AB Previous studies in a mouse model of retinitis pigmentosa indicate that the GABAergic system in the retina may be overactive. GABA is known to act on GABA(C) receptors present on the axon terminals of bipolar cells to inhibit the release of excitatory neurotransmitter from these cells. The present study examined the effects of a GABA(C) receptor antagonist on the light-evoked responses of retinal ganglion cells (RGCs) in a rat model of retinitis pigmentosa. Extracellular recordings were made from RGCs in retinas isolated from P23H transgenic rats and non-dystrophic Sprague-Dawley (SD) rats. Spike activity of RGCs was measured in response to brief flashes of light over a range of light intensities. Intensity response curves were evaluated prior to and during bath application of the GABA(C) receptor antagonist TPMPA. I found that TPMPA consistently increased the sensitivity of P23H rat RGCs to light flashes. For ON-center RGCs (n = 21), the average increase in light sensitivity was 0.63 log unit. For OFF-center RGCs (n = 6), the average increase was 0.38 log unit. TPMPA increased the maximum peak response of ON-center RGCs by 22% and OFF-center RGCs by 11%. However, the increase in maximum peak response of OFF-center RGCs was not statistically significant. TPMPA had no significant effect on the dynamic operating range of either ON-center or OFF-center RGCs. Nine ON-center SD rat RGCs were also tested. In contrast to what was observed for P23H rat RGCs, TPMPA decreased the sensitivity of these RGCs to light flashes, on average by 0.20 log unit. In conclusion, GABA(C) receptors may be novel targets for therapeutic interventions aimed at increasing light responsiveness in patients with retinitis pigmentosa or other diseases involving degeneration of photoreceptors. Published by Elsevier Ltd. C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Jensen, RJ (reprint author), VA Boston Healthcare Syst, Mail Stop 151E,150 S Huntington Ave, Boston, MA 02130 USA. EM Ralph.jensen@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service. NR 27 TC 7 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD DEC PY 2012 VL 105 BP 21 EP 26 DI 10.1016/j.exer.2012.10.005 PG 6 WC Ophthalmology SC Ophthalmology GA 052CZ UT WOS:000312176600004 PM 23085337 ER PT J AU Foley, D Murphy, M Ghobrial, I O'Gorman, P Weinstock, M Anderson, K AF Foley, D. Murphy, M. Ghobrial, I O'Gorman, P. Weinstock, M. Anderson, K. TI OCCURRENCE OF EXTRA-MEDULLARY DISEASE IN MULTIPLE MYELOMA SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Meeting Abstract C1 [Foley, D.; Murphy, M.; Ghobrial, I; Weinstock, M.; Anderson, K.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Foley, D.; O'Gorman, P.] Mater Misericordiae Univ Hosp, Dept Haematol, Dublin, Ireland. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0021-1265 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD DEC PY 2012 VL 181 SU 11 MA 19 BP S448 EP S448 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 053HA UT WOS:000312260800020 ER PT J AU Murphy, M Foley, D Aljawai, Y Ghobrial, I Anderson, K AF Murphy, M. Foley, D. Aljawai, Y. Ghobrial, I. Anderson, K. TI ANALYSIS OF TUMOR MARKER EXPRESSION, KARYOTYPE AND CYTOGENETIC MUTATIONS IN PATIENTS WITH MULTIPLE MYELOMA AT DFCI SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Meeting Abstract C1 [Murphy, M.; Foley, D.; Aljawai, Y.; Ghobrial, I.; Anderson, K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0021-1265 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD DEC PY 2012 VL 181 SU 11 MA 28 BP S451 EP S451 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 053HA UT WOS:000312260800029 ER PT J AU Tanpowpong, P Broder-Fingert, S Katz, AJ Camargo, CA AF Tanpowpong, Pornthep Broder-Fingert, Sarabeth Katz, Aubrey J. Camargo, Carlos A., Jr. TI Clinical and histopathological features of children with type I diabetes and positive celiac disease serology SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 [Tanpowpong, Pornthep; Broder-Fingert, Sarabeth; Katz, Aubrey J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD DEC PY 2012 VL 27 SU 5 SI SI BP 140 EP 140 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 053AV UT WOS:000312242700431 ER PT J AU Tanpowpong, P Broder-Fingert, S Katz, AJ Camargo, CA AF Tanpowpong, Pornthep Broder-Fingert, Sarabeth Katz, Aubrey J. Camargo, Carlos A., Jr. TI Predictors of gluten avoidance in adults without previously diagnosed celiac disease SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 [Tanpowpong, Pornthep; Broder-Fingert, Sarabeth; Katz, Aubrey J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD DEC PY 2012 VL 27 SU 5 SI SI BP 141 EP 142 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 053AV UT WOS:000312242700435 ER PT J AU Fagin, AP Susarla, SM Donoff, RB Kaban, LB Dodson, TB AF Fagin, Adam P. Susarla, Srinivas M. Donoff, Robert B. Kaban, Leonard B. Dodson, Thomas B. TI What Factors Are Associated With Functional Sensory Recovery Following Lingual Nerve Repair? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID INFERIOR ALVEOLAR NERVE; MANDIBULAR 3RD MOLARS; MANAGEMENT; REMOVAL; MICROSURGERY; INJURIES; DAMAGE AB Purpose: To identify factors associated with functional sensory recovery (FSR) after lingual nerve repair. Materials and Methods: This retrospective cohort study was composed of subjects who underwent lingual nerve repair from 2004 through 2010. The predictor variables were demographic, anatomic, and operative measurements. The primary outcome measurement was FSR (ie, FSR achieved, yes or no). The secondary outcome measurements were time to FSR and an improvement of at least 2 levels on the British Medical Research Council scale of neurosensory function. Descriptive, bivariate, and multiple logistic regression statistics were computed to identify associations between the predictor variables and FSR. A Cox proportional hazards model was used to identify associations between the predictors and time to FSR. P <= .05 was considered statistically significant. Results: The sample was composed of 55 subjects with a mean age of 30.7 +/- 11.2 years. The mean duration from injury to repair was 151.6 days (range, 41 to 384 days). Most patients (74.5%) achieved FSR postoperatively, with a mean time to FSR of 262.8 days (median, 208 days). Eighty-six percent of subjects showed an improvement of at least 2 levels on the British Medical Research Council scale. In multiple regression models, younger subjects were more likely to achieve FSR (odds ratio, 1.10; 95% confidence interval, 1.01 to 1.18; P = .02); subjects with better preoperative neurosensory function achieved FSR faster (hazard ratio, 1.9; 95% confidence interval, 1.2 to 3.1; P = .01). Conclusion: Most patients undergoing lingual nerve repair achieved FSR. Younger subjects were more likely to achieve FSR. Subjects with better preoperative neurosensory function achieved FSR faster. (c) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:2907-2915, 2012 C1 [Fagin, Adam P.; Donoff, Robert B.; Kaban, Leonard B.; Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, WRN 1201, Boston, MA 02114 USA. EM tbdodson@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU Massachusetts General Hospital Physicians Organization; Department of Oral and Maxillofacial Surgery Education and Research Fund; Center for Applied Clinical Investigation; Oral and Maxillofacial Surgery Foundation Fellowship in Clinical Investigation FX This work was supported by the Massachusetts General Hospital Physicians Organization (T.B.D., L.B.K.), the Department of Oral and Maxillofacial Surgery Education and Research Fund (A.F., S.M.S.), the Center for Applied Clinical Investigation (S.M.S., T.B.D.), and the Oral and Maxillofacial Surgery Foundation Fellowship in Clinical Investigation (S.M.S.). NR 23 TC 7 Z9 7 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 2012 VL 70 IS 12 BP 2907 EP 2915 DI 10.1016/j.joms.2012.03.019 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 053IC UT WOS:000312263700033 PM 22695009 ER PT J AU Lovejoy, TI Turk, DC Morasco, BJ AF Lovejoy, Travis I. Turk, Dennis C. Morasco, Benjamin J. TI Evaluation of the Psychometric Properties of the Revised Short-Form McGill Pain Questionnaire SO JOURNAL OF PAIN LA English DT Article DE Chronic pain; McGill Pain Questionnaire; psychometric reliability; validity ID NEUROPATHIC PAIN; VALIDATION; INVENTORY; SCALE AB The recently revised version of the Short-Form McGill Pain Questionnaire (SF-MPQ-2) was created to assess both neuropathic and non-neuropathic pain. The current study extends prior research by testing the reliability and validity of the SF-MPQ-2 in a sample of U.S. veteran patients with a range of chronic pain diagnoses. Participants (N = 186) completed the SF-MPQ-2, a sociodemographic questionnaire, the Structured Clinical Interview for the DSM-IV, and self-report pain and psychiatric measures. Pain diagnoses were extracted from the electronic medical record. The SF-MPQ-2 total and scale scores demonstrated good-to-excellent internal consistency. Convergent and discriminant validity were supported, and SF-MPQ-2 total and scale scores increased with number of pain diagnoses and pain severity. Confirmatory factor analyses indicated that a 4-factor model fit the data better than a single-factor model. However, high intercorrelations among the 4 latent constructs were observed, and a second-order global pain construct also emerged. Overall, the SF-MPQ-2 demonstrated excellent reliability and validity in a sample of U.S. veteran patients with chronic neuropathic and non-neuropathic pain. Future psychometric studies of the SF-MPQ-2 should employ longitudinal data to evaluate the ability of scale scores to uniquely predict clinical and health service outcomes. Perspective: This article presents the psychometric properties of a revised version of the SF-MPQ-2. This measure may have great utility as a screening tool in clinical practice and as an outcome measure in clinical trials. Published by Elsevier Inc. on behalf of the American Pain Society C1 [Lovejoy, Travis I.; Morasco, Benjamin J.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97239 USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Morasco, Benjamin J.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Lovejoy, TI (reprint author), Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, P3MHDC,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM travis.lovejoy@va.gov FU United States National Institute on Drug Abuse [K23DA023467]; Endo; Johnson Johnson; Philips Respironics; National Institutes of Health; Eli Lilly; OrthoMcNeill- Janssen; Pfizer; SK LifeScience FX This material is the result of work supported with resources and the use of facilities at the Portland VA Medical Center. This study was supported in part by award K23DA023467 from the United States National Institute on Drug Abuse to Dr. Morasco. Dr. Turk has received research support from Endo, Johnson & Johnson, Philips Respironics, and the National Institutes of Health, and consulting fees from Eli Lilly, OrthoMcNeill- Janssen, Pfizer, Philips Respironics, and SK LifeScience. He is also a Special Government Employee of the U.S. Food and Drug Administration. No other author reports having any potential conflict of interest. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs or the National Institute on Drug Abuse. NR 28 TC 20 Z9 22 U1 3 U2 25 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD DEC PY 2012 VL 13 IS 12 BP 1250 EP 1257 DI 10.1016/j.jpain.2012.09.011 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 053NR UT WOS:000312280200012 PM 23182230 ER PT J AU Mercier, PP Lysaght, AC Bandyopadhyay, S Chandrakasan, AP Stankovic, KM AF Mercier, Patrick P. Lysaght, Andrew C. Bandyopadhyay, Saurav Chandrakasan, Anantha P. Stankovic, Konstantina M. TI Energy extraction from the biologic battery in the inner ear SO NATURE BIOTECHNOLOGY LA English DT Article ID BIOFUEL CELL; ELECTRICITY; CIRCUIT; HEARING AB Endocochlear potential (EP) is a battery-like electrochemical gradient found in and actively maintained by the inner ear(1,2). Here we demonstrate that the mammalian EP can be used as a power source for electronic devices. We achieved this by designing an anatomically sized, ultra-low quiescent-power energy harvester chip integrated with a wireless sensor capable of monitoring the EP itself. Although other forms of in vivo energy harvesting have been described in lower organisms(3-5), and thermoelectric(6), piezoelectric(7) and biofuel(8,9) devices are promising for mammalian applications, there have been few, if any, in vivo demonstrations in the vicinity of the ear, eye and brain. In this work, the chip extracted a minimum of 1.12 nW from the EP of a guinea pig for up to 5 h, enabling a 2.4 GHz radio to transmit measurement of the EP every 40-360 s. With future optimization of electrode design, we envision using the biologic battery in the inner ear to power chemical and molecular sensors, or drug-delivery actuators for diagnosis and therapy of hearing loss and other disorders. C1 [Mercier, Patrick P.; Bandyopadhyay, Saurav; Chandrakasan, Anantha P.] MIT, Microsyst Technol Labs, Cambridge, MA 02139 USA. [Lysaght, Andrew C.; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Lysaght, Andrew C.; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Lysaght, Andrew C.; Stankovic, Konstantina M.] Harvard Massachusetts Inst Technol, Program Speech & Hearing Biosci & Technol, Joint Div Hlth Sci & Technol, Cambridge, MA USA. [Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Chandrakasan, AP (reprint author), MIT, Microsyst Technol Labs, Cambridge, MA 02139 USA. EM anantha@mtl.mit.edu; konstantina_stankovich@meei.harvard.edu FU C2S2 Focus Center; Interconnect Focus Center; Focus Center Research Program (FCRP); Semiconductor Research Corporation entity; US National Institutes of Health [K08 DC010419, T32 DC00038]; Bertarelli Foundation FX We acknowledge support from the C2S2 Focus Center and the Interconnect Focus Center, two of six research centers funded under the Focus Center Research Program (FCRP), a Semiconductor Research Corporation entity (A. P. C., P. P. M., S. B.), and from US National Institutes of Health grants K08 DC010419 (K. M. S.) and T32 DC00038 (A. C. L.) and the Bertarelli Foundation (K. M. S.). We thank J.J. Guinan Jr. for experimental assistance and advice, and B. Zhu for preliminary studies. NR 31 TC 53 Z9 54 U1 8 U2 79 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2012 VL 30 IS 12 BP 1240 EP + DI 10.1038/nbt.2394 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 050ZA UT WOS:000312092400028 PM 23138225 ER PT J AU Milber, JM Noorigian, JV Morley, JF Petrovitch, H White, L Ross, GW Duda, JE AF Milber, Joshua M. Noorigian, Joseph V. Morley, James F. Petrovitch, Helen White, Lon Ross, G. Webster Duda, John E. TI Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease SO NEUROLOGY LA English DT Article ID ALPHA-SYNUCLEIN PATHOLOGY; SUBSTANTIA-NIGRA; BODY DISEASE; DEMENTIA; BRAIN; BODIES; RELEVANCE; DEATH; MEN AB Objective: To determine whether evidence of neuronal dysfunction or demise preceded deposition of Lewy pathology in vulnerable neurons in Parkinson disease (PD). Methods: We examined the extent of nigral dysfunction and degeneration among 63 normal, incidental Lewy body disease (ILBD), and PD cases based on tyrosine hydroxylase (TH) immunoreactivity and neuron densities, respectively. The relationship between these markers and Lewy pathology (LP) burden in the substantia nigra (SN) and Braak PD stage was assessed. Results: Compared with normal subjects, ILBD cases displayed a significantly higher percentage of TH-negative cells and lower neuronal densities in the SN as early as Braak PD stages 1 and 2, before LP deposition in the nigrostriatal system. ILBD nigral neuron densities were intermediate between normal subjects and PD cases, and TH-negative percentages were higher in ILBD than either normal or PD cases. Furthermore, neuron density and neuronal dysfunction levels remained relatively constant across Braak PD stages in ILBD. Conclusions: These results suggest that significant neurodegeneration and cellular dysfunction precede LP in the SN, challenging the pathogenic role of LP in PD and the assumption that ILBD always represents preclinical PD. Neurology (R) 2012; 79: 2307-2314 C1 [Milber, Joshua M.; Noorigian, Joseph V.; Morley, James F.; Duda, John E.] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Morley, James F.; Duda, John E.] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Petrovitch, Helen; Ross, G. Webster] Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. [Petrovitch, Helen; White, Lon; Ross, G. Webster] Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA. [Petrovitch, Helen; White, Lon; Ross, G. Webster] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA. [Petrovitch, Helen; White, Lon; Ross, G. Webster] Kuakini Med Ctr, Honolulu Asian Aging Study, Honolulu, HI USA. RP Duda, JE (reprint author), Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. EM john.duda@va.gov FU Biomedical Laboratory Research and Development Service of the Department of Veterans Affairs; United States Department of the Army [DAMD17-98-1-8621]; National Institutes of Health: National Institute of Neurological Disorders and Stroke [5 R01 NS041265]; National Institute on Aging [1 U01 AG19349, 5 R01 AG017155]; Office of Research and Development, Medical Research Service Department of Veterans Affairs; Department of Defense; NINDS, NIH; NIA, NIH; Northwestern Foundation; Michael J. Fox Foundation; Department of Veterans Affairs; NIH; Michael J. Fox Foundation for Parkinson Research; Samueli Institute FX Supported by a Merit Award from the Biomedical Laboratory Research and Development Service of the Department of Veterans Affairs (J.E. Duda, PI) and by the United States Department of the Army, grant DAMD17-98-1-8621; National Institutes of Health: National Institute of Neurological Disorders and Stroke grant 5 R01 NS041265; National Institute on Aging grants 1 U01 AG19349 and 5 R01 AG017155; and the Office of Research and Development, Medical Research Service Department of Veterans Affairs.; J. Milber and J. Noorigian have no disclosures. J. Morley has received compensation for articles written in the PD Monitor and Commentary, a publication supported by an educational grant from Teva Neuroscience. H. Petrovitch and L. White have no disclosures. G. Webster Ross receives salary support from the Department of Veterans Affairs and research support from the Department of Defense; NINDS, NIH; NIA, NIH; Northwestern Foundation; and the Michael J. Fox Foundation. J. Duda has received research support from the Department of Veterans Affairs, the NIH, the Michael J. Fox Foundation for Parkinson Research, and the Samueli Institute. He holds common stock in C. R. Bard, Inc., Celgene Corp., Clarient, Inc., and Johnson & Johnson. Go to Neurology.org for full disclosures. NR 34 TC 34 Z9 34 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 2012 VL 79 IS 24 BP 2307 EP 2314 DI 10.1212/WNL.0b013e318278fe32 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 053MA UT WOS:000312274500007 PM 23152586 ER PT J AU Auriel, E Gurol, ME Ayres, A Dumas, AP Schwab, KM Vashkevich, A Martinez-Ramirez, S Rosand, J Viswanathan, A Greenberg, SM AF Auriel, Eitan Gurol, Mahmut Edip Ayres, Alison Dumas, Andrew P. Schwab, Kristin M. Vashkevich, Anastasia Martinez-Ramirez, Sergi Rosand, Jonathan Viswanathan, Anand Greenberg, Steven M. TI Characteristic distributions of intracerebral hemorrhage-associated diffusion-weighted lesions SO NEUROLOGY LA English DT Article ID CEREBRAL AMYLOID ANGIOPATHY; BLOOD-PRESSURE REDUCTION; CORTICAL MICROINFARCTS; VASCULAR DEMENTIA; BRAIN; INFARCTS; DISEASE; BURDEN; IMAGES; IMPACT AB Objectives: To determine whether small diffusion-weighted imaging (DWI) lesions occur beyond the acute posthemorrhage time window in patients with intracerebral hemorrhage (ICH) and to characterize their spatial distribution in patients with lobar and deep cerebral hemorrhages. Methods: In this cross-sectional study, we retrospectively analyzed 458 MRI scans obtained in the acute (<7 days after ICH) or nonacute (>14 days after ICH) phases from 392 subjects with strictly lobar (n = 276) and deep (n = 116) ICH (48.7% women; mean age 72.8 +/- 11.7 years). DWI, apparent diffusion coefficient maps, fluid-attenuated inversion recovery, and T2* MRIs were reviewed for the presence and location of DWI lesions. Results: We identified 103 DWI hyperintense lesions on scans from 62 subjects, located mostly in lobar brain regions (90 of 103, 87.4%). The lesions were not uniformly distributed throughout the brain lobes; patients with strictly lobar ICH had relative overrepresentation of lesions in frontal lobe, and patients with deep ICH in parietal lobe (p = 0.002). Although the frequency of DWI lesions tended to be greater on scans performed within 7 days after ICH (39 of 214, 18.2%), they continued at high frequency in the nonacute period as well (23 of 178, 12.9%, odds ratio 1.5, 95% confidence interval 0.86-2.6 for acute vs nonacute). There was also no difference in frequency of lesions on acute and nonacute scans among 66 subjects with MRIs in both time periods (8 of 66 acute, 10 of 66 nonacute, odds ratio 0.77, 95% confidence interval 0.25-2.4). Conclusions: The high frequency of DWI lesions beyond the acute post-ICH period and their characteristic distributions suggest that they are products of the small vessel diseases that underlie ICH. Neurology (R) 2012;79:2335-2341 C1 [Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. EM sgreenberg@partners.org RI Gurol, Edip/J-2279-2014; OI Gurol, Edip/0000-0002-2169-4457; Ayres, Alison/0000-0002-5492-1695 FU National Institutes of Health [R01AG026484]; American Heart Association FX All funding entities had no involvement in study design, data collection, analysis, and interpretation, writing of the manuscript, or in the decision to submit for publication. The project described was supported by grant R01AG026484 from the National Institutes of Health.; E. Auriel, M.E. Gurol, A. Ayres, A.P. Dumas, K.M. Schwab, A. Vashkevich, and S. Martinez-Ramirez report no disclosures. J. Rosand receives research support from the NIH and American Heart Association. A. Viswanathan reports no disclosures. S.M. Greenberg receives research support from the NIH and serves as consultant and on the advisory board of Hoffman-La Roche. NR 38 TC 18 Z9 18 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 2012 VL 79 IS 24 BP 2335 EP 2341 DI 10.1212/WNL.0b013e318278b66f PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 053MA UT WOS:000312274500011 PM 23197745 ER PT J AU Frisbie, JH Sharma, GVRK AF Frisbie, J. H. Sharma, G. V. R. K. TI Response: Pulmonary embolism in chronic spinal cord injury SO SPINAL CORD LA English DT Letter ID PROPHYLACTIC ANTICOAGULANT-THERAPY C1 [Frisbie, J. H.; Sharma, G. V. R. K.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02114 USA. RP Frisbie, JH (reprint author), Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02114 USA. EM jfrisbie@comcast.net NR 7 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD DEC PY 2012 VL 50 IS 12 BP 932 EP 932 DI 10.1038/sc.2012.115 PG 1 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 052MA UT WOS:000312200700019 ER PT J AU Bonatti, H Barroso, LF Sawyer, RG Kotton, CN Sifri, CD AF Bonatti, H. Barroso, L. F., II Sawyer, R. G. Kotton, C. N. Sifri, C. D. TI Cryptosporidium enteritis in solid organ transplant recipients: multicenter retrospective evaluation of 10 cases reveals an association with elevated tacrolimus concentrations SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE tacrolimus toxicity; Cryptosporidium; cryptosporidiosis; enteritis; parasitic infection; infection; transplantation; diarrhea ID DIFFICILE-ASSOCIATED DIARRHEA; HUMAN-IMMUNODEFICIENCY-VIRUS; SINGLE-CENTER EXPERIENCE; ALLOGENEIC BONE-MARROW; RENAL-TRANSPLANT; CLOSTRIDIUM-DIFFICILE; LIVER-TRANSPLANTATION; SCLEROSING CHOLANGITIS; PARASITIC INFECTIONS; WATERBORNE OUTBREAK AB Background Cryptosporidial enteritis, a diarrheal infection of the small intestine caused by the apicomplexan protozoa Cryptosporidium, is infrequently recognized in transplant recipients from developed countries. Methods A retrospective review of all cases of cryptosporidiosis in solid organ transplant (SOT) recipients at 2 centers from January 2001 to October 2010 was performed and compared with transplant recipients with community-onset Clostridium difficile infection (CDI). A literature search was performed with regard to reported cases of cryptosporidiosis in SOT recipients. Results Eight renal, 1 liver, and 1 lung transplant recipient were diagnosed with cryptosporidiosis at median 46.0 months (interquartile range [IQR] 25.262.8) following SOT. Symptoms existed for a median 14 days (IQR 10.514.8) before diagnosis. For the 9 patients receiving tacrolimus (TAC), mean TAC levels increased from 6.3 +/- 1.1 to 21.3 +/- 9.2 ng/mL (P = 0.0007) and median serum creatinine increased temporarily from 1.3 (IQR 1.11.7) to 2.4 (IQR 2.04.6) mg/dL (P = 0.008). By comparison, 8 SOT recipients (6 kidney, 2 liver) hospitalized with community-onset CDI had a mean TAC level of 10.8 +/- 2.8 ng/dL during disease compared with 9.2 +/- 2.3 ng/mL at baseline (P = 0.07) and had no change in median creatinine. All patients recovered from Cryptosporidium enteritis after receiving various chemotherapeutic regimens. Conclusions Cryptosporidiosis should be recognized as an important cause of diarrhea after SOT and is associated with elevated TAC levels and acute kidney injury. Increased TAC levels may reflect altered drug metabolism in the small intestine. C1 [Barroso, L. F., II; Sifri, C. D.] Univ Virginia Hlth Syst, Div Infect Dis & Int Hlth, Dept Med, Charlottesville, VA 22908 USA. [Bonatti, H.; Sawyer, R. G.] Univ Virginia Hlth Syst, Dept Surg, Charlottesville, VA 22908 USA. [Kotton, C. N.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Sifri, CD (reprint author), Univ Virginia Hlth Syst, Div Infect Dis & Int Hlth, Dept Med, POB 800473, Charlottesville, VA 22908 USA. EM csifri@virginia.edu NR 90 TC 14 Z9 14 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-2273 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD DEC PY 2012 VL 14 IS 6 BP 635 EP 648 DI 10.1111/j.1399-3062.2012.00719.x PG 14 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 051TA UT WOS:000312149100021 PM 22340660 ER PT J AU Williams, EC Bradley, KA Gupta, S Harris, AHS AF Williams, Emily C. Bradley, Katharine A. Gupta, Shalini Harris, Alex H. S. TI Association Between Alcohol Screening Scores and Mortality in Black, Hispanic, and White Male Veterans SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol; Race; Ethnicity; Mortality; AUDIT-C ID ALL-CAUSE MORTALITY; BEHAVIORAL-COUNSELING INTERVENTIONS; DEATH REPORTING SYSTEM; PRIMARY-CARE PATIENTS; UNITED-STATES; HEALTH-STATUS; RACIAL-DIFFERENCES; PROBLEM DRINKING; VIOLENT DEATHS; PUBLIC-HEALTH AB Background Scores on the Alcohol Use Disorders Identification Test Consumption (AUDIT-C) questionnaire are associated with mortality, but whether or how associations vary across race/ethnicity is unknown. Methods Self-reported black (n = 13,068), Hispanic (n = 9,466), and white (n = 182,688) male Veterans Affairs (VA) outpatients completed the AUDIT-C via mailed survey. Logistic regression models evaluated whether race/ethnicity modified the association between AUDIT-C scores (0, 1 to 4, 5 to 8, and 9 to 12) and mortality after 24 months, adjusting for demographics, smoking, and comorbidity. Results Adjusted mortality rates were 0.036, 0.033, and 0.054, for black, Hispanic, and white patients with AUDIT-C scores of 1 to 4, respectively. Race/ethnicity modified the association between AUDIT-C scores and mortality (p = 0.0022). Hispanic and white patients with scores of 0, 5 to 8, and 9 to 12 had significantly increased risk of death compared to those with scores of 1 to 4; Hispanic ORs: 1.93, 95% CI 1.50 to 2.49; 1.57, 1.07 to 2.30; 1.82, 1.04 to 3.17, respectively; white ORs: 1.34, 95% CI 1.29 to 1.40; 1.12, 1.03 to 1.21; 1.81, 1.59 to 2.07, respectively. Black patients with scores of 0 and 5 to 8 had increased risk relative to scores of 1 to 4 (ORs 1.28, 1.06 to 1.56 and 1.50, 1.13 to 1.99), but there was no significant increased risk for scores of 9 to 12 (ORs 1.27, 0.77 to 2.09). Post hoc exploratory analyses suggested an interaction between smoking and AUDIT-C scores might account for some of the observed differences across race/ethnicity. Conclusions Among male VA outpatients, associations between alcohol screening scores and mortality varied significantly depending on race/ethnicity. Findings could be integrated into systems with automated risk calculators to provide demographically tailored feedback regarding medical consequences of drinking. C1 [Williams, Emily C.] Vet Affairs VA Puget Sound Hlth Care Syst, NW Ctr Excellence Hlth Serv Res & Dev HSR&D, Seattle, WA USA. [Williams, Emily C.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. [Williams, Emily C.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, NW Ctr Excellence HSR&D, Seattle, WA 98101 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. [Gupta, Shalini; Harris, Alex H. S.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA USA. RP Williams, EC (reprint author), VA Puget Sound Hlth Care Syst, NW Ctr Excellence HSR&D, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM emily.williams3@va.gov FU VA Office of Quality and Performance; VA Health Services Research and Development (HSRD); VA Substance Use Disorders Quality Enhancement Research Initiative (SUD-QuERI); National Institute of Alcohol Abuse and Alcoholism [R03 AA016793-01]; NIAAA [1R03AA016793-01A1]; VA Health Services Research and Development; VA Palo Alto Healthcare System Center for Healthcare Evaluation; Substance Use Disorders QUERI FX The authors gratefully acknowledge Rachel M. Thomas, MPH, for assistance with manuscript preparation. This study was supported by the VA Office of Quality and Performance, VA Health Services Research and Development (HSR&D), VA Substance Use Disorders Quality Enhancement Research Initiative (SUD-QuERI), and a grant from the National Institute of Alcohol Abuse and Alcoholism (R03 AA016793-01; Harris, PI). This study was funded by NIAAA 1R03AA016793-01A1 and conducted with support from the VA Health Services Research and Development, VA Palo Alto Healthcare System Center for Healthcare Evaluation, and the Substance Use Disorders QUERI and the VA Office of Quality and Performance. NR 61 TC 4 Z9 4 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2012 VL 36 IS 12 BP 2132 EP 2140 DI 10.1111/j.1530-0277.2012.01842.x PG 9 WC Substance Abuse SC Substance Abuse GA 051MN UT WOS:000312131400014 PM 22676340 ER PT J AU Greene, SJ Harinstein, ME Vaduganathan, M Subacius, H Konstam, MA Zannad, F Maggioni, AP Swedberg, K Butler, J Gheorghiade, M AF Greene, Stephen J. Harinstein, Matthew E. Vaduganathan, Muthiah Subacius, Haris Konstam, Marvin A. Zannad, Faiez Maggioni, Aldo P. Swedberg, Karl Butler, Javed Gheorghiade, Mihai CA EVEREST Trial Investigators TI Prognostic Value of Monocyte Count in Patients Hospitalized for Heart Failure With Reduced Ejection Fraction (from the EVEREST Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CELL-ADHESION MOLECULES; PERIPHERAL MONOCYTOSIS; DOUBLE-BLIND; INFLAMMATION; TOLVAPTAN; LYMPHOCYTES; ACTIVATION; THERAPY AB Monocytes play a critical role in the pathophysiology of heart failure (HF), but few studies have evaluated the prognostic implications of an increased monocyte count in patients with HF and reduced ejection fraction (EF). The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) examined the effects of tolvaptan in patients with worsening HF and EF <= 40%. This post hoc analysis evaluated the primary end points of all-cause mortality and cardiovascular mortality or HF hospitalization in 3,717 patients. At baseline, 265 (7.1%) had an increased monocyte count defined by >= 800/mu l. Patients with increased monocyte count tended to have an increased EF and were less likely to have a history of diabetes mellitus, hypercholesterolemia, or coronary revascularization but were more likely to have higher HF functional class and to be taking HF therapies such as diuretics, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, and digoxin (p <0.05 for all comparisons). At median follow-up of 9.9 months, increased monocyte count was predictive of all-cause mortality (hazard ratio 1.27, 95% confidence interval 1.003 to 1.60, p = 0.047) but was not associated with cardiovascular mortality or HF hospitalization (hazard ratio 1.06, 95% confidence interval 0.87 to 1.30, p = 0.55). Similar results were seen when monocyte count was analyzed as a continuous variable. However, after adjustment for baseline clinical risk factors, monocyte count was not predictive of either primary end point. In conclusion, increased monocyte count occurs in a minority of patients hospitalized with HF and is associated with poor postdischarge prognosis. However, it does not contribute prognostic value above other more traditional risk factors. (c) 2012 Published by Elsevier Inc. (Am J Cardiol 2012;110:1657-1662) C1 [Greene, Stephen J.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Harinstein, Matthew E.] Univ Pittsburgh, Med Ctr, Inst Heart & Vasc, Pittsburgh, PA USA. [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Subacius, Haris] Northwestern Univ, Feinberg Sch Med, Div Cardiol, Dept Med, Chicago, IL 60611 USA. [Konstam, Marvin A.] Tufts Med Ctr, Div Cardiol, Dept Med, Boston, MA USA. [Zannad, Faiez] Univ Lorraine, CHU Cardiol, Inserm CIC 9501, Nancy, France. [Zannad, Faiez] Univ Lorraine, CHU Cardiol, U961, Nancy, France. [Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy. [Swedberg, Karl] Univ Gothenburg, Dept Mol & Clin Med, Sahlgrenska Acad, Gothenburg, Sweden. [Butler, Javed] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu OI Subacius, Haris/0000-0003-4061-1220; Maggioni, Aldo Pietro/0000-0003-2764-6779 FU Otsuka, Inc., Rockville, Maryland; Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois FX Financial and material support for the EVEREST trial was provided by Otsuka, Inc., Rockville, Maryland. Database management was performed by the sponsor. Mr. Subacius conducted all final analyses for this report with funding from the Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois. NR 20 TC 3 Z9 3 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2012 VL 110 IS 11 BP 1657 EP 1662 DI 10.1016/j.amjcard.2012.07.035 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 047UW UT WOS:000311868000018 PM 22917555 ER PT J AU Neilan, TG Coelho-Filho, OR Pena-Herrera, D Shah, RV Jerosch-Herold, M Francis, SA Moslehi, J Kwong, RY AF Neilan, Tomas G. Coelho-Filho, Otavio R. Pena-Herrera, Diego Shah, Ravi V. Jerosch-Herold, Michael Francis, Sanjeev A. Moslehi, Javid Kwong, Raymond Y. TI Left Ventricular Mass in Patients With a Cardiomyopathy After Treatment With Anthracyclines SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR MAGNETIC-RESONANCE; ACUTE LYMPHOBLASTIC-LEUKEMIA; DIFFUSE MYOCARDIAL FIBROSIS; DOXORUBICIN THERAPY; HEART-FAILURE; DYSFUNCTION; CHILDHOOD; CANCER; ECHOCARDIOGRAPHY; QUANTIFICATION AB We aimed to describe the cardiac magnetic resonance (CMR) findings and determine the prognostic variables in patients with a cardiomyopathy after treatment with anthracyclines. CMR imaging was performed in 91 patients (58% men, mean age 43 +/- 18 years, and mean anthracycline dose of 276 +/- 82 mg/m(2)) with a reduced ejection fraction after anthracycline-based chemotherapy. Major adverse cardiovascular events were defined as cardiovascular death, appropriate implantable cardioverter-defibrillator therapy, and admission for decompensated heart failure. Patients presented a median of 88 months (interquartile range 37 to 138) after chemotherapy and were followed for 27 months (interquartile range 22 to 38). Late gadolinium enhancement was an uncommon finding (5 patients, 6%) despite a reduced ejection fraction (36 +/- 8%). An inverse association was found between the anthracycline dose and the indexed left ventricular (LV) mass by CMR (r = -0.67, p < 0.001). A total of 52 adverse cardiac events occurred (event rate of 22%/year). When the patients were grouped according to the presence or absence of a major adverse cardiovascular event, the indexed LV mass and glomerular filtration rate were lower and the anthracycline dose was greater among the patients who experienced an adverse event. In a multivariate model, the indexed LV mass demonstrated the strongest association with major adverse cardiovascular events (hazard ratio 0.89, chi-square 26, p < 0.001). In conclusion, myocardial scar by late gadolinium enhancement-CMR is infrequent in patients with anthracycline-cardiomyopathy despite a reduced ejection fraction, the event rate in patients with established anthracycline-cardiotoxicity is high, and indexed LV mass by CMR imaging is a predictor of adverse cardiovascular events. (c) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:1679-1686) C1 [Neilan, Tomas G.; Coelho-Filho, Otavio R.; Pena-Herrera, Diego; Shah, Ravi V.; Moslehi, Javid; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Jerosch-Herold, Michael] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Neilan, Tomas G.; Shah, Ravi V.; Francis, Sanjeev A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Moslehi, Javid] Harvard Univ, Sch Med, Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. RP Neilan, TG (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. EM tneilan@partners.org FU American Heart Association Dallas, Texas [12FTF12060588]; National Institutes of Health (T32 Training) [T32HL09430101A1]; Career Development grant [K08HL097031-02]; [R01HL090634-01A1]; [R01HL091157] FX This work was supported in part by the American Heart Association (Fellow to Faculty grant 12FTF12060588, to T. G. N.; Dallas, Texas), the National Institutes of Health (T32 Training Grant T32HL09430101A1, to T. G. N.; and Career Development grant K08HL097031-02, to J. M.; and project grants R01HL090634-01A1 [to M. J. H.] and R01HL091157 [to R. Y. K.]; Bethesda, Maryland). NR 28 TC 27 Z9 28 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2012 VL 110 IS 11 BP 1679 EP 1686 DI 10.1016/j.amjcard.2012.07.040 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 047UW UT WOS:000311868000021 PM 22917553 ER PT J AU Hughes, KR Gandara, RMC Javkar, T Sablitzky, F Hock, H Potten, CS Mahida, YR AF Hughes, Kevin R. Gandara, Ricardo M. C. Javkar, Tanvi Sablitzky, Fred Hock, Hanno Potten, Christopher S. Mahida, Yashwant R. TI Heterogeneity in histone 2B-green fluorescent protein-retaining putative small intestinal stem cells at cell position 4 and their absence in the colon SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE epithelial stem cells; apoptosis; regeneration; Paneth cells ID TEMPLATE DNA STRANDS; PANETH CELLS; EPITHELIAL-CELLS; MURINE SMALL; MOUSE; POPULATIONS; RENEWAL; CYCLE; CRYPTS; GENE AB Hughes KR, G ndara RM, Javkar T, Sablitzky F, Hock H, Potten CS, Mahida YR. Heterogeneity in histone 2B-green fluorescent protein-retaining putative small intestinal stem cells at cell position 4 and their absence in the colon. Am J Physiol Gastrointest Liver Physiol 303: G1188-G1201, 2012. First published September 20, 2012; doi: 10.1152/ajpgi.00080.2012.-Stem cells have been identified in two locations in small intestinal crypts; those intercalated between Paneth cells and another population (which retains DNA label) are located above the Paneth cell zone, at cell position 4. Because of disadvantages associated with the use of DNA label, doxycycline-induced transient transgenic expression of histone 2B (H2B)-green fluorescent protein (GFP) was investigated. H2B-GFP-retaining putative stem cells were consistently seen, with a peak at cell position 4, over chase periods of up to 112 days. After a 28-day chase, a subpopulation of the H2B-GFP-retaining cells was cycling, but the slow cycling status of the majority was illustrated by lack of expression of pHistone H3 and Ki67. Although some H2B-GFP-retaining cells were sensitive to low-dose radiation, the majority was resistant to low-and high-dose radiation-induced cell death, and a proportion of the surviving cells proliferated during subsequent epithelial regeneration. Long-term retention of H2B-GFP in a subpopulation of small intestinal Paneth cells was also seen, implying that they are long lived. In contrast to the small intestine, H2B-GFP-retaining epithelial cells were not seen in the colon from 28-day chase onward. This implies important differences in stem cell function between these two regions of the gastrointestinal tract, which may have implications for region-specific susceptibility to diseases (such as cancer and ulcerative colitis), in which epithelial stem cells and their progeny are involved. C1 [Hughes, Kevin R.; Gandara, Ricardo M. C.; Javkar, Tanvi; Potten, Christopher S.; Mahida, Yashwant R.] Univ Nottingham, Inst Infect Immun & Inflammat, Queens Med Ctr, Nottingham NG7 2UH, England. [Sablitzky, Fred] Univ Nottingham, Sch Biol, Nottingham NG7 2RD, England. [Hock, Hanno] Harvard Univ, Sch Med, Boston, MA USA. [Hock, Hanno] Massachusetts Gen Hosp, Ctr Canc, Harvard Stem Cell Inst, Boston, MA USA. [Hock, Hanno] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Potten, Christopher S.] Epistem, Manchester, Lancs, England. RP Mahida, YR (reprint author), Univ Nottingham, Inst Infect Immun & Inflammat, Queens Med Ctr, C Floor,West Block, Nottingham NG7 2UH, England. EM yash.mahida@nottingham.ac.uk RI Sablitzky, Fred/A-2276-2011 OI Sablitzky, Fred/0000-0001-9718-1546 FU Medical Research Council; FCT-Portuguese Foundation for Science and Technology [SFRH/BD/22873/2005] FX These studies were supported by the Medical Research Council and FCT-Portuguese Foundation for Science and Technology (Fellowship SFRH/BD/22873/2005, to R. Gandara). NR 39 TC 11 Z9 11 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD DEC PY 2012 VL 303 IS 11 BP G1188 EP G1201 DI 10.1152/ajpgi.00080.2012 PG 14 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 048YC UT WOS:000311948100002 PM 22997199 ER PT J AU Abrahamson, MJ Peters, A AF Abrahamson, Martin J. Peters, Anne TI Intensification of insulin therapy in patients with type 2 diabetes mellitus: An algorithm for basal-bolus therapy SO ANNALS OF MEDICINE LA English DT Review DE Basal-bolus; insulin; intensification; type 2 diabetes mellitus ID BLOOD-GLUCOSE CONTROL; RAPID-ACTING INSULIN; BETA-CELL FUNCTION; TO-TARGET TRIAL; CONSENSUS STATEMENT; GLYCEMIC CONTROL; EUROPEAN-ASSOCIATION; MEDICAL-MANAGEMENT; INITIATING INSULIN; MEALTIME TREATMENT AB The incidence of diabetes mellitus is projected to continue to increase worldwide over the next 20 years leading to increased costs in the management of the disease and its associated co-morbidities. Insulin replacement is one of many treatment options that can help to bring about near normoglycemia in the patient with type 2 diabetes mellitus (T2DM). Glycemic control as close to normoglycemia as possible can help to reduce the risk of microvascular and macrovascular complications, yet less than one-half of patients with T2DM achieve glycemic targets as recommended by practice guidelines. The purpose of this review is to provide guidance to primary care physicians for the initiation and intensification of basal-bolus insulin therapy in patients with T2DM. Two treatment algorithms that can be both patient- and physician-driven are proposed: a stepwise approach and a multiple daily injections approach. Evidence shaping the two approaches will be discussed alongside management issues that surround the patient treated with insulin: hypoglycemia, weight gain, patient education, and quality of life. C1 [Abrahamson, Martin J.] Harvard Univ, Joslin Diabet Ctr, Sch Med, Boston, MA 02215 USA. [Peters, Anne] Univ So Calif, Keck Sch Med, Div Endocrinol, Los Angeles, CA 90033 USA. RP Abrahamson, MJ (reprint author), Harvard Univ, Joslin Diabet Ctr, Sch Med, 1 Joslin Pl, Boston, MA 02215 USA. EM martin.abrahamson@joslin.harvard.edu OI Peters, Anne/0000-0003-0520-0776 FU Novo Nordisk, US FX Preparation of this manuscript was supported by Novo Nordisk, US. The authors did not receive any compensation for this work. NR 60 TC 8 Z9 8 U1 0 U2 3 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0785-3890 J9 ANN MED JI Ann. Med. PD DEC PY 2012 VL 44 IS 8 BP 836 EP 846 DI 10.3109/07853890.2012.699715 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 049UK UT WOS:000312008700009 PM 22822902 ER PT J AU Luthra, M Khan, H Suhail, MF Avadhani, V AF Luthra, Munish Khan, Hina Suhail, M. Faizul Avadhani, Vaidehi TI Primary pulmonary leiomyosarcoma - A case report SO ARCHIVOS DE BRONCONEUMOLOGIA LA Spanish DT Article DE Leiomyosarcoma; Spindle cell neoplasm; Mesenchymal tumor; Computed tomography ID LUNG AB Sarcomas are mesenchymal tumors that originate from the stromal elements of the bronchial wall or from interstices of lung parenchyma. Pulmonary sarcomatous neoplasms are a rare and diagnostically challenging group of tumors. They constitute only 0.2%-0.5% of all primary lung malignancies. Primary pulmonary leiomyosarcomas are subdivided into those originating from pulmonary parenchyma, bronchial tree or pulmonary arteries. Here we present a case of 43-year-old African-American female who with chronic cough, fatigue and weight loss. Early detection is the key to the successful management of these patients. The available treatment option is complete resection of tumor. These cases provide an interesting juxtaposition to the management of typical lung cancer. (C) 2012 SEPAR. Published by Elsevier Espana, S.L. All rights reserved. C1 [Luthra, Munish] Mt Sinai Sch Med, Dept Crit Care Med, New York, NY USA. [Khan, Hina] Mt Sinai Sch Med, James J Peters VA Med Ctr, Dept Internal Med, Bronx, NY USA. [Suhail, M. Faizul] Albert Einstein Coll Med, Dept Pulm Med, Bronx, NY 10467 USA. [Avadhani, Vaidehi] Columbia Univ, St Lukes Roosevelt Hosp Med Ctr, Dept Pathol, New York, NY 10027 USA. RP Luthra, M (reprint author), Mt Sinai Sch Med, Dept Crit Care Med, New York, NY USA. EM munish74@gmail.com NR 6 TC 0 Z9 0 U1 1 U2 2 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0300-2896 J9 ARCH BRONCONEUMOL JI Arch. Bronconeumol. PD DEC PY 2012 VL 48 IS 12 BP 476 EP 478 DI 10.1016/j.arbres.2012.01.006 PG 3 WC Respiratory System SC Respiratory System GA 050IG UT WOS:000312046400008 PM 22410283 ER PT J AU van der Vos, KE Coffer, PJ AF van der Vos, Kristan E. Coffer, Paul J. TI Glutamine metabolism links growth factor signaling to the regulation of autophagy SO AUTOPHAGY LA English DT Editorial Material DE PI3K; FOXO; glutamine metabolism; MTOR; autophagy AB Activation of the PI3K-AKT1-FOXO module by growth factors increases survival and stress resistance. We identified the gene encoding glutamine synthetase (GLUL, glutamate-ammonia ligase) as a novel transcriptional target of this signaling cascade. Growth factor removal increases glutamine synthetase expression and activity through activation of FOXO transcription factors. Surprisingly, increased levels of glutamine synthetase inhibit MTOR signaling by blocking its lysosomal translocation. Furthermore, FOXO activation induces autophagosome formation and autophagic flux in a glutamine synthetase-dependent manner. This may be important for maintaining cell survival during conditions of growth factor and nutrient deprivation since inhibition of autophagy induces cell death. These studies reveal that glutamine metabolism can play an important regulatory role in the regulation of autophagy by growth factor signaling. In addition, the induction of autophagy by FOXO-mediated glutamine synthetase expression might contribute to the tumor suppressive function of FOXOs. C1 [Coffer, Paul J.] Univ Med Ctr Utrecht, Dept Cell Biol, Utrecht, Netherlands. [van der Vos, Kristan E.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [van der Vos, Kristan E.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [van der Vos, Kristan E.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Coffer, Paul J.] Wilhelmina Childrens Hosp, Div Pediat, Utrecht, Netherlands. RP Coffer, PJ (reprint author), Univ Med Ctr Utrecht, Dept Cell Biol, Utrecht, Netherlands. EM P.J.Coffer@umcutrecht.nl NR 0 TC 10 Z9 10 U1 2 U2 15 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD DEC PY 2012 VL 8 IS 12 BP 1862 EP 1864 DI 10.4161/auto.22152 PG 3 WC Cell Biology SC Cell Biology GA 049AD UT WOS:000311953500028 PM 22996802 ER PT J AU Coopey, SB Mazzola, E Buckley, JM Sharko, J Belli, AK Kim, EMH Polubriaginof, F Parmigiani, G Garber, JE Smith, BL Gadd, MA Specht, MC Guidi, AJ Roche, CA Hughes, KS AF Coopey, Suzanne B. Mazzola, Emanuele Buckley, Julliette M. Sharko, John Belli, Ahmet K. Kim, Elizabeth M. H. Polubriaginof, Fernanda Parmigiani, Giovanni Garber, Judy E. Smith, Barbara L. Gadd, Michele A. Specht, Michelle C. Guidi, Anthony J. Roche, Constance A. Hughes, Kevin S. TI The role of chemoprevention in modifying the risk of breast cancer in women with atypical breast lesions SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Review DE Atypical hyperplasia; Lobular carcinoma in situ; Breast cancer; Chemoprevention ID CARCINOMA-IN-SITU; SURGICAL ADJUVANT BREAST; LOBULAR NEOPLASIA; POSTMENOPAUSAL WOMEN; BOWEL PROJECT; FOLLOW-UP; HYPERPLASIA; DISEASE; PREVENTION; RALOXIFENE AB Women with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and severe ADH are at increased risk of breast cancer, but a systematic quantification of this risk and the efficacy of chemoprevention in the clinical setting is still lacking. The objective of this study is to evaluate a woman's risk of breast cancer based on atypia type and to determine the effect of chemoprevention in decreasing this risk. Review of 76,333 breast pathology reports from three institutions within Partners Healthcare System, Boston, from 1987 to 2010 using natural language processing was carried out. This approach identified 2,938 women diagnosed with atypical breast lesions. The main outcome of this study is breast cancer occurrence. Of the 2,938 patients with atypical breast lesions, 1,658 were documented to have received no chemoprevention, and 184/1,658 (11.1 %) developed breast cancer at a mean follow-up of 68 months. Estimated 10-year cancer risks were 17.3 % with ADH, 20.7 % with ALH, 23.7 % with LCIS, and 26.0 % with severe ADH. In a subset of patients treated from 1999 on (the chemoprevention era), those who received no chemoprevention had an estimated 10-year breast cancer risk of 21.3 %, whereas those treated with chemoprevention had a 10-year risk of 7.5 % (p < 0.001). Chemoprevention use significantly reduced breast cancer risk for all atypia types (p < 0.05). The risk of breast cancer with atypical breast lesions is substantial. Physicians should counsel patients with ADH, ALH, LCIS, and severe ADH about the benefit of chemoprevention in decreasing their breast cancer risk. C1 [Coopey, Suzanne B.; Buckley, Julliette M.; Sharko, John; Belli, Ahmet K.; Polubriaginof, Fernanda; Smith, Barbara L.; Gadd, Michele A.; Specht, Michelle C.; Roche, Constance A.; Hughes, Kevin S.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Mazzola, Emanuele; Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Kim, Elizabeth M. H.] Wayne State Univ, Dept Surg & Oncol, Detroit, MI USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Garber, Judy E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Guidi, Anthony J.] Newton Wellesley Hosp, Dept Pathol, Newton, MA USA. RP Coopey, SB (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. EM scoopey@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 31 TC 30 Z9 31 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2012 VL 136 IS 3 BP 627 EP 633 DI 10.1007/s10549-012-2318-8 PG 7 WC Oncology SC Oncology GA 050RF UT WOS:000312071000001 PM 23117858 ER PT J AU Bradbury, AR Patrick-Miller, L Egleston, BL Schwartz, LA Sands, CB Shorter, R Moore, CW Tuchman, L Rauch, P Malhotra, S Rowan, B Van Decker, S Schmidheiser, H Bealin, L Sicilia, P Daly, MB AF Bradbury, Angela R. Patrick-Miller, Linda Egleston, Brian L. Schwartz, Lisa A. Sands, Colleen B. Shorter, Rebecca Moore, Cynthia W. Tuchman, Lisa Rauch, Paula Malhotra, Shreya Rowan, Brianne Van Decker, Stephanie Schmidheiser, Helen Bealin, Lisa Sicilia, Patrick Daly, Mary B. TI Knowledge and perceptions of familial and genetic risks for breast cancer risk in adolescent girls SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Adolescents; Breast cancer; Breast cancer prevention; Cancer risk assessment; Perceived risk of cancer ID HEALTH-CARE; QUALITATIVE RESEARCH; GENOMIC MEDICINE; EARLY ADULTHOOD; BRCA MUTATION; EARLY-LIFE; CHILDREN; ILLNESS; WOMEN; AGE AB Evidence suggests early events might modify adult breast cancer risk and many adolescents learn of familial and genetic risks for breast cancer. Little is known about how adolescent girls understand and respond to breast cancer risk. Semi-structured interviews with 11-19 year-old girls at high-risk and population-risk for breast cancer evaluated knowledge and perceptions of breast cancer risk and risk modification. Framework analysis and descriptive statistics were utilized to analyze open-ended responses. Risk group and age differences were evaluated by Fisher's exact and McNemar's tests. Fifty-four girls (86 % of invited), 35 high-risk (65 %), and 19 population-risk (35 %) completed interviews. The most frequently reported risk for breast cancer was family history/hereditary predisposition (66 %). Only 17 % of girls were aware of BRCA1/2 genes. The majority (76 %) of high-risk girls perceive themselves to be at increased risk for breast cancer, compared to 22 % of population-risk girls (p = 0.001). Half of girls reported that women can get breast cancer before 20-years-old. The majority believe there are things women (70 %) and girls (67 %) can do to prevent breast cancer. Mother was the most frequently reported source of information for breast cancer among both high-risk (97 %) and population-risk (89 %) girls. In this study, many high-risk girls perceive themselves to be at increased risk for breast cancer, and many girls believe that breast cancer can occur in teens. Yet, most girls believe there are things women and girls can do to prevent breast cancer. Research evaluating the impact of awareness and perceptions of breast cancer risk on psychosocial, health, and risk behaviors is needed to develop strategies to optimize responses to cancer risk. C1 [Bradbury, Angela R.; Sands, Colleen B.; Shorter, Rebecca; Sicilia, Patrick] Univ Penn, Div Hematol Oncol, Dept Med, Philadelphia, PA 19104 USA. [Bradbury, Angela R.] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Patrick-Miller, Linda] Univ Chicago, Dept Med, Div Hematol Oncol, Chicago, IL 60637 USA. [Patrick-Miller, Linda] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA. [Egleston, Brian L.] Fox Chase Canc Ctr, Biostat Facil, Philadelphia, PA 19111 USA. [Schwartz, Lisa A.] Childrens Hosp Philadelphia, Dept Pediat, Div Oncol, Philadelphia, PA 19104 USA. [Moore, Cynthia W.; Rauch, Paula] Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Boston, MA 02114 USA. [Tuchman, Lisa] Ctr Clin & Community Res, Div Adolescent & Young Adult Med, Childrens Natl Med Ctr, Childrens Res Inst, Washington, DC USA. [Malhotra, Shreya; Rowan, Brianne; Van Decker, Stephanie; Schmidheiser, Helen; Bealin, Lisa; Daly, Mary B.] Fox Chase Canc Ctr, Dept Clin Genet, Philadelphia, PA 19111 USA. RP Bradbury, AR (reprint author), Univ Penn, Div Hematol Oncol, Dept Med, 3 W Perelman Ctr 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM angela.bradbury@uphs.upenn.edu FU American Cancer Society, Mentored Research Scholar Award [MRSG 07-014-01-CPPB]; NIH [P30 CA006927]; Fox Chase Cancer Center Keystone Program in Personalized Risk and Prevention FX American Cancer Society, Mentored Research Scholar Award (MRSG 07-014-01-CPPB). Support was also provided by NIH grant P30 CA006927 and the Fox Chase Cancer Center Keystone Program in Personalized Risk and Prevention. NR 62 TC 6 Z9 6 U1 1 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2012 VL 136 IS 3 BP 749 EP 757 DI 10.1007/s10549-012-2254-7 PG 9 WC Oncology SC Oncology GA 050RF UT WOS:000312071000012 PM 23065030 ER PT J AU Wasan, KM Goss, PE Pritchard, PH Shepherd, L Tu, DS Ingle, JN AF Wasan, Kishor M. Goss, Paul E. Pritchard, P. Haydn Shepherd, Lois Tu, Dongsheng Ingle, James N. TI Lipid concentrations in postmenopausal women on letrozole after 5 years of tamoxifen: an NCIC CTG MA.17 sub-study SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Letrozole; Serum lipids; Primary breast cancer; Tamoxifen; Postmenopausal women; 5-year follow-up ID BREAST-CANCER; HORMONE-THERAPY; LIPOPROTEIN; TRIAL; REPLACEMENT; PREVENTION; ESTROGEN; DISEASE; PROTEIN; PROFILE AB To evaluate changes in serum lipid parameters (cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and lipoprotein(a) [Lp(a)]), in postmenopausal women receiving letrozole after tamoxifen therapy. MA.17L is a sub-study of MA.17, a double-blind, placebo-controlled trial of extended adjuvant letrozole. Eligible postmenopausal women were non-hyperlipidemic and not on lipid-lowering drugs. This analysis considers the 183 patients on the letrozole arm. Lipid parameters evaluated at baseline, 6 months, 12 months, and yearly thereafter until completion of 5 years of letrozole. The median duration of letrozole treatment was 5.0 years with a range from 0.03 to 6.05 years. After 5 year tamoxifen, patients on letrozole experienced significant increases from baseline in total cholesterol, LDL cholesterol, and Lp(a) at all study time points but no statistically significant changes in triglycerides. Specifically, a statistically significant increase was found at 60 months in total cholesterol [mean percentage change from baseline (PC) 5.27; p = 0.003], HDL cholesterol (mean PC 6.75; p = 0.003), LDL cholesterol (mean PC 10.02; p = 0.001), Lp(a) (mean PC 105.95; p < 0.0001). 103 (56 %) women in the study had clinically significantly elevated levels of Lp(a) (106 % above baseline) after 5 years of therapy. The results were similar after excluding the 21 % of patients who had ever received anti-lipid treatment. Significant increases in total cholesterol, HDL cholesterol, LDL cholesterol, and, most notably, Lp(a) in postmenopausal women were observed following 5 years of adjuvant letrozole treatment and after 5 years of tamoxifen therapy and such patients should have monitoring of their lipid levels in clinical practice. C1 [Wasan, Kishor M.] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC V6T 1Z3, Canada. [Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Pritchard, P. Haydn] St Pauls Hosp, Hlth Heart Program, Vancouver, BC V6Z 1Y6, Canada. [Shepherd, Lois; Tu, Dongsheng] Queens Univ, Clin Trials Grp, Natl Canc Inst Canada, Queens Canc Res Inst, Kingston, ON K7L 3N6, Canada. [Ingle, James N.] Mayo Clin, Rochester, MN USA. RP Wasan, KM (reprint author), Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC V6T 1Z3, Canada. EM Kishor.Wasan@ubc.ca FU National Cancer Institute of Canada; Novartis [MA.17L]; Avon Foundation, New York FX This study was supported with a grant cosponsored from the National Cancer Institute of Canada and Novartis (MA.17L; lipid sub-study). The authors would like to thank all the women who participated in this study, the investigators of the NCCTG and NCIC CTG and Catherine Elliot and Curtis McMahon who managed the data collected for this trial. PEG is supported by the Avon Foundation, New York. This is original research which has not been published elsewhere. NR 24 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2012 VL 136 IS 3 BP 769 EP 776 DI 10.1007/s10549-012-2294-z PG 8 WC Oncology SC Oncology GA 050RF UT WOS:000312071000014 PM 23089983 ER PT J AU Warner, ET Tamimi, RM Hughes, ME Ottesen, RA Wong, YN Edge, SB Theriault, RL Blayney, DW Niland, JC Winer, EP Weeks, JC Partridge, AH AF Warner, Erica T. Tamimi, Rulla M. Hughes, Melissa E. Ottesen, Rebecca A. Wong, Yu-Ning Edge, Stephen B. Theriault, Richard L. Blayney, Douglas W. Niland, Joyce C. Winer, Eric P. Weeks, Jane C. Partridge, Ann H. TI Time to diagnosis and breast cancer stage by race/ethnicity SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Minority health Diagnosis delay; Disparities ID LOW-INCOME WOMEN; RACIAL-DIFFERENCES; FOLLOW-UP; SOCIOECONOMIC-FACTORS; ABNORMAL MAMMOGRAPHY; PATIENT NAVIGATION; DELAY; POPULATION; SURVIVAL; RACE AB We examined differences in time to diagnosis by race/ethnicity, the relationship between time to diagnosis and stage, and the extent to which it explains differences in stage at diagnosis across racial/ethnic groups. Our analytic sample includes 21,427 non-Hispanic White (White), Hispanic, non-Hispanic Black (Black) and non-Hispanic Asian/Pacific Islander (Asian) women diagnosed with stage I to IV breast cancer between January 1, 2000 and December 31, 2007 at one of eight National Comprehensive Cancer Network centers. We measured time from initial abnormal mammogram or symptom to breast cancer diagnosis. Stage was classified using AJCC criteria. Initial sign of breast cancer modified the association between race/ethnicity and time to diagnosis. Among symptomatic women, median time to diagnosis ranged from 36 days among Whites to 53.6 for Blacks. Among women with abnormal mammograms, median time to diagnosis ranged from 21 days among Whites to 29 for Blacks. Blacks had the highest proportion (26 %) of Stage III or IV tumors. After accounting for time to diagnosis, the observed increased risk of stage III/IV breast cancer was reduced from 40 to 28 % among Hispanics and from 113 to 100 % among Blacks, but estimates remained statistically significant. We were unable to fully account for the higher proportion of late-stage tumors among Blacks. Blacks and Hispanics experienced longer time to diagnosis than Whites, and Blacks were more likely to be diagnosed with late-stage tumors. Longer time to diagnosis did not fully explain differences in stage between racial/ethnicity groups. C1 [Warner, Erica T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Warner, Erica T.; Tamimi, Rulla M.] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA. [Warner, Erica T.; Tamimi, Rulla M.; Hughes, Melissa E.; Winer, Eric P.; Weeks, Jane C.; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Ottesen, Rebecca A.; Niland, Joyce C.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Wong, Yu-Ning] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Edge, Stephen B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Theriault, Richard L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Blayney, Douglas W.] Stanford Univ, Ctr Canc, Palo Alto, CA 94305 USA. RP Warner, ET (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM ewarner@hsph.harvard.edu FU National Cancer Institute [5T32CA009001-36]; National Institute of General Medical Sciences [5R25GM055353-14]; National Comprehensive Cancer Network FX The authors would like to thank Graham A. Colditz, Bernard A. Rosner and Julie R. Palmer for their review of early drafts of the manuscript. We also thank the participants in the NCCN breast cancer outcomes database. Erica T. Warner was supported by National Cancer Institute grant number 5T32CA009001-36 and National Institute of General Medical Sciences grant number 5R25GM055353-14. This paper was also supported by the National Comprehensive Cancer Network. NR 40 TC 15 Z9 15 U1 1 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2012 VL 136 IS 3 BP 813 EP 821 DI 10.1007/s10549-012-2304-1 PG 9 WC Oncology SC Oncology GA 050RF UT WOS:000312071000019 PM 23099438 ER PT J AU Toi, M Benson, JR Winer, EP Forbes, JF von Minckwitz, G Golshan, M Robertson, JFR Sasano, H Cole, BF Chow, LWC Pegram, MD Han, W Huang, CS Ikeda, T Kanao, S Lee, ES Noguchi, S Ohno, S Partridge, AH Rouzier, R Tozaki, M Sugie, T Yamauchi, A Inamoto, T AF Toi, Masakazu Benson, John R. Winer, Eric P. Forbes, John F. von Minckwitz, Gunter Golshan, Mehra Robertson, John F. R. Sasano, Hironobu Cole, Bernard F. Chow, Louis W. C. Pegram, Mark D. Han, Wonshik Huang, Chiun-Sheng Ikeda, Tadashi Kanao, Shotaro Lee, Eun-Sook Noguchi, Shinzaburo Ohno, Shinji Partridge, Ann H. Rouzier, Roman Tozaki, Mitsuhiro Sugie, Tomoharu Yamauchi, Akira Inamoto, Takashi TI Preoperative systemic therapy in locoregional management of early breast cancer: highlights from the Kyoto Breast Cancer Consensus Conference SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Preoperative systemic therapy; Sentinel lymph node; Breast-conserving therapy ID PATHOLOGICAL COMPLETE RESPONSE; LYMPH-NODE BIOPSY; NEOADJUVANT CHEMOTHERAPY; EXPRESSION; TRIAL; TRASTUZUMAB; METASTASIS; DISSECTION; SURVIVAL; DISEASE AB Data reviewed at the Kyoto Breast Cancer Consensus Conference (KBCCC) showed that preoperative systemic therapy (PST) could optimize surgery through the utilization of information relating to pre- and post-PST tumor stage, therapeutic sensitivity, and treatment-induced changes in the biological characteristics of the tumor. As such, it was noted that the biological characteristics of the tumor, such as hormone receptors, human epidermal growth factor receptor-2, histological grade, cell proliferative activity, mainly defined by the Ki67 labeling index, and the tumor's multi-gene signature, should be considered in the planning of both systemic and local therapy. Furthermore, the timing of axillary sentinel lymph node diagnosis (i.e., before or after the PST) was also noted to be critical in that it may influence the likelihood of axillary preservation, even in node positive cases. In addition, axillary diagnosis with ultrasound and concomitant fine needle aspiration cytology or core needle biopsy (CNB) was reported to contribute to the construction of a treatment algorithm for patient-specific or individualized axillary surgery. Following PST, planning for breast surgery should therefore be based on tumor subtype, tumor volume and extent, therapeutic response to PST, and patient preference. Nomograms for predicting nodal status and drug sensitivity were also recognized as a tool to support decision-making in the selection of surgical treatment. Overall, review of data at the KBCCC showed that PST increases the likelihood of patients receiving localized surgery and individualized treatment regimens. C1 [Toi, Masakazu; Sugie, Tomoharu] Kyoto Univ, Grad Sch Med, Sakyo Ku, Kyoto 6068507, Japan. [Benson, John R.] Univ Cambridge, Addenbrookes Hosp, Cambridge Breast Unit, Cambridge CB2 2QQ, England. [Winer, Eric P.; Partridge, Ann H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Oncol Ctr,Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Forbes, John F.] Univ Newcastle, Newcastle, NSW 2300, Australia. [von Minckwitz, Gunter] German Breast Grp, Neu Isenburg, Germany. [Robertson, John F. R.] Univ Nottingham, Royal Derby Hosp, Nottingham NG7 2RD, England. [Sasano, Hironobu] Tohoku Univ, Sch Med, Sendai, Miyagi 980, Japan. [Cole, Bernard F.] Univ Vermont, Coll Engn & Math Sci, Burlington, VT USA. [Chow, Louis W. C.] Univ Hong Kong, UNIMED Med Inst, Hong Kong, Hong Kong, Peoples R China. [Pegram, Mark D.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Han, Wonshik] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Huang, Chiun-Sheng] Natl Taiwan Univ, Coll Med, Natl Taiwan Univ Hosp, Taipei 10764, Taiwan. [Ikeda, Tadashi] Teikyo Univ, Tokyo 173, Japan. [Lee, Eun-Sook] Natl Canc Ctr, Res Inst & Hosp, Ctr Breast Canc, Div Covergence Technol, Goyang Si, Gyeonggi Do, South Korea. [Noguchi, Shinzaburo] Osaka Univ, Grad Sch Med, Osaka, Japan. [Ohno, Shinji] Kyushu Natl Canc Ctr, Dept Breast Oncol, Fukuoka, Japan. [Rouzier, Roman] Univ Paris 06, Tenon Hosp, Paris, France. [Tozaki, Mitsuhiro] Kameda Med Ctr, Kamogawa, Japan. [Yamauchi, Akira] Kitano Hosp, Tazuke Kofukai Med Res Inst, Osaka, Japan. [Inamoto, Takashi] Tenri Hosp, Dept Breast Surg, Nara, Japan. RP Toi, M (reprint author), Kyoto Univ, Grad Sch Med, Sakyo Ku, 54 Shogoin Kawara Cho, Kyoto 6068507, Japan. EM info@kyoto-breast-cancer.org RI Han, Wonshik/B-3699-2008; OI Huang, Chiun-Sheng/0000-0002-6557-211X NR 43 TC 3 Z9 4 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2012 VL 136 IS 3 BP 919 EP 926 DI 10.1007/s10549-012-2333-9 PG 8 WC Oncology SC Oncology GA 050RF UT WOS:000312071000030 PM 23143284 ER PT J AU Ono, H Iwasaki, M Kuchiba, A Kasuga, Y Yokoyama, S Onuma, H Nishimura, H Kusama, R Ohnami, S Sakamoto, H Yoshida, T Tsugane, S AF Ono, Hiroe Iwasaki, Motoki Kuchiba, Aya Kasuga, Yoshio Yokoyama, Shiro Onuma, Hiroshi Nishimura, Hideki Kusama, Ritsu Ohnami, Sumiko Sakamoto, Hiromi Yoshida, Teruhiko Tsugane, Shoichiro TI Association of dietary and genetic factors related to one-carbon metabolism with global methylation level of leukocyte DNA SO CANCER SCIENCE LA English DT Article ID MODERATE FOLATE-DEPLETION; COMMON MUTATION; METHYLENETETRAHYDROFOLATE REDUCTASE; CANCER SUSCEPTIBILITY; BLADDER-CANCER; RISK-FACTOR; HYPOMETHYLATION; WOMEN; HOMOCYSTEINE; VITAMIN-B12 AB Global hypomethylation of leukocyte DNA has been associated with an increased risk of cancer. As dietary and genetic factors related to one-carbon metabolism may influence both the methylation and synthesis of DNA, we investigated associations between these factors and the global methylation level of peripheral blood leukocyte DNA based on a cross-sectional study of 384 Japanese women. Dietary intake of folate and vitamins B2, B6, and B12 was assessed with a validated semiquantitative food frequency questionnaire. Five polymorphisms in methylenetetrahydrofolate reductase (MTHFR) (rs1801133 and rs1801131), methionine synthase (MTR) (rs1805087), and methionine synthase reductase (MTRR) (rs10380 and rs162049) were genotyped. Global DNA methylation of leukocyte DNA was quantified using Luminometric Methylation Assay. A linear trend of association between methylation and dietary and genetic factors was evaluated by regression coefficients in a multivariable linear regression model. Mean global methylation level (standard deviation) was 70.2% (3.4) and range was from 59.0% to 81.2%. Global methylation level significantly decreased by 0.36% (95% confidence interval, 0.030.69) per quartile category for folate level. Subgroup analysis suggested that alcohol drinking modified the association between folate intake and global methylation level (Pinteraction= 0.01). However, no statistically significant association was observed for intake of vitamins B2, B6, and B12, alcohol consumption, or five single nucleotide polymorphisms of MTHFR, MTR, and MTRR. We found that higher folate intake was significantly associated with a lower level of global methylation of leukocyte DNA in a group of healthy Japanese females. (Cancer Sci 2012; 103: 2159-2164) C1 [Iwasaki, Motoki; Tsugane, Shoichiro] Natl Canc Ctr, Epidemiol & Prevent Div, Res Ctr Canc Prevent & Screening, Tokyo 104, Japan. [Ono, Hiroe; Ohnami, Sumiko; Sakamoto, Hiromi; Yoshida, Teruhiko] Natl Canc Ctr, Res Inst, Div Genet, Tokyo 104, Japan. [Ono, Hiroe] Tokyo Med & Dent Univ, Biomed Sci PhD Program, Tokyo, Japan. [Kuchiba, Aya] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kasuga, Yoshio] Nagano Matsushiro Gen Hosp, Dept Surg, Nagano, Japan. [Yokoyama, Shiro; Onuma, Hiroshi] Nagano Red Cross Hosp, Dept Breast & Thyroid Surg, Nagano, Japan. [Nishimura, Hideki] Nagano Municipal Hosp, Dept Surg, Nagano, Japan. [Kusama, Ritsu] Nagano Hokushin Gen Hosp, Dept Surg, Nagano, Japan. RP Iwasaki, M (reprint author), Natl Canc Ctr, Epidemiol & Prevent Div, Res Ctr Canc Prevent & Screening, Tokyo 104, Japan. EM moiwasak@ncc.go.jp RI Tsugane, Shocichiro/A-2424-2015 FU Ministry of Health, Labor and Welfare of Japan; Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation; Ministry of Education, Culture, Sports, Science, and Technology of Japan [17015049, 221S0001, 22700934]; Japan Society for the Promotion of Science; Foundation for Promotion of Cancer Research in Japan FX We thank Yoko Odaka and Misuzu Okuyama for their technical assistance. This study was supported by: a Grants-in-Aid for the Third Term Comprehensive Ten-Year Strategy for Cancer Control and for Research on Applying Health Technology from the Ministry of Health, Labor and Welfare of Japan; the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation; and Grants-in-Aid for Scientific Research on Priority Areas (17015049), for Scientific Research on Innovative Areas (221S0001), and for Young Scientists (B) (22700934) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Japan Society for the Promotion of Science, and the Foundation for Promotion of Cancer Research in Japan. NR 36 TC 13 Z9 13 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD DEC PY 2012 VL 103 IS 12 BP 2159 EP 2164 DI 10.1111/cas.12013 PG 6 WC Oncology SC Oncology GA 050DF UT WOS:000312032100017 PM 22957669 ER PT J AU Kottakis, F Bardeesy, N AF Kottakis, Filippos Bardeesy, Nabeel TI LKB1-AMPK axis revisited SO CELL RESEARCH LA English DT Editorial Material ID ACTIVATED PROTEIN-KINASE; ENERGY STRESS; CANCER-CELLS; LUNG-CANCER; LKB1; AMPK; SURVIVAL; INACTIVATION; DEPRIVATION; METASTASIS C1 [Kottakis, Filippos; Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Bardeesy, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. EM bardeesy.nabeel@mgh.harvard.edu NR 15 TC 8 Z9 9 U1 0 U2 10 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD DEC PY 2012 VL 22 IS 12 BP 1617 EP 1620 DI 10.1038/cr.2012.108 PG 4 WC Cell Biology SC Cell Biology GA 048ZN UT WOS:000311951900001 PM 22801477 ER PT J AU Inoue, A Matoba, S Zhang, Y AF Inoue, Azusa Matoba, Shogo Zhang, Yi TI Transcriptional activation of transposable elements in mouse zygotes is independent of Tet3-mediated 5-methylcytosine oxidation SO CELL RESEARCH LA English DT Article DE DNA demethylation; transposable element; preimplantation embryo; Tet3 ID SMALL INTERFERING RNAS; PREIMPLANTATION DEVELOPMENT; PATERNAL GENOME; GERM-CELLS; L1 RETROTRANSPOSITION; ACTIVE-DEMETHYLATION; DNA METHYLATION; MAMMALIAN DNA; TET PROTEINS; CPG-SITES AB The methylation state of the paternal genome is rapidly reprogrammed shortly after fertilization. Recent studies have revealed that loss of 5-methylcytosine (5mC) in zygotes correlates with appearance of 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). This process is mediated by Tet3 and the 5mC oxidation products generated in zygotes are gradually lost during preimplantation development through a replication-dependent dilution process. Despite these findings, the biological significance of Tet3-mediated oxidation of 5mC to 5hmC/5fC/5caC in zygotes is unknown. DNA methylation plays an important role in silencing gene expression including the repression of transposable elements (TEs). Given that the activation of TEs during preimplantation development correlates with loss of DNA methylation, it is believed that paternal DNA demethylation may have an important role in TE activation. Here we examined this hypothesis and found that Tet3-mediated 5mC oxidation does not have a significant contribution to TE activation. We show that the expression of LINE-1 (long interspersed nucleotide element 1) and ERVL (endogenous retroviruses class III) are activated from both paternal and maternal genomes in zygotes. Inhibition of 5mC oxidation by siRNA-mediated depletion of Tet3 affected neither TE activation, nor global transcription in zygotes. Thus, our study provides the first evidence demonstrating that activation of both TEs and global transcription in zygotes are independent of Tet3-mediated 5mC oxidation. C1 [Inoue, Azusa; Matoba, Shogo; Zhang, Yi] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Inoue, Azusa; Matoba, Shogo; Zhang, Yi] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Inoue, Azusa; Matoba, Shogo; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Inoue, Azusa; Matoba, Shogo; Zhang, Yi] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Zhang, Y (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, 200 Longwood Ave, Boston, MA 02115 USA. EM yzhang@genetics.med.harvard.edu FU HHMI; NIH [U01DK089565] FX We thank Dr Guoliang Xu for a Tet3 antibody. We are grateful to Dr Shinpei Yamaguchi for reading the manuscript. This work was supported by HHMI and NIH (U01DK089565). AI is a research fellow for Research Abroad of the Japan Society for the Promotion of Science. YZ is an investigator of the HHMI. NR 45 TC 20 Z9 20 U1 0 U2 14 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD DEC PY 2012 VL 22 IS 12 BP 1640 EP 1649 DI 10.1038/cr.2012.160 PG 10 WC Cell Biology SC Cell Biology GA 048ZN UT WOS:000311951900008 PM 23184059 ER PT J AU Courties, G Nahrendorf, M AF Courties, Gabriel Nahrendorf, Matthias TI Enlightened Stem Cells in the Heart More Efficient and Safer Reporter Gene Imaging SO CIRCULATION RESEARCH LA English DT Editorial Material DE bioluminescence; imaging; PET; stem cells ID MYOCARDIAL-INFARCTION; SURVIVAL C1 [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu FU NHLBI NIH HHS [R01HL096576, R01HL095629]; PHS HHS [HHSN268201000044C] NR 10 TC 1 Z9 2 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC PY 2012 VL 111 IS 12 BP 1486 EP 1487 DI 10.1161/CIRCRESAHA.112.280982 PG 2 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 049PD UT WOS:000311994700039 PM 23223928 ER PT J AU Berghausen, EM Janssen, W Vantler, M Alcazar, MA ten Freyhaus, H Pullamsetti, S Zhao, JJ Schermuly, RT Rosenkranz, S AF Berghausen, Eva M. Janssen, Wiebke Vantler, Marius Alcazar, Miguel A. ten Freyhaus, Henrik Pullamsetti, Soni Zhao, Jean J. Schermuly, Ralph T. Rosenkranz, Stephan TI Ablation of p110 alpha PI3-Kinase Activity in Vascular Smooth Muscle Cells Prevents Vascular Remodeling and Hypoxia-Induced Pulmonary Hypertension in Mice SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association CY NOV 03-07, 2012 CL Los Angeles, CA SP Amer Heart Assoc DE Pulmonary hypertension; Cell signaling; Hypoxia; Remodeling; Vascular C1 [Berghausen, Eva M.; Vantler, Marius; Alcazar, Miguel A.; ten Freyhaus, Henrik; Schermuly, Ralph T.; Rosenkranz, Stephan] Univ Cologne, D-50931 Cologne, Germany. [Janssen, Wiebke; Pullamsetti, Soni] Univ Giessen, D-35392 Giessen, Germany. [Zhao, Jean J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC PY 2012 VL 111 IS 12 BP E386 EP E386 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 049PD UT WOS:000311994700029 ER PT J AU Lee, JY Khedkar, SA Choudhury, S Samad, M Zhang, DS Thadhani, RI Karumanchi, SA Rigby, AC Kang, PM AF Lee, Ji Yoo Khedkar, Santosh A. Choudhury, Sangita Samad, Mohammed Zhang, Dongsheng Thadhani, Ravi I. Karumanchi, S. A. Rigby, Alan C. Kang, Peter M. TI Identification of Novel Non-steroidal Modulators of Vitamin D Receptor with Cardioprotective Property without Hypercalcemic Effect SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association CY NOV 03-07, 2012 CL Los Angeles, CA SP Amer Heart Assoc DE Heart failure; Hypertrophy; Vitamins; Calcium; Drugs C1 [Lee, Ji Yoo; Khedkar, Santosh A.; Choudhury, Sangita; Samad, Mohammed; Zhang, Dongsheng; Karumanchi, S. A.; Rigby, Alan C.; Kang, Peter M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Thadhani, Ravi I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC PY 2012 VL 111 IS 12 BP E381 EP E381 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 049PD UT WOS:000311994700009 ER PT J AU Wang, DY Lee, HP Gordon, BR AF Wang, De Yun Lee, Heow Peuh Gordon, Bruce R. TI Impacts of Fluid Dynamics Simulation in Study of Nasal Airflow Physiology and Pathophysiology in Realistic Human Three-Dimensional Nose Models SO CLINICAL AND EXPERIMENTAL OTORHINOLARYNGOLOGY LA English DT Review DE Computational fluid dynamics; Nose models; Nasal airflow dynamics; Airflow physiology and pathophysiology ID ENDOSCOPIC SINUS SURGERY; INFERIOR TURBINATE HYPERTROPHY; NUMERICAL-SIMULATION; SEPTAL PERFORATION; SURGICAL INTERVENTION; ACOUSTIC RHINOMETRY; ODORANT TRANSPORT; DRUG-DELIVERY; NITRIC-OXIDE; CAVITY AB During the past decades, numerous computational fluid dynamics (CFD) studies, constructed from CT or MRI images, have simulated human nasal models. As compared to rhinomanometry and acoustic rhinometry, which provide quantitative information only of nasal airflow, resistance, and cross sectional areas, CFD enables additional measurements of airflow passing through the nasal cavity that help visualize the physiologic impact of alterations in intranasal structures. Therefore, it becomes possible to quantitatively measure, and visually appreciate, the airflow pattern (laminar or turbulent), velocity, pressure, wall shear stress, particle deposition, and temperature changes at different flow rates, in different parts of the nasal cavity. The effects of both existing anatomical factors, as well as post-operative changes, can be assessed. With recent improvements in CFD technology and computing power, there is a promising future for CFD to become a useful tool in planning, predicting, and evaluating outcomes of nasal surgery. This review discusses the possibilities and potential impacts, as well as technical limitations, of using CFD simulation to better understand nasal airflow physiology. C1 [Wang, De Yun] Natl Univ Singapore, Dept Otolaryngol, Yong Loo Lin Sch Med, Singapore 119260, Singapore. [Lee, Heow Peuh] Natl Univ Singapore, Dept Engn, Fac Engn, Singapore 119260, Singapore. [Gordon, Bruce R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Gordon, Bruce R.] Cape Cod Hosp, Div Otolaryngol, Hyannis, MA USA. RP Wang, DY (reprint author), Natl Univ Singapore, Dept Otolaryngol, Yong Loo Lin Sch Med, 10 Lower Kent Ridge Rd, Singapore 119260, Singapore. EM entwdy@nus.edu.sg RI Lee, Heow Pueh/I-7834-2014 OI Lee, Heow Pueh/0000-0002-4380-3888 FU National University of Singapore [R190-000-028-123]; Ministry of Education, Singapore [T208A3103] FX This study was supported by Cross-Faculty Research Grant (R190-000-028-123) from the National University of Singapore and the Academic Research Grant (T208A3103) from the Ministry of Education, Singapore. NR 54 TC 13 Z9 13 U1 1 U2 21 PU KOREAN SOC OTORHINOLARYNGOL PI SEOUL PA DEPT OTORHINOLARYNGOL-HEAD & NECK SURG, SAMSUNG MED CTR, 50 ILWON-DONG, GANGNAM-GU, SEOUL, 135-710, SOUTH KOREA SN 1976-8710 EI 2005-0720 J9 CLIN EXP OTORHINOLAR JI Clin. Exp. Otorhinolaryngol. PD DEC PY 2012 VL 5 IS 4 BP 181 EP 187 DI 10.3342/ceo.2012.5.4.181 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 050IL UT WOS:000312046900001 ER PT J AU Coglianese, EE Larson, MG Vasan, RS Ho, JE Ghorbani, A McCabe, EL Cheng, S Fradley, MG Kretschman, D Gao, W O'Connor, G Wang, TJ Januzzi, JL AF Coglianese, Erin E. Larson, Martin G. Vasan, Ramachandran S. Ho, Jennifer E. Ghorbani, Anahita McCabe, Elizabeth L. Cheng, Susan Fradley, Michael G. Kretschman, Dana Gao, Wei O'Connor, George Wang, Thomas J. Januzzi, James L. TI Distribution and Clinical Correlates of the Interleukin Receptor Family Member Soluble ST2 in the Framingham Heart Study SO CLINICAL CHEMISTRY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; NATRIURETIC PEPTIDE; ACUTE EXACERBATION; FAILURE; MORTALITY; PROTEIN; DISEASE; PLASMA; RISK; INDIVIDUALS AB BACKGROUND: Soluble ST2 (sST2) is a cardiac biomarker whose concentration rises in response to myocardial strain. Increased sST2 concentrations may predict adverse outcomes in patients with heart failure and myocardial infarction. Because sST2 was largely undetectable with first-generation assays in ambulatory individuals, there are few data regarding its distribution and correlates in community-based populations. METHODS: We measured sST2 using a highly sensitive ELISA in 3450 Framingham Heart Study participants who attended a routine examination. We used multivariable linear regression models to identify covariates associated with sST2 in the general sample. We obtained a reference sample (n = 1136) by excluding individuals with prevalent coronary disease, heart failure, atrial fibrillation, diabetes, hypertension, obesity, valvular disease, left ventricular systolic dysfunction, and pulmonary and renal dysfunction. We used empiric and quantile regression techniques to estimate the 2.5th, 50th, 97.5th, and 99th quantiles. RESULTS: In the general sample (mean age 59 years, 55% women), systolic blood pressure (P = 0.006), antihypertensive medication use (P = 0.03), and diabetes (P < 0.001) were associated with sST2 concentrations. In the reference sample (mean age 55, 59% women), male sex (P < 0.0001) and older age (P = 0.004) were predictive of higher sST2 concentrations. Quantile and empirical methods were used to define the reference intervals. Using the empirical approach, upper 99% percentile values in different age groups ranged from 46.6 to 64.4 mu g/L in men and 36.7 to 53.0 mu g/L in women. CONCLUSIONS: In a well-characterized, community-based cohort, values for sST2 differ between men and women, increase with age, and are associated with diabetes and hypertension. (C) 2012 American Association for Clinical Chemistry C1 [Ho, Jennifer E.; Ghorbani, Anahita; Fradley, Michael G.; Wang, Thomas J.; Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Coglianese, Erin E.] Loyola Univ Hlth Syst, Div Cardiol, Maywood, IL USA. [Larson, Martin G.; Vasan, Ramachandran S.; Cheng, Susan; Wang, Thomas J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Larson, Martin G.; McCabe, Elizabeth L.; Gao, Wei] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Prevent Med & Epidemiol Sect, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Cardiol Sect, Boston, MA 02215 USA. [Cheng, Susan] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Kretschman, Dana; O'Connor, George] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org OI Larson, Martin/0000-0002-9631-1254; Ho, Jennifer/0000-0002-7987-4768; O'Connor, George/0000-0002-6476-3926; Ramachandran, Vasan/0000-0001-7357-5970 FU Ellison Foundation; Roman W. DeSanctis Clinical Scholar Fund; [N01-HC-25195]; [K99HL107642]; [R01-HL-086875] FX N01-HC-25195, a contract to the Framingham Heart Study. S. Cheng, grant K99HL107642 and the Ellison Foundation; T.J. Wang, R01-HL-086875; J.L. Januzzi, endowment from the Roman W. DeSanctis Clinical Scholar Fund. NR 36 TC 36 Z9 41 U1 0 U2 9 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD DEC PY 2012 VL 58 IS 12 BP 1673 EP 1681 DI 10.1373/clinchem.2012.192153 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 049KJ UT WOS:000311981600014 PM 23065477 ER PT J AU Treon, SP Tripsas, C Hanzis, C Ioakimidis, L Patterson, CJ Manning, RJ Sheehy, P Turnbull, B Hunter, ZR AF Treon, Steven P. Tripsas, Christina Hanzis, Christina Ioakimidis, Leukothea Patterson, Christopher J. Manning, Robert J. Sheehy, Patricia Turnbull, Barry Hunter, Zachary R. TI Familial Disease Predisposition Impacts Treatment Outcome in Patients With Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Article DE Bortezomib; Familial predisposition; Rituximab; Waldenstrom macroglobulinemia ID RITUXIMAB; MALIGNANCIES; SURVIVAL; LYMPHOMA; THERAPY AB Familial disease is common in Waldenstrom macroglobulinemia (WM). We examined the impact of familiall disease status on treatment outcome in WM and observed that familial disease was associated with inferior outcomes. However patients with familial WM receiving a bortezomib-containing regimen showed improved treatment outcomes vs. those receiving non bortezomib-containing regimens. Bortezomib-containing regimens may therefore represent a more optimal treatment approach for patients with familial WM. Background: We examined the impact of familial predisposition on treatment outcome in 135 patients with Waldenstrom macroglobulinemia (WM), 26.7% of whom had first- or second-degree relatives with a B-cell lymphoproliferative disorder. Patients and Methods: All patients were rituximab naive and received a rituximab-containing regimen. There were no significant differences in baseline characteristics between cohorts. Results: Overall response (93.9% vs. 75.0%; P = .029) and complete response/very good partial response (CRNGPR) (23.2% vs. 16.7%; P < .0001), time to progression (TTP) (45.5 vs. 21 months; P = .015) and time to next therapy (TINT) (50.0 vs. 33.0 months; P = .024) favored patients with sporadic WM. By multivariate analysis, familial predisposition was an independent marker for disease progression (hazard ratio, 0.554). Patients with familial but not sporadic disease exhibited better responses, including CRNGPR attainment (P = .0006) and a trend for longer progression-free survival (> 33 vs. 20.6 months; P = .08), with bortezomib-containing therapy. Conclusion: The findings convey that familial predisposition is an important determinant of treatment outcome in WM. Prospective studies to confirm these observations are needed. Clinical Lymphoma, Myeloma & Leukemia, Vol. 12, No. 6, 433-7 (C) 2012 Elsevier Inc. All rights reserved. C1 [Treon, Steven P.; Tripsas, Christina; Hanzis, Christina; Ioakimidis, Leukothea; Patterson, Christopher J.; Manning, Robert J.; Sheehy, Patricia; Hunter, Zachary R.] Harvard Univ, Bing Ctr Waldenstroms Macroglobulinemia, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Turnbull, Barry] Biobridges Inc, Boston, MA USA. RP Treon, SP (reprint author), Harvard Univ, Bing Ctr Waldenstroms Macroglobulinemia, Sch Med, Dana Farber Canc Inst, M547, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 FU Takeda/Millenium Pharmaceuticals; Celgene Inc.; Genentech BioOncology Inc.; Biogen IDEC Pharmaceuticals FX Dr. Treon has received research funding, consultation fees, and/or speaking honoraria from Takeda/Millenium Pharmaceuticals, Celgene Inc., Genentech BioOncology Inc., and Biogen IDEC Pharmaceuticals. NR 16 TC 8 Z9 8 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD DEC PY 2012 VL 12 IS 6 BP 433 EP 437 DI 10.1016/j.clml.2012.08.006 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 050JL UT WOS:000312049500009 PM 23084402 ER PT J AU Seaquist, ER Lattemann, DF Dixon, RA AF Seaquist, Elizabeth R. Lattemann, Dianne Figlewicz Dixon, Roger A. TI American Diabetes Association Research Symposium: Diabetes and the Brain SO DIABETES LA English DT Article C1 [Seaquist, Elizabeth R.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Lattemann, Dianne Figlewicz] Univ Washington, Seattle, WA 98195 USA. [Lattemann, Dianne Figlewicz] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Dixon, Roger A.] Univ Alberta, Dept Psychol, Edmonton, AB, Canada. RP Seaquist, ER (reprint author), Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA. EM seaqu001@umn.edu FU NIDDK NIH HHS [R01 DK040963] NR 0 TC 4 Z9 4 U1 0 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2012 VL 61 IS 12 BP 3056 EP 3062 DI 10.2337/db12-0489 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050GR UT WOS:000312041700003 PM 23172952 ER PT J AU Sobrin, L AF Sobrin, Lucia TI Longitudinal Validation of Hemoglobin A(1c) Criteria for Diabetes Diagnosis: Risk of Retinopathy SO DIABETES LA English DT Editorial Material ID GLYCATED HEMOGLOBIN; EXPERT COMMITTEE; GLUCOSE; POPULATION C1 [Sobrin, Lucia] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Sobrin, Lucia] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. [Sobrin, Lucia] Massachusetts Eye & Ear Infirm, Uveitis Serv, Boston, MA 02114 USA. RP Sobrin, L (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. EM lucia_sobrin@meei.harvard.edu OI Sobrin, Lucia/0000-0003-1575-0819 NR 15 TC 4 Z9 4 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2012 VL 61 IS 12 BP 3074 EP 3075 DI 10.2337/db12-1226 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050GR UT WOS:000312041700009 PM 23172958 ER PT J AU Wang, P Yigit, MV Ran, CZ Ross, A Wei, LL Dai, GP Medarova, Z Moore, A AF Wang, Ping Yigit, Mehmet V. Ran, Chongzhao Ross, Alana Wei, Lingling Dai, Guangping Medarova, Zdravka Moore, Anna TI A Theranostic Small Interfering RNA Nanoprobe Protects Pancreatic Islet Grafts From Adoptively Transferred Immune Rejection SO DIABETES LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; BETA-CELLS; ALLOGRAFT-REJECTION; TRANSPLANTATION; MICE; EXPRESSION; SURVIVAL; XENOGRAFTS; BETA-2-MICROGLOBULIN; XENOTRANSPLANTATION AB Islet transplantation has recently emerged as an acceptable clinical modality for restoring normoglycemia in patients with type 1 diabetes mellitus (T1DM). The long-term survival and function of islet grafts is compromised by immune rejection-related factors. Downregulation of factors that mediate immune rejection using RNA interference holds promise for improving islet graft resistance to damaging factors after transplantation. Here, we used a dual-purpose therapy/imaging small interfering (si)RNA magnetic nanoparticle (MN) probe that targets beta(2) microglobulin (B2M), a key component of the major histocompatibility class I complex (MHC I). In addition to serving as a siRNA carrier, this MN-siB2M probe enables monitoring of graft persistence noninvasively using magnetic resonance imaging (MRI). Human islets labeled with these MNs before transplantation into B2M (null) NOD/scid mice showed significantly improved preservation of graft volume starting at 2 weeks, as determined by longitudinal MRI in an adoptive transfer model (P < 0.05). Furthermore, animals transplanted with MN-siB2M-labeled islets demonstrated a significant delay of up to 23.8 +/- 4.8 days in diabetes onset after the adoptive transfer of T cells relative to 6.5 +/- 4.5 days in controls. This study demonstrated that our approach could protect pancreatic islet grafts from immune rejection and could potentially be applied to allotransplantation and prevention of the autoimmune recurrence of T1DM in islet transplantation or endogenous islets. Diabetes 61:3247-3254, 2012 C1 [Wang, Ping; Yigit, Mehmet V.; Ran, Chongzhao; Ross, Alana; Dai, Guangping; Medarova, Zdravka; Moore, Anna] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol,Mol Imaging Lab,Sch Med, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imag, Boston, MA 02114 USA. [Wei, Lingling] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol,Mol Imaging Lab,Sch Med, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imag, Boston, MA 02114 USA. EM amoore@helix.mgh.harvard.edu OI Wang, Ping/0000-0001-6712-8939 FU National Institutes of Health [5R01DK-080784, RO1DK-072137] FX This study was supported by National Institutes of Health Grants 5R01DK-080784 and RO1DK-072137 to A.M. NR 46 TC 15 Z9 15 U1 0 U2 15 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2012 VL 61 IS 12 BP 3247 EP 3254 DI 10.2337/db12-0441 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050GR UT WOS:000312041700031 PM 22923469 ER PT J AU Tsugawa, Y Takahashi, O Meigs, JB Davis, RB Imamura, F Fukui, T Taylor, WC Wee, CC AF Tsugawa, Yusuke Takahashi, Osamu Meigs, James B. Davis, Roger B. Imamura, Fumiaki Fukui, Tsuguya Taylor, William C. Wee, Christina C. TI New Diabetes Diagnostic Threshold of Hemoglobin A(1c) and the 3-Year Incidence of Retinopathy SO DIABETES LA English DT Article ID EURODIAB PROSPECTIVE COMPLICATIONS; RISK-FACTORS; MICROVASCULAR COMPLICATIONS; GLYCATED HEMOGLOBIN; REGRESSION-MODELS; EXPERT COMMITTEE; PROGRESSION; ASSOCIATION; GLUCOSE; POPULATION AB The new diagnostic threshold of hemoglobin A(1c) was made based on evidence from cross-sectional studies, and no longitudinal study supports its validity. To examine whether hemoglobin A(1c) of 6.5% or higher defines a threshold for elevated risk of incident retinopathy, we analyzed longitudinal data of 19,897 Japanese adults who underwent a health checkup in 2006 and were followed up 3 years later. We used logistic regression models and restricted cubic spline models to examine the relationship between baseline hemoglobin A(1c) levels and the prevalence and the 3-year incidence of retinopathy. The restricted cubic spline model indicated a possible threshold for the risk of incident retinopathy at hemoglobin A(1c) levels of 6.0-7.0%. Logistic regression analysis found that individuals with hemoglobin A(1c) levels of 6.5-6.9% were at significantly higher risk of developing retinopathy at 3 years compared with those with hemoglobin A(1c) levels of 5.0-5.4% (adjusted odds ratio, 2.35 [95% CI 1.08-5.11]). Those with hemoglobin A(1c) levels between 5.5 and 6.4% exhibited no evidence of elevated risks. We did not observe a threshold in the analysis of prevalent retinopathy. Our longitudinal results support the validity of the new hemoglobin A(1c) threshold of 6.5% or higher for diagnosing diabetes. Diabetes 61:3280-3284, 2012 C1 [Tsugawa, Yusuke; Davis, Roger B.; Taylor, William C.; Wee, Christina C.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Tsugawa, Yusuke; Davis, Roger B.; Taylor, William C.; Wee, Christina C.] Harvard Univ, Sch Med, Boston, MA USA. [Takahashi, Osamu; Fukui, Tsuguya] St Lukes Int Hosp, Div Gen Internal Med, Tokyo, Japan. [Meigs, James B.] Massachusetts Gen Hosp, Gen Internal Med Unit, Boston, MA 02114 USA. [Davis, Roger B.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Imamura, Fumiaki] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Tsugawa, Y (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. EM ytsugawa@bidmc.harvard.edu OI Imamura, Fumiaki/0000-0002-6841-8396 FU Beth Israel Deaconess Medical Center (Boston, MA); Joint Japan/World Bank Graduate Scholarship Program; St. Luke's Life Science Institute (Tokyo, Japan); National Institutes of Health [K24-DK-087932]; National Institute for Diabetes and Digestive and Kidney Diseases [K24-DK-080140]; Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH) [UL1-RR-025758]; Harvard University and its affiliated academic health care centers FX Y.T. is supported by Shigeaki Hinohara, MD, Primary Care Fellowship at Beth Israel Deaconess Medical Center (Boston, MA), Joint Japan/World Bank Graduate Scholarship Program, and St. Luke's Life Science Institute (Tokyo, Japan). C.C.W. is supported by a midcareer mentorship award from the National Institutes of Health (Grant K24-DK-087932). J.B.M. is supported by National Institute for Diabetes and Digestive and Kidney Diseases (Grant K24-DK-080140). R.B.D. is supported by Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH Award UL1-RR-025758 and financial contributions from Harvard University and its affiliated academic health care centers). NR 41 TC 18 Z9 18 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD DEC PY 2012 VL 61 IS 12 BP 3280 EP 3284 DI 10.2337/db12-0103 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050GR UT WOS:000312041700035 PM 22891221 ER PT J AU Jimenez, M Hu, FB Marino, M Li, Y Joshipura, KJ AF Jimenez, Monik Hu, Frank B. Marino, Miguel Li, Yi Joshipura, Kaumudi J. TI Type 2 diabetes mellitus and 20 year incidence of periodontitis and tooth loss SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Epidemiology; Oral disease; Type 2 diabetes mellitus; Periodontitis ID CORONARY-HEART-DISEASE; SMOKING HISTORY; PIMA-INDIANS; ORAL-HEALTH; CLASSIFICATION; DIAGNOSIS; VALIDITY; DIET; MEN AB Aims: The objective of this study was to evaluate the prospective associations between type 2 diabetes mellitus (T2DM) and the risk of periodontitis and tooth loss. Methods: 35,247 male participants of the Health Professionals Follow-Up Study who were dentate, free of periodontitis and cancer at baseline, were followed from 1986 to 2006. Data on self-reported diabetes, periodontitis, tooth loss and potential confounders were collected at baseline and biennially through mailed questionnaires. The multivariable adjusted relationships between diabetes and first report of periodontitis and tooth loss were estimated using time-varying Cox models. Results: There were 3009 incident self-reported periodontitis and 10,017 tooth loss events over 591,941 person-years. Men with T2DM showed a 29% (HR = 1.29; 95% CI: 1.13-1.47) increased risk of periodontitis compared to those without, when adjusted for age, race, smoking, BMI, fruit and vegetable intake, physical activity, alcohol consumption and dental profession. Men with T2DM with total fruit and vegetable intake < median were 49% as likely to report incident periodontitis compared to those without T2DM (HR = 1.49; 95% CI: 1.23-1.80; p-value for interaction = 0.03). The multivariable adjusted risk of tooth loss was 1.10 (95% CI: 1.02-1.18). Conclusions: Type 2 diabetes mellitus was associated with a significantly greater risk of self-reported periodontitis. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Hu, Frank B.; Joshipura, Kaumudi J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Jimenez, Monik] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. [Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Marino, Miguel; Li, Yi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Yi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Joshipura, Kaumudi J.] Univ Puerto Rico, Sch Dent, San Juan, PR 00935 USA. RP Joshipura, KJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM kaumudi.joshipura@upr.edu OI Joshipura, Kaumudi/0000-0003-1964-7579 FU [NIH-R25GM55353]; [T32DE07151]; [K24DE016884]; [R01HL088521-02S1] FX Grant support: NIH-R25GM55353, T32DE07151, K24DE016884, R01HL088521-02S1. NR 29 TC 15 Z9 18 U1 0 U2 20 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD DEC PY 2012 VL 98 IS 3 BP 494 EP 500 DI 10.1016/j.diabres.2012.09.039 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 051NI UT WOS:000312133700024 PM 23040240 ER PT J AU Campbell, JA Walker, RJ Smalls, BL Egede, LE AF Campbell, Jennifer A. Walker, Rebekah J. Smalls, Brittany L. Egede, Leonard E. TI Glucose control in diabetes: the impact of racial differences on monitoring and outcomes SO ENDOCRINE LA English DT Review DE Diabetes; Racial differences; Self-monitoring; Glucose control; Lipids; Blood pressure ID QUALITY-OF-CARE; ETHNIC-DIFFERENCES; CARDIOVASCULAR-DISEASE; GLYCEMIC CONTROL; US ADULTS; MANAGEMENT; HEALTH; RACE; ASSOCIATION; DISPARITIES AB Type 2 diabetes is the seventh leading cause of death in the US and is projected to increase in prevalence globally. Minorities are disproportionately affected by diabetes and data suggest that clinical outcomes consistently fall below American Diabetes Association recommendations. The purpose of this systematic review was to examine ethnic differences in self-monitoring and outcomes in adults with type 2 diabetes. Medline was searched for articles published between January 1990 and January 2012 by means of a reproducible strategy. Inclusion criteria included (1) published in English, (2) targeted African Americans, Hispanic, or Asian adults, ages 18+ years with type 2 diabetes, (3) cross-sectional, cohort, or intervention study, and (4) measured change in glycemic control, BP, lipids, or quality of life by race. Twenty-two papers met the inclusion criteria and were reviewed. Overall, significant racial differences and barriers were found in published studies in diabetes management as it pertains to self-monitoring and outcomes. African Americans tend to consistently exhibit worse outcomes and control when compared to other minority populations and non-Hispanic Whites. In conclusion, significant racial differences and barriers exist in diabetes management as it pertains to self-monitoring and outcomes when compared to non-Hispanic Whites. Explanatory and intervention studies are needed to determine the mechanisms and mediators of these differences and strategies to reduce these disparities. In addition, more research is needed to investigate the impact of racial differences in self-monitoring and outcomes on quality of life. C1 [Campbell, Jennifer A.; Walker, Rebekah J.; Smalls, Brittany L.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Walker, Rebekah J.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Charleston VA REAP, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Dept Med, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280G,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU NIDDK NIH HHS [K24 DK093699, R01 DK081121] NR 31 TC 31 Z9 31 U1 1 U2 17 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1355-008X J9 ENDOCRINE JI Endocrine PD DEC PY 2012 VL 42 IS 3 BP 471 EP 482 DI 10.1007/s12020-012-9744-6 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050SE UT WOS:000312073500006 PM 22815042 ER PT J AU Mijailovich, SM Kayser-Herold, O Li, XC Griffiths, H Geeves, MA AF Mijailovich, Srboljub M. Kayser-Herold, Oliver Li, Xiaochuan Griffiths, Hugh Geeves, Michael A. TI Cooperative regulation of myosin-S1 binding to actin filaments by a continuous flexible Tm-Tn chain SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article DE Tropomyosin chain; Myosin-S1 binding; Ca2+ sensitivity; Stopped flow ID MUSCLE THIN-FILAMENTS; TROPONIN-TROPOMYOSIN COMPLEX; RAY FIBER DIFFRACTION; SKELETAL-MUSCLE; STRETCH-ACTIVATION; IRREVERSIBLE-PROCESSES; RECIPROCAL RELATIONS; ELECTRON-MICROSCOPY; PERSISTENCE LENGTH; STRUCTURAL BASIS AB The regulation of striated muscle contraction involves cooperative interactions between actin filaments, myosin-S1 (S1), tropomyosin (Tm), troponin (Tn), and calcium. These interactions are modeled by treating overlapping tropomyosins as a continuous flexible chain (CFC), weakly confined by electrostatic interactions with actin. The CFC is displaced locally in opposite directions on the actin surface by the binding of either S1 or Troponin I (TnI) to actin. The apparent rate constants for myosin and TnI binding to and detachment from actin are then intrinsically coupled via the CFC model to the presence of neighboring bound S1s and TnIs. Monte Carlo simulations at prescribed values of the CFC stiffness, the CFC's degree of azimuthal confinement, and the angular displacements caused by the bound proteins were able to predict the stopped-flow transients of S1 binding to regulated F-actin. The transients collected over a large range of calcium concentrations could be well described by adjusting a single calcium-dependent parameter, the rate constant of TnI detachment from actin, k (-I). The resulting equilibrium constant varied sigmoidally with the free calcium, increasing from 0.12 at low calcium (pCa > 7) to 12 at high calcium (pCa < 5.5) with a Hill coefficient of similar to 2.15. The similarity of the curves for excess-actin and excess-myosin data confirms their allosteric relationship. The spatially explicit calculations confirmed variable sizes for the cooperative units and clustering of bound myosins at low calcium concentrations. Moreover, inclusion of negative cooperativity between myosin units predicted the observed slowing of myosin binding at excess-myosin concentrations. C1 [Mijailovich, Srboljub M.] Tufts Univ, Sch Med, Dept Med, CBR, Boston, MA 02135 USA. [Mijailovich, Srboljub M.; Kayser-Herold, Oliver; Li, Xiaochuan] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Mijailovich, Srboljub M.] Steward St Elizabeths Med Ctr, Boston, MA 02135 USA. [Griffiths, Hugh; Geeves, Michael A.] Univ Kent, Dept Biosci, Canterbury CT2 7NJ, Kent, England. RP Mijailovich, SM (reprint author), Tufts Univ, Sch Med, Dept Med, CBR, Room 406, Boston, MA 02135 USA. EM smijailo@gmail.com OI Mijailovich, Srboljub/0000-0003-1498-308X FU NIH [R01 AR048776]; Welcome Trust [085309] FX We gratefully acknowledge Drs. D. A. Smith, T. Irving, and R.J. Gilbert for useful discussions and critical review of an earlier version of this article. We also thank Dr. B. Stojanovic and Mr. D. Nedic for running additional simulations and the data analysis. This work was supported by grants NIH R01 AR048776 (S. M. M.) and Welcome Trust 085309 (M.A.G.). NR 59 TC 16 Z9 16 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD DEC PY 2012 VL 41 IS 12 BP 1015 EP 1032 DI 10.1007/s00249-012-0859-8 PG 18 WC Biophysics SC Biophysics GA 050OH UT WOS:000312062900002 PM 23052974 ER PT J AU Huang, LY St Denis, TG Xuan, Y Huang, YY Tanaka, M Zadlo, A Sarna, T Hamblin, MR AF Huang, Liyi St Denis, Tyler G. Xuan, Yi Huang, Ying-Ying Tanaka, Masamitsu Zadlo, Andrzej Sarna, Tadeusz Hamblin, Michael R. TI Paradoxical potentiation of methylene blue-mediated antimicrobial photodynamic inactivation by sodium azide: Role of ambient oxygen and azide radicals SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Sodium azide; Antimicrobial photodynamic therapy (APDT); Hydroxyl radical; Single oxygen; Azidyl radical ID GRAM-NEGATIVE BACTERIA; OF-THE-ART; HYDROGEN-PEROXIDE; OUTER-MEMBRANE; SINGLET OXYGEN; IN-VIVO; WOUND INFECTIONS; ESCHERICHIA-COLI; ANTIBIOTIC ERA; THERAPY AB Sodium azide (NaN3) is widely employed to quench singlet oxygen during photodynamic therapy (PDT), especially when PDT is used to kill bacteria in suspension. We observed that addition of NaN3 (100 mu M or 10 mM) to gram-positive Staphylococcus aureus and gram-negative Escherichia coli incubated with methylene blue (MB) and illuminated with red light gave significantly increased bacterial killing (1-3 logs), rather than the expected protection from killing. A different antibacterial photosensitizer, the conjugate between polyethylenimine and chlorin(e6) (PEI-ce6), showed reduced PDT killing (1-2 logs) after addition of 10 mM NaN3. Azide (0.5 mM) potentiated bacterial killing by Fenton reagent (hydrogen peroxide and ferrous sulfate) by up to 3 logs, but protected against killing mediated by sodium hypochlorite and hydrogen peroxide (considered to be a chemical source of singlet oxygen). The intermediacy of N center dot(3) was confirmed by spin-trapping and electron spin resonance studies in both MB-photosensitized reactions and Fenton reagent with addition of NaN3. We found that N center dot(3) was formed and bacteria were killed even in the absence of oxygen, suggesting the direct one-electron oxidation of azide anion by photoexcited MB. This observation suggests a possible mechanism to carry out oxygen-independent PDT. (C) 2012 Elsevier Inc. All rights reserved. C1 [Huang, Liyi; St Denis, Tyler G.; Xuan, Yi; Huang, Ying-Ying; Tanaka, Masamitsu; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Dept Infect Dis, Nanning 530021, Peoples R China. [Huang, Liyi; Huang, Ying-Ying; Tanaka, Masamitsu; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [St Denis, Tyler G.] Columbia Univ, New York, NY USA. [Xuan, Yi] Tufts Univ, Sch Engn, Medford, MA 02155 USA. [Huang, Ying-Ying; Tanaka, Masamitsu] Guangxi Med Univ, Dept Pathol, Nanning, Guangxi, Peoples R China. [Zadlo, Andrzej; Sarna, Tadeusz] Natl Def Med Coll, Dept Orthopaed Surg, Tokorozawa, Saitama 3598513, Japan. [Hamblin, Michael R.] Jagiellonian Univ, Dept Biophys, Fac Biochem Biophys & Biotechnol, Krakow, Poland. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01A1050875]; US Air Force MFEL Program [FA9550-04-1-0079]; Columbia University; National Natural Science Foundation of China [81260239]; National Science Centre [2011/03/B/NZ1/00007] FX This work was supported by NIH (R01A1050875 to M.R.H.) and US Air Force MFEL Program (FA9550-04-1-0079). Research conducted by Tyler St. Denis was supported by the Columbia University I. I. Rabi Fellowship. Liyi Huang was supported by National Natural Science Foundation of China (Grant No. 81260239). Research carried out by A.Z. and T.S. in Poland was supported in part by the National Science Centre (Grant 2011/03/B/NZ1/00007). NR 63 TC 27 Z9 27 U1 2 U2 33 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC 1 PY 2012 VL 53 IS 11 BP 2062 EP 2071 DI 10.1016/j.freeradbiomed.2012.09.006 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 050MV UT WOS:000312058300008 PM 23044264 ER PT J AU Wang, DL Smith, KB Esparza, S Leigh, FA Muzikansky, A Park, ER Plotkin, SR AF Wang, Daphne L. Smith, Kelly B. Esparza, Sonia Leigh, Fawn A. Muzikansky, Alona Park, Elyse R. Plotkin, Scott R. TI Emotional functioning of patients with neurofibromatosis tumor suppressor syndrome SO GENETICS IN MEDICINE LA English DT Article DE emotional function; neurofibromatosis 1; neurofibromatosis 2; schwannomatosis; tumor suppressor syndromes ID QUALITY-OF-LIFE; EPITHELIAL OVARIAN-CANCER; DEPRESSIVE SYMPTOMS; TYPE-1; POPULATION; COMORBIDITY; KNOWLEDGE; ANXIETY; STRESS; SAMPLE AB Purpose: Although patients with neurofibromatosis are predisposed to multiple nerve sheath tumors that can develop anywhere in the body and cause significant morbidity (e. g., hearing loss; pain), little research has examined emotional correlates of neurofibromatosis. The purpose of this study was to examine emotional functioning among adult patients with neurofibromatosis. Methods: A total of 248 patients with neurofibromatosis (neurofibromatosis 1, neurofibromatosis 2, or schwannomatosis) who received care at a specialized clinic completed validated measures to assess symptoms of depression and anxiety, level of perceived stress, and self-esteem. Results: Patients with neurofibromatosis reported significantly more symptoms of depression and anxiety, higher levels of perceived stress, and lower levels of self-esteem as compared with general population norms. No significant differences were found among patients with neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis, and emotional functioning was not significantly associated with disease severity. However, increased symptoms of depression and anxiety, higher levels of perceived stress, and lower levels of self-esteem were associated with a higher frequency of self-reported medical visits in the past year (P values <= 0.05). Conclusion: Neurofibromatosis appears to be associated with reduced emotional functioning. Although further research is needed, these findings suggest a role for a multidisciplinary treatment approach to address emotional distress among adult patients with neurofibromatosis. Genet Med 2012: 14(12): 977-982 C1 [Wang, Daphne L.; Esparza, Sonia; Leigh, Fawn A.; Plotkin, Scott R.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wang, Daphne L.; Esparza, Sonia; Leigh, Fawn A.; Plotkin, Scott R.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Smith, Kelly B.; Park, Elyse R.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Smith, Kelly B.] Univ British Columbia, Dept Obstet & Gynaecol, Vancouver, BC V5Z 1M9, Canada. [Muzikansky, Alona] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Biostat, Boston, MA USA. [Park, Elyse R.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. RP Plotkin, SR (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM splotkin@partners.org FU Michael Smith Foundation for Health Research FX Kelly B. Smith is currently supported by a Clinical Research Trainee Award from the Michael Smith Foundation for Health Research. The authors thank Vanessa Merker for her helpful comments regarding the manuscript. NR 39 TC 12 Z9 12 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD DEC PY 2012 VL 14 IS 12 BP 977 EP 982 DI 10.1038/gim.2012.85 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 049OD UT WOS:000311991800005 PM 22878510 ER PT J AU Epstein, AJ Johnson, SJ AF Epstein, Andrew J. Johnson, Scott J. TI Physician response to financial incentives when choosing drugs to treat breast cancer SO INTERNATIONAL JOURNAL OF HEALTH CARE FINANCE & ECONOMICS LA English DT Article DE Agency; Physician treatment decisions; Financial incentives; Medicare; Reimbursement ID SEER-MEDICARE DATA; HEALTH-CARE; PRESCRIPTION DECISION; PATIENTS PREFERENCES; CESAREAN DELIVERY; MODELS; ENDOGENEITY; PATTERNS; DOCTORS; CHOICES AB This paper considers physician agency in choosing drugs to treat metastatic breast cancer, a clinical setting in which patients have few protections from physicians' rent seeking. Physicians have explicit financial incentives attached to each potential drug treatment, with profit margins ranging more than a hundred fold. SEER-Medicare claims and Medispan pricing data were formed into a panel of 4,503 patients who were diagnosed with metastatic breast cancer and treated with anti-cancer drugs from 1992 to 2002. We analyzed the effects of product attributes, including profit margin, randomized controlled trial citations, FDA label, generic status, and other covariates on therapy choice. Instruments and drug fixed effects were used to control for omitted variables and possible measurement error associated with margin. We find that increasing physician margin by 10% yields between an 11 and 177% increase in the likelihood of drug choice on average across drugs. Physicians were more likely to use drugs with which they had experience, had more citations, and were FDA-approved to treat breast cancer. Oncologists are susceptible to financial incentives when choosing drugs, though other factors play a large role in their choice of drug. C1 [Johnson, Scott J.] Precis Hlth Econ, Boston, MA 02111 USA. [Epstein, Andrew J.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Epstein, Andrew J.] Univ Penn, Dept Med, Div Gen Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Epstein, Andrew J.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Johnson, SJ (reprint author), Precis Hlth Econ, 711 Atlantic Ave, Boston, MA 02111 USA. EM scott.johnson@precisionhealtheconomics.com NR 44 TC 4 Z9 4 U1 0 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1389-6563 J9 INT J HEALTH CARE FI JI Int. J. Health Care Financ. Econ. PD DEC PY 2012 VL 12 IS 4 BP 285 EP 302 DI 10.1007/s10754-012-9117-y PG 18 WC Business, Finance; Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 052GE UT WOS:000312184900003 PM 23124970 ER PT J AU Balagurumoorthy, P Xu, X Wang, KT Adelstein, SJ Kassis, AI AF Balagurumoorthy, Pichumani Xu, Xiang Wang, Ketai Adelstein, S. James Kassis, Amin I. TI Effect of distance between decaying I-125 and DNA on Auger-electron induced double-strand break yield SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article DE Auger electron; I-125 decays; double-strand break; scavenger ID MAMMALIAN-CELLS; PLASMID DNA; NEOPLASTIC MENINGITIS; POSITIONAL CHANGES; EMITTING I-125; CANCER CELLS; RADIOTOXICITY; BINDING; HOECHST-33258; EMITTERS AB Purpose: To determine the possible effects of I-125-to-DNA distance on the magnitude and mechanism of Auger-electron induced-double-strand break (DSB) production. Materials and methods: We have synthesized a series of I-125-labeled Hoechst (H) derivatives ((IE)-I-125-H, (IB)-I-125-H, I-125-C-8-H and I-125-C-12-H). While all four molecules share a common DNA minor groove binding bis-benzimidazole motif, they are designed to position I-125 at varying distances from the DNA helix. Each Hoechst derivative was incubated at 4 degrees C in phosphate buffered saline (PBS) together with supercoiled (SC) H-3-pUC19 plasmid DNA (ratio 3: 1) +/- the center dot OH scavenger dimethyl sulfoxide (DMSO) (0.2 M). Aliquots were analyzed on agarose gels over time and DSB yields per decay of I-125 atom were determined. Docking of the iodinated compounds on a DNA molecule was carried out to determine the distance between the iodine atom and the central axis of DNA. Results: In the absence of DMSO, the results show that the DSB yields decrease monotonically as the I-125 atom is distanced - by 10.5 angstrom to 13.9 angstrom - from the DNA helix ((IEH)-I-125: 0.52 +/- 0.01; (IB)-I-125-H: 0.24 +/- 0.03; I-125-C-8-H: 0.18 +/- 0.02; I-125-C-12-H: 0.10 +/- 0.00). In the presence of DMSO, DSB yields for (IEH)-I-125 (0.49 +/- 0.02) and (IB)-I-125-H (0.26 +/- 0.04) remain largely unchanged indicating that DSB are entirely produced by direct effects. Strikingly, I-125-C-8-H or I-125-C-12-H, did not produce detectable DSB in the presence of DMSO under similar conditions suggesting when I-125 atom is positioned >12 angstrom from the DNA, DSB are entirely produced by indirect effects. Conclusion: These results suggest that at a critical distance between the I-125 atom and the DNA helix, DSB production switches from an 'all' direct to an 'all' indirect mechanism, the latter situation being comparable to the decay of I-125 free in solution. These experimental findings were correlated with theoretical expectations based on microdosimetry. C1 [Balagurumoorthy, Pichumani; Wang, Ketai; Adelstein, S. James; Kassis, Amin I.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Xu, Xiang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Balagurumoorthy, P (reprint author), Harvard Univ, Sch Med, Dept Radiol, 200 Longwood Ave,Armenise Bldg,Room 138, Boston, MA 02115 USA. EM pbalagurumoorthy@hms.harvard.edu FU National Institutes of Health [5R01 CA015523]; National Research Service Award under National Institutes of Health [5T32 CA009078] FX This work was supported by National Institutes of Health 5R01 CA015523 to AIK. PB was a recipient of National Research Service Award under National Institutes of Health 5T32 CA009078. NR 64 TC 18 Z9 18 U1 1 U2 12 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD DEC PY 2012 VL 88 IS 12 BP 998 EP 1008 DI 10.3109/09553002.2012.706360 PG 11 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 047JS UT WOS:000311837000021 PM 22732063 ER PT J AU Mitchell, DM Regan, S Cooley, MR Lauter, KB Vrla, MC Becker, CB Burnett-Bowie, SAM Mannstadt, M AF Mitchell, Deborah M. Regan, Susan Cooley, Michael R. Lauter, Kelly B. Vrla, Michael C. Becker, Carolyn B. Burnett-Bowie, Sherri-Ann M. Mannstadt, Michael TI Long-Term Follow-Up of Patients with Hypoparathyroidism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BASAL GANGLIA CALCIFICATION; PARATHYROID-HORMONE 1-34; RANDOMIZED CROSSOVER TRIAL; GLOMERULAR-FILTRATION-RATE; IDIOPATHIC HYPOPARATHYROIDISM; CALCIUM; CALCITRIOL; THERAPY; PARATHYROID-HORMONE-1-34; HOMEOSTASIS AB Context: Despite tremendous interest in hypoparathyroidism, large cohort studies describing typical treatment patterns, laboratory parameters, and rates of complications are lacking. Objective: Our objective was to characterize the course of disease in a large cohort of hypoparathyroid patients. Design and Setting: We conducted a chart review of patients with permanent hypoparathyroidism identified via a clinical patient data registry. Patients were seen at a Boston tertiary-care hospital system between 1988 and 2009. Patients: We identified 120 patients. Diagnosis was confirmed by documented hypocalcemia with a simultaneous low or inappropriately normal PTH level for at least 1 yr. Mean age at the end of the observation period was 52 +/- 19 (range 2-87) yr, and the cohort was 73% female. Main Outcome Measure: We evaluated serum and urine laboratory results and renal and brain imaging. Results: We calculated time-weighted average serum calcium measurements for all patients. The time-weighted average for calcium was between 7.5 and 9.5 mg/dl for the majority (88%) of patients. Using linear interpolation, we estimated the proportion of time within the target calcium range for each patient with a median of 86% (interquartile range 67-98%). Of those with a 24-h urine collection for calcium (n = 53), 38% had at least one measurement over 300 mg/d. Of those with renal imaging (n = 54), 31% had renal calcifications, and 52% of those with head imaging (n = 31) had basal ganglia calcifications. Rates of chronic kidney disease stage 3 or higher were 2- to 17-fold greater than age-appropriate norms. Conclusions: Hypoparathyroidism and its treatment carry a large burden of disease. Renal abnormalities are particularly common. (J Clin Endocrinol Metab 97: 4507-4514, 2012) C1 [Mitchell, Deborah M.; Lauter, Kelly B.; Vrla, Michael C.; Burnett-Bowie, Sherri-Ann M.; Mannstadt, Michael] Harvard Univ, Massachusetts Gen Hosp, Endocrine Unit, Sch Med, Boston, MA 02114 USA. [Mitchell, Deborah M.] Harvard Univ, Massachusetts Gen Hosp, Pediat Endocrine Unit, Sch Med, Boston, MA 02114 USA. [Regan, Susan] Harvard Univ, Massachusetts Gen Hosp, Dept Biostat, Sch Med, Boston, MA 02114 USA. [Cooley, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Boston, MA 02114 USA. [Becker, Carolyn B.] Harvard Univ, Brigham & Womens Hosp, Endocrine Unit, Sch Med, Boston, MA 02114 USA. RP Mannstadt, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Endocrine Unit, Sch Med, Thier 10,55 Fruit St, Boston, MA 02114 USA. EM mmannstadt@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X; Mitchell, Deborah/0000-0003-0364-9107 FU National Institutes of Health [K08DK081669-01, T32DK007028-37] FX This research was supported by National Institutes of Health Grants K08DK081669-01 to M. M. and T32DK007028-37 to D.M.M. NR 32 TC 68 Z9 75 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2012 VL 97 IS 12 BP 4507 EP 4514 DI 10.1210/jc.2012-1808 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049SO UT WOS:000312003900051 PM 23043192 ER PT J AU Fong, SL Visser, JA Welt, CK de Rijke, YB Eijkemans, MJC Broekmans, FJ Roes, EM Peters, WHM Hokken-Koelega, ACS Fauser, BCJM Themmen, APN de Jong, FH Schipper, I Laven, JSE AF Fong, S. Lie Visser, J. A. Welt, C. K. de Rijke, Y. B. Eijkemans, M. J. C. Broekmans, F. J. Roes, E. M. Peters, W. H. M. Hokken-Koelega, A. C. S. Fauser, B. C. J. M. Themmen, A. P. N. de Jong, F. H. Schipper, I. Laven, J. S. E. TI Serum Anti-Mullerian Hormone Levels in Healthy Females: A Nomogram Ranging from Infancy to Adulthood SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; FOLLICLE-STIMULATING-HORMONE; ANTIMULLERIAN HORMONE; NORMAL WOMEN; REPRODUCTIVE AGE; PROVEN FERTILITY; INHIBIN-B; PREVALENCE; MENOPAUSE; CRITERIA AB Context: Anti-Mullerian hormone (AMH) is an accurate marker of ovarian reserve. However, sufficiently large sets of normative data from infancy to the end of reproductive life are scarce. Objective: This study was an assessment of serum AMH levels in healthy females. Subjects: In 804 healthy females ranging from infancy until the end of the reproductive period, serum AMH levels were measured with an enzyme-linked immunometric assay. All adults had regular menstrual cycles. The majority was proven fertile and none of them had used oral contraceptive pills prior to study inclusion. Results: In the total cohort, AMH was inversely correlated with age (r = -0.24; P < 0.001). The age at which the maximum AMH value was attained was at 15.8 yr. In girls younger than 15.8 yr, serum AMH and age were positively correlated (r = +0.18; P = 0.007). Thereafter AMH levels remained stable (r = -0.33; P = 0.66), whereas from the age of 25.0 yr onward, an inverse correlation between AMH and age (r = -0.47; P < 0.001) was observed. At any given age, considerable interindividual differences in serum AMH levels were observed. Conclusion: During infancy AMH levels increase, whereas during adolescence, a plateau until the age of 25 yr was observed. From the age of 25 yr onward, serum AMH levels correlate inversely with age, implying that AMH is applicable as a marker of ovarian reserve only in women of 25 yr old and older. Our nomogram may facilitate counseling women on their reproductive potential. (J Clin Endocrinol Metab 97: 4650-4655, 2012) C1 [Fong, S. Lie; Schipper, I.; Laven, J. S. E.] Univ Med Ctr, Dept Obstet & Gynecol, Erasmus Med Ctr, Div Reprod Med, NL-3000 CA Rotterdam, Netherlands. [Visser, J. A.; Themmen, A. P. N.; de Jong, F. H.] Univ Med Ctr, Dept Internal Med, Erasmus Med Ctr, NL-3000 CA Rotterdam, Netherlands. [de Rijke, Y. B.] Univ Med Ctr, Dept Clin Chem, Erasmus Med Ctr, NL-3000 CA Rotterdam, Netherlands. [Roes, E. M.] Univ Med Ctr, Div Gynecol Oncol, Erasmus Med Ctr, Dept Obstet & Gynecol, NL-3000 CA Rotterdam, Netherlands. [Welt, C. K.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Eijkemans, M. J. C.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands. [Broekmans, F. J.; Fauser, B. C. J. M.] Univ Med Ctr Utrecht, Div Reprod Med, Dept Reprod Med & Gynecol, NL-3508 GA Utrecht, Netherlands. [Peters, W. H. M.] Radboud Univ Nijmegen, Med Ctr, Dept Gastroenterol, NL-6500 HB Nijmegen, Netherlands. [Hokken-Koelega, A. C. S.] Sophia Childrens Univ Hosp, Erasmus MC, Div Endocrinol, Dept Pediat, NL-3000 CB Rotterdam, Netherlands. RP Fong, SL (reprint author), Univ Med Ctr, Dept Obstet & Gynecol, Erasmus Med Ctr, Div Reprod Med, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM s.liefong@erasmusmc.nl RI Visser, Jenny /F-8156-2011; Peters, W.H.M./L-4572-2015; OI Welt, Corrine/0000-0002-8219-5504 FU Pfizer; Novo Nordisk; Andromed; Ardana; Ferring; Merck Serono; Organon; Pantharei Bioscience; PregLem; Schering Plough; Schering; Serono; Wyeth; Genovum; Merck-Serono; MSD; Schering-Plough FX A.C.S.H.-K. receives financial support from Pfizer and Novo Nordisk to carry out investigator-initiated clinical trial; B.C.J.M.F. has received fees and grant support from the following companies: Andromed, Ardana, Ferring, Merck Serono, Organon, Pantharei Bioscience, PregLem, Schering Plough, Schering, Serono, and Wyeth; A.P.N.T. consults for ANSHlabs; and J.S.E.L. has received fees and grant support from the following companies: Ferring, Genovum, Merck-Serono, MSD, Organon, Schering-Plough, and Serono. NR 38 TC 37 Z9 37 U1 0 U2 11 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2012 VL 97 IS 12 BP 4650 EP 4655 DI 10.1210/jc.2012-1440 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049SO UT WOS:000312003900067 ER PT J AU Makimura, H Feldpausch, MN Rope, AM Hemphill, LC Torriani, M Lee, H Grinspoon, SK AF Makimura, Hideo Feldpausch, Meghan N. Rope, Alison M. Hemphill, Linda C. Torriani, Martin Lee, Hang Grinspoon, Steven K. TI Metabolic Effects of a Growth Hormone-Releasing Factor in Obese Subjects with Reduced Growth Hormone Secretion: A Randomized Controlled Trial SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PANCREATIC-ISLET TUMOR; CORONARY-HEART-DISEASE; ADULT GH DEFICIENCY; BODY-MASS INDEX; RISK-FACTORS; CAROTID ATHEROSCLEROSIS; INSULIN SENSITIVITY; ABDOMINAL OBESITY; ENDOGENOUS GH; VISCERAL FAT AB Context: Obesity is associated with reduced GH secretion and increased cardiovascular disease risk. Objective: We performed this study to determine the effects of augmenting endogenous GH secretion on body composition and cardiovascular disease risk indices in obese subjects with reduced GH secretion. Design, Patients and Methods: A randomized, double-blind, placebo-controlled study was performed involving 60 abdominally obese subjects with reduced GH secretion. Subjects received tesamorelin, a GHRH(1-44) analog, 2 mg once daily, or placebo for 12 months. Abdominal visceral adipose tissue (VAT) was assessed by abdominal computed tomography scan, and carotid intima-media thickness(cIMT) was assessed by ultrasound. Treatment effect was determined by longitudinal linear mixed-effects modeling. Results: VAT [-16 +/- 9 vs. 19 +/- 9 cm(2), tesamorelin vs. placebo; treatment effect (95% confidence interval): -35 (-58, -12) cm(2); P = 0.003], cIMT (-0.03 +/- 0.01 vs. 0.01 +/- 0.01 mm; -0.04 (-0.07, -0.01) mm; P = 0.02), log C-reactive protein (-0.17 +/- 0.04 vs. -0.03 +/- 0.05 mg/liter; -0.15 (-0.30, -0.01) mg/liter, P = 0.04), and triglycerides (-26 +/- 16 vs. 12 +/- 8 mg/dl; -37 (-67, -7) mg/dl; P = 0.02) improved significantly in the tesamorelin group vs. placebo. No significant effects on abdominal sc adipose tissue (-6 +/- 6 vs. 3 +/- 11 cm(2); -10 (-32, +13) cm(2); P = 0.40) were seen. IGF-I increased (86 +/- 21 vs. -6 +/- 8 mu g/liter; 92 (+52, +132) mu g/liter; P < 0.0001). No changes in fasting, 2-h glucose, or glycated hemoglobin were seen. There were no serious adverse events or differences in adverse events between the groups. Conclusion: Among obese subjects with relative reductions in GH, tesamorelin selectively reduces VAT without significant effects on sc adipose tissue and improves triglycerides, C-reactive protein, and cIMT, without aggravating glucose. (J Clin Endocrinol Metab 97: 4769-4779, 2012) C1 [Makimura, Hideo; Feldpausch, Meghan N.; Rope, Alison M.; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab & Neuroendocrine Unit, Boston, MA 02114 USA. [Grinspoon, Steven K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hemphill, Linda C.] Massachusetts Gen Hosp, Boston Heart Fdn, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab & Neuroendocrine Unit, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU National Institutes of Health [K23DK087857, R01HL085268, P30DK040561, K24DK064545, M01RR01066, UL1RR025758] FX This work was supported by National Institutes of Health Grant K23DK087857 to H. M.; Grants R01HL085268, P30DK040561, and K24DK064545 to S. K. G.; and Grants M01RR01066 and UL1RR025758 to the Harvard Clinical and Translational Science Center from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Partial research funding and study drug was provided by Theratechnologies, Inc. NR 40 TC 14 Z9 14 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2012 VL 97 IS 12 BP 4769 EP 4779 DI 10.1210/jc.2012-2794 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049SO UT WOS:000312003900081 PM 23015655 ER PT J AU Turan, S Ignatius, J Moilanen, JS Kuismin, O Stewart, H Mann, NP Linglart, A Bastepe, M Juppner, H AF Turan, Serap Ignatius, Jaakko Moilanen, Jukka S. Kuismin, Outi Stewart, Helen Mann, Nicholas P. Linglart, Agnes Bastepe, Murat Jueppner, Harald TI De Novo STX16 Deletions: An Infrequent Cause of Pseudohypoparathyroidism Type Ib that Should Be Excluded in Sporadic Cases SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ALBRIGHTS HEREDITARY OSTEODYSTROPHY; PARATHYROID-HORMONE RESISTANCE; IMPRINTING CONTROL ELEMENT; GNAS LOCUS; AUTOSOMAL-DOMINANT; MOLECULAR DIAGNOSIS; EPIGENETIC DEFECTS; URIC-ACID; METHYLATION; REGION AB Context: Maternally inherited 3-kb STX16 deletions cause autosomal dominant pseudohypoparathyroidism type Ib (PHP-Ib) characterized by PTH resistance with loss of methylation restricted to the GNAS exon A/B. Objective: The objective of the study was to search for the 3-kb STX16 deletion and to establish haplotypes for the GNAS region for two PHP-Ib patients and their families. Setting: The study was conducted at a research laboratory and tertiary care hospitals. Patients: The index cases presented at the ages 8 and 9.5 yr, respectively, with hypocalcemia, hyperphosphatemia, and elevated PTH. Interventions: There were no interventions. Results: DNA analyses of the index cases revealed an isolated loss of the GNAS exon A/B methylation and the 3-kb STX16 deletion. In the first family, the patient's healthy mother and sister showed no genetic or epigenetic abnormality, yet microsatellite analysis of the GNAS region indicated that both siblings share the same maternal allele, with the exception of an allelic loss for marker 261P9-CA1 (located within STX16), leading to the conclusion that a de novo mutation had occurred on the maternal allele. In the second family, three siblings of the index case are also affected, and an analysis of their DNA revealed the 3-kb STX16 deletion, which was also found in the healthy mother and a maternal uncle. Analysis of the siblings of the deceased maternal grandfather and some of their descendants excluded the 3-kb STX16 deletion, but haplotype analysis of the GNAS region suggested that he had acquired the mutation de novo. Conclusions: De novo 3-kb STX16 deletions, reported only once previously, are infrequent but should be excluded in all cases of PHP-Ib, even when the family history is negative for an inherited form of this disorder. (J Clin Endocrinol Metab 97: E2314-E2319, 2012) C1 [Turan, Serap; Bastepe, Murat; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ignatius, Jaakko] Univ Turku, Turku Univ Hosp, Dept Clin Genet, FI-20014 Turku, Finland. [Moilanen, Jukka S.; Kuismin, Outi] Univ Oulu, Oulu Univ Hosp, Dept Clin Genet, FI-90014 Oulu, Finland. [Stewart, Helen] Oxford Univ Hosp Natl Hlth Serv Trust, Dept Clin Genet, Oxford OX3 7LE, England. [Mann, Nicholas P.] Royal Berkshire Hosp, Dept Paediat, Reading RG1 5AN, Berks, England. [Linglart, Agnes] Hop Bicetre Paris Sud, Assistance Publ Hop Paris, Dept Pediat Endocrinol, F-94270 Le Kremlin Bicetre, France. Hop Bicetre Paris Sud, Ctr Reference Malad Rares Calcium & Phosphore, F-94270 Le Kremlin Bicetre, France. [Linglart, Agnes] INSERM, U986, F-94275 Le Kremlin Bicetre, France. Univ Paris 11, F-75006 Le Kremlin Bicetre, France. [Turan, Serap] Marmara Univ, Dept Pediat Endocrinol, TR-34722 Istanbul, Turkey. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM hjueppner@partners.org RI Moilanen, Jukka/G-2604-2012 OI Moilanen, Jukka/0000-0002-8041-3205 FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK073911, R37 DK46718]; Fulbright Scholarship Program FX This work was supported by Research Grants R01 DK073911 (to M. B.) and R37 DK46718 (to H.J.) from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. S. T. was a recipient of a grant from the Fulbright Scholarship Program. NR 39 TC 12 Z9 12 U1 0 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2012 VL 97 IS 12 BP E2314 EP E2319 DI 10.1210/jc.2012-2920 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049SO UT WOS:000312003900016 PM 23087324 ER PT J AU Miriovsky, BJ Shulman, LN Abernethy, AP AF Miriovsky, Benjamin J. Shulman, Lawrence N. Abernethy, Amy P. TI Importance of Health Information Technology, Electronic Health Records, and Continuously Aggregating Data to Comparative Effectiveness Research and Learning Health Care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CANCER-CARE; PERSONALIZED-MEDICINE; MEANINGFUL USE; LUNG-CANCER; SYSTEM; MORTALITY; DISEASE AB Rapidly accumulating clinical information can support cancer care and discovery. Future success depends on information management, access, use, and reuse. Electronic health records (EHRs) are highlighted as a critical component of evidence development and implementation, but to fully harness the potential of EHRs, they need to be more than electronic renderings of the traditional paper medical chart. Clinical informatics and structured accessible secure data captured through EHR systems provide mechanisms through which EHRs can facilitate comparative effectiveness research (CER). Use of large linked administrative databases to answer comparative questions is an early version of informatics-enabled CER familiar to oncologists. An updated version of informatics-enabled CER relies on EHR-derived structured data linked with supplemental information to provide patient-level information that can be aggregated and analyzed to support hypothesis generation, comparative assessment, and personalized care. As implementation of EHRs continues to expand, electronic databases containing information collected via EHRs will continuously aggregate; aggregating data enhanced with real-time analytics can provide point-of-care evidence to oncologists, tailored to patient-level characteristics. The system learns when clinical care informs research, and insights derived from research are reinvested in care. Challenges must be overcome, including interoperability, standardization, access, and development of real-time analytics. J Clin Oncol 30:4243-4248. (C) 2012 by American Society of Clinical Oncology C1 [Abernethy, Amy P.] Duke Univ, Med Ctr, Div Med Oncol, Dept Med, Durham, NC 27710 USA. [Shulman, Lawrence N.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Abernethy, AP (reprint author), Duke Univ, Med Ctr, Div Med Oncol, Dept Med, Box 3436, Durham, NC 27710 USA. EM amy.abernethy@duke.edu FU Pfizer; Helsinn Therapeutics; Amgen; KangLai Te USA; Alexion; Bio Vex; Mi-Co; Eli Lilly; Endo Pharmaceuticals; Bristol-Myers Squibb; Genentech FX Research Funding: Amy P. Abernethy, Pfizer, Helsinn Therapeutics, Amgen, KangLai Te USA, Alexion, Bio Vex, Mi-Co, Eli Lilly, Endo Pharmaceuticals, Bristol-Myers Squibb, Genentech NR 32 TC 43 Z9 43 U1 3 U2 29 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2012 VL 30 IS 34 BP 4243 EP 4248 DI 10.1200/JCO.2012.42.8011 PG 6 WC Oncology SC Oncology GA 048DA UT WOS:000311889200011 PM 23071233 ER PT J AU Basch, E Abernethy, AP Mullins, CD Reeve, BB Smith, ML Coons, SJ Sloan, J Wenzel, K Chauhan, C Eppard, W Frank, ES Lipscomb, J Raymond, SA Spencer, M Tunis, S AF Basch, Ethan Abernethy, Amy P. Mullins, C. Daniel Reeve, Bryce B. Smith, Mary Lou Coons, Stephen Joel Sloan, Jeff Wenzel, Keith Chauhan, Cynthia Eppard, Wayland Frank, Elizabeth S. Lipscomb, Joseph Raymond, Stephen A. Spencer, Merianne Tunis, Sean TI Recommendations for Incorporating Patient-Reported Outcomes Into Clinical Comparative Effectiveness Research in Adult Oncology SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; CANCER CARE MONITOR; HEALTH; CHEMOTHERAPY; SYMPTOMS; COMMUNICATION; EQUIVALENCE; ASSESSMENTS; POINTS AB Examining the patient's subjective experience in prospective clinical comparative effectiveness research (CER) of oncology treatments or process interventions is essential for informing decision making. Patient-reported outcome (PRO) measures are the standard tools for directly eliciting the patient experience. There are currently no widely accepted standards for developing or implementing PRO measures in CER. Recommendations for the design and implementation of PRO measures in CER were developed via a standardized process including multistakeholder interviews, a technical working group, and public comments. Key recommendations are to include assessment of patient-reported symptoms as well as health-related quality of life in all prospective clinical CER studies in adult oncology; to identify symptoms relevant to a particular study population and context based on literature review and/or qualitative and quantitative methods; to assure that PRO measures used are valid, reliable, and sensitive in a comparable population (measures particularly recommended include EORTC QLQ-C30, FACT, MDASI, PRO-CTCAE, and PROMIS); to collect PRO data electronically whenever possible; to employ methods that minimize missing patient reports and include a plan for analyzing and reporting missing PRO data; to report the proportion of responders and cumulative distribution of responses in addition to mean changes in scores; and to publish results of PRO analyses simultaneously with other clinical outcomes. Twelve core symptoms are recommended for consideration in studies in advanced or metastatic cancers. Adherence to methodologic standards for the selection, implementation, and analysis/reporting of PRO measures will lead to an understanding of the patient experience that informs better decisions by patients, providers, regulators, and payers. J Clin Oncol 30:4249-4255. (C) 2012 by American Society of Clinical Oncology C1 [Basch, Ethan] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, Hlth Outcomes Res Grp,Dept Biostat, New York, NY 10065 USA. [Abernethy, Amy P.] Duke Univ, Durham, NC 27706 USA. [Reeve, Bryce B.] Univ N Carolina, Chapel Hill, NC USA. [Mullins, C. Daniel] Univ Maryland, College Pk, MD 20742 USA. [Spencer, Merianne; Tunis, Sean] Ctr Med Technol Policy, Baltimore, MD USA. [Smith, Mary Lou] Res Advocacy Network, Plano, TX USA. [Coons, Stephen Joel] Crit Path Inst, Tucson, AZ USA. [Sloan, Jeff] Mayo Clin, Rochester, MN 55905 USA. [Eppard, Wayland] Patient Advocacy Comm, N Cent Canc Treatment Grp, Rochester, MN USA. [Frank, Elizabeth S.] Dana Farber Canc Inst, Boston, MA USA. [Raymond, Stephen A.] PHT Corp, Boston, MA USA. [Lipscomb, Joseph] Emory Univ, Atlanta, GA 30322 USA. RP Basch, E (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, Hlth Outcomes Res Grp,Dept Biostat, 307 E 63rd St, New York, NY 10065 USA. EM ebasch@mskcc.org FU Pfizer; Helsinn Therapeutics; Amgen; KangLaiTe USA; Alexion; BioVex; DARA BioSciences; Mi-Co; Eli Lilly; Endo Pharmaceuticals; Bristol-Myers Squibb; Genentech; Bayer Pharmaceuticals FX Research Funding: Amy P. Abernethy, Pfizer, Helsinn Therapeutics, Amgen, KangLaiTe USA, Alexion, BioVex, DARA BioSciences, Mi-Co, Eli Lilly, Endo Pharmaceuticals, Bristol-Myers Squibb, Genentech; C. Daniel Mullins, Bayer Pharmaceuticals, Pfizer NR 30 TC 137 Z9 140 U1 3 U2 24 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2012 VL 30 IS 34 BP 4249 EP 4255 DI 10.1200/JCO.2012.42.5967 PG 7 WC Oncology SC Oncology GA 048DA UT WOS:000311889200012 PM 23071244 ER PT J AU Pearson, SD AF Pearson, Steven D. TI Cost, Coverage, and Comparative Effectiveness Research: The Critical Issues for Oncology SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID EFFECTIVENESS INFORMATION; REIMBURSEMENT SCHEMES; CANCER DRUGS; CARE; COUNTRIES; OUTCOMES AB A new national initiative in comparative effectiveness research (CER) is part of a broad and long-term evolution toward greater reliance on scientific evidence in clinical practice and medical policy. But CER has been controversial because of its high profile in the health care reform effort, its instantiation in a prominent new national research institute, and lingering concerns that the ultimate goal of CER is to empower the government and private insurers to reduce health care costs by restricting access to expensive new medical tests and treatments. This article presents an analysis of the policy development behind CER and focuses on its potential impact on insurance coverage and payment for oncology services. By itself, CER will not solve the tension that exists between the goal of innovative, personalized care and the eroding affordability of cancer treatment in the United States. But CER does offer an important opportunity for progress. Oncologists have taken important first steps in acknowledging their responsibility for addressing cost issues; as a professional society, they should now move forward to assume leadership in the effort to integrate clinical evidence with considerations of cost effectiveness to guide clinical practice and insurer policies. J Clin Oncol 30:4275-4281. (C) 2012 by American Society of Clinical Oncology C1 [Pearson, Steven D.] NIH, Bethesda, MD 20892 USA. [Pearson, Steven D.] Massachusetts Gen Hosp, Inst Clin & Econ Review, Inst Technol Assessment, Boston, MA 02114 USA. RP Pearson, SD (reprint author), NIH, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM pearsonsd@cc.nih.gov FU Merck; Johnson Johnson FX Research Funding: Steven D. Pearson, Merck, Johnson & Johnson NR 34 TC 15 Z9 15 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2012 VL 30 IS 34 BP 4275 EP 4281 DI 10.1200/JCO.2012.42.6601 PG 7 WC Oncology SC Oncology GA 048DA UT WOS:000311889200016 PM 23071229 ER PT J AU Florez, H Pan, Q Ackermann, RT Marrero, DG Barrett-Connor, E Delahanty, L Kriska, A Saudek, CD Goldberg, RB Rubin, RR AF Florez, Hermes Pan, Qing Ackermann, Ronald T. Marrero, David G. Barrett-Connor, Elizabeth Delahanty, Linda Kriska, Andrea Saudek, Christopher D. Goldberg, Ronald B. Rubin, Richard R. CA Diabet Prevention Program Res Grp TI Impact of Lifestyle Intervention and Metformin on Health-Related Quality of Life: the Diabetes Prevention Program Randomized Trial SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE quality of life; lifestyle; metformin; diabetes risk; weight loss ID BODY-MASS INDEX; INSULIN-RESISTANCE; PHYSICAL-ACTIVITY; SURVEY SF-36; WEIGHT-LOSS; POPULATION; MELLITUS; GLUCOSE; CLASSIFICATION; ASSOCIATION AB BACKGROUND: Adults at high risk for diabetes may have reduced health-related quality of life (HRQoL). OBJECTIVE: To assess changes in HRQoL after interventions aimed at diabetes risk reduction. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial, the Diabetes Prevention Program, was conducted in 27 centers in the United States, in 3,234 non-diabetic persons with elevated fasting and post-load plasma glucose, mean age 51 years, mean BMI 34 Kg/mA(2); 68 % women, and 45 % members of minority groups. INTERVENTIONS: Intensive lifestyle (ILS) program with the goals of at least 7 % weight loss and 150 min of physical activity per week, metformin (MET) 850 mg twice daily, or placebo (PLB). MEASUREMENTS: HRQoL using the 36-Item Short-Form (SF-36) health survey to evaluate health utility index (SF-6D), physical component summaries (PCS) and mental component summaries (MCS). A minimally important difference (MID) was met when the mean of HRQoL scores between groups differed by at least 3 %. RESULTS: After a mean follow-up of 3.2 years, there were significant improvements in the SF-6D (+0.008, p = 0.04) and PCS (+1.57, p < 0.0001) scores in ILS but not in MET participants (+0.002 and +0.15, respectively, p = 0.6) compared to the PLB group. ILS participants showed improvements in general health (+3.2, p < 0.001), physical function (+3.6, p < 0.001), bodily pain (+1.9, p = 0.01), and vitality (+2.1, p = 0.01) domain scores. Treatment effects remained significant after adjusting sequentially for baseline demographic factors, and for medical and psychological comorbidities. Increased physical activity and weight reduction mediated these ILS treatment effects. Participants who experienced weight gain had significant worsening on the same HRQoL specific domains when compared to those that had treatment-related (ILS or MET) weight loss. No benefits with ILS or MET were observed in the MCS score. CONCLUSION: Overweight/obese adults at high risk for diabetes show small improvement in most physical HRQoL and vitality scores through the weight loss and increased physical activity achieved with an ILS intervention. C1 [Florez, Hermes] George Washington Univ, Diabet Prevent Program Coordinating Ctr, Ctr Biostat, Rockville, MD 20852 USA. [Florez, Hermes; Goldberg, Ronald B.] Univ Miami, Coral Gables, FL 33124 USA. [Pan, Qing] George Washington Univ, Washington, DC USA. [Ackermann, Ronald T.; Marrero, David G.] Indiana Univ, Bloomington, IN 47405 USA. [Barrett-Connor, Elizabeth] Univ Calif, Oakland, CA USA. [Delahanty, Linda] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kriska, Andrea] Univ Pittsburgh, Pittsburgh, PA USA. [Saudek, Christopher D.; Rubin, Richard R.] Johns Hopkins Univ, Baltimore, MD USA. [Florez, Hermes] Miami VAHS Geriatr Res Educ & Clin Ctr, Miami, FL USA. RP Florez, H (reprint author), George Washington Univ, Diabet Prevent Program Coordinating Ctr, Ctr Biostat, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM hflorez@med.miami.edu OI Kriska, Andrea/0000-0002-3522-0869 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK; Indian Health Service; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; Office of Research on Women's Health; American Diabetes Association; McKesson BioServices Corp.; Matthews Media Group, Inc.; Henry M. Jackson Foundation; VA-GRECC/University of Miami CTSI program; HHS/NIH [1R18AE000049-01] FX The Investigators gratefully acknowledge the commitment and dedication of the participants of the DPP. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centers and the Coordinating Center for the design and conduct of the study; and collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women's Health, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported, in part by the intramural research program of the NIDDK. LifeScan Inc., Health O Meter, Hoechst Marion Roussel, Inc., Merck-Medco Managed Care, Inc., Merck and Co., Nike Sports Marketing, Slim Fast Foods Co., and Quaker Oats Co. donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices Corp., Matthews Media Group, Inc., and the Henry M. Jackson Foundation provided support services under subcontract with the Coordinating Center. The opinions expressed are those of the investigators and do not necessarily reflect the views of the Indian Health Service or other funding agencies. A complete list of Centers, investigators, and staff can be found in the online appendix.; The work was also supported in part by the VA-GRECC/University of Miami CTSI program and HHS/NIH grant 1R18AE000049-01[HF]. NR 37 TC 19 Z9 19 U1 2 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2012 VL 27 IS 12 BP 1594 EP 1601 DI 10.1007/s11606-012-2122-5 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 050RR UT WOS:000312072200007 PM 22692637 ER PT J AU Partin, MR Powell, AA Bangerter, A Halek, K Burgess, JF Fisher, DA Nelson, DB AF Partin, Melissa R. Powell, Adam A. Bangerter, Ann Halek, Krysten Burgess, James F., Jr. Fisher, Deborah A. Nelson, David B. TI Levels and Variation in Overuse of Fecal Occult Blood Testing in the Veterans Health Administration SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE colorectal neoplasms; mass screening; utilization; clinical practice variation; veterans ID COLORECTAL-CANCER; PREVENTIVE SERVICES; MEDICARE POPULATION; UNITED-STATES; CARE-SYSTEM; COLONOSCOPY; RECOMMENDATION; COMORBIDITY; IMPACT; US AB BACKGROUND: Policy-makers have called for efforts to reduce overuse of cancer screening tests, including colorectal cancer screening (CRCS). Overuse of CRCS tests other than colonoscopy has not been well documented. OBJECTIVE: To estimate levels and correlates of fecal occult blood test (FOBT) overuse in a national Veterans Health Administration (VHA) sample. DESIGN: Observational PARTICIPANTS: Participants included 1,844 CRCS-eligible patients who responded to a 2007 CRCS survey conducted in 24 VHA facilities and had one or more FOBTs between 2003 and 2009. MAIN MEASURES: We combined survey data on race, education, and income with administrative data on region, age, gender, CRCS procedures, and outpatient visits to estimate overuse levels and variation. We coded FOBTs as overused if they were conducted < 10 months after prior FOBT, < 9.5 years after prior colonoscopy, or < 4.5 years after prior barium enema. We used multinomial logistic regression models to examine variation in overuse by reason (sooner than recommended after prior FOBT; sooner than recommended after colonoscopy, barium enema, or a combination of procedures), adjusting for clustering of procedures within patients, and patients within facilities. KEY RESULTS: Of 4,236 FOBTs received by participants, 885 (21 %) met overuse criteria, with 323 (8 %) sooner than recommended after FOBT, and 562 (13 %) sooner than recommended after other procedures. FOBT overuse varied across facilities (9-32 %, p < 0.0001) and region (12-23 %, p < .0012). FOBT overuse after prior FOBT declined between 2003 and 2009 (8 %-5 %, p = .0492), but overuse after other procedures increased (11-19 %, p = .0002). FOBT overuse of both types increased with number of outpatient visits (OR 1.15, p < 0.001), but did not vary by patient demographics. More than 11 % of overused FOBTs were followed by colonoscopy within 12 months. CONCLUSIONS: Many FOBTs are performed sooner than recommended in the VHA. Variation in overuse by facility, region, and outpatient visits suggests addressing FOBT overuse will require system-level solutions. C1 [Partin, Melissa R.; Powell, Adam A.; Bangerter, Ann; Halek, Krysten; Nelson, David B.] Minneapolis Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. [Partin, Melissa R.; Powell, Adam A.; Nelson, David B.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Burgess, James F., Jr.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Burgess, James F., Jr.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Fisher, Deborah A.] Durham VA Med Ctr, Ctr Excellence Primary Care, Durham, NC USA. [Fisher, Deborah A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Partin, MR (reprint author), Minneapolis Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, 1 Vet Dr,2E-152, Minneapolis, MN 55417 USA. EM melissa.partin@va.gov OI Burgess, James/0000-0002-6646-7071 FU VA Health Services Research Development [PPO 09-292, CDA 08-024] FX The study was supported by VA Health Services Research & Development grants #PPO 09-292 (Partin) and #CDA 08-024 (Powell). The funding organization had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 47 TC 8 Z9 8 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2012 VL 27 IS 12 BP 1618 EP 1625 DI 10.1007/s11606-012-2163-9 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 050RR UT WOS:000312072200010 PM 22810358 ER PT J AU Bokhour, BG Cohn, ES Cortes, DE Solomon, JL Fix, GM Elwy, AR Mueller, N Katz, LA Haidet, P Green, AR Borzecki, AM Kressin, NR AF Bokhour, Barbara G. Cohn, Ellen S. Cortes, Dharma E. Solomon, Jeffrey L. Fix, Gemmae M. Elwy, A. Rani Mueller, Nora Katz, Lois A. Haidet, Paul Green, Alexander R. Borzecki, Ann M. Kressin, Nancy R. TI The Role of Patients' Explanatory Models and Daily-Lived Experience in Hypertension Self-Management SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hypertension; medication adherence; qualitative methods; health behavior; self-management ID BLOOD-PRESSURE CONTROL; MEDICATION ADHERENCE; HEALTH BELIEFS; CARE; ILLNESS; ASTHMA; RECOMMENDATIONS; POPULATION; ROUTINES; DOCTORS AB BACKGROUND: Uncontrolled hypertension remains a significant problem for many patients. Few interventions to improve patients' hypertension self-management have had lasting effects. Previous work has focused largely on patients' beliefs as predictors of behavior, but little is understood about beliefs as they are embedded in patients' social contexts. OBJECTIVE: This study aims to explore how patients' "explanatory models" of hypertension (understandings of the causes, mechanisms or pathophysiology, course of illness, symptoms and effects of treatment) and social context relate to their reported daily hypertension self-management behaviors. DESIGN: Semi-structured qualitative interviews with a diverse group of patients at two large urban Veterans Administration Medical centers. PARTICIPANTS (OR PATIENTS OR SUBJECTS): African-American, white and Latino Veterans Affairs (VA) primary care patients with uncontrolled blood pressure. APPROACH: We conducted thematic analysis using tools of grounded theory to identify key themes surrounding patients' explanatory models, social context and hypertension management behaviors. RESULTS: Patients' perceptions of the cause and course of hypertension, experiences of hypertension symptoms, and beliefs about the effectiveness of treatment were related to different hypertension self-management behaviors. Moreover, patients' daily-lived experiences, such as an isolated lifestyle, serious competing health problems, a lack of habits and routines, barriers to exercise and prioritizing lifestyle choices, also interfered with optimal hypertension self-management. CONCLUSIONS: Designing interventions to improve patients' hypertension self-management requires consideration of patients' explanatory models and their daily-lived experience. We propose a new conceptual model - the dynamic model of hypertension self-management behavior - which incorporates these key elements of patients' experiences. C1 [Bokhour, Barbara G.; Solomon, Jeffrey L.; Fix, Gemmae M.; Elwy, A. Rani; Mueller, Nora; Borzecki, Ann M.] ENRM Vet Affairs Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Bokhour, Barbara G.; Elwy, A. Rani] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Borzecki, Ann M.; Kressin, Nancy R.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Cohn, Ellen S.] Boston Univ, Dept Occupat Therapy, Coll Hlth & Rehabil Sci, Boston, MA 02215 USA. [Cortes, Dharma E.] Cambridge Hlth Alliance, Cambridge, MA USA. [Katz, Lois A.] VA New York Harbor Healthcare Syst, New York, NY USA. [Katz, Lois A.] NYU, Sch Med, New York, NY USA. [Haidet, Paul] Penn State Univ, Off Med Educ, Coll Med, Hershey, PA USA. [Haidet, Paul] Penn State Univ, Dept Med, Coll Med, Hershey, PA USA. [Haidet, Paul] Penn State Univ, Dept Humanities, Coll Med, Hershey, PA USA. [Haidet, Paul] Penn State Univ, Dept Publ Hlth Sci, Coll Med, Hershey, PA USA. [Green, Alexander R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Green, Alexander R.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Cortes, Dharma E.; Green, Alexander R.] Harvard Univ, Sch Med, Boston, MA USA. RP Bokhour, BG (reprint author), ENRM Vet Affairs Med Ctr, Ctr Hlth Qual, Bedford, MA 01730 USA. EM Barbara.Bokhour@va.gov OI Bokhour, Barbara/0000-0001-8238-0745; Kressin, Nancy/0000-0003-2767-4286; Fix, Gemmae/0000-0001-6055-4177 FU Department of Veterans Affairs, Health Services Research and Development grant [IIR 05-062]; Department of Veterans Affairs, Health Services Research & Development Service [RCS 02-066-1] FX This study was supported by the Department of Veterans Affairs, Health Services Research and Development grant #IIR 05-062. Dr. Kressin is supported by a Senior Research Career Scientist award from the Department of Veterans Affairs, Health Services Research & Development Service (RCS 02-066-1). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. A version of this paper was presented as a poster at the Society of General Internal Medicine in May 2009 and the VA Health Services Research and Development annual meeting in February 2009. NR 33 TC 14 Z9 14 U1 4 U2 33 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2012 VL 27 IS 12 BP 1626 EP 1634 DI 10.1007/s11606-012-2141-2 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 050RR UT WOS:000312072200011 PM 22821569 ER PT J AU Ratanawongsa, N Korthuis, PT Saha, S Roter, D Moore, RD Sharp, VL Beach, MC AF Ratanawongsa, Neda Korthuis, P. Todd Saha, Somnath Roter, Debra Moore, Richard D. Sharp, Victoria L. Beach, Mary Catherine TI Clinician Stress and Patient-Clinician Communication in HIV Care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient; clinician; stress; communication; HIV ID INTERNAL-MEDICINE; PHYSICIAN BURNOUT; PERCEIVED STRESS; WOMEN PHYSICIANS; SATISFACTION; OUTCOMES; EMPATHY; HEALTH; PERFORMANCE; BEHAVIOR AB BACKGROUND: Clinician stress is common, but few studies have examined its relationship with communication behaviors. OBJECTIVE: To investigate associations between clinician stress and patient-clinician communication in primary HIV care. DESIGN: Observational study. PARTICIPANTS: Thirty-three primary HIV clinicians and 350 HIV-infected adult, English-speaking patients at three U.S. HIV specialty clinic sites. MAIN MEASURES: Clinicians completed the Perceived Stress Scale, and we categorized scores in tertiles. Audio-recordings of patient-clinician encounters were coded using the Roter Interaction Analysis System. Patients rated the quality of their clinician's communication and overall quality of medical care. We used regression with generalized estimating equations to examine associations between clinician stress and communication outcomes, controlling for clinician gender, clinic site, and visit length. KEY RESULTS: Among the 33 clinicians, 70 % were physicians, 64 % were women, 67 % were non-Hispanic white, and the mean stress score was 3.9 (SD 2.4, range 0-8). Among the 350 patients, 34 % were women, 55 % were African American, 23 % were non-Hispanic white, 16 % were Hispanic, and 30 % had been with their clinicians > 5 years. Verbal dominance was higher for moderate-stress clinicians (ratio = 1.93, p < 0.01) and high-stress clinicians (ratio = 1.76, p = 0.01), compared with low-stress clinicians (ratio 1.45). More medical information was offered by moderate-stress clinicians (145.5 statements, p < 0.01) and high-stress clinicians (125.9 statements, p = 0.02), compared with low-stress clinicians (97.8 statements). High-stress clinicians offered less psychosocial information (17.1 vs. 19.3, p = 0.02), and patients of high-stress clinicians rated their quality of care as excellent less frequently than patients of low-stress clinicians (49.5 % vs. 66.9 %, p < 0.01). However, moderate-stress clinicians offered more partnering statements (27.7 vs. 18.2, p = 0.04) and positive affect (3.88 vs. 3.78 score, p = 0.02) than low-stress clinicians, and their patients' ratings did not differ. CONCLUSIONS: Although higher stress was associated with verbal dominance and lower patient ratings, moderate stress was associated with some positive communication behaviors. Prospective mixed methods studies should examine the complex relationships across the continuum of clinician well-being and health communication. C1 [Ratanawongsa, Neda] San Francisco Gen Hosp, UCSF Ctr Vulnerable Populat, San Francisco, CA 94110 USA. [Ratanawongsa, Neda] Univ Calif San Francisco, Ctr Trauma, San Francisco, CA 94110 USA. [Korthuis, P. Todd; Saha, Somnath] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Roter, Debra; Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Baltimore, MD USA. [Sharp, Victoria L.] St Lukes Roosevelt Hosp, New York, NY USA. RP Ratanawongsa, N (reprint author), San Francisco Gen Hosp, UCSF Ctr Vulnerable Populat, 1001 Potrero Ave,Box 1364, San Francisco, CA 94110 USA. EM ratanawongsan@medsfgh.ucsf.edu RI Roter, Debra/N-8830-2014 FU Health Resources Service Administration; Agency for Healthcare Research and Quality [AHRQ 290-01-0012, K08 HS013903-05]; National Institute of Drug Abuse [K23 DA019808]; Robert Wood Johnson Generalist Physician Faculty Scholars Awards; Department of Veterans Affairs FX This research was supported by a contract from the Health Resources Service Administration and the Agency for Healthcare Research and Quality (AHRQ 290-01-0012). In addition, Dr. Korthuis was supported by the National Institute of Drug Abuse (K23 DA019808). Dr. Beach was supported by the Agency for Healthcare Research and Quality (K08 HS013903-05), and both Drs. Beach and Saha were supported by Robert Wood Johnson Generalist Physician Faculty Scholars Awards. Dr. Saha was supported by the Department of Veterans Affairs. NR 63 TC 4 Z9 4 U1 2 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2012 VL 27 IS 12 BP 1635 EP 1642 DI 10.1007/s11606-012-2157-7 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 050RR UT WOS:000312072200012 PM 22821571 ER PT J AU Sudore, RL Karter, AJ Huang, ES Moffet, HH Laiteerapong, N Schenker, Y Adams, A Whitmer, RA Liu, JY Miao, YH John, PM Schillinger, D AF Sudore, Rebecca L. Karter, Andrew J. Huang, Elbert S. Moffet, Howard H. Laiteerapong, Neda Schenker, Yael Adams, Alyce Whitmer, Rachel A. Liu, Jennifer Y. Miao, Yinghui John, Priya M. Schillinger, Dean TI Symptom Burden of Adults with Type 2 Diabetes Across the Disease Course: Diabetes & Aging Study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE palliative care; diabetes mellitus type 2; quality of life ID QUALITY-OF-LIFE; NORTHERN CALIFORNIA DISTANCE; PALLIATIVE CARE; ADVANCED CANCER; OLDER-ADULTS; HOSPITALIZED-PATIENTS; COMORBIDITY INDEX; GLYCEMIC CONTROL; KIDNEY-DISEASE; HEART-FAILURE AB BACKGROUND: Reducing symptom burden is paramount at the end-of-life, but typically considered secondary to risk factor control in chronic disease, such as diabetes. Little is known about the symptom burden experienced by adults with type 2 diabetes and the need for symptom palliation. OBJECTIVE: To examine pain and non-pain symptoms of adults with type 2 diabetes over the disease course - at varying time points before death and by age. DESIGN: Survey follow-up study. PARTICIPANTS: 13,171 adults with type 2 diabetes, aged 30-75 years, from Kaiser Permanente, Northern California, who answered a baseline symptom survey in 2005-2006. MAIN MEASURES: Pain and non-pain symptoms were identified by self-report and medical record data. Survival status from baseline was categorized into a parts per thousand currency sign6, > 6-24, or alive > 24 months. KEY RESULTS: Mean age was 60 years; 48 % were women, and 43 % were non-white. Acute pain was prevalent (41.8 %) and 39.7 % reported chronic pain, 24.6 % fatigue, 23.7 % neuropathy, 23.5 % depression, 24.2 % insomnia, and 15.6 % physical/emotional disability. Symptom burden was prevalent in all survival status categories, but was more prevalent among those with shorter survival, p < .001. Adults a parts per thousand yen60 years who were alive > 24 months reported more physical symptoms such as acute pain and dyspnea, whereas participants < 60 years reported more psychosocial symptoms, such as depressed mood and insomnia. Adjustment for duration of diabetes and comorbidity reduced the association between age and pain, but did not otherwise change our results. CONCLUSIONS: In a diverse cohort of adults with type 2 diabetes, pain and non-pain symptoms were common among all patients, not only among those near the end of life. However, symptoms were more prevalent among patients with shorter survival. Older adults reported more physical symptoms, whereas younger adults reported more psychosocial symptoms. Diabetes care management should include not only good cardiometabolic control, but also symptom palliation across the disease course. C1 [Sudore, Rebecca L.; Miao, Yinghui] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Sudore, Rebecca L.; Miao, Yinghui] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Karter, Andrew J.; Moffet, Howard H.; Adams, Alyce; Whitmer, Rachel A.; Liu, Jennifer Y.] Kaiser Permanente, Div Res, Oakland, CA USA. [Huang, Elbert S.; Laiteerapong, Neda; John, Priya M.] Univ Chicago, Dept Med, Gen Internal Med Sect, Chicago, IL 60637 USA. [Schenker, Yael] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Schillinger, Dean] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Schillinger, Dean] Univ Calif San Francisco, Ctr Vulnerable Populat, San Francisco, CA 94143 USA. [Schillinger, Dean] Calif Dept Publ Hlth, Calif Diabet Program, Sacramento, CA USA. RP Sudore, RL (reprint author), San Francisco VA Med Ctr, 4150 Clement St 151R, San Francisco, CA 94121 USA. EM rebecca.sudore@ucsf.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development, the San Francisco Research Enhancement Award Program; National Institutes of Health (NIH) National Institutes of Diabetes, Digestive and Kidney Diseases (NIDDK) for the Diabetes and Aging Study [RO1-DK-081796]; Diabetes Study of Northern California (DISTANCE) [R01-DK-065664, R01-DK080726, R01-HD46113]; Agency for Healthcare Research and Quality [T32-HS000084]; NIDDK [F32-DK-089973]; NIDDK Diabetes and Research Training Center at the University of Chicago [P60-DK-20595]; NIDDK Centers for Diabetes Translation Research at Kaiser Permanente; University of California, San Francisco [P30 DK092924]; University of Chicago [P30 DK092949] FX Dr. Sudore was supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development, the San Francisco Research Enhancement Award Program. This work was performed with support by the National Institutes of Health (NIH) National Institutes of Diabetes, Digestive and Kidney Diseases (NIDDK) for the Diabetes and Aging Study (RO1-DK-081796) and the Diabetes Study of Northern California (DISTANCE) (R01-DK-065664, R01-DK080726 and R01-HD46113). Dr. Laiteerapong was supported by the Agency for Healthcare Research and Quality, T32-HS000084 and the NIDDK F32-DK-089973. Dr. Laiteerapong, Ms. John, and Dr. Huang are members of the NIDDK Diabetes and Research Training Center at the University of Chicago (grant P60-DK-20595). Investigators were also supported by NIDDK Centers for Diabetes Translation Research at Kaiser Permanente and University of California, San Francisco (P30 DK092924) and the University of Chicago (P30 DK092949). The funding organization had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. NR 45 TC 18 Z9 18 U1 3 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2012 VL 27 IS 12 BP 1674 EP 1681 DI 10.1007/s11606-012-2132-3 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 050RR UT WOS:000312072200017 PM 22854982 ER PT J AU Kruse, GR Kelley, JHK Linder, JA Park, ER Rigotti, NA AF Kruse, Gina R. Kelley, Jennifer H. K. Linder, Jeffrey A. Park, Elyse R. Rigotti, Nancy A. TI Implementation of an Electronic Health Record-Based Care Management System to Improve Tobacco Treatment SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE care management; technology assessment; primary care; smoking cessation ID RANDOMIZED-CONTROLLED-TRIAL; SMOKING-CESSATION; UNITED-STATES; CLINICAL-TRIAL; QUITLINE; SMOKERS; REFERRALS; SERVICES; PROGRAM; PATIENT AB BACKGROUND: Tobacco treatment is underused in primary care. We designed a Tobacco Care Management system to increase the delivery of treatment and reduce the burden on primary care providers (PCPs). A one-click functionality added to the electronic health record (EHR) allowed PCPs to refer smokers to a centralized tobacco treatment coordinator (TTC) who called smokers, provided brief counseling, connected them to ongoing treatment and gave feedback to PCPs. OBJECTIVE: To study the system's feasibility and acceptability among PCPs, and its utilization by smokers. DESIGN: Using a mixed methods design, we documented system utilization quantitatively from February 1, 2010 to July 31, 2011, and conducted two focus groups with PCPs in June 2011. PARTICIPANTS: Thirty-six PCPs and 2,894 smokers from two community health centers in Massachusetts. MAIN MEASURES: Quantitative: One-click referral utilization by PCPs, proportion of smokers referred and connected to treatment. Qualitative: PCPs' reasons for use, barriers to use, and experiences with feedback. KEY RESULTS: Twenty-nine PCPs (81 %) used the functionality more than once, generating 466 referrals for 15 % of known smokers seen during the study. The TTC reached 260 (56 %) of the referrals and connected 135 (29 %) to additional treatment. The director of one center sent PCPs monthly feedback about their utilization compared to peers. These PCPs referred a greater proportion of their known smokers (18 % vs. 9 %, p < 0.0001) and reported that monthly feedback motivated referrals. PCPs attending focus groups (n = 24) appreciated the system's simplicity, access to updated resources, and time-efficient way to address smoking, and wanted more feedback about cessation outcomes. They collectively supported the system's continuation. CONCLUSIONS: A novel EHR-based Tobacco Care Management system was adopted by PCPs, especially those receiving performance feedback, and connected one-third of referred smokers to treatment. The model has the potential to improve the delivery and outcomes of evidence-based tobacco treatment in primary care. C1 [Kruse, Gina R.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. [Kruse, Gina R.; Linder, Jeffrey A.; Park, Elyse R.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. [Kelley, Jennifer H. K.; Park, Elyse R.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Dept Med, Boston, MA 02114 USA. [Kelley, Jennifer H. K.] Partners HealthCare, High Performance Med, Boston, MA USA. [Linder, Jeffrey A.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Park, Elyse R.; Rigotti, Nancy A.] Mongan Inst Hlth Policy, Boston, MA USA. [Park, Elyse R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Kruse, GR (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM gkruse@partners.org FU Partners Healthcare, Inc.; Health Resources and Services Administration for the Harvard General Medicine Fellowship [T32HP12706-03-00]; NIH [K24-HL08880]; Nabi Biopharmaceuticals; Pfizer; UpToDate FX Partners Healthcare, Inc. funded the Tobacco Care Management program and supported the Tobacco Care coordinator. Dr. Kruse's effort was supported by grant #T32HP12706-03-00 from the Health Resources and Services Administration for the Harvard General Medicine Fellowship. Dr. Rigotti's effort was supported by NIH grant #K24-HL08880. The funders of these grants had no role in study design, conduct, data analysis, interpretation, or manuscript preparation, review, or approval.; The authors declare that they do not have a conflict of interest. Nancy A. Rigotti reports unpaid consultancy for Pfizer and Alere Wellbeing, research grants to MGH from Nabi Biopharmaceuticals and Pfizer, and royalties from UpToDate. NR 24 TC 8 Z9 8 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2012 VL 27 IS 12 BP 1690 EP 1696 DI 10.1007/s11606-012-2174-6 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 050RR UT WOS:000312072200019 PM 22865018 ER PT J AU Catana, C Drzezga, A Heiss, WD Rosen, BR AF Catana, Ciprian Drzezga, Alexander Heiss, Wolf-Dieter Rosen, Bruce R. TI PET/MRI for Neurologic Applications SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE simultaneous PET/MRI; multimodal imaging; neurology ID POSITRON-EMISSION-TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT; VOXEL-BASED MORPHOMETRY; CEREBRAL-BLOOD-FLOW; VOLUME EFFECT CORRECTION; TEMPORAL-LOBE EPILEPSY; MAGNETIC-RESONANCE; ALZHEIMERS-DISEASE; MOTION CORRECTION; ISCHEMIC PENUMBRA AB PET and MRI provide complementary information in the study of the human brain. Simultaneous PET/MRI data acquisition allows the spatial and temporal correlation of the measured signals, creating opportunities impossible to realize using stand-alone instruments. This paper reviews the methodologic improvements and potential neurologic and psychiatric applications of this novel technology. We first present methods for improving the performance and information content of each modality by using the information provided by the other technique. On the PET side, we discuss methods that use the simultaneously acquired MRI data to improve the PET data quantification. On the MRI side, we present how improved PET quantification can be used to validate several MRI techniques. Finally, we describe promising research, translational, and clinical applications that can benefit from these advanced tools. C1 [Catana, Ciprian; Rosen, Bruce R.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Catana, Ciprian; Rosen, Bruce R.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Drzezga, Alexander] Tech Univ Munich, Klinikum Rechts Isar, Nukl Med Klin & Poliklin, D-8000 Munich, Germany. [Heiss, Wolf-Dieter] Max Planck Inst Neurol Res, D-50931 Cologne, Germany. RP Catana, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA. EM ccatana@nmr.mgh.harvard.edu RI Catana, Ciprian/A-1246-2013 FU NCI NIH HHS [R01 CA137254] NR 89 TC 77 Z9 80 U1 1 U2 23 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 2012 VL 53 IS 12 BP 1916 EP 1925 DI 10.2967/jnumed.112.105346 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 051GX UT WOS:000312115400017 PM 23143086 ER PT J AU Enguidanos, S Vesper, E Lorenz, K AF Enguidanos, Susan Vesper, Evie Lorenz, Karl TI 30-Day Readmissions among Seriously III Older Adults SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID HOSPITAL PALLIATIVE CARE; OF-LIFE; MEDICARE BENEFICIARIES; HEART-FAILURE; LAST YEAR; END; COSTS; DEATH; CANCER; HEALTH AB Background: Inpatient palliative consultation are generally provided to seriously ill hospitalized patients with the intent to alleviate pain and suffering and develop a plan of care for the patient. Although numerous benefits of this service have been documented, little is known about hospital readmission rates and factors associated with these readmissions. Objective: Our aim was to investigate factors associated with 30-day hospital readmission among patients receiving a consultation from an inpatient palliative care (ICP) team. Design: We conducted a retrospective cohort study. Setting/Subjects: Data from 408 managed care patients 65 years old and older were collected in 2007-2009 following an IPC consultation and subsequent hospital discharge. Measurements: IPC and medical service use records were utilized. Results: Among IPC patients, 10% of those discharged from the hospital were readmitted within 30 days. Factors associated with hospital readmission included being discharged from the hospital with no care in the home or to a nursing facility. Receipt of hospice or home-based palliative care post-discharge was associated with significantly lower odds of hospital readmission. Conclusions: This study found that receipt of palliative care following hospital discharge was an important factor in reducing 30-day hospital readmissions. Further study is needed to evaluate the effectiveness of longitudinal palliative care models in reducing 30-day hospital readmissions among seriously ill patients. C1 [Enguidanos, Susan] Univ So Calif, Leonard Davis Sch Gerontol, Los Angeles, CA 90089 USA. [Vesper, Evie] Kaiser Permanente, Downey, CA USA. [Lorenz, Karl] VA Greater Los Angeles, Los Angeles, CA USA. RP Enguidanos, S (reprint author), Univ So Calif, Davis Sch Gerontol, 3715 McClintock Ave,Gero 228-B, Los Angeles, CA 90089 USA. EM Enguidan@usc.edu OI Enguidanos, Susan/0000-0002-5112-288X FU National Palliative Care Research Center (NPCRC) FX This study was supported in full by a career development award from the National Palliative Care Research Center (NPCRC). Evie Vesper was an employee of the health care organization at the time of the study. NR 35 TC 32 Z9 32 U1 2 U2 11 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC PY 2012 VL 15 IS 12 BP 1356 EP 1361 DI 10.1089/jpm.2012.0259 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 048UB UT WOS:000311937500012 PM 23045990 ER PT J AU Lindley, LC Mixer, S Mack, JW AF Lindley, Lisa C. Mixer, Sandy Mack, Jennifer W. TI Profit Status and Delivery of Hospice Care for Infants: The Mediating Role of Pediatric Knowledge SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; VITAL-STATISTICS; END; ORGANIZATIONS; CHILDREN; HOME AB Background: Infant mortality is a persistent problem in the United States, and yet, hospice care is rarely provided for infants at the end of life. Objective: To examine the influence of profit status on delivery of hospice care for infants, and to explore the mediating role of pediatric knowledge (pediatric program and pediatric knowledge) on the relationship between profit status and the delivery of infant care. Methods: Our study was a cross-sectional secondary analysis, using data from the 2008 California State Utilization Data File of Home Health Agencies and Hospice Facilities survey. Results: Of the hospices in the sample, 13% delivered care for infants. Nonprofit hospices were more likely to delivery care for infants (B = 0.67, p < 0.05), have a specialized pediatric program (B = 0.85, p < 0.05) and have more experience caring for pediatric patients (B = 1.49, p < 0.05). Regarding the mediator variables, hospices with a pediatric program were no more likely to deliver care to infants than hospices without a pediatric program (B = 0.82, p > 0.05). Experience with greater numbers of any pediatric patients facilitated the delivery of hospice infant care in nonprofits (B = 0.86, p < 0.05). Conclusion: Hospices may need to explore ways to direct resources toward assisting hospice staff members in gaining pediatric experience. C1 [Lindley, Lisa C.; Mixer, Sandy] Univ Tennessee, Coll Nursing, Knoxville, TN 37996 USA. [Mack, Jennifer W.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Mack, Jennifer W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. [Mack, Jennifer W.] Dana Farber Canc Inst, Div Populat Sci, Ctr Outcomes & Policy Res, Boston, MA USA. RP Lindley, LC (reprint author), Univ Tennessee, Coll Nursing, 1200 Volunteer Blvd 147, Knoxville, TN 37996 USA. EM llindley@utk.edu OI Lindley, Lisa C./0000-0003-2960-7896 NR 24 TC 3 Z9 3 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC PY 2012 VL 15 IS 12 BP 1369 EP 1373 DI 10.1089/jpm.2012.0214 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 048UB UT WOS:000311937500014 PM 23030306 ER PT J AU McCannon, JB O'Donnell, WJ Thompson, BT El-Jawahri, A Chang, YC Ananian, L Bajwa, EK Currier, PF Parikh, M Temel, JS Cooper, Z Wiener, RS Volandes, AE AF McCannon, Jessica B. O'Donnell, Walter J. Thompson, B. Taylor El-Jawahri, Areej Chang, Yuchiao Ananian, Lillian Bajwa, Ednan K. Currier, Paul F. Parikh, Mihir Temel, Jennifer S. Cooper, Zara Wiener, Renda Soylemez Volandes, Angelo E. TI Augmenting Communication and Decision Making in the Intensive Care Unit with a Cardiopulmonary Resuscitation Video Decision Support Tool: A Temporal Intervention Study SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; RANDOMIZED CONTROLLED-TRIAL; END; IMPROVEMENT; ICU; KNOWLEDGE; DEMENTIA; MAKERS; IMAGES; ILL AB Objective: Effective communication between intensive care unit (ICU) providers and families is crucial given the complexity of decisions made regarding goals of therapy. Using video images to supplement medical discussions is an innovative process to standardize and improve communication. In this six-month, quasi-experimental, pre-post intervention study we investigated the impact of a cardiopulmonary resuscitation (CPR) video decision support tool upon knowledge about CPR among surrogate decision makers for critically ill adults. Methods: We interviewed surrogate decision makers for patients aged 50 and over, using a structured questionnaire that included a four-question CPR knowledge assessment similar to those used in previous studies. Surrogates in the post-intervention arm viewed a three-minute video decision support tool about CPR before completing the knowledge assessment and completed questions about perceived value of the video. Results: We recruited 23 surrogates during the first three months (pre-intervention arm) and 27 surrogates during the latter three months of the study (post-intervention arm). Surrogates viewing the video had more knowledge about CPR (p = 0.008); average scores were 2.0 (SD 1.1) and 2.9 (SD 1.2) (out of a total of 4) in pre-intervention and post-intervention arms. Surrogates who viewed the video were comfortable with its content (81% very) and 81% would recommend the video. CPR preferences for patients at the time of ICU discharge/death were distributed as follows: pre-intervention: full code 78%, DNR 22%; post-intervention: full code 59%, DNR 41% (p = 0.23). C1 [Volandes, Angelo E.] Massachusetts Gen Hosp, Gen Med Unit, Dept Med, Sect Gen Med, Boston, MA 02114 USA. [McCannon, Jessica B.; O'Donnell, Walter J.; Thompson, B. Taylor; El-Jawahri, Areej; Chang, Yuchiao; Ananian, Lillian; Bajwa, Ednan K.; Currier, Paul F.; Parikh, Mihir; Temel, Jennifer S.; Cooper, Zara; Volandes, Angelo E.] Harvard Univ, Sch Med, Boston, MA USA. [McCannon, Jessica B.; O'Donnell, Walter J.; Thompson, B. Taylor; Ananian, Lillian; Bajwa, Ednan K.; Currier, Paul F.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Temel, Jennifer S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Cooper, Zara] Brigham & Womens Hosp, Div Trauma Burns & Crit Care, Boston, MA 02115 USA. [Wiener, Renda Soylemez] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. [Wiener, Renda Soylemez] ENRM VA Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. RP Volandes, AE (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Dept Med, Sect Gen Med, 50 Staniford St, Boston, MA 02114 USA. EM avolandes@partners.org OI Wiener, Renda/0000-0001-7712-2135 FU AHRQ HHS [K08 HS018780]; NCI NIH HHS [K07 CA138772] NR 24 TC 17 Z9 17 U1 6 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC PY 2012 VL 15 IS 12 BP 1382 EP 1387 DI 10.1089/jpm.2012.0215 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 048UB UT WOS:000311937500016 PM 23098632 ER PT J AU Fava, M Targum, SD Nierenberg, AA Bleicher, LS Carter, TA Wedel, PC Hen, R Gage, FH Barlow, C AF Fava, Maurizio Targum, Steven D. Nierenberg, Andrew A. Bleicher, Leo S. Carter, Todd A. Wedel, Pamela C. Hen, Rene Gage, Fred H. Barlow, Carrolee TI An exploratory study of combination buspirone and melatonin SR in Major Depressive Disorder (MDD): A possible role for neurogenesis in drug discovery SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Major depressive disorder; Neurogenesis; 5 HT1a agonists; Augmentation treatments ID ADULT HIPPOCAMPAL NEUROGENESIS; STAR-ASTERISK-D; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; GEPIRONE EXTENDED-RELEASE; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; ANTIDEPRESSANT TREATMENT; CHRONIC FLUOXETINE; RECEPTOR AGONIST; DSM-IV AB We used in vitro neurogenesis-based human neural stem cell (hNSCs) assays and rodent in vivo behavioral assays to identify potential novel antidepressants. A combination of buspirone and melatonin displayed antidepressant activity in these assays whereas neither buspirone nor melatonin alone showed any antidepressant-like profile. After evaluating numerous combination ratios, we determined that low dose buspirone 15 mg combined with melatonin-SR 3 mg yielded optimal antidepressant efficacy in our pre-clinical platform. The low dose of buspirone suggested that antidepressant efficacy might be achieved with only minimal adverse event liability. Based on these data, we conducted an exploratory 6-week, multi-center, double-blind, randomized, placebo- and comparator-controlled study of the combination of buspirone and melatonin in subjects with acute Major Depressive Disorder (MDD). The combination treatment revealed a significant antidepressant response in subjects with MDD on several measures (Clinical Global Impression of Severity and improvement, Inventory of Depressive Symptomatology) compared to either placebo or buspirone 15 mg monotherapy. These preliminary findings have clinical implications and suggest that a platform of pre-clinical neurogenesis matched with confirmatory behavioral assays may be useful as a drug discovery strategy. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Fava, Maurizio; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Targum, Steven D.; Bleicher, Leo S.; Carter, Todd A.; Wedel, Pamela C.; Barlow, Carrolee] BrainCells Inc, San Diego, CA USA. [Hen, Rene] Columbia Univ, Dept Psychiat, New York, NY 10027 USA. [Hen, Rene] Columbia Univ, Dept Neurosci, New York, NY 10027 USA. [Gage, Fred H.] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA. RP Targum, SD (reprint author), 505 Tremont St 907, Boston, MA 02116 USA. EM sdtargum@yahoo.com FU BrainCells Inc.; Clinical trial Network (CTNI) at the Massachusetts General Hospital; Abbott Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Clinical Trials Solutions, LLC; Clintara, LLC; Covance; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmavite(R) LLC; Photothera; Roche Pharmaceuticals; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories FX BrainCells Inc. sponsored this investigator initiated trial conducted under the auspices of the Clinical trial Network (CTNI) at the Massachusetts General Hospital.; Research Support: Abbott Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Clinical Trials Solutions, LLC; Clintara, LLC; Covance; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM): National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmavite (R) LLC; Photothera; Roche Pharmaceuticals; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories. NR 73 TC 23 Z9 23 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD DEC PY 2012 VL 46 IS 12 BP 1553 EP 1563 DI 10.1016/j.jpsychires.2012.08.013 PG 11 WC Psychiatry SC Psychiatry GA 049KY UT WOS:000311983100004 PM 22998742 ER PT J AU Alvarenga, PG do Rosario, MC Batistuzzo, MC Diniz, JB Shavitt, RG Duran, FLS Dougherty, DD Bressan, RA Miguel, EC Hoexter, MQ AF Alvarenga, Pedro G. do Rosario, Maria C. Batistuzzo, Marcelo C. Diniz, Juliana B. Shavitt, Roseli G. Duran, Fabio L. S. Dougherty, Darin D. Bressan, Rodrigo A. Miguel, Euripedes C. Hoexter, Marcelo Q. TI Obsessive-compulsive symptom dimensions correlate to specific gray matter volumes in treatment-naive patients SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Obsessive-compulsive disorder (OCD); Symptom dimensions; Neuroimaging; Voxel-based morphometry (VBM); Treatment-naive; Gray matter (GM) ID VOXEL-BASED MORPHOMETRY; DISORDER; BRAIN; ABNORMALITIES; METAANALYSIS; CORTEX; MODEL; SCALE AB Background: Clinical and sociodemographic findings have supported that OCD is heterogeneous and composed of multiple potentially overlapping and stable symptom dimensions. Previous neuroimaging investigations have correlated different patterns of OCD dimension scores and gray matter (GM) volumes. Despite their relevant contribution, some methodological limitations, such as patient's previous medication intake, may have contributed to inconsistent findings. Method: Voxel-based morphometry was used to investigate correlations between regional GM volumes and symptom dimensions severity scores in a sample of 38 treatment-naive OCD patients. Several standardized instruments were applied, including an interview exclusively developed for assessing symptom dimensions severity (DY-BOCS). Results: Scores on the "aggression" dimension were positively correlated with GM volumes in lateral parietal cortex in both hemispheres and negatively correlated with bilateral insula, left putamen and left inferior OFC. Scores on the "sexual/religious" dimension were positively correlated with GM volumes within the right middle lateral OFC and right DLPFC and negatively correlated with bilateral ACC. Scores on the "hoarding" dimension were positively correlated with GM volumes in the left superior lateral OFC and negatively correlated in the right parahippocampal gyrus. No significant correlations between GM volumes and the "contamination" or "symmetry" dimensions were found. Conclusions: Building upon preexisting findings, our data with treatment-naive OCD patients have demonstrated distinct GM substrates implicated in both cognitive and emotion processing across different OCS dimensions. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Alvarenga, Pedro G.; Batistuzzo, Marcelo C.; Diniz, Juliana B.; Shavitt, Roseli G.; Duran, Fabio L. S.; Miguel, Euripedes C.; Hoexter, Marcelo Q.] Univ Sao Paulo, Sch Med, Dept & Inst Psychiat, BR-05403010 Sao Paulo, Brazil. [do Rosario, Maria C.] Fed Univ Sao Paulo UNIFESP, Dept Psychiat, Child & Adolescent Psychiat Unit UPIA, Sao Paulo, Brazil. [Dougherty, Darin D.; Hoexter, Marcelo Q.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Bressan, Rodrigo A.; Hoexter, Marcelo Q.] Fed Univ Sao Paulo UNIFESP, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LiNC, Sao Paulo, Brazil. RP Hoexter, MQ (reprint author), Univ Sao Paulo, Sch Med, Dept & Inst Psychiat, Rua Ovidio Pires de Campos 785,3 Andar Ala N,Sala, BR-05403010 Sao Paulo, Brazil. EM mqhoexter@gmail.com RI Duran, Fabio/A-9744-2013; Miguel, Euripedes/B-2871-2008; Hoexter, Marcelo/D-7620-2013; Batistuzzo, Marcelo/H-7790-2015; Duran, Fabio/L-1371-2013; Duran, Fabio/I-5704-2012; Bressan, Rodrigo/E-9178-2010 OI Duran, Fabio/0000-0002-7603-6152; Hoexter, Marcelo/0000-0002-9302-4380; Duran, Fabio/0000-0002-7603-6152; Duran, Fabio/0000-0003-2494-7250; Bressan, Rodrigo/0000-0002-0868-4449 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo) [2005/55628-8]; FAPESP [06/61459-7, 06/50273-0, 2005/04206-6]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Agency for Support and Evaluation of Graduate Education) [4375/08-4]; Astra Zeneca; Bristol; Janssen; Lundbeck; Eli Lilly; Novartis; Roche FX This study received financial support in the form of grants provided by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo) to Dr. Miguel (2005/55628-8) and from FAPESP grants to Dr. Shavitt (06/61459-7) and to Dr. Diniz (06/50273-0). Dr. Hoexter was supported by a PhD grant from FAPESP (2005/04206-6) and by a doctorate "sandwich" scholarship from the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Agency for Support and Evaluation of Graduate Education) (4375/08-4).; Dr. de Alvarenga, Mr. Batistuzzo, Dr. Diniz, Dr. Shavitt, Dr. Duran, Dr. Miguel and Dr. Hoexter have declared no conflict of interest. Dr. Dougherty has acted as a consultant for Medtronic, Eli Lilly, Brand Ideas, McNeil and Reed Elsevier: has received research funding from Medtronic, Eli Lilly, McNeil and Cyberonics. Dr. Rosario has acted as a speaker for Novartis and Shire in the past two years. Dr. Bressan has received honoraria and/or consultations fees from Astra Zeneca, Bristol, Janssen and Lundbeck; has received research funding from Janssen, Eli Lilly, Lundbeck, Novartis and Roche. NR 44 TC 22 Z9 22 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD DEC PY 2012 VL 46 IS 12 BP 1635 EP 1642 DI 10.1016/j.jpsychires.2012.09.002 PG 8 WC Psychiatry SC Psychiatry GA 049KY UT WOS:000311983100016 PM 23040160 ER PT J AU Proverbs-Singh, T Chiu, SK Liu, ZY Seng, S Sonpavde, G Choueiri, TK Tsao, CK Yu, MG Hahn, NM Oh, WK Galsky, MD AF Proverbs-Singh, Tracy Chiu, Sophia K. Liu, Ziyue Seng, Sonia Sonpavde, Guru Choueiri, Toni K. Tsao, Che-Kai Yu, Menggang Hahn, Noah M. Oh, William K. Galsky, Matthew D. TI Arterial Thromboembolism in Cancer Patients Treated With Cisplatin: A Systematic Review and Meta-analysis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID EVENTS; CHEMOTHERAPY; CARCINOMA AB Cisplatin has been associated with an increased risk of arterial thromboembolic events (ATEs). However, because this association is mostly based on case reports and retrospective studies, we conducted a systemic review and meta-analysis of randomized controlled trials evaluating the incidence and risk of ATEs associated with cisplatin. Eligible studies included prospective randomized phase II and III trials evaluating cisplatin-based vs non-cisplatin-based chemotherapy in patients with solid tumors, which were identified from PubMed articles published between 1990 and 2010. Incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using a random effects model. A total of 8216 patients from 38 trials were included. Among patients treated with cisplatin-based chemotherapy, the summary incidence of ATEs was 0.67% (95% CI = 0.40% to 0.95%), and the RR of ATEs was 1.36 (95% CI = 0.86 to 2.17; P = .19). No increase in ATEs was detected in any prespecified subgroup. J Natl Cancer Inst 2012:104;1837-1840 C1 [Proverbs-Singh, Tracy; Chiu, Sophia K.; Tsao, Che-Kai; Oh, William K.; Galsky, Matthew D.] Mt Sinai Med Ctr, Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol Oncol, New York, NY 10029 USA. [Liu, Ziyue] Indianan Univ Sch Med, Dept Biostat, Indianapolis, IN USA. [Hahn, Noah M.] Indianan Univ Sch Med, Div Med Oncol, Simon Canc Ctr, Indianapolis, IN USA. [Seng, Sonia] Southcoast Ctr Canc Care, Div Med Oncol, Fairhaven, MA USA. [Sonpavde, Guru] Univ Alabama Birmingham, Div Hematol Oncol, Birmingham, AL USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Yu, Menggang] Univ Wisconsin Sch Med, Dept Biostat & Med Informat, Madison, WI USA. RP Galsky, MD (reprint author), Mt Sinai Med Ctr, Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol Oncol, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM matthew-galsky@mssm.edu RI Oh, William/B-9163-2012; Liu, Ziyue/J-3065-2013 OI Oh, William/0000-0001-5113-8147; FU Prostate Cancer Foundation FX MDG is supported by a Prostate Cancer Foundation Young Investigator award. NR 14 TC 8 Z9 8 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC PY 2012 VL 104 IS 23 BP 1837 EP 1840 DI 10.1093/jnci/djs435 PG 4 WC Oncology SC Oncology GA 051EZ UT WOS:000312109500013 PM 23093559 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Measuring Hope: Patient Expectations of Chemotherapy for Advanced Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 1 TC 0 Z9 0 U1 1 U2 7 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD DEC PY 2012 VL 10 IS 12 BP 1459 EP 1460 PG 2 WC Oncology SC Oncology GA 051GM UT WOS:000312114200001 PM 23221783 ER PT J AU Zelenetz, AD Wierda, WG Abramson, JS Advani, RH Andreadis, CB Bartlett, N Bellam, N Byrd, JC Czuczman, MS Fayad, L Glenn, MJ Gockerman, JP Gordon, LI Harris, NL Hoppe, RT Horwitz, SM Kelsey, CR Kim, YH Krivacic, S LaCasce, AS Nademanee, A Porcu, P Press, O Pro, B Reddy, N Sokol, L Swinnen, L Tsien, C Vose, JM Yahalom, J Zafar, N Naganuma, M Dwyer, MA AF Zelenetz, Andrew D. Wierda, William G. Abramson, Jeremy S. Advani, Ranjana H. Andreadis, C. Babis Bartlett, Nancy Bellam, Naresh Byrd, John C. Czuczman, Myron S. Fayad, Luis Glenn, Martha J. Gockerman, Jon P. Gordon, Leo I. Harris, Nancy Lee Hoppe, Richard T. Horwitz, Steven M. Kelsey, Christopher R. Kim, Youn H. Krivacic, Susan LaCasce, Ann S. Nademanee, Auayporn Porcu, Pierluigi Press, Oliver Pro, Barbara Reddy, Nishitha Sokol, Lubomir Swinnen, Lode Tsien, Christina Vose, Julie M. Yahalom, Joachim Zafar, Nadeem Naganuma, Maoko Dwyer, Mary A. TI Non-Hodgkin's Lymphomas, Version 3.2012 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MANTLE-CELL LYMPHOMA; PREVIOUSLY UNTREATED PATIENTS; PROGRESSION-FREE SURVIVAL; WISCONSIN-ONCOLOGY-NETWORK; PHASE-II TRIAL; FOLLOW-UP; MAINTENANCE RITUXIMAB; BENDAMUSTINE; MULTICENTER AB These NCCN Guidelines Insights summarize several key updates to the 2012 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Hodgkin's Lymphomas (NHL) and describe the clinical evidence supporting the updates. The featured updates include changes to the recommendations for treatment options in patients with chronic lymphocytic leukemia (including in elderly or frail patients and patients with poor-risk cytogenetics), guidance surrounding surveillance imaging for follow-up of patients with NHL, and the addition of first-line consolidation options for patients with mantle cell lymphoma. (JNCCN 2012;10:1487-1498) C1 [Zelenetz, Andrew D.; Horwitz, Steven M.; Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wierda, William G.; Fayad, Luis; Harris, Nancy Lee] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Abramson, Jeremy S.; Hoppe, Richard T.; Kim, Youn H.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Advani, Ranjana H.] Stanford Canc Inst, Stanford, CA USA. [Andreadis, C. Babis] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Bartlett, Nancy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Bellam, Naresh] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Byrd, John C.; Porcu, Pierluigi] Ohio State Univ, Comprehens Canc Ctr, James Canc Hosp, Columbus, OH 43210 USA. [Byrd, John C.] Solove Res Inst, Columbus, OH USA. [Glenn, Martha J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY USA. [Gordon, Leo I.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Press, Oliver] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Pro, Barbara] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Reddy, Nishitha] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Tsien, Christina] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA. [Vose, Julie M.] Univ Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE 68198 USA. [Zafar, Nadeem] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. RP Zelenetz, AD (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. OI Gordon, Leo/0000-0003-1666-7064 FU NCI NIH HHS [P30 CA016672] NR 34 TC 21 Z9 22 U1 0 U2 4 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD DEC PY 2012 VL 10 IS 12 BP 1487 EP 1498 PG 12 WC Oncology SC Oncology GA 051GM UT WOS:000312114200005 PM 23221787 ER PT J AU Phillips, JG Hong, TS Ryan, DP AF Phillips, John G. Hong, Theodore S. Ryan, David P. TI Multidisciplinary Management of Early-Stage Rectal Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID METASTATIC COLORECTAL-CANCER; TOTAL MESORECTAL EXCISION; POSTOPERATIVE ADJUVANT CHEMOTHERAPY; III COLON-CANCER; PHASE-I TRIAL; PREOPERATIVE RADIOTHERAPY; RADIATION-THERAPY; RANDOMIZED-TRIAL; COMPUTED-TOMOGRAPHY; TUMOR ANGIOGENESIS AB Because patients with locally advanced rectal cancer are at high risk for both recurrence and distant disease, they require adjuvant therapy. In the United States, the current standard of care is neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy. Neoadjuvant chemoradiation has been shown to improve local recurrence rates and decrease toxicity. However in the era of total mesorectal excision surgery, no study has shown a survival benefit to either chemoradiation or postoperative chemotherapy. Newer biologic therapies, although promising in initial early trials, have yet to show a significant benefit in adjuvant therapy for rectal cancer. (JNCCN 2012;10:1577-1585) C1 [Ryan, David P.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA. [Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Ctr Canc, Boston, MA 02114 USA. [Phillips, John G.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Dept Med, Ctr Canc, Yawkey 7E,55 Fruit St, Boston, MA 02114 USA. EM dpryan@partners.org NR 67 TC 1 Z9 1 U1 0 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD DEC PY 2012 VL 10 IS 12 BP 1577 EP 1585 PG 9 WC Oncology SC Oncology GA 051GM UT WOS:000312114200010 PM 23221792 ER PT J AU Nikolic, B Rose, SC Ortiz, J Martin, LG Zaki, R Borsa, JJ Oklu, R Saad, WA AF Nikolic, Boris Rose, Steven C. Ortiz, Jorge Martin, Louis G. Zaki, Radi Borsa, John J. Oklu, Rahmi Saad, Wael A. TI Standards of Reporting for Interventional Radiology Treatment of Renal and Pancreatic Transplantation Complications SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; QUALITY IMPROVEMENT GUIDELINES; VASC INTERV RADIOL; ARTERY-STENOSIS; LOWER-EXTREMITY; POSTOPERATIVE LYMPHOCELES; URETERAL OBSTRUCTIONS; STENT PLACEMENT; SCORING SYSTEM; RISK-FACTORS C1 [Nikolic, Boris] Albert Einstein Med Ctr, Dept Radiol, Philadelphia, PA 19141 USA. [Ortiz, Jorge; Zaki, Radi] Albert Einstein Med Ctr, Dept Transplant Surg, Philadelphia, PA 19141 USA. [Rose, Steven C.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Martin, Louis G.] Emory Univ Hosp, Dept Radiol, Atlanta, GA 30322 USA. [Borsa, John J.] Univ Missouri, St Lukes Hosp, Dept Radiol, Kansas City, MO 64110 USA. [Oklu, Rahmi] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Saad, Wael A.] Univ Virginia, Dept Radiol, Charlottesville, VA USA. RP Nikolic, B (reprint author), Albert Einstein Med Ctr, Dept Radiol, 5501 Old York Rd,Levy Bldg,Ground Floor, Philadelphia, PA 19141 USA. EM nikolicb@einstein.edu FU Siemens (Forchheim, Germany) FX W.A.S. is a paid consultant for Boston Scientific (Natick, Massachusetts), has research funded by Siemens (Forchheim, Germany), and serves on the speakers bureau for Atrium Medical (Corinth, Texas). None of the other authors have identified a conflict of interest. NR 74 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2012 VL 23 IS 12 BP 1547 EP 1556 DI 10.1016/j.jvir.2012.09.009 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 050KG UT WOS:000312051600001 PM 23177100 ER PT J AU Chan, D Downing, D Keough, CE Saad, WA Annamalai, G d'Othee, BJ Ganguli, S Itkin, M Kalva, SP Khan, AA Krishnamurthy, V Nikolic, B Owens, CA Postoak, D Roberts, AC Rose, SC Sacks, D Siddiqi, NH Swan, TL Thornton, RH Towbin, R Wallace, MJ Walker, TG Wojak, JC Wardrope, RR Cardella, JF AF Chan, Danny Downing, Denise Keough, Christine E. Saad, Wael A. Annamalai, Ganesh d'Othee, B. Janne Ganguli, Suvranu Itkin, Maxim Kalva, Sanjeeva P. Khan, Arshad Ahmed Krishnamurthy, Venkataramu Nikolic, Boris Owens, Charles A. Postoak, Darren Roberts, Anne C. Rose, Steven C. Sacks, David Siddiqi, Nasir H. Swan, Timothy L. Thornton, Raymond H. Towbin, Richard Wallace, Michael J. Walker, T. Gregory Wojak, Joan C. Wardrope, Ronald R. Cardella, John F. TI Joint Practice Guideline for Sterile Technique during Vascular and Interventional Radiology Procedures: From the Society of Interventional Radiology, Association of periOperative Registered Nurses, and Association for Radiologic and Imaging Nursing, for the Society of Interventional Radiology (Wael Saad, MD, Chair), Standards of Practice Committee, and Endorsed by the Cardiovascular Interventional Radiological Society of Europe and the Canadian Interventional Radiology Association SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID SURGICAL WOUND INFECTIONS; SKIN; CONTAMINATION; TIME; CATHETERIZATION; DISINFECTION; PREVENTION; EFFICACY; SURGERY; COSTS C1 [Chan, Danny] Univ Texas SW, Dallas, TX USA. [Downing, Denise] Assoc PeriOperat Registered Nurses, Ctr Nursing Practice, Denver, CO USA. [Keough, Christine E.] Univ Rochester, Med Ctr, Dept Imaging Sci, Rochester, NY 14642 USA. [Saad, Wael A.] Univ Virginia Hlth Syst, Dept Radiol, Charlottesville, VA USA. [Annamalai, Ganesh] Sunnybrook Hlth Sci Ctr, Dept Med Imaging, Toronto, ON M4N 3M5, Canada. [d'Othee, B. Janne] Univ Maryland, Sch Med, Dept Radiol, Div Intervent Radiol, Baltimore, MD 21201 USA. [Ganguli, Suvranu] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Walker, T. Gregory] Massachusetts Gen Hosp, Sect Cardiovasc Imaging & Intervent, Boston, MA 02114 USA. [Itkin, Maxim] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Itkin, Maxim] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kalva, Sanjeeva P.] Massachussetts Gen Hosp, Boston, MA USA. [Khan, Arshad Ahmed] Washington Hosp Ctr, Dept Intervent Radiol, Washington, DC 20010 USA. [Krishnamurthy, Venkataramu] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Nikolic, Boris] Albert Einstein Med Ctr, Dept Radiol, Philadelphia, PA 19141 USA. [Owens, Charles A.] Univ Illinois, Med Ctr, Chicago, IL USA. [Postoak, Darren] Univ Florida, Gainesville, FL USA. [Roberts, Anne C.] UCSD Med Ctr, Thornton Hosp, Dept Radiol, La Jolla, CA USA. [Rose, Steven C.] UCSD Med Ctr, Noninvas Vasc Lab, San Diego, CA USA. [Sacks, David] Reading Hosp Med Ctr, Reading, PA USA. [Siddiqi, Nasir H.] St Louis Univ, Sch Med, Dept Radiol, St Louis, MO USA. [Swan, Timothy L.] Marshfield Clin Fdn Med Res & Educ, Dept Radiol, Marshfield, WI USA. [Thornton, Raymond H.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Towbin, Richard] Phoenix Childrens Hosp, Dept Radiol, Phoenix, AZ USA. [Wallace, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Intervent Radiol, Houston, TX 77030 USA. [Wojak, Joan C.] Our Lady Lourdes Reg Med Ctr, Lafayette, LA USA. [Wardrope, Ronald R.] Johns Hopkins Univ Hosp, Dept Pediat Radiol, Baltimore, MD 21287 USA. [Wardrope, Ronald R.] Johns Hopkins Univ Hosp, Dept Pediat Body Computed Tomog, Baltimore, MD 21287 USA. [Wardrope, Ronald R.] Johns Hopkins Univ Hosp, Dept Nucl Med, Baltimore, MD 21287 USA. [Cardella, John F.] Geisinger Hlth Syst, Dept Syst Radiol, Danville, PA USA. RP Chan, D (reprint author), Care of Katsarelis D, 3975 Fair Ridge Dr,Ste 400 N, Fairfax, VA 22033 USA. FU Siemens Medical FX M.J.W. received research support from Siemens Medical. None of the other authors have identified a conflict of interest. NR 58 TC 11 Z9 11 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2012 VL 23 IS 12 BP 1603 EP 1612 DI 10.1016/j.jvir.2012.07.017 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 050KG UT WOS:000312051600009 PM 23177106 ER PT J AU Egan, KR Gleason, CE AF Egan, Kelly R. Gleason, Carey E. TI Longer Duration of Hormonal Contraceptive Use Predicts Better Cognitive Outcomes Later in Life SO JOURNAL OF WOMENS HEALTH LA English DT Article ID CONJUGATED EQUINE ESTROGENS; HEALTH INITIATIVE MEMORY; POSTMENOPAUSAL WOMEN; ALZHEIMERS-DISEASE; ORAL-CONTRACEPTIVES; REPLACEMENT THERAPY; ABILITIES; BRAIN; SEX; PERFORMANCE AB Background: The cognitive effects of postmenopausal hormone therapy (HT) have been studied extensively, but little is known about the relationship between premenopausal hormone use and cognition. Hormonal contraceptive use vs. nonuse may be a potential factor influencing cognitive processes in midlife. The aim of this study is to explore the effect of modification of hormone milieu through use of hormonal contraception in premenopausal women and midlife cognitive function. Methods: Subjects were 261 cognitively normal women, aged 40-65 (mean mu = 52), enrolled in the Wisconsin Registry for Alzheimer's Prevention. All women completed the Women's Health History Questionnaire and a self-report health history questionnaire and were administered a battery of neuropsychologic tests. Cognitive results were analyzed using summary scores for the domains of Verbal Ability, Visuo-spatial Ability, Working Memory, Verbal Learning & Memory, and Speed & Flexibility derived using a confirmatory factor analysis. Results: Hormonal contraceptive ever users performed significantly better than never users in the domains of Visuo-spatial Ability (mu = 0.75, 95% confidence interval [CI] 0.23-1.28, p = 0.005) and Speed & Flexibility (mu = 0.52, 95% CI -0.16-1.04, p = 0.007), with duration-dependent increases in performance, especially in ever users with >= 15 years of use. Conclusions: These data provide preliminary evidence that hormonal contraceptive use may influence cognitive outcomes, even years after use is discontinued. Hormonal contraceptive users scored better in domains of Visuo-spatial Ability and Speed & Flexibility than never users, with a duration-dependent trend. Further research is needed to explore the use of hormonal contraceptives to prevent or delay cognitive decline and to clarify the physiologic basis of this phenomenon. C1 [Egan, Kelly R.] Univ Wisconsin, Sch Med & Publ Hlth, Hlth Sci Learning Ctr, Madison, WI 53705 USA. [Gleason, Carey E.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Egan, KR (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Hlth Sci Learning Ctr, 750 Highland Ave, Madison, WI 53705 USA. EM kellyegan@wisc.edu RI Egan Huibregtse, Kelly/F-9947-2013 OI Egan Huibregtse, Kelly/0000-0001-5798-9743 FU National Institutes of Health (NIH) [R01 AG027161]; Wisconsin Alzheimer's Disease Research Center [NIH-NIA P50 AG033514] FX This research was supported by National Institutes of Health (NIH) Research Project grant R01 AG027161 and the Wisconsin Alzheimer's Disease Research Center (NIH-NIA P50 AG033514). We thank Drs. Whitney Wharton, Mark Sagar, Asenath LaRue, and Bruce Hermann and Ms. Janet Rowley for their hard work in coordinating and carrying out data collection. We are grateful to Dr. Norca Maritza Dowling, who conducted the factor analysis and developed the factor scores, and Dr. Ron Gangnon for his advice and guidance on statistical analysis. Thank you for the support of the staff of the William S. Middleton Memorial Veterans Hospital and to all Wisconsin Registry for Alzheimer's Prevention study participants. NR 50 TC 4 Z9 4 U1 1 U2 20 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD DEC PY 2012 VL 21 IS 12 BP 1259 EP 1266 DI 10.1089/jwh.2012.3522 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 049AT UT WOS:000311955100009 PM 22994984 ER PT J AU Sahin-Efe, A Katsikeris, F Mantzoros, CS AF Sahin-Efe, A. Katsikeris, F. Mantzoros, Christos S. TI Advances in adipokines SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID ADIPONECTIN CONCENTRATIONS; INFLAMMATORY CYTOKINES; SERUM ADIPONECTIN; LEPTIN; RISK; EXPRESSION; RECEPTORS; CHILDREN; GROWTH; VASPIN C1 [Sahin-Efe, A.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Sch Med, Boston, MA 02215 USA. RP Sahin-Efe, A (reprint author), Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu NR 39 TC 31 Z9 33 U1 0 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 2012 VL 61 IS 12 BP 1659 EP 1665 DI 10.1016/j.metabol.2012.09.001 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050LB UT WOS:000312053700001 PM 23021039 ER PT J AU Huh, JY Panagiotou, G Mougios, V Brinkoetter, M Vamvini, MT Schneider, BE Mantzoros, CS AF Huh, Joo Young Panagiotou, Grigorios Mougios, Vassilis Brinkoetter, Mary Vamvini, Maria T. Schneider, Benjamin E. Mantzoros, Christos S. TI FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Irisin; FNDC5; Exercise; Weight loss ID ENERGY DEPRIVATION ALTERS; BROWN ADIPOSE-TISSUE; SKELETAL-MUSCLE; INSULIN-RESISTANCE; PHYSICAL-ACTIVITY; GLUCOSE-HOMEOSTASIS; INDEPENDENT MANNER; ACTIVIN-A; LEPTIN; OBESITY AB Objective. In mouse, PGC1-alpha overexpression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. One prior study has shown that FNDC5 induces browning of subcutaneous fat in mice and mediates beneficial effects of exercise on metabolism, but a more recent study using gene expression arrays failed to detect a robust increase in FNDC5 mRNA in human muscles from exercising subjects. No prior study has reported on the physiological regulation and role of circulating irisin and FNDC5 in humans. Materials/Methods. A. FNDC5 gene expression studies: We first examined tissue distribution of FNDC5 in humans. B. Cross-sectional studies: Predictors of FNDC5 mRNA expression levels were examined in muscle tissues from 18 healthy subjects with a wide range of BMI. Assays were optimized to measure circulating FNDC5 and irisin levels, and their associations with anthropometric and metabolic parameters were analyzed in two cross-sectional studies that examined 117 middle-aged healthy women and 14 obese subjects, respectively. C. Interventional studies: The effect of weight loss on FNDC5 mRNA and/or circulating irisin levels was examined in 14 obese subjects before and after bariatric surgery. The effect of acute and chronic exercise was then assessed in 15 young healthy adults who performed intermittent sprint running sessions over an 8 week period. Results. Tissue arrays demonstrated that in humans, the FNDC5 gene is predominantly expressed in muscle. Circulating irisin was detected in the serum or plasma of all subjects studied, whereas circulating FNDC5 was detected in only a distinct minority of the subjects. Cross-sectional studies revealed that circulating irisin levels were positively correlated with biceps circumference (used as a surrogate marker of muscle mass herein), BMI, glucose, ghrelin, and IGF-1. In contrast, irisin levels were negatively correlated with age, insulin, cholesterol, and adiponectin levels, indicating a possible compensatory role of irisin in metabolic regulation. Multivariate regression analysis revealed that biceps circumference was the strongest predictor of circulating irisin levels underlying the association between irisin and metabolic factors in humans at baseline. Both muscle FNDC5 mRNA levels and circulating irisin levels were significantly downregulated 6months after bariatric surgery. Circulating irisin levels were significantly upregulated 30min after acute exercise and were correlated mainly with ATP levels and secondarily with metabolites related to glycolysis and lipolysis in muscle. Conclusions. Similar to mice, the FNDC5 gene is expressed in human muscle. Age and muscle mass are the primary predictors of circulating irisin, with young male athletes having several fold higher irisin levels than middle-aged obese women. Circulating irisin levels increase in response to acute exercise whereas muscle FNDC5 mRNA and circulating irisin levels decrease after surgically induced weight loss in parallel to decrease in body mass. Further studies are needed to study the regulation of irisin levels and its physiological effects in humans and to elucidate the mechanisms underlying these effects. Published by Elsevier Inc. C1 [Huh, Joo Young; Panagiotou, Grigorios; Brinkoetter, Mary; Vamvini, Maria T.; Mantzoros, Christos S.] Harvard Univ, Sch Med, BethIsrael Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Mougios, Vassilis] Aristotle Univ Thessaloniki, Dept Phys Educ & Sports Sci, Thessaloniki 54124, Greece. [Schneider, Benjamin E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Minimally Invas Surg, Sch Med, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Endocrinol Sect, Boston VA Healthcare Syst, Sch Med, Boston, MA 02130 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, JP9B52A, Boston, MA 02130 USA. EM cmantzor@bidmc.harvard.edu OI Panagiotou, Grigorios/0000-0003-0690-1478 FU National Institute of Diabetes and Digestive and Kidney Diseases [8785, 79929, 81913]; Clinical Science Research and Development Service of the VA Office of Research and Development [1101CX000422-01A1] FX The Mantzoros Laboratory is supported by the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785, 79929 and 81913 as well as Award Number 1101CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. NR 31 TC 271 Z9 301 U1 10 U2 98 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 2012 VL 61 IS 12 BP 1725 EP 1738 DI 10.1016/j.metabol.2012.09.002 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050LB UT WOS:000312053700010 PM 23018146 ER PT J AU Metes-Kosik, N Luptak, I DiBello, PM Handy, DE Tang, SS Zhi, H Qin, FZ Jacobsen, DW Loscalzo, J Joseph, J AF Metes-Kosik, Nicole Luptak, Ivan DiBello, Patricia M. Handy, Diane E. Tang, Shiow-Shih Zhi, Hui Qin, Fuzhong Jacobsen, Donald W. Loscalzo, Joseph Joseph, Jacob TI Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE Collagen; Homocysteine; Methylation; Oxidant Stress; Selenium ID ABERRANT CRYPT FORMATION; CHRONIC HEART-FAILURE; DIETARY SELENIUM; DNA METHYLATION; KESHAN-DISEASE; RAT-LIVER; HOMOCYSTEINE CONCENTRATIONS; HYPERHOMOCYSTEINEMIA LEADS; ENDEMIC CARDIOMYOPATHY; PLASMA HOMOCYSTEINE AB Scope Selenium has complex effects in vivo on multiple homeostatic mechanisms such as redox balance, methylation balance, and epigenesis, via its interaction with the methionine-homocysteine cycle. In this study, we examined the hypothesis that selenium status would modulate both redox and methylation balance and thereby modulate myocardial structure and function. Methods and results We examined the effects of selenium-deficient (<0.025 mg/kg), control (0.15 mg/kg), and selenium-supplemented (0.5 mg/kg) diets on myocardial histology, biochemistry and function in adult C57/BL6 mice. Selenium deficiency led to reactive myocardial fibrosis and systolic dysfunction accompanied by increased myocardial oxidant stress. Selenium supplementation significantly reduced methylation potential, DNA methyltransferase activity and DNA methylation. In mice fed the supplemented diet, inspite of lower oxidant stress, myocardial matrix gene expression was significantly altered resulting in reactive myocardial fibrosis and diastolic dysfunction in the absence of myocardial hypertrophy. Conclusion Our results indicate that both selenium deficiency and modest selenium supplementation leads to a similar phenotype of abnormal myocardial matrix remodeling and dysfunction in the normal heart. The crucial role selenium plays in maintaining the balance between redox and methylation pathways needs to be taken into account while optimizing selenium status for prevention and treatment of heart failure. C1 [Joseph, Jacob] VA Boston Healthcare Syst, Cardiol Sect 111, W Roxbury, MA 02132 USA. [Luptak, Ivan; Qin, Fuzhong; Joseph, Jacob] Boston Univ, Sch Med, Boston, MA 02118 USA. [DiBello, Patricia M.; Jacobsen, Donald W.] Cleveland Clin, Dept Cell Biol, Lerner Res Inst, Cleveland, OH 44106 USA. [Handy, Diane E.; Tang, Shiow-Shih; Zhi, Hui; Loscalzo, Joseph; Joseph, Jacob] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Jacobsen, Donald W.] Case Western Reserve Univ, Cleveland Clin, Dept Mol Med, Lerner Coll Med, Cleveland, OH USA. RP Joseph, J (reprint author), VA Boston Healthcare Syst, Cardiol Sect 111, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM jjoseph16@partners.org OI Luptak, Ivan/0000-0001-7498-7694 FU National Institutes of Health [HL89734, HL52234, HL61795, HL70819, HL48743, HL107192, HL108630] FX This work was supported by the National Institutes of Health (grant number HL89734 to J. Joseph), (grant number HL52234 to D. W. Jacobsen), and (grant numbers HL61795, HL70819, HL48743, HL107192, and HL108630 to J. Loscalzo). NR 60 TC 25 Z9 25 U1 0 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD DEC PY 2012 VL 56 IS 12 BP 1812 EP 1824 DI 10.1002/mnfr.201200386 PG 13 WC Food Science & Technology SC Food Science & Technology GA 051MV UT WOS:000312132300008 PM 23097236 ER PT J AU Shalek, AK Gaublomme, JT Wang, LL Yosef, N Chevrier, N Andersen, MS Robinson, JT Pochet, N Neuberg, D Gertner, RS Amit, I Brown, JR Hacohen, N Regev, A Wu, CJ Park, H AF Shalek, Alex K. Gaublomme, Jellert T. Wang, Lili Yosef, Nir Chevrier, Nicolas Andersen, Mette S. Robinson, Jacob T. Pochet, Nathalie Neuberg, Donna Gertner, Rona S. Amit, Ido Brown, Jennifer R. Hacohen, Nir Regev, Aviv Wu, Catherine J. Park, Hongkun TI Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia SO NANO LETTERS LA English DT Article DE Nanowires; delivery; immune cells; perturbation; chronic lymphocytic leukemia ID GENE-EXPRESSION SIGNATURE; EMBRYONIC STEM; CLL CELLS; TGF-BETA; B-CELLS; CANCER; BIOMOLECULES; PHENOTYPE; APOPTOSIS; TOXICITY AB A circuit level understanding of immune cells and hematological cancers has been severely impeded by a lack of techniques that enable intracellular perturbation without significantly altering cell viability and function. Here, we demonstrate that vertical silicon nanowires (NWs) enable gene-specific manipulation of diverse murine and human immune cells with negligible toxicity. To illustrate the power of the technique, we then apply NW-mediated gene silencing to investigate the role of the Wnt signaling pathway in chronic lymphocytic leukemia (CLL). Remarkably, CLL-B cells from different patients exhibit tremendous heterogeneity in their response to the knockdown of a single gene, LEF1. This functional heterogeneity defines three distinct patient groups not discernible by conventional CLL cytogenetic markers and provides a prognostic indicator for patients' time to first therapy. Analyses of gene expression signatures associated with these functional patient subgroups reveal unique insights into the underlying molecular basis for disease heterogeneity. Overall, our findings suggest a functional classification that can potentially guide the selection of patient-specific therapies in CLL and highlight the opportunities for nanotechnology to drive biological inquiry. C1 [Shalek, Alex K.; Gaublomme, Jellert T.; Robinson, Jacob T.; Gertner, Rona S.; Park, Hongkun] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Andersen, Mette S.; Park, Hongkun] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Wang, Lili; Brown, Jennifer R.; Wu, Catherine J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Wang, Lili; Wu, Catherine J.] Canc Vaccine Ctr, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Yosef, Nir; Chevrier, Nicolas; Pochet, Nathalie; Amit, Ido; Hacohen, Nir; Regev, Aviv] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Regev, Aviv] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02140 USA. RP Park, H (reprint author), Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA. EM Hongkun_Park@harvard.edu OI Shalek, Alex K./0000-0001-5670-8778 FU NIH [5DP1OD003893-03, 1P50HG006193-01, U54 AI057159, DP2 OD002230]; Broad Institute; Blavatnik Family Foundation; Damon-Runyon Cancer Research Foundation [CI-38-07]; AACR; HHMI; NHLBI [1RO1HL103532-01]; NCI [1R01CA155010-01A1]; Merkin Foundation for Stem Cell Research at the Broad Institute; FWO; American Society of Hematology; Leukemia and Lymphoma Society FX H.P. was supported by an NIH Pioneer Award (5DP1OD003893-03), an NIH CEGS Award (1P50HG006193-01), and the Broad Institute. C.J.W. was supported by the Blavatnik Family Foundation, the Damon-Runyon Cancer Research Foundation (CI-38-07), an AACR SU2C Innovative Research Grant, HHMI Early Physician-Scientist Career Development Award, NHLBI (1RO1HL103532-01) and NCI (1R01CA155010-01A1). A.R. was supported by an NIH Pioneer Award, an NIH CEGS Award (1P50HG006193-01), HHMI, and the Merkin Foundation for Stem Cell Research at the Broad Institute. N.P. was supported by an FWO fellowship. N.H. was supported by an NIH grant (U54 AI057159) and an NIH New Innovator Award (DP2 OD002230). J.R.B. was supported by the American Society of Hematology and the Leukemia and Lymphoma Society. N.P. is a Broad Fellow of the Broad Institute and a postdoctoral research fellow of the Fund for Scientific Research Flanders (FWO Vlaanderen), Belgium. H.P., C.J.W., A.R, and N.H. conceived the ideas and directed the work. AS., C.W., and H.P. designed research. A.S., J.G., MA., N.C., J.R., L.W., R.G., N.Y., and I.A. performed experiments. A.S., J.G., and H.P. wrote the manuscript; all authors read and edited the manuscript extensively. doubt in NR 41 TC 55 Z9 55 U1 0 U2 47 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD DEC PY 2012 VL 12 IS 12 BP 6498 EP 6504 DI 10.1021/nl3042917 PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 051JI UT WOS:000312122100075 PM 23190424 ER PT J AU Uygun, BE Yarmush, ML Uygun, K AF Uygun, Basak E. Yarmush, Martin L. Uygun, Korkut TI Application of whole-organ tissue engineering in hepatology SO NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY LA English DT Article ID PLURIPOTENT STEM-CELLS; ACUTE LIVER-FAILURE; EXTRACELLULAR-MATRIX; REGENERATIVE MEDICINE; STEM/PROGENITOR CELLS; DECELLULARIZED MATRIX; RAT-LIVER; TRANSPLANTATION; SCAFFOLDS; HEPATOCYTES AB Initially hailed as the ultimate solution to organ failure, engineering of vascularized tissues such as the liver has stalled because of the need for a well-structured circulatory system that can maintain the cells seeded inside the construct. A new approach has evolved to overcome this obstacle. Whole-organ decellularization is a method that retains most of the native vascular structures of the organ, providing microcirculatory support and structure, which can be anastomosed with the recipient circulation. The technique was first applied to the heart and then adapted for the liver. Several studies have shown that cells can be eliminated, the extracellular matrix and vasculature are reasonably preserved and, after repopulation with hepatocytes, these grafts can perform hepatic functions in vitro and in vivo. Progress is rapidly being made as researchers are addressing several key challenges to whole-organ tissue engineering, such as ensuring correct cell distribution, nonparenchymal cell seeding, blood compatibility, immunological concerns, and the source of cells and matrices. Uygun, B. E. et al. Nat. Rev. Gastroenterol. Hepatol. 9, 738-744 (2012); published online 14 August 2012; doi:10.1038/nrgastro.2012.140 C1 [Uygun, Basak E.; Yarmush, Martin L.; Uygun, Korkut] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Uygun, Basak E.; Yarmush, Martin L.; Uygun, Korkut] Shriners Hosp Children, Boston, MA 02114 USA. RP Uygun, BE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM uygun.korkut@mgh.harvard.edu RI Uygun, Basak/I-1792-2012 OI Uygun, Basak/0000-0002-2600-7900 FU National Institutes of Health [R01DK084053, R01DK096075R01, K99DK088962]; National Science Foundation [CBET 0853569]; Shriners Hospitals for Children FX Funding from the National Institutes of Health (R01DK084053, R01DK096075R01, K99DK088962), National Science Foundation (CBET 0853569) and the Shriners Hospitals for Children are gratefully acknowledged. NR 64 TC 20 Z9 23 U1 0 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5045 J9 NAT REV GASTRO HEPAT JI Nat. Rev. Gastroenterol. Hepatol. PD DEC PY 2012 VL 9 IS 12 BP 738 EP 744 DI 10.1038/nrgastro.2012.140 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 048XI UT WOS:000311946100009 PM 22890112 ER PT J AU Elmer, J Pallin, DJ Liu, S Pearson, C Chang, YC Camargo, CA Greenberg, SM Rosand, J Goldstein, JN AF Elmer, Jonathan Pallin, Daniel J. Liu, Shan Pearson, Catherine Chang, Yuchiao Camargo, Carlos A., Jr. Greenberg, Steven M. Rosand, Jonathan Goldstein, Joshua N. TI Prolonged Emergency Department Length of Stay is not Associated with Worse Outcomes in Patients with Intracerebral Hemorrhage SO NEUROCRITICAL CARE LA English DT Article DE Emergency medicine; Emergency department crowding; Emergency department length of stay; Intracerebral hemorrhage ID ACUTE MYOCARDIAL-INFARCTION; CRITICALLY-ILL PATIENTS; NOT-RESUSCITATE ORDERS; PERFORMANCE-MEASURES; MECHANICAL VENTILATION; HEMATOMA EXPANSION; MEDICAL PATIENTS; DELAYED TRANSFER; STROKE PATIENTS; UNITED-STATES AB Background Prolonged emergency department length of stay (EDLOS) has been associated with worse patient outcomes, longer inpatient stays, and failure to meet quality measures in several acute medical conditions, but these findings have not been consistently reproduced. We performed this study to explore the hypothesis that longer EDLOS would be associated with worse outcomes in a large cohort of patients presenting with spontaneous intracerebral hemorrhage (ICH). Methods We performed a secondary analysis of a prospective cohort of consecutive patients with spontaneous ICH who presented to a single academic referral center from February 2005 to October 2009. The primary exposure variable was EDLOS, and our primary outcome was neurologic status at hospital discharge, measured with a modified Rankin scale (mRS). Secondary outcomes were ICU length of stay, total hospital length of stay, and total hospital costs. Results Our cohort included 616 visits of which 42 were excluded, leaving 574 patient encounters for analysis. Median age was 75 years (IQR 63-82), median EDLOS 5.1 h (IQR 3.7-7.1) and median discharge mRS 4 (IQR 3-6). Thirty percent of the subjects died in-hospital. Multivariable proportional odds logistic regression, controlling for age, initial Glasgow Coma Scale, initial hematoma volume, ED occupancy at registration, and the need for intubation or surgical intervention, demonstrated no association between EDLOS and outcome. Furthermore, multivariable analysis revealed no association of increased EDLOS with ICU or hospital length of stay or hospital costs. Conclusion We found no effect of EDLOS on neurologic outcome or resource utilization for patients presenting with spontaneous ICH. C1 [Elmer, Jonathan; Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Pallin, Daniel J.] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. [Elmer, Jonathan; Liu, Shan; Pearson, Catherine; Camargo, Carlos A., Jr.; Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Elmer, J (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM jelmer@partners.org RI Pallin, Daniel/H-6382-2013; Goldstein, Joshua/H-8953-2016 OI Pallin, Daniel/0000-0002-8517-9702; FU National Institute of Neurologic Disorders and Stroke [NINDS-NS059774]; Massachusetts College of Emergency Physicians Resident Research Grant FX The authors gratefully acknowledge the financial support that this study received from The National Institute of Neurologic Disorders and Stroke (NINDS-NS059774) and the Massachusetts College of Emergency Physicians Resident Research Grant. NR 64 TC 6 Z9 8 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD DEC PY 2012 VL 17 IS 3 BP 334 EP 342 DI 10.1007/s12028-011-9629-1 PG 9 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 050QP UT WOS:000312069400004 PM 21912953 ER PT J AU Battey, TWK Falcone, GJ Ayres, AM Schwab, K Viswanathan, A McNamara, KA DiPucchio, ZY Greenberg, SM Sheth, KN Goldstein, JN Rosand, J AF Battey, Thomas W. K. Falcone, Guido J. Ayres, Alison M. Schwab, Kristin Viswanathan, Anand McNamara, Kristen A. DiPucchio, Zora Y. Greenberg, Steven M. Sheth, Kevin N. Goldstein, Joshua N. Rosand, Jonathan TI Confounding by Indication in Retrospective Studies of Intracerebral Hemorrhage: Antiepileptic Treatment and Mortality SO NEUROCRITICAL CARE LA English DT Article DE Intracerebral hemorrhage; Antiepileptic; Outcome; Confounding; Confounding by indication ID SEIZURES; DRUG AB Introduction Intracerebral hemorrhage (ICH) is a highly fatal disease with few proven treatments. Data to guide clinician decisions for therapies, including antiepileptic drugs (AED), are limited. Published studies on AED treatment in ICH have provided conflicting results. We investigated the effect of AED treatment on 90-day mortality after ICH in a large prospectively ascertained cohort. Methods We conducted a retrospective analysis of a prospectively assembled cohort of patients with ICH in the supratentorial regions, comparing 90-day mortality and modified Rankin Score among 543 patients treated with AED during hospitalization and 639 AED-free ICH. Supratentorial ICH location was categorized as lobar or deep hemispheric. Results Multivariate analysis demonstrated an association between AED treatment and reduced 90-day mortality in supratentorial ICH (OR = 0.62, 95 % CI 0.42-0.90, p = 0.01) and the subset of lobar ICH (OR = 0.49, 95 % CI 0.25-0.96, p = 0.04). When analyses were restricted to subjects surviving longer than 5 days from ICH, however, no association between AED treatment and a 90-day outcome, regardless of hemorrhage location (all p > 0.15), was detected, despite more than adequate power to detect the originally observed association. Conclusion These results suggest that AED treatment in acute ICH is not associated with 90-day mortality or outcome and that any detected association could arise by confounding by indication, in which the most severely affected patients are those in whom AEDs are prescribed. They provide a cautionary example of the limitations of drawing conclusions about treatment effects from observational data. C1 [Battey, Thomas W. K.; Falcone, Guido J.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Sheth, Kevin N.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Battey, Thomas W. K.; Falcone, Guido J.; Ayres, Alison M.; Schwab, Kristin; Viswanathan, Anand; McNamara, Kristen A.; DiPucchio, Zora Y.; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Battey, Thomas W. K.; Falcone, Guido J.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM jrosand@partners.org RI Goldstein, Joshua/H-8953-2016; Falcone, Guido/L-2287-2016; OI Falcone, Guido/0000-0002-6407-0302; Ayres, Alison/0000-0002-5492-1695 FU National Institute for Neurological Disease and Stroke [RO1NS059727, NIH R01NS073344, NIH K23NS059774] FX This work was funded by the National Institute for Neurological Disease and Stroke RO1NS059727, NIH R01NS073344, NIH K23NS059774. The authors thank Shawn Murphy and Henry Chueh and the Partners Health Care Research Patient Data Registry group for facilitating use of their database. NR 12 TC 9 Z9 9 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD DEC PY 2012 VL 17 IS 3 BP 361 EP 366 DI 10.1007/s12028-012-9776-z PG 6 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 050QP UT WOS:000312069400008 PM 22965324 ER PT J AU Brouwers, HB Falcone, GJ McNamara, KA Ayres, AM Oleinik, A Schwab, K Romero, JM Viswanathan, A Greenberg, SM Rosand, J Goldstein, JN AF Brouwers, H. Bart Falcone, Guido J. McNamara, Kristen A. Ayres, Alison M. Oleinik, Alexandra Schwab, Kristin Romero, Javier M. Viswanathan, Anand Greenberg, Steven M. Rosand, Jonathan Goldstein, Joshua N. TI CTA Spot Sign Predicts Hematoma Expansion in Patients with Delayed Presentation After Intracerebral Hemorrhage SO NEUROCRITICAL CARE LA English DT Article DE Intracerebral hemorrhage; CT angiography; CTA spot sign; Hematoma expansion; Late presentation ID ACTIVATED FACTOR-VII; BLOOD-PRESSURE REDUCTION; CONTRAST EXTRAVASATION; IDENTIFIES PATIENTS; HEMOSTATIC THERAPY; HIGHEST RISK; MORTALITY; GROWTH; TRIAL; SCORE AB Background Hematoma expansion after acute intracerebral hemorrhage occurs most frequently in patients presenting within 3 h of symptom onset. However, the majority of patients present outside this window or with an unknown onset time. We investigated the prevalence of hematoma expansion in these patients and assessed the accuracy of the CT angiography (CTA) spot sign for identifying risk of hematoma expansion. Methods We analyzed 391 consecutive patients undergoing CTA and a followup CT. CTA spot sign readings were performed by two experienced readers and hematoma expansion was assessed by means of semi-automated software. Results Hematoma expansion occurred in 18 % of patients. When stratified by time from symptom onset to initial CT, hematoma expansion rates were: 39 % within 3 h; 11 % between 3 and 6 h, 11 % beyond 6 h (but with known onset), and 20 % in patients with unknown symptom onset. Of patients who developed hematoma expansion, only 38 % presented within 3 h. The accuracy of the spot sign in predicting hematoma expansion was 0.67 for patients presenting within 3 h, 0.83 between 3 and 6 h, 0.88 after 6 h, and 0.76 for patients presenting with an unknown onset time. Conclusions A substantial number of patients destined to suffer from hematoma expansion present either late or with an unknown symptom onset time. The CTA spot sign accurately identifies patients destined to expand regardless of time from symptom onset, and may therefore open a path to offer clinical trials and novel therapies to the many patients who do not present acutely. C1 [Brouwers, H. Bart; Falcone, Guido J.; Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Rosand Lab, Boston, MA 02114 USA. [Brouwers, H. Bart; McNamara, Kristen A.; Ayres, Alison M.; Oleinik, Alexandra; Schwab, Kristin; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan; Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Brouwers, H. Bart; Falcone, Guido J.; Viswanathan, Anand; Rosand, Jonathan; Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neurocrit Care & Emergency Neurol,Dept Neurol, Boston, MA 02114 USA. [Romero, Javier M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Serv,Dept Radiol, Boston, MA 02114 USA. [Brouwers, H. Bart; Falcone, Guido J.; McNamara, Kristen A.; Ayres, Alison M.; Oleinik, Alexandra; Schwab, Kristin; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan; Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. RP Brouwers, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Rosand Lab, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM brouwers@chgr.mgh.harvard.edu RI Goldstein, Joshua/H-8953-2016; Falcone, Guido/L-2287-2016; OI Falcone, Guido/0000-0002-6407-0302; Ayres, Alison/0000-0002-5492-1695 FU National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) [R01NS073344, R01NS059727, 5K23NS059774]; American Heart Association [0755984T]; NIH-NINDS SPOTRIAS [P50NS051343]; NIH FX All funding entities had no involvement in study design, data collection, analysis and interpretation, writing of the manuscript, and in the decision to submit for publication. The project described was supported by the Grant Numbers R01NS073344, R01NS059727, and 5K23NS059774 from the National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) and the American Heart Association Grant Number 0755984T. Dr. Brouwers was supported by the NIH-NINDS SPOTRIAS fellowship grant P50NS051343. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health.; H. B. Brouwers, none; G.J. Falcone, none; K. A. McNamara, none; A. M. Ayres, none; A. Oleinik, none; K. Schwab, none; J.M. Romero, Imaging Committee DIAS trial/advisory board Lundbeck pharmaceuticals; A. Viswanathan, none; S. M. Greenberg, Research Grant NIH, Honoraria: Medtronic, Pfizer, Consultant/advisory board: Hoffman-La Roche, Janssen Alzheimer Immunotherapy, Bristol-Myers Squibb Company; J. Rosand, Research Grant NIH and American Heart Association; J.N. Goldstein, Research Grant NIH-NINDS, Consultant/advisory board CSL Behring. NR 23 TC 29 Z9 32 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD DEC PY 2012 VL 17 IS 3 BP 421 EP 428 DI 10.1007/s12028-012-9765-2 PG 8 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 050QP UT WOS:000312069400017 PM 22878870 ER PT J AU Lieberman, J Wheeler, LA Trifonova, R Vrbanac, V Basar, E McKernan, S Xu, Z Seung, E Deruaz, M Dudek, T Allen, TM Luster, AD Tager, AM Dykxhoorn, DM AF Lieberman, J. Wheeler, L. A. Trifonova, R. Vrbanac, V. Basar, E. McKernan, S. Xu, Z. Seung, E. Deruaz, M. Dudek, T. Allen, T. M. Luster, A. D. Tager, A. M. Dykxhoorn, D. M. TI Knocking Down HIV Transmission Using CD4 Aptamer-siRNAs SO NUCLEIC ACID THERAPEUTICS LA English DT Meeting Abstract CT 8th Annual Meeting of the Oligonucleotide-Therapeutics-Society CY OCT 28-31, 2012 CL Boston, MA SP Oligonucleotide Therapeut Soc C1 [Lieberman, J.; Wheeler, L. A.; Trifonova, R.; Basar, E.; McKernan, S.; Xu, Z.; Dykxhoorn, D. M.] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Cambridge, MA 02138 USA. [Vrbanac, V.; Seung, E.; Deruaz, M.; Luster, A. D.; Tager, A. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015; Allen, Todd/F-5473-2011 NR 0 TC 1 Z9 1 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2159-3337 J9 NUCLEIC ACID THER JI Nucl. Acid Ther. PD DEC PY 2012 VL 22 IS 6 MA 32 BP A11 EP A11 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Research & Experimental Medicine GA 047IJ UT WOS:000311832900033 ER PT J AU Yonekawa, Y Jakobiec, FA Zakka, FR Fay, A AF Yonekawa, Yoshihiro Jakobiec, Frederick A. Zakka, Fouad R. Fay, Aaron TI Sebaceoma of the Eyelid SO OPHTHALMOLOGY LA English DT Letter ID TUMORS; LESIONS C1 [Yonekawa, Yoshihiro; Jakobiec, Frederick A.; Zakka, Fouad R.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Yonekawa, Yoshihiro; Fay, Aaron] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Oculoplast Surg,Dept Ophthalmol, Boston, MA USA. RP Yonekawa, Y (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2012 VL 119 IS 12 BP 2645 EP + PG 6 WC Ophthalmology SC Ophthalmology GA 049AL UT WOS:000311954300033 ER PT J AU Lee, JJ Waak, K Grosse-Sundrup, M Xue, FF Lee, J Chipman, D Ryan, C Bittner, EA Schmidt, U Eikermann, M AF Lee, Jeanette J. Waak, Karen Grosse-Sundrup, Martina Xue, Feifei Lee, Jarone Chipman, Daniel Ryan, Cheryl Bittner, Edward A. Schmidt, Ulrich Eikermann, Matthias TI Global Muscle Strength But Not Grip Strength Predicts Mortality and Length of Stay in a General Population in a Surgical Intensive Care Unit SO PHYSICAL THERAPY LA English DT Article ID CRITICALLY-ILL PATIENTS; CRITICAL ILLNESS POLYNEUROPATHY; ICU-ACQUIRED PARESIS; ACUTE-RENAL-FAILURE; HANDGRIP STRENGTH; RISK-FACTORS; INTEROBSERVER AGREEMENT; HOSPITAL MORTALITY; ORGAN FAILURE; ADMISSION HYPERGLYCEMIA AB Background. Paresis acquired in the intensive care unit (ICU) is common in patients who are critically ill and independently predicts mortality and morbidity. Manual muscle testing (MMT) and handgrip dynamometry assessments have been used to evaluate muscle weakness in patients in a medical ICU, but similar data for patients in a surgical ICU (SICU) are limited. Objective. The purpose of this study was to evaluate the predictive value of strength measured by MMT and handgrip dynamometry at ICU admission for in-hospital mortality, SICU length of stay (LOS), hospital LOS, and duration of mechanical ventilation. Design. This investigation was a prospective, observational study. Methods. One hundred ten patients were screened for eligibility for testing in the SICU of a large, academic medical center. The Acute Physiology and Chronic Health Evaluation (APACHE) II score, diagnoses, and laboratory data were collected. Measurements were obtained by MMT quantified with the sum (total) score on the Medical Research Council Scale and by handgrip dynamometry. Outcome data, including in-hospital mortality, SICU LOS, hospital LOS, and duration of mechanical ventilation, were collected for all participants. Results. One hundred seven participants were eligible for testing; 89% were tested successfully at a median of 3 days (25th-75th percentiles=3-6 days) after admission. Sedation was the most frequent barrier to testing (70.6%). Manual muscle testing was identified as an independent predictor of mortality, SICU LOS, hospital LOS,. and duration of mechanical ventilation. Grip strength was not independently associated with these outcomes. Limitations. This study did not address whether muscle weakness translates to functional outcome impairment. Conclusions. In contrast to handgrip strength, MMT reliably predicted in-hospital mortality, duration of mechanical ventilation, SICU LOS, and hospital LOS. C1 [Waak, Karen] Massachusetts Gen Hosp, Dept Phys & Occupat Therapy Serv, Boston, MA 02114 USA. [Lee, Jeanette J.; Grosse-Sundrup, Martina; Xue, Feifei; Lee, Jarone; Bittner, Edward A.; Schmidt, Ulrich; Eikermann, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Eikermann, Matthias] Essen Duisburg Univ, Klin Anaesthesiol & Intens Med, Essen, Germany. [Chipman, Daniel] Massachusetts Gen Hosp, Dept Resp Care Serv, Boston, MA 02114 USA. [Ryan, Cheryl] Massachusetts Gen Hosp, Dept Clin Nursing Serv, Boston, MA 02114 USA. RP Waak, K (reprint author), Massachusetts Gen Hosp, Dept Phys & Occupat Therapy Serv, 15 Parkman St,WACC 136, Boston, MA 02114 USA. EM kwaak@partners.org OI Lee, Jarone/0000-0002-4532-8523 NR 50 TC 21 Z9 21 U1 1 U2 10 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD DEC PY 2012 VL 92 IS 12 BP 1546 EP 1555 DI 10.2522/ptj.20110403 PG 10 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 050KJ UT WOS:000312051900009 PM 22976446 ER PT J AU Maguen, S Madden, E Cohen, BE Bertenthal, D Seal, KH AF Maguen, Shira Madden, Erin Cohen, Beth Ellen Bertenthal, Daniel Seal, Karen Hope TI Time to Treatment Among Veterans of Conflicts in Iraq and Afghanistan With Psychiatric Diagnoses SO PSYCHIATRIC SERVICES LA English DT Article ID MENTAL-HEALTH-SERVICES; POSTTRAUMATIC-STRESS-DISORDER; ETHNIC DISPARITIES; GENDER-DIFFERENCES; UNITED-STATES; CARE; BARRIERS; VA; INTERVENTION; BELIEFS AB Objective: Early mental health treatment after military deployment may reduce chronic mental health problems. The authors described time to, and predictors of time to, initiation of a first primary care visit, a first mental health outpatient visit, and minimally adequate mental health care (eight or more outpatient visits within 12 months) among veterans with psychiatric diagnoses. Methods: The authors conducted a retrospective cohort analysis of medical records of veterans of the conflicts in Iraq and Afghanistan who enrolled in Veterans Affairs (VA) health care, had a psychiatric diagnosis, and had used primary or mental health outpatient care between October 7, 2001, and September 30, 2011 (N=314,717). Results: The median time from the end of the last deployment to engagement in mental health care was over two years. More than three years postdeployment, 75% of the veterans in the VA system for at least one year had not engaged in minimally adequate mental health care. There was a median lag of nearly 7.5 years between initial mental health treatment session and initiation of minimally adequate mental health care. Men waited nearly two years longer than women to initiate minimally adequate mental health care. Younger age and minority racial or ethnic status were also associated with greater time to initial mental health outpatient visit and to minimally adequate mental health care. Conclusions: Delays in initiating and completing minimally adequate mental health care by veterans using VA services highlight the importance of attending to the timing of care, particularly among newly returning veterans. (Psychiatric Services 63:1206-1212, 2012; doi: 10.1176/appi.ps.201200051) C1 [Maguen, Shira; Madden, Erin] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. [Cohen, Beth Ellen; Seal, Karen Hope] San Francisco VA Med Ctr, Med Serv, San Francisco, CA 94121 USA. [Bertenthal, Daniel] San Francisco VA Med Ctr, Mental Illness Res Educ & Clin Ctr, San Francisco, CA 94121 USA. [Maguen, Shira; Seal, Karen Hope] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Cohen, Beth Ellen; Seal, Karen Hope] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, Mental Hlth Serv, 4150 Clement St,116-P, San Francisco, CA 94121 USA. EM shira.maguen@va.gov FU U.S. Department of Defense [W81XWH-08-2-0077]; VA Health Services Research and Development Career Development Award RCD [06-042] FX This research was supported by U.S. Department of Defense Concept Award Grant W81XWH-08-2-0077 and by VA Health Services Research and Development Career Development Award RCD 06-042 to Dr. Maguen. NR 29 TC 22 Z9 22 U1 0 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2012 VL 63 IS 12 BP 1206 EP 1212 DI 10.1176/appi.ps.201200051 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 049KS UT WOS:000311982500007 PM 23070131 ER PT J AU Kilbourne, AM Goodrich, DE Lai, ZS Clogston, J Waxmonsky, J Bauer, MS AF Kilbourne, Amy M. Goodrich, David E. Lai, Zongshan Clogston, Julia Waxmonsky, Jeanette Bauer, Mark S. TI Life Goals Collaborative Care for Patients With Bipolar Disorder and Cardiovascular Disease Risk SO PSYCHIATRIC SERVICES LA English DT Article ID DEPRESSION; INTERVENTION; RATIONALE; SERVICES; ILLNESS; CENTERS; TRIAL; MODEL AB Objective: This pilot study compared Life Goals Collaborative Care (LGCC) with enhanced treatment as usual in reducing cardiometabolic risk factors and improving outcomes for persons with bipolar disorder. Methods: Participants were randomly assigned to LGCC (N=34) or enhanced treatment as usual (N=34). LGCC included four weekly self-management sessions and monthly telephone contacts for six months thereafter. Enhanced treatment as usual included wellness mailings. Outcomes were blood pressure, body mass index (BMI), quality of life, functioning, and symptoms. Results: Compared with enhanced treatment as usual, LGCC was not associated with reductions in cardiometabolic risk factors in 12-month repeated-measures analyses. Among patients with a BMI of >= 30 or systolic blood pressure of >= 140, LGCC was associated with improvements in functioning (beta=-2.2 and beta =-3.8, respectively, p=.04) and reduced depressive symptoms (beta=-2.0 and -3.5, respectively, p=.04). Conclusions: Further research is needed to determine whether LGCC improves outcomes for patients with elevated cardiometabolic risk. (Psychiatric Services 63: 1234-1238, 2012; doi: 10.1176/appi.ps.201100528) C1 [Kilbourne, Amy M.; Goodrich, David E.; Lai, Zongshan; Clogston, Julia] Vet Affairs VA Ann Arbor, Hlth Serv Res & Dev Ctr Clin Management Res, Ann Arbor, MI 48105 USA. [Waxmonsky, Jeanette] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Brockton, MA USA. RP Kilbourne, AM (reprint author), Vet Affairs VA Ann Arbor, Hlth Serv Res & Dev Ctr Clin Management Res, 2215 Fuller Ed, Ann Arbor, MI 48105 USA. EM amykilbo@umich.edu RI Waxmonsky, Jeanette/L-4739-2013; OI Goodrich, David/0000-0003-3232-2189 FU National Institute of Mental Health [R34 MH74509, R01 MH79994]; U.S. Department of Veterans Affairs (VA), Veterans Health Administration FX This work was supported by the National Institute of Mental Health (grants R34 MH74509 and R01 MH79994) and the U.S. Department of Veterans Affairs (VA), Veterans Health Administration. The views expressed in this article are those of the authors and do not necessarily represent the views of the VA. NR 15 TC 17 Z9 17 U1 2 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2012 VL 63 IS 12 BP 1234 EP 1238 DI 10.1176/appi.ps.201100528 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 049KS UT WOS:000311982500012 PM 23203358 ER PT J AU Eisen, SV Schultz, MR Mueller, LN Degenhart, C Clark, JA Resnick, SG Christiansen, CL Armstrong, M Bottonari, KA Rosenheck, RA Sadow, D AF Eisen, Susan V. Schultz, Mark R. Mueller, Lisa N. Degenhart, Curt Clark, Jack A. Resnick, Sandra G. Christiansen, Cindy L. Armstrong, Moe Bottonari, Kathryn A. Rosenheck, Robert A. Sadow, Dolly TI Outcome of a Randomized Study of a Mental Health Peer Education and Support Group in the VA SO PSYCHIATRIC SERVICES LA English DT Article ID CONTROLLED-TRIAL; CONSUMER; SERVICES; EMPOWERMENT; ILLNESS; RECOVERY AB Objectives: Study objectives were to compare mental health outcomes of a peer-led recovery group, a clinician-led recovery group, and usual treatment and to examine the effect of group attendance on outcomes. Methods: The study used a randomized design with three groups: a recovery-oriented peer-led group (Vet-to-Vet), a clinician-led recovery group, and usual treatment. The sample included 240 veterans. Recovery and mental health assessments were obtained at enrollment and three months later. Intention-to-treat analysis using mixed-model regression was performed to examine the effect of the intervention. "As treated" analysis was performed to examine the effect of group attendance. Results: There were no statistically significant differences in improvement among the groups. Across groups, depression and functioning, psychotic symptoms, and overall mental health improved significantly. Better group attendance was associated with more improvement. Conclusions: This study adds to the evidence suggesting no short-term incremental benefit (or harm) from peer services beyond usual care. (Psychiatric Services 63: 1243-1246, 2012; doi: 10.1176/appi.ps.201100348) C1 [Eisen, Susan V.; Schultz, Mark R.; Clark, Jack A.; Christiansen, Cindy L.] ENRM Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Eisen, Susan V.; Schultz, Mark R.; Clark, Jack A.; Christiansen, Cindy L.] ENRM Vet Hosp, MIRECC, Vet Integrated Serv Network 1, Bedford, MA 01730 USA. [Eisen, Susan V.; Clark, Jack A.; Christiansen, Cindy L.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Degenhart, Curt] Massachusetts Sch Profess Psychol, Boston, MA USA. [Resnick, Sandra G.] Vet Affairs VA Med Ctr, NE Program Evaluat Ctr, West Haven, CT USA. [Resnick, Sandra G.; Rosenheck, Robert A.] Yale Univ, Sch Med, New Haven, CT USA. [Armstrong, Moe] VA Connecticut Healthcare Syst, Errera Community Care Ctr, West Haven, CT USA. [Bottonari, Kathryn A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Bottonari, Kathryn A.] Med Univ S Carolina, Charleston, SC USA. [Rosenheck, Robert A.] VA Connecticut Healthcare Syst, VA New England MIRECC, West Haven, CT USA. [Sadow, Dolly] MedOptions Inc, Bedford, MA USA. RP Eisen, SV (reprint author), ENRM Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd 152, Bedford, MA 01730 USA. EM susan.eisen@va.gov RI Resnick, Sandra/F-3883-2014; OI Resnick, Sandra/0000-0001-6373-1482; Clark, Jack/0000-0002-7424-1670; Christiansen, Cindy/0000-0001-9951-480X FU VA Rehabilitation Research and Development Service [D4464R] FX This study was supported by the VA Rehabilitation Research and Development Service grant D4464R. The views expressed in this report are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. The authors thank Matthew Chinman, Ph.D., Patrick Furlong, B.A., Alexandra Howard, B.A., James Silas, B.A., and Nicole Del Vecchio, M.S., for their contribution to this research. NR 15 TC 14 Z9 14 U1 1 U2 16 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2012 VL 63 IS 12 BP 1243 EP 1246 DI 10.1176/appi.ps.201100348 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 049KS UT WOS:000311982500014 PM 23203360 ER PT J AU Bernhard, J Butow, P Aldridge, J Juraskova, I Ribi, K Brown, R AF Bernhard, Juerg Butow, Phyllis Aldridge, Julie Juraskova, Ilona Ribi, Karin Brown, Richard TI Communication about standard treatment options and clinical trials: can we teach doctors new skills to improve patient outcomes? SO PSYCHO-ONCOLOGY LA English DT Article DE communication skills training; shared decision making; cross-cultural differences; breast cancer; oncology ID SHARED DECISION-MAKING; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; SEEKING INFORMED-CONSENT; CANCER-PATIENTS PREFERENCES; BREAST-CANCER; ADJUVANT THERAPY; GENERAL-PRACTICE; PARTICIPATION; INFORMATION AB Background The International Breast Cancer Study Group conducted a phase III trial in Australian/New Zealand (ANZ) and Swiss/German/Austrian (SGA) centres on training doctors in clear and ethical information delivery about treatment options and strategies to encourage shared decision making. Methods Medical, surgical, gynaecological and radiation oncologists, and their patients for whom adjuvant breast cancer therapy was indicated, were eligible. Doctors were randomised to participate in a workshop with standardised teaching material and role playing. Patients were recruited in the experimental and control groups before and after the workshop. Results In ANZ centres, 21 eligible doctors recruited a total of 304 assessable patients. In SGA centres, 41 doctors recruited 390 patients. The training was well accepted. There was no overall effect on patient decisional conflict (primary endpoint) 2?weeks after the consultation. Overall, patients were satisfied with their treatment decision, their consultation and their doctors' consultation skills. Considerable variation was observed in patient outcomes between SGA and ANZ centres; the effect sizes of the intervention were marginal (<0.2). Conclusions Shared decision making remains a challenge. A sustained training effect may require more intensive training tailored to the local setting. Cross-cultural differences need attention in conducting trials on communication interventions. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Bernhard, Juerg; Ribi, Karin] IBCSG Coordinating Ctr, CH-3008 Bern, Switzerland. [Bernhard, Juerg] Univ Hosp Bern, Inselspital, Dept Med Oncol, CH-3010 Bern, Switzerland. [Butow, Phyllis; Juraskova, Ilona] Univ Sydney, Sch Psychol, Ctr Med Psychol & Evidence Based Decis Making CeM, Camperdown, NSW 2006, Australia. [Butow, Phyllis] Univ Sydney, Psychooncol Cooperat Res Grp PoCoG, Sydney, NSW 2006, Australia. [Aldridge, Julie] Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG Stat Ctr, Boston, MA 02115 USA. [Brown, Richard] Virginia Commonwealth Univ, Sch Med, Dept Social & Behav Hlth, Richmond, VA 23298 USA. RP Bernhard, J (reprint author), IBCSG Coordinating Ctr, Effingerstr 40, CH-3008 Bern, Switzerland. EM juerg.bernhard@ibcsg.org FU National Breast Cancer Foundation of Australia; Oncosuisse/Swiss Cancer League [OCS-01165-09-2001/KLS-01648-02-2005]; Deutsche Krebshilfe [106668]; IBCSG; US National Cancer Institute [CA-75362] FX We would like to thank the National Breast Cancer Foundation of Australia, Oncosuisse/Swiss Cancer League (OCS-01165-09-2001/KLS-01648-02-2005), Deutsche Krebshilfe (106668), and IBCSG for funding this trial. The IBCSG Statistical Center (J.A.) is partially funded through a grant from the US National Cancer Institute (CA-75362). NR 52 TC 12 Z9 13 U1 1 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD DEC PY 2012 VL 21 IS 12 BP 1265 EP 1274 DI 10.1002/pon.2044 PG 10 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 049HO UT WOS:000311973600002 PM 23208837 ER PT J AU Mahalingaiah, S Hauser, R Patterson, DG Woudneh, M Racowsky, C AF Mahalingaiah, Shruthi Hauser, Russ Patterson, Donald G., Jr. Woudneh, Million Racowsky, Catherine TI Bisphenol A is not detectable in media or selected contact materials used in IVF SO REPRODUCTIVE BIOMEDICINE ONLINE LA English DT Article DE bisphenol A; endocrine disruptors; IVF; media; gamete; embryo ID EXPOSURE; URINARY; WOMEN AB There is a lack of data regarding potential exposure of gametes to bisphenol A during IVF. Detectable concentrations of bisphenol A were not found in commonly used IVF plastic culture dishes, suction tubing or growth media under normal-use conditions. RBMOnline (c) 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. C1 [Mahalingaiah, Shruthi] Boston Univ, Med Ctr, Dept Obstet & Gynecol, Boston, MA 02118 USA. [Mahalingaiah, Shruthi; Racowsky, Catherine] Boston Med Ctr, Dept Obstet & Gynecol, Boston, MA USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. [Patterson, Donald G., Jr.; Woudneh, Million] AXYS Analyt Serv Ltd, Sidney, BC, Canada. RP Mahalingaiah, S (reprint author), Boston Univ, Med Ctr, Dept Obstet & Gynecol, 85 E Concord St,6th Floor, Boston, MA 02118 USA. EM shruthi.mahalingaiah@bmc.org OI Mahalingaiah, Shruthi/0000-0002-5527-5787 FU Expanding the Boundaries grant from the Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital FX This work was supported by an Expanding the Boundaries grant from the Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital. The authors thank Larisa Altshul for her expertise and Berhan Bogale, embryologist, for his stewardship of the IVF laboratory. NR 9 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1472-6483 J9 REPROD BIOMED ONLINE JI Reprod. Biomed. Online PD DEC PY 2012 VL 25 IS 6 BP 608 EP 611 DI 10.1016/j.rbmo.2012.08.008 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 049BA UT WOS:000311955800009 PM 23063817 ER PT J AU Nikolaou, V Stratigos, AJ Tsao, H AF Nikolaou, Vasiliki Stratigos, Alexander J. Tsao, Hensin TI Hereditary Nonmelanoma Skin Cancer SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY LA English DT Article DE BCC; SCC; basal cell nevus syndrome; xeroderma pigmentosum; hereditary cancer syndromes ID CELL CARCINOMA SYNDROME; INHERITED EPIDERMOLYSIS-BULLOSA; ROTHMUND-THOMSON-SYNDROME; DUPRE-CHRISTOL-SYNDROME; BLOOMS-SYNDROME; ROMBO-SYNDROME; CLINICAL MANIFESTATIONS; AFFECTED INDIVIDUALS; GORLIN-SYNDROME; FANCONI-ANEMIA AB Cutaneous basal and squamous cell carcinomas are among the most frequent malignancies in the white population, with the annual incidence estimates ranging from 1 million to 3.5 million cases in the United States. These tumors can occur either sporadically or in the context of hereditary genodermatoses with cancer predisposition, such as basal cell nevus syndrome, xeroderma pigmentosum, epidermolysis bullosa, or oculocutaneous albinism. Different genes and signaling pathways have been shown to play a central role in the development and growth of these tumors. This article overviews the clinical features, diagnostic criteria, and the most recent data on genetic routes of the major hereditary syndromes predisposed to the development of nonmelanoma skin cancer. Semin Cutan Med Surg 31:204-210 (C) 2012 Frontline Medical Communications C1 [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Ctr Canc, Boston, MA 02114 USA. [Nikolaou, Vasiliki; Stratigos, Alexander J.] Univ Athens, Sch Med, Dermatooncol Unit, Andreas Sygros Hosp,Dept Dermatol, GR-11527 Athens, Greece. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM htsao@partners.org FU United States National Institutes of Health [K24 CA149202]; MGH Millennium Melanoma Fund; National Institutes of Health; Department of Defense; American Skin Association; Melanoma Research Alliance; Cephalon FX This activity was supported in part by the United States National Institutes of Health (K24 CA149202) and by the generous donors to the MGH Millennium Melanoma Fund.; The authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. Drs Nikolaou and Stratigos have no conflicts to report. Dr Tsao has received compensation for Board membership from Journal Watch; consultancy services for Scibase, Quest, World Care Clinical, and Genenteh. Dr Tsao's institution has grants or grants pending with National Institutes of Health, Department of Defense, American Skin Association, Melanoma Research Alliance and Cephalon. Dr Tsao has received royalties from Up to Date and compensation for travel from Pacific Dermatology Association and Cutaneous Malignancies. NR 40 TC 11 Z9 11 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1085-5629 J9 SEMIN CUTAN MED SURG JI Semin. Cutan. Med. Surg. PD DEC PY 2012 VL 31 IS 4 BP 204 EP 210 DI 10.1016/j.sder.2012.08.005 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 050GU UT WOS:000312042000002 PM 23174490 ER PT J AU Prescott, JD Sadow, PM Hodin, RA Le, LP Gaz, RD Randolph, GW Stephen, AE Parangi, S Daniels, GH Lubitz, CC AF Prescott, Jason D. Sadow, Peter M. Hodin, Richard A. Long Phi Le Gaz, Randall D. Randolph, Gregory W. Stephen, Antonia E. Parangi, Sareh Daniels, Gilbert H. Lubitz, Carrie C. TI BRAF(V600E) status adds incremental value to current risk classification systems in predicting papillary thyroid carcinoma recurrence SO SURGERY LA English DT Article ID CENTRAL NECK DISSECTION; BRAF MUTATION; UNITED-STATES; INCREASING INCIDENCE; CANCER PROGRESSION; FEATURES; THERAPY AB Background. Papillary thyroid cancer (PTC) recurrence risk is difficult to predict. No current risk classification system incorporates BRAF mutational status. Here, we assess the incremental value of BRAF mutational status in predicting PTC recurrence relative to existing recurrence risk algorithms. Methods. Serial data were collected for a historical cohort having undergone total thyroidectomy for papillary thyroid carcinoma (PTC) during a 5-year period. Corresponding BRAF(V600E) testing was performed and Cox proportional hazard regression modeling, with and without BRAF status, was used to evaluate existing recurrence risk algorithms. Results. The 5-year cumulative PTC recurrence incidence within our 356 patient cohort was 15%. A total of 205 (81%) of associated archived specimens were successfully genotyped, and 110 harbored the BRAF(V600E) mutation. The 5-year cumulative recurrence incidence among BRAF(V600E) patients was 20% versus 8% among BRAF wild type. BRAF(V600E) was significantly associated with time to recurrence when added to the following algorithms: AMES (hazard ratio [HR] 2.43 [confidence interval 1.08-5.49]), MACIS category (HR 2.46 [1.09-5.54]), AJCC-TNM (HR 2.51 [1.11-5.66]), and ATA recurrence-risk category (HR 2.44 [1.08-5.50]), and model discrimination improved (incremental c-index range 0.046-0.109). Conclusion. The addition of BRAF mutational status to established risk algorithms improves the discrimination of risk recurrence in patients undergoing total thyroidectomy for PTC. (Surgery 2012;152:984-90.) C1 [Lubitz, Carrie C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Oncol Associates,Endocrine Surg Unit,Dept Su, Boston, MA 02114 USA. [Sadow, Peter M.; Long Phi Le] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Randolph, Gregory W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Daniels, Gilbert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Unit,Dept Med, Boston, MA 02114 USA. RP Lubitz, CC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Oncol Associates,Endocrine Surg Unit,Dept Su, 55 Fruit St,YAW 7B, Boston, MA 02114 USA. EM clubitz@partners.org FU Ellison Foundation; Program in Cancer Outcomes Research Training Grant [NCI R25CA092203] FX This work was funded in part by a grant award from the Ellison Foundation (to G.H.D.) and by the Program in Cancer Outcomes Research Training Grant (NCI R25CA092203; C.C.L.). NR 27 TC 35 Z9 42 U1 0 U2 5 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 DEC PY 2012 VL 152 IS 6 BP 984 EP 990 DI 10.1016/j.surg.2012.08.039 PG 7 WC Surgery SC Surgery GA 052AQ UT WOS:000312170500011 PM 23158172 ER PT J AU Lin, CI Whang, EE Lorch, JH Ruan, DT AF Lin, Chi-Iou Whang, Edward E. Lorch, Jochen H. Ruan, Daniel T. TI Autophagic activation potentiates the antiproliferative effects of tyrosine kinase inhibitors in medullary thyroid cancer SO SURGERY LA English DT Article ID CELL-DEATH; APOPTOSIS; EGFR AB Background. We hypothesized that autophagy inhibition would enhance the anticancer efficacy of ret protooncogene-targeted therapy in medullary thyroid cancer. Methods. Medullary thyroid cancer-1.1 and TT cells were treated with sunitinib or sorafenib in the presence or absence of everolimus, trehalose, or small interfering RNA directed against autophagy Protein 5. Results. Sunitinib and sorafenib each robustly induced light chain 3-II expression, indicating autophagy activation. Autophagy protein 5 silencing diminished the antiproliferative effects of sunitinib and sorafenib by 44% (P <.05) and 41% (P <.05), respectively, in medullary thyroid cancer-1.1 cells and by 43% <.01) and 39% (P <.05), respectively, in TT cells. In contrast, everolimus increased the antiproliferative effects of sunitinib and sorafenib by 24% (P <.01) and 27% (P <.01), respectively, in medullary thyroid cancer-1.1 cells and by 20% (P <.05) and 23% (P <.05), respectively, in TT cells. Trehalose increased the antiproliferative effects of sunitinib and sorafenib by 26% (P <.01) and 27% (P <.01), respectively, in medullary thyroid cancer-1.1 cells and by 28% (P <.05) and 29% (P <.05), respectively, in TT cells. Autophagy protein 5 silencing abrogated both everolimus and trehalose-induced increases in tyrosine kinase inhibitor efficacy. Conclusion. Loss (gain) of autophagy diminishes (improves) the efficacy of sunitinib and sorafenib. Our findings suggest that autophagic activation should be combined with targeted ret protooncogene therapy for patients with advanced medullary thyroid cancer (Surgery 2012;152:1142-9.) C1 [Lin, Chi-Iou; Whang, Edward E.; Ruan, Daniel T.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Lorch, Jochen H.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Ruan, DT (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM druan@partners.org FU Department of Surgery at Brigham and Women's Hospital FX Supported by a Fish Family Junior Faculty Research Grant from the Department of Surgery at Brigham and Women's Hospital. NR 18 TC 21 Z9 22 U1 0 U2 8 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 DEC PY 2012 VL 152 IS 6 BP 1142 EP 1149 DI 10.1016/j.surg.2012.08.016 PG 8 WC Surgery SC Surgery GA 052AQ UT WOS:000312170500049 PM 23158184 ER PT J AU Pitman, JT Harris, NS AF Pitman, Justin Thomas Harris, N. Stuart TI Possible Association with Amphetamine Usage and Development of High Altitude Pulmonary Edema SO WILDERNESS & ENVIRONMENTAL MEDICINE LA English DT Letter ID HYPERTENSION C1 [Pitman, Justin Thomas] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Harris, N. Stuart] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Pitman, JT (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 5 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 1080-6032 J9 WILD ENVIRON MED JI Wildern. Environ. Med. PD WIN PY 2012 VL 23 IS 4 BP 374 EP 376 PG 3 WC Public, Environmental & Occupational Health; Sport Sciences SC Public, Environmental & Occupational Health; Sport Sciences GA 048MD UT WOS:000311914700015 PM 23022060 ER PT J AU Skaron, A Li, K Zhou, XH AF Skaron, Annie Li, Kang Zhou, Xiao-Hua TI Statistical Methods for MRMC ROC Studies SO ACADEMIC RADIOLOGY LA English DT Article DE AUC; classification; ROC; variable selection ID DORFMAN-BERBAUM-METZ; MULTIREADER ROC; READERS; CURVES; MODEL AB Rationale and Objectives: In radiology, multireader, multicase (MRMC) receiver-operating characteristic studies are commonly used to evaluate the accuracy of diagnostic imaging systems. The special feature of an MRMC receiver-operating characteristic study requires that the same set of patients' images be examined by the same set of doctors. One main difficulty of analyzing MRMC data is a complicated correlation structure. Four commonly used methods are available for dealing with this complicated correlation structure. The authors conducted an extensive simulation study to assess the performance of these methods in finite sample sizes. They summarize the relative strengths and weaknesses of these methods and make recommendations on the use of these methods. Materials and Methods: A comprehensive simulation study was conducted to assess finite-sample performance of these methods with continuous data. The use of these methods for magnetic resonance imaging to predict extracapsular extension of prostate gland tumors is also illustrated. Results: The results indicate that when test outcomes are continuous, all four methods perform well for estimating the difference in areas under the curves for two diagnostic tests. On the basis of these results, it seems that any of these approaches is appropriate for analyzing an MRMC data set with continuous or pseudocontinuous data. Conclusions: The Dorfman-Berbaum-Metz method is the most practical analysis method to implement in a wide variety of scenarios. Also, in MRMC studies, radiologists should be encouraged to use the entire rating scale rather than tending toward a binary "diseased" or "not diseased" decision. C1 [Skaron, Annie; Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98101 USA. [Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Li, Kang; Zhou, Xiao-Hua] Harbin Med Univ, Dept Biostat, Harbin, Peoples R China. RP Zhou, XH (reprint author), VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98101 USA. EM azhou@uw.edu NR 16 TC 4 Z9 7 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD DEC PY 2012 VL 19 IS 12 BP 1499 EP 1507 DI 10.1016/j.acra.2012.09.005 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 044WB UT WOS:000311654800009 PM 23122569 ER PT J AU Louis, DN AF Louis, David N. TI The next step in brain tumor classification: "Let us now praise famous men" ... or molecules? SO ACTA NEUROPATHOLOGICA LA English DT Editorial Material C1 [Louis, David N.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Louis, David N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, 55 Fruit St,Warren 225, Boston, MA 02114 USA. EM louis@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA057683] NR 0 TC 12 Z9 14 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD DEC PY 2012 VL 124 IS 6 BP 761 EP 762 DI 10.1007/s00401-012-1067-4 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 046FU UT WOS:000311751700001 PM 23151844 ER PT J AU Samelson, EJ Booth, SL Fox, CS Tucker, KL Wang, TJ Hoffmann, U Cupples, LA O'Donnell, CJ Kiel, DP AF Samelson, Elizabeth J. Booth, Sarah L. Fox, Caroline S. Tucker, Katherine L. Wang, Thomas J. Hoffmann, Udo Cupples, L. Adrienne O'Donnell, Christopher J. Kiel, Douglas P. TI Calcium intake is not associated with increased coronary artery calcification: the Framingham Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; BONE-VASCULAR AXIS; VITAMIN-D; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; AORTIC CALCIFICATION; DIETARY ASSESSMENT; WOMENS HEALTH; HEART-DISEASE; RISK AB Background: Adequate calcium intake is known to protect the skeleton. However, studies that have reported adverse effects of calcium supplementation on vascular events have raised widespread concern. Objective: We assessed the association between calcium intake (from diet and supplements) and coronary artery calcification, which is a measure of atherosclerosis that predicts risk of ischemic heart disease independent of other risk factors. Design: This was an observational, prospective cohort study. Participants included 690 women and 588 men in the Framingham Offspring Study (mean age: 60 y; range: 36-83 y) who attended clinic visits and completed food-frequency questionnaires in 1998 2001 and underwent computed tomography scans 4 y later in 2002 2005. Results: The mean age-adjusted coronary artery calcification Agatston score decreased with increasing total calcium intake, and the trend was not significant after adjustment for age, BMI, smoking, alcohol consumption, vitamin D supplement use, energy intake, and, for women, menopause status and estrogen use. Mu Invariable-adjusted mean Agatston scores were 2.36, 2.52, 2.16, and 2.39 (P-trend = 0.74) with an increasing quartile of total calcium intake in women and 4.32, 4.39, 4.19, and 4.37 (P-trend = 0.94) in men, respectively. Results were similar for dietary calcium and calcium supplement use. Conclusions: Our study does not support the hypothesis that high calcium intake increases coronary artery calcification, which is an important measure of atherosclerosis burden. The evidence is not sufficient to modify current recommendations for calcium intake to protect skeletal health with respect to vascular calcification risk. Am Clin Nutr 2012;96:1274-80. C1 [Samelson, Elizabeth J.; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA. [Samelson, Elizabeth J.; Kiel, Douglas P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Booth, Sarah L.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Fox, Caroline S.; O'Donnell, Christopher J.] Natl Heart Lung & Blood Insts Framingham Heart St, Framingham, MA USA. [Tucker, Katherine L.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Wang, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Samelson, EJ (reprint author), Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM samelson@hsl.harvard.edu OI Cupples, L. Adrienne/0000-0003-0273-7965; Kiel, Douglas/0000-0001-8474-0310; Tucker, Katherine/0000-0001-7640-662X FU National Institute of Arthritis. Musculoskeletal, and Skin Diseases [K01 AR053118, R01 AR/AG41398]; National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study (NIH/NHLBI ) [N01-HC-25195] FX Supported by National Institute of Arthritis. Musculoskeletal, and Skin Diseases grants K01 AR053118 and R01 AR/AG41398 and the National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study (NIH/NHLBI contract N01-HC-25195). NR 55 TC 36 Z9 37 U1 1 U2 17 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 2012 VL 96 IS 6 BP 1274 EP 1280 DI 10.3945/ajcn.112.044230 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 043HK UT WOS:000311533300005 PM 23134889 ER PT J AU Spira, AP Rebok, GW Stone, KL Kramer, JH Yaffe, K AF Spira, Adam P. Rebok, George W. Stone, Katie L. Kramer, Joel H. Yaffe, Kristine TI Depressive Symptoms in Oldest-Old Women: Risk of Mild Cognitive Impairment and Dementia SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Depression; dementia; mild cognitive impairment; oldest-old; women ID APOLIPOPROTEIN E4 ALLELE; MINI-MENTAL STATE; ALZHEIMER-DISEASE; MAJOR DEPRESSION; LATE-LIFE; NEUROPSYCHIATRIC SYMPTOMS; INFORMANT QUESTIONNAIRE; CARDIOVASCULAR HEALTH; HIPPOCAMPAL VOLUME; ELDERLY IQCODE AB Objectives: Increasing evidence suggests that depression is a risk factor for cognitive impairment, but it is unclear if this is true among the oldest old. We determined whether elevated depressive symptoms predicted 5-year incident mild cognitive impairment (MCI) or dementia, and neuropsychological test performance among oldest-old women. Design: Prospective. Setting: Three study sites. Participants: 302 women >= 85 years (mean, 87 +/- 2). Measurements: Depressive symptoms were measured with the 15-item Geriatric Depression Scale (GDS); scores of 6 or more indicated elevated symptoms. Five years later, participants completed neuropsychological testing and clinical cognitive status was adjudicated. Results: In analyses of MCI versus normal cognition, 70% of women with GDS score 6 or more at baseline developed MCI versus 37% with GDS score less than 6. After adjustment for age, education, alcohol, and benzodiazepine use, and study site, GDS score 6 or more remained independently associated with much greater likelihood of developing MCI (multivariable odds ratio [MOR] = 3.71, 95% confidence interval (CI): 1.30-10.59). In analyses of dementia versus normal cognition, 65% of women with GDS score 6 or more developed dementia compared with 37% of those with GDS score less than 6 (MOR = 3.15, 95% CI: 1.03-9.65). Only 19% of women with GDS score 6 or more had normal cognitive status 5 years later, compared with 46% of those with GDS score less than 6 (MOR = 0.28, 95% CI: 0.11-0.73). Women with elevated depressive symptoms had worse scores on tests of global cognition and working memory. Conclusion: Elevated depressive symptoms are an important risk factor for cognitive disorders and lower cognitive performance among women living to their ninth and tenth decades. (Am J Geriatr Psychiatry 2012; 20:1006-1015) C1 [Spira, Adam P.; Rebok, George W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Stone, Katie L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Kramer, Joel H.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Spira, AP (reprint author), 624 N Broadway,Hampton House,Rm 794, Baltimore, MD 21205 USA. EM aspira@jhsph.edu FU National Institutes of Health [AG026720, AG05394, AG05407, AR35582, AR35583, AR35584, R01 AG005407, R01 AG027576-22, 2 R01 AG005394-22A1, 2 R01 AG027574-22A1, R01 MH086498, NIA K24 AG031155]; Alzheimer's Association [IIRG-08-88872]; National Institute on Aging [1K01AG033195]; NIMH FX This project was supported by National Institutes of Health Grants AG026720, AG05394, AG05407, AR35582, AR35583, AR35584, R01 AG005407, R01 AG027576-22, 2 R01 AG005394-22A1, 2 R01 AG027574-22A1, R01 MH086498, NIA K24 AG031155, and Alzheimer's Association award IIRG-08-88872.; APS is supported by a Mentored Research Scientist Development Award (1K01AG033195) from the National Institute on Aging. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. KY is on the data safety monitoring board (DSMB) of the NIMH-funded CitAD trial and on DSMBs for Pfizer and Medivation trials. Other authors have no disclosures to report. NR 56 TC 18 Z9 18 U1 2 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD DEC PY 2012 VL 20 IS 12 BP 1006 EP 1015 DI 10.1097/JGP.0b013e318235b611 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 045RW UT WOS:000311715500002 PM 22015706 ER PT J AU Teng, E Tassniyom, K Lu, PH AF Teng, Edmond Tassniyom, Kanida Lu, Po H. TI Reduced Quality-of-Life Ratings in Mild Cognitive Impairment: Analyses of Subject and Informant Responses SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Cognitive; functional; mild cognitive impairment; neuropsychiatric; quality of life ID ALZHEIMERS-DISEASE SCALE; QOL-AD SCALE; NEUROPSYCHIATRIC SYMPTOMS; CLINICAL SUBTYPES; OLDER ADULTS; DEMENTIA; MCI; COMMUNITY; PATIENT; PROGRESSION AB Objectives: To determine whether quality-of-life (QOL) ratings are reduced in mild cognitive impairment (MCI) and analyze correlations between QOL ratings and cognitive, neuropsychiatric, and functional indices in MCI. Design: Cross-sectional. Setting: The Easton Center for Alzheimer's Disease Research at the University of California, Los Angeles. Participants: A total of 205 individuals who met criteria for normal cognition (n = 97) or MCI (n = 108). The MCI group included amnestic (n = 72) and nonamnestic (n = 36) MCI. Measurements: QOL was assessed using subject and informant ratings on the Quality of Life-Alzheimer's Disease (QOL-AD) scale. Cognitive performance was assessed with the National Alzheimer's Disease Coordinating Center Uniform Data Set neuropsychological battery. Neuropsychiatric symptoms were assessed with the Geriatric Depression Scale (GDS) and the Neuropsychiatric Inventory. Functional abilities were assessed with the Functional Activities Questionnaire (FAQ). Results: The normal cognition group had significantly higher QOL-AD scores than the MCI group on both subject and informant assessments. Individual item analyses indicated that the largest group differences were seen on the mood and memory items. Similar QOL-AD scores were seen in the amnestic and nonamnestic MCI subgroups. Multiple regression analyses within the MCI group indicated that QOL-AD ratings were not correlated with neuropsychological performance. Subject QOL-AD ratings were inversely correlated with GDS scores and informant QOL-AD ratings were inversely correlated with GDS, Neuropsychiatric Inventory, and FAQ scores. Conclusions: Significant declines in QOL are seen in MCI and are associated with neuropsychiatric symptoms and functional decline. Interventions targeting mood symptoms and/or instrumental activities of daily living may improve QOL in MCI. (Am J Geriatr Psychiatry 2012; 201016-1025) C1 [Teng, Edmond] Vet Affairs Greater Los Angeles Healthcare Syst, Neurobehav Unit, Los Angeles, CA USA. [Teng, Edmond] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Teng, Edmond; Lu, Po H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Tassniyom, Kanida] Khon Kaen Univ, Fac Med, Dept Psychiat, Khon Kaen, Thailand. RP Teng, E (reprint author), W Los Angeles VA Healthcare Ctr, Neurobehav Unit 116AF, Bldg 401,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eteng@ucla.edu FU National Institute on Aging [P50 AG 16570, K23 AG 028727, K08 AG 34628]; NIA [P50 AG 16570, K23 AG 028727, K08 AG 34628]; AFAR [P50 AG 16570, K23 AG 028727, K08 AG 34628]; John A. Hartford Foundation [P50 AG 16570, K23 AG 028727, K08 AG 34628]; Atlantic Philanthropies [P50 AG 16570, K23 AG 028727, K08 AG 34628]; Starr Foundation [P50 AG 16570, K23 AG 028727, K08 AG 34628]; Alzheimer's Disease Research Centers of California; Sidell-Kagan Foundation FX This research was supported by grants from the National Institute on Aging (P50 AG 16570, K23 AG 028727 [to PL], and K08 AG 34628 [to ET; jointly sponsored by NIA, AFAR, the John A. Hartford Foundation, the Atlantic Philanthropies, the Starr Foundation and an anonymous donor]), the Alzheimer's Disease Research Centers of California, and the Sidell-Kagan Foundation. NR 40 TC 22 Z9 23 U1 2 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD DEC PY 2012 VL 20 IS 12 BP 1016 EP 1025 DI 10.1097/JGP.0b013e31826ce640 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 045RW UT WOS:000311715500003 PM 23018474 ER PT J AU Munro, CA Longmire, CF Drye, LT Martin, BK Frangakis, CE Meinert, CL Mintzer, JE Porsteinsson, AP Rabins, PV Rosenberg, PB Schneider, LS Weintraub, D Lyketsos, CG AF Munro, Cynthia A. Longmire, Crystal Flynn Drye, Lea T. Martin, Barbara K. Frangakis, Constantine E. Meinert, Curtis L. Mintzer, Jacobo E. Porsteinsson, Anton P. Rabins, Peter V. Rosenberg, Paul B. Schneider, Lon S. Weintraub, Daniel Lyketsos, Constantine G. CA Depression Alzheimer's Dis Study-2 TI Cognitive Outcomes After Sertaline Treatment in Patients With Depression of Alzheimer Disease SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Alzheimer disease; clinical trial; cognitive; depression; neuropsychology; sertraline ID EXECUTIVE DYSFUNCTION; MAJOR DEPRESSION; LATE-LIFE; SERTRALINE; PREDICTORS; CRITERIA AB Objectives: Although many depressed patients with Alzheimer disease (AD) are treated with antidepressants, the effect of such treatment on cognitive performance in these patients is not known. The authors report cognitive outcomes in patients with depression of AD (dAD) after a 24-week trial of sertraline or placebo. Design: Placebo-controlled, randomized, double-blind trial. Setting: Outpatient memory clinics at five academic medical centers in the United States. Participants: A total of 131 patients with dAD (60 men) and Mini-Mental State Examination scores of 10-26. Intervention: Sertraline (n = 67), target dose of 100 mg daily or matching placebo (n = 64). Caregivers received standardized psychosocial intervention throughout the trial. Measurements: Mini-Mental State Examination, cognitive subscale of the Alzheimer's Disease Assessment Scale, letter fluency, backward digit span, Symbol Digit Modalities Test, and Finger Tapping Test, administered at baseline, and 8, 16, and 24 weeks following baseline. Results: A series of linear models indicated no effect of treatment or of depression remission on cognitive test performance at 24 weeks. Regardless of treatment condition, very little change in cognitive test performance was noted in general. Conclusions: Treatment with sertraline in patients with dAD is not associated with greater improvement in cognition at week 24 than treatment with placebo. (Am J Geriatr Psychiatry 2012; 20:1036-1044) C1 [Munro, Cynthia A.; Rabins, Peter V.; Rosenberg, Paul B.; Lyketsos, Constantine G.] Johns Hopkins Sch Med, Baltimore, MD USA. [Drye, Lea T.; Martin, Barbara K.; Frangakis, Constantine E.; Meinert, Curtis L.; Lyketsos, Constantine G.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Longmire, Crystal Flynn; Mintzer, Jacobo E.] Med Univ S Carolina, Charleston, SC USA. [Longmire, Crystal Flynn; Mintzer, Jacobo E.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Porsteinsson, Anton P.] Univ Rochester, Sch Med, Rochester, NY USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Weintraub, Daniel] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Munro, CA (reprint author), Johns Hopkins Univ Hosp, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 218, Baltimore, MD 21287 USA. EM cmunro@jhmi.edu OI Drye, Lea/0000-0002-2964-1878 FU National Institute of Mental Health [1U01MH066136, 1U01MH068014, 1U01MH066174, 1U01MH066175, 1U01MH066176, 1U01MH066177]; Pfizer; Merck; Wyeth; Lilly; Boehringer Ingelheim; Eli Lilly [PF04494700]; Forest FX This study was supported by National Institute of Mental Health grants 1U01MH066136, 1U01MH068014, 1U01MH066174, 1U01MH066175, 1U01MH066176, and 1U01MH066177. NIMH scientific collaborators participated on the trial's Steering Committee.; These disclosures include any anticipated conflicts through 9/31/11, according to the DIADS-2 Conflict of Interest Policy (available upon request from the study PI). Barbara Martin is involved in another trial for which Pfizer donated a different drug. Paul Rosenberg has received research funds from Pfizer and Merck in amounts greater than $10,000. Jacobo Mintzer is a current grant recipient for Wyeth, Lilly, and Pfizer. Daniel Weintraub has received research support from Boehringer Ingelheim; Dr. Weintraub has also been a paid consultant for Acadia Pharmaceuticals, Novartis Pharmaceuticals, Boehringer Ingelheim, Osmotica Pharmaceutical, BrainCells Inc., EMD Serono, and Sanofi Aventis, and has participated on a Speaker's Bureau for Pfizer. Anton Porsteinsson is involved in research sponsored by Pfizer to study donepezil and PF04494700, Eli Lilly to study atomoxetine, a gamma-secretase inhibitor and a beta amyloid antibody, Wyeth to study a beta amyloid antibody, GSK to study a PPAR inhibitor and Forest to study memantine and neramexane; Dr. Porsteinsson has been a paid consultant and participated on a Speaker's Bureau for Pfizer and Forest. Lon S. Schneider is involved in research sponsored by Pfizer, the manufacturer of sertraline and other drugs used to treatmood disorders; Dr. Schneider has been a paid consultant for Abbott, AstraZeneca, Eli Lilly, Forest, GlaxoSmithKline, Johnson and Johnson, Lundbeck, Merck, and Wyeth, manufacturers of antidepressants or drugs used to treat mood disorders. Constantine Frangakis and Lea Drye have no conflict of interests. Peter Rabins has participated on Speaker's Bureaus for Wyeth, Eli Lilly, and Pfizer for more than 2 years. He has provided legal testimony for Janssen Pharmaceutica. Cynthia Munro has no conflict of interests. Curtis Meinert is involved in another trial for which Pfizer donated a different drug; Dr. Meinert owns shares of GSK stock. Constantine Lyketsos was involved in another trial for which Pfizer donated a different drug; he was also involved in research sponsored by Forest to study escitalopram and citalopram and Pfizer to study sertraline and donepezil. Dr. Lyketsos served as a consultant for Organon, Eisai, GSK, Lilly, Wyeth, and Pfizer. NR 32 TC 20 Z9 20 U1 0 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD DEC PY 2012 VL 20 IS 12 BP 1036 EP 1044 DI 10.1097/JGP.0b013e31826ce4c5 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 045RW UT WOS:000311715500005 PM 23032478 ER PT J AU Cheng, YW Kaimal, AJ Snowden, JM Nicholson, JM Caughey, AB AF Cheng, Yvonne W. Kaimal, Anjali J. Snowden, Jonathan M. Nicholson, James M. Caughey, Aaron B. TI Induction of labor compared to expectant management in low-risk women and associated perinatal outcomes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cesarean; induction; neonatal outcomes ID CESAREAN DELIVERY; NULLIPAROUS WOMEN; GESTATIONAL-AGE; POSTTERM PREGNANCY; UNFAVORABLE CERVIX; FAVORABLE CERVIX; TERM; TRIAL AB OBJECTIVE: We sought to examine the association of labor induction and perinatal outcomes. STUDY DESIGN: This was a retrospective cohort study of low-risk nulliparous women with term, live births. Women who had induction at a given gestational age (eg, 39 weeks) were compared to delivery at a later gestation (eg, 40, 41, or 42 weeks). RESULTS: Compared to delivery at a later gestational age, those induced at 39 weeks had a lower risk of cesarean (adjusted odds ratio [aOR], 0.90; 95% confidence interval [CI], 0.88-0.91) and labor dystocia (aOR, 0.88; 95% CI, 0.84-0.94). Their neonates had lowered risk of having 5-minute Apgar <7 (aOR, 0.81; 95% CI, 0.72-0.92), meconium aspiration syndrome (aOR, 0.30; 95% CI, 0.19-0.48), and admission to neonatal intensive care unit (aOR, 0.87; 95% CI, 0.78-0.97). Similar findings were seen for women who were induced at 40 weeks compared to delivery later. CONCLUSION: Induction of labor in low-risk women at term is not associated with increased risk of cesarean delivery compared to delivery later. C1 [Cheng, Yvonne W.] Univ Calif San Francisco, Sch Med, Dept Obstet Gynecol & Reprod Med, Div Maternal Fetal Med, San Francisco, CA 94143 USA. [Kaimal, Anjali J.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA. [Snowden, Jonathan M.; Caughey, Aaron B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. [Nicholson, James M.] Univ Penn, Sch Med, Dept Family & Community Med, Philadelphia, PA 19104 USA. RP Cheng, YW (reprint author), Univ Calif San Francisco, Sch Med, Dept Obstet Gynecol & Reprod Med, Div Maternal Fetal Med, San Francisco, CA 94143 USA. FU University of California San Francisco Women's Reproductive Health Research Career Development Award, National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development [K12 HD001262] FX Y.W.C. is supported by the University of California San Francisco Women's Reproductive Health Research Career Development Award, National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12 HD001262). NR 26 TC 0 Z9 0 U1 5 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2012 VL 207 IS 6 AR 502.e1 DI 10.1016/j.ajog.2012.09.019 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 042PM UT WOS:000311483300028 PM 23063017 ER PT J AU Garrett, LA Boruta, DM AF Garrett, Leslie A. Boruta, David M., II TI Laparoendoscopic single-site radical hysterectomy The first report of LESS type III hysterectomy involves a woman with cervical cancer SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material DE cervical cancer; laparoendoscopic single-site surgery; radical hysterectomy; single incision laparoscopy AB Laparoendoscopic single-site surgery is a logical advance in the evolution of minimally invasive surgery and is being utilized to perform increasingly complex procedures. We report its use for completion of radical hysterectomy as treatment for cervical cancer. C1 [Garrett, Leslie A.; Boruta, David M., II] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol,Div Gynecol Oncol, Boston, MA 02114 USA. RP Garrett, LA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol,Div Gynecol Oncol, Boston, MA 02114 USA. NR 9 TC 0 Z9 1 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2012 VL 207 IS 6 AR 518.e1 DI 10.1016/j.ajog.2012.10.868 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 042PM UT WOS:000311483300037 PM 23111114 ER PT J AU Cheng, SF Dastjerdi, MH Ferrari, G Okanobo, A Bower, KS Ryan, DS Amparo, F Stevenson, W Hamrah, P Nallasamy, N Dana, R AF Cheng, Sheng-Fu Dastjerdi, Mohammad H. Ferrari, Giulio Okanobo, Andre Bower, Kraig S. Ryan, Denise S. Amparo, Francisco Stevenson, William Hamrah, Pedram Nallasamy, Nambi Dana, Reza TI Short-Term Topical Bevacizumab in the Treatment of Stable Corneal Neovascularization SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; AVASTIN; ANGIOGENESIS; RANIBIZUMAB; EFFICACY; RECEPTOR; VESSELS; CANCER; VEGF AB center dot PURPOSE: To evaluate the safety and efficacy of topical bevacizumab in the treatment of corneal neovascularization. center dot DESIGN: Prospective, nonrandomized, interventional case series. center dot METHODS: SETTING: Institutional, multicenter clinical trial. STUDY POPULATION: Twenty eyes from 20 patients with stable corneal neovascularization. INTERVENTION PROCEDURES: Patients were treated with topical 1.0% bevacizumab for 3 weeks and were monitored for a total of 24 weeks. MAIN OUTCOME MEASURES: Primary outcome measures included: neovascular area, defined as the area of the corneal vessels themselves; vessel caliber, defined as the mean corneal vessel diameter; and invasion area, defined as the fraction of the total cornea into which the vessels extended. The occurrence of ocular and systemic adverse events was monitored closely. center dot RESULTS: As compared with the baseline visit, patients exhibited a statistically significant improvement in neovascular area by week 6 (P = .007) and in vessel caliber by week 12 (P = .006). At the final visit, neovascular area, vessel caliber, and invasion area were reduced by 47.5%, 36.2%, and 20%, respectively. The decreases in neovascular area and vessel caliber were statistically significant (P < .001 and P = .003, respectively); however, the reduction in invasion area did not reach statistical significance (P = .06). There were no significant changes in the secondary outcomes, and there were no adverse events. center dot CONCLUSIONS: Short-term topical bevacizumab treatment reduced the extent of stable corneal neovascularization as measured by neovascular area and vessel caliber with no associated adverse events. Interestingly, the degree of treatment efficacy was inversely proportional to the baseline invasion area. (Am J Ophthalmol 2012;154:940-948. (C) 2012 by Elsevier Inc. All rights reserved.) C1 [Cheng, Sheng-Fu; Dastjerdi, Mohammad H.; Ferrari, Giulio; Okanobo, Andre; Amparo, Francisco; Stevenson, William; Hamrah, Pedram; Nallasamy, Nambi; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Cornea Serv, Dept Ophthalmol,Sch Med, Boston, MA 02114 USA. [Cheng, Sheng-Fu] Shin Kong Wu Ho Su Mem Hosp, Dept Ophthalmol, Taipei, Taiwan. [Bower, Kraig S.] Johns Hopkins Sch Med, Wilmer Eye Inst, Div Cornea Cataract & External Dis, Baltimore, MD USA. [Ryan, Denise S.] Walter Reed Army Med Ctr, Ophthalmol Serv, Washington, DC 20307 USA. RP Dana, R (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Cornea Serv, Dept Ophthalmol,Sch Med, 243 Charles St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu RI ferrari, giulio/J-9260-2016 OI ferrari, giulio/0000-0001-6474-9908 FU National Institutes of Health, Bethesda, Maryland [K24 EY019098]; Prevent Blindness America, Chicago, Illinois FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF interest and none were reported. Supported in part by Grant K24 EY019098 from the National Institutes of Health, Bethesda, Maryland; and by Prevent Blindness America, Chicago, Illinois. Involved in Design of study (M.H.D., RD.); Conduct of study (S.-F.C., M.H.D., K.S.B., R.D.); Collection of data (K.S.B., PH., R.D.); Management, analysis, and interpretation of data (S.-F.C., M.H.D., G.F., A.O., D.S.R., F.A., W.S., N.N., R.D.); and Preparation of manuscript (S.-F.C., W.S., R.D).). This was a prospective protocol-driven study approved by the institutional review boards of the Massachusetts Eye & Ear Infirmary and Walter Reed Army Medical Center. The study also complied with the Health Insurance Portability and Accountability Act. Informed consent was obtained from all patients before enrollment. The clinical trial was registered (registration no.: NCT00559936) and can be accessed on the web site www.clinicaltrials.gov. The authors thank Leila Smaga, Massachusetts Eye & Ear Infirmary, for her invaluable support in the clinical trial management. NR 31 TC 15 Z9 16 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2012 VL 154 IS 6 BP 940 EP 948 DI 10.1016/j.ajo.2012.06.007 PG 9 WC Ophthalmology SC Ophthalmology GA 047ZA UT WOS:000311878800005 PM 22967868 ER PT J AU Nativ, NI Maguire, TJ Yarmush, G Brasaemle, DL Henry, SD Guarrera, JV Berthiaume, F Yarmush, ML AF Nativ, N. I. Maguire, T. J. Yarmush, G. Brasaemle, D. L. Henry, S. D. Guarrera, J. V. Berthiaume, F. Yarmush, M. L. TI Liver Defatting: An Alternative Approach to Enable Steatotic Liver Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE Defatting; fatty liver; ischemia-reperfusion (I/R); liver; machine perfusion; normothermic; steatosis; transplantation ID ISCHEMIA-REPERFUSION INJURY; SUBNORMOTHERMIC MACHINE PERFUSION; RAT FATTY LIVER; HEPATIC STEATOSIS; PRESERVATION INJURY; DEFICIENT DIET; COLD-STORAGE; ACID; MACROSTEATOSIS; HEPATOCYTES AB Macrovesicular steatosis in greater than 30% of hepatocytes is a significant risk factor for primary graft nonfunction due to increased sensitivity to ischemia reperfusion (I/R) injury. The growing prevalence of hepatic steatosis due to the obesity epidemic, in conjunction with an aging population, may negatively impact the availability of suitable deceased liver donors. Some have suggested that metabolic interventions could decrease the fat content of liver grafts prior to transplantation. This concept has been successfully tested through nutritional supplementation in a few living donors. Utilization of deceased donor livers, however, requires defatting of explanted organs. Animal studies suggest that this can be accomplished by ex vivo warm perfusion in a time scale of a few hours. We estimate that this approach could significantly boost the size of the donor pool by increasing the utilization of steatotic livers. Here we review current knowledge on the mechanisms whereby excessive lipid storage and macrosteatosis exacerbate hepatic I/R injury, and possible approaches to address this problem, including ex vivo perfusion methods as well as metabolically induced defatting. We also discuss the challenges ahead that need to be addressed for clinical implementation. C1 [Nativ, N. I.; Maguire, T. J.; Yarmush, G.; Berthiaume, F.; Yarmush, M. L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. [Brasaemle, D. L.] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. [Henry, S. D.; Guarrera, J. V.] Columbia Univ, Med Ctr, Dept Surg, Ctr Liver Dis & Transplantat, New York, NY USA. [Yarmush, M. L.] Massachusetts Gen Hosp, Surg Serv, Ctr Engn Med, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. EM yarmush@rci.rutgers.edu OI Brasaemle, Dawn/0000-0002-8553-8285 FU NIH [R01DK059766] FX This work was partially supported by NIH grant R01DK059766. N.I.N. and G.Y. were supported by an NIH-funded Biotechnology Training Fellowship. NR 40 TC 21 Z9 23 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2012 VL 12 IS 12 BP 3176 EP 3183 DI 10.1111/j.1600-6143.2012.04288.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 047QE UT WOS:000311854800005 PM 23057797 ER PT J AU Myaskovsky, L Posluszny, DM Schulz, R DiMartini, AF Switzer, GE Dabbs, AD McNulty, ML Kormos, RL Toyoda, Y Dew, MA AF Myaskovsky, L. Posluszny, D. M. Schulz, R. DiMartini, A. F. Switzer, G. E. Dabbs, A. DeVito McNulty, M. L. Kormos, R. L. Toyoda, Y. Dew, M. A. TI Predictors and Outcomes of Health-Related Quality of Life in Caregivers of Cardiothoracic Transplant Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Cardiothoracic transplant; caregivers; psychosocial resources; quality of life ID LUNG-TRANSPLANT; HEART-TRANSPLANT; FAMILY CAREGIVERS; PSYCHOLOGICAL DISTRESS; LIVER-TRANSPLANTATION; COPING STRATEGIES; SOCIAL SUPPORT; CANDIDATES; EXPERIENCE; SPOUSES AB Cardiothoracic transplant programs generally require that transplant recipients have family caregivers to assist them posttransplant. The burden of caregiving on the family members remains poorly understood. If caregivers well-being is compromised by caregiving, it may bode poorly for transplant recipients own health in the long-term posttransplant. We examined caregiver health-related quality of life (HRQOL) during the first year after their family member's transplant, its predictors and its relationship to subsequent patient survival. Adult (aged 18+) caregivers of 242 cardiothoracic transplant recipients (lung = 134; heart = 108) completed assessments of demographics, psychosocial characteristics and caregiver burden at 2 months posttransplant, and HRQOL at 2, 7 and 12 months posttransplant. Recipients survival time was obtained from medical records. Caregiver HRQOL was generally high across the first-year posttransplant in emotional and social functioning; caregiver physical functioning significantly worsened. There were no differences by type of recipient transplant. Greater caregiver burden predicted poorer caregiver HRQOL in several physical domains at 12 months posttransplant. Transplant recipients whose caregivers had lower perceived general health at 12 months posttransplant showed poorer survival rates during the subsequent 7 years of follow up. Transplant teams should identify those caregivers at risk for poorer general health posttransplant to maximize positive outcomes for the entire family. C1 [Myaskovsky, L.; Switzer, G. E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15213 USA. [Myaskovsky, L.; Posluszny, D. M.; Switzer, G. E.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Myaskovsky, L.; Schulz, R.; DiMartini, A. F.; Switzer, G. E.; McNulty, M. L.; Dew, M. A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Schulz, R.; Dew, M. A.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Schulz, R.] Univ Pittsburgh, Dept Sociol Community Hlth & Hlth & Rehabil Sci, Pittsburgh, PA USA. [DiMartini, A. F.; Kormos, R. L.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Dabbs, A. DeVito] Univ Pittsburgh, Sch Nursing, Dept Acute & Tertiary Care, Pittsburgh, PA 15261 USA. [Toyoda, Y.] Temple Univ, Sch Med, Dept Surg, Pittsburgh, PA USA. [Dew, M. A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Dew, M. A.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. RP Myaskovsky, L (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15213 USA. EM larissa.myaskovsky@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service [IIR-06-220]; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK081325]; National Institute of Mental Health [R01 MH59229] FX Work on this manuscript was supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service (IIR-06-220; Myaskovsky, PI), the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK081325; Myaskovsky, PI) and the National Institute of Mental Health (R01 MH59229; Dew, PI). NR 66 TC 7 Z9 7 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2012 VL 12 IS 12 BP 3387 EP 3397 DI 10.1111/j.1600-6143.2012.04243.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 047QE UT WOS:000311854800023 PM 22958758 ER PT J AU Ruddy, KJ Pitcher, BN Archer, LE Cohen, HJ Winer, EP Hudis, CA Muss, HB Partridge, AH AF Ruddy, K. J. Pitcher, B. N. Archer, L. E. Cohen, H. J. Winer, E. P. Hudis, C. A. Muss, H. B. Partridge, A. H. TI Persistence, adherence, and toxicity with oral CMF in older women with early-stage breast cancer (Adherence Companion Study 60104 for CALGB 49907) SO ANNALS OF ONCOLOGY LA English DT Article DE antineoplastic combined chemotherapy protocols; breast neoplasms; geriatrics; medication adherence; patient compliance; toxicity ID ADJUVANT TAMOXIFEN; ENDOCRINE THERAPY; PILL COUNTS; DISCONTINUATION; CHEMOTHERAPY; NONADHERENCE; PREDICTORS; COHORT AB Cyclophosphamide-methotrexate-5-fluorouracil (CMF) is often selected as adjuvant chemotherapy for older patients with early-stage breast cancer due to perceived superior tolerability. We sought to measure persistence with CMF, adherence to oral cyclophosphamide, and the association of these with toxic effects. CALGB 49907 was a randomized trial comparing standard chemotherapy (CMF or AC, provider/patient choice) with capecitabine in patients aged >= 65 with stage I-IIIB breast cancer. Those randomized to standard therapy and choosing CMF were prescribed oral cyclophosphamide 100 mg/m(2) for 14 consecutive days in six 28-day cycles. Persistence was defined as being prescribed six cycles of at least one of the three CMF drugs. Adherence was the number of cyclophosphamide doses that women reported they had taken divided by the number prescribed. Persistence and adherence were based on case report forms and medication calendars. Of 317 randomized to standard chemotherapy, 133 received CMF. Median age was 73 (range 65-88). Seventy-one percent submitted at least one medication calendar; 65% persisted with CMF. Non-persistence was associated with node negativity (P = 0.019), febrile neutropenia (P = 0.002), and fatigue (P = 0.044). Average adherence was 97% during prescribed cycles. Self-reported adherence to cyclophosphamide was high, but persistence was lower, which may be attributable to toxic effects. C1 [Ruddy, K. J.; Winer, E. P.; Partridge, A. H.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Pitcher, B. N.; Archer, L. E.; Cohen, H. J.] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC 27706 USA. [Hudis, C. A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Muss, H. B.] Univ N Carolina, Chapel Hill, NC USA. RP Ruddy, KJ (reprint author), Dana Farber Canc Inst, 450 Brookline Pl, Boston, MA 02215 USA. EM kruddy@partners.org FU University of Oklahoma, Oklahoma, [CA37447]; Christiana Care Health Services, Inc., CCOP, Wilmington [CA45418]; Dana-Farber Cancer Institute, Boston [CA32291]; Dartmouth Medical School - Norris Cotton Cancer Center, Lebanon [CA04326]; Duke University Medical Center, Durham [CA47577]; Hematology-Oncology Associates of Central New York CCOP, Syracuse [CA45389]; Illinois Oncology Research Association, Peoria [CA35113]; Long Island Jewish Medical Center, Lake Success [CA35279]; Memorial Sloan-Kettering Cancer Center, New York [CA77651]; Missouri Baptist Medical Center, St Louis [CA114558-02]; Mount Sinai Medical Center, Miami [CA45564]; Mount Sinai School of Medicine, New York [CA04457]; North Shore-Long Island Jewish Health System, New Hyde Park [CA35279]; Northern Indiana Cancer Research Consortium CCOP, South Bend [CA86726]; Roswell Park Cancer Institute, Buffalo [CA59518]; Southeast Cancer Control Consortium, Inc. [CA45808]; State University of New York Upstate Medical University [CA21060]; The Ohio State University Medical Center, Columbus [CA77658]; University of California at San Diego, San Diego [CA11789]; University of Chicago, Chicago [CA41287]; University of Maryland Greenebaum Cancer Center, Baltimore [CA31983]; University of Massachusetts Medical School, Worcester [CA37135]; University of Minnesota, Minneapolis [CA16450]; University of Missouri/Ellis Fischel Cancer Center [CA12046]; University of North Carolina at Chapel Hill, Chapel Hill [CA47559]; University of Vermont, Burlington, VT-Steven [CA77406]; Washington University School of Medicine, St Louis [CA77440]; Eastern Cooperative Oncology Group, Philadelphia [CA21115]; Southwest Oncology Group, San Antonio [CA32102]; National Cancer Institute of Canada, Toronto [CA77202]; National Cancer Institute at the National Institutes of Health [CA32291, CA77651, CA77406, CA21115, CA32102, CA77202, CA33601, CA25224, CA105409, CA31946] FX University of Oklahoma, Oklahoma, OK-Howard Ozer, MD, supported by CA37447;; Christiana Care Health Services, Inc., CCOP, Wilmington, DE -Stephen Grubbs, MD, supported by CA45418;; Dana-Farber Cancer Institute, Boston, MA-Harold J. Burstein, MD, supported by CA32291;; Dartmouth Medical School - Norris Cotton Cancer Center, Lebanon, NH-Konstantin Dragnev, MD, supported by CA04326;; Duke University Medical Center, Durham, NC-Jeffrey Crawford, MD, supported by CA47577;; Hematology-Oncology Associates of Central New York CCOP, Syracuse, NY-Jeffrey Kirshner, MD, supported by CA45389;; Illinois Oncology Research Association, Peoria, IL-John W. Kugler, MD, supported by CA35113;; Long Island Jewish Medical Center, Lake Success, NY-Kanti R. Rai, MD, supported by CA35279;; Memorial Sloan-Kettering Cancer Center, New York, NY-Clifford A. Hudis, MD, supported by CA77651;; Missouri Baptist Medical Center, St Louis, MO-Alan P. Lyss, MD, supported by CA114558-02;; Mount Sinai Medical Center, Miami, FL-Rogerio C. Lilenbaum, MD, supported by CA45564;; Mount Sinai School of Medicine, New York, NY-Lewis R. Silverman, MD, supported by CA04457;; North Shore-Long Island Jewish Health System, New Hyde Park, NY-Daniel Budman, MD, supported by CA35279;; Northern Indiana Cancer Research Consortium CCOP, South Bend, IN-Rafat Ansari, MD, supported by CA86726;; Roswell Park Cancer Institute, Buffalo, NY-Ellis Levine, MD, supported by CA59518;; Southeast Cancer Control Consortium, Inc., CCOP, Goldsboro, NC-James N. Atkins, MD, supported by CA45808;; State University of New York Upstate Medical University, Syracuse, NY-Stephen L. Graziano, MD, supported by CA21060;; The Ohio State University Medical Center, Columbus, OH-Clara D. Bloomfield, MD, supported by CA77658;; University of California at San Diego, San Diego, CA-Barbara A. Parker, MD, supported by CA11789;; University of Chicago, Chicago, IL-Hedy L. Kindler, MD, supported by CA41287;; University of Maryland Greenebaum Cancer Center, Baltimore, MD-Martin Edelman, MD, supported by CA31983;; University of Massachusetts Medical School, Worcester, MA-William V. Walsh, MD, supported by CA37135;; University of Minnesota, Minneapolis, MN-Bruce A. Peterson, MD, supported by CA16450;; University of Missouri/Ellis Fischel Cancer Center, Columbia, MO-Michael C. Perry, MD, supported by CA12046;; University of North Carolina at Chapel Hill, Chapel Hill, NC-Thomas C. Shea, MD, supported by CA47559;; University of Vermont, Burlington, VT-Steven M. Grunberg, MD, supported by CA77406;; Washington University School of Medicine, St Louis, MO-Nancy Bartlett, MD, supported by CA77440;; Eastern Cooperative Oncology Group, Philadelphia, PA-Robert L. Comis, MD, Chairman, supported by CA21115;; Southwest Oncology Group, San Antonio, TX-Laurence H. Baker, DO, Chairman, supported by CA32102;; North Central Cancer Treatment Group, Rochester, MN-Jan Buckner, MD, Chairman, supported by CA25224;; National Cancer Institute of Canada, Toronto, ON-Elizabeth Eisenhauer, MD, President; supported by CA77202.; This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers CA32291, CA33601, CA32102, CA77202, CA25224, CA21115, CA105409, CA77651, and CA77406; grant number CA31946 to the Cancer and Leukemia Group B and Richard L. Schilsky; and grant number CA33601 to the CALGB Statistical Center and Stephen George, PhD). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. NR 23 TC 12 Z9 12 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2012 VL 23 IS 12 BP 3075 EP 3081 DI 10.1093/annonc/mds133 PG 7 WC Oncology SC Oncology GA 044RX UT WOS:000311642100012 PM 22767584 ER PT J AU Morton, LM Gilbert, ES Hall, P Andersson, M Joensuu, H Vaalavirta, L Dores, GM Stovall, M Holowaty, EJ Lynch, CF Curtis, RE Smith, SA Kleinerman, RA Kaijser, M Storm, HH Pukkala, E Weathers, RE Linet, MS Rajaraman, P Fraumeni, JF Brown, LM van Leeuwen, FE Fossa, SD Johannesen, TB Langmark, F Lamart, S Travis, LB Aleman, BMP AF Morton, L. M. Gilbert, E. S. Hall, P. Andersson, M. Joensuu, H. Vaalavirta, L. Dores, G. M. Stovall, M. Holowaty, E. J. Lynch, C. F. Curtis, R. E. Smith, S. A. Kleinerman, R. A. Kaijser, M. Storm, H. H. Pukkala, E. Weathers, R. E. Linet, M. S. Rajaraman, P. Fraumeni, J. F., Jr. Brown, L. M. van Leeuwen, F. E. Fossa, S. D. Johannesen, T. B. Langmark, F. Lamart, S. Travis, L. B. Aleman, B. M. P. TI Risk of treatment-related esophageal cancer among breast cancer survivors SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; esophageal cancer; radiotherapy; second cancer ID LUNG-CANCER; RANDOMIZED-TRIALS; RADIATION-THERAPY; 15-YEAR SURVIVAL; HODGKINS-DISEASE; RADIOTHERAPY; MALIGNANCIES; WOMEN; ADENOCARCINOMA; CHEMOTHERAPY AB Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use. Nested case-control study of esophageal cancer among 289 748 >= 5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records. The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (P-trend < 0.001), with doses of >= 35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7-28]. Patients with hormonal therapy < 5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2-0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking). Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up. C1 [Morton, L. M.; Gilbert, E. S.; Dores, G. M.; Curtis, R. E.; Kleinerman, R. A.; Linet, M. S.; Rajaraman, P.; Fraumeni, J. F., Jr.; Lamart, S.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20892 USA. [Hall, P.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Andersson, M.] Copenhagen Univ Hosp, Dept Oncol, Copenhagen, Denmark. [Joensuu, H.; Vaalavirta, L.] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. [Dores, G. M.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Stovall, M.; Smith, S. A.; Weathers, R. E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Holowaty, E. J.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Lynch, C. F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Kaijser, M.] Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden. [Storm, H. H.] Danish Canc Soc, Copenhagen, Denmark. [Pukkala, E.] Finnish Canc Registry, Inst Stat & Epidemiol Canc Res, FIN-00170 Helsinki, Finland. [Brown, L. M.] RTI Int, Stat & Epidemiol, Rockville, MD USA. [van Leeuwen, F. E.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Fossa, S. D.] Oslo Univ Hosp, Dept Oncol, Oslo, Norway. [Fossa, S. D.] Univ Oslo, Oslo, Norway. [Johannesen, T. B.; Langmark, F.] Canc Registry Norway, Oslo, Norway. [Travis, L. B.] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14627 USA. [Aleman, B. M. P.] Netherlands Canc Inst, Dept Radiotherapy, Amsterdam, Netherlands. RP Morton, LM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS 7040,MSC 7238, Rockville, MD 20892 USA. EM mortonli@mail.nih.gov RI Morton, Lindsay/B-5234-2015; OI Morton, Lindsay/0000-0001-9767-2310; Storm, Hans/0000-0001-7223-8198; Kleinerman, Ruth/0000-0001-7415-2478; Joensuu, Heikki/0000-0003-0281-2507 FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services; National Cancer Institute [NO1-CP-31157]; Danish Cancer Society, Copenhagen, Denmark [NO1-CP-31019]; Finnish Cancer Registry, Helsinki, Finland [NO1-CP-31154]; Information Management Services, Inc., Silver Spring, USA [N01-CP-31003]; Karolinska Institute, Stockholm, Sweden [NO1-CP-31156]; University of Iowa, Iowa City, USA [NO1-CP-31155]; University of Texas MD Anderson Cancer Center, Houston, USA [N02-CP-55503]; Westat, Inc., Rockville, USA [N02-CP-31136] FX This work was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and National Cancer Institute contracts to Cancer Care Ontario, Toronto, Canada (NO1-CP-31157); Danish Cancer Society, Copenhagen, Denmark (NO1-CP-31019); Finnish Cancer Registry, Helsinki, Finland (NO1-CP-31154); Information Management Services, Inc., Silver Spring, USA (N01-CP-31003); Karolinska Institute, Stockholm, Sweden (NO1-CP-31156); University of Iowa, Iowa City, USA (NO1-CP-31155); The University of Texas MD Anderson Cancer Center, Houston, USA (N02-CP-55503); and Westat, Inc., Rockville, USA (N02-CP-31136). NR 42 TC 21 Z9 21 U1 0 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2012 VL 23 IS 12 BP 3081 EP 3091 DI 10.1093/annonc/mds144 PG 11 WC Oncology SC Oncology GA 044RX UT WOS:000311642100013 PM 22745217 ER PT J AU George, S Reichardt, P Lechner, T Li, S Cohen, DP Demetri, GD AF George, S. Reichardt, P. Lechner, T. Li, S. Cohen, D. P. Demetri, G. D. TI Hypertension as a potential biomarker of efficacy in patients with gastrointestinal stromal tumor treated with sunitinib SO ANNALS OF ONCOLOGY LA English DT Article DE biomarker; gastrointestinal stromal tumor; hypertension; sunitinib ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; KINASE INHIBITOR SUNITINIB; LUNG-CANCER; BEVACIZUMAB; TOXICITY; THERAPY; SU11248; VEGF AB Background: Reliable biomarkers of sunitinib response in gastrointestinal stromal tumor (GIST) are lacking. Hypertension (HTN), an on-target class effect of vascular endothelial growth factor signaling-pathway inhibitors, has been shown to correlate with clinical outcome in advanced renal cell carcinoma treated with sunitinib. Patients and methods: This retrospective analysis examined correlations between sunitinib-associated HTN and antitumor efficacy (N = 319) and safety (N = 1565) across three advanced GIST studies. Blood pressure (BP) was measured on days 1 and 28 of each treatment cycle at a minimum. Time-to-event endpoints were estimated using Kaplan-Meier methods, and patient subgroups with and without HTN (maximum systolic BP >= 140 mmHg and/or diastolic BP >= 90 mmHg) were compared using Cox proportional hazards models. Landmark analyses evaluated associations between early HTN and efficacy endpoints. Adverse events (AEs) were compared between groups. Results: Sunitinib-associated HTN correlated with improved objective response rates, time to tumor progression, progression-free survival, and overall survival. Almost all benefits remained significant in multivariate and landmark analyses. Overall incidences of HTN-related AEs were low and similar between groups; incidences of cardiovascular AEs were somewhat higher in patients with HTN. Conclusion: Sunitinib-associated HTN appeared to correlate with improved clinical outcomes in GIST, while incidences of HTN-associated AEs were generally low and manageable. C1 [George, S.; Demetri, G. D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Reichardt, P.] HELIOS Klinikum Bad Saarow, Dept Internal Med, Bad Saarow Pieskow, Germany. [Li, S.] Pfizer Oncol, Shanghai, Peoples R China. [Lechner, T.] Pfizer Oncol, New York, NY USA. [Demetri, G. D.] Harvard Univ, Sch Med, Ludwig Ctr Dana Farber, Harvard Canc Ctr, Boston, MA USA. [Cohen, D. P.] Pfizer Oncol, La Jolla, CA USA. RP George, S (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Dana 1212, Boston, MA 02215 USA. EM suzanne_george@dfci.harvard.edu FU Pfizer Inc.; Pfizer; Novartis; Bayer; Ariad; Johnson Johnson; Bristol-Myers Squibb; Infinity; Daiichi-Sankyo FX This retrospective exploratory analysis was sponsored by Pfizer Inc.; SG was compensated as an advisor for Pfizer and Novartis and received research funding from Pfizer, Novartis, and Bayer. PR was compensated as an advisor for and received honoraria from Pfizer. TL was and DPC is an employee of Pfizer and held/holds Pfizer stock. SL is an employee of Pfizer. GDD has received commercial research support from Pfizer, Novartis, Ariad, Johnson & Johnson, Bristol-Myers Squibb, Infinity, and Daiichi-Sankyo; and has served as a consultant for Pfizer, Novartis, Ariad, Johnson & Johnson, Genentech, Infinity, Bayer, EMD-Serono, GlaxoSmithKline, Amgen, Daiichi-Sankyo, ArQule, Enzon, and Millenium/Takeda. He has also served as a member of an advisory board for ZioPharm. All remaining authors have declared no conflicts of interest. NR 42 TC 32 Z9 32 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2012 VL 23 IS 12 BP 3180 EP 3187 DI 10.1093/annonc/mds179 PG 8 WC Oncology SC Oncology GA 044RX UT WOS:000311642100027 PM 22858558 ER PT J AU Roussos, P Katsel, P Davis, KL Siever, LJ Haroutunian, V AF Roussos, Panos Katsel, Pavel Davis, Kenneth L. Siever, Larry J. Haroutunian, Vahram TI A System-Level Transcriptomic Analysis of Schizophrenia Using Postmortem Brain Tissue Samples SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID GENOME-WIDE ASSOCIATION; MILD ALZHEIMER-DISEASE; NETWORK ANALYSIS; GENE-EXPRESSION; MICROARRAYS; DISORDER; OLIGODENDROCYTES; ABNORMALITIES; METAANALYSIS; PATHWAYS AB Context: Schizophrenia is a common, highly heritable, neurodevelopmental mental illness, characterized by genetic heterogeneity. Objective: To identify abnormalities in the transcriptome organization among older persons with schizophrenia and controls. Design: Weighted gene coexpression network analysis based on microarray transcriptomic profiling. Setting: Research hospital. Patients: Postmortem brain tissue samples from 4 different cerebrocortical regions (the dorsolateral prefrontal cortex, the middle temporal area, the temporopolar area, and the anterior cingulate cortex) from 21 persons with schizophrenia and 19 controls. Main Outcome Measures: Results from gene expression microarray analysis, from analysis of coexpression networks, and from module eigengene, module preservation, and enrichment analysis of schizophrenia-related genetic variants. Results: The oligodendrocyte, microglial, mitochondrial, and neuronal (GABAergic and glutamatergic) modules were associated with disease status. Enrichment analysis of genome-wide association studies in schizophrenia and other illnesses demonstrated that the neuronal (GABAergic and glutamatergic) and oligodendrocyte modules are enriched for genetically associated variants, whereas the microglial and mitochondrial modules are not, providing independent support for more direct involvement of these gene expression networks in schizophrenia. Interregional coexpression network analysis showed that the gene expression patterns that typically differentiate the frontal, temporal, and cingulate cortices in controls diminish significantly in persons with schizophrenia. Conclusions: These results support the existence of convergent molecular abnormalities in schizophrenia, providing a molecular neuropathological basis for the disease. C1 [Roussos, Panos; Katsel, Pavel; Davis, Kenneth L.; Siever, Larry J.; Haroutunian, Vahram] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Roussos, Panos; Siever, Larry J.; Haroutunian, Vahram] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Haroutunian, V (reprint author), Mt Sinai Sch Med, Dept Psychiat, Room 4F-33,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM vahram.haroutunian@mssm.edu RI Roussos, Panos/J-7090-2013 OI Roussos, Panos/0000-0002-4640-6239 FU National Institutes of Health [MH066392, MH064673]; Veterans Administration Mental Illness Research, Education; Clinical Centers award; Clinical Merit award FX This work was supported by National Institutes of Health grants MH066392 and MH064673 (to Dr Haroutunian) and by Veterans Administration Mental Illness Research, Education, and Clinical Centers and Merit awards (to Drs Siever and Haroutunian, respectively). NR 38 TC 31 Z9 31 U1 0 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 2012 VL 69 IS 12 BP 1205 EP 1215 DI 10.1001/archgenpsychiatry.2012.704 PG 11 WC Psychiatry SC Psychiatry GA 046ZL UT WOS:000311804500003 PM 22868662 ER PT J AU Ernst, C Marshall, CR Shen, YP Metcalfe, K Rosenfeld, J Hodge, JC Torres, A Blumenthal, I Chiang, C Pillalamarri, V Crapper, L Diallo, AB Ruderfer, D Pereira, S Sklar, P Purcell, S Wildin, RS Spencer, AC Quade, BF Harris, DJ Lemyre, E Wu, BL Stavropoulos, DJ Geraghty, MT Shaffer, LG Morton, CC Scherer, SW Gusella, JF Talkowski, ME AF Ernst, Carl Marshall, Christian R. Shen, Yiping Metcalfe, Kay Rosenfeld, Jill Hodge, Jennelle C. Torres, Alcy Blumenthal, Ian Chiang, Colby Pillalamarri, Vamsee Crapper, Liam Diallo, Alpha B. Ruderfer, Douglas Pereira, Shahrin Sklar, Pamela Purcell, Shaun Wildin, Robert S. Spencer, Anne C. Quade, Bradley F. Harris, David J. Lemyre, Emanuelle Wu, Bai-lin Stavropoulos, Dimitri J. Geraghty, Michael T. Shaffer, Lisa G. Morton, Cynthia C. Scherer, Stephen W. Gusella, James F. Talkowski, Michael E. TI Highly Penetrant Alterations of a Critical Region Including BDNF in Human Psychopathology and Obesity SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID NEUROTROPHIC FACTOR GENE; COPY NUMBER VARIATION; KNOCKOUT MICE; TARGETED DISRUPTION; DEVELOPMENTAL DELAY; SOCIAL DEFEAT; WAGR SYNDROME; HUMAN GENOME; BRAIN; ASSOCIATION AB Context: Brain-derived neurotrophic factor (BDNF) is suspected of being a causative factor in psychiatric disorders based on case reports or studies involving large structural anomalies. Objective: To determine the involvement of BDNF in human psychopathology. Design: Case-control study. Setting: Microarray-based comparative genomic hybridization data from 7 molecular diagnostic centers including 38 550 affected subjects and 28 705 unaffected subjects. Patients: Subjects referred to diagnostic screening centers for microarray-based comparative genomic hybridization for physical or cognitive impairment. Main Outcome Measures: Genomic copy number gains and losses. Results: We report 5 individuals with psychopathology and genomic deletion of a critical region including BDNF. The defined critical region was never disrupted in control subjects or diagnostic cases without developmental abnormalities. Conclusion: Hemizygosity of the BDNF region contributes to variable psychiatric phenotypes including anxiety, behavioral, and mood disorders. C1 [Ernst, Carl; Crapper, Liam; Diallo, Alpha B.] McGill Univ, Dept Psychiat, Verdun, PQ H4H 1R3, Canada. [Lemyre, Emanuelle] St Justine Hosp, Montreal, PQ, Canada. [Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada. [Stavropoulos, Dimitri J.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Geraghty, Michael T.] Univ Ottawa, Childrens Hosp Eastern Ontario, Ottawa, ON, Canada. [Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Talkowski, Michael E.] Harvard Univ, Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Neurol,Med Sch, Boston, MA 02114 USA. [Ernst, Carl; Gusella, James F.; Talkowski, Michael E.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Morton, Cynthia C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Shen, Yiping; Harris, David J.; Wu, Bai-lin] Boston Childrens Hosp, Dept Lab Med & Pathol, Boston, MA USA. [Torres, Alcy] Boston Childrens Hosp, Dept Pediat, Boston, MA USA. [Harris, David J.] Boston Childrens Hosp, Div Clin Genet, Boston, MA USA. [Quade, Bradley F.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Pereira, Shahrin; Quade, Bradley F.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Ernst, Carl; Morton, Cynthia C.; Gusella, James F.; Talkowski, Michael E.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, England. [Wu, Bai-lin] Fudan Univ, Shanghai Med Coll, Childrens Hosp, Shanghai 200433, Peoples R China. [Wu, Bai-lin] Fudan Univ, Inst Biomed Sci, Shanghai Med Coll, Shanghai 200433, Peoples R China. [Shen, Yiping] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Shanghai 200030, Peoples R China. [Metcalfe, Kay] Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Rosenfeld, Jill; Shaffer, Lisa G.] PerkinElmer Inc, Signature Genom Labs, Spokane, WA USA. [Hodge, Jennelle C.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Sklar, Pamela] Mt Sinai Sch Med, New York, NY USA. [Wildin, Robert S.] Idaho State Genet Serv Program, Boise, ID USA. [Wildin, Robert S.] St Lukes Childrens Hosp, Boise, ID USA. [Spencer, Anne C.] Coll Idaho, Dept Philosophy & Relig, Caldwell, NJ USA. RP Ernst, C (reprint author), McGill Univ, Dept Psychiat, 6875 LaSalle Blvd,Frank Common Bldg,Room 2101-2, Verdun, PQ H4H 1R3, Canada. EM carl.ernst@mcgill.ca; talkowski@chgr.mgh.harvard.edu RI Scherer, Stephen /B-3785-2013; Ruderfer, Douglas/M-5795-2016; OI Scherer, Stephen /0000-0002-8326-1999; Ruderfer, Douglas/0000-0002-2365-386X; Chiang, Colby/0000-0002-4113-6065; Torres, Alcy/0000-0001-5798-9161 FU Canada Research Chair in Psychiatric Genetics from the Canadian Institute of Health Research; National Institutes of Health [GM061354, HD065286, MH095687]; Simons Foundation Autism Research Initiative; National Basic Research Program of China (973 Program) [2010CB529601]; Science and Technology Council of Shanghai [09JC1402400, 09ZR1404500] FX This work was funded by a Canada Research Chair in Psychiatric Genetics from the Canadian Institute of Health Research (Dr Ernst), grants GM061354 (Drs Morton and Gusella), HD065286 (Dr Gusella), and MH095687 (Dr Talkowski) from the National Institutes of Health, the Simons Foundation Autism Research Initiative (Drs Gusella and Talkowski), grant 2010CB529601 from the National Basic Research Program of China (973 Program) (Dr Wu), and grants 09JC1402400 and 09ZR1404500 from the Science and Technology Council of Shanghai (Dr Wu). NR 44 TC 10 Z9 10 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 2012 VL 69 IS 12 BP 1238 EP 1246 DI 10.1001/archgenpsychiatry.2012.660 PG 9 WC Psychiatry SC Psychiatry GA 046ZL UT WOS:000311804500006 PM 23044507 ER PT J AU Lyoo, IK Yoon, S Jacobson, AM Hwang, J Musen, G Kim, JE Simonson, DC Bae, S Bolo, N Kim, DJ Weinger, K Lee, JH Ryan, CM Renshaw, PF AF Lyoo, In Kyoon Yoon, Sujung Jacobson, Alan M. Hwang, Jaeuk Musen, Gail Kim, Jieun E. Simonson, Donald C. Bae, Sujin Bolo, Nicolas Kim, Dajung J. Weinger, Katie Lee, Junghyun H. Ryan, Christopher M. Renshaw, Perry F. TI Prefrontal Cortical Deficits in Type 1 Diabetes Mellitus Brain Correlates of Comorbid Depression SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; SURFACE-BASED ANALYSIS; POOR GLYCEMIC CONTROL; COGNITIVE PERFORMANCE; MAJOR DEPRESSION; MOOD DISORDERS; BIDIRECTIONAL ASSOCIATION; STRUCTURAL ABNORMALITIES; COORDINATE SYSTEM AB Context: Neural substrates that may be responsible for the high prevalence of depression in type 1 diabetes mellitus (T1DM) have not yet been elucidated. Objective: To investigate neuroanatomic correlates of depression in T1DM. Design: Case-control study using high-resolution brain magnetic resonance images. Settings: Joslin Diabetes Center and McLean Hospital, Massachusetts, and Seoul National University Hospital, South Korea. Participants: A total of 125 patients with T1DM (44 subjects with >= 1 previous depressive episodes [T1DM-depression group] and 81 subjects who had never experienced depressive episodes [T1DM-only group]), 23 subjects without T1DM but with 1 or more previous depressive episodes (depression group), and 38 healthy subjects (control group). Main Outcome Measures: Spatial distributions of cortical thickness for each diagnostic group were compared with the control group using a surface-based approach. Among patients with T1DM, associations between metabolic control measures and cortical thickness deficits were examined. Results: Thickness reduction in the bilateral superior prefrontal cortical regions was observed in the T1DM-depression, T1DM-only, and depression groups relative to the control group at corrected P<.01. Conjunction analyses demonstrated that thickness reductions related to the influence of T1DM and those related to past depressive episode influence were observed primarily in the superior prefrontal cortical region. Long-term glycemic control levels were associated with superior prefrontal cortical deficits in patients with T1DM (beta=-0.19, P=.02). Conclusions: This study provides evidence that thickness reduction of prefrontal cortical regions in patients with T1DM, as modified by long-term glycemic control, could contribute to the increased risk for comorbid depression. C1 [Lyoo, In Kyoon; Kim, Jieun E.] Ewha Womans Univ, Ewha Brain Inst, Seoul 120750, South Korea. [Lyoo, In Kyoon; Kim, Jieun E.] Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul 120750, South Korea. [Yoon, Sujung] Catholic Univ Korea, Coll Med, Dept Psychiat, Seoul, South Korea. [Hwang, Jaeuk] Soonchunhyang Univ, Dept Psychiat, Coll Med, Seoul, South Korea. [Bae, Sujin; Kim, Dajung J.; Lee, Junghyun H.] Seoul Natl Univ, Dept Psychiat, Seoul, South Korea. [Bae, Sujin; Kim, Dajung J.; Lee, Junghyun H.] Seoul Natl Univ, Interdisciplinary Program Neurosci, Seoul, South Korea. [Lyoo, In Kyoon; Yoon, Sujung; Renshaw, Perry F.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Lyoo, In Kyoon; Yoon, Sujung; Renshaw, Perry F.] Univ Utah, Inst Brain, Salt Lake City, UT USA. [Jacobson, Alan M.; Musen, Gail; Weinger, Katie] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Musen, Gail; Bolo, Nicolas; Weinger, Katie] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Simonson, Donald C.] Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. [Bolo, Nicolas] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Bolo, Nicolas] McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. [Jacobson, Alan M.] Winthrop Univ Hosp, Dept Psychiat, Mineola, NY 11501 USA. [Ryan, Christopher M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. RP Lyoo, IK (reprint author), Ewha Womans Univ, Ewha Brain Inst, 52 Ewhayeodaegil, Seoul 120750, South Korea. EM inkylyoo@gmail.com FU Eli Lilly and Company; AstraZeneca; GlaxoSmithKline; Lundbeck; Roche; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [DK-060754, DK-084202]; Brain Research Center of the 21st Century Frontier Research Program [2010K000814]; Global Research Network Program, the Korea Research Foundation [KRF-2008-220-E00021] FX Dr Lyoo has received research support from Eli Lilly and Company, AstraZeneca, GlaxoSmithKline, and Lundbeck. Dr Renshaw has been a consultant to Roche, Novartis, Kyowa Hakko, and Repligen, and he has received research support from GlaxoSmithKline and Roche.; This study was supported by grants DK-060754 and DK-084202 from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (Dr Jacobson), grant 2010K000814 from the Brain Research Center of the 21st Century Frontier Research Program (Dr Lyoo), and grant KRF-2008-220-E00021 from the Global Research Network Program, the Korea Research Foundation (Dr Lyoo). NR 99 TC 12 Z9 12 U1 3 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-990X EI 1538-3636 J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 2012 VL 69 IS 12 BP 1267 EP 1276 DI 10.1001/archgenpsychiatry.2012.543 PG 10 WC Psychiatry SC Psychiatry GA 046ZL UT WOS:000311804500009 PM 23090665 ER PT J AU Brawner, BM AF Brawner, Bridgette M. TI Attitudes and Beliefs Regarding Depression, HIV/AIDS, and HIV Risk-Related Sexual Behaviors Among Clinically Depressed African American Adolescent Females SO ARCHIVES OF PSYCHIATRIC NURSING LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; REDUCTION INTERVENTIONS; PLANNED BEHAVIOR; PREDICTORS; COMMUNICATION; KNOWLEDGE; SYMPTOMS; VALIDITY; GIRLS AB Individuals' attitudes and beliefs toward behaviors are key indicators of behavioral performance. The purposes of this study were to elucidate attitudes and beliefs about depression, HIV/AIDS, and HIV risk-related sexual behaviors among clinically depressed African American adolescent females and to develop an understanding of their context for HIV risk. For this descriptive qualitative inquiry, semistructured interviews and surveys were employed (N=24). The narratives reveal that behavioral sequelae of depression (i.e., loneliness) can produce risk for HIV. These findings may guide psychiatric nurse educators, scientists, and practitioners to modify HIV risk among clinically depressed African American adolescent females. (C) 2012 Elsevier Inc. All rights reserved. C1 Univ Penn, Ctr Hlth Equ Res, Sch Nursing, Philadelphia, PA 19104 USA. RP Brawner, BM (reprint author), Univ Penn, Ctr Hlth Equ Res, Sch Nursing, 418 Curie Blvd,Floor 2L,Room 236, Philadelphia, PA 19104 USA. EM brawnerb@nursing.upenn.edu FU Substance Abuse and Mental Health Services Administration at the American Nurses Association Minority Fellowship Program [5 SM058566-02]; Hampton-Penn Center for Health Disparities Research [NINR P20NR008361]; Fontaine Society Fellowship at the University of Pennsylvania FX Funding for this research was provided by the Substance Abuse and Mental Health Services Administration at the American Nurses Association Minority Fellowship Program (5 SM058566-02), the Hampton-Penn Center for Health Disparities Research (NINR P20NR008361), and the Fontaine Society Fellowship at the University of Pennsylvania. NR 39 TC 0 Z9 0 U1 1 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9417 J9 ARCH PSYCHIAT NURS JI Arch. Psychiatr. Nurs. PD DEC PY 2012 VL 26 IS 6 BP 464 EP 476 DI 10.1016/j.apnu.2012.06.003 PG 13 WC Nursing; Psychiatry SC Nursing; Psychiatry GA 047CD UT WOS:000311814400005 PM 23164403 ER PT J AU Lee, IS Spector, M AF Lee, In-Seop Spector, Myron TI The people behind the papers, and how much data is enough? SO BIOMEDICAL MATERIALS LA English DT Editorial Material C1 [Lee, In-Seop] Yonsei Univ, Seoul 120749, South Korea. [Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Lee, IS (reprint author), Yonsei Univ, Seoul 120749, South Korea. NR 1 TC 0 Z9 0 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 J9 BIOMED MATER JI Biomed. Mater. PD DEC PY 2012 VL 7 IS 6 AR 060201 DI 10.1088/1748-6041/7/6/060201 PG 2 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 046GN UT WOS:000311753600001 ER PT J AU Zhang, D Mita, M Shapiro, GI Poon, J Small, K Tzontcheva, A Kantesaria, B Zhu, YL Bannerji, R Statkevich, P AF Zhang, Da Mita, Monica Shapiro, Geoffrey I. Poon, Jennifer Small, Karen Tzontcheva, Anjela Kantesaria, Bhavna Zhu, Yali Bannerji, Rajat Statkevich, Paul TI Effect of aprepitant on the pharmacokinetics of the cyclin-dependent kinase inhibitor dinaciclib in patients with advanced malignancies SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Dinaciclib; Aprepitant; Drug-drug interactions; Cyclin-dependent kinase; Malignancies ID RNA-POLYMERASE-II; CELL-CYCLE; SCH 727965; CANCER; POTENT AB Dinaciclib, a selective inhibitor of cyclin-dependent kinase (CDK) 1, CDK2, CDK5, and CDK9, is metabolized via CYP3A4. Aprepitant, a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting, is an inhibitor and inducer of CYP3A4. We conducted a randomized, crossover study to investigate the effects of single oral doses of aprepitant when coadministered with dinaciclib. As part of a phase 1 dose-escalation trial, subjects with advanced malignancies were randomized into a 2-period, multi-cycle, crossover study to investigate the effect of single doses of oral aprepitant on the pharmacokinetics of 29.6 mg/m(2) dinaciclib administered by 2-h intravenous infusion. During cycle 1 and cycle 2, subjects received dinaciclib with aprepitant in one cycle and dinaciclib without aprepitant in the other cycle; aprepitant was administered at a dose of 125 mg orally on day 1 and 80 mg orally on days 2 and 3, along with standard dosing regimens of ondansetron and dexamethasone. Twelve patients completed the study; T (max) occurred approximately 2 h after the initiation of the infusion. The percent geometric mean ratio (dinaciclib + aprepitant vs. dinaciclib alone) was 106 % (90 % confidence interval [CI] 89-126 %) and 111 % (90 % CI 93-132 %) for dinaciclib C (max) and AUC([I]), respectively. The half-life and clearance of dinaciclib were similar, with or without aprepitant. Coadministration of dinaciclib with aprepitant resulted in no clinically significant effect on the pharmacokinetics and did not alter the safety profile of dinaciclib in patients with advanced malignancies. C1 [Statkevich, Paul] Merck & Co Inc, Pharmacokinet Pharmacodynam & Drug Metab, Kenilworth, NJ 07059 USA. [Zhang, Da; Small, Karen; Tzontcheva, Anjela; Kantesaria, Bhavna; Zhu, Yali] Merck Sharp & Dohme Corp, Whitehouse Stn, NJ USA. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. RP Statkevich, P (reprint author), Merck & Co Inc, Pharmacokinet Pharmacodynam & Drug Metab, 2000 Galloping Hill Rd, Kenilworth, NJ 07059 USA. EM paul.statkevich@merck.com FU Merck Sharp Dohme Corp. FX The study was sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (Whitehouse Station, NJ). Medical writing and editorial assistance were provided by Kakuri M. Omari, PhD, of Integrus Scientific, a division of Medicus International New York (New York, NY). This assistance was funded by Merck Sharp & Dohme Corp. The authors are fully responsible for all content and editorial decisions and received no financial support or other compensation related to the development of the manuscript. NR 13 TC 9 Z9 9 U1 3 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD DEC PY 2012 VL 70 IS 6 BP 891 EP 898 DI 10.1007/s00280-012-1967-y PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 042ZZ UT WOS:000311513200013 PM 23053255 ER PT J AU Tanwar, PS Commandeur, AE Zhang, LH Taketo, MM Teixeira, JM AF Tanwar, Pradeep S. Commandeur, Arno E. Zhang, LiHua Taketo, Makoto M. Teixeira, Jose M. TI The Mullerian inhibiting substance type 2 receptor suppresses tumorigenesis in testes with sustained beta-catenin signaling SO CARCINOGENESIS LA English DT Article ID GRANULOSA-CELL TUMOR; HUMAN OVARIAN-CANCER; II RECEPTOR; WNT/BETA-CATENIN; LEYDIG-CELLS; IN-VITRO; DUCT SYNDROME; CONDITIONAL DELETION; ENDOMETRIAL CANCER; SEXUAL DEVELOPMENT AB Dysregulated WNT/-catenin signaling in murine testes results in a phenotype with complete germ cell loss that resembles human Sertoli cell-only syndrome. In other systems, including the ovary, dysregulated WNT/-catenin induces tumorigenesis but no tumors are observed in the mutant testes without deletion of a tumor suppressor, such as phosphatase and tensin homolog (PTEN). Mllerian inhibiting substance (MIS, also known as AMH), a member of the transforming growth factor- family of growth factors responsible for Mllerian duct regression in fetal males, has been shown to inhibit tumor growth in vitro and in vivo but its role as an endogenous tumor suppressor has never been reported. We have deleted the MIS type 2 receptor (MISR2), and thus MIS signaling, in mice with dysregulated WNT/-catenin and show that these mice develop testicular stromal tumors with 100% penetrance within a few months postnatal. The tumors are highly proliferative and have characteristics of either Sertoli cell tumors or progenitor Leydig cell tumors based on their marker profiles and histology. Phosphorylated Sma and mothers against decapentaplegic-related homolog 1/5/8 is absent in the tumors and -catenin target genes are induced. The tumor suppressor TP53 is also highly expressed in the tumors, as is phosphorylated H2AX, which is indicative of DNA damage. The phenotype of these tumors closely resembles those observed when PTEN is also deleted in mice with dysregulated WNT/-catenin. Tumorigenesis in these mice provides conclusive evidence that physiological MIS signaling is a tumor suppressor mechanism and suggests that targeted treatment of MISR2-expressing cancers with therapeutic MIS should have a beneficial effect on tumor progression. C1 [Tanwar, Pradeep S.; Commandeur, Arno E.; Zhang, LiHua; Teixeira, Jose M.] Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Tanwar, Pradeep S.; Commandeur, Arno E.; Zhang, LiHua; Teixeira, Jose M.] Harvard Univ, Sch Med, Boston, MA USA. [Taketo, Makoto M.] Kyoto Univ, Grad Sch Med, Kyoto, Japan. RP Teixeira, JM (reprint author), Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. EM teixeira@helix.mgh.harvard.edu FU National Institute of Child Health and Human Development [HD052701]; Vincent Memorial Research Funds FX National Institute of Child Health and Human Development to J.M.T. (HD052701); Vincent Memorial Research Funds. NR 67 TC 6 Z9 8 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2012 VL 33 IS 12 BP 2351 EP 2361 DI 10.1093/carcin/bgs281 PG 11 WC Oncology SC Oncology GA 048IB UT WOS:000311903500006 PM 22962306 ER PT J AU Huang, YY Balasubramanian, T Yang, E Luo, DZ Diers, JR Bocian, DF Lindsey, JS Holten, D Hamblin, MR AF Huang, Ying-Ying Balasubramanian, Thiagarajan Yang, Eunkyung Luo, Dianzhong Diers, James R. Bocian, David F. Lindsey, Jonathan S. Holten, Dewey Hamblin, Michael R. TI Stable Synthetic Bacteriochlorins for Photodynamic Therapy: Role of Dicyano Peripheral Groups, Central Metal Substitution (2H, Zn, Pd), and Cremophor EL Delivery SO CHEMMEDCHEM LA English DT Article DE antitumor agents; Cremophor EL micelles; photodynamic therapy; photostability; reactive oxygen species; synthetic bacteriochlorins ID TOPOISOMERASE-I INHIBITORS; ANTITUMOR-ACTIVITY; HYDROPHILIC CAMPTOTHECIN; BIOLOGICAL EVALUATION; PRECLINICAL PROFILE; INDUCED APOPTOSIS; DNA; NEUROBLASTOMA; XENOGRAFTS; CHEMISTRY AB A series of four stable synthetic bacteriochlorins was tested in vitro in HeLa cells for their potential in photodynamic therapy (PDT). The parent bacteriochlorin (BC), dicyano derivative (NC)(2)BC and corresponding zinc chelate (NC)(2)BC-Zn and palladium chelate (NC)(2)BC-Pd were studied. Direct dilution of a solution of bacteriochlorin in an organic solvent (N,N-dimethylacetamide) into serum-containing medium was compared with the dilution of bacteriochlorin in Cremophor EL (CrEL; polyoxyethylene glycerol triricinoleate) micelles into the same medium. CrEL generally reduced aggregation (as indicated by absorption and fluorescence) and increased activity up to tenfold (depending on bacteriochlorin), although it decreased cellular uptake. The order of PDT activity against HeLa human cancer cells after 24 h incubation and illumination with 10 J cm(-2) of near-infrared (NIR) light is (NC)(2)BC-Pd (LD50=25 nm) > (NC)(2)BC > (NC)(2)BC-Zn approximate to BC. Subcellular localization was determined to be in the endoplasmic reticulum, mitochondria and lysosomes, depending on the bacteriochlorin. (NC)(2)BC-Pd showed PDT-mediated damage to mitochondria and lysosomes, and the greatest production of hydroxyl radicals as determined using a hydroxyphenylfluorescein probe. The incorporation of cyano substituents provides an excellent motif for the enhancement of the photoactivity and photostability of bacteriochlorins as PDT photosensitizers. C1 [Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Huang, Ying-Ying; Luo, Dianzhong] Guangxi Med Univ, Dept Pathol, Nanning 530021, Guangxi, Peoples R China. [Balasubramanian, Thiagarajan; Lindsey, Jonathan S.] N Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA. [Yang, Eunkyung; Holten, Dewey] Washington Univ, Dept Chem, St Louis, MO 63130 USA. [Diers, James R.; Bocian, David F.] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Huang, YY (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Lindsey, Jonathan/J-7761-2012; Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU US National Institutes of Health (NIH) [R01AI050875]; Jimmy V-North Carolina State University Cancer Therapeutics Training Program; US National Institute of Allergy and Infectious Diseases (NIAID) [R41AI072854]; Division of Chemical Sciences, Geosciences and Biosciences, Office of Basic Energy Sciences, US Department of Energy [DE-FG02-05ER15660, DE-FG02-05ER15661] FX This work was supported by the US National Institutes of Health (NIH) (R01AI050875 to M.R.H.) and the Jimmy V-North Carolina State University Cancer Therapeutics Training Program. Y.-Y.H. and T.B. were supported by a grant from the US National Institute of Allergy and Infectious Diseases (NIAID) to NIRvana Pharmaceuticals, Inc. (R41AI072854). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID or the NIH. Photochemical characterization of the bacteriochlorins described herein was initially motivated by solar-energy studies and supported by grants from the Division of Chemical Sciences, Geosciences and Biosciences, Office of Basic Energy Sciences, US Department of Energy (DE-FG02-05ER15660 to D.F.B., DE-FG02-05ER15661 to D.H.). D.F.B., D.H., and J.S.L. are cofounders of NIRvana Sciences Inc., successor to NIRvana Pharmaceuticals, which develops bacteriochlorins for clinical diagnostics. The company did not provide research support for the studies described herein. NR 41 TC 26 Z9 26 U1 1 U2 36 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1860-7179 J9 CHEMMEDCHEM JI ChemMedChem PD DEC PY 2012 VL 7 IS 12 BP 2155 EP 2167 DI 10.1002/cmdc.201200351 PG 13 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 045HK UT WOS:000311685800012 PM 23065820 ER PT J AU Suzuki, E Karam, E Williams, S Watson, DK Gilkeson, G Zhang, XK AF Suzuki, Eiji Karam, Eva Williams, Sarah Watson, Dennis K. Gilkeson, Gary Zhang, Xian K. TI Fli-1 transcription factor affects glomerulonephritis development by regulating expression of monocyte chemoattractant protein-1 in endothelial cells in the kidney SO CLINICAL IMMUNOLOGY LA English DT Article DE Glomerulonephritis; Inflammatory chemokines; Infiltrations; Transcription factors ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; NF-KAPPA-B; RENAL-DISEASE; ETS FAMILY; CHEMOKINE RECEPTOR; MRL-FAS(LPR) MICE; GENE-EXPRESSION; NEPHRITIS; MCP-1; INFLAMMATION AB Expression of transcription factor Fli-1 is implicated in the development of glomerulonephritis. Fli-1 heterozygous knockout (Fli1(+/-)) NZM2410 mice, a murine model of lupus, had significantly improved survival and reduced glomerulonephritis. In this study, we found that infiltrated inflammatory cells were significantly decreased in the kidneys from NZM2410 mice. The expression of monocyte chemoattractant protein-1 (MCP-1) was significantly decreased in kidneys from Fli-1(+/-) NZM2410 mice. The primary endothelial cells isolated from the kidneys of Fli-1(+/-)NZM2410 mice produced significantly less MCP-1. In endothelial cells transfected with specific Fli-1 siRNA the production of MCP-1 was significantly reduced compared to cells transfected with negative control siRNA. By Chromatin Immunoprecipitation (ChIP) assay, we further demonstrated that Fli-1 directly binds to the promoter of the MCP-1 gene. Our data indicate that Fli-1 impacts glomerulonephritis development by regulating expression of inflammatory chemokine MCP-1 and inflammatory cell infiltration in the kidneys in the NZM2410 mice. Published by Elsevier Inc. C1 [Suzuki, Eiji; Karam, Eva; Gilkeson, Gary; Zhang, Xian K.] Med Univ S Carolina, Div Rheumatol & Immunol, Dept Med, Charleston, SC 29425 USA. [Williams, Sarah; Gilkeson, Gary; Zhang, Xian K.] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC 29403 USA. [Watson, Dennis K.] Med Univ S Carolina, Dept Lab Med & Pathol, Charleston, SC 29425 USA. RP Zhang, XK (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, Dept Med, Suite 912,96 Jonathan Lucas St,MSC637, Charleston, SC 29425 USA. EM zhangjo@musc.edu FU National Institutes of Health [R01AR056670]; Medical Research Service, Department of Veterans Affairs FX This study was supported in part by National Institutes of Health grants (R01AR056670 to X.K.Z.) and the Medical Research Service, Department of Veterans Affairs (to G.G. and X.K.Z.). We thank Mr. Jeremy Mathenia and Mr. Emanuel Reyes-Cortes for their excellent technical supports. NR 50 TC 14 Z9 14 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD DEC PY 2012 VL 145 IS 3 BP 201 EP 208 DI 10.1016/j.clim.2012.09.006 PG 8 WC Immunology SC Immunology GA 044YQ UT WOS:000311661500003 PM 23108091 ER PT J AU Lochner, C Grant, JE Odlaug, BL Woods, DW Keuthen, NJ Stein, DJ AF Lochner, Christine Grant, Jon E. Odlaug, Brian L. Woods, Douglas W. Keuthen, Nancy J. Stein, Dan J. TI DSM-5 FIELD SURVEY: HAIR-PULLING DISORDER (TRICHOTILLOMANIA) SO DEPRESSION AND ANXIETY LA English DT Article DE hair-pulling disorder; trichotillomania; diagnostics; DSM ID COMORBIDITY; INVENTORY; CHILDREN; PULLERS AB Background The aim of this multisite field survey was to examine the DSM-IV-TR criteria, proposed DSM-5 diagnostic criteria, as well as a number of possible additional diagnostic criteria, in patients with hair-pulling disorder (HPD, or trichotillomania). Methods Four sites were involved. Participants older than 10 years of age, male or female, with hair-pulling symptoms in the last 4 weeks were included. Participants were assessed with two modules based on the Structured Clinical Interview for DSM (SCID-I/P), which addressed the DSM-IV-TR criteria set as well as proposed DSM-5 diagnostic criteria for HPD, respectively. Additional questions were established to test other possible diagnostic criteria. Results Eighty-four (79 female, 5 male, 83 adult) participants with current hair-pulling symptoms were included. All of these participants had recurrent hair-pulling and most (n = 82 [98%]) reported repeated attempts to decrease or stop hair-pulling, and 70 (n = 70 [83%]) met the clinical significance criterion. Diagnostic criteria focused on urge, tension, need, drive, or impulse to pull, or pleasure, gratification or relief during or after pulling, were endorsed by many, but not all. Individuals who did endorse such criteria had significantly more severe hair-pulling symptoms. Conclusions These data support the proposed diagnostic criteria for HPD in adults. Although most adult patients have urges to pull or experience a sense of relief on pulling, as in the case of skin-picking disorder, such phenomena are not universal and so should not be included in the diagnostic criteria. An additional criterion focused on repeated attempts to decrease or stop hair-pulling seems warranted. Depression and Anxiety 29: 1025-1031, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Lochner, Christine; Stein, Dan J.] Univ Stellenbosch, Dept Psychiat, MRC Unit Anxiety & Stress Disorders, ZA-7505 Tygerberg, South Africa. [Grant, Jon E.; Odlaug, Brian L.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. [Odlaug, Brian L.] Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark. [Woods, Douglas W.] Univ Wisconsin, Dept Psychol, Milwaukee, WI 53201 USA. [Keuthen, Nancy J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Stein, Dan J.] Univ Cape Town, Dept Psychiat & Mental Hlth, ZA-7700 Rondebosch, South Africa. RP Lochner, C (reprint author), Univ Stellenbosch, Dept Psychiat, MRC Unit Anxiety & Stress Disorders, POB 19063, ZA-7505 Tygerberg, South Africa. EM cl2@sun.ac.za RI Odlaug, Brian/C-5586-2013; Stein, Dan/A-1752-2008 OI Odlaug, Brian/0000-0001-5407-0686; Stein, Dan/0000-0001-7218-7810 FU Trichotillomania Learning Centre; Center for Excellence in Gambling Research grant; Institute for Responsible Gaming (NCRG); American Recovery and Reinvestment Act (ARRA) grant from the National Institute on Drug Abuse [1RC1DA028279-01]; Forest Pharmaceuticals; Psyadon Pharmaceuticals; Transcept Pharmaceuticals; University of South Florida; National Institute of Mental Health [1R01MH080966-01A2]; National Institutes of Health; Tourette Syndrome Association; Springer Press; Guilford Press; New Harbinger Press; Oxford University Press; Trichotillomania Learning Center; Eli Lilly; Abbott; Astra Zeneca; GlaxoSmithKline; Jazz Pharmaceuticals; Johnson Johnson; Lundbeck; Orion; Pfizer; Pharmacia; Roche; Servier; Solvay; Sumitomo; Takeda; Tikvah; Wyeth FX Dr. Lochner is a member of the Trichotillomania International Consortium for Research (TrIC Research) and has received a research grant from the Trichotillomania Learning Centre. Dr. Grant is supported by a Center for Excellence in Gambling Research grant by the Institute for Responsible Gaming (NCRG) and an American Recovery and Reinvestment Act (ARRA) grant from the National Institute on Drug Abuse (1RC1DA028279-01) and has also received research grants from Forest Pharmaceuticals, Psyadon Pharmaceuticals, Transcept Pharmaceuticals, and the University of South Florida. He also serves as the Editor-in-Chief of the Journal of Gambling Studies. Mr. Odlaug has received a research grant from the Trichotillomania Learning Center and honoraria from Oxford University Press. This project was also supported in part, by a grant from the National Institute of Mental Health (1R01MH080966-01A2; D. Woods: PI) from the National Institutes of Health. Dr. Woods has also received grant support from the Tourette Syndrome Association and receives royalties from Springer Press, Guilford Press, New Harbinger Press, and Oxford University Press. Dr. Keuthen has received funding from the Trichotillomania Learning Center and from Forest Pharmaceuticals and Eli Lilly. She has equity holdings in Allergan Inc., GlaxoSmithKline, Johnson & Johnson, Merck & Co Inc., Pfizer Inc., and Procter & Gamble Co. She receives honoraria from New Harbinger Press. She also is a member of the Scientific Advisory Board of the Trichotillomania Learning Centre and the Trichotillomania International Consortium for Research (TrIC Research). Dr. Stein has received research grants and/or consultancy honoraria from Abbott, Astra Zeneca, Eli-Lilly, GlaxoSmithKline, Jazz Pharmaceuticals, Johnson & Johnson, Lundbeck, Orion, Pfizer, Pharmacia, Roche, Servier, Solvay, Sumitomo, Takeda, Tikvah, and Wyeth. He also is a member of the Scientific Advisory Board of the Trichotillomania Learning Centre and the Trichotillomania International Consortium for Research (TrIC Research). NR 14 TC 16 Z9 16 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD DEC PY 2012 VL 29 IS 12 BP 1025 EP 1031 DI 10.1002/da.22011 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 048KT UT WOS:000311911000005 PM 23124891 ER PT J AU Uher, R Perlis, RH Placentino, A Dernovsek, MZ Henigsberg, N Mors, O Maier, W McGuffin, P Farmer, A AF Uher, Rudolf Perlis, Roy H. Placentino, Anna Dernovsek, Mojca Zvezdana Henigsberg, Neven Mors, Ole Maier, Wolfgang McGuffin, Peter Farmer, Anne TI SELF-REPORT AND CLINICIAN-RATED MEASURES OF DEPRESSION SEVERITY: CAN ONE REPLACE THE OTHER? SO DEPRESSION AND ANXIETY LA English DT Article DE depression; assessment/diagnosis; clinical trials; antidepressants; treatment; mood disorders ID CARROLL RATING-SCALE; STAR-ASTERISK-D; MONTGOMERY-ASBERG; OBSERVER RATINGS; QUICK INVENTORY; OUTCOMES; ANTIDEPRESSANTS; SYMPTOMATOLOGY; SYMPTOMS; DISCREPANCIES AB Background It has been suggested that clinician-rated scales and self-report questionnaires may be interchangeable in the measurement of depression severity, but it has not been tested whether clinically significant information is lost when assessment is restricted to either clinician-rated or self-report instruments. The aim of this study is to test whether self-report provides information relevant to short-term treatment outcomes that is not captured by clinician-rating and vice versa. Methods In genome-based drugs for depression (GENDEP), 811 patients with major depressive disorder treated with escitalopram or nortriptyline were assessed with the clinician-rated Montgomery angstrom sberg Depression Rating Scale (MADRS), Hamilton Rating Scale for Depression (HRSD), and the self-report Beck Depression Inventory (BDI). In sequenced treatment alternatives to relieve depression (STAR*D), 4,041 patients treated with citalopram were assessed with the clinician-rated and self-report versions of the Quick Inventory of Depressive Symptomatology (QIDS-C and QIDS-SR) in addition to HRSD. Results In GENDEP, baseline BDI significantly predicted outcome on MADRS/HRSD after adjusting for baseline MADRS/HRSD, explaining additional 3 to 4% of variation in the clinician-rated outcomes (both P < .001). Likewise, each clinician-rated scale significantly predicted outcome on BDI after adjusting for baseline BDI and explained additional 1% of variance in the self-reported outcome (both P < .001). The results were confirmed in STAR*D, where self-report and clinician-rated versions of the same instrument each uniquely contributed to the prediction of treatment outcome. Conclusions Complete assessment of depression should include both clinician-rated scales and self-reported measures. Depression and Anxiety 29: 1043-1049, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Uher, Rudolf] Dalhousie Univ, Dept Psychiat, Mood Disorders Program, Halifax, NS B3H 2E2, Canada. [Uher, Rudolf; McGuffin, Peter; Farmer, Anne] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London, England. [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Placentino, Anna] Spedali Civili Hosp Brescia, Dept Mental Hlth, Psychiat Unit UOP 23, Lombardei, Italy. [Placentino, Anna] Univ Milano Bicocca, Fac Psychol, Milan, Italy. [Placentino, Anna] IRCCS FBF, Biol Psychiat Unit, Brescia, Italy. [Dernovsek, Mojca Zvezdana] Univ Psychiat Clin, Ljubljana, Slovenia. [Henigsberg, Neven] Univ Zagreb, Sch Med, Croatian Inst Brain Res, Zagreb 41000, Croatia. [Mors, Ole] Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark. [Maier, Wolfgang] Univ Bonn, Dept Psychiat, Bonn, Germany. RP Uher, R (reprint author), Dalhousie Univ, Dept Psychiat, Mood Disorders Program, Abbie J Lane Bldg,Room 3089,5909 Vet Mem Lane, Halifax, NS B3H 2E2, Canada. EM rudolf.uher@kcl.ac.uk RI McGuffin, Peter/A-1565-2012; Uher, Rudolf/A-5477-2008; OI McGuffin, Peter/0000-0002-9888-2907; Uher, Rudolf/0000-0002-2998-0546; Henigsberg, Neven/0000-0002-5303-1834 FU European Commission [LSHB-CT-2003-503428]; GlaxoSmithKline; UK National Institute for Health Research of the Department of Health; NIMH [N01MH90003, MH086026]; Innovative Medicines Initiative of the European Commission [115008]; Canada Research Chair program; Proteus Biomedical; Concordant Rater Systems; RIDventures FX Contract grant sponsor: European Commission Framework 6; Contract grant number: LSHB-CT-2003-503428; Contract grant sponsor: GlaxoSmithKline; Contract grant sponsor: UK National Institute for Health Research of the Department of Health; Contract grant sponsor: NIMH; Contract grant number: N01MH90003; Contract grant sponsor: Innovative Medicines Initiative of the European Commission; Contract grant number: 115008; Contract grant sponsor: NIMH; Contract grant number: MH086026.; Lundbeck provided nortriptyline and escitalopram for the GENDEP study. GlaxoSmithKline and the UK National Institute for Health Research of the Department of Health contributed to the funding of the sample collection at the Institute of Psychiatry, London. The sponsors had no role in the design and conduct of the study, in data collection, analysis, interpretation or writing the report. Data for the replication study were obtained from the limited access datasets (version no. 2) distributed from the NIH-supported "Sequenced Treatment Alternatives to Relieve Depression" (STAR*D). STAR*D was supported by NIMH Contract no. N01MH90003 to the University of Texas Southwestern Medical Center. The ClinicalTrials.gov identifier is NCT00021528. This manuscript reflects the views of the authors and may not reflect the opinions or views of the STAR*D Study Investigators or the NIH. Dr. Uher is supported by the Canada Research Chair program (http://www.chairs-chaires.gc.ca/) and a grant from the Innovative Medicines Initiative of the European Commission (Grant Agreement no. 115008). Dr. Perlis is supported by NIMH MH086026. We thank A. John Rush for comments on an earlier version of the manuscript.; Uher consults for the World Health Organization. Perlis has received consulting fees from Proteus Biomedical, Concordant Rater Systems, and RIDventures. Henigsberg has received honoraria for participating in expert panels from pharmaceutical companies including Lundbeck. Placentino, Dernovsek, Mors, Maier; McGuffin and Farmer have no conflicts of interest. NR 50 TC 26 Z9 26 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD DEC PY 2012 VL 29 IS 12 BP 1043 EP 1049 DI 10.1002/da.21993 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 048KT UT WOS:000311911000007 PM 22933451 ER PT J AU Cyranowski, JM Schott, LL Kravitz, HM Brown, C Thurston, RC Joffe, H Matthews, KA Bromberger, JT AF Cyranowski, Jill M. Schott, Laura L. Kravitz, Howard M. Brown, Charlotte Thurston, Rebecca C. Joffe, Hadine Matthews, Karen A. Bromberger, Joyce T. TI PSYCHOSOCIAL FEATURES ASSOCIATED WITH LIFETIME COMORBIDITY OF MAJOR DEPRESSION AND ANXIETY DISORDERS AMONG A COMMUNITY SAMPLE OF MID-LIFE WOMEN: THE SWAN MENTAL HEALTH STUDY SO DEPRESSION AND ANXIETY LA English DT Article DE major depressive disorder; anxiety disorders; comorbidity; child abuse; social support; stress, psychological ID DSM-IV ANXIETY; MOOD DISORDERS; PANIC DISORDER; CO-MORBIDITY; PSYCHIATRIC-DISORDERS; MENOPAUSAL SYMPTOMS; GENERAL-POPULATION; FOLLOW-UP; STRESS; SUICIDE AB Background In clinical samples, comorbidity between depressive and anxiety disorders is associated with greater symptom severity and elevated suicide risk. Less is known, however, regarding the long-term psychosocial impact that a lifetime history of both major depressive disorder (MDD) and one or more anxiety disorders has in community samples. This report evaluates clinical, psychological, social, and stress-related characteristics associated with a lifetime history of MDD and anxiety. Methods Data from 915 women aged 4252 who were recruited as part of the the Study of Women's Health across the Nation (SWAN) Mental Health Study were used to examine clinical and psychosocial features across groups of women with a lifetime history of MDD alone, anxiety alone, both MDD and anxiety, or neither MDD nor anxiety. Results As compared with women with a history of either MDD or anxiety alone, women with a comorbid history were more likely to report recurrent MDD, multiple and more severe lifetime anxiety disorders, greater depressive and anxiety symptoms, diminished social support, and more past-year distressing life events. Exploratory analyses indicated that women with a comorbid history also report more childhood abuse/neglect and diminished self-esteem, as compared with women with a history of either disorder alone. Conclusions Midlife women with a comorbid history that includes both MDD and anxiety disorders report diminished social support, more symptomatic distress, and a more severe and recurrent psychiatric history. Future research is needed to clarify the biological and psychosocial risk factors associated with this comorobid profile, and to develop targeted interventions for this at-risk group. Depression and Anxiety 00:1-8, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Cyranowski, Jill M.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. [Cyranowski, Jill M.; Matthews, Karen A.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Schott, Laura L.; Matthews, Karen A.; Bromberger, Joyce T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Kravitz, Howard M.] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. [Kravitz, Howard M.] Rush Univ, Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA. [Joffe, Hadine] Massachusetts Gen Hosp, Dept Psychiat, Ctr Womens Mental Hlth, Boston, MA 02114 USA. RP Cyranowski, JM (reprint author), Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. EM cyranowskijm@upmc.edu RI mahmood, zaniab/C-9578-2014 FU NIH [MH085874]; Pittsburgh Foundation; Cephalon; National Institutes of Health (NIH); National Institute on Aging (NIA); National Institute of Nursing Research (NINR); NIH Office of Research on Women's Health (ORWH) [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495]; National Institute of Mental Health (NIMH) [MH59689, MH59770, MH59688] FX Drs. Schott, Kravitz, Brown, Thurston, Matthews, and Bromberger have received research grant support from the NIH; Dr. Cyranowski has received grant support from NIH (MH085874) and the Pittsburgh Foundation; Dr. Joffe has received grant support from NIH and Cephalon, and has served as a consultant for Noven, Pfizer and Sunovion.; The Study of Women's Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH); DHHS, through the National Institute on Aging (NIA); the National Institute of Nursing Research (NINR); and the NIH Office of Research on Women's Health (ORWH) (Grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, 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. Supplemental funding from the National Institute of Mental Health (NIMH) is also gratefully acknowledged (Grants MH59689, MH59770, MH59688). NR 42 TC 11 Z9 11 U1 6 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD DEC PY 2012 VL 29 IS 12 BP 1050 EP 1057 DI 10.1002/da.21990 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 048KT UT WOS:000311911000008 PM 22930404 ER PT J AU Mather, KJ Christophi, CA Jablonski, KA Knowler, WC Goldberg, RB Kahn, SE Spector, T Dastani, Z Waterworth, D Richards, JB Funahashi, T Pi-Sunyer, FX Pollin, TI Florez, JC Franks, PW AF Mather, K. J. Christophi, C. A. Jablonski, K. A. Knowler, W. C. Goldberg, R. B. Kahn, S. E. Spector, T. Dastani, Z. Waterworth, D. Richards, J. B. Funahashi, T. Pi-Sunyer, F. X. Pollin, T. I. Florez, J. C. Franks, P. W. CA Diabetes Prevention Program Res TI Common variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the Diabetes Prevention Program SO DIABETIC MEDICINE LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISM; INSULIN-RESISTANCE; CAUCASIAN POPULATION; METABOLIC SYNDROME; FRENCH CAUCASIANS; APM1 GENE; TYPE-2; ASSOCIATION; PROMOTER; RISK AB Diabet. Med. 29, 15791588 (2012) Abstract Aims Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population. Methods Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling. Results Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions of rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with similar to 18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations. Conclusions ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations. C1 [Mather, K. J.] Indiana Univ, Div Endocrinol & Metab, Indianapolis, IN 46204 USA. [Christophi, C. A.; Jablonski, K. A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Knowler, W. C.] NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Goldberg, R. B.] Univ Miami, Lipid Disorders Clin, Div Endocrinol Diabet & Metab, Miami, FL USA. [Goldberg, R. B.] Univ Miami, Diabet Res Inst, Leonard M Miller Sch Med, Miami, FL USA. [Kahn, S. E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, S. E.] Univ Washington, Seattle, WA 98195 USA. [Spector, T.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Dastani, Z.; Richards, J. B.] McGill Univ, Dept Med, Montreal, PQ, Canada. [Dastani, Z.; Richards, J. B.] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Dastani, Z.; Richards, J. B.] McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada. [Waterworth, D.] GlaxoSmithKline, Genet, King Of Prussia, PA USA. [Funahashi, T.] Osaka Univ, Grad Sch Med, Dept Internal Med & Mol Sci, Suita, Osaka, Japan. [Pi-Sunyer, F. X.] Columbia Univ Coll Phys & Surg, Dept Med, St Lukes Roosevelt Hosp, New York, NY 10032 USA. [Pollin, T. I.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Pollin, T. I.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Florez, J. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, J. C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, J. C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Florez, J. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Franks, P. W.] Lund Univ, Skania Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. [Franks, P. W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Mather, KJ (reprint author), Indiana Univ, Div Endocrinol & Metab, Indianapolis, IN 46204 USA. EM dppmail@biostat.bsc.gwu.edu OI Franks, Paul/0000-0002-0520-7604; Kahn, Steven/0000-0001-7307-9002 FU Swedish Research Council; Swedish Heart-Lung Foundation; Pahlssons Foundation; Swedish Diabetes Association; Novo Nordisk; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK; Indian Health Service; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; Office of Research on Women's Health; American Diabetes Association; Henry M. Jackson Foundation; [DK072041] FX The Investigators gratefully acknowledge the commitment and dedication of the participants of the DPP. The design and conduct of the trial was made possible in large part by the National Institutes of Health, along with Foundation and Industry partners as listed in the Support section. The genetic analyses were supported by DK072041 (to JCF). PWF was supported by grants from the Swedish Research Council, Swedish Heart-Lung Foundation, Pahlssons Foundation, Swedish Diabetes Association, and Novo Nordisk. Adiponectin analyses were supported by the Sandra A. Daugherty foundation (to KJM). The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centres and the Coordinating Center for the design and conduct of the study; and collection, management, analysis and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources supported data collection at many of the clinical centres. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women's Health and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported, in part, by the intramural research program of the NIDDK. LifeScan Inc., Health O Meter, Hoechst Marion Roussel Inc., Merck-Medco Managed Care Inc., Merck and Co., Nike Sports Marketing, Slim Fast Foods Co. and Quaker Oats Co. donated materials, equipment or medicines for concomitant conditions. McKesson BioServices Corp., Matthews Media Group Inc. and the Henry M. Jackson Foundation provided support services under subcontract with the Coordinating Center. The opinions expressed are those of the investigators and do not necessarily reflect the views of the Indian Health Service or other funding agencies. A complete list of centres, investigators and staff can be found in the Supporting Information (Appendix S1). NR 30 TC 11 Z9 11 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD DEC PY 2012 VL 29 IS 12 BP 1579 EP 1588 DI 10.1111/j.1464-5491.2012.03662.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 036TO UT WOS:000311054600026 PM 22443353 ER PT J AU Hegde, M Santos-Sanchez, C Hess, CP Kabir, AA Garcia, PA AF Hegde, Manu Santos-Sanchez, Carlos Hess, Christopher P. Kabir, Arif A. Garcia, Paul A. TI Seizure exacerbation in two patients with focal epilepsy following marijuana cessation SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy, partial; Cannabis; Marijuana smoking; Tetrahydocannabinol; Cannabidiol ID TEMPORAL-LOBE EPILEPSY; ENDOCANNABINOID SYSTEM; IN-VIVO; CANNABIDIOL; ACTIVATION; MODEL AB While animal models of epilepsy suggest that exogenous cannabinoids may have anticonvulsant properties, scant evidence exists for these compounds' efficacy in humans. Here, we report on two patients whose focal epilepsy was nearly controlled through regular outpatient marijuana use. Both stopped marijuana upon admission to our epilepsy monitoring unit (EMU) and developed a dramatic increase in seizure frequency documented by video-EEG telemetry. These seizures occurred in the absence of other provocative procedures, including changes to anticonvulsant medications. We review these cases and discuss mechanisms for the potentially anticonvulsant properties of cannabis, based on a review of the literature. Published by Elsevier Inc. C1 [Hegde, Manu; Santos-Sanchez, Carlos; Garcia, Paul A.] Univ Calif San Francisco, Epilepsy Ctr, Dept Neurol, San Francisco, CA 94143 USA. [Hess, Christopher P.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Hegde, Manu; Kabir, Arif A.] San Francisco VA Med Ctr, Epilepsy Ctr Excellence, San Francisco, CA USA. RP Hegde, M (reprint author), Univ Calif San Francisco, Epilepsy Ctr, Dept Neurol, 521 Parnassus Ave,Room C-440, San Francisco, CA 94143 USA. EM manu.hegde@ucsf.edu OI Hess, Christopher/0000-0002-5132-5302 NR 17 TC 13 Z9 13 U1 1 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD DEC PY 2012 VL 25 IS 4 BP 563 EP 566 DI 10.1016/j.yebeh.2012.09.024 PG 4 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 046SH UT WOS:000311784200017 PM 23159379 ER PT J AU Uppuluri, P Chaturvedi, AK Jani, N Pukkila-Worley, R Monteagudo, C Mylonakis, E Kohler, JR Ribot, JLL AF Uppuluri, Priya Chaturvedi, Ashok K. Jani, Niketa Pukkila-Worley, Read Monteagudo, Carlos Mylonakis, Eleftherios Koehler, Julia R. Ribot, Jose L. Lopez TI Physiologic Expression of the Candida albicans Pescadillo Homolog Is Required for Virulence in a Murine Model of Hematogenously Disseminated Candidiasis SO EUKARYOTIC CELL LA English DT Article ID BLOOD-STREAM INFECTIONS; FILAMENTOUS FORMS; YEAST; CELL; MICE; PROLIFERATION; MORPHOGENESIS; MORPHOLOGY; PROTEIN; HOST AB Morphogenetic conversions contribute to the pathogenesis of Candida albicans invasive infections. Many studies to date have convincingly demonstrated a link between filamentation and virulence; however, relatively little is known regarding the role of the filament-to-yeast transition during the pathogenesis of invasive candidiasis. We previously identified the C. albicans pescadillo homolog (PES1) as essential during yeast growth and growth of lateral yeast on hyphae but not during hyphal growth. Furthermore, we demonstrated that PES1 is required for virulence in vivo in a Galleria mellonella larva model of candidiasis. Here, we have used a regulatable tetO-PES1/pes1 strain to assess the contribution of C. albicans PES1 to pathogenesis in the commonly used and clinically relevant murine model of hematogenously disseminated candidiasis. Our results indicate that a physiologically controlled level of PES1 expression is required for full virulence in this animal model, with virulence defects observed both when PES1 is overexpressed and and when it is depleted. The pathogenetic defect of cells depleted of PES1 is not due to a general growth defect, as demonstrated by the fact that PES1-depleted cells still kill Caenorhabditis elegans as efficiently as the wild type due to hyphal outgrowth through worm tissues. Our results suggest a critical role of lateral yeast growth in the ability of C. albicans to normally proliferate within tissues, as well as a pivotal role for Pes1 in the normal developmental cycle of C. albicans within the mammalian host during infection. C1 [Jani, Niketa; Koehler, Julia R.] Harvard Univ, Childrens Hosp Boston, Sch Med, Div Infect Dis, Boston, MA 02115 USA. [Uppuluri, Priya; Chaturvedi, Ashok K.; Ribot, Jose L. Lopez] Univ Texas San Antonio, Dept Biol, San Antonio, TX USA. [Pukkila-Worley, Read; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Monteagudo, Carlos] Univ Valencia, Fac Med & Odontol, Dept Pathol, Valencia, Spain. RP Kohler, JR (reprint author), Harvard Univ, Childrens Hosp Boston, Sch Med, Div Infect Dis, Boston, MA 02115 USA. EM julia.koehler@childrens.harvard.edu; jose.lopezribot@utsa.edu RI Lopez-Ribot, Jose/D-2048-2010; Monteagudo, Carlos/H-6555-2016 FU Public Health Service from the National Institute of Allergy and Infectious Diseases [RO1AI064562, R21 AI064715]; American Heart Association [10POST4280033]; Cancer Research Institute; NIAID/NIH [AI081747]; Army Research Office of the Department of Defense [W911NF-11-1-0136] FX This work was funded by Public Health Service grants RO1AI064562 and R21 AI064715 from the National Institute of Allergy and Infectious Diseases to J.L.L.R. and J.R.K., respectively. P. U. is supported by a postdoctoral fellowship, 10POST4280033, from the American Heart Association. R.P.-W. was supported by the Irvington Institute Fellowship Program of the Cancer Research Institute and K08 award AI081747 from NIAID/NIH. Additional support was provided by the Army Research Office of the Department of Defense under contract no. W911NF-11-1-0136. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 1 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD DEC PY 2012 VL 11 IS 12 BP 1552 EP 1556 DI 10.1128/EC.00171-12 PG 5 WC Microbiology; Mycology SC Microbiology; Mycology GA 046QD UT WOS:000311778600013 PM 23104566 ER PT J AU Schwab, FJ Hawkinson, N Lafage, V Smith, JS Hart, R Mundis, G Burton, DC Line, B Akbarnia, B Boachie-Adjei, O Hostin, R Shaffrey, CI Arlet, V Wood, K Gupta, M Bess, S Mummaneni, PV AF Schwab, Frank J. Hawkinson, Nicola Lafage, Virginie Smith, Justin S. Hart, Robert Mundis, Gregory Burton, Douglas C. Line, Breton Akbarnia, Behrooz Boachie-Adjei, Oheneba Hostin, Richard Shaffrey, Christopher I. Arlet, Vincent Wood, Kirkham Gupta, Munish Bess, Shay Mummaneni, Praveen V. CA Int Spine Study Grp TI Risk factors for major peri-operative complications in adult spinal deformity surgery: a multi-center review of 953 consecutive patients SO EUROPEAN SPINE JOURNAL LA English DT Review DE Complications; Surgery; Adult; Spinal deformity; Risk factor ID 2-YEAR FOLLOW-UP; NONOPERATIVE TREATMENT; LUMBAR SCOLIOSIS; INFECTION; PAIN; DISABILITY; MANAGEMENT; SYSTEM; AGE AB Purpose Major peri-operative complications for adult spinal deformity (ASD) surgery remain common. However, risk factors have not been clearly defined. Our objective was to identify patient and surgical parameters that correlate with the development of major peri-operative complications with ASD surgery. Methods This is a multi-center, retrospective, consecutive, case-control series of surgically treated ASD patients. All patients undergoing surgical treatment for ASD at eight centers were retrospectively reviewed. Each center identified 10 patients with major peri-operative complications. Randomization tables were used to select a comparably sized control group of patients operated during the same time period that they did not suffer major complications. The two groups were analyzed for differences in clinical and surgical factors. Analysis was restricted to non-instrumentation related complications. Results At least one major complication occurred in 80 of 953 patients (8.4 %), including 72 patients with non-instrumentation related complications. There were no significant differences between the complications and control groups based on the demographics, ASA grade, co-morbidities, body mass index, prior surgeries, pre-operative anemia, smoking, operative time or ICU stay (p > 0.05). Hospital stay was significantly longer for the complications group (14.4 vs. 7.9 days, p = 0.001). The complications group had higher percentages of staged procedures (46 vs. 37 %, p = 0.011) and combined anterior-posterior approaches (56 vs. 32 %, p = 0.011) compared with the control group. Conclusion The major peri-operative complication rate was 8.4 % for 953 surgically treated ASD patients. Significantly higher rates of complications were associated with staged and combined anterior-posterior surgeries. None of the patient factors assessed were significantly associated with the occurrence of major peri-operative complications. Improved understanding of risk profiles and procedure-related parameters may be useful for patient counseling and efforts to reduce complication rates. C1 [Smith, Justin S.; Shaffrey, Christopher I.] Univ Virginia, Dept Neurosurg, Charlottesville, VA 22908 USA. [Schwab, Frank J.; Hawkinson, Nicola; Lafage, Virginie] NYU, Hosp Joint Dis, New York, NY USA. [Hart, Robert] Oregon Hlth & Sci Univ, Dept Orthoped Surg, Portland, OR USA. [Mundis, Gregory; Akbarnia, Behrooz] San Diego Ctr Spinal Disorders, La Jolla, CA USA. [Burton, Douglas C.] Univ Kansas, Dept Orthoped Surg, Kansas City, KS USA. [Line, Breton; Bess, Shay] Rocky Mt Hosp Children Denver, Denver, CO USA. [Boachie-Adjei, Oheneba] Hosp Special Surg, Dept Orthoped Surg, New York, NY 10021 USA. [Hostin, Richard] Baylor Scoliosis Ctr, Dept Orthoped Surg, Plano, TX USA. [Arlet, Vincent] Univ Penn, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. [Wood, Kirkham] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. [Gupta, Munish] Univ Calif Davis, Dept Orthoped Surg, Davis, CA 95616 USA. [Mummaneni, Praveen V.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA. RP Smith, JS (reprint author), Univ Virginia, Dept Neurosurg, POB 800212, Charlottesville, VA 22908 USA. EM jss7f@virginia.edu OI Lafage, Virginie/0000-0002-0119-7111; bess, shay/0000-0002-9697-8999 FU DePuy FX Research grant from DePuy to fund the International Spine Study Group. IRB approval was obtained from all contributing institutions. NR 31 TC 35 Z9 36 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0940-6719 J9 EUR SPINE J JI Eur. Spine J. PD DEC PY 2012 VL 21 IS 12 BP 2603 EP 2610 DI 10.1007/s00586-012-2370-4 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 046QR UT WOS:000311780000027 PM 22592883 ER PT J AU Fung, SJ Xi, MC Zhang, JH Sampogna, S Chase, MH AF Fung, Simon J. Xi, MingChu Zhang, JianHua Sampogna, Sharon Chase, Michael H. TI Apnea produces excitotoxic hippocampal synapses and neuronal apoptosis SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Hypoxia; Rat model; Obstructive sleep apnea; CA1; fEPSP; Excitotoxicity; Neurodegeneration; Plasticity; Cognitive processes ID OBSTRUCTIVE SLEEP-APNEA; PAIRED-PULSE FACILITATION; SYNAPTIC-TRANSMISSION; INTERMITTENT HYPOXIA; CA1 REGION; LONG-TERM; POSTSYNAPTIC MECHANISMS; BRAIN MORPHOLOGY; NMDA RECEPTORS; CARBON-DIOXIDE AB Obstructive sleep apnea (OSA) results in the degeneration of neurons in the hippocampus that eventuates in neurocognitive deficits. We were therefore interested in determining the effects of apnea on monosynaptic excitatory processes in a hippocampal pathway (cornu ammonis 3-cornu ammonis 1, CA3-CA1) that has been shown to mediate the processing of cognitive information. In addition, to substantiate an anatomical basis for the cognitive dysfunction that occurs in OSA patients, we examined the effects of apnea with respect to neurodegenerative changes (apoptosis) in the same hippocampal pathway. In order to determine the effects of apnea, an automated system for the generation and analysis of single and recurrent periods of apnea was developed. Utilizing this system, the field excitatory postsynaptic potential (fEPSP) generated by pyramidal neurons in the CA1 region of the hippocampus was monitored in alpha-chloralose anesthetized rats following stimulation of glutamatergic afferents in the CA3 region. A stimulus-response (input-output) curve for CA3-CA1 synaptic activity was determined. In addition, a paired-pulse paradigm was employed to evaluate, electrophysiologically, the presynaptic release of glutamate. Changes in the synaptic efficacy were assessed following single episodes of apnea induced by ventilatory arrest (60 to 80 s duration, mean = 72 s; mean oxygen desaturation was 53% of normoxia level). Apnea resulted in a significant potentiation of the amplitude (mean = 126%) and slope (mean = 117%) of the baseline CA1 fEPSP. This increase in the fEPSP was accompanied by a significant decrease in the amplitude (71%) and slope (81%) of normalized paired-pulse facilitation (PPF) ratios. Since the potentiation of the fEPSP is inversely proportional to changes in PPF ratio, the potentiated fEPSP accompanied by the reduced PPF reveals that apnea produces an abnormal increase in the preterminal release of glutamate that results in the over-activation (and calcium overloading) of hippocampal CA1 neurons. Thus, we conclude that individual episodes of apnea result in the development of excitotoxic processes in the hippocampal CA3-CA1 pathway that is critically involved in the processing of cognitive information. Morphologically, the deleterious effect of recurrent apnea was substantiated by the finding of apoptosis in CA1 neurons of apneic (but not normoxic) animals. (C) 2012 Elsevier Inc. All rights reserved. C1 [Fung, Simon J.; Xi, MingChu; Zhang, JianHua; Sampogna, Sharon; Chase, Michael H.] WebSci Int, Los Angeles, CA 90024 USA. [Fung, Simon J.; Xi, MingChu; Zhang, JianHua; Chase, Michael H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Chase, Michael H.] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. RP Fung, SJ (reprint author), WebSci Int, 1251 Westwood Blvd, Los Angeles, CA 90024 USA. EM sfung@websciences.org FU [1|01BX000819]; [TCS-109219] FX This work was supported by grants 1|01BX000819 and TCS-109219. The authors gratefully acknowledge the expert technical assistance of Vince Lim and John Lopatto. We are indebted to Johnathan Lim for his successful development of the Automated Recurrent Apnea Program which was adopted to regulate the apnea protocols in this study. NR 51 TC 8 Z9 11 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 2012 VL 238 IS 2 BP 107 EP 113 DI 10.1016/j.expneurol.2012.08.006 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 046KE UT WOS:000311763100004 PM 22921462 ER PT J AU Hoffmann, U Sukhotinsky, I Atalay, YB Eikermann-Haerter, K Ayata, C AF Hoffmann, Ulrike Sukhotinsky, Irma Atalay, Yahya Burak Eikermann-Haerter, Katharina Ayata, Cenk TI Increased glucose availability does not restore prolonged spreading depression durations in hypotensive rats without brain injury SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Hyperglycemia; Hypotension; Spreading depression ID BLOOD-FLOW RESPONSE; PLASMA-GLUCOSE; POTASSIUM; HYPEREMIA; TRANSPORT; RECOVERY; ISCHEMIA; CORTEX AB Maintenance of transmembrane ionic gradients and their restoration after cortical spreading depression (CSD) are energy dependent. We recently showed an inverse relationship between blood pressure and CSD duration that is independent of tissue oxygenation. Here, we tested the alternative hypothesis that glucose availability becomes rate-limiting for CSD recovery upon reduced blood pressure in anesthetized rats under full systemic physiological monitoring. Hypotension induced by controlled exsanguination significantly prolonged CSD durations, reduced propagation speeds, and diminished the blood flow response. Hyperglycemia failed to restore the prolonged CSD durations in hypotensive rats and did not significantly alter the propagation speed or the blood flow response. These data suggest that prolonged CSD durations during reduced cerebral perfusion pressure are independent of tissue energy status, and implicate alternative mechanisms of CSD recovery such as vascular clearance of extracellular K+. (C) 2012 Elsevier Inc. All rights reserved. C1 [Hoffmann, Ulrike; Sukhotinsky, Irma; Atalay, Yahya Burak; Eikermann-Haerter, Katharina; Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab,Sch Med, Charlestown, MA 02129 USA. [Hoffmann, Ulrike] Tech Univ Munich, Klinikum Rechts Isar, Klin Anaesthesiol, D-81675 Munich, Germany. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Stroke Serv,Sch Med, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Neurosci Intens Care Unit,Sch Med, Charlestown, MA 02129 USA. RP Ayata, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab,Sch Med, 149 13th St,Room 6408, Charlestown, MA 02129 USA. EM cayata@partners.org FU National Institute of Health [NS061505, NS055104]; Deutsche Forschungsgemeinschaft [HO4211/1-1]; American Heart Association [10SDG2610275] FX This work was supported by the National Institute of Health (NS061505, NS055104), Deutsche Forschungsgemeinschaft (HO4211/1-1) and the American Heart Association (10SDG2610275). We would like to thank Dr. Brian Healy of the MGH Biostatistics Center for his critical insights during data analysis. NR 15 TC 5 Z9 5 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 2012 VL 238 IS 2 BP 130 EP 132 DI 10.1016/j.expneurol.2012.08.013 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 046KE UT WOS:000311763100007 PM 22981452 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Emerging therapies for gout SO EXPERT OPINION ON EMERGING DRUGS LA English DT Review DE emerging therapies; gout; hyperuricemia; rilonacept; canakinumab; lesinurad ID QUALITY-OF-LIFE; EVIDENCE BASED RECOMMENDATIONS; RHEUMATOLOGY GUIDELINES; ACUTE FLARES; TASK-FORCE; PHASE-II; MANAGEMENT; ARTHRITIS; HYPERURICEMIA; HEALTH AB Introduction: Gout is the commonest inflammatory arthritis in adults that affects 4% of the US population. Gout is symptomatic, leading to joint pain and inflammation, frequent acute flares associated with disability, pain and suffering. When not treated optimally, chronic inflammation can lead to chronic pain, joint destruction and deformities and decrements in function and quality of life. Areas covered: Different therapeutic strategies that are being developed in preclinical and clinical settings are discussed. Expert opinion: Multiple new treatment approaches have emerged for gout. Several target acute inflammation of gout flares by inhibiting interleukin-1, either with an antibody or with a molecule that traps interleukin-1. Two drugs in this category are rilonacept and canakinumab. Similarly, new approaches targeting and increasing urate excretion by the kidney are emerging. One such promising drug is lesinurad that decreases serum urate through inhibition of the uric acid transporter (URAT1) in the proximal tubule of the kidney. We hope these and other new treatments and new strategies for gout will lead to additional options. The expansion of the armamentarium for gout treatment will allow clinicians and patients to increase the chances to have gout remission. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Div Rheumatol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU National Institute of Aging; National Cancer Institute; National Institute of Arthritis and Musculoskeletal Diseases (NIAMS); Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs); Birmingham VA Medical Center, Alabama, USA; Takeda; Savient; Ardea; Regeneron; Allergan; URL pharmaceuticals; Novartis FX JA Singh is supported by research grants from National Institute of Aging, National Cancer Institute, National Institute of Arthritis and Musculoskeletal Diseases (NIAMS), Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), and the resources and the use of facilities at the Birmingham VA Medical Center, Alabama, USA. No funding was received for this manuscript. JAS has received research grants from Takeda and Savient and consultant fees from Savient, Takeda, Ardea, Regeneron, Allergan, URL pharmaceuticals and Novartis. JA Singh is a member of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 36 companies; a member of the American College of Rheumatology's Guidelines Subcommittee of the Quality of Care Committee; and a member of the Veterans Affairs Rheumatology Field Advisory Committee. NR 38 TC 4 Z9 4 U1 0 U2 22 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8214 EI 1744-7623 J9 EXPERT OPIN EMERG DR JI Expert Opin Emerg. Drugs PD DEC PY 2012 VL 17 IS 4 BP 511 EP 518 DI 10.1517/14728214.2012.736488 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 044OX UT WOS:000311631100006 PM 23126250 ER PT J AU van Driel, B Liao, GX Romero, X O'Keeffe, MS Wang, GX Faubion, WA Berger, SB Magelky, EM Manocha, M Azcutia, V Grisham, M Luscinskas, FW Mizoguchi, E Malefyt, RD Reinecker, HC Bhan, AK Wang, NH Terhorst, C AF van Driel, Boaz Liao, Gongxian Romero, Xavier O'Keeffe, Michael S. Wang, Guoxing Faubion, William A. Berger, Scott B. Magelky, Erica M. Manocha, Monika Azcutia, Veronica Grisham, Matthew Luscinskas, Francis W. Mizoguchi, Emiko Malefyt, Rene de Waal Reinecker, Hans-Christian Bhan, Atul K. Wang, Ninghai Terhorst, Cox TI Signaling Lymphocyte Activation Molecule Regulates Development of Colitis in Mice SO GASTROENTEROLOGY LA English DT Article DE Immune Regulation; Mouse Model; TNF; Inflammatory Bowel Disease ID INFLAMMATORY-BOWEL-DISEASE; INTESTINAL INFLAMMATION; IMMUNE-RESPONSES; DENDRITIC CELLS; LAMINA PROPRIA; T-CELLS; MACROPHAGES; SLAM; MONOCYTES; INNATE AB BACKGROUND & AIMS: Signaling lymphocyte activation molecule (Slamf) 1 is a co-stimulatory receptor on T cells and regulates cytokine production by macrophages and dendritic cells. Slamf1 regulates microbicidal mechanisms in macrophages, therefore we investigated whether the receptor affects development of colitis in mice. METHODS: We transferred CD45RB(hi) CD4(+) T cells into Rag(-/-) or Slamf1(-/-) Rag(-/-) mice to induce colitis. We also induced colitis by injecting mice with an antibody that activates CD40. We determined the severity of enterocolitis based on disease activity index, histology scores, and levels of cytokine production, and assessed the effects of antibodies against Slamf1 on colitis induction. We quantified migration of monocytes and macrophage to inflamed tissues upon induction of colitis or thioglycollate-induced peritonitis and in response to tumor necrosis factor-alpha in an air-pouch model of leukocyte migration. RESULTS: Colitis was reduced in Slamf1(-/-) Rag(-/-) mice, compared with Rag(-/-) mice, after transfer of CD45RB(hi) CD4 broken vertical bar T cells or administration of the CD40 agonist. The numbers of monocytes and macrophages were reduced in inflamed tissues of Slamf1(-/-) Rag(-/-) mice, compared with Rag(-/-) mice, after induction of colitis and other inflammatory disorders. An antibody that inhibited Slamf1 reduced the level of enterocolitis in Rag(-/-) mice. CONCLUSIONS: Slamf1 contributes to the development of colitis in mice. It appears to indirectly regulate the appearance of monocytes and macrophages in inflamed intestinal tissues. Antibodies that inhibit Slamf1 reduce colitis in mice, so human SLAMF1 might be a therapeutic target for inflammatory bowel disease. C1 [van Driel, Boaz; Liao, Gongxian; Romero, Xavier; O'Keeffe, Michael S.; Wang, Guoxing; Berger, Scott B.; Magelky, Erica M.; Manocha, Monika; Wang, Ninghai; Terhorst, Cox] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02115 USA. [Faubion, William A.] Mayo Clin, Dept Internal Med, Rochester, MN USA. [Azcutia, Veronica; Luscinskas, Francis W.] Harvard Univ, Div Vasc Res, Dept Pathol, Brigham & Womens Hosp,Sch Med, Boston, MA 02115 USA. [Grisham, Matthew] Louisiana State Univ, Dept Mol & Cellular Physiol, Hlth Sci Ctr, Shreveport, LA 71105 USA. [Mizoguchi, Emiko; Reinecker, Hans-Christian] Harvard Univ, Dept Med, Gastrointestinal Unit, Sch Med, Boston, MA 02115 USA. [Mizoguchi, Emiko] Harvard Univ, Ctr Study Inflammatory Bowel Dis, Sch Med, Boston, MA 02115 USA. [Bhan, Atul K.] Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Malefyt, Rene de Waal] Merck Res Labs, Dept Immunol, Palo Alto, CA USA. RP Terhorst, C (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02115 USA. EM cterhors@bidmc.harvard.edu RI Wang, Guoxing/G-6586-2013; Azcutia, Veronica/A-7704-2017 OI Azcutia, Veronica/0000-0003-2160-5175 FU National Institutes of Health [AI-15066, DK-52510, DK-80070, DO-136028, DR-068181, AI-093588, DR-033506]; Center for the Study of IBD [DK-43351]; Crohn's and Colitis Foundation of America; American Heart Association Fellowship FX Supported by grants from the National Institutes of Health (AI-15066 and DK-52510 to C.T.; DK-80070 to E.M.; DO-136028 to F.W.L.; DR-068181, AI-093588, and DR-033506 to H.C.R.) and the Center for the Study of IBD (DK-43351). Xavier Romero and Scott Berger were supported by fellowships from the Crohn's and Colitis Foundation of America, and Veronica Azcutia was supported by an American Heart Association Fellowship. NR 28 TC 7 Z9 7 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2012 VL 143 IS 6 BP 1544 EP + DI 10.1053/j.gastro.2012.08.042 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 042XJ UT WOS:000311505100032 PM 22960654 ER PT J AU Villanueva, A Alsinet, C Yanger, K Hoshida, Y Zong, YW Toffanin, S Rodriguez-Carunchio, L Sole, M Thung, S Stanger, BZ Llovet, JM AF Villanueva, Augusto Alsinet, Clara Yanger, Kilangsungla Hoshida, Yujin Zong, Yiwei Toffanin, Sara Rodriguez-Carunchio, Leonardo Sole, Manel Thung, Swan Stanger, Ben Z. Llovet, Josep M. TI Notch Signaling Is Activated in Human Hepatocellular Carcinoma and Induces Tumor Formation in Mice SO GASTROENTEROLOGY LA English DT Article DE Genetically Engineered Mouse Model; Notch Activation; Gene Expression Profiling ID GENE-EXPRESSION; HUMAN CANCER; LUNG-CANCER; CELLS; DIFFERENTIATION; GROWTH; LIVER; ENCYCLOPEDIA; MAINTENANCE; RECURRENCE AB BACKGROUND & AIMS: The Notch signaling pathway is activated in leukemia and solid tumors (such as lung cancer), but little is known about its role in liver cancer. METHODS: The intracellular domain of Notch was conditionally expressed in hepatoblasts and their progeny (hepatocytes and cholangiocytes) in mice. This was achieved through Cre expression under the control of an albumin and alpha-fetoprotein (AFP) enhancer and promoter (AFP-Notch intracellular domain [NICD]). We used comparative functional genomics to integrate transcriptome data from AFP-NICD mice and human hepatocellular carcinoma (HCC) samples (n = 683). A Notch gene signature was generated using the nearest template prediction method. RESULTS: AFP-NICD mice developed HCC with 100% penetrance when they were 12 months old. Activation of Notch signaling correlated with activation of 3 promoters of insulin-like growth factor 2; these processes appeared to contribute to hepatocarcinogenesis. Comparative functional genomic analysis identified a signature of Notch activation in 30% of HCC samples from patients. These samples had altered expression in Notch pathway genes and activation of insulin-like growth factor signaling, despite a low frequency of mutations in regions of NOTCH1 associated with cancer. Blocking Notch signaling in liver cancer cells with the Notch activation signature using gamma-secretase inhibitors or by expressing a dominant negative form of mastermind-like 1 reduced their proliferation in vitro. CONCLUSIONS: Notch signaling is activated in human HCC samples and promotes formation of liver tumors in mice. The Notch signature is a biomarker of response to Notch inhibition in vitro. C1 [Villanueva, Augusto; Alsinet, Clara; Llovet, Josep M.] Univ Barcelona, HCC Translat Res Lab, Barcelona Clin Liver Canc Grp, Inst Invest Biomed August Pi & Sunyer, Barcelona, Catalonia, Spain. [Villanueva, Augusto; Alsinet, Clara; Llovet, Josep M.] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain. [Yanger, Kilangsungla; Zong, Yiwei; Stanger, Ben Z.] Univ Penn, Dept Med, Abramson Family Canc Res Inst, Perelman Sch Med, Philadelphia, PA 19104 USA. [Yanger, Kilangsungla; Zong, Yiwei; Stanger, Ben Z.] Univ Penn, Dept Cell & Dev Biol, Abramson Family Canc Res Inst, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hoshida, Yujin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Hoshida, Yujin] Broad Inst, Canc Program, Cambridge, MA USA. [Hoshida, Yujin; Toffanin, Sara; Thung, Swan] Mt Sinai Sch Med, Mt Sinai Liver Canc Program, Div Liver Dis & Pathol, New York, NY USA. [Toffanin, Sara] Natl Canc Inst, Gastrointestinal Surg & Liver Transplantat Unit, I-20133 Milan, Italy. [Toffanin, Sara] Natl Canc Inst, Dept Expt Oncol, I-20133 Milan, Italy. [Rodriguez-Carunchio, Leonardo; Sole, Manel] Hosp Clin Barcelona, Barcelona Clin Liver Canc Grp, Dept Pathol, Barcelona, Spain. [Llovet, Josep M.] Inst Catalana Recerca & Estudis Avancats, Barcelona, Catalonia, Spain. RP Llovet, JM (reprint author), Hosp Clin Barcelona, Res BCLC Grp, IDIBAPS, Liver Unit, Villarroel 170, E-08036 Barcelona, Spain. EM bstanger@exchange.upenn.edu; jmllovet@clinic.ub.es RI Augusto, Villanueva/F-9378-2012; Yanger, Kilang/N-2888-2015; Llovet, Josep M /D-4340-2014 OI Augusto, Villanueva/0000-0003-3585-3727; Yanger, Kilang/0000-0002-1710-5306; Llovet, Josep M /0000-0003-0547-2667 FU Instituto de Salud Carlos III [ISCIII/FIS FI09/00605]; US National Institute of Diabetes and Digestive and Kidney Diseases [1R01DK076986, R01-DK083355, DP2-DK083111]; European Commission [259744]; Samuel Waxman Cancer Research Foundation; Spanish National Health Institute [SAF-2010-16055]; Asociacion Espanola Contra el Cancer; Landon Foundation - American Association for Cancer Research Innovator Award for International Collaboration in Cancer Research; Pew Charitable Trusts FX C.A. is supported by a grant from Instituto de Salud Carlos III (ISCIII/FIS FI09/00605). J.M.L. is supported by grants from the US National Institute of Diabetes and Digestive and Kidney Diseases (J.M.L: 1R01DK076986), European Commission Framework Programme 7 (HEPTROMIC, Proposal No: 259744), The Samuel Waxman Cancer Research Foundation, the Spanish National Health Institute (J.M.L: SAF-2010-16055), and the Asociacion Espanola Contra el Cancer. The study was supported by the Landon Foundation - American Association for Cancer Research Innovator Award for International Collaboration in Cancer Research. B.Z.S. is supported by US National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK083355 and DP2-DK083111) and a grant from the Pew Charitable Trusts. NR 49 TC 104 Z9 106 U1 2 U2 33 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2012 VL 143 IS 6 BP 1660 EP + DI 10.1053/j.gastro.2012.09.002 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 042XJ UT WOS:000311505100043 PM 22974708 ER PT J AU Yurgelun, MB Mercado, R Rosenblatt, M Dandapani, M Kohlmann, W Conrad, P Blanco, A Shannon, KM Chung, DC Terdiman, J Gruber, SB Garber, JE Syngal, S Stoffel, EM AF Yurgelun, Matthew B. Mercado, Rowena Rosenblatt, Margery Dandapani, Monica Kohlmann, Wendy Conrad, Peggy Blanco, Amie Shannon, Kristen M. Chung, Daniel C. Terdiman, Jonathan Gruber, Stephen B. Garber, Judy E. Syngal, Sapna Stoffel, Elena M. TI Impact of genetic testing on endometrial cancer risk-reducing practices in women at risk for Lynch syndrome SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Lynch syndrome; Endometrial cancer screening; Prophylactic hysterectomy; Genetic testing ID NONPOLYPOSIS COLORECTAL-CANCER; COST-EFFECTIVENESS ANALYSIS; SALPINGO-OOPHORECTOMY; COLON-CANCER; MUTATION CARRIERS; BRCA2 MUTATION; INHERITED PREDISPOSITION; PROPHYLACTIC SURGERY; GYNECOLOGIC CANCERS; SURVEILLANCE AB Objective. Due to the increased lifetime risk of endometrial cancer (EC), guidelines recommend that women with Lynch syndrome (LS) age >= 35 undergo annual EC surveillance or prophylactic hysterectomy (PH). The aim of this study was to examine the uptake of these risk-reducing strategies. Methods. The study population included women meeting clinical criteria for genetic evaluation for LS. Data on cancer risk-reducing behaviors were collected from subjects enrolled in two distinct studies: (1) a multicenter cross-sectional study involving completion of a one-time questionnaire, or (2) a single-center longitudinal study in which subjects completed questionnaires before and after undergoing genetic testing. The main outcome was uptake of EC risk-reducing practices. Results. In the cross-sectional cohort, 58/77 (75%) women at risk for LS-associated EC reported engaging in EC risk-reduction. Personal history of genetic testing was associated with uptake of EC surveillance or PH (OR 17.1; 95% Cl 4.1-70.9). Prior to genetic testing for LS, 26/40 (65%) women in the longitudinal cohort reported engaging in EC risk-reduction. At one-year follow-up, 16/16 (100%) mismatch repair (MMR) gene mutation carriers were adherent to guidelines for EC risk-reduction, 9 (56%) of whom had undergone PH. By three-year follow-up, 11/16 (69%) MMR mutation carriers had undergone PH. Among women with negative or uninformative genetic test results, none underwent PH after testing. Conclusions. Genetic testing for LS is strongly associated with uptake of EC risk-reducing practices. Women found to have LS in this study underwent prophylactic gynecologic surgery at rates comparable to those published for BRCA1/2 mutation carriers. (C) 2012 Elsevier Inc. All rights reserved. C1 [Stoffel, Elena M.] Univ Michigan Hlth Syst, Div Gastroenterol, Taubman Ctr 3912, Ann Arbor, MI 48109 USA. [Yurgelun, Matthew B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Yurgelun, Matthew B.; Mercado, Rowena; Rosenblatt, Margery; Dandapani, Monica; Garber, Judy E.; Syngal, Sapna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Conrad, Peggy; Blanco, Amie; Terdiman, Jonathan] Univ Calif San Francisco, Ctr Canc, San Francisco, CA USA. [Shannon, Kristen M.; Chung, Daniel C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yurgelun, Matthew B.; Chung, Daniel C.; Garber, Judy E.; Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. [Gruber, Stephen B.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Syngal, Sapna] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Stoffel, EM (reprint author), Univ Michigan Hlth Syst, Div Gastroenterol, Taubman Ctr 3912, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM estoffel@med.umich.edu OI Blanco, Amie/0000-0003-3690-0038 FU NIH/NCI [K07CA120448-5, K24113433] FX NIH/NCI K07CA120448-5 (E. Stoffel) and NIH/NCI K24113433 (S. Syngal). NR 46 TC 4 Z9 4 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2012 VL 127 IS 3 BP 544 EP 551 DI 10.1016/j.ygyno.2012.08.031 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 043FO UT WOS:000311528500019 PM 22940489 ER PT J AU del Carmen, MG Birrer, M Schorge, JO AF del Carmen, Marcela G. Birrer, Michael Schorge, John O. TI Uterine papillary serous cancer: A review of the literature SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Uterine serous cancer; Surgery; Chemotherapy; Radiation ID GYNECOLOGIC-ONCOLOGY-GROUP; PLATINUM-BASED CHEMOTHERAPY; RISK ENDOMETRIAL CANCER; PHASE-III TRIAL; POSITRON-EMISSION-TOMOGRAPHY; WHOLE ABDOMINAL RADIOTHERAPY; POLYMERASE-CHAIN-REACTION; IN-SITU HYBRIDIZATION; CLINICAL STAGE-I; BREAST-CANCER AB Objective. Uterine papillary serous carcinoma (UPSC) represents a distinct subtype of endometrial cancer. UPSC is less common than endometrioid carcinoma (ECC) but accounts for a disproportionate number of uterine cancer related deaths. This article critically reviews the literature pertinent to the pathology, pathogenesis, diagnosis, management, and outcome of patients with UPSC. Methods. MEDLINE was searched for all research articles published in English between January 1, 1967-January 1, 2012 which reported on patients diagnosed with UPSC. Given the rarity of this tumor, studies were not limited by design or number of reported patients. Results. UPSC represents a histologically aggressive subtype of endometrial cancer. It commonly presents with extra uterine disease involvement which can be identified by comprehensive surgical staging. Optimal cytoreduction and systemic platinum/taxane-based adjuvant therapy appear to confer a survival advantage. Conclusions. UPSC is a biologically distinct entity, different from ECC. Future studies should explore the role of targeted therapies in the management of UPSC. (C) 2012 Elsevier Inc. All rights reserved. C1 [del Carmen, Marcela G.; Schorge, John O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Birrer, Michael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Med Oncol, Boston, MA 02114 USA. RP del Carmen, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 143 TC 34 Z9 34 U1 0 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2012 VL 127 IS 3 BP 651 EP 661 DI 10.1016/j.ygyno.2012.09.012 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 043FO UT WOS:000311528500037 PM 23000148 ER PT J AU Sung, RK Massie, BM Varosy, PD Moore, H Rumsfeld, J Lee, BK Keung, E AF Sung, Raphael K. Massie, Barry M. Varosy, Paul D. Moore, Hans Rumsfeld, John Lee, Byron K. Keung, Edmund TI Long-term electrical survival analysis of Riata and Riata ST silicone leads: National Veterans Affairs experience SO HEART RHYTHM LA English DT Article DE ICD; High-voltage leads; Lead failure; Ventricular tachycardia; Lead extraction ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; SINGLE-CENTER; PERFORATION; FAILURE; SHOCKS AB BACKGROUND A medical device advisory issued by St Jude Medical in November 2011 estimated 0.63% all-cause abrasion rate on their Riata and Riata ST silicone high-voltage lead families (Riata/ST), leading to Food and Drug Administration class I recall. We performed an independent comparative, long-term electrical survival analysis of Riata/ST and 3 other high-voltage lead families in a large national cohort of patients. OBJECTIVE To evaluate long-term electrical survival of Riata/ST leads relative to other commonly evaluated high-voltage leads. METHODS Failure rates of Riata/ST, Sprint Quattro Secure (Quattro), Sprint Fidelis (Fidelis), and Endotak Reliance G/SG (Endotak) leads from the Veterans Administration's National Cardiac Device Surveillance Center database, consisting of 24,145 patients with remote transmissions since 2003, were analyzed. Survival Probabilities were determined with Kaplan-Meier survival analysis and compared using the log-rank test. RESULTS Of 1,403 Riata/ST, 6,091 Quattro, 5,073 Fidelis, and 2,401 Endotak leads identified, 5-year survival probability of Riata/ST leads (97.5%) was significantly lower than that of Quattro (99.3%) and Endotak (99.4%) leads (P < .0001) but higher than that of Fidelis leads (89.6%) (P < .0001). Riata ST leads showed a 5-year survival of 95.5% (95% confidence interval 92.4-97.4) compared to 98.4% (95% confidence interval 97.1-99.1) in Riata leads (P = .003). CONCLUSIONS There is decreased survival probability of Riata/ST leads compared to other contemporary high-voltage leads, with decreased survival of Riata ST silicone compared to Riata lead series. Careful long-term follow-up should be maintained in patients with Riata/ST leads in order to prevent inappropriate shocks or failed device interventions. Our results were determined in advance of Food and Drug Administration class I recall, which suggested that large-scale remote monitoring may be an effective tool for continued implantable cardioverter-defibrillator system surveillance. C1 [Massie, Barry M.; Keung, Edmund] San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA 94121 USA. [Sung, Raphael K.; Lee, Byron K.] Univ Calif San Francisco, Dept Med, Div Cardiol, Electrophysiol Sect, San Francisco, CA 94143 USA. [Varosy, Paul D.; Rumsfeld, John] Univ Colorado, VA Eastern Colorado Hlth Care Syst, Cardiovasc Outcomes Res CCOR Grp, Denver, CO 80202 USA. [Moore, Hans] Washington DC VA Med Ctr, Div Cardiol, Washington, DC USA. [Moore, Hans; Keung, Edmund] VA Natl Cardiac Device Surveillance Program, San Francisco, CA USA. [Moore, Hans; Keung, Edmund] VA Natl Cardiac Device Surveillance Program, Washington, DC USA. RP Keung, E (reprint author), San Francisco VA Med Ctr, Div Cardiol, 4150 Clement Str, San Francisco, CA 94121 USA. EM edmund.keung@ucsf.edu FU VA's Health Services Research and Development Service [IIR 04-046]; Biotronik; Medtronic FX This study was funded by the VA's Health Services Research and Development Service Research Grant IIR 04-046 (to Dr Massie). Dr Lee received moderate consulting fees and honorarium from Biotronik and moderate research funding from Medtronic. Address reprint requests and correspondence: Dr Edmund Keung, MD, Division of Cardiology, San Francisco VA Medical Center, 4150 Clement Str, San Francisco, CA 94121. E-mail address: edmund.keung@ucsf.edu. NR 18 TC 41 Z9 42 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD DEC PY 2012 VL 9 IS 12 BP 1954 EP 1961 DI 10.1016/j.hrthm.2012.08.006 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 046VG UT WOS:000311791900017 PM 22871583 ER PT J AU Huang, Q Shi, J Sun, Q Fan, XS Feng, AN Wu, HY Zhou, Q Yu, CG Mashimo, H Lauwers, GY AF Huang, Qin Shi, Jiong Sun, Qi Fan, Xiangshan Feng, Anning Wu, Hongyan Zhou, Qiang Yu, Chenggong Mashimo, Hiroshi Lauwers, Gregory Y. TI Distal esophageal carcinomas in Chinese patients vary widely in histopathology, but adenocarcinomas remain rare SO HUMAN PATHOLOGY LA English DT Article DE Esophagus; Barrett's esophagus; Chinese; Squamous cell carcinoma; Adenocarcinoma ID SMALL-CELL CARCINOMA; BARRETTS-ESOPHAGUS; CLINICOPATHOLOGICAL FEATURES; GASTROESOPHAGEAL JUNCTION; ADENOSQUAMOUS CARCINOMA; TREND AB In Western countries, distal esophageal adenocarcinoma has outnumbered squamous cell carcinoma because of a dramatic increase in the prevalence of columnar-lined esophagus. Because the relative prevalence of these diseases remains unknown in China, we investigated the histopathology of distal esophageal neoplasm in resection specimens from a high-volume medical center in China. A computerized search of esophageal cancer was conducted in the pathology database between 2004 and 2010. Cancers with epicenter located within 5 cm above the gastroesophageal junction were retained for analysis. Pathology reports were reviewed along with medical, radiologic, and endoscopic records. All histology slides of selected cases were reevaluated (median, 13 per case). Conventional and basaloid squamous cell, adenosquamous, mucoepidermoid, and neuroendocrine carcinomas and esophageal adenocarcinoma were categorized according to the World Health Organization classification of esophageal cancers. The presence of columnar-lined esophagus and other pathologic changes were assessed in cases with residual esophageal mucosa. Among 1101 resections, 204 (19%) qualified for the study. Conventional and basaloid squamous cell, adenosquamous, mucoepidermoid, and neuroendocrine carcinomas and esophageal adenocarcinoma represented 76%, 11%, 3%, 2%, 6%, and 1% of the cases, respectively. Synchronous carcinomas were found in 12% and consisted of primarily squamous cell carcinoma (50%) and proximal gastric adenocarcinoma (38%). Columnar-lined esophagus was detected in 18% of the cases, among which intestinal metaplasia was present in 30% and low-grade dysplasia in 7%. In conclusion, distal esophageal carcinomas in Chinese patients showed a wide histopathologic spectrum with predominant squamous cell carcinoma and rare esophageal adenocarcinoma. Although common, columnar-lined esophagus appears pathogenetically insignificant for most distal esophageal carcinomas. Published by Elsevier Inc. C1 [Huang, Qin] Vet Affairs Boston Healthcare Syst, Dept Pathol, W Roxbury, MA 02132 USA. [Huang, Qin; Shi, Jiong; Sun, Qi; Fan, Xiangshan; Feng, Anning; Wu, Hongyan; Zhou, Qiang] Nanjing Drum Tower Hosp, Dept Pathol, Nanjing 210008, Peoples R China. [Huang, Qin; Mashimo, Hiroshi; Lauwers, Gregory Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yu, Chenggong] Nanjing Drum Tower Hosp, Dept Gastroenterol, Nanjing 210008, Peoples R China. [Mashimo, Hiroshi] Vet Affairs Boston Healthcare Syst, Dept Gastroenterol, W Roxbury, MA 02132 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Huang, Q (reprint author), Vet Affairs Boston Healthcare Syst, Dept Pathol & Lab Med, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Qinhuang0122@gmail.com FU Science and Technology Development Project of the Nanjing City, Nanjing, China [ZKX05013, ZKX07011]; Nanjing Drum Tower Hospital, Nanjing, China FX This research project was financed partially by key grants from the Science and Technology Development Project of the Nanjing City (ZKX05013, ZKX07011), Nanjing, China, and a special grant from the Nanjing Drum Tower Hospital, Nanjing, China. NR 35 TC 14 Z9 20 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD DEC PY 2012 VL 43 IS 12 BP 2138 EP 2148 DI 10.1016/j.humpath.2012.02.018 PG 11 WC Pathology SC Pathology GA 046JY UT WOS:000311762500006 PM 22658274 ER PT J AU Dunlap, J Beadling, C Warrick, A Neff, T Fleming, WH Loriaux, M Heinrich, MC Kovacsovics, T Kelemen, K Leeborg, N Gatter, K Braziel, RM Press, R Corless, CL Fan, G AF Dunlap, Jennifer Beadling, Carol Warrick, Andrea Neff, Tanaya Fleming, William H. Loriaux, Marc Heinrich, Michael C. Kovacsovics, Tibor Kelemen, Katalin Leeborg, Nicky Gatter, Ken Braziel, Rita M. Press, Richard Corless, Christopher L. Fan, Guang TI Multiplex high-throughput gene mutation analysis in acute myeloid leukemia SO HUMAN PATHOLOGY LA English DT Article DE Acute myeloid leukemia; Molecular; Genetics; Gene mutation ID INTERNAL TANDEM DUPLICATION; AML; IDH1; FLT3; DIAGNOSIS; PROGNOSIS; CANCER; COHORT; IMPACT AB Classification of acute myeloid leukemia increasingly depends on genetic analysis. However, the number of known mutations in acute myeloid leukemia is expanding rapidly. Therefore, we tested a high-throughput screening method for acute myeloid leukemia mutation analysis using a multiplex mass spectrometry based approach. To our knowledge, this is the first reported application of this approach to genotype leukemias in a clinical setting. One hundred seven acute myeloid leukemia cases were screened for mutations using a panel that covers 344 point mutations across 31 genes known to be associated with leukemia. The analysis was performed by multiplex polymerase chain reaction for mutations in genes of interest followed by primer extension reactions. Products were analyzed on a Sequenom MassARRAY system (San Diego, CA). The multiplex panel yielded mutations in 58% of acute myeloid leukemia cases with normal cytogenetics and 21% of cases with abnormal cytogenetics. Cytogenetics and routine polymerase chain reaction based screening of NPM1, CEBPA, FLT3-ITD, and KIT was also performed on a subset of cases. When combined with the results of these standard polymerase chain reaction based tests, the mutation frequency reached 78% in cases with normal cytogenetics. Of these, 42% harbored multiple mutations primarily involving NPM1 with NRAS, KRAS, CEBPA, PTPN11, IDH1, or FLT3. In contrast, cases with abnormal cytogenetics rarely harbored more than 1 mutation (1.5%), suggesting different underlying biology. This study demonstrates the feasibility and utility of broad-based mutation profiling of acute myeloid leukemia in a clinical setting. This approach will be helpful in defining prognostic subgroups of acute myeloid leukemia and contribute to the selection of patients for enrollment into trials with novel inhibitors. (C) 2012 Elsevier Inc. All rights reserved. C1 [Dunlap, Jennifer; Loriaux, Marc; Kelemen, Katalin; Leeborg, Nicky; Gatter, Ken; Braziel, Rita M.; Press, Richard; Corless, Christopher L.; Fan, Guang] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. [Beadling, Carol; Fleming, William H.; Heinrich, Michael C.; Kovacsovics, Tibor] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Beadling, Carol; Warrick, Andrea; Neff, Tanaya; Fleming, William H.; Loriaux, Marc; Heinrich, Michael C.; Kovacsovics, Tibor; Braziel, Rita M.; Press, Richard; Corless, Christopher L.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Fleming, William H.] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97239 USA. [Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Fan, G (reprint author), Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. EM fang@ohsu.edu NR 24 TC 6 Z9 8 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD DEC PY 2012 VL 43 IS 12 BP 2167 EP 2176 DI 10.1016/j.humpath.2012.03.002 PG 10 WC Pathology SC Pathology GA 046JY UT WOS:000311762500009 PM 22658276 ER PT J AU Ehrlich, S Williams, PL Missmer, SA Flaws, JA Ye, XY Calafat, AM Petrozza, JC Wright, D Hauser, R AF Ehrlich, Shelley Williams, Paige L. Missmer, Stacey A. Flaws, Jodi A. Ye, Xiaoyun Calafat, Antonia M. Petrozza, John C. Wright, Diane Hauser, Russ TI Urinary bisphenol A concentrations and early reproductive health outcomes among women undergoing IVF SO HUMAN REPRODUCTION LA English DT Article DE bisphenol A; oocyte; fertility; human; women; reproduction ID IN-VITRO FERTILIZATION; STEROID-HORMONE PRODUCTION; OVARIAN GRANULOSA-CELLS; INTRAUTERINE IMPLANTATION; FOLLICULAR ATRESIA; EXPOSURE; STIMULATION; VARIABILITY; PREDICTORS; APOPTOSIS AB In women undergoing IVF, are urinary bisphenol A (BPA) concentrations associated with ovarian response and early reproductive outcomes, including oocyte maturation and fertilization, Day 3 embryo quality and blastocyst formation? Higher urinary BPA concentrations were found to be associated with decreased ovarian response, number of fertilized oocytes and decreased blastocyst formation. Experimental animal and in vitro studies have reported associations between BPA exposure and adverse reproductive outcomes. We previously reported an association between urinary BPA and decreased ovarian response [peak serum estradiol (E-2) and oocyte count at the time of retrieval] in women undergoing IVF; however, there are limited human data on reproductive health outcomes, such as fertilization and embryo development. Prospective preconception cohort study. One hundred and seventy-four women aged 1845 years and undergoing 237 IVF cycles were recruited at the Massachusetts General Hospital Fertility Center, Boston, MA, USA, between November 2004 and August 2010. These women were followed until they either had a live birth or discontinued treatment. Cryothaw and donor egg cycles were not included in the analysis. Urinary BPA concentrations were measured by online solid-phase extraction-high-performance liquid chromatography-isotope dilution-tandem mass spectrometry. Mixed effect models, poisson regression and multivariate logistic regression models were used wherever appropriate to evaluate the association between cycle-specific urinary BPA concentrations and measures of ovarian response, oocyte maturation (metaphase II), fertilization, embryo quality and cleavage rate. We accounted for correlation among multiple IVF cycles in the same woman using generalized estimating equations. The geometric mean (SD) for urinary BPA concentrations was 1.50 (2.22) g/l. After adjustment for age and other potential confounders (Day 3 serum FSH, smoking, BMI), there was a significant linear doseresponse association between increased urinary BPA concentrations and decreased number of oocytes (overall and mature), decreased number of normally fertilized oocytes and decreased E-2 levels (mean decreases of 40, 253 and 471 pg/ml for urinary BPA quartiles 2, 3 and 4, when compared with the lowest quartile, respectively; P-value for trend 0.001). The mean number of oocytes and normally fertilized oocytes decreased by 24 and 27, respectively, for the highest versus the lowest quartile of urinary BPA (trend test P 0.001 and 0.002, respectively). Women with urinary BPA above the lowest quartile had decreased blastocyst formation (trend test P-value 0.08). Potential limitations include exposure misclassification due to the very short half-life of BPA and its high variability over time; uncertainty about the generalizability of the results to the general population of women conceiving naturally and limited sample. The results from this extended study, using IVF as a model to study early reproductive health outcomes in humans, indicate a negative doseresponse association between urinary BPA concentrations and serum peak E-2 and oocyte yield, confirming our previous findings. In addition, we found significantly decreased metaphase II oocyte count and number of normally fertilizing oocytes and a suggestive association between BPA urinary concentrations and decreased blastocyst formation, thus indicating that BPA may alter reproductive function in susceptible women undergoing IVF. This work was supported by grants ES009718 and ES000002 from the National Institute of Environmental Health Sciences and grant OH008578 from the National Institute for Occupational Safety and Health. None of the authors has actual or potential competing financial interests. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. C1 [Ehrlich, Shelley; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Missmer, Stacey A.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Missmer, Stacey A.] Harvard Univ, Sch Med, Boston, MA USA. [Missmer, Stacey A.; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Flaws, Jodi A.] Univ Illinois, Dept Comparat Biosci, Urbana, IL USA. [Ye, Xiaoyun; Calafat, Antonia M.; Petrozza, John C.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Wright, Diane; Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,14th Floor, Boston, MA 02115 USA. EM rhauser@hsph.harvard.edu RI Ehrlich , Shelley/L-6991-2015 FU National Institute of Environmental Health Sciences [ES009718, ES000002]; National Institute for Occupational Safety and Health [OH008578] FX This work was supported by grants ES009718 and ES000002 from the National Institute of Environmental Health Sciences and grant OH008578 from the National Institute for Occupational Safety and Health. NR 53 TC 60 Z9 60 U1 5 U2 32 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD DEC PY 2012 VL 27 IS 12 BP 3583 EP 3592 DI 10.1093/humrep/des328 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 044SU UT WOS:000311644700028 PM 23014629 ER PT J AU Sonnenberg, A Genta, RM AF Sonnenberg, Amnon Genta, Robert M. TI Geographic distributions of microscopic colitis and inflammatory bowel disease in the United States SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE collagenous colitis; Crohn's disease; epidemiology of inflammatory bowel disease; geographic distribution; microscopic colitis; ulcerative colitis ID COLLAGENOUS COLITIS; CROHNS-DISEASE; EPIDEMIOLOGY; NORTH AB Background: Crohn's disease (CD) and ulcerative colitis (UC) are characterized by similar geographic distributions. We used a large database of pathology reports to analyze the geographic distribution of microscopic colitis (MC) and compare it with those of UC and CD. Methods: A population of 671,176 individual patients with colonic biopsies was studied stratified by gender and state of residence. The occurrence of each diagnosis MC, UC, or CD, was expressed as proportional rate per 1000 colonoscopies with biopsies from each individual state. Results: UC and CD tended to be common in states in the Northeast or North Central regions of the U.S. and relatively rare among several southern states. MC appeared to follow a somewhat inverse pattern, as it was most common among some states from the Southwest (Colorado, New Mexico, Arizona, Nevada) and other states of southern latitude, such as Florida, Georgia, California, but relatively uncommon among states in the Northeast. The geographic distributions of UC and CD were significantly correlated with each other (R = 0.60 and P = 0.0004). No significant correlation was observed between MC and UC or CD. Conclusions: The differences in epidemiologic behavior point at a dissimilar set of risk factors that shape the occurrence of MC as opposed to UC or CD. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Genta, Robert M.] Caris Life Sci, Irving, TX USA. [Genta, Robert M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Genta, Robert M.] Dallas VA Med Ctr, Dallas, TX USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu FU Takeda Pharmaceuticals FX Conflicts of interests: Amnon Sonnenberg is supported by a grant from Takeda Pharmaceuticals. Robert M. Genta is employed by Caris Life Sciences, Irving, TX. Author Contributions: conception and design: Amnon Sonnenberg; Robert M. Genta; pathological interpretation of specimens: Robert M. Genta; analysis of data: Amnon Sonnenberg, Robert M. Genta; writing of article: Amnon Sonnenberg, Robert M. Genta. NR 14 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2012 VL 18 IS 12 BP 2288 EP 2293 DI 10.1002/ibd.22932 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 039JR UT WOS:000311242400012 PM 22374913 ER PT J AU Cheifetz, AS Melmed, GY Spiegel, B Talley, J Devlin, SM Raffals, L Irving, PM Jones, J Kaplan, GG Kozuch, P Sparrow, M Velayos, F Baidoo, L Bressler, B Siegel, CA AF Cheifetz, A. S. Melmed, G. Y. Spiegel, B. Talley, J. Devlin, S. M. Raffals, L. Irving, P. M. Jones, J. Kaplan, G. G. Kozuch, P. Sparrow, M. Velayos, F. Baidoo, L. Bressler, B. Siegel, C. A. TI Setting priorities for comparative effectiveness research in inflammatory bowel disease: Results of an international provider survey, expert rand panel, and patient focus groups SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE comparative effective research; Crohn's disease; ulcerative colitis ID CROHNS-DISEASE AB Background: Comparative effectiveness research (CER) is an emerging field that compares the relative effectiveness of alternative strategies to prevent, diagnose, or treat patients who are typical of day-to-day practice. We developed a priority list of CER topics for inflammatory bowel disease (IBD). Methods: Following the Institute of Medicine's approach, we developed and administered a survey to gastroenterologists asking for important CER topics in IBD. Two patient focus groups were convened to solicit additional CER studies. CER topics were presented to the expert panel using the RAND/UCLA methodology. Following initial ratings, the panel met to discuss and re-rate priorities. The top 10 CER topics were identified using a point-allocation system. Results: Responses were collated into 234 CER topics across 21 categories, of which 87 were prioritized for discussion and re-rated. Disagreement regarding priorities was observed in 5 of 87 studies. We utilized a point-allocation system to prioritize the top-10 CER topics. These related to comparing the effectiveness of: biomarkers in IBD; withdrawal of anti-tumor necrosis factor (TNF) or immunomodulators for Crohn's disease in remission; mucosal healing as an endpoint of treatment; infliximab levels versus standard infliximab dosing; anti-TNF monotherapy versus combination therapy in patients failing thiopurines; safety of long-term treatment options; anti-TNF versus thiopurines for prevention of postoperative recurrence; and treatment options for steroid-refractory UC. Conclusions: We systematically developed a list of high-priority IBD topics for CER based on a survey of gastroenterologists, expert review, and patient input. This list may guide IBD research toward the most important CER studies. C1 [Cheifetz, A. S.] Beth Israel Deaconess Med Ctr, Ctr IBD, Boston, MA 02215 USA. [Melmed, G. Y.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Spiegel, B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Talley, J.] CURE Digest Dis Res Ctr, Los Angeles, CA USA. [Devlin, S. M.; Kaplan, G. G.] Univ Calgary, Calgary, AB, Canada. [Raffals, L.] Mayo Clin, Rochester, MN USA. [Irving, P. M.] Guys & St Thomas Hosp, London SE1 9RT, England. [Jones, J.] Univ Saskatchewan, Saskatoon, SK, Canada. [Kozuch, P.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Sparrow, M.] Alfred Hosp, Melbourne, Vic, Australia. [Velayos, F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Baidoo, L.] Univ Pittsburgh, Pittsburgh, PA USA. [Bressler, B.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Siegel, C. A.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Cheifetz, AS (reprint author), Beth Israel Deaconess Med Ctr, Ctr IBD, 330 Brookline Ave,Rabb 425, Boston, MA 02215 USA. EM acheifet@bidmc.harvard.edu OI kozuch, patricia/0000-0002-7465-9671; Kaplan, Gilaad/0000-0003-2719-0556 FU Warner-Chilcott; Abbott; Shire; Salix; UCB; Centocor; Setpoint; Amgen; Celgene; Elan; PG; Merck; GlaxoSmithKline; Millenium Pharmaceuticals; Genentech; Bristol-Myers Squibb; Schering-Plough Canada; UCB Pharma; Ferring Pharmaceuticals; Abbott Pharmaceuticals; Glycominds FX Unrestricted funding for the in-person Scottsdale RAND Appropriateness Panel meeting was generously provided by Warner-Chilcott, Abbott, and Shire. Unrestricted funding for the BRIDGe group is provided by Abbott, Salix, Shire, UCB, and Warner-Chilcott; The authors thank Dr. Harold Sox for contributions in consulting on study design and following IOM methodology and for article review. Disclosures: A. S. C.: Advisory Board (Warner Chilcott, Abbott, UCB); G.Y.M.: Consultant and/or Research Support (Centocor, Setpoint, Amgen, Celgene), Speaker Bureau (Abbott, Prometheus), Advisory Board (UCB); C. A. S.: Advisory Board (Abbott, UCB, P&G), Consultant and Research Support (Elan, P&G), CME activities (Abbott, UCB); B. M. S.: Research (Shire Pharmaceuticals, Ironwood Pharmaceuticals, Takeda Pharma, Rose Pharma A/G), Advisory Board (Prometheus, Salix, Boehringer Inngelheim, Ironwood, AstraZeneca, Pfizer); B. B.: Advisory Board (Abbott, Schering-Plough Canada, Shire, Ferring, Merck, Warner Chilcott, Genentech), Speaker Bureau (Janssen Ortho, Abbott, Merck, Shire, Takeda, Ferring, Warner Chilcott) Research Support (Abbott, Merck, Amgen, GlaxoSmithKline, Millenium Pharmaceuticals, Genentech, Bristol-Myers Squibb); J.J.: Consulting, Speaker's Bureau and Educational Funding (Schering-Plough Canada, UCB Pharma, Shire, P&G and Abbott); M. S.: Research Support (Ferring Pharmaceuticals, Abbott Pharmaceuticals), Advisory Board (Schering-Plough Pharmaceuticals); F. V.: Research Support (P & G); P. M. I.: Advisory Board (Abbott, MSD, Shire, Falk), Speaker's Bureau (Shire, Abbott, MSD, Merck); S. M. D.: Speaker (Schering-Plough, Abbott, Merck, Shire), Advisory Board (Abbott, UCB, Schering-Plough, Shire, Merck); G. G. K.: Advisory Board (Schering-Plough, Abbott, UCB, Shire); L. H.: Consultant (Abbott, Salix), Research support (Glycominds); L. B.: Advisory Board (UCB), Speaker's Bureau (Centocor, Salix); P. K.: None. Contributions: A. S. Cheifetz: study concept and design, drafting of the article, acquisition of data, analysis and interpretation of data, critical revision of the article for important intellectual content of the article; G.Y. Melmed, B. Spiegel, C. A. Siegel: study concept and design, acquisition of data, analysis and interpretation of data, critical revision of the article for important intellectual content of the article; J. Talley: acquisition of data, analysis and interpretation of data, critical revision of the article for important intellectual content of the article; S. M. Devlin, L. Harrell, P. M. Irving, J. Jones, G. G. Kaplan, P. Kozuch, M. Sparrow, F. Velayos, L. Baidoo, B. Bressler: acquisition of data, interpretation of data, critical revision of the article for important intellectual content. NR 9 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2012 VL 18 IS 12 BP 2294 EP 2300 DI 10.1002/ibd.22920 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 039JR UT WOS:000311242400013 PM 22337359 ER PT J AU Fazeli, PK Calder, GL Miller, KK Misra, M Lawson, EA Meenaghan, E Lee, H Herzog, D Klibanski, A AF Fazeli, Pouneh K. Calder, Genevieve L. Miller, Karen K. Misra, Madhusmita Lawson, Elizabeth A. Meenaghan, Erinne Lee, Hang Herzog, David Klibanski, Anne TI Psychotropic medication use in anorexia nervosa between 1997 and 2009 SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE Anorexia Nervosa; SSRI; Atypical Antipsychotic ID BONE-MINERAL DENSITY; CONTROLLED-TRIAL; AMITRIPTYLINE THERAPY; EATING-DISORDERS; DOUBLE-BLIND; FOLLOW-UP; FLUOXETINE; RISK; OLANZAPINE; WOMEN AB Objective: Despite a lack of data demonstrating benefit, psychotropic medications are frequently prescribed for patients with anorexia nervosa. Method: We studied 525 women (1854 years of age) with anorexia nervosa who presented to the Clinical Research Center at the Massachusetts General Hospital between January 1997 and December 2009. For this analysis, participants were a priori divided into two groups based on date of presentation (Group I: participants presenting between 1997 and 2002; Group II: participants presenting between 2003 and 2009). Results: Overall, 53% of participants reported current use of any psychotropic medication; 48.4% reported use of an antidepressant and 13% reported use of an antipsychotic. Twice as many participants in Group II (18.5%) reported using atypical antipsychotics as compared to Group I (8.9%) (p = 0.002). Discussion: A majority of participants with anorexia nervosa report using psychotropic medications despite lack of data supporting their efficacy. These data are concerning given the known adverse effects of these medications. (c) 2012 by Wiley Periodicals, Inc. C1 [Fazeli, Pouneh K.; Calder, Genevieve L.; Miller, Karen K.; Misra, Madhusmita; Lawson, Elizabeth A.; Meenaghan, Erinne; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Boston, MA 02114 USA. [Fazeli, Pouneh K.; Calder, Genevieve L.; Miller, Karen K.; Misra, Madhusmita; Lawson, Elizabeth A.; Meenaghan, Erinne; Herzog, David; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA USA. [Calder, Genevieve L.] Univ Melbourne, Sch Med, Melbourne, Vic 3010, Australia. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Herzog, David] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Bulfinch 457B, Boston, MA 02114 USA. EM aklibanski@partners.org FU National Institutes of Health [R01 DK052625, DK062249, DK084970, MH083657, ULIRR0257801, M01 RR01066] FX Supported by R01 DK052625, DK062249, DK084970, MH083657, ULIRR0257801, M01 RR01066 from National Institutes of Health. NR 47 TC 12 Z9 12 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD DEC PY 2012 VL 45 IS 8 BP 970 EP 976 DI 10.1002/eat.22037 PG 7 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 040AB UT WOS:000311289700009 PM 22733643 ER PT J AU Olson, KR Caldwell, A Sihombing, M Guarino, AJ Nelson, BD AF Olson, Kristian R. Caldwell, Aya Sihombing, Melva Guarino, Anthony J. Nelson, Brett D. TI Community-based newborn resuscitation among frontline providers in a low-resource country SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE Birth asphyxia; Low-resource country; Neonatal mortality; Newborn health; Traditional birth attendant ID NEONATAL SURVIVAL; UNDER-5 MORTALITY; NORTH-INDIA; BIRTH; CARE; ATTENDANCE; INDONESIA; SETTINGS; DEATHS; HEALTH AB Objective: To evaluate a birth asphyxia management program among community midwives in a low-resource rural setting. Methods: Concise training with provision of positive-pressure ventilation devices was implemented in Indonesia in 2005. The effectiveness of the intervention among community-based midwives between October 2007 and September 2008 was evaluated. The intervention cohort was compared with a neighboring control cohort. Results: Overall, 242 intervention and 106 control midwives were surveyed. In total, 3116 births were attended, 84.0% of deliveries occurred at home, and 97.4% of midwives had not previously owned a resuscitation device. When positive-pressure ventilation was administered, newborn survival on day 1 was equivalent in the 2 cohorts (88.4% versus 84.4%; P=0.66). However, significantly more newborns in the intervention group underwent ventilation (risk ratio 23: 95% confidence interval, 1.4-8.0). The intervention group had significantly greater scores on both knowledge (t[144.35] = 10.52; P<0.001) and confidence (t[134.17] = 11.66; P<0.001). Conclusion: Focused community-based resuscitation training and device delivery resulted in a significantly increased proportion of newborns receiving life-saving positive-pressure breaths, in addition to improved provider knowledge and confidence. Furthermore, the program demonstrated the establishment of an effective training infrastructure within a disrupted health system. (C) 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Olson, Kristian R.; Caldwell, Aya] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Olson, Kristian R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Olson, Kristian R.; Nelson, Brett D.] Massachusetts Gen Hosp, Dept Pediat, Div Global Hlth, Boston, MA 02114 USA. [Olson, Kristian R.; Caldwell, Aya; Nelson, Brett D.] Harvard Univ, Sch Med, Boston, MA USA. [Sihombing, Melva] Int Org Migrat, Geneva, Switzerland. [Sihombing, Melva] Univ Indonesia, Dept Publ Hlth, Jakarta, Indonesia. [Guarino, Anthony J.] MGH Inst Hlth Profess, Charlestown, MA USA. RP Olson, KR (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM krolson@partners.org OI Nelson, Brett/0000-0002-5049-1798 NR 24 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD DEC PY 2012 VL 119 IS 3 BP 244 EP 247 DI 10.1016/j.ijgo.2012.07.012 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 042ID UT WOS:000311464000011 PM 23040406 ER PT J AU Liersch, R Hirakawa, S Berdel, WE Mesters, RM Detmar, M AF Liersch, Ruediger Hirakawa, Satoshi Berdel, Wolfgang E. Mesters, Rolf M. Detmar, Michael TI Induced lymphatic sinus hyperplasia in sentinel lymph nodes by VEGF-C as the earliest premetastatic indicator SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE metastasis; sentinel lymph node; VEGF-C; lymphatic sinuses; lymphatic endothelial cells ID NEGATIVE BREAST-CARCINOMA; GROWTH-FACTOR-C; PROMOTES TUMOR-METASTASIS; PROGNOSTIC-SIGNIFICANCE; CANCER PATIENTS; INDUCED LYMPHANGIOGENESIS; MELANOMA METASTASIS; EXPRESSION; CELLS; ANGIOGENESIS AB Research on tumor-induced lymphangiogenesis has predominantly focused on alterations and abnormal growth of peritumoral and intratumoral lymphatic vessels. However, recent evidence indicates that lymphangiogenesis of sentinel lymph nodes might also contribute to cancer progression. In clinical oncology, the sentinel lymph nodes play an important role in diagnosis, staging and management of disease. The prognostic value that may be placed in the analysis of various parameters in tumor-free lymph nodes is still under debate. We, therefore, chose to investigate genetically fluorescent MDA-MB-435/green fluorescent protein human cancer cells transfected to overexpress VEGF-C in a nude mouse model and investigated metastasis, lymph node lymphangiogenesis, lymph node angiogenesis and size of sentinel lymph nodes. The nature of MDA-MB-435, identified as a breast cancer cell line for several decades, has recently been reidentified as being from melanoma origin. Vascular endothelial growth factor-C overexpression induced early metastasis and significantly increased the lymphatic vessel area in sentinel lymph nodes even before the tumor metastasis. At early time-points, expansion of the lymphatic network was observed even though no difference of blood vessel area and lymph node size was detected. These results suggest that primary tumors -via secretion of VEGF-C- can induce hyperplasia of the sentinel lymph node lymphatic vessel network and thereby promote their further spread. In cases of tumor-free lymph nodes the increased lymphatic network of sentinel lymph nodes is a very early premetastatic sign and may provide a new prognostic indicator and target for aggressive diseases. C1 [Liersch, Ruediger; Berdel, Wolfgang E.; Mesters, Rolf M.] Univ Munster, Dept Med Hematol & Oncol A, D-48149 Munster, Germany. [Liersch, Ruediger; Hirakawa, Satoshi; Detmar, Michael] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Liersch, Ruediger; Hirakawa, Satoshi; Detmar, Michael] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Liersch, Ruediger; Detmar, Michael] Swiss Fed Inst Technol, Inst Pharmaceut Sci, CH-8092 Zurich, Switzerland. RP Liersch, R (reprint author), Univ Munster, Dept Med Hematol & Oncol A, Albert Schweitzer Campus 1, D-48149 Munster, Germany. EM rliersch@uni-muenster.de FU NIH [CA69184, CA86410, CA92644]; American Cancer Society [99-23901]; Swiss National Fund [3100A0-108207]; Fonds fur wissenschaftliche Forderung [S9408-B11]; Deutsche Krebshilfe FX We thank M. Constant, L. Janes and L. Nguyen for expert technical assistance. This work was supported by NIH grants CA69184, CA86410, CA92644 (MD), American Cancer Society Research Project Grant 99-23901 (MD), Swiss National Fund grant 3100A0-108207 (MD), Fonds fur wissenschaftliche Forderung grant S9408-B11 (MD), and by the Deutsche Krebshilfe (RL). NR 47 TC 18 Z9 19 U1 0 U2 3 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD DEC PY 2012 VL 41 IS 6 BP 2073 EP 2078 DI 10.3892/ijo.2012.1665 PG 6 WC Oncology SC Oncology GA 043YZ UT WOS:000311587900020 PM 23076721 ER PT J AU Hammer, MD Schwamm, L Starkman, S Schellinger, PD Jovin, T Nogueira, R Burgin, WS Sen, S Diener, HC Watson, T Michel, P Shuaib, A Dillon, W Liebeskind, DS AF Hammer, M. D. Schwamm, L. Starkman, S. Schellinger, P. D. Jovin, T. Nogueira, R. Burgin, W. S. Sen, S. Diener, H. C. Watson, T. Michel, P. Shuaib, A. Dillon, W. Liebeskind, D. S. TI Safety and feasibility of NeuroFlo use in eight- to 24-hour ischemic stroke patients SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE acute stroke therapy; cerebral blood flow; cerebral infarction; clinical trial; intervention; stroke ID TISSUE-PLASMINOGEN ACTIVATOR; CEREBRAL-BLOOD-FLOW; OCCLUSION; PERFUSION; TRIALS; AORTA AB Background Acute treatment of ischemic stroke patients presenting more than eight-hours after symptom onset remains limited and largely unproven. Partial aortic occlusion using the NeuroFlo catheter can augment cerebral perfusion in animals. We investigated the safety and feasibility of employing this novel catheter to treat ischemic stroke patients eight-hours to 24h following symptom onset. Methods A multicenter, single-arm trial enrolled ischemic stroke patients at nine international academic medical centers. Eligibility included age 1885 years old, National Institutes of Health stroke scale (NIHSS) score between four and 20, within eight-hours to 24h after symptom onset, and perfusiondiffusion mismatch confirmed by magnetic resonance imaging. The primary outcome was all adverse events occurring from baseline to 30 days posttreatment. Secondary outcomes included stroke severity on neurological indices through 90 days. This study is registered with ClinicalTrials.gov, number NCT00436592. Results A total of 26 patients were enrolled. Of these, 25 received treatment (one excluded due to aortic morphology); five (20%) died. Favorable neurological outcome at 90 days (modified Rankin score 02 vs. 36) was associated with lower baseline NIHSS (P<0.001) and with longer duration from symptom discovery to treatment. There were no symptomatic intracranial hemorrhages or parenchymal hematomas. Asymptomatic intracranial hemorrhage was visible on computed tomography in 32% and only on microbleed in another 20%. Conclusions Partial aortic occlusion using the NeuroFlo catheter, a novel collateral therapeutic strategy, appears safe and feasible in stroke patients eight-hours to 24h after symptom onset. C1 [Hammer, M. D.] Univ Pittsburgh, Med Ctr, Stroke Inst, Dept Neurol, Pittsburgh, PA 15213 USA. [Schwamm, L.; Nogueira, R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Starkman, S.; Liebeskind, D. S.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Schellinger, P. D.] Univ Klinikum Erlangen, Dept Neurol, Erlangen, Germany. [Burgin, W. S.] Univ Rochester, Dept Neurol, Rochester, NY USA. [Sen, S.] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. [Diener, H. C.] Univ Klinikum Duisburg Essen, Dept Neurol, Essen, Germany. [Michel, P.] CHUV Lausanne, Lausanne, Switzerland. [Watson, T.] Univ Calgary, Dept Neurol, Calgary, AB, Canada. [Shuaib, A.] Univ Alberta, Stroke Program, Edmonton, AB, Canada. [Dillon, W.] UCSF, Dept Radiol, San Francisco, CA USA. RP Hammer, MD (reprint author), Univ Pittsburgh, Med Ctr, Stroke Inst, Dept Neurol, 200 Lothrop St,PUH C-419, Pittsburgh, PA 15213 USA. EM hammermd@upmc.edu OI Schwamm, Lee/0000-0003-0592-9145 FU CoAxia, Inc., Maple Grove, MN; NINDS [K23054084]; CoAxia FX Funding for this study was provided by CoAxia, Inc., Maple Grove, MN. DSL received grant support from NINDS K23054084.; All of the authors are members of the steering committee for the Flo24 clinical trial, which is sponsored by CoAxia, and as such, have received minor payments from CoAxia for consultative work. In addition, the following authors have received major payments from CoAxia for consultative work: Ashfaq Schwaib and Peter Schellinger. NR 17 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD DEC PY 2012 VL 7 IS 8 BP 655 EP 661 DI 10.1111/j.1747-4949.2011.00719.x PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 034KI UT WOS:000310871300011 PM 22264202 ER PT J AU Gu, JW Herrmann, BS Levine, RA Melcher, JR AF Gu, Jianwen Wendy Herrmann, Barbara S. Levine, Robert A. Melcher, Jennifer R. TI Brainstem Auditory Evoked Potentials Suggest a Role for the Ventral Cochlear Nucleus in Tinnitus SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE auditory brainstem response (ABR); brainstem auditory evoked potential (BAEP); auditory nerve; ventral cochlear nucleus; spherical bushy cells; inferior colliculus; dorsal cochlear nucleus ID INDUCED HEARING-LOSS; PSYCHOMETRIC PROPERTIES; CAT; RESPONSES; NERVE; DEGENERATION; GENERATORS; INVENTORY; SENSITIVITY; PROJECTIONS AB Numerous studies have demonstrated elevated spontaneous and sound-evoked brainstem activity in animal models of tinnitus, but data on brainstem function in people with this common clinical condition are sparse. Here, auditory nerve and brainstem function in response to sound was assessed via auditory brainstem responses (ABR) in humans with tinnitus and without. Tinnitus subjects showed reduced wave I amplitude (indicating reduced auditory nerve activity) but enhanced wave V (reflecting elevated input to the inferior colliculi) compared with non-tinnitus subjects matched in age, sex, and pure-tone threshold. The transformation from reduced peripheral activity to central hyperactivity in the tinnitus group was especially apparent in the V/I and III/I amplitude ratios. Compared with a third cohort of younger, non-tinnitus subjects, both tinnitus, and matched, non-tinnitus groups showed elevated thresholds above 4 kHz and reduced wave I amplitude, indicating that the differences between tinnitus and matched non-tinnitus subjects occurred against a backdrop of shared peripheral dysfunction that, while not tinnitus specific, cannot be discounted as a factor in tinnitus development. Animal lesion and human neuroanatomical data combine to indicate that waves III and V in humans reflect activity in a pathway originating in the ventral cochlear nucleus (VCN) and with spherical bushy cells (SBC) in particular. We conclude that the elevated III/I and V/I amplitude ratios in tinnitus subjects reflect disproportionately high activity in the SBC pathway for a given amount of peripheral input. The results imply a role for the VCN in tinnitus and suggest the SBC pathway as a target for tinnitus treatment. C1 [Gu, Jianwen Wendy; Levine, Robert A.; Melcher, Jennifer R.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Gu, Jianwen Wendy; Herrmann, Barbara S.; Melcher, Jennifer R.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Herrmann, Barbara S.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Herrmann, Barbara S.; Levine, Robert A.; Melcher, Jennifer R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Levine, Robert A.] Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Melcher, JR (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Jennifer_Melcher@meei.harvard.edu FU Tinnitus Research Initiative; American Tinnitus Association; NIH/NIDCD [P30DC005209] FX The authors thank Inge Knudson for insightful comments on the work, assistance with data collection and subject recruitment and comments on the manuscript, Barbara Norris for her assistance with study coordination and figure making, and M. Charles Liberman for comments on the thesis on which this manuscript is based. Support was provided by the Tinnitus Research Initiative, the American Tinnitus Association, and NIH/NIDCD P30DC005209. NR 46 TC 57 Z9 59 U1 2 U2 22 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD DEC PY 2012 VL 13 IS 6 BP 819 EP 833 DI 10.1007/s10162-012-0344-1 PG 15 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 043IC UT WOS:000311535100007 PM 22869301 ER PT J AU Barr, CJ Barbalace, RJ Wessinger, SJ Bragdon, CR Kwon, YM Malchau, H AF Barr, Christopher J. Barbalace, Richard J. Wessinger, Sara J. Bragdon, Charles R. Kwon, Young-Min Malchau, Henrik TI Validation of a Hospital-Based Joint Registry Quantification of Errors and Maximizing Utility SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total joint arthroplasty; clinical data registry; clinical outcomes assessment; data validation; quality assurance ID TOTAL HIP-ARTHROPLASTY; REPLACEMENT; COMPLETENESS; TERM; AGE AB Data quality standards for multicenter arthroplasty registries have been previously established. However, no studies have assessed a hospital-based arthroplasty registry. A total of 6912 hip and knee procedures were queried in a hospital-based arthroplasty registry (HJR) and an administrative research database (Research Patient Data Registry). The HJR demonstrated a 93.8% capture rate. Four hundred seventy-seven cases contained data errors, with 65.7% occurring in the HJR. Most of these conflicts were attributable to random error. Systematic miscoding of procedures was observed in both databases and was most likely due to unclear definitions of procedural classifications. Our results confirm the validity of data in the HJR and suggest that using automated data capture systems and establishing a clear consensus on procedural terminology can improve the quality of data registries. C1 [Barr, Christopher J.; Barbalace, Richard J.; Wessinger, Sara J.; Bragdon, Charles R.; Kwon, Young-Min; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. RP Barr, CJ (reprint author), 55 Fruit St,GRJ 1125, Boston, MA 02114 USA. OI Malchau, Henrik/0000-0002-4291-2441 NR 22 TC 2 Z9 2 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 2012 VL 27 IS 10 BP 1766 EP 1771 DI 10.1016/j.arth.2012.04.028 PG 6 WC Orthopedics SC Orthopedics GA 043XH UT WOS:000311583500005 PM 22743121 ER PT J AU Fang, H Caranto, JD Mendoza, R Taylor, AB Hart, PJ Kurtz, DM AF Fang, Han Caranto, Jonathan D. Mendoza, Rosalinda Taylor, Alexander B. Hart, P. John Kurtz, Donald M., Jr. TI Histidine ligand variants of a flavo-diiron protein: effects on structure and activities SO JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY LA English DT Article DE Non-heme iron; Nitric oxide; Dioxygen; X-ray crystallography; Enzyme kinetics; Site-directed mutagenesis ID NITRIC-OXIDE REDUCTASE; PARASITE GIARDIA-INTESTINALIS; FLAVODIIRON PROTEINS; DESULFOVIBRIO-GIGAS; ESCHERICHIA-COLI; MOORELLA-THERMOACETICA; CRYSTAL-STRUCTURES; SITE STRUCTURE; IN-VIVO; FLAVORUBREDOXIN AB Flavo-diiron proteins (FDPs) contain non-heme diiron and proximal flavin mononucleotide (FMN) active sites and function as terminal components of a nitric oxide reductase (NOR) and/or a four-electron dioxygen reductase (O2R). While most FDPs show similar structural, spectroscopic, and redox properties, O2R and NOR activities vary significantly among FDPs. A potential source of this variability is the iron ligation status of a conserved His residue that provides an iron ligand in all known FDP structures but one, where this His residue is rotated away from iron and replaced by a solvent ligand. In order to test the effect of this His ligation status, we changed this ligating His residue (H90) in Thermotoga maritima (Tm) FDP to either Asn or Ala. The wild-type Tm FDP shows significantly higher O2R than NOR activity. Single crystal X-ray crystallography revealed a remarkably conserved diiron site structure in the H90N and -A variants, differing mainly by either Asn or solvent coordination, respectively, in place of H90. The steady-state activities were minimally affected by the H90 substitutions, remaining significantly higher for O2R versus NOR. The pre-steady-state kinetics of the fully reduced FDP with O-2 were also minimally affected by the H90 substitutions. The results indicate that the coordination status of this His ligand does not significantly modulate the O2R or NOR activities, and that FDPs can retain these activities when the individual iron centers are differentiated by His ligand substitution. This differentiation may have implications for the O2R and NOR mechanisms of FDPs. C1 [Fang, Han; Caranto, Jonathan D.; Mendoza, Rosalinda; Kurtz, Donald M., Jr.] Univ Texas San Antonio, Dept Chem, San Antonio, TX 78249 USA. [Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Hart, P. John] S Texas Vet Hlth Care Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Kurtz, DM (reprint author), Univ Texas San Antonio, Dept Chem, San Antonio, TX 78249 USA. EM donald.kurtz@utsa.edu FU National Institute of Health [RO1 GM040388]; Robert A. Welch Foundation [AQ-1399] FX This work was supported by grants from National Institute of Health (RO1 GM040388 to D. M. K. Jr.) and the Robert A. Welch Foundation (AQ-1399 to P. J. H.). Support for the X-ray Crystallography Core Laboratory by the University of Texas Health Sciences Center at San Antonio Executive Research Committee and the Cancer Therapy & Research Center is gratefully acknowledged. We thank Professor Heather Shipley for access to and assistance with the inductively coupled plasma mass spectrometer. NR 36 TC 8 Z9 9 U1 0 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0949-8257 J9 J BIOL INORG CHEM JI J. Biol. Inorg. Chem. PD DEC PY 2012 VL 17 IS 8 BP 1231 EP 1239 DI 10.1007/s00775-012-0938-4 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 045BL UT WOS:000311669200009 PM 22990880 ER PT J AU Juppner, H Wolf, M AF Jueppner, Harald Wolf, Myles TI alpha Klotho: FGF23 coreceptor and FGF23-regulating hormone SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID FIBROBLAST GROWTH FACTOR-23; HYPOPHOSPHATEMIC RICKETS; MICE; EXPRESSION; PHOSPHATE; HYPERPHOSPHATEMIA; METABOLISM; ABLATION; MUTATION; DIETARY AB Low levels of phosphate can disrupt bone ossification and predispose to fractures. FGF23 is one of the major determinants of phosphate-homeostasis, acting to increase urinary phosphate excretion. However, the regulation of FGF23 is incompletely understood. In this issue of the JCI, Smith et al. show that the cleaved form of alpha Klotho, the membrane bound form of which is an FGF23 coreceptor, serves as a novel endocrine regulator of phosphate homeostasis, capable of inducing FGF23 production in osteocytes. C1 [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, Miami, FL 33136 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 10, Boston, MA 02114 USA. EM hjueppner@partners.org FU NCATS NIH HHS [U54TR000255]; NIDDK NIH HHS [R01DK094796, R01DK081374, R01 DK094796, P01 DK011794, K24 DK093723, K24DK093723, P01DK011794, R01 DK046718, R01DK46718] NR 23 TC 7 Z9 8 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2012 VL 122 IS 12 BP 4336 EP 4339 DI 10.1172/JCI67055 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 048PY UT WOS:000311926200010 PM 23187136 ER PT J AU Rodig, SJ Cheng, JW Wardzala, J DoRosario, A Scanlon, JJ Laga, AC Martinez-Fernandez, A Barletta, JA Bellizzi, AM Sadasivam, S Holloway, DT Cooper, DJ Kupper, TS Wang, LDC DeCaprio, JA AF Rodig, Scott J. Cheng, Jingwei Wardzala, Jacek DoRosario, Andrew Scanlon, Jessica J. Laga, Alvaro C. Martinez-Fernandez, Alejandro Barletta, Justine A. Bellizzi, Andrew M. Sadasivam, Subhashini Holloway, Dustin T. Cooper, Dylan J. Kupper, Thomas S. Wang, Linda C. DeCaprio, James A. TI Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LARGE T-ANTIGEN; NEUROENDOCRINE CARCINOMAS; RETINOBLASTOMA PROTEIN; C-KIT; EXPRESSION; P53; MUTATIONS; INFECTION; TUMORS; GENE AB A human polyomavirus was recently discovered in Merkel cell carcinoma (MCC) specimens. The Merkel cell polyomavirus (MCPyV) genome undergoes clonal integration into the host cell chromosomes of MCC tumors and expresses small T antigen and truncated large T antigen. Previous studies have consistently reported that MCPyV can be detected in approximately 80% of all MCC tumors. We sought to increase the sensitivity of detection of MCPyV in MCC by developing antibodies capable of detecting large T antigen by immunohistochemistry. In addition, we expanded the repertoire of quantitative PCR primers specific for MCPyV to improve the detection of viral DNA in MCC. Here we report that a novel monoclonal antibody detected MCPyV large T antigen expression in 56 of 58 (97%) unique MCC tumors. PCR analysis specifically detected viral DNA in all 60 unique MCC tumors tested. We also detected inactivating point substitution mutations of TP53 in the two MCC specimens that lacked large T antigen expression and in only 1 of 56 tumors positive for large T antigen. These results indicate that MCPyV is present in MCC tumors more frequently than previously reported and that mutations in TP53 tend to occur in MCC tumors that fail to express MCPyV large T antigen. C1 [Cheng, Jingwei; Wardzala, Jacek; Martinez-Fernandez, Alejandro; Sadasivam, Subhashini; Cooper, Dylan J.; DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Rodig, Scott J.; Laga, Alvaro C.; Barletta, Justine A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Rodig, Scott J.; Cheng, Jingwei; DoRosario, Andrew; Scanlon, Jessica J.; Laga, Alvaro C.; Barletta, Justine A.; Sadasivam, Subhashini; Kupper, Thomas S.; Wang, Linda C.; DeCaprio, James A.] Harvard Univ, Sch Med, Boston, MA USA. [Cheng, Jingwei; Sadasivam, Subhashini; DeCaprio, James A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [DoRosario, Andrew; Kupper, Thomas S.; Wang, Linda C.] Dana Farber Brigham & Womens Canc Ctr, Ctr Cutaneous Oncol, Boston, MA USA. [Scanlon, Jessica J.; Kupper, Thomas S.; Wang, Linda C.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Bellizzi, Andrew M.] Univ Iowa, Carver Coll Med, Dept Pathol, Iowa City, IA USA. [Holloway, Dustin T.] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02215 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM james_decaprio@dfci.harvard.edu FU Claudia Adams Barr Program in Innovative Basic Cancer Research at the Dana-Farber Cancer Institute; DF/HCC Development Award; Skin Cancer SPORE [P50 CA93683]; Fundacion Caja Madrid, Spain; Eilian Family Research Fund for Merkel Cell Carcinoma at the Dana-Farber Cancer Institute FX We appreciate the gift of the MCC cell lines MKL-1, MKL-2, and MS-1 from Masahiro Shuda, Yuan Chang, and Patrick Moore (University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA) and WaGa from Jurgen Becker (Medical University of Graz, Graz, Austria). OncoMap profiling was performed under the direction of Laura MacConaill and Emanuele Palescandolo at the Center for Cancer Genome Discovery, Dana-Farber Cancer Institute. Tumor specimens were processed by Helen Kuo, Translational Research Resource Core, Department of Dermatology, Brigham and Women's Hospital. DNA extraction from tumor specimens was performed by Guiducci and Shannon Powers, Biological Samples Platform, Broad Institute, Cambridge, Massachusetts, USA. We thank the Monoclonal Antibody, Specialized Histopathology, and Tissue Microarray and Imaging Core facilities of the Dana-Farber/Harvard Cancer Center. (DF/HCC). We acknowledge the support of the Claudia Adams Barr Program in Innovative Basic Cancer Research at the Dana-Farber Cancer Institute to J.A. DeCaprio, DF/HCC Development Award to T.S. Kupper, L.C. Wang, and J.A. DeCaprio, and support by the Skin Cancer SPORE (P50 CA93683) to T.S. Kupper. A. Martinez-Fernandez is supported by a fellowship from Fundacion Caja Madrid, Spain. We gratefully acknowledge the support of the Eilian Family Research Fund for Merkel Cell Carcinoma at the Dana-Farber Cancer Institute. NR 48 TC 85 Z9 85 U1 0 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2012 VL 122 IS 12 BP 4645 EP 4653 DI 10.1172/JCI64116 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 048PY UT WOS:000311926200036 PM 23114601 ER PT J AU Haas, JT Winter, HS Lim, E Kirby, A Blumenstiel, B DeFelice, M Gabriel, S Jalas, C Branski, D Grueter, CA Toporovski, MS Walther, TC Daly, MJ Farese, RV AF Haas, Joel T. Winter, Harland S. Lim, Elaine Kirby, Andrew Blumenstiel, Brendan DeFelice, Matthew Gabriel, Stacey Jalas, Chaim Branski, David Grueter, Carrie A. Toporovski, Mauro S. Walther, Tobias C. Daly, Mark J. Farese, Robert V., Jr. TI DGAT1 mutation is linked to a congenital diarrheal disorder SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DIACYLGLYCEROL ACYLTRANSFERASE; IDENTIFICATION; DYSLIPIDEMIA; DEFICIENCY; RESISTANCE; INHIBITORS; DISEASES; OBESITY; ENZYME; MICE AB Congenital diarrheal disorders (CDDs) are a collection of rare, heterogeneous enteropathies with early onset:. and often severe outcomes. Here, we report a family of Ashkenazi Jewish descent, with 2 one Of A children affected by CDD. Both affected children presented 3 days after birth With Severe, intractable diarrhea. One child died from complications at age 17 months. The second child showed Marked improvement, with resolution of most symptoms at 10 to 12 months of age. Using exome Sequencing, we identified a rare splice site Mutation in the DGAT1 gene and found that both affected children Were homozygous carriers. Molecular analysis of the mutant allele indicated a total loss of function, with no detectable DGAT1 protein or activity produced : The precise cause of diarrhea is unknown, but we speculate that it relates to abnormal fat absorption and buildup of DGAT substrates in the intestinal mucosa. Our results identify DGAT1 loss-of-function mutations as a rare cause of CDDs. These findings prompt concern for DGAT1 inhibition in humans, which is being assessed for treating metabolic and other diseases. C1 [Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Haas, Joel T.; Grueter, Carrie A.; Farese, Robert V., Jr.] Gladstone Inst Cardiovasc Dis, San Francisco, CA USA. [Haas, Joel T.; Farese, Robert V., Jr.] UCSF, Dept Biochem & Biophys, San Francisco, CA USA. [Winter, Harland S.] MassGen Hosp Children, Div Pediat Gastroenterol, Boston, MA USA. [Lim, Elaine; Kirby, Andrew; Blumenstiel, Brendan; DeFelice, Matthew; Gabriel, Stacey; Daly, Mark J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Jalas, Chaim] Ctr Rare Jewish Genet Disorders, New York, NY USA. [Branski, David] Hadassah Univ Hosp, Dept Pediat, IL-91120 Jerusalem, Israel. [Toporovski, Mauro S.] Sch Med, Dept Pediat, Santa Casa De Sao Paulo, Brazil. [Walther, Tobias C.] Yale Univ, Dept Cell Biol, New Haven, CT USA. [Farese, Robert V., Jr.] UCSF, Dept Med, San Francisco, CA USA. RP Daly, MJ (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Analyt & Translat Genet Unit, 185 Cambridge St, Boston, MA 02114 USA. EM mjdaly@atgu.mgh.harvard.edu; bfarese@gladstone.ucsf.edu OI Jalas, Chaim/0000-0002-3788-0924; Grueter, Carrie/0000-0002-1913-2527 FU NIH [2R56DK56084]; Gladstone Institutes; National Science Foundation; Pediatric IBD Foundation; Martin Schlaff; [NIH/NCRR CO6 RR018928] FX We thank Sekar Kathiresan for advice, Daryl Jones for manuscript preparation, Delphine Eberle for helpful comments, Gary Howard and Anna Lisa Lucido for editorial assistance, and Chaim Jalas (Center for Rare Jewish Genetic Disorders) for assistance in sample acquisition. This work was supported by NIH grant 2R56DK56084 (to R.V. Farese, Jr.), animal facilities grant NIH/NCRR CO6 RR018928, the Gladstone Institutes, the National Science Foundation (to J.T. Haas), the Pediatric IBD Foundation (to H.S. Winter), and funding from Martin Schlaff (to H.S. Winter). NR 26 TC 32 Z9 33 U1 0 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2012 VL 122 IS 12 BP 4680 EP 4684 DI 10.1172/JCI64873 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 048PY UT WOS:000311926200040 PM 23114594 ER PT J AU Liverant, GI Suvak, MK Pineles, SL Resick, PA AF Liverant, Gabrielle I. Suvak, Michael K. Pineles, Suzanne L. Resick, Patricia A. TI Changes in Posttraumatic Stress Disorder and Depressive Symptoms During Cognitive Processing Therapy: Evidence for Concurrent Change SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE PTSD; depression; treatment; psychotherapy; cognitive processing therapy ID PROLONGED EXPOSURE; BEHAVIORAL THERAPY; MULTILEVEL MODELS; MAJOR DEPRESSION; CLINICAL-TRIAL; SEXUAL-ABUSE; GULF-WAR; MEDIATION; TRAUMA; VICTIMS AB Objective: Trauma-focused psychotherapies reduce both posttraumatic stress disorder (PTSD) and co-occurring depression. However, little is known about the relationship between changes in PTSD and depression during treatment. This study examined the association between changes in PTSD and depression during the course of cognitive processing therapy (CPT) and its treatment components. Method: Data were drawn from a dismantling trial investigating the comparative efficacy of the components of CPT (Resick, Galovski, et al., 2008). One hundred twenty-six women (mean age = 36.14 years) from the original randomized intent-to-treat sample (N = 150) who attended at least 1 treatment session were included in this study. Participants diagnosed with PTSD were assigned to 1 of 3 treatment conditions: the full CPT protocol (n = 44), the cognitive therapy component of CPT (n = 39), and the written account component of CFT (n = 43). The majority of the sample self-identified as Caucasian (67%; 29% African American and 4% Other). Primary outcome measures included the Posttraumatic Diagnostic Scale and Beck Depression Inventory II, administered at 8 time points (baseline, weekly throughout 6 weeks of treatment, and posttreatment). Results: Multilevel regression analyses were conducted to examine relationships between PTSD and depression during treatment. Results indicated that changes in PTSD and depression were strongly related. Multilevel mediation analyses revealed that changes in PTSD and depression occurred concurrently, with lagged analyses providing no evidence that changes in symptoms of 1 disorder preceded changes in the other. Conclusions: Results suggest that changes in PTSD and depression occur contemporaneously during CPT. C1 [Liverant, Gabrielle I.] VA Boston Healthcare Syst, Psychol Serv, Brockton, MA 02301 USA. [Liverant, Gabrielle I.; Pineles, Suzanne L.; Resick, Patricia A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Suvak, Michael K.; Pineles, Suzanne L.; Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Brockton, MA 02301 USA. [Resick, Patricia A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Liverant, GI (reprint author), VA Boston Healthcare Syst, Psychol Serv, Brockton Campus 116A,940 Belmont St, Brockton, MA 02301 USA. EM gabrielle.liverant@va.gov FU NIMH NIH HHS [2-R01-MH51509] NR 58 TC 9 Z9 9 U1 9 U2 33 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2012 VL 80 IS 6 BP 957 EP 967 DI 10.1037/a0030485 PG 11 WC Psychology, Clinical SC Psychology GA 047DI UT WOS:000311817500001 PM 23067427 ER PT J AU Sullivan, AF Bachireddy, C Steptoe, AP Oldfield, J Wilson, T Camargo, CA AF Sullivan, Ashley F. Bachireddy, Chethan Steptoe, Anne P. Oldfield, Justin Wilson, Taneisha Camargo, Carlos A., Jr. TI A PROFILE OF FREESTANDING EMERGENCY DEPARTMENTS IN THE UNITED STATES, 2007 SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE emergency care; urgent care AB Background: Freestanding Emergency Departments (FSEDs) have emerged as an alternative to traditional hospital-based emergency care. Study Objective: We sought to determine the number, basic types, distribution, and characteristics of United States (US) FSEDs in 2007. Methods: Combining data from the 2007 National Emergency Department Inventory-USA database, the 2007 American Hospital Association Annual Survey of Hospitals, Internet searches, and telephone calls, we established an inventory of FSEDs. We define FSEDs as emergency care facilities physically distinct from a hospital. FSEDs include "satellite'' Emergency Departments (EDs), which are owned by a parent hospital, and "autonomous'' EDs, which lack such an affiliation. Results: We identified 80 FSEDs operating in 2007, representing 1.6% of all US EDs; 73 (91%) in 20 states were satellite EDs, and seven (9%) in three states were autonomous EDs. Most FSEDs (92%; 95% confidence interval 83-97%) were located in urban areas, which is considerably higher than the proportion for hospital-based EDs (58%). The median distance from a satellite ED to a parent hospital ED was 10.6 miles. In 2007, FSED annual visit volumes ranged from 700 to 56,545 visits. The 2007 median visit volume was 18,769 (interquartile range 11,106-23,504; n = 52). This value did not vary by geographic region and is almost identical to the 2007 median visit volume for hospital-based EDs (18,776 visits). Conclusions: FSEDs represent <2% of US EDs, with satellite EDs comprising a majority of all FSEDs. Most (92%) FSEDs are located in urban areas. (C) 2012 Elsevier Inc. C1 [Sullivan, Ashley F.; Bachireddy, Chethan; Steptoe, Anne P.; Oldfield, Justin; Wilson, Taneisha; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. NR 12 TC 4 Z9 4 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD DEC PY 2012 VL 43 IS 6 BP 1175 EP 1180 DI 10.1016/j.jemermed.2012.02.078 PG 6 WC Emergency Medicine SC Emergency Medicine GA 046ZT UT WOS:000311805600081 PM 23047195 ER PT J AU Martindale, JL Hayden, EM AF Martindale, Jennifer L. Hayden, Emily M. TI NEUROLOGIC COMPLAINTS IN A PATIENT WITH INFECTIVE ENDOCARDITIS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE mycotic aneurysm; intracranial hemorrhage; endocarditis ID CEREBRAL MYCOTIC-ANEURYSMS; ENDOVASCULAR TREATMENT; MANAGEMENT AB Background: Infectious intracranial aneurysms constitute a small subgroup of all intracranial aneurysms, but are an important cause of neurologic complaints in patients with infective endocarditis. Objective: To describe a potentially fatal cause of neurologic complaints in patients with endocarditis. Case Report: We report a case of a 33-year-old woman with Streptococcus sanguinis endocarditis and several neurologic complaints including right arm numbness, confusion, and occasional word-finding difficulty that were found to be secondary to infectious intracranial aneurysm. Conclusion: Early consideration of intracranial infectious aneurysm in patients with infective endocarditis and neurologic symptoms is critical. Therapeutic intervention is often effective, and risk of aneurysm rupture is high. (C) 2012 Elsevier Inc. C1 [Martindale, Jennifer L.; Hayden, Emily M.] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Div Emergency Med,Med Sch, Boston, MA 02114 USA. RP Martindale, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Div Emergency Med,Med Sch, 5 Emerson Pl, Boston, MA 02114 USA. NR 14 TC 1 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD DEC PY 2012 VL 43 IS 6 BP E429 EP E433 DI 10.1016/j.jemermed.2011.05.026 PG 5 WC Emergency Medicine SC Emergency Medicine GA 046ZT UT WOS:000311805600011 PM 21763096 ER PT J AU Martindale, JL Konstantopoulos, WLM AF Martindale, Jennifer L. Konstantopoulos, Wendy L. Macias TI LOCALLY ACQUIRED WEST NILE ENCEPHALITIS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE arbovirus; encephalitis; West Nile Virus ID VIRUS-INFECTION; UNITED-STATES; NEW-YORK; TRANSMISSION; DISEASE AB Background: West Nile virus (WNV) has spread rapidly across the United States since 1999, causing epidemics of neurologic illnesses including meningitis, encephalitis, and acute flaccid paralysis. West Nile encephalitis can be fatal; recovery can be incomplete; and constitutional and neurological symptoms can persist for months to years. Objectives: To raise awareness of an important epidemiologic cause of febrile illness with neurologic involvement in the United States. Case Report: We report the case of a 46-year-old woman who presented with fever, altered mental status, and maculopapular rash, who was diagnosed with locally acquired WNV encephalitis. Conclusion: Infection with WNV should be considered in patients presenting to emergency departments with fever and neurologic symptoms. Recommended evaluation includes serologic testing of cerebrospinal fluid and serum. (C) 2012 Elsevier Inc. C1 [Martindale, Jennifer L.] Harvard Affiliated Emergency Med Residency, Boston, MA 02115 USA. [Konstantopoulos, Wendy L. Macias] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Konstantopoulos, Wendy L. Macias] Harvard Univ, Sch Med, Boston, MA USA. RP Martindale, JL (reprint author), Harvard Affiliated Emergency Med Residency, Neville House,75 Francis St, Boston, MA 02115 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD DEC PY 2012 VL 43 IS 6 BP E435 EP E438 DI 10.1016/j.jemermed.2011.05.054 PG 4 WC Emergency Medicine SC Emergency Medicine GA 046ZT UT WOS:000311805600012 PM 21865003 ER PT J AU Smith, JG Almgren, P Engstrom, G Hedblad, B Platonov, PG Newton-Cheh, C Melander, O AF Smith, J. G. Almgren, P. Engstrom, G. Hedblad, B. Platonov, P. G. Newton-Cheh, C. Melander, O. TI Genetic polymorphisms for estimating risk of atrial fibrillation: a literature-based meta-analysis SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE atrial fibrillation; genetics; genome-wide association studies; meta-analysis; prediction; single-nucleotide polymorphisms ID CHROMOSOME 4Q25; FAMILIAL AGGREGATION; HEART-DISEASE; ASSOCIATION; VARIANTS; POPULATION; MODEL; REPLICATION; RS2200733; MARKERS AB Smith JG, Almgren P, Engstrom G, Hedblad B, Platonov PG, Newton-Cheh C, Melander O (Department of Cardiology, Lund University, Lund, Sweden; Department of Clinical Sciences, Lund University, Malmo, Sweden; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA; and Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA). Genetic polymorphisms for estimating risk of atrial fibrillation: a literature-based meta-analysis. J Intern Med 2012; doi: 10.1111/j.1365-2796.2012.02563.x Background. Genetic polymorphisms associated with common aetiologically complex diseases have recently been identified through genome-wide association studies. Direct-to-consumer genetic testing for such polymorphisms, with provision of absolute genetic risk estimates, is marketed by several commercial companies. Polymorphisms associated with atrial fibrillation (AF) have shown relatively large risk estimates, but the robustness of such estimates across populations and study designs has not been investigated. Design. A systematic literature review with meta-analysis and assessment of between-study heterogeneity was carried out for single-nucleotide polymorphisms (SNPs) in the six genetic regions associated with AF in genome-wide or candidate gene studies. Results. Data were identified from 18 samples of European ancestry (n = 12 100 cases, 115,702 controls) for the single-nucleotide polymorphisms (SNP) on chromosome 4q25 (rs220733), from 16 samples (n = 12 694 cases, 132 602 controls) for the SNP on 16q22 (rs2106261) and from four samples (n = 5272 cases, 59 725 controls) for the SNP in KCNH2 (rs1805123). Only the publications in which the associations were initially reported were identified for SNPs on 1q21 and in GJA5 and IL6R, why meta-analyses were not performed for those SNPs. In overall random-effects meta-analyses, association with AF was observed for both SNPs on chromosomes 4q25 [odds ratio (OR), 1.67; 95% CI, 1.50-1.86, P = 2 x 10-21] and 16q22 (OR, 1.21; 95% CI, 1.13-1.29, P = 1 x 10-8) from genome-wide studies, but not the SNP in KCNH2 from candidate gene studies (P = 0.15). There was substantial effect heterogeneity across casecontrol and cross-sectional studies for both polymorphisms (I2 = 0.500.78, P < 0.05), but not across prospective cohort studies (I2 = 0.39, P = 0.15). Both polymorphisms were robustly associated with AF for each study design individually (P < 0.05). Conclusions. In meta-analyses including up to 150 000 individuals, polymorphisms in two genetic regions were robustly associated with AF across all study designs but with substantial context-dependency of risk estimates. C1 [Smith, J. G.; Platonov, P. G.] Lund Univ, Dept Cardiol, SE-22185 Lund, Sweden. [Smith, J. G.; Almgren, P.; Engstrom, G.; Hedblad, B.; Melander, O.] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Smith, J. G.; Newton-Cheh, C.] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA USA. [Newton-Cheh, C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, C.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, C.] Harvard Univ, Sch Med, Boston, MA USA. RP Smith, JG (reprint author), Lund Univ, Skane Univ Hosp, Fac Med, Dept Cardiol, SE-22185 Lund, Sweden. EM gustav.smith@med.lu.se OI Engstrom, Gunnar/0000-0002-8618-9152 FU Swedish Heart-Lung Foundation; Skane University Hospital; Medical Faculty of Lund University; Thorsten Westerstrom Foundation; NIH [K23-HL-080025]; Doris Duke Charitable Foundation Clinical Scientist Development Award; Burroughs Wellcome Fund Career Award for Medical Scientists; Swedish Medical Research Council; European Research Council [StG-282255]; Medical Faculty of Lund University, Skane University Hospital in Malmo; Albert Pahlsson Research Foundation; Crafoord Foundation; Swedish National Health Service; Hulda and Conrad Mossfelt Foundation; Ernhold Lundstroms Research Foundation; King Gustaf V and Queen Victoria Fund; Lennart Hanssons Memorial Fund; Marianne and Marcus Wallenberg Foundation; Knut and Alice Wallenberg Foundation; Craaford Foundation FX Drs Smith, Hedblad, Engstrom, Melander and Platonov gratefully acknowledge financial support from the Swedish Heart-Lung Foundation. Dr Smith was also supported by Skane University Hospital, the Medical Faculty of Lund University and the Thorsten Westerstrom Foundation. Dr Newton-Cheh was supported by NIH grant K23-HL-080025, a Doris Duke Charitable Foundation Clinical Scientist Development Award, and a Burroughs Wellcome Fund Career Award for Medical Scientists. Drs Hedblad and Melander were supported by the Swedish Medical Research Council. Dr Melander was supported by grants from the European Research Council (StG-282255), the Medical Faculty of Lund University, Skane University Hospital in Malmo, the Albert Pahlsson Research Foundation, the Crafoord Foundation, the Swedish National Health Service, the Hulda and Conrad Mossfelt Foundation, the Ernhold Lundstroms Research Foundation, the King Gustaf V and Queen Victoria Fund, the Lennart Hanssons Memorial Fund, the Marianne and Marcus Wallenberg Foundation and the Knut and Alice Wallenberg Foundation. Dr Platonov was supported by the Swedish National Health Service, Skane University Hospital and the Craaford Foundation. NR 35 TC 8 Z9 8 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD DEC PY 2012 VL 272 IS 6 BP 573 EP 582 DI 10.1111/j.1365-2796.2012.02563.x PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 041HH UT WOS:000311390400005 PM 22690879 ER PT J AU Nwaneshiudu, A Kuschal, C Sakamoto, FH Anderson, RR Schwarzenberger, K Young, RC AF Nwaneshiudu, Adaobi Kuschal, Christiane Sakamoto, Fernanda H. Anderson, R. Rox Schwarzenberger, Kathryn Young, Roger C. TI Introduction to Confocal Microscopy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Review C1 [Nwaneshiudu, Adaobi] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA. [Kuschal, Christiane] NIH, Bethesda, MD 20892 USA. [Sakamoto, Fernanda H.; Anderson, R. Rox] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Schwarzenberger, Kathryn] Univ Vermont, Coll Med, Dept Med, Div Dermatol, Burlington, VT 05405 USA. [Young, Roger C.] Univ Vermont, Coll Med, Dept Obstet & Gynecol, Burlington, VT 05405 USA. RP Nwaneshiudu, A (reprint author), Univ Chicago, Dept Med, Dermatol Sect, 5841 S Maryland Ave,MC 5067, Chicago, IL 60637 USA. EM adaobi.nwaneshiudu@uchospitals.edu OI Kuschal, Christiane/0000-0001-6113-3585 NR 6 TC 19 Z9 20 U1 6 U2 57 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2012 VL 132 IS 12 BP 1 EP 5 DI 10.1038/jid.2012.429 PG 5 WC Dermatology SC Dermatology GA 046PY UT WOS:000311778100001 PM 23187113 ER PT J AU Walsh, CJ Meskers, AJH Slocum, AH Gupta, R AF Walsh, Conor J. Meskers, Arjan J. H. Slocum, Alexander H. Gupta, Rajiv TI CT-Compatible Medical Drilling Stylet SO JOURNAL OF MEDICAL DEVICES-TRANSACTIONS OF THE ASME LA English DT Article DE medical robotics; computed tomography; X-ray; drill; interventional radiology; bone ID GUIDED BONE-BIOPSY; OSTEOID OSTEOMA; IN-VITRO; SYSTEM; ROBOT AB This paper describes the design of a compact, lightweight CT-compatible, drill-press that is designed to be used in either a hand-held or stand-alone mode to assist with percutaneous bone based interventions. Previous medical drilling tools that have been developed have a metal structure and typically have one actuator for advancing the drill (feed) and another for rotating it (speed). After defining the device functional requirements and specifications, a deterministic design process was followed to generate several design concepts that were then evaluated based on their ability to satisfy the functional requirements. A final concept that uses a custom screw-spline to achieve helical motion of a shaft that is attached to a standard orthopedic drill was selected for prototyping. The design uses a single actuator to drive both the screw and spline nuts through two different gear ratios, resulting in a fixed ratio between the feed and speed. Apart from the motor which is placed away from the central drill axis, the device is largely made from plastic materials. A custom experimental setup was developed that enabled drilling into bone inside a CT scanner to be examined. Results showed that the device was successfully able to penetrate thick cortical bone and that its structure did not appreciably distort the medical images. [DOI: 10.1115/1.4007280] C1 [Walsh, Conor J.; Slocum, Alexander H.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Walsh, Conor J.; Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Meskers, Arjan J. H.] Delft Univ Technol, Dept Biomed Engn, NL-2600 AA Delft, Netherlands. RP Walsh, CJ (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. NR 22 TC 0 Z9 0 U1 0 U2 5 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 1932-6181 J9 J MED DEVICES JI J. Med. Devices PD DEC PY 2012 VL 6 IS 4 AR 041001 DI 10.1115/1.4007280 PG 8 WC Engineering, Biomedical SC Engineering GA 049EI UT WOS:000311964600001 ER PT J AU Matyal, R Chu, L Mahmood, F Robich, MP Wang, A Hess, PE Shahul, S Pinto, DS Khabbaz, K Sellke, FW AF Matyal, Robina Chu, Louis Mahmood, Feroze Robich, Michael P. Wang, Angela Hess, Philip E. Shahul, Sajid Pinto, Duane S. Khabbaz, Kamal Sellke, Frank W. TI Neuropeptide Y improves myocardial perfusion and function in a swine model of hypercholesterolemia and chronic myocardial ischemia SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Angiogenesis; Metabolic syndrome; Chronic ischemia; Neuropeptide Y ID FIBROBLAST GROWTH FACTOR-2; CORONARY-ARTERY-DISEASE; COLLATERAL DEVELOPMENT; METABOLIC SYNDROME; VESSEL MATURATION; DIABETES-MELLITUS; ANGIOGENESIS; EXPRESSION; NEOVASCULARIZATION; ANGIOSTATIN AB Pharmacologically induced angiogenesis could be a promising option in clinical situations with diffuse inoperable coronary artery disease e.g. metabolic syndrome and diabetes mellitus. The failure of focused cytokine, stem cell and gene therapies to achieve both perfusion and functional improvement in clinical trials suggests a more centralized control mechanism. Neuropeptide-Y (NPY) is one such natural neurotransmitter that is known to exert a multifaceted role during neo-angiogenesis and can possibly act as the central control. To date, the ability to harness the 'master switch' nature of NPY in a specific experimental model of metabolic syndrome and chronic myocardial ischemia has not been conclusively demonstrated. We hypothesized that infiltration of NPY into an area of chronic ischemia in a metabolic syndrome swine model would induce angiogenesis and improve myocardial perfusion and function. An osmotic pump was inserted three weeks after surgical induction of focal myocardial ischemia. We delivered either NPY or placebo for five weeks, after which the myocardial tissue was harvested for analysis. Assessments of myocardial perfusion and function were performed at each stage of the experiment. Local infiltration of NPY significantly improved collateral vessel formation, blood flow and myocardial function. We believe activation of NPY receptors may be a potential target therapy for patients with diffuse coronary artery disease. (C) 2012 Published by Elsevier Ltd. C1 [Matyal, Robina; Chu, Louis; Mahmood, Feroze; Robich, Michael P.; Hess, Philip E.; Shahul, Sajid; Pinto, Duane S.; Khabbaz, Kamal; Sellke, Frank W.] Harvard Univ, Sch Med, Boston, MA USA. [Sellke, Frank W.] Rhode Isl Hosp, Cardiovasc Res Ctr, Dept Surg, Providence, RI 02903 USA. [Sellke, Frank W.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. RP Wang, A (reprint author), Beth Israel Deaconess Med Ctr CC 454, 1 Deaconess Rd, Boston, MA 02215 USA. EM awang3@bidmc.harvard.edu RI Hess, Philip/A-8577-2013; Mahmood, Feroze/B-1383-2008 OI Hess, Philip/0000-0002-1206-0102; Mahmood, Feroze/0000-0002-7071-0476 FU Department of Anesthesia and Critical Care at the Beth Israel Deaconess Medical Center; National Institute of Health [5T32-HL094300, T-32 HL007734] FX Research was funded by the Department of Anesthesia and Critical Care at the Beth Israel Deaconess Medical Center and the National Institute of Health Training Grants 5T32-HL094300 (LMC) and T-32 HL007734 (MPR). NR 40 TC 7 Z9 8 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD DEC PY 2012 VL 53 IS 6 BP 891 EP 898 DI 10.1016/j.yjmcc.2012.08.027 PG 8 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 044XJ UT WOS:000311658200017 PM 22982235 ER PT J AU Holt, CL Schulz, E Williams, B Clark, EM Wang, MQ Southward, PL AF Holt, Cheryl L. Schulz, Emily Williams, Beverly Clark, Eddie M. Wang, Min Qi Southward, Penny L. TI Assessment of Religious and Spiritual Capital in African American Communities SO JOURNAL OF RELIGION & HEALTH LA English DT Article DE Social capital; Religious capital; Spiritual capital; Reliability; Validity ID SELF-RATED HEALTH; WOMEN; MODEL AB African American faith communities are an important source of social capital. The present study adapted a theory-based social capital instrument to result in religious (e.g., from organized worship) and spiritual (e.g., from relationship with higher power) capital measures. Data from a national sample of 803 African Americans suggest the instruments have high internal reliability and are distinct from general religiosity. Measurement models confirmed factor structures. Religious capital was positively associated with self-rated health status. Religious and spiritual capital were negatively associated with depressive symptoms, but these associations largely became nonsignificant in multivariate models that controlled for demographic characteristics. An exception is for spiritual capital in the form of community participation, which retained a negative association with depressive symptoms. These instruments may have applied value for health promotion research and practice in African American communities. C1 [Holt, Cheryl L.; Wang, Min Qi] Univ Maryland, Sch Publ Hlth, Dept Behav & Community Hlth, College Pk, MD 20742 USA. [Schulz, Emily] Arizona Sch Hlth Sci, Dept Occupat Therapy, Mesa, AZ USA. [Williams, Beverly] Univ Alabama Birmingham, Dept Med, Birmingham VA Med Ctr, Div Gerontol Geriatr Palliat Care, Birmingham, AL 35294 USA. [Clark, Eddie M.] St Louis Univ, Dept Psychol, St Louis, MO 63103 USA. [Southward, Penny L.] Univ Alabama Birmingham, Sch Med, Div Prevent Med, Birmingham, AL USA. RP Holt, CL (reprint author), Univ Maryland, Sch Publ Hlth, Dept Behav & Community Hlth, 2369 Sch Publ Hlth,Bldg 255, College Pk, MD 20742 USA. EM cholt14@umd.edu NR 39 TC 5 Z9 5 U1 1 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-4197 J9 J RELIG HEALTH JI J. Relig. Health PD DEC PY 2012 VL 51 IS 4 BP 1061 EP 1074 DI 10.1007/s10943-012-9635-4 PG 14 WC Public, Environmental & Occupational Health; Religion SC Public, Environmental & Occupational Health; Religion GA 040HO UT WOS:000311313500005 PM 22810197 ER PT J AU Lyamin, OI Pavlova, IF Kosenko, PO Mukhametov, LM Siegel, JM AF Lyamin, Oleg I. Pavlova, Ivetta F. Kosenko, Peter O. Mukhametov, Lev M. Siegel, Jerome M. TI Regional differences in cortical electroencephalogram (EEG) slow wave activity and interhemispheric EEG asymmetry in the fur seal SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE interhemispheric EEG asymmetry; local sleep; slow wave activity; unihemispheric sleep; northern fur seal ID SLEEP-DEPRIVATION; RAT; STIMULATION; DYNAMICS; POWER AB Slow wave sleep (SWS) in the northern fur seal (Callorhinus ursinus) is characterized by a highly expressed interhemispheric electroencephalogram (EEG) asymmetry, called unihemispheric or asymmetrical SWS. The aim of this study was to examine the regional differences in slow wave activity (SWA; power in the range of 1.24.0 Hz) within one hemisphere and differences in the degree of interhemispheric EEG asymmetry within this species. Three seals were implanted with 10 EEG electrodes, positioned bilaterally (five in each hemisphere) over the frontal, occipital and parietal cortex. The expression of interhemispheric SWA asymmetry between symmetrical monopolar recordings was estimated based on the asymmetry index [AI = (L-R)/(L+R), where L and R are the power in the left and right hemispheres, respectively]. Our findings indicate an anteriorposterior gradient in SWA during asymmetrical SWS in fur seals, which is opposite to that described for other mammals, including humans, with a larger SWA recorded in the parietal and occipital cortex. Interhemispheric EEG asymmetry in fur seals was recorded across the entire dorsal cerebral cortex, including sensory (visual and somatosensory), motor and associative (parietal or suprasylvian) cortical areas. The expression of asymmetry was greatest in occipitallateral and parietal derivations and smallest in frontalmedial derivations. Regardless of regional differences in SWA, the majority (90%) of SWS episodes with interhemispheric EEG asymmetry meet the criteria for unihemispheric SWS (one hemisphere is asleep while the other is awake). The remaining episodes can be described as episodes of bilateral SWS with a local activation in one cerebral hemisphere. C1 [Lyamin, Oleg I.] VA GLAHS Sepulveda, Ctr Sleep Res, North Hills, CA 91343 USA. [Lyamin, Oleg I.; Siegel, Jerome M.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Lyamin, Oleg I.; Pavlova, Ivetta F.; Kosenko, Peter O.; Mukhametov, Lev M.] Utrish Dolphinarium Ltd, Moscow, Russia. [Lyamin, Oleg I.; Mukhametov, Lev M.] Severtsov Inst Ecol & Evolut, Moscow, Russia. [Kosenko, Peter O.] S Fed Univ, Rostov Na Donu, Russia. RP Lyamin, OI (reprint author), VA GLAHS Sepulveda, Ctr Sleep Res, Plummer St 16111, North Hills, CA 91343 USA. EM olyamin@ucla.edu FU NSF [0919929]; NIH [069640]; Utrish Dolphinarium Ltd. FX This study was supported by NSF (0919929), NIH (069640) and Utrish Dolphinarium Ltd. The authors are thankful to J. Lapierre for comments on this manuscript. NR 30 TC 3 Z9 3 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD DEC PY 2012 VL 21 IS 6 BP 603 EP 611 DI 10.1111/j.1365-2869.2012.01023.x PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 045HS UT WOS:000311686700002 PM 22676149 ER PT J AU Cambria, RP AF Cambria, Richard P. TI The endovascular revolution stopped at the carotid bifurcation ... or did it? SO JOURNAL OF VASCULAR SURGERY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; VASCULAR-SURGERY; ARTERY STENOSIS; STROKE PREVENTION; MEDICARE BENEFICIARIES; CEREBRAL-ISCHEMIA; AMERICAN-COLLEGE; RISK PATIENTS; ENDARTERECTOMY; OUTCOMES C1 [Cambria, Richard P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Cambria, Richard P.] Harvard Univ, Sch Med, Boston, MA USA. RP Cambria, RP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, 15 Parkman St,WACC 410, Boston, MA 02114 USA. EM rcambria@partners.org NR 79 TC 4 Z9 4 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 2012 VL 56 IS 6 BP 1748 EP 1760 DI 10.1016/j.jvs.2012.10.010 PG 13 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 042RX UT WOS:000311489800044 PM 23182486 ER PT J AU Reiman, EM Quiroz, YT Fleisher, AS Chen, KW Velez-Pardo, C Jimenez-Del-Rio, M Fagan, AM Shah, AR Alvarez, S Arbelaez, A Giraldo, M Acosta-Baena, N Sperling, RA Dickerson, B Stern, CE Tirado, V Munoz, C Reiman, RA Huentelman, MJ Alexander, GE Langbaum, JBS Kosik, KS Tariot, PN Lopera, F AF Reiman, Eric M. Quiroz, Yakeel T. Fleisher, Adam S. Chen, Kewei Velez-Pardo, Carlos Jimenez-Del-Rio, Marlene Fagan, Anne M. Shah, Aarti R. Alvarez, Sergio Arbelaez, Andres Giraldo, Margarita Acosta-Baena, Natalia Sperling, Reisa A. Dickerson, Brad Stern, Chantal E. Tirado, Victoria Munoz, Claudia Reiman, Rebecca A. Huentelman, Matthew J. Alexander, Gene E. Langbaum, Jessica B. S. Kosik, Kenneth S. Tariot, Pierre N. Lopera, Francisco TI Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the presenilin 1 E280A kindred: a case-control study SO LANCET NEUROLOGY LA English DT Article ID AMYLOID-BETA; IN-VIVO; EPSILON-4 ALLELE; APOLIPOPROTEIN-E; GAMMA-SECRETASE; MILD; DEPOSITION; DEMENTIA; CARRIERS; MEMORY AB Background We have previously characterised functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's disease. To gain further knowledge on the preclinical phase of Alzheimer's disease, we sought to characterise structural and functional MRI, CSF, and plasma biomarkers in a cohort of young adults carrying a high-penetrance autosomal dominant mutation that causes early-onset Alzheimer's disease. Methods Between January and August, 2010, 18-26-year-old presenilin 1 (PSEN1) E280A mutation carriers and non-carriers from the Colombian Alzheimer's Prevention Initiative Registry in Medellin Antioquia, Colombia, had structural MRI, functional MRI during associative memory encoding and novel viewing and control tasks, and cognitive assessments. Consenting participants also had lumbar punctures and venepunctures. Outcome measures were task-dependent hippocampal or parahippocampal activations and precuneus or posterior cingulate deactivations, regional grey matter reductions, CSF A beta(1-42), total tau and phospho-tau, concentrations, and plasma A beta(1-42) concentrations and A beta(1-42):A beta(1-40) ratios. Structural and functional Mill data were compared using automated brain mapping algorithms and search regions related to Alzheimer's disease. Cognitive and fluid biomarkers were compared using Mann-Whitney tests. Findings 44 participants were included: 20 P SEN1 E280A mutation carriers and 24 non-carriers. The carrier and non-carrier groups did not differ significantly in their dementia ratings, neuropsychological test scores, or proportion of apolipoprotein E (APOE) epsilon 4 carriers. Compared with non-carriers, carriers had greater right hippocampal and parahippocampal activation (p=0.001 and p<0.014, respectively, after correction for multiple comparisons), less precuneus and posterior cingulate deactivation (all p<0.010 after correction), and less grey matter in several parietal regions (all p<0.002 uncorrected and corrected p=0.009 in the right parietal search region). In the 20 participants (ten P SEN1 E280A mutation carriers and ten non-carriers) who had lumbar punctures and venepunctures, mutation carriers had higher CSF A beta(1-42) concentrations (p=0.008) and plasma A beta(1-42) concentrations (p=0.01) than non-carriers. Interpretation Young adults at genetic risk for autosomal dominant Alzheimer's disease have functional and structural MRI findings and CSF and plasma biomarker findings consistent with A beta(1-42) overproduction. Although the extent to which the underlying brain changes are either neurodegenerative or developmental remain to be determined, this study shows the earliest known biomarker changes in cognitively normal people at genetic risk for autosomal dominant Alzheimer's disease. C1 [Reiman, Eric M.; Fleisher, Adam S.; Langbaum, Jessica B. S.; Tariot, Pierre N.] Banner Alzheimers Inst, Phoenix, AZ 85006 USA. [Reiman, Eric M.; Tariot, Pierre N.] Univ Arizona, Dept Psychiat, Phoenix, AZ USA. [Chen, Kewei] Univ Arizona, Dept Radiol, Phoenix, AZ USA. [Alexander, Gene E.] Univ Arizona, Dept Psychol, Phoenix, AZ USA. [Alexander, Gene E.] Univ Arizona, McKnight Brain Inst, Phoenix, AZ USA. [Reiman, Eric M.; Tariot, Pierre N.] Univ Arizona, Dept Psychiat, Tucson, AZ USA. [Alexander, Gene E.] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. [Chen, Kewei] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. [Alexander, Gene E.] Univ Arizona, McKnight Brain Inst, Tucson, AZ USA. [Reiman, Eric M.; Reiman, Rebecca A.; Huentelman, Matthew J.] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA. [Reiman, Eric M.; Fleisher, Adam S.; Chen, Kewei; Reiman, Rebecca A.; Huentelman, Matthew J.; Alexander, Gene E.; Langbaum, Jessica B. S.; Tariot, Pierre N.] Arizona Alzheimers Consortium, Phoenix, AZ USA. [Quiroz, Yakeel T.; Stern, Chantal E.] Boston Univ, Dept Psychol, Ctr Memory & Brain, Boston, MA 02215 USA. [Chen, Kewei] Arizona State Univ, Dept Math, Tempe, AZ 85287 USA. [Quiroz, Yakeel T.; Velez-Pardo, Carlos; Jimenez-Del-Rio, Marlene; Giraldo, Margarita; Acosta-Baena, Natalia; Tirado, Victoria; Munoz, Claudia; Lopera, Francisco] Univ Antioquia, Medellin, Colombia. [Fagan, Anne M.; Shah, Aarti R.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Fleisher, Adam S.] Univ Calif San Diego, Dept Neurol, San Diego, CA 92103 USA. [Alvarez, Sergio; Arbelaez, Andres] Hosp Pablo Tobon Uribe, Medellin, Colombia. [Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol,Med Sch, Boston, MA 02115 USA. [Sperling, Reisa A.; Dickerson, Brad] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Stern, Chantal E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sperling, Reisa A.; Dickerson, Brad; Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Kosik, Kenneth S.] Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA. RP Reiman, EM (reprint author), Banner Alzheimers Inst, 901 E Willetta St, Phoenix, AZ 85006 USA. EM eric.reiman@bannerhealth.com RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 FU Banner Alzheimer's Foundation; Nomis Foundation; Anonymous Foundation; Forget Me Not Initiative; Boston University Department of Psychology; Colciencias [1115-408-20512, 1115-545-31651]; National Institute on Aging [R01 AG031581, P30 AG19610, U01 AG024904, RO1 AG025526, RF1AG041705]; National Institute of Neurological Disorders and Stroke [F31-NS078786]; State of Arizona FX This study was supported by a grant from an Anonymous Foundation (EMR, FL) and by the Banner Alzheimer's Foundation, the Nomis Foundation, and the Boston University Department of Psychology (CES, YTQ). Additional support for structural MRI analyses was provided by the National Institute on Aging (R01 AG031581 [EMR], P30 AG19610 [EMR], U01 AG024904 [Michael Weiner, ADNI primary investigator], RO1 AG025526 [GEA], and RF1AG041705 [EMR, PNT, FL]), the National Institute of Neurological Disorders and Stroke (F31-NS078786 [YTQ]), Colciencias (1115-408-20512 [FL], 1115-545-31651 [FL]), and the state of Arizona. We thank Natalia Montes, Feliza Restrepo, Sandra Lainez, Erika Munoz, and their colleagues from the Hospital Pablo Tobon Uribe; our colleagues at the University of Antioquia; and Xiaofen Liu, Pradeep Thiyyagura, Hua Mo, Hillary Protas, Napatkamon Ayutyanont, Wendy Lee, Auttawut Roontiva, Stephanie Parks, Mark Nishimura, and Weihua Chen from the Banner Alzheimer's Institute for their technical assistance. We thank Paul Thompson and his colleagues for the software used to help generate the cortical surface maps in figures 2 and 3. We thank our research participants and other members of the PSEN1 E280A mutation kindred for their invaluable dedication and inspiration. NR 35 TC 134 Z9 138 U1 5 U2 37 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD DEC PY 2012 VL 11 IS 12 BP 1048 EP 1056 DI 10.1016/S1474-4422(12)70228-4 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 044CX UT WOS:000311598100013 PM 23137948 ER PT J AU LaCroix, AZ Freeman, EW Larson, J Carpenter, JS Joffe, H Reed, SD Newton, KM Seguin, RA Sternfeld, B Cohen, L Ensrud, KE AF LaCroix, Andrea Z. Freeman, Ellen W. Larson, Joseph Carpenter, Janet S. Joffe, Hadine Reed, Susan D. Newton, Katherine M. Seguin, Rebecca A. Sternfeld, Barbara Cohen, Lee Ensrud, Kristine E. TI Effects of escitalopram on menopause-specific quality of life and pain in healthy menopausal women with hot flashes: A randomized controlled trial SO MATURITAS LA English DT Article DE Antidepressants; Escitalopram; Menopausal quality of life; Randomized controlled trial; Vasomotor symptoms ID VASOMOTOR SYMPTOMS; POSTMENOPAUSAL WOMEN; SEXUAL FUNCTION; UNITED-STATES; QUESTIONNAIRE; INDEX; TRANSITION; SEVERITY; IMPACT; SLEEP AB Objective: To evaluate the effects of escitalopram 10-20 mg/day on menopause-related quality of life and pain in healthy menopausal women with hot flashes. Study design: A double-blind, placebo-controlled randomized trial of escitalopram 10-20 mg/day vs. identical placebo was conducted among 205 women ages 40-62 years with an average of >= 4 daily hot flashes recruited at 4 clinical sites from July 2009 to June 2010. Main outcome measures: The primary trial outcomes, reported previously, were the frequency and severity of vasomotor symptoms at 8 weeks. Here, we report on the pre-specified secondary endpoints of total and domain scores from the Menopause-Specific Quality of Life Questionnaire (MENQOL) and the pain intensity and interference scale (PEG). Results: Outcome data were collected on 97% of randomized women and 87% of women took at least 70% of their study medication. Treatment with escitalopram resulted in significantly greater improvement in total MENQOL scores (mean difference at 8 weeks of -0.41; 95% confidence interval (CI) -0.71 to -0.11; p < 0.001). as well as Vasomotor. Psychosocial, and Physical domain scores with the largest difference seen in the Vasomotor domain (mean difference -0.75; 95% CI -1.28 to -0.22; p = 0.02). There was no significant treatment group difference for the Sexual Function domain. Escitalopram treatment resulted in statistically significant improvements in PEG scores compared to placebo (mean treatment group difference at 8 weeks of -0.33; 95% CI -0.81 to 0.15; p = 0.045). Conclusions: Treatment with escitalopram 10-20 mg/day in healthy women with vasomotor symptoms significantly improved menopause-related quality of life and pain. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [LaCroix, Andrea Z.; Larson, Joseph] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Freeman, Ellen W.] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Freeman, Ellen W.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Carpenter, Janet S.] Indiana Univ, Sch Nursing, Indianapolis, IN 46202 USA. [Joffe, Hadine; Cohen, Lee] Massachusetts Gen Hosp CWMH, Boston, MA 02114 USA. [Reed, Susan D.; Newton, Katherine M.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [Sternfeld, Barbara] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55415 USA. [Seguin, Rebecca A.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. RP LaCroix, AZ (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M3-A410,POB 19024, Seattle, WA 98109 USA. EM alacroix@whi.org; freemane@mail.med.upenn.edu; jlarson@whi.org; carpentj@iupui.edu; hjoffe@partners.org; reeds@u.washington.edu; newton.k@ghc.org; rebeccaseguin@cornell.edu; Barbara.Sternfeld@kp.org; lcohen2@partners.org; ensru001@umn.edu FU Forest Laboratories, Inc.; Wyeth; Pfizer; Xanodyne Pharmaceuticals; National Alliance for Research on Schizophrenia and Depression; Astra-Zeneca Pharmaceuticals; Sepracor Inc.; Bayer HealthCare; Bristol-Myers; Stanley Foundation; Ortho-McNeill Jansen; Pfizer, Inc.; Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD); National Center for Complementary and Alternative Medicine (NCCAM); Office of Research and Women's Health (ORWH); NIA [U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700]; Indiana Clinical and Translational Sciences Institute; National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences Award [UL1 RR025761] FX Dr. LaCroix reported serving on scientific advisory boards for Pfizer, Sanofi-Adventis and Amgen. Dr. Freeman reported research support from Forest Laboratories, Inc., Wyeth, Pfizer, and Xanodyne Pharmaceuticals; honoraria for consulting and presentations from Wyeth, Forest Laboratories, Inc., Pherin Pharmaceuticals, and Bayer Health Care. Dr. Cohen reported research support from National Alliance for Research on Schizophrenia and Depression, Astra-Zeneca Pharmaceuticals, Sepracor, Inc., Bayer HealthCare, Bristol-Myers, Stanley Foundation, Ortho-McNeill Jansen, Pfizer, Inc.; Advisory/consulting: Eli Lilly, GlaxoSmithKline, JDS/Noven Pharmaceuticals, Wyeth-Ayerst Pharmaceuticals; Honoraria: Eli Lilly, Forest Laboratories, Inc., GlaxosmithKline, Pfizer, Inc., and Wyeth-Ayerst Pharmaceuticals. Dr. Joffe reported research support from Cephalon/Teva; Advisory/ Consulting, Noven and Sunovion. No other authors reported having a financial conflict of interest.; The study was supported by a cooperative agreement issued by the National Institute of Aging (NIA), in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD), the National Center for Complementary and Alternative Medicine (NCCAM) and the Office of Research and Women's Health (ORWH), and grants U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700 from the NIA. At the Indiana University site, the project was funded in part with support from the Indiana Clinical and Translational Sciences Institute, funded in part by grant UL1 RR025761 from the National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences Award. Escitalopram and matching placebo pills were provided by Forest Research Institute. Trial registration clinicaltrials.gov Identifier: NCT00894543 NR 30 TC 10 Z9 10 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-5122 J9 MATURITAS JI Maturitas PD DEC PY 2012 VL 73 IS 4 BP 361 EP 368 DI 10.1016/j.maturitas.2012.09.006 PG 8 WC Geriatrics & Gerontology; Obstetrics & Gynecology SC Geriatrics & Gerontology; Obstetrics & Gynecology GA 046OC UT WOS:000311773300016 PM 23031421 ER PT J AU Le Gallo, M O'Hara, AJ Rudd, ML Urick, ME Hansen, NF O'Neil, NJ Price, JC Zhang, S England, BM Godwin, AK Sgroi, DC Hieter, P Mullikin, JC Merino, MJ Bell, DW AF Le Gallo, Matthieu O'Hara, Andrea J. Rudd, Meghan L. Urick, Mary Ellen Hansen, Nancy F. O'Neil, Nigel J. Price, Jessica C. Zhang, Suiyuan England, Bryant M. Godwin, Andrew K. Sgroi, Dennis C. Hieter, Philip Mullikin, James C. Merino, Maria J. Bell, Daphne W. CA NIH Intramural Sequencing Ctr NISC TI Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes SO NATURE GENETICS LA English DT Article ID DNA-DAMAGE; HISTONE DEACETYLASE; FREQUENT MUTATIONS; RENAL-CARCINOMA; PROSTATE-CANCER; CELL CARCINOMA; FACTOR CHD4; ARID1A; NURD; SUPPRESSOR AB Endometrial cancer is the sixth most commonly diagnosed cancer in women worldwide, causing similar to 74,000 deaths annually(1). Serous endometrial cancers are a clinically aggressive subtype with a poorly defined genetic etiology(2-4). We used whole-exome sequencing to comprehensively search for somatic mutations within similar to 22,000 protein-encoding genes in 13 primary serous endometrial tumors. We subsequently resequenced 18 genes, which were mutated in more than 1 tumor and/or were components of an enriched functional grouping, from 40 additional serous tumors. We identified high frequencies of somatic mutations in CHD4 (17%), EP300 (8%), ARID1A (6%), TSPYL2 (6%), FBXW7 (29%), SPOP (8%), MAP3K4 (6%) and ABCC9 (6%). Overall, 36.5% of serous tumors had a mutated chromatin-remodeling gene, and 35% had a mutated ubiquitin ligase complex gene, implicating frequent mutational disruption of these processes in the molecular pathogenesis of one of the deadliest forms of endometrial cancer. C1 [Le Gallo, Matthieu; O'Hara, Andrea J.; Rudd, Meghan L.; Urick, Mary Ellen; Price, Jessica C.; England, Bryant M.; Bell, Daphne W.] NHGRI, Canc Genet Branch, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA. [Hansen, Nancy F.; Zhang, Suiyuan; Mullikin, James C.] NHGRI, Genome Technol Branch, US NIH, Bethesda, MD 20892 USA. [O'Neil, Nigel J.; Hieter, Philip] Univ British Columbia, Michael Smith Labs, Vancouver, BC, Canada. [Sgroi, Dennis C.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Sgroi, Dennis C.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Mullikin, James C.; NIH Intramural Sequencing Ctr NISC] NISC, US NIH, Bethesda, MD USA. [Merino, Maria J.] NCI, US NIH, Bethesda, MD 20892 USA. RP Bell, DW (reprint author), NHGRI, Canc Genet Branch, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA. EM belldaph@mail.nih.gov RI O'Neil, Nigel/J-4012-2014; OI O'Neil, Nigel/0000-0002-1992-6976; Le Gallo, Matthieu/0000-0001-9085-8155 FU National Human Genome Research Institute, US NIH; NIH [R01CA112021, R01CA140323, CA016519]; Avon Foundation; Ovarian Cancer Fund; Canadian Institutes for Health Research [MOP-38096] FX The study was funded in part by the Intramural Program of the National Human Genome Research Institute, US NIH (D.W.B., J.C.M. and M.J.M.); NIH grant R01CA112021 (D.C.S.); the Avon Foundation (D.C.S.); NIH grant R01CA140323 (A.K.G.); and the Ovarian Cancer Fund (A.K.G.). P.H. is supported by grants from the NIH (CA016519) and by the Canadian Institutes for Health Research (MOP-38096). NR 59 TC 140 Z9 143 U1 4 U2 37 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2012 VL 44 IS 12 BP 1310 EP 1315 DI 10.1038/ng.2455 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 045QZ UT WOS:000311713200007 PM 23104009 ER PT J AU Whitcomb, DC LaRusch, J Krasinskas, AM Klei, L Smith, JP Brand, RE Neoptolemos, JP Lerch, MM Tector, M Sandhu, BS Guda, NM Orlichenko, L Alkaade, S Amann, ST Anderson, MA Baillie, J Banks, PA Conwell, D Cote, GA Cotton, PB DiSario, J Farrer, LA Forsmark, CE Johnstone, M Gardner, TB Gelrud, A Greenhalf, W Haines, JL Hartman, DJ Hawes, RA Lawrence, C Lewis, M Mayerle, J Mayeux, R Melhem, NM Money, ME Muniraj, T Papachristou, GI Pericak-Vance, MA Romagnuolo, J Schellenberg, GD Sherman, S Simon, P Singh, VP Slivka, A Stolz, D Sutton, R Weiss, FU Wilcox, CM Zarnescu, NO Wisniewski, SR O'Connell, MR Kienholz, ML Roeder, K Barmada, MM Yadav, D Devlin, B Albert, MS Albin, RL Apostolova, LG Arnold, SE Baldwin, CT Barber, R Barnes, LL Beach, TG Beecham, GW Beekly, D Bennett, DA Bigio, EH Bird, TD Blacker, D Boxer, A Burke, JR Buxbaum, JD Cairns, NJ Cantwell, LB Cao, CH Carney, RM Carroll, SL Chui, HC Clark, DG Cribbs, DH Crocco, EA Cruchaga, C DeCarli, C Demirci, FY Dick, M Dickson, DW Duara, R Ertekin-Taner, N Faber, KM Fallon, KB Farlow, MR Ferris, S Foroud, TM Frosch, MP Galasko, DR Ganguli, M Gearing, M Geschwind, DH Ghetti, B Gilbert, JR Gilman, S Glass, JD Goate, AM Graff-Radford, NR Green, RC Growdon, JH Hakonarson, H Hamilton-Nelson, KL Hamilton, RL Harrell, LE Head, E Honig, LS Hulette, CM Hyman, BT Jicha, GA Jin, LW Jun, G Kamboh, MI Karydas, A Kaye, JA Kim, R Koo, EH Kowall, NW Kramer, JH Kramer, P Kukull, WA LaFerla, FM Lah, JJ Leverenz, JB Levey, AI Li, G Lin, CF Lieberman, AP Lopez, OL Lunetta, KL Lyketsos, CG Mack, WJ Marson, DC Martin, ER Martiniuk, F Mash, DC Masliah, E Mckee, AC Mesulam, M Miller, BL Miller, CA Miller, JW Montine, TJ Morris, JC Murrell, JR Naj, AC Olichney, JM Parisi, JE Peskind, E Petersen, RC Pierce, A Poon, WW Potter, H Quinn, JF Raj, A Raskind, M Reiman, EM Reisberg, B Reitz, C Ringman, JM Roberson, ED Rosen, HJ Rosenberg, RN Sano, M Saykin, AJ Schneider, JA Schneider, LS Seeley, WW Smith, AG Sonnen, JA Spina, S Stern, RA Tanzi, RE Trojanowski, JQ Troncoso, JC Tsuang, DW Valladares, O Van Deerlin, VM Van Eldik, LJ Vardarajan, BN Vinters, HV Vonsattel, JP Wang, LS Weintraub, S Welsh-Bohmer, KA Williamson, J Woltjer, RL Wright, CB Younkin, SG Yu, CE Yu, L AF Whitcomb, David C. LaRusch, Jessica Krasinskas, Alyssa M. Klei, Lambertus Smith, Jill P. Brand, Randall E. Neoptolemos, John P. Lerch, Markus M. Tector, Matt Sandhu, Bimaljit S. Guda, Nalini M. Orlichenko, Lidiya Alkaade, Samer Amann, Stephen T. Anderson, Michelle A. Baillie, John Banks, Peter A. Conwell, Darwin Cote, Gregory A. Cotton, Peter B. DiSario, James Farrer, Lindsay A. Forsmark, Chris E. Johnstone, Marianne Gardner, Timothy B. Gelrud, Andres Greenhalf, William Haines, Jonathan L. Hartman, Douglas J. Hawes, Robert A. Lawrence, Christopher Lewis, Michele Mayerle, Julia Mayeux, Richard Melhem, Nadine M. Money, Mary E. Muniraj, Thiruvengadam Papachristou, Georgios I. Pericak-Vance, Margaret A. Romagnuolo, Joseph Schellenberg, Gerard D. Sherman, Stuart Simon, Peter Singh, Vijay P. Slivka, Adam Stolz, Donna Sutton, Robert Weiss, Frank Ulrich Wilcox, C. Mel Zarnescu, Narcis Octavian Wisniewski, Stephen R. O'Connell, Michael R. Kienholz, Michelle L. Roeder, Kathryn Barmada, M. Michael Yadav, Dhiraj Devlin, Bernie Albert, Marilyn S. Albin, Roger L. Apostolova, Liana G. Arnold, Steven E. Baldwin, Clinton T. Barber, Robert Barnes, Lisa L. Beach, Thomas G. Beecham, Gary W. Beekly, Duane Bennett, David A. Bigio, Eileen H. Bird, Thomas D. Blacker, Deborah Boxer, Adam Burke, James R. Buxbaum, Joseph D. Cairns, Nigel J. Cantwell, Laura B. Cao, Chuanhai Carney, Regina M. Carroll, Steven L. Chui, Helena C. Clark, David G. Cribbs, David H. Crocco, Elizabeth A. Cruchaga, Carlos DeCarli, Charles Demirci, F. Yesim Dick, Malcolm Dickson, Dennis W. Duara, Ranjan Ertekin-Taner, Nilufer Faber, Kelley M. Fallon, Kenneth B. Farlow, Martin R. Ferris, Steven Foroud, Tatiana M. Frosch, Matthew P. Galasko, Douglas R. Ganguli, Mary Gearing, Marla Geschwind, Daniel H. Ghetti, Bernardino Gilbert, John R. Gilman, Sid Glass, Jonathan D. Goate, Alison M. Graff-Radford, Neill R. Green, Robert C. Growdon, John H. Hakonarson, Hakon Hamilton-Nelson, Kara L. Hamilton, Ronald L. Harrell, Lindy E. Head, Elizabeth Honig, Lawrence S. Hulette, Christine M. Hyman, Bradley T. Jicha, Gregory A. Jin, Lee-Way Jun, Gyungah Kamboh, M. Ilyas Karydas, Anna Kaye, Jeffrey A. Kim, Ronald Koo, Edward H. Kowall, Neil W. Kramer, Joel H. Kramer, Patricia Kukull, Walter A. LaFerla, Frank M. Lah, James J. Leverenz, James B. Levey, Allan I. Li, Ge Lin, Chiao-Feng Lieberman, Andrew P. Lopez, Oscar L. Lunetta, Kathryn L. Lyketsos, Constantine G. Mack, Wendy J. Marson, Daniel C. Martin, Eden R. Martiniuk, Frank Mash, Deborah C. Masliah, Eliezer McKee, Ann C. Mesulam, Marsel Miller, Bruce L. Miller, Carol A. Miller, Joshua W. Montine, Thomas J. Morris, John C. Murrell, Jill R. Naj, Adam C. Olichney, John M. Parisi, Joseph E. Peskind, Elaine Petersen, Ronald C. Pierce, Aimee Poon, Wayne W. Potter, Huntington Quinn, Joseph F. Raj, Ashok Raskind, Murray Reiman, Eric M. Reisberg, Barry Reitz, Christiane Ringman, John M. Roberson, Erik D. Rosen, Howard J. Rosenberg, Roger N. Sano, Mary Saykin, Andrew J. Schneider, Julie A. Schneider, Lon S. Seeley, William W. Smith, Amanda G. Sonnen, Joshua A. Spina, Salvatore Stern, Robert A. Tanzi, Rudolph E. Trojanowski, John Q. Troncoso, Juan C. Tsuang, Debby W. Valladares, Otto Van Deerlin, Vivianna M. Van Eldik, Linda J. Vardarajan, Badri N. Vinters, Harry V. Vonsattel, Jean Paul Wang, Li-San Weintraub, Sandra Welsh-Bohmer, Kathleen A. Williamson, Jennifer Woltjer, Randall L. Wright, Clinton B. Younkin, Steven G. Yu, Chang-En Yu, Lei CA Alzheimer's Dis Genetics Consortiu TI Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis SO NATURE GENETICS LA English DT Article ID CLAUDIN-2 EXPRESSION; RECURRENT ACUTE; PATHOGENESIS; ACTIVATION; DIAGNOSIS; PROMOTER AB Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 (P < 1 x 10(-12)) and X-linked CLDN2 (P < 1 x 10(-21)) through a two-stage genome-wide study (stage 1: 676 cases and 4,507 controls; stage 2: 910 cases and 4,170 controls). The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous in males) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men (male hemizygote frequency is 0.26, whereas female homozygote frequency is 0.07). C1 [Whitcomb, David C.; LaRusch, Jessica; Brand, Randall E.; Orlichenko, Lidiya; Gelrud, Andres; Papachristou, Georgios I.; Singh, Vijay P.; Slivka, Adam; Zarnescu, Narcis Octavian; O'Connell, Michael R.; Kienholz, Michelle L.; Yadav, Dhiraj] Univ Pittsburgh, Sch Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15260 USA. [Whitcomb, David C.; Stolz, Donna] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA USA. [Whitcomb, David C.; Barmada, M. Michael; Devlin, Bernie; Demirci, F. Yesim] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Krasinskas, Alyssa M.; Hartman, Douglas J.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Klei, Lambertus; Melhem, Nadine M.; Devlin, Bernie; Ganguli, Mary] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Smith, Jill P.] Penn State Univ, Div Gastroenterol & Liver Dis, Hershey, PA USA. [Neoptolemos, John P.; Johnstone, Marianne; Greenhalf, William; Sutton, Robert] Univ Liverpool, Inst Translat Med, Natl Inst Hlth Res Liverpool Pancreas Biomed Res, Dept Mol & Clin Canc Med, Liverpool L69 3BX, Merseyside, England. [Tector, Matt; Guda, Nalini M.] St Lukes Med Ctr, Aurora Hlth Care Syst, Milwaukee, WI USA. [Lerch, Markus M.; Mayerle, Julia; Simon, Peter; Weiss, Frank Ulrich] Univ Med Greifswald, Dept Med A, Greifswald, Germany. [Sandhu, Bimaljit S.] Virginia Commonwealth Univ, Med Ctr, Div Gastroenterol Hepatol & Nutr, Richmond, VA USA. [Alkaade, Samer] St Louis Univ, Dept Med, St Louis, MO USA. [Amann, Stephen T.] N Mississippi Med Ctr, Tupelo, MS USA. [Anderson, Michelle A.] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Baillie, John; Burke, James R.; Welsh-Bohmer, Kathleen A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Conwell, Darwin] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Cote, Gregory A.; Sherman, Stuart] Indiana Univ, Med Ctr, Dept Med, Indianapolis, IN USA. [Cotton, Peter B.; Hawes, Robert A.; Lawrence, Christopher; Romagnuolo, Joseph] Med Univ S Carolina, Ctr Digest Dis, Charleston, SC 29425 USA. [DiSario, James] Univ Utah, Hlth Sci Ctr, Dept Med, Salt Lake City, UT 84132 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med, Biomed Genet Sect, Boston, MA 02118 USA. [Forsmark, Chris E.] Univ Florida, Dept Med, Gainesville, FL USA. [Gardner, Timothy B.] Dartmouth Hitchcock Med Ctr, Div Gastroenterol & Hepatol, Dept Med, Hanover, NH USA. [Haines, Jonathan L.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Haines, Jonathan L.] Vanderbilt Univ, Vanderbilt Ctr Human Genet Res, Nashville, TN USA. [Lewis, Michele] Mayo Clin, Div Gastroenterol & Hepatol, Jacksonville, FL 32224 USA. [Mayeux, Richard; Reitz, Christiane; Vardarajan, Badri N.] Columbia Univ, Dept Neurol, Gertrude H Sergievsky Ctr, New York, NY USA. [Mayeux, Richard; Honig, Lawrence S.; Reitz, Christiane; Vardarajan, Badri N.; Vonsattel, Jean Paul; Williamson, Jennifer] Columbia Univ, Dept Neurol, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA. [Money, Mary E.] Meritus Med Ctr, Hagerstown, MD USA. [Muniraj, Thiruvengadam] Yale Univ, Dept Internal Med, Derby, CT USA. [Muniraj, Thiruvengadam] Griffin Hosp, Derby, CT USA. [Pericak-Vance, Margaret A.; Beecham, Gary W.; Gilbert, John R.; Hamilton-Nelson, Kara L.; Martin, Eden R.; Naj, Adam C.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA. [Pericak-Vance, Margaret A.; Beecham, Gary W.; Gilbert, John R.; Hamilton-Nelson, Kara L.; Naj, Adam C.] Univ Miami, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL USA. [Schellenberg, Gerard D.; Cantwell, Laura B.; Lin, Chiao-Feng; Trojanowski, John Q.; Valladares, Otto; Van Deerlin, Vivianna M.; Wang, Li-San] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA USA. [Wilcox, C. Mel] Univ Alabama Birmingham, Dept Med, Div Gastroenterol & Hepatol, Birmingham, AL 35294 USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Epidemiol Data Ctr, Pittsburgh, PA USA. [Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Albert, Marilyn S.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Albin, Roger L.; Gilman, Sid] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Albin, Roger L.] VA Ann Arbor Healthcare Syst VAAAHS, GRECC, Ann Arbor, MI USA. [Apostolova, Liana G.; Ringman, John M.; Vinters, Harry V.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Arnold, Steven E.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Baldwin, Clinton T.; Jun, Gyungah] Boston Univ, Genet Program, Dept Med, Boston, MA USA. [Barber, Robert] Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX USA. [Barnes, Lisa L.; Bennett, David A.; Schneider, Julie A.; Yu, Lei] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Barnes, Lisa L.] Rush Univ, Med Ctr, Dept Behav Sci, Chicago, IL USA. [Beach, Thomas G.] Banner Sun Hlth Res Inst, Civin Lab Neuropathol, Phoenix, AZ USA. [Beekly, Duane] Univ Washington, Natl Alzheimers Coordinating Ctr, Seattle, WA 98195 USA. [Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL USA. [Bigio, Eileen H.] Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA. [Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA USA. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Blacker, Deborah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Boxer, Adam; Karydas, Anna; Miller, Bruce L.; Rosen, Howard J.; Seeley, William W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Buxbaum, Joseph D.; Sano, Mary] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Cairns, Nigel J.; Morris, John C.] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA. [Cao, Chuanhai; Potter, Huntington; Raj, Ashok; Smith, Amanda G.] Univ S Florida, Hlth Byrd Alzheimers Inst, Tampa, FL USA. [Carney, Regina M.] Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. [Carroll, Steven L.; Fallon, Kenneth B.] Univ Alabama, Dept Pathol, Birmingham, TN USA. [Chui, Helena C.; Schneider, Lon S.] Univ So Calif, Dept Neurol, Los Angeles, CA USA. [Clark, David G.; Harrell, Lindy E.; Marson, Daniel C.; Roberson, Erik D.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Cribbs, David H.; Pierce, Aimee] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. [Crocco, Elizabeth A.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. [Cruchaga, Carlos; Goate, Alison M.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Cruchaga, Carlos; Goate, Alison M.] Washington Univ, Sch Med, Hope Ctr Program Prot Aggregat & Neurodegenerat, St Louis, MO USA. [DeCarli, Charles; Olichney, John M.] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. [Dick, Malcolm; Poon, Wayne W.] Univ Calif Irvine, Inst Memory Impairments & Neurol Disorders, Irvine, CA USA. [Dickson, Dennis W.; Ertekin-Taner, Nilufer; Graff-Radford, Neill R.; Younkin, Steven G.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Duara, Ranjan] Mt Sinai Med Ctr, Wien Ctr Alzheimers Dis & Memory Disorders, Miami Beach, FL 33140 USA. [Ertekin-Taner, Nilufer; Graff-Radford, Neill R.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Faber, Kelley M.; Foroud, Tatiana M.; Murrell, Jill R.; Saykin, Andrew J.] Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN USA. [Farlow, Martin R.; Reisberg, Barry] Indiana Univ, Dept Neurol, Indianapolis, IN USA. [Ferris, Steven] NYU, Dept Psychiat, New York, NY 10016 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Charlestown, MA USA. [Galasko, Douglas R.; Koo, Edward H.; Masliah, Eliezer] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Gearing, Marla] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Gearing, Marla] Emory Univ, Emory Alzheimers Dis Ctr, Atlanta, GA 30322 USA. [Geschwind, Daniel H.] Univ Calif Los Angeles, Neurogenet Program, Los Angeles, CA USA. [Ghetti, Bernardino; Murrell, Jill R.; Spina, Salvatore] Indiana Univ, Dept Pathol & Lab Med, Indianapolis, IN 46204 USA. [Glass, Jonathan D.; Lah, James J.; Levey, Allan I.] Emory Univ, Dept Neurol, Atlanta, GA USA. [Green, Robert C.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Green, Robert C.] Brigham & Womens Hosp, Partners Ctr Personalized Genet Med, Boston, MA 02115 USA. [Growdon, John H.; Hyman, Bradley T.; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Hamilton, Ronald L.] Univ Pittsburgh, Dept Pathol Neuropathol, Pittsburgh, PA USA. [Head, Elizabeth] Univ Kentucky, Dept Mol & Biomed Pharmacol, Sanders Brown Ctr Aging, Lexington, KY USA. [Hulette, Christine M.] Duke Univ, Dept Pathol, Durham, NC 27706 USA. [Jicha, Gregory A.] Univ Kentucky, Dept Neurol, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Jin, Lee-Way; Miller, Joshua W.] Univ Calif Davis, Dept Pathol & Lab Med, Sacramento, CA 95817 USA. [Farrer, Lindsay A.; Jun, Gyungah] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Farrer, Lindsay A.; Jun, Gyungah; Lunetta, Kathryn L.] Boston Univ, Dept Ophthalmol, Boston, MA USA. [Kamboh, M. Ilyas; Lopez, Oscar L.] Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA USA. [Kaye, Jeffrey A.; Kramer, Patricia; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Kaye, Jeffrey A.] Portland VA Med Ctr, Dept Neurol, Portland, OR USA. [Kim, Ronald] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA USA. [Farrer, Lindsay A.; Kowall, Neil W.; McKee, Ann C.; Stern, Robert A.] Boston Univ, Dept Neurol, Boston, MA USA. [Kowall, Neil W.; McKee, Ann C.] Boston Univ, Dept Pathol, Boston, MA USA. [Kramer, Joel H.] Univ Calif San Francisco, Dept Neuropsychol, San Francisco, CA 94143 USA. [Kramer, Patricia] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. [Kukull, Walter A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [LaFerla, Frank M.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA. [Leverenz, James B.; Montine, Thomas J.; Sonnen, Joshua A.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Li, Ge; Peskind, Elaine; Raskind, Murray; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Lieberman, Andrew P.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Lyketsos, Constantine G.] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. [Mack, Wendy J.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Martiniuk, Frank] NYU, Dept Med Pulm, New York, NY USA. [Mash, Deborah C.] Univ Miami, Dept Neurol, Miami, FL USA. [Masliah, Eliezer] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Mesulam, Marsel; Weintraub, Sandra] Northwestern Univ, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA. [Miller, Carol A.] Univ So Calif, Dept Pathol, Los Angeles, CA 90089 USA. [Morris, John C.] Washington Univ, Dept Neurol, St Louis, MO USA. [Parisi, Joseph E.] Mayo Clin, Dept Anat Pathol, Rochester, MN USA. [Parisi, Joseph E.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Reiman, Eric M.] Arizona Alzheimers Consortium, Phoenix, AZ USA. [Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ USA. [Reiman, Eric M.] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ USA. [Reisberg, Barry] NYU, Alzheimers Dis Ctr, New York, NY USA. [Rosenberg, Roger N.] Univ Texas SW, Dept Neurol, Dallas, TX USA. [Saykin, Andrew J.] Indiana Univ, Dept Radiol & Imaging Sci, Indianapolis, IN 46204 USA. [Schneider, Julie A.] Rush Univ, Med Ctr, Dept Pathol Neuropathol, Chicago, IL USA. [Schneider, Lon S.] Univ So Calif, Dept Psychiat, Los Angeles, CA USA. [Troncoso, Juan C.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Van Eldik, Linda J.] Univ Kentucky, Dept Anat & Neurobiol, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Vinters, Harry V.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. [Welsh-Bohmer, Kathleen A.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Woltjer, Randall L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Wright, Clinton B.] Univ Miami, Miller Sch Med, Dept Neurol, Evelyn F McKnight Brain Inst, Miami, FL 33136 USA. [Yu, Chang-En] Univ Washington, Dept Med, Seattle, WA USA. RP Whitcomb, DC (reprint author), Univ Pittsburgh, Sch Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15260 USA. EM whitcomb@pitt.du; devlinbj@upmc.edu RI Melhem, Nadine/G-1510-2013; Kowall, Neil/G-6364-2012; Saykin, Andrew/A-1318-2007; MORAN, CATHERINE/C-9539-2015; Lerch, Markus M./E-2206-2016; Johnstone, Marianne/K-8887-2012; Greenhalf, William/A-2680-2013; Weiss, Frank/A-6386-2009; Sutton, Robert/I-3587-2016; Hollyman, Marianne/J-8362-2016; Tsuang, Debby/L-7234-2016; OI Farrer, Lindsay/0000-0001-5533-4225; Stern, Robert/0000-0002-5008-077X; Reisberg, Barry/0000-0002-9104-7423; Carroll, Steven/0000-0001-6714-4373; Demirci, F. Yesim/0000-0001-6907-9843; Dickson, Dennis W/0000-0001-7189-7917; Kaye, Jeffrey/0000-0002-9971-3478; Kukull, Walter/0000-0001-8761-9014; Kamboh, M. Ilyas/0000-0002-3453-1438; Barmada, M Michael/0000-0002-3604-6460; Wisniewski, Stephen/0000-0002-3877-9860; Kowall, Neil/0000-0002-6624-0213; Saykin, Andrew/0000-0002-1376-8532; Lerch, Markus M./0000-0002-9643-8263; Johnstone, Marianne/0000-0001-7785-4213; Sutton, Robert/0000-0001-6600-562X; Hollyman, Marianne/0000-0002-5972-0454; Tsuang, Debby/0000-0002-4716-1894; Jun, Gyungah/0000-0002-3230-8697; Lunetta, Kathryn/0000-0002-9268-810X; Cruchaga, Carlos/0000-0002-0276-2899; Ferris, Steven/0000-0001-8641-6223; Weiss, Frank Ulrich/0000-0003-3369-6369; Buxbaum, Joseph/0000-0001-8898-8313; Roberson, Erik/0000-0002-1810-9763 FU US National Institutes of Health (NIH) [R56DK061451, R01DK054709, T32DK063922, R01MH057881, R01CA117926, R01DK077906, UL1RR024153, UL1TR000005]; Digestive Disease Training Program [T32DK063922]; American Gastroenterology Association; National Institute for Health Research (NIHR) Biomedical Research Unit award; National Pancreas Foundation; Frieda G. and Saul E Shapira BRCA-Associated Cancer Research Program; Wayne Fusaro Pancreatic Cancer Research Fund; Gift of Life Foundation; Alzheimer's Disease Genetics Consortium (ADGC): The NIH-National Institute on Aging (NIH-NIA) [U01AG032984, RC2AG036528]; National Alzheimer's Coordinating Center (NACC) [U01AG016976]; National Cell Repository for Alzheimer's Disease (NCRAD) [U24AG021886]; Banner Sun Health Research Institute [P30AG019610]; Boston University [P30AG013846, U01AG10483, R01CA129769, R01MH080295, R01AG017173, R01AG025259, R01AG33193]; Columbia University [P50AG008702, R37AG015473]; Duke University [P30AG028377, AG05128]; Emory University [AG025688]; Indiana University [P30AG10133]; Johns Hopkins University [P50AG005146, R01AG020688]; Massachusetts General Hospital [P50AG005134]; Mayo Clinic [P50AG016574]; Mount Sinai School of Medicine [P50AG005138, P01AG002219]; New York University [P30AG08051, MO1RR00096, UL1RR029893]; Northwestern University [P30AG013854]; Oregon Health & Science University [P30AG008017, R01AG026916]; Rush University [P30AG010161, R01AG019085, R01AG15819, R01AG17917, R01AG30146]; University of Alabama at Birmingham [P50AG016582, UL1RR02777]; University of Arizona [R01AG031581]; University of California, Davis [P30AG010129]; University of California, Irvine [P50AG016573, P50AG016575, P50AG016576, P50AG016577]; University of California, Los Angeles [P50AG016570]; University of California, San Diego [P50AG005131]; University of California, San Francisco [P50AG023501, P01AG019724]; University of Kentucky [P30AG028383, AG05144]; University of Michigan [P50AG008671]; University of Pennsylvania [P30AG010124]; University of Pittsburgh [P50AG005133, AG030653]; University of Southern California [P50AG005142]; University of Texas Southwestern [P30AG012300]; University of Miami [R01AG027944, AG010491, AG027944, AG021547, AG019757]; University of Washington [P50AG005136]; Vanderbilt University [R01AG019085]; Washington University [P50AG005681, P01AG03991]; National Institute of Neurological Disorders and Stroke (NINDS) [NS39764]; National Institute of Mental Health (NIMH) [MH60451]; GlaxoSmithKline FX Technical support was provided by K. Stello, S. Das, D. Dwyer, A. Rowland, P.A. Blake, M. Ross, C. McGovern, L. Kish, H. Nawaz, S. Solomon, S. Boggiano, R. Ostroff, M. Goss and J. Timm. Data management was provided by L. Silfies and D. Protivnak. Clinical support was provided by S. Boggaino, M. Hendricks, B. Elinoff, L. McHenry, G. Lehman,). Watkins, E. Fogel and L. Lazzell-Pannell. Additional samples were provided by F. Burton (deceased; St. Louis University School of Medicine); S. Lo (Cedars-Sinai Medical Center, University of California, Los Angeles); M.T. DeMeo (Rush University Medical Center); W.M. Steinberg (Washington Hospital Center); M.L. Kochman (University of Pennsylvania); B. Etemad (Ochsner Medical Center); and H. Zeh, A.). Moser and K.K. Lee (University of Pittsburgh). This publication was made possible by grants R56DK061451 (D.C.W.), R01DK054709 (D.C.W), T32DK063922 (D.C.W.), R01MH057881 (B.D. and K.R.), R01CA117926 (J.P.S.), R01DK077906 (D.C.W. and D.Y.), UL1RR024153 and UL1TR000005 from the US National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NIH. This project used the University of Pittsburgh Genomics and Proteomics Core laboratories (UL1RR024153, UL1RR024153 and UL1TR000005) and the University of Pittsburgh Cancer Institute (UPCI) Clinical Genomics Immunoproteomics and Sequencing Facility (NIH P30CA047904). J.L. was supported by Digestive Disease Training Program T32DK063922 (D.C.W.). N.O.Z. was supported by the American Gastroenterology Association John I Isenberg International Scholar Award. The Liverpool cohort was supported by the National Institute for Health Research (NIHR) Biomedical Research Unit award. Additional support was provided by the National Pancreas Foundation (D.C.W.), the Frieda G. and Saul E Shapira BRCA-Associated Cancer Research Program (D.C.W.) and the Wayne Fusaro Pancreatic Cancer Research Fund (D.C.W.) and Gift of Life Foundation (J.P.S.).; Alzheimer's Disease Genetics Consortium (ADGC): The NIH-National Institute on Aging (NIH-NIA) supported this work through the following grants: ADGC, U01AG032984 and RC2AG036528; National Alzheimer's Coordinating Center (NACC), U01AG016976; National Cell Repository for Alzheimer's Disease (NCRAD), U24AG021886; Banner Sun Health Research Institute, P30AG019610; Boston University P30AG013846, U01AG10483, R01CA129769, R01MH080295, R01AG017173, R01AG025259 and R01AG33193; Columbia University, P50AG008702 and R37AG015473; Duke University, P30AG028377 and AG05128; Emory University, AG025688; Indiana University, P30AG10133; Johns Hopkins University, P50AG005146 and R01AG020688; Massachusetts General Hospital, P50AG005134; Mayo Clinic, P50AG016574; Mount Sinai School of Medicine, P50AG005138 and P01AG002219; New York University, P30AG08051, MO1RR00096 and UL1RR029893; Northwestern University, P30AG013854; Oregon Health & Science University, P30AG008017 and R01AG026916; Rush University, P30AG010161, R01AG019085, R01AG15819, R01AG17917 and R01AG30146; University of Alabama at Birmingham, P50AG016582 and UL1RR02777; University of Arizona, R01AG031581; University of California, Davis, P30AG010129; University of California, Irvine, P50AG016573, P50AG016575, P50AG016576 and P50AG016577; University of California, Los Angeles, P50AG016570; University of California, San Diego, P50AG005131; University of California, San Francisco, P50AG023501 and P01AG019724; University of Kentucky, P30AG028383 and AG05144; University of Michigan, P50AG008671; University of Pennsylvania, P30AG010124; University of Pittsburgh, P50AG005133 and AG030653; University of Southern California, P50AG005142; University of Texas Southwestern, P30AG012300; University of Miami, R01AG027944, AG010491, AG027944, AG021547 and AG019757; University of Washington, P50AG005136; Vanderbilt University, R01AG019085; and Washington University, P50AG005681 and P01AG03991. The Kathleen Price Bryan Brain Bank at the Duke University Medical Center is funded by National Institute of Neurological Disorders and Stroke (NINDS) grant NS39764 and National Institute of Mental Health (NIMH) grant MH60451 and by GlaxoSmithKline. We thank D.S. Snyder and M. Miller who are ex officio ADGC members. NR 31 TC 66 Z9 66 U1 3 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2012 VL 44 IS 12 BP 1349 EP 1354 DI 10.1038/ng.2466 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 045QZ UT WOS:000311713200014 PM 23143602 ER PT J AU Alvarez-Breckenridge, CA Yu, JH Price, R Wojton, J Pradarelli, J Mao, HY Wei, M Wang, Y He, S Hardcastle, J Fernandez, SA Kaur, B Lawler, SE Vivier, E Mandelboim, O Moretta, A Caligiuri, MA Chiocca, EA AF Alvarez-Breckenridge, Christopher A. Yu, Jianhua Price, Richard Wojton, Jeffrey Pradarelli, Jason Mao, Hsiaoyin Wei, Min Wang, Yan He, Shun Hardcastle, Jayson Fernandez, Soledad A. Kaur, Balveen Lawler, Sean E. Vivier, Eric Mandelboim, Ofer Moretta, Alessandro Caligiuri, Michael A. Chiocca, E. Antonio TI NK cells impede glioblastoma virotherapy through NKp30 and NKp46 natural cytotoxicity receptors SO NATURE MEDICINE LA English DT Article ID HERPES-SIMPLEX-VIRUS; VESICULAR STOMATITIS-VIRUS; HUMAN DENDRITIC CELLS; KILLER-CELLS; TUMOR MICROENVIRONMENT; DEPENDENT MECHANISMS; TRIGGERING RECEPTOR; GLIOMA VIROTHERAPY; ONCOLYTIC VIRUSES; IMMUNE-RESPONSES AB The role of the immune response to oncolytic Herpes simplex viral (oHSV) therapy for glioblastoma is controversial because it might enhance or inhibit efficacy. We found that within hours of oHSV infection of glioblastomas in mice, activated natural killer (NK) cells are recruited to the site of infection. This response substantially diminished the efficacy of glioblastoma virotherapy. oHSV-activated NK cells coordinated macrophage and microglia activation within tumors. In vitro, human NK cells preferentially lysed oHSV-infected human glioblastoma cell lines. This enhanced killing depended on the NK cell natural cytotoxicity receptors (NCRs) NKp30 and NKp46, whose ligands are upregulated in oHSV-infected glioblastoma cells. We found that HSV titers and oHSV efficacy are increased in Ncr1(-/-) mice and a Ncr1(-/-) NK cell adoptive transfer model of glioma, respectively. These results demonstrate that glioblastoma virotherapy is limited partially by an antiviral NK cell response involving specific NCRs, uncovering new potential targets to enhance cancer virotherapy. C1 [Alvarez-Breckenridge, Christopher A.; Price, Richard; Wojton, Jeffrey; Pradarelli, Jason; Wang, Yan; Hardcastle, Jayson; Kaur, Balveen; Lawler, Sean E.; Chiocca, E. Antonio] Ohio State Univ, Med Ctr, Dept Neurol Surg, Dardinger Lab Neurooncol & Neurosci, Columbus, OH 43210 USA. [Alvarez-Breckenridge, Christopher A.; Yu, Jianhua; Price, Richard; Wojton, Jeffrey; Pradarelli, Jason; Mao, Hsiaoyin; Wei, Min; Wang, Yan; He, Shun; Hardcastle, Jayson; Fernandez, Soledad A.; Kaur, Balveen; Lawler, Sean E.; Caligiuri, Michael A.; Chiocca, E. Antonio] James Canc Hosp, Columbus, OH USA. [Alvarez-Breckenridge, Christopher A.; Yu, Jianhua; Price, Richard; Wojton, Jeffrey; Pradarelli, Jason; Mao, Hsiaoyin; Wei, Min; Wang, Yan; He, Shun; Hardcastle, Jayson; Fernandez, Soledad A.; Kaur, Balveen; Lawler, Sean E.; Caligiuri, Michael A.; Chiocca, E. Antonio] Solove Res Inst, Columbus, OH USA. [Alvarez-Breckenridge, Christopher A.; Price, Richard] Ohio State Univ, Med Ctr, Med Scientist Training Program, Columbus, OH 43210 USA. [Yu, Jianhua; Caligiuri, Michael A.] Ohio State Univ, Med Ctr, Div Hematol, Columbus, OH 43210 USA. [Yu, Jianhua; Mao, Hsiaoyin; Wei, Min; He, Shun; Fernandez, Soledad A.; Kaur, Balveen; Caligiuri, Michael A.; Chiocca, E. Antonio] Ohio State Univ, Med Ctr, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Fernandez, Soledad A.] Ohio State Univ, Med Ctr, Ctr Biostat, Columbus, OH 43210 USA. [Vivier, Eric] Univ Aix Marseille 2, INSERM, U631, Ctr Immunol Marseille Luminy, Marseille, France. [Mandelboim, Ofer] Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, Inst Med Res Israel Canada, IL-91010 Jerusalem, Israel. [Moretta, Alessandro] Univ Genoa, Dipartimento Med Sperimentale, Genoa, Italy. [Moretta, Alessandro] Univ Genoa, Ctr Eccellenza Ric Biomed, Genoa, Italy. [Chiocca, E. Antonio] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Dept Neurosurg, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Ohio State Univ, Med Ctr, Dept Neurol Surg, Dardinger Lab Neurooncol & Neurosci, Columbus, OH 43210 USA. EM michael.caligiuri@osumc.edu; eachiocca@partners.org RI kaur, Balveen/E-3355-2011; He, Shun/K-7448-2014 FU US National Institutes of Health [7U01NS061811, CA069246, CA068458, CA095426, TL1RR025753, CA163205]; American Medical Association Foundation Seed Grant; Dardinger Neuro-oncology Laboratory FX This work was supported by US National Institutes of Health grants 7U01NS061811 (to E.A.C.), CA069246 (to E.A.C.), CA068458 (to M.A.C.), CA095426 (to M.A.C.), TL1RR025753 (to C.A.A.-B.) and CA163205 (to E.A.C., M.A.C. and B.K.). C.A.A.-B. was supported by an American Medical Association Foundation Seed Grant. This work was also supported by the Dardinger Neuro-oncology Laboratory. NR 59 TC 47 Z9 47 U1 3 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2012 VL 18 IS 12 BP 1827 EP + DI 10.1038/nm.3013 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 049QZ UT WOS:000311999800031 PM 23178246 ER PT J AU Shao, HL Chung, J Balaj, L Charest, A Bigner, DD Carter, BS Hochberg, FH Breakefield, XO Weissleder, R Lee, H AF Shao, Huilin Chung, Jaehoon Balaj, Leonora Charest, Alain Bigner, Darell D. Carter, Bob S. Hochberg, Fred H. Breakefield, Xandra O. Weissleder, Ralph Lee, Hakho TI Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy SO NATURE MEDICINE LA English DT Article ID GROWTH-FACTOR RECEPTOR; INTEGRATED GENOMIC ANALYSIS; PARAMETRIC RESPONSE MAP; MOLECULAR MARKER; CANCER; EGFR; MULTIFORME; BIOMARKERS; EXOSOMES; TARGET AB Glioblastomas shed large quantities of small, membrane-bound microvesicles into the circulation. Although these hold promise as potential biomarkers of therapeutic response, their identification and quantification remain challenging. Here, we describe a highly sensitive and rapid analytical technique for profiling circulating microvesicles directly from blood samples of patients with glioblastoma. Microvesicles, introduced onto a dedicated microfluidic chip, are labeled with target-specific magnetic nanoparticles and detected by a miniaturized nuclear magnetic resonance system. Compared with current methods, this integrated system has a much higher detection sensitivity and can differentiate glioblastoma multiforme (GBM) microvesicles from nontumor host cell-derived microvesicles. We also show that circulating GBM microvesicles can be used to analyze primary tumor mutations and as a predictive metric of treatment-induced changes. This platform could provide both an early indicator of drug efficacy and a potential molecular stratifier for human clinical trials. C1 [Shao, Huilin; Chung, Jaehoon; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Shao, Huilin] Harvard Univ, Sch Med, Harvard Biophys Program, Boston, MA USA. [Balaj, Leonora; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Boston, MA 02114 USA. [Charest, Alain] Tufts Univ, Sch Med, Mol Oncol Res Inst, Boston, MA 02111 USA. [Bigner, Darell D.] Duke Univ, Med Ctr, Dept Pathol, Brain Tumor Ctr, Durham, NC 27710 USA. [Carter, Bob S.] 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 USA. [Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Lee, H (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; hlee@mgh.harvard.edu FU NIH [U54CA151884, R01EB010011, R01EB004626, P01CA069246, P50CA86355, U01CA141556, U24CA092782, R21CA14122]; Singapore Agency for Science, Technology and Research; American Cancer Society Research Scholar Award [117409] FX We thank T. Reiner (Massachusetts General Hospital (MGH)) for preparing TCO, N. Sergeyev (MGH) for synthesizing MNPs, S. Hilderbrand (MGH) for synthesizing reactive TZ, M. Pittet (MGH) for LNZ308 cells and T. Chan (Memorial Sloan-Kettering Cancer Center) for SkMG3 cells, as well as M. Liong and A. Ghazani for assay assistance, B. Marinelli for mu NMR measurements, C. Min for software implementation, M. McKee for transmission electron microscopy, J. Skog for advice on NTA measurements, L. Zhu and S. Sivaraman for technical assistance and Y. Fisher-Jeffes for critical reading of the manuscript. Special thanks to C. Castro, J. Carlson and clinical colleagues for many helpful discussions. This work was supported in part by NIH grants U54CA151884, R01EB010011, R01EB004626, P01CA069246, P50CA86355, U01CA141556, U24CA092782 and R21CA14122; H.S. received a BS-PhD National Science Scholarship awarded by the Singapore Agency for Science, Technology and Research; A.C. received an American Cancer Society Research Scholar Award 117409. NR 38 TC 161 Z9 163 U1 10 U2 120 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2012 VL 18 IS 12 BP 1835 EP + DI 10.1038/nm.2994 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 049QZ UT WOS:000311999800032 PM 23142818 ER PT J AU Kheirbek, MA Klemenhagen, KC Sahay, A Hen, R AF Kheirbek, Mazen A. Klemenhagen, Kristen C. Sahay, Amar Hen, Rene TI Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders SO NATURE NEUROSCIENCE LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; ADULT HIPPOCAMPAL NEUROGENESIS; SPATIAL-PATTERN SEPARATION; ENHANCED SYNAPTIC PLASTICITY; LEARNING-THEORY PERSPECTIVE; NATIONAL COMORBIDITY SURVEY; IDENTICAL-TWINS DISCORDANT; NEWLY GENERATED NEURONS; DENTATE GYRUS; GRANULE CELLS AB Although an influence of adult neurogenesis in mediating some of the effects of antidepressants has received considerable attention in recent years, much less is known about how alterations in this form of plasticity may contribute to psychiatric disorders such as anxiety and depression. One way to begin to address this question is to link the functions of adult-born hippocampal neurons with specific endophenotypes of these disorders. Recent studies have implicated adult-born hippocampal neurons in pattern separation, a process by which similar experiences or events are transformed into discrete, non-overlapping representations. Here we propose that impaired pattern separation underlies the overgeneralization often seen in anxiety disorders, specifically post-traumatic stress disorder and panic disorder, and therefore represents an endophenotype for these disorders. The development of new, pro-neurogenic compounds may therefore have therapeutic potential for patients who display pattern separation deficits. C1 [Kheirbek, Mazen A.; Hen, Rene] Columbia Univ, Dept Neurosci, New York, NY 10027 USA. [Kheirbek, Mazen A.; Hen, Rene] Columbia Univ, Dept Psychiat, New York, NY USA. [Kheirbek, Mazen A.; Hen, Rene] New York State Psychiat Inst & Hosp, Div Integrat Neurosci, New York, NY 10032 USA. [Klemenhagen, Kristen C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Sahay, Amar] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Sahay, Amar] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sahay, Amar] Harvard Stem Cell Inst, Boston, MA USA. [Sahay, Amar] Harvard Univ, Sch Med, Boston, MA USA. [Hen, Rene] Columbia Univ, Dept Pharmacol, New York, NY USA. RP Hen, R (reprint author), Columbia Univ, Dept Neurosci, New York, NY 10027 USA. EM sahay.amar@mgh.harvard.edu; rh95@columbia.edu RI Kheirbek, Mazen/J-3656-2015 OI Kheirbek, Mazen/0000-0003-2029-802X FU US National Institute of Mental Health [1F32MH092101-01A1, 1K01MH099371-01, 4R00MH086615-03]; Sackler Institute Award; NARSAD Young Investigator Award; Ellison Medical Foundation New Scholar in Aging; Whitehall Foundation; NARSAD; New York Stem Cell Initiative; US National Institutes of Health [R01 MH068542]; Hope for Depression Research Foundation FX We thank L. Drew for comments on the manuscript. The authors are supported by US National Institute of Mental Health grants 1F32MH092101-01A1 and 1K01MH099371-01; a Sackler Institute Award and a NARSAD Young Investigator Award (M. A. K.); US National Institute of Mental Health grant 4R00MH086615-03, the Ellison Medical Foundation New Scholar in Aging and the Whitehall Foundation (A. S.); and NARSAD, the New York Stem Cell Initiative, US National Institutes of Health grant R01 MH068542, and Hope for Depression Research Foundation grants (R.H.). NR 98 TC 157 Z9 170 U1 10 U2 78 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2012 VL 15 IS 12 BP 1613 EP 1620 DI 10.1038/nn.3262 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 045OR UT WOS:000311706700005 PM 23187693 ER PT J AU Shanechi, MM Hu, RC Powers, M Wornell, GW Brown, EN Williams, ZM AF Shanechi, Maryam M. Hu, Rollin C. Powers, Marissa Wornell, Gregory W. Brown, Emery N. Williams, Ziv M. TI Neural population partitioning and a concurrent brain-machine interface for sequential motor function SO NATURE NEUROSCIENCE LA English DT Article ID LATERAL PREFRONTAL CORTEX; DORSAL PREMOTOR CORTEX; MULTIPLE MOVEMENTS; NEURONAL-ACTIVITY; TEMPORAL ORGANIZATION; COMPUTER INTERFACE; CORTICAL-NEURONS; SPIKING ACTIVITY; CEREBRAL-CORTEX; REACHING TASK AB Although brain-machine interfaces (BMIs) have focused largely on performing single-targeted movements, many natural tasks involve planning a complete sequence of such movements before execution. For these tasks, a BMI that can concurrently decode the full planned sequence before its execution may also consider the higher-level goal of the task to reformulate and perform it more effectively. Using population-wide modeling, we discovered two distinct subpopulations of neurons in the rhesus monkey premotor cortex that allow two planned targets of a sequential movement to be simultaneously held in working memory without degradation. Such marked stability occurred because each subpopulation encoded either only currently held or only newly added target information irrespective of the exact sequence. On the basis of these findings, we developed a BMI that concurrently decodes a full motor sequence in advance of movement and can then accurately execute it as desired. C1 [Shanechi, Maryam M.; Hu, Rollin C.; Powers, Marissa; Williams, Ziv M.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Shanechi, Maryam M.; Wornell, Gregory W.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Shanechi, Maryam M.; Hu, Rollin C.; Brown, Emery N.; Williams, Ziv M.] Harvard Univ, Sch Med, Boston, MA USA. [Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Harvard MIT Hlth Sci & Technol Program, Cambridge, MA 02139 USA. RP Williams, ZM (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. EM zwilliams@partners.org FU Neuroscience Research and Education Foundation; US National Institutes of Health (NIH) [DP1 OD003646]; NIH [5R01-HD059852]; Whitehall Foundation FX R.C.H. is funded by the Neuroscience Research and Education Foundation, E.N.B. is funded by US National Institutes of Health (NIH) DP1 OD003646, and Z.M.W. is funded by NIH 5R01-HD059852, a Presidential Early Career Award for Scientists and Engineers and the Whitehall Foundation. NR 53 TC 26 Z9 26 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2012 VL 15 IS 12 BP 1715 EP + DI 10.1038/nn.3250 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 045OR UT WOS:000311706700018 PM 23143511 ER PT J AU Mitin, T Efstathiou, JA Shipley, WU AF Mitin, Timur Efstathiou, Jason A. Shipley, William U. TI UROLOGICAL CANCER The benefits of intermittent androgen-deprivation therapy SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID ADVANCED PROSTATE-CANCER; SUPPRESSION; RADIATION C1 [Mitin, Timur; Efstathiou, Jason A.; Shipley, William U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Shipley, WU (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM wshipley@partners.org NR 10 TC 2 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD DEC PY 2012 VL 9 IS 12 BP 672 EP 673 DI 10.1038/nrclinonc.2012.201 PG 2 WC Oncology SC Oncology GA 047GW UT WOS:000311828200002 PM 23165125 ER PT J AU Nathan, DM AF Nathan, David M. TI DIABETES Long-acting insulin analogues-are benefits worth the cost? SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Editorial Material ID TYPE-1; THERAPY; ASPART; TRIAL C1 [Nathan, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA 02114 USA. [Nathan, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Nathan, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, 50 Staniford St,Suite 340, Boston, MA 02114 USA. EM dnathan@partners.org NR 10 TC 2 Z9 2 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD DEC PY 2012 VL 8 IS 12 BP 699 EP 700 DI 10.1038/nrendo.2012.208 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 042RG UT WOS:000311488100001 PM 23147577 ER PT J AU Coron, E Auksorius, E Pieretti, A Mahe, MM Liu, L Steiger, C Bromberg, Y Bouma, B Tearney, G Neunlist, M Goldstein, AM AF Coron, E. Auksorius, E. Pieretti, A. Mahe, M. M. Liu, L. Steiger, C. Bromberg, Y. Bouma, B. Tearney, G. Neunlist, M. Goldstein, A. M. TI Full-field optical coherence microscopy is a novel technique for imaging enteric ganglia in the gastrointestinal tract SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE enteric nervous system; enteric neuropathies; Hirschsprung's disease; optical coherence microscopy; optical coherence tomography ID INTERNATIONAL WORKING GROUP; NERVOUS-SYSTEM; HIRSCHSPRUNG-DISEASE; THICKNESS RESECTION; MYENTERIC PLEXUS; HUMAN COLON; IN-VIVO; TOMOGRAPHY; BIOPSIES; BEHALF AB Background Noninvasive methods are needed to improve the diagnosis of enteric neuropathies. Full-field optical coherence microscopy (FFOCM) is a novel optical microscopy modality that can acquire 1 mu m resolution images of tissue. The objective of this research was to demonstrate FFOCM imaging for the characterization of the enteric nervous system (ENS). Methods Normal mice and EdnrB-/- mice, a model of Hirschsprungs disease (HD), were imaged in three-dimensions ex vivo using FFOCM through the entire thickness and length of the gut. Quantitative analysis of myenteric ganglia was performed on FFOCM images obtained from whole-mount tissues and compared with immunohistochemistry imaged by confocal microscopy. Key Results Full-field optical coherence microscopy enabled visualization of the full thickness gut wall from serosa to mucosa. Images of the myenteric plexus were successfully acquired from the stomach, duodenum, colon, and rectum. Quantification of ganglionic neuronal counts on FFOCM images revealed strong interobserver agreement and identical values to those obtained by immunofluorescence microscopy. In EdnrB-/- mice, FFOCM analysis revealed a significant decrease in ganglia density along the colorectum and a significantly lower density of ganglia in all colorectal segments compared with normal mice. Conclusions & Inferences Full-field optical coherence microscopy enables optical microscopic imaging of the ENS within the bowel wall along the entire intestine. FFOCM is able to differentiate ganglionic from aganglionic colon in a mouse model of HD, and can provide quantitative assessment of ganglionic density. With further refinements that enable bowel wall imaging in vivo, this technology has the potential to revolutionize the characterization of the ENS and the diagnosis of enteric neuropathies. C1 [Pieretti, A.; Steiger, C.; Goldstein, A. M.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Coron, E.; Auksorius, E.; Liu, L.; Bromberg, Y.; Bouma, B.; Tearney, G.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Coron, E.; Auksorius, E.; Pieretti, A.; Liu, L.; Steiger, C.; Bromberg, Y.; Bouma, B.; Tearney, G.; Goldstein, A. M.] Harvard Univ, Sch Med, Boston, MA USA. [Coron, E.; Mahe, M. M.; Neunlist, M.] INSERM, UMR 913, Nantes, France. [Coron, E.; Mahe, M. M.; Neunlist, M.] Univ Hosp Nantes, Inst Digest Dis, Nantes, France. [Coron, E.; Mahe, M. M.; Neunlist, M.] Univ Nantes, Fac Med, Nantes, France. [Bouma, B.; Tearney, G.] Harvard Div Hlth Sci & Technol, Boston, MA USA. [Tearney, G.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Goldstein, AM (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, Warren 1153, Boston, MA 02114 USA. EM agoldstein@partners.org RI Auksorius, Egidijus/H-3324-2012; Neunlist, Michel/K-2388-2015; Bromberg, Yaron/F-6570-2010; Coron, Emmanuel/K-2415-2015 OI Bromberg, Yaron/0000-0003-2565-7394; FU NIH [R01HL076398, R01HL093717, R01CA103769, R01DK091923]; University Hospital of Nantes; SanTdige Foundation; Nantes Metropole; [R01DK080914] FX This work was supported by NIH R01HL076398, R01HL093717, R01CA103769, and R01DK091923 to GT. EC was supported by the University Hospital of Nantes and by a grant from the SanTdige Foundation. MM was supported by a grant from Nantes Metropole. AMG was supported by R01DK080914. NR 42 TC 6 Z9 6 U1 2 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD DEC PY 2012 VL 24 IS 12 BP e611 EP e621 DI 10.1111/nmo.12035 PG 11 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 043RS UT WOS:000311565300005 PM 23106847 ER PT J AU Koerte, IK Kaufmann, D Hartl, E Bouix, S Pasternak, O Kubicki, M Rauscher, A Li, DKB Dadachanji, SB Taunton, JA Forwell, LA Johnson, AM Echlin, PS Shenton, ME AF Koerte, Inga K. Kaufmann, David Hartl, Elisabeth Bouix, Sylvain Pasternak, Ofer Kubicki, Marek Rauscher, Alexander Li, David K. B. Dadachanji, Shiroy B. Taunton, Jack A. Forwell, Lorie A. Johnson, Andrew M. Echlin, Paul S. Shenton, Martha E. TI A prospective study of physician-observed concussion during a varsity university hockey season: white matter integrity in ice hockey players. Part 3 of 4 SO NEUROSURGICAL FOCUS LA English DT Article DE ice hockey; mild traumatic brain injury; axial diffusivity; diffusion tensor imaging; sports-related concussion; radial diffusivity; fractional anisotropy; Canada ID TRAUMATIC BRAIN-INJURY; PROFESSIONAL FOOTBALL PLAYERS; DIFFUSE AXONAL INJURY; RECURRENT CONCUSSION; SPORTS CONCUSSION; LONG-TERM; CORPUS-CALLOSUM; NCAA CONCUSSION; RUGBY UNION; HEAD-INJURY AB Object. The aim of this study was to investigate the effect of repetitive head impacts on white matter integrity that were sustained during 1 Canadian Interuniversity Sports (CIS) ice hockey season, using advanced diffusion tensor imaging (DTI). Methods. Twenty-five male ice hockey players between 20 and 26 years of age (mean age 22.24 +/- 1.59 years) participated in this study. Participants underwent pre- and postseason 3-T MRI, including DTI. Group analyses were performed using paired-group tract-based spatial statistics to test for differences between preseason and postseason changes. Results. Tract-based spatial statistics revealed an increase in trace, radial diffusivity (RD), and axial diffusivity (AD) over the course of 1 season. Compared with preseason data, postseason images showed higher trace, AD, and RD values in the right precentral region, the right corona radiata, and the anterior and posterior limb of the internal capsule. These regions involve parts of the corticospinal tract, the corpus callosum, and the superior longitudinal fasciculus. No significant differences were observed between preseason and postseason for fractional anisotropy. Conclusions. Diffusion tensor imaging revealed changes in white matter diffusivity in male ice hockey players over the course of 1 season. The origin of these findings needs to be elucidated. (http://thejns.org/doi/abs/10.3171/2012.10.FOCUS12303) C1 [Echlin, Paul S.] Elliott Sports Med Clin, Burlington, ON L7N 2G3, Canada. [Koerte, Inga K.; Kaufmann, David; Hartl, Elisabeth; Bouix, Sylvain; Pasternak, Ofer; Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Koerte, Inga K.; Kaufmann, David] Univ Munich, Inst Clin Radiol, Munich, Germany. [Rauscher, Alexander; Li, David K. B.] Univ British Columbia, Dept Radiol, Vancouver, BC, Canada. [Dadachanji, Shiroy B.; Taunton, Jack A.] Univ British Columbia, Dept Med, Div Sports Med, Vancouver, BC, Canada. [Forwell, Lorie A.] Univ Western Ontario, Fowler Kennedy Sport Med Clin, London, ON, Canada. [Forwell, Lorie A.; Johnson, Andrew M.] Univ Western Ontario, Fac Hlth Sci, London, ON, Canada. [Shenton, Martha E.] VA Boston Healthcare Syst, Dept Psychiat, Neurosci Lab, Clin Neurosci Div, Brockton, MA USA. RP Echlin, PS (reprint author), Elliott Sports Med Clin, 1100 Walkers Line,Suite 2, Burlington, ON L7N 2G3, Canada. EM psechlin@gmail.com OI Bouix, Sylvain/0000-0003-1326-6054; Rauscher, Alexander/0000-0002-1961-8252; Johnson, Andrew/0000-0002-7269-3016 NR 63 TC 18 Z9 18 U1 1 U2 16 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD DEC PY 2012 VL 33 IS 6 AR E3 DI 10.3171/2012.10.FOCUS12303 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 048GI UT WOS:000311898500004 ER PT J AU Bergmark, B Bergmark, R De Beaudrap, P Boum, Y Mwanga-Amumpaire, J Carroll, R Zapol, W AF Bergmark, Brian Bergmark, Regan De Beaudrap, Pierre Boum, Yap Mwanga-Amumpaire, Juliet Carroll, Ryan Zapol, Warren TI Inhaled Nitric Oxide and Cerebral Malaria: Basis of a Strategy for Buying Time for Pharmacotherapy SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE inhaled nitric oxide; cerebral malaria; nitric oxide synthase; Plasmodium falciparum ID PLASMODIUM-FALCIPARUM MALARIA; PROMOTER POLYMORPHISM; TANZANIAN CHILDREN; GHANAIAN CHILDREN; AFRICAN CHILDREN; INTERFERON-GAMMA; INDIAN ADULTS; TNF-ALPHA; SYNTHASE; PLASMA AB There are approximately 225-600 million new malaria infections worldwide annually, with severe and cerebral malaria representing major causes of death internationally. The role of nitric oxide (NO) in the host response in cerebral malaria continues to be elucidated, with numerous known functions relating to the cytokine, endovascular and cellular responses to infection with Plasmodium falciparum. Evidence from diverse modes of inquiry suggests NO to be critical in modulating the immune response and promoting survival in patients with cerebral malaria. This line of investigation has culminated in the approval of 2 phase II randomized prospective clinical trials in Uganda studying the use of inhaled NO as adjuvant therapy in children with severe malaria. The strategy underlying both trials is to use the sytemic antiinflammatory properties of inhaled NO to "buy time" for chemical antiparasite therapy to lower the parasite load. This article reviews the nexus of malaria and NO biology with a primary focus on cerebral malaria in humans. C1 [Bergmark, Brian] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Bergmark, Regan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [De Beaudrap, Pierre] Inst Rech Dev, Marseilles, France. [Mwanga-Amumpaire, Juliet] Mbarara Univ, Mbarara, Uganda. [Carroll, Ryan; Zapol, Warren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. RP Bergmark, B (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM bbergmark@partners.org NR 59 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD DEC PY 2012 VL 31 IS 12 BP E250 EP E254 DI 10.1097/INF.0b013e318266c113 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 046WC UT WOS:000311794100004 PM 22760538 ER PT J AU Del Vecchio, DA AF Del Vecchio, Daniel A. TI "SIEF"-Simultaneous Implant Exchange with Fat: A New Option in Revision Breast Implant Surgery SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID PRE-EXPANSION; TRANSPLANTATION; RECONSTRUCTION AB A technique of implant exchange is reported using recipient-site preexpansion followed by autologous fat transplantation to the breast in 12 consecutive patients with breast implants who desired implant removal. Recipient-site preexpansion, used 2 weeks before fat grafting, may have both practical and theoretical benefits in increasing the breast subcutaneous space and stimulating the recipient-site microcellular environment overlying the prosthetic implant, allowing the subcutaneous insertion of a sufficient core volume of donor graft at the time of prosthetic explantation. In the cases described, the postexplantation breast volume at 9 months to 1 year postoperatively by quantitative three-dimensional imaging was equal to or greater than the preexplantation composite volume of breast and implant. Preexpansion before implant exchange with fat affords amore abundant space, completely independent from the subglandular or submuscular planes. In this new space, the "third space" of the breast, it is possible to technically place graft into the breast subcutaneous tissue and alleviate breast asymmetry resulting from pocket distortions caused by capsular contracture or by implant pocket drift. Observing breast augmentation with implants and with fat grafting in the same patient affords a unique opportunity to analyze some of the key differences between the two techniques. Recipient-site preexpansion and simultaneous implant exchange with fat (SIEF) should be added to the list of applications where fat grafting to the breasts may have early clinical utility and portends the use of fat used in conjunction with breast implants to achieve better patient outcomes. (Plast. Reconstr. Surg. 130: 1187, 2012.) C1 [Del Vecchio, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. RP Del Vecchio, DA (reprint author), Back Bay Plast Surg, 38 Newbury St, Boston, MA 02116 USA. EM dandelvecchio@aol.com NR 13 TC 14 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD DEC PY 2012 VL 130 IS 6 BP 1187 EP 1196 DI 10.1097/PRS.0b013e31826d9c3c PG 10 WC Surgery SC Surgery GA 047IY UT WOS:000311834800041 PM 23190803 ER PT J AU Upadhyay, GA Mela, T Singh, JP AF Upadhyay, Gaurav A. Mela, Theofanie Singh, Jagmeet P. TI The burden of inappropriate shocks in young people and how to avoid them SO POSTGRADUATE MEDICAL JOURNAL LA English DT Editorial Material ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; RAPID VENTRICULAR-TACHYCARDIA; PROGNOSTIC IMPORTANCE; ATRIAL-FIBRILLATION; PRIMARY PREVENTION; HEART-FAILURE; ICD; TRIAL; THERAPY; MORTALITY C1 [Upadhyay, Gaurav A.] Harvard Univ, Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv,Med Sch, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv,Med Sch, Gray Bldg 109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org NR 21 TC 0 Z9 0 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0032-5473 J9 POSTGRAD MED J JI Postgrad. Med. J. PD DEC PY 2012 VL 88 IS 1046 BP 719 EP 728 DI 10.1136/postgradmedj-2012-301861rep PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 042RF UT WOS:000311488000009 ER PT J AU Huddle, TS Bailey, FA AF Huddle, Thomas S. Bailey, F. Amos TI Pacemaker deactivation: withdrawal of support or active ending of life? SO THEORETICAL MEDICINE AND BIOETHICS LA English DT Article DE Pacemaker deactivation; Withdrawal of support; End of life care; Medical ethics; Physician assisted suicide ID INTENSIVE-CARE; PERSPECTIVES AB In spite of ethical analyses assimilating the palliative deactivation of pacemakers to commonly accepted withdrawings of life-sustaining therapy, many clinicians remain ethically uncomfortable with pacemaker deactivation at the end of life. Various reasons have been posited for this discomfort. Some cardiologists have suggested that reluctance to deactivate pacemakers may stem from a sense that the pacemaker has become part of the patient's "self." The authors suggest that Daniel Sulmasy is correct to contend that any such identification of the pacemaker is misguided. The authors argue that clinicians uncomfortable with pacemaker deactivation are nevertheless correct to see it as incompatible with the traditional medical ethics of withdrawal of support. Traditional medical ethics is presently taken by many to sanction pacemaker deactivation when such deactivation honors the patient's right to refuse treatment. The authors suggest that the right to refuse treatment applies to treatments involving ongoing physician agency. This right cannot underwrite patient demands that physicians reverse the effects of treatments previously administered, in which ongoing physician agency is no longer implicated. The permanently indwelling pacemaker is best seen as such a treatment. As such, its deactivation in the pacemaker-dependent patient is best seen not as withdrawal of support but as active ending of life. That being the case, clinicians adhering to the usual ethical analysis of withdrawal of support are correct to be uncomfortable with pacemaker deactivation at the end of life. C1 [Huddle, Thomas S.] UAB, Div Gen Internal Med, Sch Med, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Bailey, F. Amos] VA Med Ctr, Birmingham, AL 35233 USA. RP Huddle, TS (reprint author), UAB, Div Gen Internal Med, Sch Med, Birmingham VA Med Ctr, FOT 744,1530 3rd Ave S, Birmingham, AL 35294 USA. EM thuddle@uab.edu NR 20 TC 9 Z9 9 U1 1 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1386-7415 J9 THEOR MED BIOETH JI Theor. Med. Bioeth. PD DEC PY 2012 VL 33 IS 6 BP 421 EP 433 DI 10.1007/s11017-012-9213-5 PG 13 WC Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Social Issues; Biomedical Social Sciences GA 045ED UT WOS:000311676900003 PM 22351107 ER PT J AU Nehra, D Le, HD Fallon, EM Carlson, SJ Woods, D White, YA Pan, AH Guo, LK Rodig, SJ Tilly, JL Rueda, BR Puder, M AF Nehra, Deepika Le, Hau D. Fallon, Erica M. Carlson, Sarah J. Woods, Dori White, Yvonne A. Pan, Amy H. Guo, Lankai Rodig, Scott J. Tilly, Jonathan L. Rueda, Bo R. Puder, Mark TI Prolonging the female reproductive lifespan and improving egg quality with dietary omega-3 fatty acids SO AGING CELL LA English DT Article DE advanced maternal age; docosahexaenoic acid; menopause; omega-3 fatty acid; oocyte; reproduction ID ADVANCED CHRONOLOGICAL AGE; ESSENTIAL FATTY-ACIDS; EVOLUTIONARY ASPECTS; MATERNAL AGE; DOCOSAHEXAENOIC ACID; IN-VITRO; OVARIAN; MICE; RATIO; OOCYTES AB Women approaching advanced maternal age have extremely poor outcomes with both natural and assisted fertility. Moreover, the incidence of chromosomal abnormalities and birth defects increases with age. As of yet, there is no effective and practical strategy for delaying ovarian aging or improving oocyte quality. We demonstrate that the lifelong consumption of a diet rich in omega-3 fatty acids prolongs murine reproductive function into advanced maternal age, while a diet rich in omega-6 fatty acids is associated with very poor reproductive success at advanced maternal age. Furthermore, even short-term dietary treatment with a diet rich in omega-3 fatty acids initiated at the time of the normal age-related rapid decline in murine reproductive function is associated with improved oocyte quality, while short-term dietary treatment with omega-6 fatty acids results in very poor oocyte quality. Thus, omega-3 fatty acids may provide an effective and practical avenue for delaying ovarian aging and improving oocyte quality at advanced maternal age. C1 [Nehra, Deepika; Le, Hau D.; Fallon, Erica M.; Carlson, Sarah J.; Pan, Amy H.; Puder, Mark] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Nehra, Deepika; Le, Hau D.; Fallon, Erica M.; Carlson, Sarah J.; Pan, Amy H.; Puder, Mark] Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Nehra, Deepika; Le, Hau D.; Fallon, Erica M.; Carlson, Sarah J.; Puder, Mark] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Woods, Dori; White, Yvonne A.; Guo, Lankai; Tilly, Jonathan L.; Rueda, Bo R.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Woods, Dori; White, Yvonne A.; Tilly, Jonathan L.; Rueda, Bo R.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Puder, M (reprint author), 300 Longwood Ave,Fegan 3, Boston, MA 02115 USA. EM mark.puder@childrens.harvard.edu FU Children's Hospital Boston Surgical Research Foundation; Children's Hospital Boston Vascular Biology Program Research Funds; Massachusetts General Hospital Vincent Memorial Research Funds; Joshua Ryan Rappaport Fellowship; [T32DK007754-13] FX This research was supported by the Children's Hospital Boston Surgical Research Foundation, the Children's Hospital Boston Vascular Biology Program Research Funds and the Massachusetts General Hospital Vincent Memorial Research Funds. D. N. was supported by grant T32DK007754-13, H. D. L. and E. M. F. were supported by the Joshua Ryan Rappaport Fellowship. NR 43 TC 21 Z9 21 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD DEC PY 2012 VL 11 IS 6 BP 1046 EP 1054 DI 10.1111/acel.12006 PG 9 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 037NP UT WOS:000311113500014 PM 22978268 ER PT J AU Sataranatarajan, K Feliers, D Mariappan, MM Lee, HJ Lee, MJ Day, RT Yalamanchili, HB Choudhury, GG Barnes, JL Van Remmen, H Richardson, A Kasinath, BS AF Sataranatarajan, Kavithalakshmi Feliers, Denis Mariappan, Meenalakshmi M. Lee, Hak Joo Lee, Myung Ja Day, Robert T. Yalamanchili, Hima Bindu Choudhury, Goutam G. Barnes, Jeffrey L. Van Remmen, Holly Richardson, Arlan Kasinath, Balakuntalam S. TI Molecular events in matrix protein metabolism in the aging kidney SO AGING CELL LA English DT Article DE albuminuria; collagen; fibrosis; microRNAs; SMAD3; TGF beta ID MESSENGER-RNA TRANSLATION; RENAL EPITHELIAL-CELLS; HIGH GLUCOSE; DIABETIC-NEPHROPATHY; EXTRACELLULAR-MATRIX; GENE-TRANSFER; FIBROSIS; EXPRESSION; GLOMERULI; KINASE AB We explored molecular events associated with aging-induced matrix changes in the kidney. C57BL6 mice were studied in youth, middle age, and old age. Albuminuria and serum cystatin C level (an index of glomerular filtration) increased with aging. Renal hypertrophy was evident in middle-aged and old mice and was associated with glomerulomegaly and increase in mesangial fraction occupied by extracellular matrix. Content of collagen types I and III and fibronectin was increased with aging; increment in their mRNA varied with the phase of aging. The content of ZEB1 and ZEB2, collagen type I transcription inhibitors, and their binding to the collagen type Ia2 promoter by ChIP assay also showed age-phase-specific changes. Lack of increase in mRNA and data from polysome assay suggested decreased degradation as a potential mechanism for kidney collagen type I accumulation in the middle-aged mice. These changes occurred with increment in TGF beta mRNA and protein and activation of its SMAD3 pathway; SMAD3 binding to the collagen type Ia2 promoter was also increased. TGF beta-regulated microRNAs (miRs) exhibited selective regulation. The renal cortical content of miR-21 and miR-200c, but not miR-192, miR-200a, or miR-200b, was increased with aging. Increased miR-21 and miR-200c contents were associated with reduced expression of their targets, Sprouty-1 and ZEB2, respectively. These data show that aging is associated with complex molecular events in the kidney that are already evident in the middle age and progress to old age. Age-phase-specific regulation of matrix protein synthesis occurs and involves matrix proteinspecific transcriptional and post-transcriptional mechanisms. C1 [Sataranatarajan, Kavithalakshmi; Feliers, Denis; Mariappan, Meenalakshmi M.; Lee, Hak Joo; Lee, Myung Ja; Day, Robert T.; Yalamanchili, Hima Bindu; Choudhury, Goutam G.; Barnes, Jeffrey L.; Van Remmen, Holly; Richardson, Arlan; Kasinath, Balakuntalam S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Sataranatarajan, Kavithalakshmi; Van Remmen, Holly; Richardson, Arlan; Kasinath, Balakuntalam S.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Mariappan, Meenalakshmi M.; Lee, Hak Joo; Choudhury, Goutam G.; Barnes, Jeffrey L.; Kasinath, Balakuntalam S.] S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. [Choudhury, Goutam G.; Van Remmen, Holly; Richardson, Arlan] Audie L Murphy Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. RP Kasinath, BS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, MC7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kasinath@uthscsa.edu FU NIH [RC2AG036613, DK077295, DK050190]; VA Research Service; Juvenile Diabetes Research Foundation; VA FX This study was supported in whole or in part by grants from the NIH RC2AG036613 (BSK, HVR, AR), DK077295 (BSK), DK050190 (GGC), and the VA Research Service (BSK, GGC, JLB) and the Juvenile Diabetes Research Foundation (DF, GGC). GGC is a recipient of Senior Research Career Scientist Award from the VA. We thank Ms. Vivian Diaz for assistance with the animal experiments. NR 45 TC 15 Z9 15 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD DEC PY 2012 VL 11 IS 6 BP 1065 EP 1073 DI 10.1111/acel.12008 PG 9 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 037NP UT WOS:000311113500016 PM 23020145 ER PT J AU Feres, F Costa, RA Bhatt, DL Leon, MB Botelho, RV King, SB de Paula, JET Mangione, JA Salvadori, D Gusmao, MO Castello, H Nicolela, E Perin, MA Devito, FS Marin-Neto, JA Abizaid, A AF Feres, Fausto Costa, Ricardo A. Bhatt, Deepak L. Leon, Martin B. Botelho, Roberto V. King, Spencer B., III de Paula, J. Eduardo T. Mangione, Jose A. Salvadori, Decio, Jr. Gusmao, Marcos O. Castello, Helio, Jr. Nicolela, Eduardo, Jr. Perin, Marco A. Devito, Fernando S. Antonio Marin-Neto, J. Abizaid, Alexandre TI Optimized Duration of Clopidogrel Therapy Following Treatment with the Endeavor Zotarolimus-Eluting Stent in Real-World Clinical Practice (OPTIMIZE) Trial: Rationale and design of a large-scale, randomized, multicenter study SO AMERICAN HEART JOURNAL LA English DT Article ID DUAL-ANTIPLATELET THERAPY; PERCUTANEOUS CORONARY INTERVENTION; INTRAVASCULAR ULTRASOUND FINDINGS; OPTICAL COHERENCE TOMOGRAPHY; BARE-METAL; ARTERY-DISEASE; DOUBLE-BLIND; PREMATURE DISCONTINUATION; VASCULAR-RESPONSE; LATE THROMBOSIS AB Background Current recommendations for antithrombotic therapy after drug-eluting stent (DES) implantation include prolonged dual antiplatelet therapy (DAPT) with aspirin and clopidogrel >= 12 months. However, the impact of such a regimen for all patients receiving any DES system remains unclear based on scientific evidence available to date. Also, several other shortcomings have been identified with prolonged DAPT, including bleeding complications, compliance, and cost. The second-generation Endeavor zotarolimus-eluting stent (E-ZES) has demonstrated efficacy and safety, despite short duration DAPT (3 months) in the majority of studies. Still, the safety and clinical impact of short-term DAPT with E-ZES in the real world is yet to be determined. Methods The OPTIMIZE trial is a large, prospective, multicenter, randomized (1: 1) non-inferiority clinical evaluation of short-term (3 months) vs long-term (12-months) DAPT in patients undergoing E-ZES implantation in daily clinical practice. Overall, 3,120 patients were enrolled at 33 clinical sites in Brazil. The primary composite endpoint is death (any cause), myocardial infarction, cerebral vascular accident, and major bleeding at 12-month clinical follow-up post-index procedure. Conclusions The OPTIMIZE clinical trial will determine the clinical implications of DAPT duration with the second generation E-ZES in real-world patients undergoing percutaneous coronary intervention. (Am Heart J 2012;164:810-816.e3.) C1 [Feres, Fausto; Costa, Ricardo A.; Abizaid, Alexandre] Inst Dante Pazzanese Cardiol, BR-04012180 Sao Paulo, Brazil. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Leon, Martin B.] Columbia Univ, Med Ctr, Cardiovasc Res Fdn, Ctr Intervent Vasc Therapy, New York, NY USA. [Botelho, Roberto V.] Inst Coracao Triangulo, Uberlandia, MG, Brazil. [King, Spencer B., III] St Josephs Med Grp, Atlanta, GA USA. [de Paula, J. Eduardo T.] Unicor Linhares, Linhares, ES, Brazil. [Mangione, Jose A.; Salvadori, Decio, Jr.] Real & Benemerita Soc Portuguesa Beneficencia, Sao Paulo, Brazil. [Gusmao, Marcos O.] Hosp Agamenon Magalhaes, Recife, PE, Brazil. [Castello, Helio, Jr.] Hosp Bandeirantes, Sao Paulo, Brazil. [Nicolela, Eduardo, Jr.] Emcor Emergencias Coracao, Piracicaba, SP, Brazil. [Perin, Marco A.] Hosp Santa Marcelina, Sao Paulo, Brazil. [Devito, Fernando S.] Cardiol Catanduva, Catanduva, SP, Brazil. [Antonio Marin-Neto, J.] Univ Sao Paulo, Hosp Clin, BR-14049 Ribeirao Preto, SP, Brazil. RP Feres, F (reprint author), Inst Dante Pazzanese Cardiol, Av Dante Pazzanense,500 Ibirapuera, BR-04012180 Sao Paulo, Brazil. EM fferes@lee.dante.br RI Perin, Marco/O-2309-2014 NR 56 TC 12 Z9 14 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2012 VL 164 IS 6 BP 810 EP + DI 10.1016/j.ahj.2012.09.009 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 044PU UT WOS:000311634500007 PM 23194480 ER PT J AU Steg, PG Mehta, SR Pollack, CV Bode, C Gaudin, C Fanouillere, K Moryusef, A Wiviott, SD Sabatine, MS AF Steg, Philippe Gabriel Mehta, Shamir R. Pollack, Charles V., Jr. Bode, Christoph Gaudin, Christophe Fanouillere, Karen Moryusef, Angele Wiviott, Stephen D. Sabatine, Marc S. TI Design and rationale of the Treatment of Acute Coronary Syndromes with Otamixaban trial: A double-blind triple-dummy 2-stage randomized trial comparing otamixaban to unfractionated heparin and eptifibatide in non-ST-segment elevation acute coronary syndromes with a planned early invasive strategy SO AMERICAN HEART JOURNAL LA English DT Article ID FACTOR XA INHIBITOR; MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; INTERVENTION; CLOPIDOGREL; BIVALIRUDIN; ENOXAPARIN; FXV673; SAFETY; THROMBOLYSIS AB Background Otamixaban is a synthetic intravenous direct factor Xa inhibitor, with rapid onset/offset, linear kinetics, and no significant renal elimination. A phase II trial in acute coronary syndromes (ACS) showed a marked reduction in the combined end point of death or myocardial infarction (MI) and similar bleeding rates with otamixaban at midrange doses, compared with unfractionated heparin (UFH) and eptifibatide. Design The TAO trial is a phase III, randomized, double-blind, triple-dummy controlled trial testing the efficacy of otamixaban over UFH plus eptifibatide in patients with non-ST-segment elevation ACS to be treated with dual oral antiplatelet therapy and an invasive strategy. Approximately 13,220 patients in 55 countries will be randomized (1: 1: 1 ratio) to receive UFH plus downstream eptifibatide (started pre-percutaneous coronary intervention and continued per label) or otamixaban (0.08 mg/kg intravenous bolus at randomization then 0.100 or 0.140 mg/kg per hour intravenous infusion). An interim analysis was performed after >= 1,969 patients per arm completed 7 days of follow-up and the Data Monitoring Committee selected 1 otamixaban dose (blinded to investigators) to be carried forward using a prespecified algorithm. The primary efficacy outcome is the composite of all-cause mortality or new MI through day 7. The primary safety outcome is thrombolysis in MI major or minor bleeding through day 7. Secondary outcomes include all-cause mortality, recurrent ischemia/infarction resulting in prolonged/recurrent hospitalization, periprocedural angiographic complications, and pharmacokinetic data in 6,000 patients. Conclusions The TAO trial will assess the clinical efficacy and safety of otamixaban in non-ST-segment elevation ACS with planned invasive strategy. (Am Heart J 2012;164:817-824.e13.) C1 [Steg, Philippe Gabriel] Hop Bichat Claude Bernard, AP HP, F-75018 Paris, France. [Steg, Philippe Gabriel] INSERM, U698, Paris, France. [Steg, Philippe Gabriel] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. [Mehta, Shamir R.] McMaster Univ, Hamilton, ON, Canada. [Mehta, Shamir R.] Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada. [Pollack, Charles V., Jr.] Penn Hosp, Dept Emergency Med, Philadelphia, PA 19107 USA. [Bode, Christoph] Med Univ Klin, Freiburg, Germany. [Gaudin, Christophe; Fanouillere, Karen] Sanofi R& D, Paris, France. [Moryusef, Angele] Sanofi, Bridgewater, NJ USA. [Wiviott, Stephen D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Div,TIMI Study Grp, Boston, MA USA. RP Steg, PG (reprint author), Hop Bichat Claude Bernard, AP HP, 46 Rue Henri Huchard, F-75018 Paris, France. EM gabriel.steg@bch.aphp.fr FU NYU School of Medicine; Sanofi; Servier; Actavis; Astellas; Bayer; GlaxoSmithKline; Lilly; Medtronic; Merck; AstraZeneca; Eli Lilly; Daiichi Sankyo; Brigham and Women's Hospital from Amgen; Bristol-Myers Squibb/Sanofi Joint Venture FX Ph.G. Steg: Research grant (to INSERM U-698) from NYU School of Medicine, Sanofi, Servier; consulting/speaking for Ablynx, Amarin, Amgen, Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers-Squibb, Daiichi Sankyo, Eisai, GlaxoSmithKline, Lilly, Medtronic, MSD, Novartis, Otsuka, Pfizer, Roche, Sanofi, Servier, The Medicines Company, Vivus; equity ownership in Aterovax. S. R. Mehta: Consultant for AstraZeneca, BMS, Eli Lilly, Sanofi. C. V. Pollack Jr: Consultant for Sanofi, Daiichi Sankyo, Janssen. C. Bode: Advisor/consultant for AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Sanofi; speaker for AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Lilly, Novartis, Pfizer, Sanofi; research grants from Actavis, Astellas, Bayer, GlaxoSmithKline, Lilly, Medtronic, Merck, Sanofi. C. Gaudin, A. Moryusef and K. Fanouillere are employees of Sanofi. S. D. Wiviott: Research funding from AstraZeneca, Eli Lilly, Daiichi Sankyo, Merck; Consultant/CME activities honoraria from Arena Pharmaceuticals, AstraZeneca, Bayer, Daiichi Sankyo, Eli Lilly, Johnson and Johnson, Merck. M. S. Sabatine: Research grant through Brigham and Women's Hospital from Amgen, AstraZeneca, Bristol-Myers Squibb/Sanofi Joint Venture, Daiichi Sankyo, Merck; consultant for Bristol-Myers-Squibb/Sanofi Joint Venture, GlaxoSmithKline, Merck, Pfizer, Sanofi. NR 38 TC 6 Z9 6 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2012 VL 164 IS 6 BP 817 EP + DI 10.1016/j.ahj.2012.10.001 PG 21 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 044PU UT WOS:000311634500008 PM 23194481 ER PT J AU Shah, RV McNulty, S O'Connor, CM Felker, GM Braunwald, E Givertz, MM AF Shah, Ravi V. McNulty, Steven O'Connor, Christopher M. Felker, G. Michael Braunwald, Eugene Givertz, Michael M. TI Effect of admission oral diuretic dose on response to continuous versus bolus intravenous diuretics in acute heart failure: An analysis from Diuretic Optimization Strategies in Acute Heart Failure SO AMERICAN HEART JOURNAL LA English DT Article ID BLOOD UREA NITROGEN; ASSOCIATION; TOLVAPTAN; MORTALITY AB Background Results from the DOSE-AHF study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in acute heart failure. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. Methods The DOSE-AHF study randomized 308 patients within 24 hours of admission to high versus low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs continuous) and outcomes in patients receiving high-dose (>= 120 mg furosemide equivalent, n = 177) versus low-dose (<120 mg furosemide equivalent, n = 131) outpatient diuretics. Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P = .01) and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P = .01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted hazard ratio 1.08 per 20-mg increment in dose, 95% CI 1.01-1.16, P = .03). Conclusions In acute heart failure, patients on higher diuretic doses have greater disease severity and may benefit from an initial bolus strategy. (Am Heart J 2012;164:862-8.) C1 [Braunwald, Eugene; Givertz, Michael M.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Shah, Ravi V.] Massachusetts Gen Hosp, Div Cardiovasc, Boston, MA 02114 USA. [McNulty, Steven] Duke Clin Res Inst, Durham, NC USA. [O'Connor, Christopher M.; Felker, G. Michael] Duke Univ, Sch Med, Duke Heart Ctr, Durham, NC USA. [Shah, Ravi V.; Braunwald, Eugene; Givertz, Michael M.] Harvard Univ, Sch Med, Boston, MA USA. RP Givertz, MM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM mgivertz@partners.org FU NHLBI NIH HHS [U10 HL110337] NR 19 TC 17 Z9 18 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2012 VL 164 IS 6 BP 862 EP 868 DI 10.1016/j.ahj.2012.08.019 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 044PU UT WOS:000311634500013 PM 23194486 ER PT J AU Mentz, RJ Chung, MJ Gheorghiade, M Pang, PS Kwasny, MJ Ambrosy, AP Vaduganathan, M O'Connor, CM Swedberg, K Zannad, F Konstam, MA Maggioni, AP AF Mentz, Robert J. Chung, Matthew J. Gheorghiade, Mihai Pang, Peter S. Kwasny, Mary J. Ambrosy, Andrew P. Vaduganathan, Muthiah O'Connor, Christopher M. Swedberg, Karl Zannad, Faiez Konstam, Marvin A. Maggioni, Aldo P. TI Atrial fibrillation or flutter on initial electrocardiogram is associated with worse outcomes in patients admitted for worsening heart failure with reduced ejection fraction: Findings from the EVEREST Trial SO AMERICAN HEART JOURNAL LA English DT Article ID QUALITY-OF-CARE; PROGNOSTIC-SIGNIFICANCE; VENTRICULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; SINUS RHYTHM; RATIONALE; MORTALITY; DISEASE; RISK; EPIDEMIOLOGY AB Background Heart failure (HF) complicated by atrial fibrillation/flutter (AF/AFL) is associated with worse outcomes. However, the clinical profile and outcomes of patients following hospitalization for HF with AF/AFL on initial electrocardiogram (ECG) has not been well studied. Methods EVEREST was a randomized trial of vasopressin-2 receptor blockade, in addition to standard therapy, in 4133 patients hospitalized with HF with ejection fraction <= 40%. A post hoc analysis was performed comparing the clinical characteristics and outcomes [all-cause mortality and cardiovascular mortality/HF hospitalization] of patients with AF/AFL versus sinus rhythm (SR) on baseline ECG, which were centrally analyzed. Times to events were compared using log-rank tests and Cox regression models. Results Of the 4133 patients, 1195 (29%) were classified with AF/AFL and 2071(50%) with SR. The remaining patients (21%) were excluded because ECGs were unavailable (n = 106), rhythm was paced (n = 727), or junctional/other supraventricular (n = 34). AF/AFL patients were older, with increased weight, faster heart rate, higher blood urea nitrogen, and natriuretic peptide levels compared to SR patients. Anticoagulation was prescribed in 67% of AF/AFL patients on discharge. AF/AFL patients were less likely to receive beta-blockers or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (all P < .05). After risk adjustment, AF/AFL was associated with increased mortality (hazard ratio 1.23; 95% CI, 1.04-1.46) and cardiovascular mortality/HF hospitalization (hazard ratio 1.26; 95% CI, 1.07-1.47). Conclusion AF/AFL on initial ECG in patients hospitalized with HF with reduced ejection fraction is associated with lower use of evidence-based therapies and increased mortality and rehospitalization compared to patients in SR. (Am Heart J 2012;164:884-892.e2.) C1 [Mentz, Robert J.; Chung, Matthew J.; O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA. [Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Ambrosy, Andrew P.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Swedberg, Karl] Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden. [Zannad, Faiez] Nancy Univ, Nancy, France. [Konstam, Marvin A.] Tufts Med Ctr, Cardiovasc Ctr, Boston, MA USA. [Maggioni, Aldo P.] Assoc Nazl Medici Cardiol Osped, Res Ctr, Florence, Italy. RP Gheorghiade, M (reprint author), 645 N Michigan Ave, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu OI Maggioni, Aldo Pietro/0000-0003-2764-6779 FU Abbott; Merck; PDL BioPharma; AstraZeneca; Servier; Amgen; Otsuka; JNJ; Trevena FX MG is a consultant for Abbott Labs, Astellas, AstraZeneca, Bayer Schering PharmaAG, CorThera Inc, Cytokinetics Inc, DebioPharm SA, ErrekappaTerapeutici (Milan, Italy), Glaxo Smith Kline, JNJ, Medtronic, Novartis Pharma AG, Otsuka, Sigma Tau, Solvay Pharmaceuticals, and Pericor Therapeutics. The other authors declare no conflict of interest. PSP has been a consultant for Astellas, Bayer, EKR Therapeutics, JNJ, the Medicines Company, Medtronic, Novartis, Otsuka, Palatin Technologies, PDL BioPharma, Pericor Therapeutics, SigmaTau, Solvay Pharmaceuticals, and Trevena; has received honoraria from Alere, Beckman-Coulter, BiogenIdec, Corthera, Ikaria, Nile Therapeutics, Momentum Research, Overcome; has received research support from Abbott, Merck and PDL BioPharma; and travel support from MyLife. CMO is a consultant for Merck, Trevena, Novella, Pfizer, GE Healthcare, Roche, Amgen, Martek, Actelion, and JNJ. KS receives research grants from AstraZeneca, Servier, and Amgen; honoraria from AstraZeneca, Otsuka, Servier, and Amgen; and is a consultant for Cytokinetics, Servier, and Novartis. FZ has received honoraria from and served on advisory boards for Pfizer. MAK receives research grants from and is a consultant for Otsuka, JNJ, Amgen, and Trevena. APM receives honoraria from Otsuka. NR 32 TC 10 Z9 10 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2012 VL 164 IS 6 BP 884 EP + DI 10.1016/j.ahj.2012.09.011 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 044PU UT WOS:000311634500016 PM 23194489 ER PT J AU Tamez, H Zoccali, C Packham, D Wenger, J Bhan, I Appelbaum, E Pritchett, Y Chang, YC Agarwal, R Wanner, C Lloyd-Jones, D Cannata, J Thompson, BT Andress, D Zhang, WY Singh, B Zehnder, D Pachika, A Manning, WJ Shah, A Solomon, SD Thadhani, R AF Tamez, Hector Zoccali, Carmine Packham, David Wenger, Julia Bhan, Ishir Appelbaum, Evan Pritchett, Yili Chang, Yuchiao Agarwal, Rajiv Wanner, Christoph Lloyd-Jones, Donald Cannata, Jorge Thompson, B. Taylor Andress, Dennis Zhang, Wuyan Singh, Bhupinder Zehnder, Daniel Pachika, Ajay Manning, Warren J. Shah, Amil Solomon, Scott D. Thadhani, Ravi TI Vitamin D reduces left atrial volume in patients with left ventricular hypertrophy and chronic kidney disease SO AMERICAN HEART JOURNAL LA English DT Article ID HEART-FAILURE; NATRIURETIC-PEPTIDE; CARDIAC STRUCTURE; D DEFICIENCY; D-RECEPTOR; 1,25-DIHYDROXYVITAMIN D-3; CARDIOVASCULAR EVENTS; GENE-TRANSCRIPTION; EJECTION FRACTION; DYSFUNCTION AB Background Left atrial enlargement, a sensitive integrator of left ventricular diastolic function, is associated with increased cardiovascular morbidity and mortality. Vitamin D is linked to lower cardiovascular morbidity, possibly modifying cardiac structure and function; however, firm evidence is lacking. We assessed the effect of an activated vitamin D analog on left atrial volume index (LAVi) in a post hoc analysis of the PRIMO trial (clinicaltrials.gov: NCT00497146). Methods and results One hundred ninety-six patients with chronic kidney disease (estimated glomerular filtration rate 15-60 mL/min per 1.73m(2)), mild to moderate left ventricular hypertrophy, and preserved ejection fraction were randomly assigned to 2 mu g of oral paricalcitol or matching placebo for 48 weeks. Two-dimensional echocardiography was obtained at baseline and at 24 and 48 weeks after initiation of therapy. Over the study period, there was a significant decrease in LAVi (-2.79 mL/m(2), 95% CI -4.00 to -1.59 mL/m(2)) in the paricalcitol group compared with the placebo group (-0.70 mL/m(2) [95% CI -1.93 to 0.53 mL/m(2)], P = .002). Paricalcitol also attenuated the rise in levels of brain natriuretic peptide (10.8% in paricalcitol vs 21.3% in placebo, P = .02). For the entire population, the change in brain natriuretic peptide correlated with change in LAVi (r = 0.17, P = .03). Conclusions Forty-eight weeks of therapy with an active vitamin D analog reduces LAVi and attenuates the rise of BNP. In a population where only few therapies alter cardiovascular related morbidity and mortality, these post hoc results warrant further confirmation. (Am Heart J 2012;164:902-909.e2.) C1 [Tamez, Hector; Wenger, Julia; Bhan, Ishir; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Div Pulm, Boston, MA 02114 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Crit Care Unit, Boston, MA 02114 USA. [Zoccali, Carmine] CNR IBIM Clin Epidemiol & Pathophysiol Renal Dis, Reggio Di Calabria, Italy. [Packham, David] Royal Melbourne Hosp, Dept Nephrol, Reservoir Private Hosp, Melbourne Renal Res Grp, Melbourne, Vic 3050, Australia. [Packham, David] Austin Hosp, Dept Nephrol, Melbourne, Vic 3084, Australia. [Appelbaum, Evan] Beth Israel Deaconess Med Ctr, Dept Med, Cardiovasc Div, Boston, MA 02215 USA. [Appelbaum, Evan] Beth Israel Deaconess Med Ctr, PERFUSE CMR Core Lab, Boston, MA 02215 USA. [Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Andress, Dennis] Abbott Labs, Abbott Pk, IL 60064 USA. [Agarwal, Rajiv] Indiana Univ Sch Med, Dept Med, Indianapolis, IN USA. [Wanner, Christoph] Univ Wurzburg, Univ Hosp, Div Nephrol, Dept Med, Wurzburg, Germany. [Lloyd-Jones, Donald] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Cannata, Jorge] Hosp Univ Cent Asturias, Inst Carlos III, Serv Metab Oseo & Mineral, Inst Reina Sofia Invest,RedinRen, Oviedo, Spain. [Singh, Bhupinder] SW Kidney Inst, Tempe, AZ USA. [Zehnder, Daniel] Univ Warwick, Warwick Med Sch, Clin Sci Res Inst, Coventry CV4 7AL, W Midlands, England. [Pachika, Ajay; Shah, Amil; Solomon, Scott D.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, 55 Fruit St,Bulfinch 127, Boston, MA 02114 USA. EM thadhani.r@mgh.harvard.edu RI Solomon, Scott/I-5789-2013; Cannata-Andia, Jorge/L-2260-2013; OI Zoccali, Carmine/0000-0002-6616-1996 FU Abbot Laboratories FX Dr. Thadhani received a coordinating grant from Abbot Laboratories to the Massachusetts General Hospital, speaker's fees and travel support from Abbot Laboratories. Drs. Pritchett, Andress, and Zhang are employees of Abbott Laboratories and may own Abbott stock or options. Drs. Agarwal, Zoccali, Wanner and Zehnder received honoraria from Abbott Laboratories for lectures or for participation in steering committee. Dr. Manning received travel support for a CMR meeting from Abbott Laboratories. Dr. Solomon is supported by a research grant from Abbott Laboratories to the Brigham and Women's Hospital. NR 38 TC 50 Z9 53 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2012 VL 164 IS 6 BP 902 EP + DI 10.1016/j.ahj.2012.09.018 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 044PU UT WOS:000311634500018 PM 23194491 ER PT J AU Goodman, A Clark, RM Bradford, LS AF Goodman, Annekathryn Clark, Rachel M. Bradford, Leslie S. TI Caring for Women With Gynecologic Cancers Around the World The Need for Global Health Training in Gynecologic Oncology Fellowship Programs SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Editorial Material ID MIDDLE-INCOME COUNTRIES; CARE; INEQUALITIES; DEATH C1 [Goodman, Annekathryn; Clark, Rachel M.; Bradford, Leslie S.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Gillette Ctr Womens Canc, Boston, MA 02114 USA. RP Goodman, A (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Gillette Ctr Womens Canc, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM agoodman@partners.org RI yan, liu/A-1822-2015 OI yan, liu/0000-0001-8517-1084 NR 27 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD DEC PY 2012 VL 35 IS 6 BP 511 EP 513 DI 10.1097/COC.0b013e318271b18a PG 3 WC Oncology SC Oncology GA 041FO UT WOS:000311384000001 PM 23165356 ER PT J AU Reddi, DM Lu, CYM Fedoriw, G Liu, YC Wang, FF Ely, S Boswell, EL Louissaint, A Arcasoy, MO Goodman, BK Wang, ED AF Reddi, Deepti M. Lu, Chuanyi M. Fedoriw, George Liu, Yen-Chun Wang, Frances F. Ely, Scott Boswell, Elizabeth L. Louissaint, Abner, Jr. Arcasoy, Murat O. Goodman, Barbara K. Wang, Endi TI Myeloid Neoplasms Secondary to Plasma Cell Myeloma: An Intrinsic Predisposition or Therapy-Related Phenomenon? A Clinicopathologic Study of 41 Cases and Correlation of Cytogenetic Features With Treatment Regimens SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Plasma cell myeloma; Myelodysplastic syndrome; Acute myeloid leukemia; Myeloproliferative neoplasm; Myeloid neoplasm; Therapy-related ID MULTIPLE-MYELOMA; MYELODYSPLASTIC SYNDROME; 2ND MALIGNANCIES; LEUKEMIA; TRANSPLANTATION; MELPHALAN; RISK; PATIENT AB We describe 41 cases of myeloid neoplasms (MNs) secondary to plasma cell myeloma (PCM). The types of MN included myelodysplastic syndrome (MDS) in 34 (82.9%), acute myeloid leukemia (AML) in 4 (9.8%), and myeloproliferative neoplasm (MPN) or MDS/MPN in 3 (7.3%) cases. The latency from treatment to diagnosis of 101 ranged from 9 to 384 months, with a median of 60 months. Of 37 cases with cytogenetic studies, complex abnormalities were detected in 22 (59.5%), -5(q)/-7(q) in 4 (10.8%), other abnormalities in 8 (21.6%), and normal karyotype in 3 (8.1%) cases. Complex abnormalities and -5(q)/-7(q) correlated directly with multiple chemotherapeutic regimens, particularly with combined melphalan/cyclophosphamide. Moreover, the features of cytogenetic abnormalities in our series were significantly different from those with concomitant PCM/MN who had significantly lower complex abnormalities. The latency, skewed proportion of MDS, and bias toward complex cytogenetic abnormalities/unbalanced aberrations of chromosomes 5/7 suggested an alkylating mutagenic effect on pathogenesis of secondary MN. Kaplan-Meier survival analysis demonstrated a median survival of 19 months, which was better than that for therapy-related (t)-MDS/AML. In contrast to t-MDS, the survival in our patients appeared to depend on subtypes of MDS as seen in de novo diseases. C1 [Reddi, Deepti M.; Boswell, Elizabeth L.; Goodman, Barbara K.; Wang, Endi] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Wang, Frances F.] Duke Univ, Med Ctr, Dept Community & Family Med, Canc Control & Prevent Program, Durham, NC 27710 USA. [Arcasoy, Murat O.] Duke Univ, Med Ctr, Dept Med, Div Hematol & Oncol, Durham, NC 27710 USA. [Lu, Chuanyi M.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Fedoriw, George] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Liu, Yen-Chun; Ely, Scott] Cornell Univ, Med Ctr, Dept Pathol & Lab Med, New York, NY 10021 USA. [Louissaint, Abner, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol & Lab Med, Boston, MA USA. RP Wang, ED (reprint author), Duke Hosp S, DUMC Box 3712,M-345 Davison Bldg Green Zone, Durham, NC 27710 USA. EM endi.wang@duke.edu NR 27 TC 9 Z9 11 U1 0 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 2012 VL 138 IS 6 BP 855 EP 866 DI 10.1309/AJCPOP7APGDT9JIU PG 12 WC Pathology SC Pathology GA 043DF UT WOS:000311522400013 PM 23161720 ER PT J AU Peralta, CA Katz, R Bonventre, JV Sabbisetti, V Siscovick, D Sarnak, M Shlipak, MG AF Peralta, Carmen A. Katz, Ronit Bonventre, Joseph V. Sabbisetti, Venkata Siscovick, David Sarnak, Mark Shlipak, Michael G. TI Associations of Urinary Levels of Kidney Injury Molecule 1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) With Kidney Function Decline in the Multi-Ethnic Study of Atherosclerosis (MESA) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Kidney injury molecule 1 (KIM-1); neutrophil gelatinase-associated lipocalin (NGAL); kidney function decline ID CYSTATIN C; CARDIAC-SURGERY; TUBULOINTERSTITIAL FIBROSIS; DISEASE; BIOMARKERS; RISK; PROGRESSION; MECHANISMS; MORTALITY; HUMANS AB Background: Whether elevations in levels of urinary biomarkers of tubular injury (urine neutrophil gelatinase-associated lipocalin [NGAL] and kidney injury molecule 1 [KIM-1]) are associated with future risk of kidney disease has not been investigated. Study Design: 1: 1 nested case-control study. Setting & Participants: 686 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Predictor: NGAL and KIM-1 were measured at baseline, expressed as log-transformed continuous variables, and categorized into deciles. Outcomes: Kidney function was estimated by cystatin C level using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Incident CKD stage 3 was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) and an eGFR decrease > 1 mL/min/1.73 m(2) per year, and rapid kidney function decrease was defined as decrease >= 3 mL/min/1.73 m(2) per year. Measurements: Cases were defined as persons with eGFR > 60 mL/min/1.73 m(2) who subsequently developed incident CKD stage 3 and/or had rapid kidney function decrease by the MESA year-5 visit. Controls were matched for age, sex, race, diabetes, and baseline eGFR. We adjusted for age, hypertension, and presence of albuminuria (albumin-creatinine ratio >= 30 mg/g). Results: Of 343 cases, 145 had incident CKD stage 3, 141 had rapid kidney function decrease, and 57 had both. Mean eGFR for controls was 81 +/- 10 mL/min/1.73 m(2) at baseline and 80 +/- 10 mL/min/1.73 m(2) at follow-up compared with 82 +/- 13 and 58 +/- 10 mL/min/1.73 m(2) for cases. Each doubling of KIM-1 level (in picograms per milliliter) was associated with an OR of 1.15 (95% CI, 1.02-1.29) for incident CKD stage 3 and/or rapid kidney function decrease. Compared with the lowest 90%, the highest decile of KIM-1 level was associated with an OR of 2.02 (95% CI, 1.15-3.56) for the outcome; these associations were independent of albuminuria. NGAL levels (in nanograms per milliliter) were not associated with incident CKD stage 3 and/or rapid kidney function decrease (OR, 1.04; 95% CI, 0.99-1.10). Results were similar when KIM-1 and NGAL levels were standardized for urine creatinine. Limitations: The case-control design limits the ability to account for persons who died or were not available for follow-up. Conclusions: Urinary KIM-1 level is associated with future risk of kidney disease independent of albuminuria. Urinary biomarkers of tubular injury are a promising tool for identifying persons at risk of CKD. Am J Kidney Dis. 60(6): 904-911. (C) 2012 by the National Kidney Foundation, Inc. C1 [Peralta, Carmen A.; Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Peralta, Carmen A.; Shlipak, Michael G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Siscovick, David] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Bonventre, Joseph V.; Sabbisetti, Venkata] Brigham & Womens Hosp, Boston, MA 02115 USA. [Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Sarnak, Mark] Tufts Med Ctr, Boston, MA USA. RP Peralta, CA (reprint author), 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM carmenalicia.peralta@ucsf.edu FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]; National Institute of Diabetes and Digestive and Kidney Diseases [1K23DK082793-01]; Robert Wood Johnson Foundation; National Institute of Aging [R01 AG027002] FX This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases (1K23DK082793-01, to Dr Peralta), the Robert Wood Johnson Foundation (Harold J. Amos Award; to Dr Peralta), and the National Institute of Aging (R01 AG027002, to Drs Sarnak and Shlipak). These funding sources had no involvement in the design or execution of this study. NR 35 TC 43 Z9 46 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 2012 VL 60 IS 6 BP 904 EP 911 DI 10.1053/j.ajkd.2012.05.014 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 034BM UT WOS:000310845100006 PM 22749388 ER PT J AU Spahillari, A Parikh, CR Sint, K Koyner, JL Patel, UD Edelstein, CL Passik, CS Thiessen-Philbrook, H Swaminathan, M Shlipak, MG AF Spahillari, Aferdita Parikh, Chirag R. Sint, Kyaw Koyner, Jay L. Patel, Uptal D. Edelstein, Charles L. Passik, Cary S. Thiessen-Philbrook, Heather Swaminathan, Madhav Shlipak, Michael G. CA TRIBE-AKI Consortium TI Serum Cystatin C- Versus Creatinine-Based Definitions of Acute Kidney Injury Following Cardiac Surgery: A Prospective Cohort Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Perioperative; acute renal failure; diagnosis; creatinine ID ACUTE-RENAL-FAILURE; GLOMERULAR-FILTRATION-RATE; CARDIOPULMONARY BYPASS; CARDIOVASCULAR EVENTS; SURGICAL-PATIENTS; HEART-FAILURE; RISK; MORTALITY; IMPACT; HEMOFILTRATION AB Background: The primary aim of this study was to compare the sensitivity and rapidity of acute kidney injury (AKI) detection by cystatin C level relative to creatinine level after cardiac surgery. Study Design: Prospective cohort study. Settings & Participants: 1,150 high-risk adult cardiac surgery patients in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) Consortium. Predictor: Changes in serum creatinine and cystatin C levels. Outcome: Postsurgical incidence of AKI. Measurements: Serum creatinine and cystatin C were measured at the preoperative visit and daily on postoperative days 1-5. To allow comparisons between changes in creatinine and cystatin C levels, AKI end points were defined by the relative increases in each marker from baseline (25%, 50%, and 100%) and the incidence of AKI was compared based on each marker. Secondary aims were to compare clinical outcomes among patients defined as having AKI by cystatin C and/or creatinine levels. Results: Overall, serum creatinine level detected more cases of AKI than cystatin C level: 35% developed a >= 25% increase in serum creatinine level, whereas only 23% had a >= 25% increase in cystatin C level (P < 0.001). Creatinine level also had higher proportions meeting the 50% (14% and 8%; P < 0.001) and 100% (4% and 2%; P = 0.005) thresholds for AKI diagnosis. Clinical outcomes generally were not statistically different for AKI cases detected by creatinine or cystatin C level. However, for each AKI threshold, patients with AKI confirmed by both markers had a significantly higher risk of the combined mortality/dialysis outcome compared with patients with AKI detected by creatinine level alone (P = 0.002). Limitations: There were few adverse clinical outcomes, limiting our ability to detect differences in outcomes between subgroups of patients based on their definitions of AKI. Conclusions: In this large multicenter study, we found that cystatin C level was less sensitive for AKI detection than creatinine level. However, confirmation by cystatin C level appeared to identify a subset of patients with AKI with a substantially higher risk of adverse outcomes. Am J Kidney Dis. 60(6): 922-929. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Spahillari, Aferdita; Shlipak, Michael G.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Parikh, Chirag R.; Sint, Kyaw] Yale Univ, Sch Med, Dept Internal Med, Clin Epidemiol Res Ctr, New Haven, CT 06510 USA. [Koyner, Jay L.] Univ Chicago, Pritzker Sch Med, Dept Med, Nephrol Sect, Chicago, IL 60637 USA. [Patel, Uptal D.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Patel, Uptal D.; Swaminathan, Madhav] Duke Univ, Sch Med, Dept Anesthesiol, Div Cardiothorac Anesthesiol & Crit Care Med, Durham, NC USA. [Edelstein, Charles L.] Univ Colorado, Div Renal Dis, Denver, CO 80202 USA. [Passik, Cary S.] Danbury Hosp, Dept Cardiothorac Surg, Danbury, CT USA. [Thiessen-Philbrook, Heather] Univ Western Ontario, Div Nephrol, Dept Med, London, ON, Canada. RP Parikh, CR (reprint author), Yale Univ, Nephrol Sect, 950 Campbell Ave,Mail Code 151B,Bldg 35 A,Rm 219, West Haven, CT 06516 USA. EM Chirag.Parikh@yale.edu FU National Heart, Lung, and Blood Institute [R01HL-085757]; National Center for Research Resources [UL1 RR024139] FX Support: The research reported in this article was supported by grant R01HL-085757 from the National Heart, Lung, and Blood Institute. The study also was supported by a Clinical and Translational Science Award grant (UL1 RR024139) from the National Center for Research Resources. NR 30 TC 35 Z9 36 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 2012 VL 60 IS 6 BP 922 EP 929 DI 10.1053/j.ajkd.2012.06.002 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 034BM UT WOS:000310845100008 PM 22809763 ER PT J AU Ramanathan, V Riosa, S Al-Sharif, AH Mansouri, MD Tranchina, A Kayyal, T Abreo, AP Aslam, S Nassar, G Darouiche, RO AF Ramanathan, Venkataraman Riosa, Sarah Al-Sharif, Atef H. Mansouri, M. David Tranchina, Andrew Kayyal, Talal Abreo, Adrian P. Aslam, Saima Nassar, George Darouiche, Rabih O. TI Characteristics of Biofilm on Tunneled Cuffed Hemodialysis Catheters in the Presence and Absence of Clinical Infection SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Biofilm; hemodialysis; catheter-related bacteremia ID ANTIBIOTIC LOCK; RISK-FACTORS; BACTEREMIA; MANAGEMENT; MORTALITY; PROTOCOL AB Background: Biofilm occurring on the surface of tunneled hemodialysis (HD) catheters is difficult to eradicate and often is associated with recurrent bacteremia. We studied biofilm formation on catheters from patients with and without bacteremia to identify the location of bacterial growth and measure biofilm thickness. Study Design: Prospective observational study. Setting & Participants: 76 adult HD patients; 26 had HD catheters removed for bacteremia and 50 had catheters removed for reasons other than infection. Predictors: Segment of catheter, reason for catheter removal. Outcomes & Measurements: Microbiological growth and biofilm thickness on the outer and luminal surfaces of extravascular and intravascular catheter segments. Results: Catheter cultures were positive in 16 (62%) patients with bacteremia and 15 (30%) when the catheter was removed for non-infection-related reasons. In catheters with positive cultures, the outer surface of the extravascular segment was the most common site of bacterial growth (15/16 [94%] and 11/15 [73%] for bacteremic and nonbacteremic patients, respectively). Bacteremic patients had significantly thicker biofilm on all catheter surfaces, and in bacteremic patients, the biofilm was significantly thicker on the outer compared with the luminal surface for both extravascular (14.53 +/- 6.17 vs 11.97 +/- 5.01 mu m; P < 0.001) and intravascular (12.21 +/- 5.3 vs 9.46 +/- 3.71 mu m; P < 0.001) segments. Extravascular segments had significantly thicker biofilm compared with intravascular segments on both the outer (P < 0.001) and luminal (P < 0.001) surfaces. Similarly, in patients for whom the catheter was removed for non-infection-related reasons, the catheter had thicker biofilm on the outer compared with the inner surface in both extravascular (2.19 +/- 2.84 vs 1.62 +/- 2.33 mu m; P < 0.001) and intravascular (1.92 +/- 2.62 vs 1.29 +/- 2.33 mu m; P < 0.001) segments. Similar to catheters from bacteremic patients, the outer and luminal surfaces of the extravascular segments of the catheters had significantly thicker biofilm compared with their corresponding surfaces on the intravascular segments. Limitations: Observational study. Conclusions: The outer surface of the extravascular segment of tunneled dialysis catheters in both bacteremic and nonbacteremic HD patients has the thickest biofilm and highest microbiological yield, and biofilm is thicker in patients with bacteremia. This knowledge is important for designing preventive strategies and also in the management of patients with catheter infection. Am J Kidney Dis. 60(6): 976-982. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Ramanathan, Venkataraman; Abreo, Adrian P.] Baylor Coll Med, Renal Sect, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Riosa, Sarah; Al-Sharif, Atef H.; Mansouri, M. David; Tranchina, Andrew; Kayyal, Talal; Darouiche, Rabih O.] Baylor Coll Med, Infect Dis Sect, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Aslam, Saima] Univ Calif San Diego, Div Infect Dis, San Diego, CA 92103 USA. [Darouiche, Rabih O.] Baylor Coll Med, Ctr Prostheses Infect, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Nassar, George] Weill Cornell Univ, Doha, Qatar. RP Ramanathan, V (reprint author), Baylor Coll Med, Renal Sect, Michael E DeBakey Vet Affairs Med Ctr, 111J,2002 Holcombe Blvd, Houston, TX 77030 USA. EM ramanath@bcm.edu FU Satellite Healthcare Inc.; National Institutes of Health/National Institute of Allergy and Infectious Diseases FX This research was supported by the Norman S. Coplon Extramural Grant from Satellite Healthcare Inc. Mr Mansouri has received support from the National Institutes of Health/National Institute of Allergy and Infectious Diseases. NR 23 TC 16 Z9 16 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 2012 VL 60 IS 6 BP 976 EP 982 DI 10.1053/j.ajkd.2012.06.003 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 034BM UT WOS:000310845100014 PM 22795945 ER PT J AU Nigwekar, SU Bhan, I Thadhani, R AF Nigwekar, Sagar U. Bhan, Ishir Thadhani, Ravi TI In Reply to "Calcidiol Deficiency in CKD Patients: The Role of Reduced Liver Synthesis" SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Letter C1 [Nigwekar, Sagar U.; Bhan, Ishir; Thadhani, Ravi] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nigwekar, SU (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 2012 VL 60 IS 6 BP 1049 EP 1049 DI 10.1053/j.ajkd.2012.08.037 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 034BM UT WOS:000310845100025 ER PT J AU Longoni, M Lage, K Russell, MK Loscertales, M Abdul-Rahman, OA Baynam, G Bleyl, SB Brady, PD Breckpot, J Chen, CP Devriendt, K Gillessen-Kaesbach, G Grix, AW Rope, AF Shimokawa, O Strauss, B Wieczorek, D Zackai, EH Coletti, CM Maalouf, FI Noonan, KM Park, JH Tracy, AA Lee, C Donahoe, PK Pober, BR AF Longoni, Mauro Lage, Kasper Russell, Meaghan K. Loscertales, Maria Abdul-Rahman, Omar A. Baynam, Gareth Bleyl, Steven B. Brady, Paul D. Breckpot, Jeroen Chen, Chih P. Devriendt, Koenraad Gillessen-Kaesbach, Gabriele Grix, Arthur W. Rope, Alan F. Shimokawa, Osamu Strauss, Bernarda Wieczorek, Dagmar Zackai, Elaine H. Coletti, Caroline M. Maalouf, Faouzi I. Noonan, Kristin M. Park, Ji H. Tracy, Adam A. Lee, Charles Donahoe, Patricia K. Pober, Barbara R. TI Congenital diaphragmatic hernia interval on chromosome 8p23.1 characterized by genetics and protein interaction networks SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE congenital diaphragmatic hernia; congenital heart defect; DNA copy number variants; deletion 8p23 1; duplication 8p23 1; CNVConnect; GATA4; SOX7; NEIL2 ID COMPARATIVE GENOMIC HYBRIDIZATION; GATA TRANSCRIPTION FACTORS; ARRAY-CGH; HEART-DEFECTS; MOLECULAR CHARACTERIZATION; MICRODELETION SYNDROME; CARDIAC DEVELOPMENT; PRENATAL-DIAGNOSIS; CANDIDATE GENES; SEPTAL-DEFECTS AB Chromosome 8p23.1 is a common hotspot associated with major congenital malformations, including congenital diaphragmatic hernia (CDH) and cardiac defects. We present findings from high-resolution arrays in patients who carry a loss (n?=?18) or a gain (n?=?1) of sub-band 8p23.1. We confirm a region involved in both diaphragmatic and heart malformations. Results from a novel CNVConnect algorithm, prioritizing proteinprotein interactions between products of genes in the 8p23.1 hotspot and products of previously known CDH causing genes, implicated GATA4, NEIL2, and SOX7 in diaphragmatic defects. Sequence analysis of these genes in 226 chromosomally normal CDH patients, as well as in a small number of deletion 8p23.1 patients, showed rare unreported variants in the coding region; these may be contributing to the diaphragmatic phenotype. We also demonstrated that two of these three genes were expressed in the E11.512.5 primordial mouse diaphragm, the developmental stage at which CDH is thought to occur. This combination of bioinformatics and expression studies can be applied to other chromosomal hotspots, as well as private microdeletions or microduplications, to identify causative genes and their interaction networks. (C) 2012 Wiley Periodicals, Inc. C1 [Longoni, Mauro; Lage, Kasper; Russell, Meaghan K.; Loscertales, Maria; Coletti, Caroline M.; Maalouf, Faouzi I.; Noonan, Kristin M.; Tracy, Adam A.; Donahoe, Patricia K.; Pober, Barbara R.] Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. [Lage, Kasper; Donahoe, Patricia K.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Lage, Kasper; Donahoe, Patricia K.] Broad Inst, Cambridge, MA USA. [Lage, Kasper] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Lage, Kasper] Univ Copenhagen, Ctr Prot Res, Copenhagen, Denmark. [Abdul-Rahman, Omar A.] Univ Mississippi, Med Ctr, Dept Pediat, Jackson, MS 39216 USA. [Baynam, Gareth] King Edward Mem Hosp, Genet Serv Western Australia, Perth, WA, Australia. [Bleyl, Steven B.; Rope, Alan F.] Univ Utah, Sch Med, Dept Pediat, Div Med Genet, Salt Lake City, UT USA. [Brady, Paul D.; Breckpot, Jeroen; Devriendt, Koenraad] Univ Hosp Leuven, Ctr Human Genet, Lab Cytogenet & Genome Res, Louvain, Belgium. [Chen, Chih P.] Mackay Mem Hosp, Dept Obstet & Gynecol, Taipei, Taiwan. [Gillessen-Kaesbach, Gabriele] Med Univ Lubeck, Inst Humangenet, D-23538 Lubeck, Germany. [Grix, Arthur W.] Kaiser Permanente, Genet, Sacramento, CA USA. [Shimokawa, Osamu] Mitsubishi Chem Medience Corp, Dept Mol Genet Testing, Nagasaki, Japan. [Strauss, Bernarda] Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Wieczorek, Dagmar] Univ Klinikum Essen, Inst Humangenet, Essen, Germany. [Zackai, Elaine H.] Childrens Hosp Philadelphia, Div Human Genet & Mol Biol, Philadelphia, PA USA. [Park, Ji H.; Lee, Charles] Brigham & Womens Hosp, Boston, MA 02115 USA. [Pober, Barbara R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Pober, Barbara R.] Childrens Hosp Boston, Dept Surg, Boston, MA USA. RP Longoni, M (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, 185 Cambridge St,CPZN 6-216, Boston, MA 02114 USA. EM mlongoni@partners.org RI Congregado, Miguel/B-9062-2009; Longoni, Mauro/I-2526-2013; OI Congregado, Miguel/0000-0002-2404-0176; Maalouf, Faouzi/0000-0001-9896-5334 FU NICHD NIH HHS [P01 HD068250] NR 65 TC 17 Z9 17 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC PY 2012 VL 158A IS 12 BP 3148 EP 3158 DI 10.1002/ajmg.a.35665 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 041KX UT WOS:000311401800023 PM 23165946 ER PT J AU Shinagare, AB Krajewski, KM Hornick, JL Zukotynski, K Kurra, V Jagannathan, JP Ramaiya, NH AF Shinagare, Atul B. Krajewski, Katherine M. Hornick, Jason L. Zukotynski, Katherine Kurra, Vikram Jagannathan, Jyothi P. Ramaiya, Nikhil H. TI MRI for Evaluation of Myeloid Sarcoma in Adults: A Single-Institution 10-Year Experience SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE chloroma; granulocytic sarcoma; MRI; myeloid sarcoma ID GRANULOCYTIC SARCOMA; MYELOGENOUS LEUKEMIA; EXTRAMEDULLARY RELAPSE; CHLOROMA; CT AB OBJECTIVE. The purpose of this study was to evaluate the utilization and role of MRI in the management of myeloid sarcoma in adults. MATERIALS AND METHODS. A retrospective study of 69 patients with pathologically proven myeloid sarcoma included 25 patients (16 men, nine women; mean age, 55 years; range, 22-78 years) who underwent pretreatment MRI at our institution from January 2001 to October 2011. A total of 71 MRI examinations were evaluated by two radiologists in consensus. RESULTS. A total of 41 sites of involvement of myeloid sarcoma were noted, most commonly bone (13/25, 52%), muscle (7/25, 28%), CNS (6/25, 24%), and head and neck (6/25, 24%). Nineteen sites were noted on MR images obtained for evaluation of a new sign or symptom, most commonly musculoskeletal (11 sites) and CNS (six sites). Fifteen sites were noted on MR images obtained for further evaluation of a previously detected abnormality, most commonly in the abdomen and pelvis (seven sites). Seven lesions were incidentally found on MR images obtained for other myeloid sarcoma-related indications, most commonly in the head and neck (three lesions) and musculoskeletal system (three lesions). The mean size of measurable lesions was 5.6 cm (range, 1-20 cm). Compared with muscle, the lesions were isointense (31/41, 75.6%) or hypointense (10/41, 24.4%) on T1-weighted images and mildly hyperintense (39/41, 95.1%) on T2-weighted images and had homogeneous enhancement (29/38, 76.3%). CONCLUSION. In our experience, MRI was most often used for evaluation of bone, muscle, the CNS, and the head and neck region. MRI is useful for evaluation of new musculoskeletal and CNS findings and for further evaluation of known abdominopelvic masses. Incidental findings are often musculoskeletal or in the soft tissues of the head and neck. C1 [Shinagare, Atul B.; Krajewski, Katherine M.; Zukotynski, Katherine; Kurra, Vikram; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Shinagare, Atul B.; Krajewski, Katherine M.; Zukotynski, Katherine; Kurra, Vikram; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Hornick, Jason L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM ashinagare@partners.org RI Xu, Yang/M-1424-2013 NR 16 TC 12 Z9 12 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 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2012 VL 199 IS 6 BP 1193 EP 1198 DI 10.2214/AJR.12.9057 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 041NL UT WOS:000311408400021 PM 23169708 ER PT J AU Carr, RB Fink, KRT Gross, JA AF Carr, Robert B. Fink, Kathleen R. Tozer Gross, Joel A. TI Imaging of Trauma: Part 1, Pseudotrauma of the Spine-Osseous Variants That May Simulate Injury SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE pseudotrauma; spine development; spine variants ID CERVICAL-SPINE; CHILDHOOD; VERTEBRA; FRACTURE; CLEFT; ARCH AB OBJECTIVE. Anatomic variants and incomplete ossification and fusion of the developing spine may result in an erroneous diagnosis of injury or disease. This article reviews some of the more common imaging findings that may present as pseudotrauma. Normal development of the spine is reviewed, including synchondroses and ossification centers. Imaging of common variants is presented, with a focus on CT. CONCLUSION. Recognition of the normal developing spine and variants can prevent an incorrect diagnosis of injury and inappropriate treatment. C1 [Carr, Robert B.; Fink, Kathleen R. Tozer; Gross, Joel A.] Univ Washington, Dept Radiol, Harborview Med Ctr, Seattle, WA 98195 USA. RP Carr, RB (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,GRB273A, Boston, MA 02114 USA. EM rcarr2@u.washington.edu NR 14 TC 2 Z9 2 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 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2012 VL 199 IS 6 BP 1200 EP 1206 DI 10.2214/AJR.12.9083 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 041NL UT WOS:000311408400022 PM 23169709 ER PT J AU Wu, CC Lee, EW Suh, RD Levine, BS Barack, BM AF Wu, Carol C. Lee, Edward W. Suh, Robert D. Levine, Barton S. Barack, Bruce M. TI Pulmonary 64-MDCT Angiography With 30 mL of IV Contrast Material: Vascular Enhancement and Image Quality SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE contrast dose; image quality; pulmonary MDCT angiography; vascular enhancement ID COMPUTED-TOMOGRAPHY; ONCOLOGY PATIENTS; CT; EMBOLISM; MANAGEMENT; EXTRAVASATION; GUIDELINES; INJURY; MDCT AB OBJECTIVE. The objective of our study was to determine whether vascular enhancement and image quality can be preserved in pulmonary CT angiography (CTA) performed on a 64-MDCT scanner with 30 mL of IV contrast material. MATERIALS AND METHODS. This retrospective matched-cohort study compared image quality of pulmonary CTA performed using 30 mL of IV contrast material versus 100 mL of IV contrast material. CT images of 50 patients (46 men, four women; mean age, 66 years) who underwent pulmonary CTA on a 64-MDCT scanner using a low dose (30 mL) of iodixanol 320 and another 50 patients (49 men, one woman; mean age, 65 years) who underwent pulmonary CTA using a regular dose (100 mL) of contrast material during the same time period were selected for review. The 30- and 100-mL pulmonary CTA studies were retrospectively evaluated by two thoracic radiologists in random order. Attenuation values were recorded over the main, right main, selected lobar, segmental, and subsegmental pulmonary arteries. Image quality was also subjectively assessed using visual scores on a scale from 1 (nondiagnostic) to 5 (excellent). RESULTS. The average attenuation measurements of the main, right main, selected lobar, segmental, and subsegmental pulmonary arteries were 260, 262, 280, 316, and 338 HU, respectively, on the 30- mL studies and 313, 301, 316, 344, and 349 HU, respectively, on the 100-mL studies. The average visual score was 4.0 for both the 30- and 100-mL groups. A visual score of 4 or 5 was given to 82% of studies in the 30- mL group and 78% of studies in the 100-mL group. CONCLUSION. Contrast agent dose for pulmonary CTA using a 64-MDCT scanner can be significantly reduced without compromising diagnostic image quality. C1 [Barack, Bruce M.] VA Greater Los Angeles Healthcare Syst, Dept Imaging, Thorac Radiol Sect, Los Angeles, CA 90073 USA. [Wu, Carol C.] Massachusetts Gen Hosp, Dept Radiol, Div Thorac Imaging & Intervent, Boston, MA 02114 USA. [Lee, Edward W.; Suh, Robert D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. [Levine, Barton S.] VA Greater Los Angeles Healthcare Syst, Dept Med, Div Nephrol, Los Angeles, CA 90073 USA. RP Barack, BM (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Imaging, Thorac Radiol Sect, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM bruce.barack@va.gov OI Lee, Edward/0000-0003-0418-1454 NR 19 TC 10 Z9 11 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2012 VL 199 IS 6 BP 1247 EP 1251 DI 10.2214/AJR.12.8739 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 041NL UT WOS:000311408400028 PM 23169715 ER PT J AU Shinagare, AB Howard, SA Krajewski, KM Zukotynski, KA Jagannathan, JP Ramaiya, NH AF Shinagare, Atul B. Howard, Stephanie A. Krajewski, Katherine M. Zukotynski, Katherine A. Jagannathan, Jyothi P. Ramaiya, Nikhil H. TI Pneumatosis Intestinalis and Bowel Perforation Associated With Molecular Targeted Therapy: An Emerging Problem and the Role of Radiologists in Its Management SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE bowel complication; perforation; cancer; fistula; intestinal pneumatosis; molecular targeted therapy ID METASTATIC COLORECTAL-CANCER; OVARIAN-CANCER; VENOUS GAS; BEVACIZUMAB; CHEMOTHERAPY; FLUOROURACIL; PROGRESSION; LEUCOVORIN; IRINOTECAN; CETUXIMAB AB OBJECTIVE. The purpose of this article is to study the imaging features, management, and outcome of pneumatosis intestinalis and bowel perforation associated with molecular targeted therapy. MATERIALS AND METHODS. In this retrospective study, 48 patients with cancer who developed pneumatosis or intestinal perforation were found by searching a radiology database. Of these patients, 24 patients (13 women and 11 men; mean age, 61 years; range, 39-83 years) receiving molecular targeted therapy without any confounding factors for pneumatosis or perforation were selected. Initial and follow-up CT scans were evaluated by two radiologists; medical records were reviewed to note clinical features, management, and outcome. RESULTS. Seventeen (70.8%) patients were asymptomatic. Colorectal cancer (n = 10) and renal cell carcinoma (n = 5) were the most common malignancies; bevacizumab (n = 14) and sunitinib (n = 6) were the most common associated drugs. Imaging findings included intestinal perforation (20 sites in 18 patients), pneumatosis (n = 10), ascites (n = 8), pneumoperitoneum (n = 7), fistula formation (n = 7), and fluid collections (six collections in five patients). Fifteen (62.5%) patients were treated conservatively, seven (29.2%) underwent surgery, and two (8.3%) underwent percutaneous drainage. Molecular targeted therapy was discontinued in 22 of 24 patients; findings resolved in 19 patients, remained stable in one, and worsened in one. One patient died after surgery. In both instances where the drug was continued, the abnormality worsened. Findings recurred in three of four patients in whom the drug was restarted after initial resolution. CONCLUSION. Radiologists should be aware of intestinal complications associated with molecular targeted therapy, including pneumatosis, bowel perforation, and fistula formation. Most patients can be treated conservatively after discontinuation of molecular targeted therapy. Continuing or restarting molecular targeted therapy can cause worsening or recurrent pneumatosis or perforation. C1 [Shinagare, Atul B.; Howard, Stephanie A.; Krajewski, Katherine M.; Zukotynski, Katherine A.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Shinagare, Atul B.; Howard, Stephanie A.; Krajewski, Katherine M.; Zukotynski, Katherine A.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM ashinagare@partners.org NR 29 TC 23 Z9 23 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 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2012 VL 199 IS 6 BP 1259 EP 1265 DI 10.2214/AJR.12.8782 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 041NL UT WOS:000311408400030 PM 23169717 ER PT J AU Elmi, A Tabatabaei, S Talab, SS Hedgire, SS Cao, K Harisinghani, M AF Elmi, Azadeh Tabatabaei, Shahin Talab, Saman Shafaat Hedgire, Sandeep S. Cao, Kai Harisinghani, Mukesh TI Incidental Findings at Initial Imaging Workup of Patients With Prostate Cancer: Clinical Significance and Outcomes SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE carcinoma; CT; incidental finding; prostate; synchronous cancer ID RENAL-CELL CARCINOMA; SCREENING CT COLONOGRAPHY; RADICAL PROSTATECTOMY; RADIATION-THERAPY; FREQUENCY; SURVIVAL; AGE AB OBJECTIVE. The purpose of this article is to evaluate the frequency and clinical relevance of incidental findings in patients with prostate cancer who underwent abdominopelvic contrast-enhanced CT examination for initial staging workup. MATERIALS AND METHODS. We retrospectively reviewed 355 initial staging abdominopelvic contrast-enhanced CT examinations conducted from January 2000 to December 2010 in patients with prostate cancer for incidental findings that were not related to prostate cancer. A finding was judged to be potentially significant if therapeutic intervention, additional imaging, or tissue sampling was deemed advisable. The rate of incidental findings was correlated to patients' age and stratified prostate cancer risk groups. RESULTS. We found 779 incidental finding in 292 patients (82.3%), of which 75 findings in 73 patients (20.6%) were potentially significant. Indeterminate masses were the most prevalent significant finding (n = 62). Synchronous malignancy was detected in 21 patients (5.9%). Kidney cancer (n = 7 [1.97%]) was the most common malignancy, followed by lymphoma (n = 4 [1.13%]). Staging of the cancers revealed that 15 patients, including all of those with renal cancer, had N0M0 disease. Significant vascular abnormalities were reported in six cases. Additionally, significant findings, synchronous malignancies in particular, were identified at a higher rate in patients older than 65 years. However, no significant differences were noticed between the different prostate cancer risk groups. CONCLUSION. Abdominal contrast-enhanced CT for initial staging of prostate cancer shows a considerable prevalence of incidental vascular events and synchronous cancers, with kidney cancers being the most common. Notably, 71.5% of these malignancies were at early stage. Our results show an incremental value of CT in prostate cancer staging, with an emphasis on focused evaluation of the kidneys. C1 [Elmi, Azadeh; Hedgire, Sandeep S.; Cao, Kai; Harisinghani, Mukesh] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. [Tabatabaei, Shahin; Talab, Saman Shafaat] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Harisinghani, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM mharisinghani@mgh.harvard.edu NR 20 TC 6 Z9 6 U1 1 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2012 VL 199 IS 6 BP 1305 EP 1311 DI 10.2214/AJR.11.8417 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 041NL UT WOS:000311408400035 PM 23169722 ER PT J AU Saboo, SS Krajewski, KM Zukotynski, K Howard, S Jagannathan, JP Hornick, JL Ramaiya, N AF Saboo, Sachin S. Krajewski, Katherine M. Zukotynski, Katherine Howard, Stephanie Jagannathan, Jyothi P. Hornick, Jason L. Ramaiya, Nikhil TI Imaging Features of Primary and Secondary Adult Rhabdomyosarcoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE adult; CT; FDG PET/CT; MRI; rhabdomyosarcoma ID PEDIATRIC RHABDOMYOSARCOMA; FDG PET/CT; MR; CHILDREN AB OBJECTIVE. Rhabdomyosarcomas are rare and aggressive soft-tissue sarcomas in adults. The purpose of this article is to describe the imaging features of primary and secondary adult rhabdomyosarcomas utilizing MRI, CT, and F-18-FDG PET/CT. CONCLUSION. MRI is the imaging technique of choice for the evaluation of primary rhabdomyosarcoma involving most body sites (extremity, pelvis, head, and neck), with the added advantages of diffusion-weighted imaging and whole-body MRI for staging. CT and FDG PET/CT play major roles in the evaluation of metastatic disease. Because the imaging features of adult rhabdomyosarcoma are nonspecific, other parameters, such as clinical findings, age, site, lymphadenopathy, and metastatic disease, should be combined to narrow the differential diagnosis. C1 [Saboo, Sachin S.; Krajewski, Katherine M.; Zukotynski, Katherine; Howard, Stephanie; Jagannathan, Jyothi P.; Ramaiya, Nikhil] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02215 USA. [Saboo, Sachin S.; Krajewski, Katherine M.; Zukotynski, Katherine; Howard, Stephanie; Jagannathan, Jyothi P.; Ramaiya, Nikhil] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. RP Saboo, SS (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, 450 Brookline Ave, Boston, MA 02215 USA. EM ssaboo@partners.org NR 20 TC 5 Z9 5 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 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2012 VL 199 IS 6 BP W694 EP W703 DI 10.2214/AJR.11.8213 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 041NL UT WOS:000311408400004 PM 23169742 ER PT J AU Lei, C Yu, BL Shahid, M Beloiartsev, A Bloch, KD Zapol, WM AF Lei, Chong Yu, Binglan Shahid, Mohd Beloiartsev, Arkadi Bloch, Kenneth D. Zapol, Warren M. TI Inhaled Nitric Oxide Attenuates the Adverse Effects of Transfusing Stored Syngeneic Erythrocytes in Mice with Endothelial Dysfunction after Hemorrhagic Shock SO ANESTHESIOLOGY LA English DT Article ID BLOOD-CELL STORAGE; UNIVERSAL LEUKOREDUCTION; INDEPENDENT PREDICTOR; PROLONGED STORAGE; OXIDATIVE STRESS; CARDIAC-SURGERY; FREE HEMOGLOBIN; CRITICALLY-ILL; SEVERE INJURY; GUINEA-PIGS AB Background: The authors investigated whether transfusion with stored erythrocytes would increase tissue injury, inflammation, oxidative stress, and mortality (adverse effects of transfusing stored erythrocytes) in a murine model of hemorrhagic shock. They tested whether the adverse effects associated with transfusing stored erythrocytes were exacerbated by endothelial dysfunction and ameliorated by inhaling nitric oxide. Methods: The authors studied mice fed a high-fat diet (HFD-fed; to induce endothelial dysfunction) or a standard diet for 4-6 weeks. Mice were subjected to 90 min of hemorrhagic shock, followed by resuscitation with leukoreduced syngeneic erythrocytes stored less than 24 h (fresh erythrocytes) or stored for 2 weeks (stored erythrocytes). Results: In standard-diet-fed mice at 2 h after resuscitation, transfusion with stored erythrocytes increased tissue injury more than transfusion with fresh erythrocytes. The adverse effects of transfusing stored erythrocytes were more marked in HFD-fed mice and associated with increased lactate levels and short-term mortality. Compared with fresh erythrocytes, resuscitation with stored erythrocytes was associated with a reduction in P-50, increased plasma hemoglobin levels, and increased indices of inflammation and oxidative stress, effects that were exacerbated in HFD-fed mice. Inhaled nitric oxide reduced tissue injury, lactate levels, and indices of inflammation and oxidative stress and improved short-term survival in HFD-fed mice resuscitated with stored erythrocytes. Conclusions: Resuscitation with stored erythrocytes adversely impacts outcome in mice with hemorrhagic shock, an effect that is exacerbated in mice with endothelial dysfunction. Inhaled nitric oxide reduces tissue injury and improves short-term survival in HFD-fed mice resuscitated with stored erythrocytes. C1 [Lei, Chong; Yu, Binglan; Shahid, Mohd; Beloiartsev, Arkadi; Bloch, Kenneth D.; Zapol, Warren M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anesthesia Ctr Crit Care Res,Dept Anesthesia Crit, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anesthesia Ctr Crit Care Res,Dept Anesthesia Crit, 55 Fruit St,Thier 503, Boston, MA 02114 USA. EM wzapol@partners.org FU Ikaria Inc.; National Natural Science Foundation of China, Xi'an, China [81000232]; Harvard Medical School, Boston, Massachusetts [217249]; Fondation LeDucq, Paris, France FX Dr. Zapol receives royalties from patents on inhaled nitric oxide licensed by Massachusetts General Hospital to Linde Corp, Munich, Germany, and Ikaria Inc., Clinton, New Jersey. Dr. Bloch has received grants from Ikaria Inc. to study inhaled nitric oxide. Drs. Zapol and Yu have applied for patents on inhaled nitric oxide and blood transfusion. The remaining authors report no conflicts of interest. Supported by grants from the National Natural Science Foundation of China, Xi'an, China (to Dr. Lei; #81000232), an Eleanor and Miles Shore 50th Anniversary Fellowship of Harvard Medical School, Boston, Massachusetts (to Dr. Yu; #217249), and a research grant from the Fondation LeDucq, Paris, France (to Dr. Bloch). Drs. Lei and Yu contributed equally to this work. NR 51 TC 16 Z9 17 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 2012 VL 117 IS 6 BP 1190 EP 1202 DI 10.1097/ALN.0b013e318272d866 PG 13 WC Anesthesiology SC Anesthesiology GA 041PY UT WOS:000311414900010 PM 23168426 ER PT J AU Galanaud, D Perlbarg, V Gupta, R Stevens, RD Sanchez, P Tollard, E de Champfleur, NM Dinkel, J Faivre, S Soto-Ares, G Veber, B Cottenceau, V Masson, F Tourdias, T Andre, E Audibert, G Schmitt, E Ibarrola, D Dailler, F Vanhaudenhuyse, A Tshibanda, L Payen, JF Le Bas, JF Krainik, A Bruder, N Girard, N Laureys, S Benali, H Puybasset, L AF Galanaud, Damien Perlbarg, Vincent Gupta, Rajiv Stevens, Robert D. Sanchez, Paola Tollard, Eleonore de Champfleur, Nicolas Menjot Dinkel, Julien Faivre, Sebastien Soto-Ares, Gustavo Veber, Benoit Cottenceau, Vincent Masson, Francoise Tourdias, Thomas Andre, Edith Audibert, Gerard Schmitt, Emmanuelle Ibarrola, Danielle Dailler, Frederic Vanhaudenhuyse, Audrey Tshibanda, Luaba Payen, Jean-Francois Le Bas, Jean-Francois Krainik, Alexandre Bruder, Nicolas Girard, Nadine Laureys, Steven Benali, Habib Puybasset, Louis CA Neuro Imaging Coma Emergence Recov TI Assessment of White Matter Injury and Outcome in Severe Brain Trauma A Prospective Multicenter Cohort SO ANESTHESIOLOGY LA English DT Article ID DIFFUSE AXONAL INJURY; COMPUTERIZED-TOMOGRAPHY; PROGNOSTIC VALUE; HEAD-INJURY; MRI; CLASSIFICATION; PREDICTION; IMPACT; IMAGE; STATE AB Background: Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging (DTI). Methods: In a multicenter study, the authors prospectively enrolled 105 patients who remained comatose at least 7 days after traumatic brain injury. Patients underwent brain magnetic resonance imaging, including DTI in 20 preselected white matter tracts. Patients were evaluated at 1 yr with a modified Glasgow Outcome Scale. A composite DTI score was constructed for outcome prognostication on this training database and then validated on an independent database (n = 38). DTI score was compared with the International Mission for Prognosis and Analysis of Clinical Trials Score. Results: Using the DTI score for prediction of unfavorable outcome on the training database, the area under the receiver operating characteristic curve was 0.84 (95% CI: 0.75-0.91). The DTI score had a sensitivity of 64% and a specificity of 95% for the prediction of unfavorable outcome. On the validation-independent database, the area under the receiver operating characteristic curve was 0.80 (95% CI: 0.54-0.94). On the training database, reclassification methods showed significant improvement of classification accuracy (P < 0.05) compared with the International Mission for Prognosis and Analysis of Clinical Trials score. Similar results were observed on the validation database. Conclusions: White matter assessment with quantitative DTI increases the accuracy of long-term outcome prediction compared with the available clinical/radiographic prognostic score. C1 [Galanaud, Damien] Hop La Pitie Salpetriere, Dept Neurol, F-75013 Paris, France. [Perlbarg, Vincent; Dinkel, Julien] Univ Paris 06, UMRS, INSERM, Paris, France. [Gupta, Rajiv; Benali, Habib] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Stevens, Robert D.] Johns Hopkins Univ, Sch Med, Div Neurosci Crit Care, Baltimore, MD USA. [Sanchez, Paola] Hop La Pitie Salpetriere, AP HP, Neurosurg Intens Care Unit, Paris, France. [Tollard, Eleonore] CHU, Dept Neuroradiol, Rouen, France. [de Champfleur, Nicolas Menjot] Guy Chauliac Hospi, Dept Neuroradiol, Montpellier, France. [Faivre, Sebastien] Roger Salengro Hosp, Dept Anesthesia, Lille, France. [Faivre, Sebastien] Roger Salengro Hosp, Surg Intens Care Unit, Lille, France. [Soto-Ares, Gustavo] Roger Salengro Hosp, Dept Neuroradiol, Lille, France. [Veber, Benoit] CHU, Surg Intens Care Unit, Rouen, France. [Tourdias, Thomas] CHU, Dept Neuroradiol, Bordeaux, France. [Masson, Francoise] CHU, Dept Anesthesia, Bordeaux, France. [Masson, Francoise] CHU, Surg Intens Care Unit, Bordeaux, France. [Andre, Edith] Guy Chauliac Hosp, Dept Anesthesia, Montpellier, France. [Andre, Edith] Guy Chauliac Hosp, Intens Care Unit, Montpellier, France. [Audibert, Gerard] CHU, Dept Anesthesia, Nancy, France. [Audibert, Gerard] CHU, Surg Intens Care Unit, Nancy, France. [Schmitt, Emmanuelle] CHU, Dept Neuroradiol, Nancy, France. [Ibarrola, Danielle] Pierre Wertheimer Neurol & Neurosurg Hosp, CERMEP, Bron, France. [Dailler, Frederic] Pierre Wertheimer Neurol & Neurosurg Hosp, Surg Intens Care Unit, Lyon, France. [Vanhaudenhuyse, Audrey] Univ Liege, Cyclotron Res Ctr, Liege, Belgium. [Tshibanda, Luaba] Univ Liege, Dept Neuroradiol, Liege, Belgium. [Payen, Jean-Francois] Michallon Hosp, Dept Anesthesia, La Tronche, France. [Payen, Jean-Francois] Michallon Hosp, Surg Intens Care Unit, La Tronche, France. [Krainik, Alexandre] Michallon Hosp, Dept Neuroradiol, La Tronche, France. [Bruder, Nicolas] La Timone Hosp, Dept Anesthesia, Marseille, France. [Bruder, Nicolas] La Timone Hosp, Intens Care Unit, Marseille, France. [Girard, Nadine] La Timone Hosp, Dept Neuroradiol, Marseille, France. [Puybasset, Louis] Hop La Pitie Salpetriere, AP HP, Neurosurg Intens Care Unit, Paris, France. RP Galanaud, D (reprint author), Hop La Pitie Salpetriere, Dept Neurol, 47 Blvd Hop, F-75013 Paris, France. EM galanaud@gmail.com RI girard, nadine/E-8537-2013; KRAINIK, Alexandre/L-5874-2014; Payen, Jean-Francois/L-6667-2014; krainik, alexandre/I-2431-2015; Laureys, Steven/A-3349-2011; Girard, Nadine/B-7109-2017; Sappey-Marinier, Dominique/L-2925-2014; OI DOUSSET, VINCENT/0000-0003-0427-3236 FU French ministry of health, Paris, France [P051061]; "Agence Nationale de la Recherche," Paris France [ANR-10-IAIHU-06] FX This work was funded by a grant from the French ministry of health (ProjetHospitalier de Recherche Clinique registration #P051061 (2005)), Paris, France, and from the "Agence Nationale de la Recherche," Paris France, for the program " investissements d'avenir" under agreement noANR-10-IAIHU-06 for the Paris Institute of Translational Neurosciences-IHU-A-ICM. Other support was provided from institutional and/or departmental sources. NR 32 TC 36 Z9 36 U1 3 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 2012 VL 117 IS 6 BP 1300 EP 1310 DI 10.1097/ALN.0b013e3182755558 PG 11 WC Anesthesiology SC Anesthesiology GA 041PY UT WOS:000311414900020 PM 23135261 ER PT J AU Luyt, CE Galanaud, D Perlbarg, V Vanhaudenhuyse, A Stevens, RD Gupta, R Besancenot, H Krainik, A Audibert, G Combes, A Chastre, J Benali, H Laureys, S Puybasset, L AF Luyt, Charles-Edouard Galanaud, Damien Perlbarg, Vincent Vanhaudenhuyse, Audrey Stevens, Robert D. Gupta, Rajiv Besancenot, Hortense Krainik, Alexandre Audibert, Gerard Combes, Alain Chastre, Jean Benali, Habib Laureys, Steven Puybasset, Louis CA Neuro Imaging Coma Emergence Recov TI Diffusion Tensor Imaging to Predict Long-term Outcome after Cardiac Arrest A Bicentric Pilot Study SO ANESTHESIOLOGY LA English DT Article ID 2010 INTERNATIONAL CONSENSUS; CARDIOVASCULAR CARE SCIENCE; CARDIOPULMONARY-RESUSCITATION; TREATMENT RECOMMENDATIONS; COMATOSE SURVIVORS; PROGNOSTIC VALUE; BRAIN-INJURY; MRI; ENCEPHALOPATHY; HYPOTHERMIA AB Background: Prognostication in comatose survivors of cardiac arrest is a major clinical challenge. The authors' objective was to determine whether an assessment with diffusion tensor imaging, a brain magnetic resonance imaging sequence, increases the accuracy of 1 yr functional outcome prediction in cardiac arrest survivors. Methods: Prospective, observational study in two intensive care units. Fifty-seven comatose survivors of cardiac arrest underwent brain magnetic resonance imaging. Fractional anisotropy (FA), a diffusion tensor imaging value, was measured in predefined white matter regions, and apparent diffusion coefficient was assessed in predefined grey matter regions. Prediction of unfavorable outcome at 1 yr was compared using four prognostic models: FA global, FA selected, apparent diffusion coefficient, and clinical classifiers. Results: Of the 57 patients included in the study, 49 had an unfavorable outcome at 12 months. Areas under the receiver operating characteristic curve (95% CI) to predict unfavorable outcome for the FA global, FA selected, clinical, and apparent diffusion coefficient models were 0.92 (0.82-0.98), 0.96 (0.87-0.99), 0.78 (0.65-0.88), and 0.86 (0.74-0.94), respectively. The FA selected model had the best overall accuracy for predicting outcome, with a score above 0.44 having 94% (95% CI, 83-99%) sensitivity and 100% (95% CI, 63-100%) specificity for the prediction of unfavorable outcome. Conclusion: Quantitative diffusion tensor imaging indicates that white matter damage is widespread after cardiac arrest. A prognostic model based on FA values in selected white matter tracts seems to predict accurately 1 yr functional outcome. These preliminary results need to be confirmed in a larger population. C1 [Luyt, Charles-Edouard; Combes, Alain; Chastre, Jean] Univ Paris 06, AP HP, Grp Hosp Pitie Salpetriere, Serv Reanimat, Paris, France. [Galanaud, Damien] Univ Paris 06, AP HP, Grp Hosp Pitie Salpetriere, Serv Neuroradiol, Paris, France. [Besancenot, Hortense] Univ Paris 06, AP HP, Grp Hosp Pitie Salpetriere, Sch Med, Paris, France. [Puybasset, Louis] Univ Paris 06, AP HP, Grp Hosp Pitie Salpetriere, Serv Anesthesie Reanimat, Paris, France. [Perlbarg, Vincent; Stevens, Robert D.] Johns Hopkins Univ, Sch Med, Div Neurosci Crit Care, Baltimore, MD USA. [Vanhaudenhuyse, Audrey; Laureys, Steven] Dept Neurol, Liege, Belgium. [Vanhaudenhuyse, Audrey; Laureys, Steven] Cyclotron Res Ctr Univ, Liege, Belgium. [Vanhaudenhuyse, Audrey; Laureys, Steven] Univ Hosp Liege Sart Tilman, Liege, Belgium. [Benali, Habib] Univ Paris 06, Unite INSERM UMR 5678, Paris, France. [Gupta, Rajiv] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Krainik, Alexandre] Hop Michalon, Serv Neuroradiol, Grenoble, France. [Audibert, Gerard] Hop Cent, Serv Anesthesie Reanimat, Nancy, France. RP Luyt, CE (reprint author), Grp Hosp Pitie Salpetriere, Inst Cardiol, Serv Reanimat Med, 47 Blvd Hop, F-75651 Paris 13, France. EM charles-edouard.luyt@psl.aphp.fr RI KRAINIK, Alexandre/L-5874-2014; krainik, alexandre/I-2431-2015; Laureys, Steven/A-3349-2011 FU French Ministry of Health, Paris, France [051061]; Agence Nationale de la Recherche [ANR-10-IAIHU-06] FX Funded by a grant from the French Ministry of Health, Paris, France (Programme Hospitalier de Recherche Clinique 2005 #051061) and from the "Agence Nationale de la Recherche" for the program "investissements d'avenir" under Agreement no ANR-10-IAIHU-06 to the Paris Institute of Translational Neurosciences-IHU-A-ICM. This work was presented at the 24th annual congress of the European Society of Intensive Care Medicine, Berlin, Germany, October 1-5 2011. Trial Registration clinicaltrials.gov Identifier: NCT00577954. NR 33 TC 33 Z9 33 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 2012 VL 117 IS 6 BP 1311 EP 1321 DI 10.1097/ALN.0b013e318275148c PG 11 WC Anesthesiology SC Anesthesiology GA 041PY UT WOS:000311414900021 PM 23135257 ER PT J AU Solt, K Chemali, JJ Van Dort, CJ Brown, EN AF Solt, Ken Chemali, Jessica J. Van Dort, Christa J. Brown, Emery N. TI Should We Use Psychostimulant Drugs to Boost the Emergence from General Anesthesia? Reply SO ANESTHESIOLOGY LA English DT Letter ID METHYLPHENIDATE C1 [Solt, Ken] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Solt, K (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ksolt@partners.org OI Solt, Ken/0000-0001-5328-2062 NR 8 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 2012 VL 117 IS 6 BP 1394 EP 1395 DI 10.1097/ALN.0b013e3182735f26 PG 2 WC Anesthesiology SC Anesthesiology GA 041PY UT WOS:000311414900036 ER PT J AU Lovejoy, TI AF Lovejoy, Travis I. TI Telephone-Delivered Motivational Interviewing Targeting Sexual Risk Behavior Reduces Depression, Anxiety, and Stress in HIV-Positive Older Adults SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE HIV; Motivational interviewing; Randomized controlled trial; Depression; Anxiety; Stress ID SCALES DASS; TRANSMISSION RISK; UNITED-STATES; SYMPTOMS; AGE; INTERVENTIONS; METAANALYSIS; HIV/AIDS; DISEASE; HEALTH AB Few studies have examined the secondary benefits of HIV risk reduction interventions to improve mental health functioning. This study aimed to examine the effectiveness of telephone-delivered motivational interviewing (MI) targeting sexual risk behavior to reduce depression, anxiety, and stress in HIV-positive older adults. Participants were 100 HIV-positive adults 45+ years old enrolled in a sexual risk reduction pilot clinical trial of telephone-delivered MI. Participants were randomly assigned to a one-session MI, four-session MI, or standard of care control condition. Telephone interviews at baseline and 3- and 6-month follow-up assessed sexual behavior, depression, anxiety, and stress. Relative to controls, participants in the one- and four-session MI conditions reported lower levels of depression, anxiety, and stress at 6-month follow-up. No between group differences were observed at 3-month follow-up or between one- and four-session MI participants at 6-month follow-up. Preliminary data suggest that telephone-delivered MI to reduce sexual risk behavior may confer secondary benefits of improving mental health functioning in HIV-positive persons. C1 Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97239 USA. RP Lovejoy, TI (reprint author), Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Rd,P3MHDC, Portland, OR 97239 USA. EM travis.lovejoy@va.gov NR 25 TC 8 Z9 8 U1 1 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2012 VL 44 IS 3 BP 416 EP 421 DI 10.1007/s12160-012-9401-6 PG 6 WC Psychology, Multidisciplinary SC Psychology GA 042TX UT WOS:000311495100015 PM 22956397 ER PT J AU Gronchi, A Raut, CP AF Gronchi, Alessandro Raut, Chandrajit P. TI Optimal Approach to Sporadic Desmoid Tumors: From Radical Surgery to Observation. Time for a Consensus? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID PROGNOSTIC-FACTORS; FIBROMATOSIS; MANAGEMENT; SERIES C1 [Gronchi, Alessandro] Fdn IRCCS Ist Nazl Tumori, Dept Surg, Sarcoma Serv, Milan, Italy. [Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Raut, Chandrajit P.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Raut, Chandrajit P.] Harvard Univ, Sch Med, Boston, MA USA. RP Gronchi, A (reprint author), Fdn IRCCS Ist Nazl Tumori, Dept Surg, Sarcoma Serv, Milan, Italy. EM alessandro.gronchi@istitutotumori.mi.it; craut@partners.org OI Gronchi, Alessandro/0000-0002-4703-3534 NR 13 TC 8 Z9 8 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2012 VL 19 IS 13 BP 3995 EP 3997 DI 10.1245/s10434-012-2636-4 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA 042ZT UT WOS:000311512400001 PM 22961405 ER PT J AU Mullen, JT DeLaney, TF Kobayashi, WK Szymonifka, J Yeap, BY Chen, YL Rosenberg, AE Harmon, DC Choy, E Yoon, SS Raskin, KA Nielsen, GP Hornicek, FJ AF Mullen, John T. DeLaney, Thomas F. Kobayashi, Wendy K. Szymonifka, Jackie Yeap, Beow Y. Chen, Yen-Lin Rosenberg, Andrew E. Harmon, David C. Choy, Edwin Yoon, Sam S. Raskin, Kevin A. Nielsen, G. Petur Hornicek, Francis J. TI Desmoid Tumor: Analysis of Prognostic Factors and Outcomes in a Surgical Series SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID AGGRESSIVE FIBROMATOSIS; RADIATION-THERAPY; ADJUVANT RADIOTHERAPY; MANAGEMENT; SURGERY; EXTREMITY; TRUNK AB Background. Desmoid tumors are rare and exhibit a highly unpredictable natural history. We sought to analyze prognostic factors associated with recurrence in a large single-institution study of patients with desmoid tumors. Methods. We performed a retrospective review of 177 patients with desmoid tumor who underwent macroscopically complete surgical resection, with or without the addition of radiotherapy (RT) or systemic therapy, from 1970 to 2009. We examined patterns of presentation, all known risk factors for recurrence, and their association with recurrence-free survival (RFS). Results. Twenty-two patients (12 %) had intra-abdominal desmoid tumors, and 155 (88 %) had extra-abdominal tumors. Patterns of presentation included primary (n = 133, 75 %) and locally recurrent (n = 44, 25 %) disease. Treatment was surgery alone in 125 patients (71 %), surgery and RT in 36 (20 %), and surgery and systemic therapy with or without RT in 20 (11 %). Median follow-up was 40 months. Overall, the local relapse rate was 29 %, and 10-year RFS was 60 %. R0 resection status was the only predictor of freedom from local recurrence on multivariate analysis (odds ratio 0.32; 95 % confidence interval 0.15-0.66; P = 0.002). The selective use of adjuvant RT appeared to improve local control in patients with positive margins. Conclusions. For patients with desmoid tumors undergoing surgery, wide excision with negative margins should be the goal, but not at the expense of function, as fewer than half of patients with positive margins will experience recurrence. C1 [Mullen, John T.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [DeLaney, Thomas F.; Kobayashi, Wendy K.; Chen, Yen-Lin] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Szymonifka, Jackie; Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Ctr Biostat, Boston, MA 02114 USA. [Rosenberg, Andrew E.; Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Raskin, Kevin A.; Hornicek, Francis J.] Massachusetts Gen Hosp, Orthoped Oncol Serv, Boston, MA 02114 USA. RP Mullen, JT (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. EM jmullen@partners.org OI Choy, Edwin/0000-0001-9896-8084 FU Proton Therapy Research and Treatment Center [C06 CA059267] FX Funded in part by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. NR 27 TC 35 Z9 35 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2012 VL 19 IS 13 BP 4028 EP 4035 DI 10.1245/s10434-012-2638-2 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 042ZT UT WOS:000311512400007 PM 22965569 ER PT J AU Lubitz, CC Stephen, AE Hodin, RA Pandharipande, P AF Lubitz, Carrie C. Stephen, Antonia E. Hodin, Richard A. Pandharipande, Pari TI Preoperative Localization Strategies for Primary Hyperparathyroidism: An Economic Analysis SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID INTRAOPERATIVE PARATHYROID-HORMONE; ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM; BILATERAL NECK EXPLORATION; MINIMALLY INVASIVE PARATHYROIDECTOMY; 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; SESTAMIBI-SPECT LOCALIZATION; 3RD INTERNATIONAL WORKSHOP; GUIDE FOCUSED EXPLORATION; CERVICAL BLOCK ANESTHESIA; COST-EFFECTIVENESS AB Strategies for localizing parathyroid pathology preoperatively vary in cost and accuracy. Our purpose was to compute and compare comprehensive costs associated with common localization strategies. A decision-analytic model was developed to evaluate comprehensive, short-term costs of parathyroid localization strategies for patients with primary hyperparathyroidism. Eight strategies were compared. Probabilities of accurate localization were extracted from the literature, and costs associated with each strategy were based on 2011 Medicare reimbursement schedules. Differential cost considerations included outpatient versus inpatient surgeries, operative time, and costs of imaging. Sensitivity analyses were performed to determine effects of variability in key model parameters upon model results. Ultrasound (US) followed by 4D-CT was the least expensive strategy ($5,901), followed by US alone ($6,028), and 4D-CT alone ($6,110). Strategies including sestamibi (SM) were more expensive, with associated expenditures of up to $6,329 for contemporaneous US and SM. Four-gland, bilateral neck exploration (BNE) was the most expensive strategy ($6,824). Differences in cost were dependent upon differences in the sensitivity of each strategy for detecting single-gland disease, which determined the proportion of patients able to undergo outpatient minimally invasive parathyroidectomy. In sensitivity analysis, US alone was preferred over US followed by 4D-CT only when both the sensitivity of US alone for detecting an adenoma was a parts per thousand yen94 %, and the sensitivity of 4D-CT following negative US was a parts per thousand currency sign39 %. 4D-CT alone was the least costly strategy when US sensitivity was a parts per thousand currency sign31 %. Among commonly used strategies for preoperative localization of parathyroid pathology, US followed by selective 4D-CT is the least expensive. C1 [Lubitz, Carrie C.; Stephen, Antonia E.; Hodin, Richard A.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Endocrine Surg Unit, Boston, MA 02115 USA. [Pandharipande, Pari] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Inst Technol Assessment, Boston, MA 02115 USA. RP Lubitz, CC (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Endocrine Surg Unit, Boston, MA 02115 USA. EM clubitz@partners.org FU Program in Cancer Outcomes Research Training Grant [NCI R25CA092203]; National Cancer Institute [K07CA133097]; Medical Imaging and Technology Alliance FX The authors thank Ekin Turan for help verifying radiation exposure estimates. This research is supported in part by the Program in Cancer Outcomes Research Training Grant (NCI R25CA092203) (Lubitz), and by Award Number K07CA133097 from the National Cancer Institute (Pandharipande). The research 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.; Dr. Pandharipande receives funding from the Medical Imaging and Technology Alliance, for unrelated research. NR 49 TC 29 Z9 29 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2012 VL 19 IS 13 BP 4202 EP 4209 DI 10.1245/s10434-012-2512-2 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 042ZT UT WOS:000311512400029 PM 22825773 ER PT J AU Badhwar, V Peterson, ED Jacobs, JP He, X Brennan, JM O'Brien, SM Dokholyan, RS George, KM Bolling, SF Shahian, DM Grover, FL Edwards, FH Gammie, JS AF Badhwar, Vinay Peterson, Eric D. Jacobs, Jeffrey P. He, Xia Brennan, J. Matthew O'Brien, Sean M. Dokholyan, Rachel S. George, Kristopher M. Bolling, Steven F. Shahian, David M. Grover, Fredrick L. Edwards, Fred H. Gammie, James S. TI Longitudinal Outcome of Isolated Mitral Repair in Older Patients: Results From 14,604 Procedures Performed From 1991 to 2007 SO ANNALS OF THORACIC SURGERY LA English DT Article ID VALVE REPAIR; CARDIAC-SURGERY; REPLACEMENT; REGURGITATION; INTERVENTIONS; SURVIVAL; DATABASE; SOCIETY; DISEASE; LINKING AB Background. Mitral valve (MV) repair is performed with less frequency than MV replacement in older persons, with referral often delayed until symptoms are severe. Surgical practice in this population remains inconsistent in the absence of national MV repair outcomes. The goal of this study was to assess durability and longitudinal outcomes after isolated primary MV repair in patients aged 65 years or more. Methods. We linked clinical data from The Society of Thoracic Surgeons adult cardiac surgery database (STS) to longitudinal claims data from the Centers for Medicare and Medicaid Services (CMS). Between January 1991 and December 2007, we identified 14,604 isolated non-emergent primary MV repair operations in STS-CMS data. These were longitudinally examined for mortality, mitral reoperation, and readmissions for heart failure, bleeding, and stroke. Predictors of 5-year death after MV repair were identified using Cox proportional hazard modeling. Results. The study cohort had a mean age of 73.3 +/- 5.5 years, ejection fraction 54.0% +/- 12.9%; 55.8% (8,148 of 14,604) were female; and 8.4% (1,233 of 14,604) were non-Caucasian. Operative mortality was 2.59% (378 of 14,604). Mean follow-up was 5.9 +/- 3.9 years (range, 1.0 to 18.0). Survival during follow-up was 74.9% (10,934 of 14,604). The number of observed events for mitral reoperation, heart failure, bleeding, and stroke were 552 of 14,604 (3.7%), 2,681 of 14,604 (18.4%), 1,051 of 14,604 (7.2%), and 1,131 of 14,604 (7.7%), respectively. The 10-year Kaplan-Meier event rates for mitral reoperation, heart failure, bleeding, and stroke were 6.2%, 30.1%, 15.3%, and 16.4%, respectively. The 10-year actuarial survival of 57.4% was equivalent to the matched US population. Conclusions. Utilizing linked STS and CMS databases, we demonstrate that MV repair is a safe and durable long-term option for older patients. Survival restored to the normal population suggests repair may suppress the longitudinal impact of mitral regurgitation in the elderly and that the practice of delayed referral should be reevaluated. These data provide a contemporary longitudinal benchmark of MV repair outcomes. (Ann Thorac Surg 2012;94:1870-9) (c) 2012 by The Society of Thoracic Surgeons C1 Duke Clin Res Inst, Durham, NC USA. Univ S Florida, All Childrens Hosp, Coll Med, Congenital Heart Inst Florida,Cardiac Surg Associ, St Petersburg, FL 33701 USA. [Badhwar, Vinay] Univ Pittsburgh, Med Ctr, Dept Cardiothorac Surg, Pittsburgh, PA 15213 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Colorado, Denver, CO 80202 USA. Univ Florida, Jacksonville, FL USA. Univ Maryland, Baltimore, MD 21201 USA. RP Badhwar, V (reprint author), Univ Pittsburgh, Med Ctr, Dept Cardiothorac Surg, 200 Lothrop St,Ste C-711, Pittsburgh, PA 15213 USA. EM badhwarv@upmc.edu RI O'Brien, Sean/H-6268-2013 FU The Society of Thoracic Surgeons Research Center through the Adult National Cardiac Database; Duke Clinical Research Institute FX This work was supported by The Society of Thoracic Surgeons Research Center through the Adult National Cardiac Database and the Duke Clinical Research Institute. The authors also thank Ms Diana Zaldonis for her assistance. NR 29 TC 40 Z9 40 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2012 VL 94 IS 6 BP 1870 EP 1879 DI 10.1016/j.athoracsur.2012.05.105 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 041XW UT WOS:000311436300024 PM 22858278 ER PT J AU Shahian, DM He, X Jacobs, JP Rankin, JS Welke, KF Filardo, G Shewan, CM O'Brien, SM AF Shahian, David M. He, Xia Jacobs, Jeffrey P. Rankin, J. Scott Welke, Karl F. Filardo, Giovanni Shewan, Cynthia M. O'Brien, Sean M. TI The Society of Thoracic Surgeons Isolated Aortic Valve Replacement (AVR) Composite Score: A Report of the STS Quality Measurement Task Force SO ANNALS OF THORACIC SURGERY LA English DT Article ID BYPASS-GRAFTING SURGERY; ADULT CARDIAC-SURGERY; CONTROLLED-TRIAL; ORAL AMIODARONE; PREVENTION AB Background. Risk-standardized mortality rates provide a valuable but incomplete assessment of provider performance. Consequently, The Society of Thoracic Surgeons (STS) previously developed a multidimensional composite quality measure for coronary artery bypass grafting, the most frequently performed cardiac surgical procedure. The current study creates a similar composite measure for isolated aortic valve replacement (AVR). Methods. Because there are few widely accepted process measures for AVR, the STS AVR composite score is based solely on outcomes, including risk-standardized mortality and any-or-none risk-standardized morbidity (occurrence of sternal infection, reoperation, stroke, renal failure, or prolonged ventilation). Isolated AVR is performed less frequently than coronary artery bypass grafting, and 1 year of data provided inadequate sample sizes for profiling. Therefore, we investigated observation periods of 3 years (July 1, 2007, to June 30, 2010: 67,138 records, 2,082 deaths, and 11,962 morbidity events) and 5 years (July 1, 2005, to June 30, 2010: 101,269 records, 3,123 deaths, and 17,514 morbidity events). We also compared results using 90%, 95%, and 98% credible intervals, corresponding to 95%, 97.5%, and 99% Bayesian probabilities, to determine "star ratings." Results. Differences between 3-year and 5-year results were small; the former was chosen because this time frame provides more current and relevant data. Using 3 years of data and 95% credible intervals, adjusted mortality and morbidity rates varied threefold from highest performing (3 stars) to lowest performing (1 star) programs. Approximately 3% of participants were 1-star, 6% were 3-star, and 91% were 2-star programs. Conclusions. STS has developed a composite mortality and morbidity outcomes measure for isolated AVR to be used in quality assessment, provider feedback, public reporting, and performance improvement. (Ann Thorac Surg 2012;94:2166-71) (c) 2012 by The Society of Thoracic Surgeons C1 [Shahian, David M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Shahian, David M.] Harvard Univ, Sch Med, Boston, MA USA. [He, Xia; O'Brien, Sean M.] Duke Clin Res Inst, Durham, NC USA. [Jacobs, Jeffrey P.] Congenital Heart Inst Florida, St Petersburg, FL USA. [Rankin, J. Scott] Vanderbilt Univ, Centennial Med Ctr, Nashville, TN USA. [Welke, Karl F.] Mary Bridge Childrens Hosp, Tacoma, WA USA. [Filardo, Giovanni] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX USA. [Shewan, Cynthia M.] Soc Thorac Surg, Chicago, IL USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org RI O'Brien, Sean/H-6268-2013 NR 9 TC 30 Z9 31 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2012 VL 94 IS 6 BP 2166 EP 2171 DI 10.1016/j.athoracsur.2012.08.120 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 041XW UT WOS:000311436300079 PM 23127768 ER PT J AU Weinstein, EA Liu, L Ordonez, AA Wang, H Hooker, JM Tonge, PJ Jain, SK AF Weinstein, E. A. Liu, L. Ordonez, A. A. Wang, H. Hooker, J. M. Tonge, P. J. Jain, S. K. TI Noninvasive Determination of 2-[F-18]-Fluoroisonicotinic Acid Hydrazide Pharmacokinetics by Positron Emission Tomography in Mycobacterium tuberculosis-Infected Mice SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CATALASE-PEROXIDASE GENE; TIGHT-BINDING INHIBITOR; DRUG-RESISTANCE; ISONIAZID RESISTANCE; INHA; KATG; REDUCTASE; SLOW; PYRAZINAMIDE; ETHAMBUTOL AB Tuberculosis (TB) is a global pandemic requiring sustained therapy to facilitate curing and to prevent the emergence of drug resistance. There are few adequate tools to evaluate drug dynamics within infected tissues in vivo. In this report, we evaluated a fluorinated analog of isoniazid (INH), 2-[F-18]fluoroisonicotinic acid hydrazide (2-[F-18]-INH), as a probe for imaging Mycobacterium tuberculosis-infected mice by dynamic positron emission tomography (PET). We developed a tail vein catheter system to safely deliver drugs to M. tuberculosis aerosol-infected mice inside sealed biocontainment devices. Imaging was rapid and noninvasive, and it could simultaneously visualize multiple tissues. Dynamic PET imaging demonstrated that 2-[F-18]-INH was extensively distributed and rapidly accumulated at the sites of infection, including necrotic pulmonary TB lesions. Compared to uninfected animals, M. tuberculosis-infected mice had a significantly higher PET signal within the lungs (P<0.05) despite similar PET activity in the liver (P>0.85), suggesting that 2-[F-18]-INH accumulated at the site of the pulmonary infection. Furthermore, our data indicated that similar to INH, 2-[F-18]-INH required specific activation and accumulated within the bacterium. Pathogen-specific metabolism makes positron-emitting INH analogs attractive candidates for development into imaging probes with the potential to both detect bacteria and yield pharmacokinetic data in situ. Since PET imaging is currently used clinically, this approach could be translated from preclinical studies to use in humans. C1 [Weinstein, E. A.; Ordonez, A. A.; Jain, S. K.] Johns Hopkins Univ, Sch Med, Ctr Infect & Inflammat Imaging, Baltimore, MD 21218 USA. [Weinstein, E. A.; Ordonez, A. A.; Jain, S. K.] Johns Hopkins Univ, Sch Med, Ctr TB Res, Baltimore, MD USA. [Weinstein, E. A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Ordonez, A. A.; Jain, S. K.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Liu, L.; Wang, H.; Tonge, P. J.] SUNY Stony Brook, Dept Chem, Inst Chem Biol & Drug Discovery, Stony Brook, NY 11794 USA. [Hooker, J. M.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Hooker, J. M.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Jain, SK (reprint author), Johns Hopkins Univ, Sch Med, Ctr Infect & Inflammat Imaging, Baltimore, MD 21218 USA. EM sjain5@jhmi.edu OI Hooker, Jacob/0000-0002-9394-7708 FU NIH [OD006492, AI084189]; [DE-AC02-98CH10886] FX This study was funded by the NIH Director's New Innovator Award OD006492 (S.K.J.) and AI084189 (P.J.T).; We thank Eric Nuermberger (JHU) for providing us with the INH-resistant M. tuberculosis strains. We also thank Ronnie Mease (JHU) for help with radiosynthesis. Part of this research was carried out at Brookhaven National Laboratory (BNL) under contract DE-AC02-98CH10886 with infrastructure support from its Office of Biological and Environmental Research. We are grateful to Joanna Fowler (BNL) for providing cyclotron and radiosynthesis facilities, Michael Schueller (BNL) for cyclotron operations, and David Alexoff (BNL) and Youwen Xu (BNL) for technical assistance. NR 43 TC 16 Z9 16 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2012 VL 56 IS 12 BP 6284 EP 6290 DI 10.1128/AAC.01644-12 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 036TA UT WOS:000311052900026 PM 23006755 ER PT J AU Parrinello, CM Landay, AL Hodis, HN Gange, SJ Norris, PJ Young, M Anastos, K Tien, PC Xue, XN Lazar, J Benning, L Tracy, RP Kaplan, RC AF Parrinello, Christina M. Landay, Alan L. Hodis, Howard N. Gange, Stephen J. Norris, Philip J. Young, Mary Anastos, Kathryn Tien, Phyllis C. Xue, Xiaonan Lazar, Jason Benning, Lorie Tracy, Russell P. Kaplan, Robert C. TI Association of subclinical atherosclerosis with lipid levels amongst antiretroviral-treated and untreated HIV-infected women in the Women's Interagency HIV study SO ATHEROSCLEROSIS LA English DT Article DE Cardiovascular diseases; Carotid arteries; HAART; HIV; Lipids ID INTIMA-MEDIA THICKNESS; CARDIOVASCULAR RISK; POSITIVE PATIENTS; SERUM-LIPIDS; THERAPY; HAART; MEN; PROGRESSION; IMPACT; HDL AB Objective: We examined serum lipids in association with carotid artery intima-media thickness (CIMT) in HIV-infected and HIV-uninfected women. Methods: In 2003-4, among 1827 Women's Interagency HIV Study participants, we measured CIMT and lipids (high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), non-HDL-c). A subset of 520 treated HIV-infected women had pre-1997 lipid measures. We used multivariable linear regression to examine associations between lipids and CIMT. Results: In HIV-uninfected women, higher TC, LDL-c and non-HDL-c were associated with increased CIMT. Among HIV-infected women, associations of lipids with CIMT were observed in treated but not untreated women. Among the HIV-infected women treated in 2003-4, CIMT was associated both with lipids measured a decade earlier in infection, and with late lipid measurements. Conclusion: Among HIV-infected women, hyperlipidemia is most strongly associated with subclinical atherosclerosis in treated women. Among treated women, the association appeared strongest early in the disease course. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Parrinello, Christina M.; Anastos, Kathryn; Xue, Xiaonan; Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Landay, Alan L.] Rush Univ, Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA. [Hodis, Howard N.] Univ So Calif, Atherosclerosis Res Unit, Los Angeles, CA USA. [Gange, Stephen J.; Benning, Lorie] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Norris, Philip J.] Blood Syst Res Inst, San Francisco, CA USA. [Norris, Philip J.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Norris, Philip J.; Tien, Phyllis C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Young, Mary] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lazar, Jason] Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. RP Kaplan, RC (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave,Belfer 1306C, Bronx, NY 10461 USA. EM Robert.kaplan@einstein.yu.edu OI Gange, Stephen/0000-0001-7842-512X FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131]; National Heart, Lung and Blood Institute [1R01HL095140, 1R01HL083760]; University of Washington's CVD and Metabolic Complications of HIV/AIDS Data Coordinating Center [5R01HL095126] FX Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington, DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is co-funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). Additional co-funding is provided by the National Heart, Lung and Blood Institute (1R01HL095140, 1R01HL083760 to R. C. K.). Partial funding for laboratory and imaging work as well as assistance with general study coordination was provided by the University of Washington's CVD and Metabolic Complications of HIV/AIDS Data Coordinating Center (5R01HL095126). NR 15 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 2012 VL 225 IS 2 BP 408 EP 411 DI 10.1016/j.atherosclerosis.2012.09.035 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 040SV UT WOS:000311344700046 PM 23089369 ER PT J AU Buchbinder, D Nugent, DJ Brazauskas, R Wang, ZW Aljurf, MD Cairo, MS Chow, R Duncan, C Eldjerou, LK Gupta, V Hale, GA Halter, J Hayes-Lattin, BM Hsu, JW Jacobsohn, DA Kamble, RT Kasow, KA Lazarus, HM Mehta, P Myers, KC Parsons, SK Passweg, JR Pidala, J Reddy, V Sales-Bonfim, CM Savani, BN Seber, A Sorror, ML Steinberg, A Wood, WA Wall, DA Winiarski, JH Yu, LC Majhail, NS AF Buchbinder, David Nugent, Diane J. Brazauskas, Ruta Wang, Zhiwei Aljurf, Mahmoud D. Cairo, Mitchell S. Chow, Robert Duncan, Christine Eldjerou, Lamis K. Gupta, Vikas Hale, Gregory A. Halter, Joerg Hayes-Lattin, Brandon M. Hsu, Jack W. Jacobsohn, David A. Kamble, Rammurti T. Kasow, Kimberly A. Lazarus, Hillard M. Mehta, Paulette Myers, Kasiani C. Parsons, Susan K. Passweg, Jakob R. Pidala, Joseph Reddy, Vijay Sales-Bonfim, Carmen M. Savani, Bipin N. Seber, Adriana Sorror, Mohamed L. Steinberg, Amir Wood, William A. Wall, Donna A. Winiarski, Jacek H. Yu, Lolie C. Majhail, Navneet S. TI Late Effects in Hematopoietic Cell Transplant Recipients with Acquired Severe Aplastic Anemia: A Report from the Late Effects Working Committee of the Center for International Blood and Marrow Transplant Research SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hematopoietic cell transplant; Allogeneic; Survivorship; Severe aplastic anemia; Late effects ID TERM-FOLLOW-UP; UNRELATED DONOR TRANSPLANTATION; TOTAL-BODY IRRADIATION; ANTITHYMOCYTE GLOBULIN; SOLID CANCERS; CONDITIONING REGIMEN; PEDIATRIC-PATIENTS; MALIGNANT-TUMORS; BONE; CYCLOPHOSPHAMIDE AB With improvements in hematopoietic cell transplant (HCT) outcomes for severe aplastic anemia (SAA), there is a growing population of SAA survivors after HCT. However, there is a paucity of information regarding late effects that occur after HCT in SAA survivors. This study describes the malignant and nonmalignant late effects in survivors with SAA after HCT. A descriptive analysis was conducted of 1718 patients post-HCT for acquired SAA between 1995 and 2006 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The prevalence and cumulative incidence estimates of late effects are reported for 1-year HCT survivors with SAA. Of the HCT recipients, 1176 (68.5%) and 542 (31.5%) patients underwent a matched sibling donor (MSD) or unrelated donor (URD) HCT, respectively. The median age at the time of HCT was 20 years. The median interval from diagnosis to transplantation was 3 months for MSD HCT and 14 months for URD HCT. The median follow-up was 70 months and 67 months for MSD and URD HCT survivors, respectively. Overall survival at I year, 2 years, and 5 years for the entire cohort was 76% (95% confidence interval [CI]: 74-78), 73% (95% CI: 71-75), and 70% (95% CI: 68-72). Among 1-year survivors of MSD HCT, 6% had 1 late effect and 1% had multiple late effects. For 1-year survivors of URD HCT, 13% had 1 late effect and 2% had multiple late effects. Among survivors of MSD HCT, the cumulative incidence estimates of developing late effects were all <3% and did not increase over time. In contrast, for recipients of URD HCT, the cumulative incidence of developing several late effects exceeded 3% by 5 years: gonadal dysfunction 10.5% (95% CI: 7.3-14.3), growth disturbance 7.2% (95% CI: 4.4-10.7), avascular necrosis 6.3% (95% CI: 3.6-9.7), hypothyroidism 5.5% (95% CI: 2.8-9.0), and cataracts 5.1% (95% CI: 2.9-8.0). Our results indicated that all patients undergoing HCT for SAA remain at risk for late effects, must be counseled about, and should be monitored for late effects for the remainder of their lives. C1 [Buchbinder, David; Nugent, Diane J.] Childrens Hosp Orange Cty, Dept Hematol, Orange, CA 92668 USA. [Brazauskas, Ruta] CIBMTR Med Coll Wisconsin, Dept Biostat, Milwaukee, WI USA. [Wang, Zhiwei] Med Coll Wisconsin, CIBMTR Stat Ctr, Milwaukee, WI 53226 USA. [Aljurf, Mahmoud D.] King Faisal Specialist Hosp & Res Ctr, Dept Oncol, Riyadh 11211, Saudi Arabia. [Cairo, Mitchell S.] New York Med Coll, Dept Pediat Hematol Oncol & Stem Cell Transplanta, Valhalla, NY 10595 USA. [Chow, Robert] Stemcyte, Covina, CA USA. [Duncan, Christine] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Eldjerou, Lamis K.; Hsu, Jack W.] Univ Florida, Dept Hematol Oncol, Gainesville, FL USA. [Gupta, Vikas] Princess Margaret Hosp, Dept Med, Toronto, ON M4X 1K9, Canada. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, Dept Pediat Hematol & Oncol, St Petersburg, FL 33701 USA. [Halter, Joerg; Passweg, Jakob R.] Univ Basel Hosp, Dept Hematol, CH-4031 Basel, Switzerland. [Hayes-Lattin, Brandon M.] Oregon Hlth & Sci Univ, Dept Hematol & Oncol, Portland, OR 97201 USA. [Jacobsohn, David A.] Childrens Natl Med Ctr, Dept Blood & Marrow Transplantat, Washington, DC 20010 USA. [Kamble, Rammurti T.] Baylor Coll Med, Ctr Cell Therapy, Dept Hematol & Oncol, Houston, TX 77030 USA. [Kasow, Kimberly A.] Univ N Carolina Hosp, Dept Pediat, Chapel Hill, NC USA. [Lazarus, Hillard M.] Univ Hosp Case, Med Ctr, Dept Med, Cleveland, OH USA. [Mehta, Paulette] Univ Arkansas Med Sci, Dept Hematol & Oncol, Little Rock, AR 72205 USA. [Myers, Kasiani C.] Cincinnati Childrens Hosp Med Ctr, Dept Bone Marrow Transplantat & Immune Deficiency, Cincinnati, OH USA. [Parsons, Susan K.] Tufts Med Ctr, Dept Med & Pediat, Boston, MA USA. [Pidala, Joseph] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Hematol & Oncol, Tampa, FL 33612 USA. [Reddy, Vijay] Florida Ctr Cellular Therapy, Dept Med, Orlando, FL USA. [Sales-Bonfim, Carmen M.] Univ Fed Parana, Dept Bone Marrow Transplantat, BR-80060000 Curitiba, Parana, Brazil. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. [Seber, Adriana] Inst Oncol Pediat, Dept Pediat, Sao Paulo, Brazil. [Sorror, Mohamed L.] Fred Hutchinson Canc Res Ctr, Dept Clin Res & Transplantat, Seattle, WA 98104 USA. [Steinberg, Amir] Mt Sinai Med Ctr, Dept Bone Marrow & Stem Cell Transplantat, New York, NY 10029 USA. [Wood, William A.] Univ N Carolina Hosp, Dept Hematol & Oncol, Chapel Hill, NC USA. [Wall, Donna A.] Univ Manitoba, CancerCare Manitoba, Dept Manitoba Blood & Marrow Transplant Program, Winnipeg, MB, Canada. [Winiarski, Jacek H.] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Dept Pediat, Stockholm, Sweden. [Yu, Lolie C.] Louisiana State Univ, Hlth Sci Ctr, Childrens Hosp, Dept Pediat, New Orleans, LA USA. [Majhail, Navneet S.] Dept Natl Marrow Donor Program, Minneapolis, MN USA. RP Majhail, NS (reprint author), Natl Marrow Donor Program, 3001 Broadway St NE,Suite 100, Minneapolis, MN 55416 USA. EM nmajhail@nmdp.org OI Wood, William/0000-0001-7439-2543 FU Public Health Service Grant from the National Cancer Institute [U24-CA76518]; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute [5U01HL069294]; National Cancer Institute; Health Resources and Services Administration/Department of Health and Human Services; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos; Amgen; Angioblast; [HHSH234200637015C] FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases; a Grant/Cooperative Agreement 5U01HL069294 from the National Heart, Lung, and Blood Institute and National Cancer Institute; a contract HHSH234200637015C with Health Resources and Services Administration/Department of Health and Human Services; 2 grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos; Amgen; Angioblast; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America; Gamida Cell Teva Joint Venture Ltd.; Genentech; Genzyme Corporation; GlaxoSmithKline; HistoGenetics; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co.; Millennium: The Takeda Oncology Co.; Milliman USA; Miltenyi Biotec; National Marrow Donor Program; Optum Healthcare Solutions; Osiris Therapeutics; Otsuka America Pharmaceutical; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience; THERAKOS; and Wellpoint. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the U.S. Government. NR 33 TC 9 Z9 10 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2012 VL 18 IS 12 BP 1776 EP 1784 DI 10.1016/j.bbmt.2012.06.018 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 044BH UT WOS:000311593900003 PM 22863842 ER PT J AU Ballen, K Mendizabal, AM Cutler, C Politikos, I Jamieson, K Shpall, EJ Dey, BR Attar, E McAfee, S Delaney, C McCarthy, P Ball, ED Kamble, R Avigan, D Maziarz, RT Ho, VT Koreth, J Alyea, E Soiffer, R Wingard, JR Boussiotis, V Spitzer, TR Antin, JH AF Ballen, Karen Mendizabal, Adam M. Cutler, Corey Politikos, Ioannis Jamieson, Katarzyna Shpall, Elizabeth J. Dey, Bimalangshu R. Attar, Eyal McAfee, Steven Delaney, Colleen McCarthy, Philip Ball, Edward D. Kamble, Ram Avigan, David Maziarz, Richard T. Ho, Vincent T. Koreth, John Alyea, Edwin Soiffer, Robert Wingard, John R. Boussiotis, Vicki Spitzer, Thomas R. Antin, Joseph H. TI Phase II Trial of Parathyroid Hormone after Double Umbilical Cord Blood Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Transplantation; Cord blood; Engraftment ID STEM-CELL NICHE; PROGENITOR CELLS; ADULTS; RECONSTITUTION; OSTEOBLASTS; EXPANSION AB Transplantation of 1 or 2 umbilical cord blood products is a useful alternative stem cell source. However, the limited number of stem cells in each infusion results in slow engraftment. In mouse models, administration of parathyroid hormone (PTH) is an effective way to enhance the ability of limited numbers of hematopoietic stem cells to support hematopoiesis. In this study, patients received either a myeloablative or a reduced-intensity double umbilical cord blood transplantation, followed by PTH at 100 mu g/day for 28 days. Thirteen patients (median age, 42 years) were enrolled. All patients engrafted; the median time to neutrophil and platelet engraftment of > 20 x 10(9) cells/L was 30 days and 61 days, respectively. The incidence of grade II-IV acute GVHD was 38.5% at day 100. Four deaths occurred before day 100, prompting early study closure. No patient who received a myeloablative regimen relapsed. Overall survival at 6 months after transplantation was 62%, and disease-free survival at 2 years was 39%. At the dose and schedule studied, there was no evidence that PTH influenced blood count recovery. Biol Blood Marrow Transplant 18: 1851-1858 (2012) (c) 2012 American Society for Blood and Marrow Transplantation C1 [Ballen, Karen; Dey, Bimalangshu R.; Attar, Eyal; McAfee, Steven; Spitzer, Thomas R.] Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. [Mendizabal, Adam M.] EMMES Corp, Rockville, MD USA. [Cutler, Corey; Ho, Vincent T.; Koreth, John; Alyea, Edwin; Soiffer, Robert; Antin, Joseph H.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Politikos, Ioannis; Avigan, David; Boussiotis, Vicki] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Jamieson, Katarzyna; Wingard, John R.] Univ Florida, Ctr Canc, Gainesville, FL USA. [Shpall, Elizabeth J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Delaney, Colleen] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [McCarthy, Philip] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Ball, Edward D.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Kamble, Ram] Baylor Coll Med, Houston, TX 77030 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Knight Canc Ctr, Portland, OR 97201 USA. RP Ballen, K (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, 0 Emerson Pl,Suite 118,Room 134, Boston, MA 02114 USA. EM kballen@partners.org OI Politikos, Ioannis/0000-0002-8925-2399 FU National Heart, Lung, and Blood Institute [U54 HL081030]; Jock and Bunny Adams Research and Education Endowment FX Supported by the National Heart, Lung, and Blood Institute (grant U54 HL081030) and the Jock and Bunny Adams Research and Education Endowment. NR 31 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2012 VL 18 IS 12 BP 1851 EP 1858 DI 10.1016/j.bbmt.2012.06.016 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 044BH UT WOS:000311593900012 PM 22766223 ER PT J AU McMurrich, S Sylvia, LG Dupuy, JM Peckham, AD Peters, AT Deckersbach, T Perlis, RH AF McMurrich, Stephanie Sylvia, Louisa G. Dupuy, Jamie M. Peckham, Andrew D. Peters, Amy T. Deckersbach, Thilo Perlis, Roy H. TI Course, outcomes, and psychosocial interventions for first-episode mania SO BIPOLAR DISORDERS LA English DT Review DE bipolar disorder; early intervention; first episode; mania; psychotherapy; schizophrenia ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; BIPOLAR-I DISORDER; MULTIFAMILY PSYCHOEDUCATION GROUPS; 1ST EPISODE PSYCHOSIS; 1-YEAR FOLLOW-UP; EARLY SCHIZOPHRENIA; WORKPLACE SKILLS; YOUNG-PEOPLE; ACUTE-PHASE AB McMurrich S, Sylvia LG, Dupuy JM, Peckham AD, Peters AT, Deckersbach T, Perlis RH. Course, outcomes, and psychosocial interventions for first-episode mania. Bipolar Disord 2012: 14: 797808. (C) 2012 The Authors. Journal compilation (C) 2012 John Wiley & Sons A/S. Objectives: The course of bipolar disorder tends to worsen over time, highlighting the importance of early intervention. Despite the recognized need for adjunctive psychosocial treatments in first-episode mania, very few studies have evaluated psychological interventions for this period of significant risk. In this empirical review, we evaluate existing research on first-episode bipolar disorder, compare this body of research to parallel studies of first-episode schizophrenia, and identify strategies for future research. Methods: A comprehensive literature search of the MEDLINE and PsychINFO databases was conducted to identify studies of first-episode mania, as well as first-episode schizophrenia. Recovery and relapse rates were compared across studies. Results: In contrast to a number of studies of first-episode schizophrenia, the authors identified only seven independent programs assessing first-episode mania. Findings from these studies suggest that, while pharmacological treatment helps patients achieve recovery from acute episodes, it fails to bring patients to sustained remission. Early psychosocial intervention may be imperative in reducing residual symptoms, preventing recurrence of mood episodes, and improving psychosocial functioning. However, very few studies of psychosocial interventions for first-episode mania have been systematically studied. Conclusions: Studies of first-episode mania indicate a gap between syndromal/symptomatic and functional recovery. Novel psychosocial interventions for first-episode mania may help bridge this gap, but require controlled study. C1 [McMurrich, Stephanie; Sylvia, Louisa G.; Dupuy, Jamie M.; Peters, Amy T.; Deckersbach, Thilo; Perlis, Roy H.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [McMurrich, Stephanie; Sylvia, Louisa G.; Dupuy, Jamie M.; Peters, Amy T.; Deckersbach, Thilo; Perlis, Roy H.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [McMurrich, Stephanie; Sylvia, Louisa G.; Dupuy, Jamie M.; Deckersbach, Thilo; Perlis, Roy H.] Harvard Univ, Sch Med, Boston, MA USA. [Peckham, Andrew D.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. RP Sylvia, LG (reprint author), Massachusetts Gen Hosp, Bipolar Clin, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM lsylvia2@partners.org NR 72 TC 10 Z9 10 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2012 VL 14 IS 8 BP 797 EP 808 DI 10.1111/bdi.12001 PG 12 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 041LP UT WOS:000311403600002 PM 22963164 ER PT J AU Hegarty, CE Foland-Ross, LC Narr, KL Sugar, CA McGough, JJ Thompson, PM Altshuler, LL AF Hegarty, Catherine E. Foland-Ross, Lara C. Narr, Katherine L. Sugar, Catherine A. McGough, James J. Thompson, Paul M. Altshuler, Lori L. TI ADHD comorbidity can matter when assessing cortical thickness abnormalities in patients with bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; attention-deficit hyperactivity disorder; comorbidity; magnetic resonance imaging; cortical thickness; cortical pattern matching; prefrontal cortex; anterior cingulate cortex; subgenual cingulate cortex; orbitofrontal cortex ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; SUBGENUAL PREFRONTAL CORTEX; VOXEL-BASED MORPHOMETRY; ORBITOFRONTAL CORTEX; VOLUME REDUCTIONS; STRUCTURAL ABNORMALITIES; RESPONSE-INHIBITION; EXECUTIVE FUNCTION; I DISORDER AB Hegarty CE, Foland-Ross LC, Narr KL, Sugar CA, McGough JJ, Thompson PM, Altshuler LL. ADHD comorbidity can matter when assessing cortical thickness abnormalities in patients with bipolar disorder. ?Bipolar Disord 2012: 14: 843855. (C) 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: Attention-deficit hyperactivity disorder (ADHD) is prevalent in patients with bipolar disorder (BP), but very few studies consider this when interpreting magnetic resonance imaging findings. No studies, to our knowledge, have screened for or controlled for the presence of ADHD when examining cortical thickness in patients with BP. We used a 2 x 2 design to evaluate the joint effects of BP and ADHD on cortical thickness and uncover the importance of ADHD comorbidity in BP subjects. Methods: The study included 85 subjects: 31 healthy controls, 17 BP-only, 19 ADHD-only, and 18 BP/ADHD. All patients with BP were subtype I, euthymic, and not taking lithium. Groups did not differ significantly in age or gender distribution. We used cortical thickness measuring tools combined with cortical pattern matching methods to align sulcal/gyral anatomy across participants. Significance maps were used to check for both main effects of BP and ADHD and their interaction. Post-hoc comparisons assessed how the effects of BP on cortical thickness varied as a function of the presence or absence of ADHD. Results: Interactions of BP and ADHD diagnoses were found in the left subgenual cingulate and right orbitofrontal cortex, demonstrating that the effect of BP on cortical thickness depends on ADHD status. Conclusions: Some brain abnormalities attributed to BP may result from the presence of ADHD. Diagnostic interactions were found in regions previously implicated in the pathophysiology of BP, making it vital to control for an ADHD comorbid diagnosis when attempting to isolate neural or genetic abnormalities specific to BP. C1 [Hegarty, Catherine E.; Sugar, Catherine A.; McGough, James J.; Thompson, Paul M.; Altshuler, Lori L.] Univ Calif Los Angeles, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Foland-Ross, Lara C.] Stanford Univ, Dept Psychol, Mood & Anxiety Disorders Lab, Stanford, CA 94305 USA. [Narr, Katherine L.; Thompson, Paul M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Lab Neuro Imaging, Los Angeles, CA 90095 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Sugar, Catherine A.; Altshuler, Lori L.] W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [McGough, James J.; Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Altshuler, LL (reprint author), UCLA Mood Disorders Res Program, 300 UCLA Med Plaza,Suite 1544,Box 956968, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu OI Hegarty, Catherine/0000-0003-4976-774X FU Furlotti Family Foundation; National Institute of Mental Health [K24 MH001848, R21 MH075944, 5F31MH078556, EB008432, EB008281, EB007813, HD050735, RR013642]; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [RR12169, RR13642, RR00865] FX The authors gratefully acknowledge the Furlotti Family Foundation, (LLA) and the National Institute of Mental Health (K24 MH001848, R21 MH075944) (LLA), 5F31MH078556) (LCF), (EB008432, EB008281, EB007813, HD050735, and RR013642) (PMT) for their financial support of this study. For generous support, the authors also wish to thank the Brain Mapping Medical Research Organization, Brain Mapping Support Foundation, Pierson-Lovelace Foundation, The Ahmanson Foundation, William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, Tamkin Foundation, Jennifer Jones-Simon Foundation, Capital Group Companies Charitable Foundation, Robson Family, and Northstar Fund. The project described was supported by grant #RR12169, #RR13642, and #RR00865 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). The contents of the paper are solely the responsibility of the authors and do not necessarily represent the official views of NIH. NR 77 TC 7 Z9 7 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2012 VL 14 IS 8 BP 843 EP 855 DI 10.1111/bdi.12024 PG 13 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 041LP UT WOS:000311403600006 PM 23167934 ER PT J AU Thorp, JM Camargo, CA McGee, PL Harper, M Klebanoff, MA Sorokin, Y Varner, MW Wapner, RJ Caritis, SN Iams, JD Carpenter, MW Peaceman, AM Mercer, BM Sciscione, A Rouse, DJ Ramin, SM Anderson, GB AF Thorp, J. M. Camargo, C. A. McGee, P. L. Harper, M. Klebanoff, M. A. Sorokin, Y. Varner, M. W. Wapner, R. J. Caritis, S. N. Iams, J. D. Carpenter, M. W. Peaceman, A. M. Mercer, B. M. Sciscione, A. Rouse, D. J. Ramin, S. M. Anderson, G. B. CA Eunice Kennedy Shriver Natl Inst C TI Vitamin D status and recurrent preterm birth: a nested case-control study in high-risk women SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article DE Perinatal nutrition; preterm birth; vitamin D ID D SUPPLEMENTATION; DOUBLE-BLIND; PREGNANCY; OUTCOMES; TRIAL; PREECLAMPSIA; CALCIUM AB Please cite this paper as: Thorp J, Camargo C, McGee P, Harper M, Klebanoff M, Sorokin Y, Varner M, Wapner R, Caritis S, Iams J, Carpenter M, Peaceman A, Mercer B, Sciscione A, Rouse D, Ramin S, Anderson G. Vitamin D status and recurrent preterm birth: a nested casecontrol study in high-risk women. BJOG 2012;119:16171623. Objective To determine whether vitamin D status is associated with recurrent preterm birth, and any interactions between vitamin D levels and fish consumption. Design A nested casecontrol study, using data from a randomised trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth. Setting Fourteen academic health centres in the USA. Population Women with prior spontaneous preterm birth. Methods In 131 cases (preterm delivery at <35 weeks of gestation) and 134 term controls, we measured serum 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography-tandem mass spectrometry (LC-MS) from samples collected at baseline (1622 weeks of gestation). Logistic regression models controlled for study centre, maternal age, race/ethnicity, number of prior preterm deliveries, smoking status, body mass index, and treatment. Main outcome measures Recurrent preterm birth at <37 and <32 weeks of gestation. Results The median mid-gestation serum 25(OH)D concentration was 67 nmol/l, and 27% had concentrations of <50 nmol/l. Serum 25(OH)D concentration was not significantly associated with preterm birth (OR 1.33; 95% CI 0.483.70 for lowest versus highest quartiles). Likewise, comparing women with 25(OH)D concentrations of 50 nmol/l, or higher, with those with <50 nmol/l generated an odds ratio of 0.80 (95% CI 0.381.69). Contrary to our expectation, a negative correlation was observed between fish consumption and serum 25(OH)D concentration (-0.18, P < 0.01). Conclusions In a cohort of women with a prior preterm birth, vitamin D status at mid-pregnancy was not associated with recurrent preterm birth. C1 [Thorp, J. M.] Univ N Carolina, Dept Obstet & Gynecol, Sch Med, Chapel Hill, NC 27599 USA. [Camargo, C. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [McGee, P. L.] George Washington Univ, Biostat Ctr, Washington, DC USA. [Harper, M.] Wake Forest Univ Hlth Sci, Dept Obstet, Winston Salem, NC USA. [Harper, M.] Wake Forest Univ Hlth Sci, Dept Gynecol, Winston Salem, NC USA. [Klebanoff, M. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Sorokin, Y.] Wayne State Univ, Detroit, MI USA. [Varner, M. W.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. [Wapner, R. J.] Columbia Univ, Columbia, NY USA. [Caritis, S. N.] Univ Pittsburgh, Pittsburgh, PA USA. [Iams, J. D.] Ohio State Univ, Columbus, OH 43210 USA. [Carpenter, M. W.] Brown Univ, Women & Infants Hosp, Providence, RI USA. [Peaceman, A. M.] Northwestern Univ, Chicago, IL 60611 USA. [Mercer, B. M.] Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA. [Sciscione, A.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Rouse, D. J.] Univ Alabama Birmingham, Birmingham, AL USA. [Ramin, S. M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Anderson, G. B.] Univ Texas Med Ctr, Galveston, TX USA. RP Thorp, JM (reprint author), Univ N Carolina, Dept Obstet & Gynecol, Sch Med, 3027 Old Clin Bldg, Chapel Hill, NC 27599 USA. EM thorp@med.unc.edu RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850; Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD27860, HD27917, HD40560, HD34208, HD40485, HD21410, HD27915, HD 40500, HD40512, HD40544, MO1-RR-000080, HD34136, HD27869, HD40545, HD36801, HD19897]; Massachusetts General Hospital Center for D-receptor Activation Research (Boston, MA, USA) FX The project described was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (HD27860, HD27917, HD40560, HD34208, HD40485, HD21410, HD27915, HD 40500, HD40512, HD40544, MO1-RR-000080, HD34136, HD27869, HD40545, HD36801, and HD19897), and does not necessarily represent the official views of the NICHD or National Institutes of Health (NIH). CAC was supported, in part, by the Massachusetts General Hospital Center for D-receptor Activation Research (Boston, MA, USA). NR 19 TC 20 Z9 21 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD DEC PY 2012 VL 119 IS 13 BP 1617 EP 1623 DI 10.1111/j.1471-0528.2012.03495.x PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 040AW UT WOS:000311292300011 PM 23078336 ER PT J AU Kimball, AB AF Kimball, A. B. TI Psoriasis and cardiovascular disease: another contribution in the hierarchy of evidence SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Kimball, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM harvardskinstudies@partners.org NR 6 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD DEC PY 2012 VL 167 IS 6 BP 1198 EP 1199 DI 10.1111/bjd.12089 PG 2 WC Dermatology SC Dermatology GA 047QN UT WOS:000311855700027 PM 23181837 ER PT J AU Beeram, M Krop, IE Burris, HA Girish, SR Yu, W Lu, MW Holden, SN Modi, S AF Beeram, Muralidhar Krop, Ian E. Burris, Howard A. Girish, Sandhya R. Yu, Wei Lu, Michael W. Holden, Scott N. Modi, Shanu TI A phase 1 study of weekly dosing of trastuzumab emtansine (T-DM1) in patients with advanced human epidermal growth factor 2-positive breast cancer SO CANCER LA English DT Article DE trastuzumab emtansine; T-DM1; breast cancer; antibody-drug conjugate; HER2-positive ID SOLID TUMORS AB BACKGROUND: We conducted a phase 1, multicenter, open-label, dose-escalation study (TDM3569g) to assess the safety, tolerability, and pharmacokinetics of single-agent trastuzumab emtansine (T-DM1) administered weekly and once every 3 weeks in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab. The weekly dose results are described here. METHODS: Patients were administered escalating doses of T-DM1 weekly, starting at 1.2 mg/kg. Additional patients were enrolled at the maximum tolerated dose (MTD) to better characterize tolerability and pharmacokinetics. RESULTS: Twenty-eight patients received weekly T-DM1, and the MTD was determined to be 2.4 mg/kg. In general, T-DM1 was well tolerated, requiring few dose modifications or discontinuations because of adverse events (AEs). Grade =3 AEs were reported in 19 patients (67.9%); treatment-related AEs occurred in 25 (89.3%) patients. Exposure to weekly T-DM1 was dose-proportional at =1.2 mg/kg, and accumulation of T-DM1 and total trastuzumab was observed. Objective partial tumor responses were reported in 13 (46.4%) patients; the median duration of response was 18.6 months, and the 6-month clinical benefit rate was 57.1%. CONCLUSION: The results suggest that a weekly dose of T-DM1 2.4 mg/kg has antitumor activity and is well tolerated in patients with HER2-positive metastatic breast cancer. Cancer 2012. (c) 2012 American Cancer Society. C1 [Beeram, Muralidhar] Inst Drug Dev, San Antonio, TX USA. [Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Burris, Howard A.] Sarah Cannon Res Inst, Nashville, TN USA. [Girish, Sandhya R.; Yu, Wei; Lu, Michael W.; Holden, Scott N.] Genentech Inc, San Francisco, CA 94080 USA. [Modi, Shanu] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Beeram, M (reprint author), S Texas Oncol & Hematol PA, START Ctr, 4383 Med Dr, San Antonio, TX 78229 USA. EM murali.beeram@stoh.com OI Modi, Shanu/0000-0001-6427-7373 FU Genentech, Inc.; Genentech FX This study was sponsored by Genentech, Inc.; Dr. Krop has received funding for clinical trials from Genentech. Dr. Girish is an employee of Genentech and has limited stock in the company. Dr. Yu is an employee of Genentech and holds stock in Roche. Dr. Lu is an employee of Genentech and owns stock in Roche. Dr. Holden is an employee of Genentech and holds stock in Roche, the owner of Genentech, the maker of T-DM1. Dr. Beeram, Dr. Burris, and Dr. Modi have no conflicts to declare. NR 12 TC 37 Z9 37 U1 0 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD DEC 1 PY 2012 VL 118 IS 23 BP 5733 EP 5740 DI 10.1002/cncr.27622 PG 8 WC Oncology SC Oncology GA 040EZ UT WOS:000311306000003 PM 22648179 ER PT J AU Wagner, AJ Goldberg, JM DuBois, SG Choy, E Rosen, L Pappo, A Geller, J Judson, I Hogg, D Senzer, N Davis, IJ Chai, F Waghorne, C Schwartz, B Demetri, GD AF Wagner, Andrew J. Goldberg, John M. DuBois, Steven G. Choy, Edwin Rosen, Lee Pappo, Alberto Geller, James Judson, Ian Hogg, David Senzer, Neil Davis, Ian J. Chai, Feng Waghorne, Carol Schwartz, Brian Demetri, George D. TI Tivantinib (ARQ 197), a selective inhibitor of MET, in patients with microphthalmia transcription factor-associated tumors SO CANCER LA English DT Article DE tivantinib; ARQ 197; proto-oncogene proteins c-met; *antagonists and inhibitors; microphthalmia-associated transcription factor; clear cell sarcoma; alveolar soft part sarcoma; renal cell carcinoma; pediatric; protein kinase inhibitors; pharmacokinetics ID SOFT PART SARCOMA; CLEAR-CELL SARCOMA; RECEPTOR TYROSINE KINASE; HEPATOCYTE GROWTH-FACTOR; C-MET; GENE FUSION; LINEAGE SURVIVAL; EXPRESSION LEVEL; SUNITINIB MALATE; LEUCINE-ZIPPER AB BACKGROUND: Microphthalmia transcription factor (MITF)-associated (MiT) tumors are a family of rare malignancies, including alveolar soft part sarcoma (ASPS), clear cell sarcoma (CCS), and translocation-associated renal cell carcinoma (tRCC) that have dysregulated expression of oncogenic MITF family proteins. The MET receptor tyrosine kinase gene is transcriptionally activated by MITF family proteins, making MET a potential therapeutic target for MiT tumors. This study assessed the activity of tivantinib (ARQ 197), a selective MET inhibitor, in patients with MiT-associated tumors. METHODS: This multicenter, single-arm, phase 2 trial enrolled patients with advanced MiT tumors. Patients initially received tivantinib 120 mg orally twice daily, then 360 mg twice daily per protocol amendment. The primary endpoint was overall response rate. Secondary endpoints included safety, progression-free survival, pharmacokinetics, and correlative studies. RESULTS: A total of 47 patients (median age, 25 years; range, 11-73 years) with ASPS (n = 27), CCS (n = 11), tRCC (n = 6), or other tumor types (n = 3) were enrolled. Common grade 3/4 drug-related adverse events included anemia (4%) and neutropenia (4%). Three patients (6.4%) experienced 4 treatment-related serious adverse events (grade 3 febrile neutropenia, thrombocytopenia, and deep vein thrombosis, and grade 4 thrombocytopenia). Best response was partial response in 1 CCS patient (2%) and stable disease in 28 patients (60%). Median progression-free survival was 3.6 months (overall), 5.5 months (ASPS), and 1.9 months (CCS and tRCC). Baseline MET expression was strongly or focally positive in tumor samples from 14 of 19 patients (74%). CONCLUSIONS: Tivantinib was safe and tolerable in patients with MiT tumors, but antitumor activity was modest. Cancer 2012. (c) 2012 American Cancer Society. C1 [Wagner, Andrew J.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02215 USA. [Goldberg, John M.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [DuBois, Steven G.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Choy, Edwin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosen, Lee] Univ Calif Los Angeles, Santa Monica, CA USA. [Pappo, Alberto] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Geller, James] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Judson, Ian] Royal Marsden NHS Fdn Trust, London, England. [Hogg, David] Univ Toronto, Toronto, ON, Canada. [Senzer, Neil] Mary Crowley Canc Res Ctr, Dallas, TX USA. [Davis, Ian J.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA. [Chai, Feng; Waghorne, Carol; Schwartz, Brian] ArQule Inc, Woburn, MA USA. RP Wagner, AJ (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM awagner@partners.org FU ArQule, Inc.; Daiichi Sankyo, Inc. FX This study was funded by ArQule, Inc. Financial support for medical editorial assistance was provided by Daiichi Sankyo, Inc., a member of the Daiichi Sankyo Group; Daiichi Sankyo Co., Ltd., Tokyo, Japan. NR 47 TC 60 Z9 64 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD DEC 1 PY 2012 VL 118 IS 23 BP 5894 EP 5902 DI 10.1002/cncr.27582 PG 9 WC Oncology SC Oncology GA 040EZ UT WOS:000311306000022 PM 22605650 ER PT J AU Sparano, JA Wang, ML Zhao, FM Stearns, V Martino, S Ligibel, JA Perez, EA Saphner, T Wolff, AC Sledge, GW Wood, WC Fetting, J Davidson, NE AF Sparano, Joseph A. Wang, Molin Zhao, Fengmin Stearns, Vered Martino, Silvana Ligibel, Jennifer A. Perez, Edith A. Saphner, Tom Wolff, Antonio C. Sledge, George W., Jr. Wood, William C. Fetting, John Davidson, Nancy E. TI Obesity at diagnosis is associated with inferior outcomes in hormone receptor-positive operable breast cancer SO CANCER LA English DT Article DE obesity; breast cancer; prognosis; hormone receptor positive; disparity ID BODY-MASS INDEX; ADJUVANT CHEMOTHERAPY; THERAPY; PROGNOSIS; SURVIVAL; WOMEN; TRIAL; FAT; TRASTUZUMAB; RECURRENCES AB BACKGROUND: Obesity has been associated with inferior outcomes in operable breast cancer, but the relation between body mass index (BMI) and outcomes by breast cancer subtype has not been previously evaluated. METHODS: The authors evaluated the relation between BMI and outcomes in 3 adjuvant trials coordinated by the Eastern Cooperative Oncology Group that included chemotherapy regimens with doxorubicin and cyclophosphamide, including E1199, E5188, and E3189. Results are expressed as hazard ratios (HRs) from Cox proportional hazards models (HR >1 indicates a worse outcome). All P values are 2-sided. RESULTS: When evaluated as a continuous variable in trial E1199, increasing BMI within the obese (BMI, =30 kg/m2) and overweight (BMI, 25-29.9 kg/m2) ranges was associated with inferior outcomes in hormone receptor-positive, human epidermal growth receptor 2 (HER-2)/neu-negative disease for disease-free survival (DFS; P = .0006) and overall survival (OS; P = .0007), but not in HER-2/neuoverexpressing or triple-negative disease. When evaluated as a categorical variable, obesity was associated with inferior DFS (HR, 1.24; 95% confidence interval [CI], 1.06-1.46; P = .0008) and OS (HR, 1.37; 95% CI, 1.13-1.67; P = .002) in hormone receptor-positive disease, but not other subtypes. In a model including obesity, disease subtype, and their interaction, the interaction term was significant for OS (P = .02) and showed a strong trend for DFS (P = .07). Similar results were found in 2 other trials (E5188, E3189). CONCLUSIONS: In a clinical trial population that excluded patients with significant comorbidities, obesity was associated with inferior outcomes specifically in patients with hormone receptor-positive operable breast cancer treated with standard chemohormonal therapy. Cancer 2012. (c) 2012 American Cancer Society. C1 [Sparano, Joseph A.] Montefiore Med Ctr, Albert Einstein Coll Med, Weiler Div, Bronx, NY 10461 USA. [Wang, Molin; Zhao, Fengmin; Ligibel, Jennifer A.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Stearns, Vered; Wolff, Antonio C.; Fetting, John] Johns Hopkins Univ, Kimmel Canc Ctr, Baltimore, MD USA. [Martino, Silvana] Angeles Clin & Res Inst, Santa Monica, CA USA. [Perez, Edith A.] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. [Saphner, Tom] Green Bay Oncol, Green Bay, WI USA. [Sledge, George W., Jr.] Indiana Univ Sch Med, Simon Canc Ctr, Indianapolis, IN USA. [Wood, William C.] Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA. [Davidson, Nancy E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Sparano, JA (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Weiler Div, 1825 Eastchester Rd, Bronx, NY 10461 USA. EM jsparano@montefiore.org OI Wolff, Antonio/0000-0003-3734-1063 FU Department of Health and Human Services; National Institutes of Health (NIH) [CA14958, CA23318, CA66636, CA21115, CA32012, CA11789, CA25224, CA49883, CA16116] FX Supported in part by grants from the Department of Health and Human Services and the National Institutes of Health (NIH): CA14958 to the Albert Einstein College of Medicine, CA23318 to the ECOG statistical center, CA66636 to the ECOG data management center, CA21115 to the ECOG coordinating center and chairman's office, CA32012 to the Southwest Oncology Group, CA11789 to the Cancer and Leukemia Group B, CA25224 to the North Central Cancer Treatment Group, CA49883 to the Indiana University School of Medicine, and CA16116 to Johns Hopkins Oncology Center. The contents of the article are solely the responsibility of the authors and do not necessary represent the official view of the National Center for Research Resources, NIH, or American Society of Clinical Oncology. NR 38 TC 58 Z9 59 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD DEC 1 PY 2012 VL 118 IS 23 BP 5937 EP 5946 DI 10.1002/cncr.27527 PG 10 WC Oncology SC Oncology GA 040EZ UT WOS:000311306000027 PM 22926690 ER PT J AU Small, AC Tsao, CK Moshier, EL Gartrell, BA Wisnivesky, JP Godbold, JH Smith, CB Sonpavde, G Oh, WK Galsky, MD AF Small, Alexander C. Tsao, Che-Kai Moshier, Erin L. Gartrell, Benjamin A. Wisnivesky, Juan P. Godbold, James H. Smith, Cardinale B. Sonpavde, Guru Oh, William K. Galsky, Matthew D. TI Prevalence and characteristics of patients with metastatic cancer who receive no anticancer therapy SO CANCER LA English DT Article DE metastatic cancer; health care disparities; National Cancer Data Base; untreated; no treatment ID CELL LUNG-CANCER; CHEMOTHERAPY; DIAGNOSIS; SURVIVAL; STAGE; DISPARITIES; SERVICES; BREAST AB BACKGROUND: A subset of patients who present with metastatic solid tumors never receive anticancer therapy. Reasons may include poor functional status, comorbidities, and patient preference. To the authors' knowledge, the prevalence and characteristics of this population have not previously been described. METHODS: The National Cancer Data Base was queried for patients diagnosed with metastatic (stage IV according to the American Joint Committee on Cancer) solid tumors (including those of the breast, cervix, colon, and kidney; small cell and nonsmall cell lung cancer [NSCLC]; and tumors of the prostate, rectum, and uterus) who received neither radiotherapy nor systemic therapy. Log-binomial regression analysis was used to estimate prevalence ratios (PRs) for the percentage of untreated to treated patients with stage IV cancer. RESULTS: Between 2000 and 2008, 773,233 patients with stage IV cancer were identified, 159,284 of whom (20.6%; 95% confidence interval, 20.5%-20.7%) received no anticancer therapy. Patients with NSCLC accounted for 55% of the untreated population. Patients with cancers of the kidney and lung had the highest rates of no treatment at 25.5% and 24.0%, respectively, whereas patients with prostate cancer had the lowest rate of no treatment at 11.1%. Across all cancer types, older age (PR range, 1.37-1.49; all P < .001), black race (PR range, 1.05-1.32; all P < .001), lack of medical insurance (PR range, 1.47-2.46; all P < .001), and lower income (except for cancer of the uterus; PR range, 0.91-0.98 for every $10,000-increase in income [all P < .001]) were associated with a lack of treatment. CONCLUSIONS: Approximately 20% of patients who present with stage IV solid tumors do not receive anticancer therapy. Although there are likely multiple reasons for this lack of treatment, including appropriate indications, these findings have potential implications with regard to health care policy and access to care. Cancer 2012.(c) 2012 American Cancer Society. C1 [Small, Alexander C.; Tsao, Che-Kai; Gartrell, Benjamin A.; Smith, Cardinale B.; Oh, William K.; Galsky, Matthew D.] Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY 10029 USA. [Moshier, Erin L.; Godbold, James H.] Mt Sinai Sch Med, Dept Prevent Med, New York, NY 10029 USA. [Wisnivesky, Juan P.] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA. [Wisnivesky, Juan P.] Mt Sinai Sch Med, Div Pulm & Crit Care Med, New York, NY 10029 USA. [Sonpavde, Guru] Texas Oncol Deke Slayton Canc Ctr, Houston, TX USA. [Sonpavde, Guru] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Med Oncol, Houston, TX 77030 USA. RP Galsky, MD (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM matthew.galsky@mssm.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU Doris Duke Charitable Foundation; Novartis Pharmaceuticals; GlaxoSmithKline FX Funding received from the Doris Duke Charitable Foundation.; Dr. Wisnivesky is a member of the research board of EHE International. He has received lecture fees from Novartis Pharmaceuticals, acted as a consultant for United BioSource Corporation, and received a chronic obstructive pulmonary disease grant from GlaxoSmithKline. NR 19 TC 10 Z9 10 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD DEC 1 PY 2012 VL 118 IS 23 BP 5947 EP 5954 DI 10.1002/cncr.27658 PG 8 WC Oncology SC Oncology GA 040EZ UT WOS:000311306000028 PM 22707387 ER PT J AU Albertini, MR Hank, JA Gadbaw, B Kostlevy, J Haldeman, J Schalch, H Gan, J Kim, K Eickhoff, J Gillies, SD Sondel, PM AF Albertini, Mark R. Hank, Jacquelyn A. Gadbaw, Brian Kostlevy, Jordan Haldeman, Jennifer Schalch, Heidi Gan, Jacek Kim, KyungMann Eickhoff, Jens Gillies, Stephen D. Sondel, Paul M. TI Phase II trial of hu14.18-IL2 for patients with metastatic melanoma SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Immunocytokine; Advanced Melanoma; Immunotherapy; Interleukin-2; Anti-ganglioside antibody; Phase II clinical trial ID RECOMBINANT INTERLEUKIN-2 THERAPY; NEUROBLASTOMA METASTASES; INCREASED EXPRESSION; CLINICAL-TRIAL; KILLER-CELLS; BONE-MARROW; ANTIBODY; IMMUNOCYTOKINE; IMMUNOTHERAPY; EMD-273063 AB Phase I testing of the hu14.18-IL2 immunocytokine in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5 mg/m(2)/day. In this phase II study, 14 patients with measurable metastatic melanoma were scheduled to receive hu14.18-IL2 at 6 mg/m(2)/day as 4-h intravenous infusions on Days 1, 2, and 3 of each 28 day cycle. Patients with stable disease (SD) or regression following cycle 2 could receive two additional treatment cycles. The primary objective was to evaluate antitumor activity and response duration. Secondary objectives evaluated adverse events and immunologic activation. All patients received two cycles of treatment. One patient had a partial response (PR) [1 PR of 14 patients = response rate of 7.1 %; confidence interval, 0.2-33.9 %], and 4 patients had SD and received cycles 3 and 4. The PR and SD responses lasted 3-4 months. All toxicities were reversible and those resulting in dose reduction included grade 3 hypotension (2 patients) and grade 2 renal insufficiency with oliguria (1 patient). Patients had a peripheral blood lymphocytosis on Day 8 and increased C-reactive protein. While one PR in 14 patients met protocol criteria to proceed to stage 2 and enter 16 additional patients, we suspended stage 2 due to limited availability of hu14.18-IL2 at that time and the brief duration of PR and SD. We conclude that subsequent testing of hu14.18-IL2 should involve melanoma patients with minimal residual disease based on compelling preclinical data and the confirmed immune activation with some antitumor activity in this study. C1 [Albertini, Mark R.] K6 530 Clin Sci Ctr, Madison, WI 53792 USA. [Albertini, Mark R.; Hank, Jacquelyn A.; Kostlevy, Jordan; Haldeman, Jennifer; Schalch, Heidi; Gan, Jacek; Kim, KyungMann; Eickhoff, Jens; Sondel, Paul M.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Albertini, Mark R.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Albertini, Mark R.] William S Middleton Mem Vet Adm Med Ctr, Med Serv, Madison, WI USA. [Hank, Jacquelyn A.; Gan, Jacek; Sondel, Paul M.] Univ Wisconsin, Dept Human Oncol, Sch Med & Publ Hlth, Madison, WI USA. [Gadbaw, Brian; Sondel, Paul M.] Univ Wisconsin, Dept Pediat, Sch Med & Publ Hlth, Madison, WI USA. [Kim, KyungMann; Eickhoff, Jens] Univ Wisconsin, Dept Biostat, Sch Med & Publ Hlth, Madison, WI USA. [Gillies, Stephen D.] Provenance Biopharmaceut Inc, Waltham, MA USA. RP Albertini, MR (reprint author), K6 530 Clin Sci Ctr, 600 Highland Ave, Madison, WI 53792 USA. EM mralbert@wisc.edu FU National Institutes of Health [CA032685, CA87025]; Midwest Athletes for Childhood Cancer Fund; Crawdaddy Foundation; CTRC grant [GM067386]; National Cancer Institute [P30 CA014520]; Gretchen and Andrew Dawes Melanoma Research Fund; Ann's Hope Foundation; Jay Van Sloan Memorial from the Steve Leuthold Family; Tim Eagle Memorial FX We thank Barrett P. Wagner for technical assistance and Laddie Johnson for assistance with manuscript preparation. We also thank the nurses on the UW CTRC for outstanding nursing care and for clinical trial support. This material was supported by National Institutes of Health Grants CA032685, CA87025, and grants from the Midwest Athletes for Childhood Cancer Fund, the Crawdaddy Foundation; CTRC grant (GM067386); grant P30 CA014520 from the National Cancer Institute; the Gretchen and Andrew Dawes Melanoma Research Fund; Ann's Hope Foundation; the Jay Van Sloan Memorial from the Steve Leuthold Family; and the Tim Eagle Memorial. NR 29 TC 19 Z9 19 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD DEC PY 2012 VL 61 IS 12 BP 2261 EP 2271 DI 10.1007/s00262-012-1286-5 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA 045AO UT WOS:000311666600006 PM 22678096 ER PT J AU Van Vliet, P Wu, SM Zaffran, S Puceat, M AF Van Vliet, Patrick Wu, Sean M. Zaffran, Stephane Puceat, Michel TI Early cardiac development: a view from stem cells to embryos SO CARDIOVASCULAR RESEARCH LA English DT Review DE Cardiac development; Cardiac cell lineages; Embryonic heart ID 2ND HEART FIELD; CARDIOVASCULAR PROGENITOR CELLS; GERM-LAYER FORMATION; GROWTH-FACTOR; MOUSE EMBRYO; VISCERAL ENDODERM; GENE-EXPRESSION; IN-VITRO; EPICARDIAL PROGENITORS; SIGNALING PATHWAYS AB From the 1920s, early cardiac development has been studied in chick and, later, in mouse embryos in order to understand the first cell fate decisions that drive specification and determination of the endocardium, myocardium, and epicardium. More recently, mouse and human embryonic stem cells (ESCs) have demonstrated faithful recapitulation of early cardiogenesis and have contributed significantly to this research over the past few decades. Derived almost 15 years ago, human ESCs have provided a unique developmental model for understanding the genetic and epigenetic regulation of early human cardiogenesis. Here, we review the biological concepts underlying cell fate decisions during early cardiogenesis in model organisms and ESCs. We draw upon both pioneering and recent studies and highlight the continued role for invitro stem cells in cardiac developmental biology. C1 [Puceat, Michel] Paris Descartes Univ, UMR633, INSERM, F-91058 Paris, France. [Van Vliet, Patrick] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA USA. [Wu, Sean M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA USA. [Wu, Sean M.] Harvard Stem Cell Inst, Cambridge, MA USA. [Zaffran, Stephane] Aix Marseille Univ, Marseille, France. [Zaffran, Stephane] Fac Med Timone, UMRS910, INSERM, Timone, France. RP Puceat, M (reprint author), Paris Descartes Univ, UMR633, INSERM, Campus Genopole 1,4 Rue Pierre Fontaine, F-91058 Paris, France. EM michel.puceat@inserm.fr RI Zaffran, Stephane/I-2955-2016; OI Zaffran, Stephane/0000-0002-0811-418X; PUCEAT, michel/0000-0001-9055-7563 FU ANR, National Agency for research [ANR-08-BLAN-0258]; FRM, Fondation pour la Recherche Medicale; Leducq Foundation (transatlantic network of excellence SHAPEHEART); NIH/NHLBI; NIH Office of the Director; Harvard Stem Cell Institute FX Research of M. P. is supported by ANR, National Agency for research (Grant specistem ANR-08-BLAN-0258), FRM, Fondation pour la Recherche Medicale, and Leducq Foundation (transatlantic network of excellence SHAPEHEART). S. M. W. is supported by NIH/NHLBI, NIH Office of the Director, and the Harvard Stem Cell Institute. We apologize for authors who could not be cited because of lack of space. NR 132 TC 43 Z9 43 U1 1 U2 53 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 DEC 1 PY 2012 VL 96 IS 3 BP 352 EP 362 DI 10.1093/cvr/cvs270 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 040FG UT WOS:000311306800006 PM 22893679 ER PT J AU Bajpai, VK Mistriotis, P Loh, YH Daley, GQ Andreadis, ST AF Bajpai, Vivek K. Mistriotis, Panagiotis Loh, Yuin-Han Daley, George Q. Andreadis, Stelios T. TI Functional vascular smooth muscle cells derived from human induced pluripotent stem cells via mesenchymal stem cell intermediates SO CARDIOVASCULAR RESEARCH LA English DT Article DE Induced pluripotent stem cells; Mesenchymal stem cells; Smooth muscle cells; 2D differentiation; Vascular contractility; Cellular senescence ID ENGINEERED BLOOD-VESSELS; BONE-MARROW; PROGENITOR CELLS; IN-VITRO; DEFINED FACTORS; TISSUE; DIFFERENTIATION; TRANSITION; INDUCTION; FIBROBLASTS AB Smooth muscle cells (SMC) play an important role in vascular homeostasis and disease. Although adult mesenchymal stem cells (MSC) have been used as a source of contractile SMC, they suffer from limited proliferation potential and culture senescence, particularly when originating from older donors. By comparison, human induced pluripotent stem cells (hiPSC) can provide an unlimited source of functional SMC for autologous cell-based therapies and for creating models of vascular disease. Our goal was to develop an efficient strategy to derive functional, contractile SMC from hiPSC. We developed a robust, stage-wise, feeder-free strategy for hiPSC differentiation into functional SMC through an intermediate stage of multipotent MSC, which could be coaxed to differentiate into fat, bone, cartilage, and muscle. At this stage, the cells were highly proliferative and displayed higher clonogenic potential and reduced senescence when compared with parental hair follicle mesenchymal stem cells. In addition, when exposed to differentiation medium, the myogenic proteins such as -smooth muscle actin, calponin, and myosin heavy chain were significantly upregulated and displayed robust fibrillar organization, suggesting the development of a contractile phenotype. Indeed, tissue constructs prepared from these cells exhibited high levels of contractility in response to receptor- and non-receptor-mediated agonists. We developed an efficient stage-wise strategy that enabled hiPSC differentiation into contractile SMC through an intermediate population of clonogenic and multipotent MSC. The high yield of MSC and SMC derivation suggests that our strategy may facilitate an acquisition of the large numbers of cells required for regenerative medicine or for studying vascular disease pathophysiology. C1 [Bajpai, Vivek K.; Mistriotis, Panagiotis; Andreadis, Stelios T.] SUNY Buffalo, Bioengn Lab, Dept Chem & Biol Engn, Amherst, NY 14260 USA. [Loh, Yuin-Han; Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Stem Cell Transplantat Program,Div Pediat Hematol, Boston, MA 02115 USA. [Loh, Yuin-Han; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Loh, Yuin-Han; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Andreadis, Stelios T.] SUNY Buffalo, Dept Biomed Engn, Amherst, NY 14260 USA. [Andreadis, Stelios T.] Ctr Excellence Bioinformat & Life Sci, Buffalo, NY 14203 USA. RP Andreadis, ST (reprint author), SUNY Buffalo, Bioengn Lab, Dept Chem & Biol Engn, 908 Furnas Hall, Amherst, NY 14260 USA. EM sandread@buffalo.edu RI Loh, Yuin-Han/E-1096-2014 OI Loh, Yuin-Han/0000-0002-4715-6454 FU National Heart and Lung Institute [R01 HL086582]; New York Stem Cell Science Fund (NYSTEM) [C024316] FX This work was supported by grants from the National Heart and Lung Institute (R01 HL086582) and the New York Stem Cell Science Fund (NYSTEM, Contract# C024316) to S. T. A. NR 60 TC 32 Z9 32 U1 4 U2 39 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD DEC 1 PY 2012 VL 96 IS 3 BP 391 EP 400 DI 10.1093/cvr/cvs253 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 040FG UT WOS:000311306800010 PM 22941255 ER PT J AU Telem, DA Pratt, JS AF Telem, Dana A. Pratt, Janey S. TI Bariatric surgery in children: how can we combat the prejudice? SO CIRUGIA ESPANOLA LA Spanish DT Editorial Material ID ADOLESCENTS; OVERWEIGHT; CRITERIA C1 [Telem, Dana A.; Pratt, Janey S.] Massachusetts Gen Hosp, Div Gastrointestinal Surg, Boston, MA 02114 USA. RP Pratt, JS (reprint author), Massachusetts Gen Hosp, Div Gastrointestinal Surg, Boston, MA 02114 USA. EM jpratt@partners.org NR 9 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0009-739X J9 CIR ESPAN JI Cir. Espan. PD DEC PY 2012 VL 90 IS 10 BP 617 EP 618 DI 10.1016/j.ciresp.2012.08.003 PG 2 WC Surgery SC Surgery GA 042SN UT WOS:000311491400004 PM 23141967 ER PT J AU Atik, A Krilis, M Shannon, K AF Atik, Alp Krilis, Matthew Shannon, Kerwin TI SMALL CELL NEUROENDOCRINE CARCINOMA OF 'SMALL BLUE CELL' SUBTYPE INITIALLY TREATED AS CELLULITIS SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Meeting Abstract C1 [Atik, Alp] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Krilis, Matthew] Sydney Eye Hosp, Sydney, NSW, Australia. [Shannon, Kerwin] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia. EM alp_atik@hotmail.com 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 1442-6404 J9 CLIN EXP OPHTHALMOL JI Clin. Exp. Ophthalmol. PD DEC PY 2012 VL 40 SU 1 SI SI BP 90 EP 90 PG 1 WC Ophthalmology SC Ophthalmology GA 041NH UT WOS:000311408000150 ER PT J AU Di Girolamo, N Atik, A McCluskey, P Wakefield, D AF Di Girolamo, Nick Atik, Alp McCluskey, Peter Wakefield, Denis TI MATRIX METALLOPROTEINASES AND THEIR INHIBITORS IN THE PATHOPHYSIOLOGY OF SQUAMOUS CELL CARCINOMA OF THE CONJUNCTIVA SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Meeting Abstract C1 [Di Girolamo, Nick; Wakefield, Denis] Univ New S Wales, Sch Med Sci, Inflammat & Infect Res Ctr, Kensington, NSW 2033, Australia. [Atik, Alp] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [McCluskey, Peter] Univ Sydney, Sydney Med Sch, Save Sight Inst, Sydney, NSW 2006, Australia. EM alp_atik@hotmail.com RI McCluskey, Peter/H-7607-2013 OI McCluskey, Peter/0000-0002-8177-1637 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 1442-6404 J9 CLIN EXP OPHTHALMOL JI Clin. Exp. Ophthalmol. PD DEC PY 2012 VL 40 SU 1 SI SI BP 90 EP 90 PG 1 WC Ophthalmology SC Ophthalmology GA 041NH UT WOS:000311408000151 ER PT J AU Atik, A Krilis, M Parker, G AF Atik, Alp Krilis, Matthew Parker, Geoffrey TI SQUASH(ED): MULTIPLE CRANIOMAXILLOFACIAL AND VERTEBRAL FRACTURES FROM SQUASH COURT COLLISION SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Meeting Abstract C1 [Atik, Alp] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Krilis, Matthew] Sydney Eye Hosp, Sydney, NSW, Australia. [Parker, Geoffrey] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia. EM alp_atik@hotmail.com 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 1442-6404 J9 CLIN EXP OPHTHALMOL JI Clin. Exp. Ophthalmol. PD DEC PY 2012 VL 40 SU 1 SI SI BP 97 EP 97 PG 1 WC Ophthalmology SC Ophthalmology GA 041NH UT WOS:000311408000168 ER PT J AU Danese, E Montagnana, M Johnson, JA Rettie, AE Zambon, CF Lubitz, SA Suarez-Kurtz, G Cavallari, LH Zhao, L Huang, M Nakamura, Y Mushiroda, T Kringen, MK Borgiani, P Ciccacci, C Au, NT Langaee, T Siguret, V Loriot, MA Sagreiya, H Altman, RB Shahin, MHA Scott, SA Khalifa, SI Chowbay, B Suriapranata, IM Teichert, M Stricker, BH Taljaard, M Botton, MR Zhang, JE Pirmohamed, M Zhang, X Carlquist, JF Horne, BD Lee, MTM Pengo, V Guidi, GC Minuz, P Fava, C AF Danese, E. Montagnana, M. Johnson, J. A. Rettie, A. E. Zambon, C. F. Lubitz, S. A. Suarez-Kurtz, G. Cavallari, L. H. Zhao, L. Huang, M. Nakamura, Y. Mushiroda, T. Kringen, M. K. Borgiani, P. Ciccacci, C. Au, N. T. Langaee, T. Siguret, V. Loriot, M. A. Sagreiya, H. Altman, R. B. Shahin, M. H. A. Scott, S. A. Khalifa, S. I. Chowbay, B. Suriapranata, I. M. Teichert, M. Stricker, B. H. Taljaard, M. Botton, M. R. Zhang, J. E. Pirmohamed, M. Zhang, X. Carlquist, J. F. Horne, B. D. Lee, M. T. M. Pengo, V. Guidi, G. C. Minuz, P. Fava, C. TI Impact of the CYP4F2 p.V433M Polymorphism on Coumarin Dose Requirement: Systematic Review and Meta-Analysis SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Review ID GENOME-WIDE ASSOCIATION; GENETIC-VARIANTS; V433M VARIANT; WARFARIN; POPULATION; CYP2C9; PHARMACOGENETICS; GENOTYPE; RS2108622; THERAPY AB A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I-2 = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to coumarin drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms. C1 [Danese, E.; Minuz, P.; Fava, C.] Univ Hosp Verona, Dept Med, Div Internal Med C, Verona, Italy. [Danese, E.; Montagnana, M.; Guidi, G. C.] Univ Hosp Verona, Clin Biochem Sect, Dept Life & Reprod Sci, Verona, Italy. [Johnson, J. A.; Langaee, T.; Shahin, M. H. A.] Univ Florida, Ctr Pharmacogen, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA. [Rettie, A. E.; Au, N. T.] Univ Washington, Sch Pharm, Dept Med Chem, Seattle, WA 98195 USA. [Zambon, C. F.] Univ Padua, Dept Med, Padua, Italy. [Lubitz, S. A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, S. A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Suarez-Kurtz, G.] Inst Nacl Canc, Div Pharmacol, Rio De Janeiro, Brazil. [Cavallari, L. H.] Univ Illinois, Dept Pharm Practice, Chicago, IL USA. [Zhao, L.; Huang, M.] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510275, Guangdong, Peoples R China. [Nakamura, Y.] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Lab Mol Med, Tokyo, Japan. [Mushiroda, T.] RIKEN Ctr Genom Med, Res Grp Pharmacogen, Yokohama, Kanagawa, Japan. [Kringen, M. K.] Oslo Univ Hosp, Dept Pharmacol, Oslo, Norway. [Borgiani, P.; Ciccacci, C.] Univ Roma Tor Vergata, Genet Unit, Dept Biomed & Prevent, Rome, Italy. [Siguret, V.] Univ Paris 05, Hop Georges Pompidou, AP HP, Dept Haematol,INSERM U765, Paris, France. [Loriot, M. A.] Univ Paris 05, Hop Georges Pompidou, AP HP, Dept Pharmacogenet,INSERM U775, Paris, France. [Sagreiya, H.; Altman, R. B.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Sagreiya, H.; Altman, R. B.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Scott, S. A.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Khalifa, S. I.] Qatar Univ, Coll Pharm, Pharmaceut Sci Sect, Doha, Qatar. [Chowbay, B.] Natl Canc Ctr, Clin Pharmacol Lab, Div Med Sci, Singapore, Singapore. [Suriapranata, I. M.] Univ Pelita Harapan, Mochtar Riady Inst Nanotechnol, Tangerang, Indonesia. [Teichert, M.; Stricker, B. H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Taljaard, M.] Univ Ottawa, Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Taljaard, M.] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. [Botton, M. R.] Univ Fed Rio Grande do Sul, Dept Genet, Porto Alegre, RS, Brazil. [Zhang, J. E.; Pirmohamed, M.] Univ Liverpool, Wolfson Ctr Personalised Med, Dept Mol & Clin Pharmacol, Liverpool L69 3BX, Merseyside, England. [Zhang, X.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Carlquist, J. F.] Univ Utah, Dept Med, Div Cardiol, Intermt Heart Inst,Intermt Med Ctr, Salt Lake City, UT 84112 USA. [Horne, B. D.] Univ Utah, Dept Med, Div Genet Epidemiol, Salt Lake City, UT 84112 USA. [Lee, M. T. M.] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Pengo, V.] Univ Padua, Dept Cardiac Thorac & Vasc Sci, Padua, Italy. [Fava, C.] Lund Univ, Univ Hosp Malmo, Dept Clin Sci, Malmo, Sweden. RP Fava, C (reprint author), Univ Hosp Verona, Dept Med, Div Internal Med C, Verona, Italy. EM cristiano.fava@med.lu.se RI Suarez-Kurtz, Guilherme/J-6648-2012; danese, elisa/K-6992-2013; Mushiroda, Taisei/E-3022-2010; Pirmohamed, Munir/H-6004-2011; Lee, Ming Ta Michael/N-5396-2015; Zambon, Carlo Federico/J-8187-2016; Danese, Elisa/N-2848-2016; OI Pirmohamed, Munir/0000-0002-7534-7266; Lee, Ming Ta Michael/0000-0003-2510-8977; Zambon, Carlo Federico/0000-0002-4244-879X; Danese, Elisa/0000-0002-2454-0410; BORGIANI, PAOLA/0000-0003-0859-4328; Pengo, Vittorio/0000-0003-2064-6071 FU National Institutes of Health [U01GM074492, U01GM092676, R01GM068797, TL1RR025016]; UK Department of Health NHS Chair of Pharmacogenetics programme FX We thank Rocio Gonzalez-Conejero, who kindly provided data necessary for our analyses. The efforts of J.A.J., A.E.R., and N.T.A. were supported, in part, by National Institutes of Health research grants U01GM074492, U01GM092676, R01GM068797, and TL1RR025016. J.E.Z. and M.P. were supported by the UK Department of Health NHS Chair of Pharmacogenetics programme. NR 50 TC 25 Z9 28 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 2012 VL 92 IS 6 BP 746 EP 756 DI 10.1038/clpt.2012.184 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 039YE UT WOS:000311283400016 PM 23132553 ER PT J AU Braun, AB Litonjua, AA Moromizato, T Gibbons, FK Giovannucci, E Christopher, KB AF Braun, Andrea B. Litonjua, Augusto A. Moromizato, Takuhiro Gibbons, Fiona K. Giovannucci, Edward Christopher, Kenneth B. TI Association of low serum 25-hydroxyvitamin D levels and acute kidney injury in the critically ill SO CRITICAL CARE MEDICINE LA English DT Article DE acute kidney injury; intensive care; RIFLE criteria; vitamin D ID REGULATORY T-CELLS; ISCHEMIA-REPERFUSION INJURY; ACUTE-RENAL-FAILURE; NF-KAPPA-B; INTENSIVE-CARE-UNIT; MEDIATED TISSUE PROTECTION; VITAMIN-D LEVELS; RIFLE CRITERIA; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; HOSPITAL MORTALITY AB Objective: Given the importance of inflammation in acute kidney injury and the relationship between vitamin D and inflammation, we sought to elucidate the effect of vitamin D on acute kidney injury. We hypothesized that deficiency in 25-hydroxyvitamin D prior to hospital admission would be associated with acute kidney injury in the critically ill. Design: Two-center observational study of patients treated in medical and surgical intensive care units. Setting: Two hundred nine medical and surgical intensive care beds in two teaching hospitals in Boston, Massachusetts. Patients: Two thousand seventy-five patients, aged >= 18 yrs, in whom serum 25-hydroxyvitamin D was measured prior to hospitalization between 1998 and 2009. Interventions: None. Measurements and Main Results: The exposure of interest was preadmission serum 25-hydroxyvitamin D and categorized a priori as deficiency (25-hydroxyvitamin D <= 15 ng/mL), insufficiency (25-hydroxyvitamin D 15-30 ng/mL), or sufficiency (25-hydroxyvitamin D >= 30 ng/mL). The primary outcome was acute kidney injury defined as meeting Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) Injury or Failure criteria. Logistic regression examined the RIFLE criteria outcome. Adjusted odds ratios were estimated by multivariate logistic regression models. Preadmission 25-hydroxyvitamin D deficiency is predictive of acute kidney injury. Patients with 25-hydroxyvitamin D deficiency have an odds ratio for acute kidney injury of 1.73 (95% confidence interval 1.30-2.30; p < .0001) relative to patients with 25-hydroxyvitamin D sufficiency. 25-Hydroxyvitamin D deficiency remains a significant predictor of acute kidney injury following multivariable adjustment (adjusted odds ratio 1.50; 95% confidence interval 1.42-2.24; p < .0001). Patients with 25-hydroxyvitamin D insufficiency have an odds ratio for acute kidney injury of 1.49 (95% confidence interval 1.15-1.94; p = .003) and an adjusted odds ratio of 1.23 (95% confidence interval 1.12-1.72; p = .003) relative to patients with 25-hydroxyvitamin D sufficiency. In addition, preadmission 25-hydroxyvitamin D deficiency is predictive of mortality. Patients with 25-hydroxyvitamin D insufficiency have an odds ratio for 30-day mortality of 1.60 (95% confidence interval 1.18-2.17; p = .003) and an adjusted odds ratio of 1.61 (95% confidence interval 1.06-1.57; p = .004) relative to patients with 25-hydroxyvitamin D sufficiency. Conclusion: Deficiency of 25-hydroxyvitamin D prior to hospital admission is a significant predictor of acute kidney injury and mortality in a critically ill patient population. (Crit Care Med 2012; 40:3170-3179) C1 [Moromizato, Takuhiro; Christopher, Kenneth B.] Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Pulm & Crit Care Div, Boston, MA 02115 USA. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Div Pulm, Boston, MA 02114 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. EM kbchristopher@partners.org OI Litonjua, Augusto/0000-0003-0422-5875 NR 120 TC 33 Z9 37 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 BP 3170 EP 3179 DI 10.1097/CCM.0b013e318260c928 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 041UQ UT WOS:000311427100008 PM 22975885 ER PT J AU Lopez-Fernandez, Y Martinez-de Azagra, A de la Oliva, P Modesto, V Sanchez, JI Parrilla, J Arroyo, MJ Reyes, SB Pons-Odena, M Lopez-Herce, J Fernandez, RL Kacmarek, RM Villar, J AF Lopez-Fernandez, Yolanda Martinez-de Azagra, Amelia de la Oliva, Pedro Modesto, Vicent Sanchez, Juan I. Parrilla, Julio Jose Arroyo, Maria Beatriz Reyes, Susana Pons-Odena, Marti Lopez-Herce, Jesus Lidia Fernandez, Rosa Kacmarek, Robert M. Villar, Jesus CA Pediat Acute Lung Injury Epidemiol TI Pediatric Acute Lung Injury Epidemiology and Natural History Study: Incidence and outcome of the acute respiratory distress syndrome in children SO CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; children; incidence; lung protective ventilation ID INTENSIVE-CARE-UNIT; LOWER TIDAL VOLUMES; CLINICAL-COURSE; MORTALITY; TRIAL; MULTICENTER; SPO(2)/FIO2; VENTILATION; DISEASE; RATIO AB Objectives: The incidence and outcome of the acute respiratory distress syndrome in children are not well-known, especially under current ventilatory practices. The goal of this study was to determine the incidence, etiology, and outcome of acute respiratory distress syndrome in the pediatric population in the setting of lung protective ventilation. Design: A 1-yr, prospective, multicenter, observational study in 12 geographical areas of Spain (serving a population of 3.77 million <= 15 yrs of age) covered by 21 pediatric intensive care units. Subjects: All consecutive pediatric patients receiving invasive mechanical ventilation and meeting American-European Consensus Criteria for acute respiratory distress syndrome. Interventions: None. Measurements and Main Results: Data on ventilatory management, gas exchange, hemodynamics, and organ dysfunction were collected. A total of 146 mechanically ventilated patients fulfilled the acute respiratory distress syndrome definition, representing a incidence of 3.9/100,000 population <= 15 yrs of age/yr. Pneumonia and sepsis were the most common causes of acute respiratory distress syndrome. At the time of meeting acute respiratory distress syndrome criteria, mean Pao(2)/Fio(2) was 99 mm Hg +/- 41 mm Hg, mean tidal volume was 7.6 mL/kg +/- 1.8 mL/kg predicted body weight, mean plateau pressure was 27 cm H2O +/- 6 cm H2O, and mean positive end-expiratory pressure was 8.9 cm +/- 2.9 cm H2O. Overall pediatric intensive care unit and hospital mortality were 26% (95% confidence interval 19.6-33.7) and 27.4% (95% confidence interval 20.8-35.1), respectively. At 24 hrs, after the assessment of oxygenation under standard ventilatory settings, 118 (80.8%) patients continued to meet acute respiratory distress syndrome criteria (Pao(2)/Fio(2) 104 mm Hg +/- 36 mm Hg; pediatric intensive care units mortality 30.5%), whereas 28 patients (19.2%) had a Pao(2)/Fio(2) > 200 mm Hg (pediatric intensive care units mortality 7.1%) (p = .014). Conclusions: This is the largest study to estimate prospectively the pediatric population-based acute respiratory distress syndrome incidence and the first incidence study performed during the routine application of lung protective ventilation in children. Our findings support a lower acute respiratory distress syndrome incidence and mortality than those reported for adults. Pao(2)/Fio(2) ratios at acute respiratory distress syndrome onset and at 24 hrs after onset were helpful in defining groups at greater risk of dying (clinical trials registered with http://www.clinicaltrials.gov; NCT 01142544) (Crit Care Med 2012; 40:3238-3245) C1 [Lopez-Fernandez, Yolanda] Hosp Univ Cruces, Pediat Intens Care Unit, Vizcaya, Spain. [Martinez-de Azagra, Amelia] Hosp Infantil Univ Nino Jesus, Pediat Intens Care Unit, Madrid, Spain. [de la Oliva, Pedro] Hosp Univ La Paz, Pediat Intens Care Unit, Madrid, Spain. [Modesto, Vicent] Hosp Univ & Politecn Fe, Pediat Intens Care Unit, Valencia, Spain. [Sanchez, Juan I.] Hosp Univ 12 Octubre, Pediat Intens Care Unit, Madrid, Spain. [Parrilla, Julio] Hosp Univ Virgen del Rocio, Pediat Intens Care Unit, Seville, Spain. [Jose Arroyo, Maria] Hosp Univ Reina Sofia, Pediat Intens Care Unit, Cordoba, Spain. [Beatriz Reyes, Susana] Hosp Virgen Arrixaca, Pediat Intens Care Unit, Murcia, Spain. [Pons-Odena, Marti] Hosp St Joan de Deu, Pediat Intens Care Unit, Barcelona, Spain. [Lopez-Herce, Jesus] Hosp Gen Univ Gregorio Maranon, Pediat Intens Care Unit, Madrid, Spain. [Lidia Fernandez, Rosa; Villar, Jesus] Hosp Univ Dr Negrin, Res Unit, Las Palmas Gran Canaria, Spain. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Dept Anesthesia, Boston, MA 02115 USA. EM jesus.villar54@gmail.com RI IBIS, NEUROPEPTIDOS/H-7482-2016; , Ivan/D-6804-2012; IBIS, HIPERCOLESTERO/P-3953-2015 OI Parrilla, Julio/0000-0001-5068-9537; Fernandez-Carrion, Francisco/0000-0002-0582-4995; PONS-ODENA, MARTI/0000-0002-1181-3547; , Ivan/0000-0002-3108-058X; Rodriguez-Nunez, Antonio/0000-0003-3414-2771; Lopez-Herce, Jesus/0000-0001-6105-9178; FU Instituto de Salud Carlos III, Madrid, Spain [PI07/0113, PI10/0393]; Asociacion Cientifica Pulmon y Ventilacion Mecanica, Spain; Hamilton Medical and Coviden; Maquet FX Supported, in part, by Instituto de Salud Carlos III, Madrid, Spain (PI07/0113, PI10/0393), and Asociacion Cientifica Pulmon y Ventilacion Mecanica, Spain.; Dr. Kacmarek has received research grants from Hamilton Medical and Coviden, honorarium for lecturing from Hamilton Medical, Maquet, and Kimberly-Clark and is a consultant for Newport Medical, Bayer, and KCI. Drs. Villar and Fernandez have received research grants from Maquet. The remaining authors have not disclosed any conflicts of interest. NR 33 TC 46 Z9 52 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2012 VL 40 IS 12 BP 3238 EP 3245 DI 10.1097/CCM.0b013e318260caa3 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 041UQ UT WOS:000311427100017 PM 22990455 ER PT J AU Hofer, AM AF Hofer, A. M. TI Interactions Between Calcium and cAMP Signaling SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE Fluorescence Resonance Energy Transfer (FRET); calcium/cAMP crosstalk; cAMP microdomains; adenylyl cyclase; protein kinase A (PKA); cAMP oscillations; STIM1 ID SOLUBLE ADENYLYL-CYCLASE; RESONANCE ENERGY-TRANSFER; KINASE-A ACTIVITY; FRET-BASED REPORTERS; CYCLIC-AMP; PROTEIN-KINASE; LIVING CELLS; SUBCELLULAR DYNAMICS; CARDIAC MYOCYTES; PHOSPHOLIPASE-C AB The calcium ion is quite possibly the single most pervasive signaling molecule used by living organisms for the purpose of communicating internal and external states. It differs from other messengers in that it is neither created nor destroyed, but just moved around inside and outside the cell via transporters, pumps and channels to alter its concentration in specific cellular locations. These changes in free [Ca2+] are then detected by a wide array of Ca2+-binding effector proteins whose affinities are appropriately tuned to respond to a particular type of [Ca2+] change. This deceptively simple paradigm dominates the function of many cell types, for example in driving contraction of muscle, action potential generation in nerves, fluid, hormone, and enzyme secretion in secretory cells, and certain immune responses. However, the Ca2+ signal does not work in strict isolation, but rather is fine-tuned by many other signals, not the least of which is the other major second messenger, cyclic AMP (cAMP). Conversely, the cAMP pathway is subject to modification by the calcium signal and its various effectors at many different levels. These two fundamental second messengers, used throughout eukaryotes and even prokaryotes, are thus inextricably intertwined. The purpose of the present article is to provide an update on some of the recently described forms of reciprocal regulation between Ca2+ and cAMP signaling circuits, with emphasis on interactions that take place in localized domains of the cell. C1 [Hofer, A. M.] Brigham & Womens Hosp, Dept Surg, W Roxbury, MA 02132 USA. [Hofer, A. M.] Harvard Univ, Sch Med, W Roxbury, MA 02132 USA. [Hofer, A. M.] Brigham & Womens Hosp, VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. RP Hofer, AM (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, 1400 VFW Pkwy,Room 2B111, W Roxbury, MA 02132 USA. EM ahofer@rics.bwh.harvard.edu RI di Ronza, Alberto/H-7674-2016 OI di Ronza, Alberto/0000-0002-9813-5143 NR 92 TC 11 Z9 11 U1 1 U2 25 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD DEC PY 2012 VL 19 IS 34 BP 5768 EP 5773 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 047AE UT WOS:000311807100002 PM 22963560 ER PT J AU Hotchkiss, JR Palevsky, PM AF Hotchkiss, John R. Palevsky, Paul M. TI Care of the critically ill patient with advanced chronic kidney disease or end-stage renal disease SO CURRENT OPINION IN CRITICAL CARE LA English DT Review DE chronic kidney disease; critical care; end-stage renal disease; prognosis ID REPLACEMENT THERAPY; DIALYSIS PATIENTS; UREMIC PATIENTS; STAPHYLOCOCCUS-AUREUS; CHRONIC-HEMODIALYSIS; CLINICAL-FEATURES; BLEEDING-TIME; UNIT; FAILURE; OUTCOMES AB Purpose of review The number of individuals with chronic kidney disease (CKD) and end-stage renal disease (ESRD) is rising, and these individuals often require intensive care. Recent findings Patients with CKD and ESRD require critical care more frequently than those without these conditions and have similar reasons for requiring critical care as the general population. However, the burden of comorbidities, overall severity of illness as assessed by standard scoring systems, and mortality are higher in patients with ESRD than in the non-ESRD critically ill. After adjustment for demographics, comorbidities, and physiologic variables, the increased mortality risk in patients with ESRD is attenuated. In comparison to patients with dialysis-requiring acute kidney injury (AKI), critically ill patients with ESRD have a more favorable prognosis. Severity of illness scoring systems such as Acute Physiology and Chronic Health Evaluation and Simplified Acute Physiology Score tend to overestimate the risk of death in critically ill ESRD patients. ICU admission does not appear to dramatically affect long-term mortality in those with ESRD who survive their initial acute illness as compared ESRD patients without critical illness. Summary Despite the manifest physiologic derangements attending CKD/ESRD, a higher burden of comorbid conditions and a greater severity of illness on presentation account for much of the increased mortality. There is no justification for therapeutic nihilism in this population. C1 [Hotchkiss, John R.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Renal Sect,Med Specialty Serv Line, Pittsburgh, PA 15240 USA. [Hotchkiss, John R.] VA Pittsburgh Healthcare Syst, Crit Care Med Serv Line, Pittsburgh, PA USA. [Hotchkiss, John R.] VA Pittsburgh Healthcare Syst, Vet Engn Resource Ctr, Pittsburgh, PA USA. [Hotchkiss, John R.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA 15240 USA. [Hotchkiss, John R.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15240 USA. RP Palevsky, PM (reprint author), Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Renal Sect,Med Specialty Serv Line, Room 7E123,111F-U,Univ Dr, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 FU Spectral Diagnostics Inc. FX P.M.P. serves on medical advisory committees for Sanofi-Aventis and Cytopherx and participates in research sponsored by Spectral Diagnostics Inc. NR 34 TC 5 Z9 5 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5295 J9 CURR OPIN CRIT CARE JI Curr. Opin. Crit. Care PD DEC PY 2012 VL 18 IS 6 BP 599 EP 606 DI 10.1097/MCC.0b013e32835a1c59 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 039IA UT WOS:000311237000004 PM 23079618 ER PT J AU Gladman, M Cudkowicz, M Zinman, L AF Gladman, Matthew Cudkowicz, Merit Zinman, Lorne TI Enhancing clinical trials in neurodegenerative disorders: lessons from amyotrophic lateral sclerosis SO CURRENT OPINION IN NEUROLOGY LA English DT Review DE amyotrophic lateral sclerosis; biomarkers; clinical trial design; consortia; motor neuron disease ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED SEQUENTIAL TRIAL; EARLY PARKINSON-DISEASE; PHASE-II; DOUBLE-BLIND; ALSFRS-R; OPEN-LABEL; BIOMARKERS; MULTICENTER; PROGRESSION AB Purpose of review This review article is focused on strategies that may enhance clinical trial efficiency in neurodegenerative disorders, as demonstrated within the research field of amyotrophic lateral sclerosis (ALS). Recent findings Unravelling ALS pathophysiology will result in an increased number of candidate therapeutics. Recent ALS clinical trials have employed novel study designs that expedite the drug development process and limit sample size, including futility, lead-in, selection, adaptive and sequential designs. The search for sensitive and specific biomarkers in ALS continues to develop, and they are essential in accelerating the drug discovery process. Several candidate cerebrospinal fluid (CSF), neuroimaging and electrophysiological biomarkers have been recently described in ALS, and some have been successfully employed as secondary outcome measures in clinical trials. The advent of web-based technologies has provided a complementary platform to expedite clinical trials, through electronic data capture, teleconferencing and online registries. In addition, the formation of ALS consortia has enhanced collaborative multicentre studies. Summary ALS research studies have employed novel strategies to accelerate the efficiency and pace of drug discovery. The importance of adapting to novel measures that enhance study efficiency is not unique to ALS and can be applied to other neurodegenerative diseases in search of effective treatments. C1 [Zinman, Lorne] Sunnybrook Hlth Sci Ctr, Dept Med, Toronto, ON M4N 3M5, Canada. [Gladman, Matthew] Univ Toronto, Dept Med, Sch Med, Toronto, ON, Canada. [Cudkowicz, Merit] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. [Cudkowicz, Merit] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Zinman, L (reprint author), Sunnybrook Hlth Sci Ctr, Dept Med, Room UG26,2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM lorne.zinman@sunnybrook.ca FU ALS Society of Canada; Canadian Institute of Health Research; National Institute of Health; University of Toronto FX Merit Cudkowicz is supported by institutional grants. Lorne Zinman has received support from the ALS Society of Canada, the Canadian Institute of Health Research, the National Institute of Health and the University of Toronto. NR 76 TC 9 Z9 10 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 2012 VL 25 IS 6 BP 735 EP 742 DI 10.1097/WCO.0b013e32835a309d PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 040ZA UT WOS:000311364500014 PM 23160423 ER PT J AU Preusser, M Berghoff, AS Schadendorf, D Lin, NU Stupp, R AF Preusser, Matthias Berghoff, Anna S. Schadendorf, Dirk Lin, Nancy U. Stupp, Roger TI Brain metastasis: opportunity for drug development? SO CURRENT OPINION IN NEUROLOGY LA English DT Review DE brain metastases; drug; prophylaxis; treatment ID HER2-POSITIVE BREAST-CANCER; CELL LUNG-CANCER; PHASE-II; EGFR MUTATION; OPEN-LABEL; MELANOMA; LAPATINIB; TRIAL; CHEMOTHERAPY; CAPECITABINE AB Purpose of review Brain metastases are a common clinical problem, and only limited treatment options exist. We review recent advances in medical brain metastasis research with a focus on the most common tumor types associated with secondary brain colonization: melanoma, breast cancer and lung cancer. We speculate on opportunities for drug development in patients with brain metastases, both as a treatment of established disease and as an adjuvant and prophylactic strategy. Recent findings BRAF inhibitors and the immunomodulatory anticytotoxic T-lymphocyte-associated antigen 4 antibody ipilimumab have shown clinically meaningful activity in melanoma patients with brain metastases. In breast cancer, current studies on drug treatment of brain metastases are mainly focusing on human epidermal growth factor receptor 2 targeting agents such as lapatinib. Emerging data seem to implicate a potential role of targeted agents including antiangiogenic compounds, pazopanib, and epithelial growth factor receptor inhibitors for prevention of brain metastasis formation in breast cancer or nonsmall cell lung cancer. Summary Novel drugs are beginning to enter clinical practice for selected patients with brain metastases. The promising findings from recent studies may fuel more research on brain metastases and their optimal drug treatment. C1 [Preusser, Matthias] Med Univ Vienna, Dept Med 1, A-1090 Vienna, Austria. [Preusser, Matthias; Berghoff, Anna S.] Med Univ Vienna, Ctr Comprehens Canc, CNS Unit, A-1090 Vienna, Austria. [Berghoff, Anna S.] Med Univ Vienna, Inst Neurol, A-1090 Vienna, Austria. [Schadendorf, Dirk] Univ Hosp Essen, Dept Dermatol, Skin Canc Ctr, Essen, Germany. [Lin, Nancy U.] Dana Farber Canc Ctr, Dept Med Oncol, Boston, MA USA. [Stupp, Roger] CHU Vaudois, Dept Neurosurg & Clin Neurosci, CH-1011 Lausanne, Switzerland. [Stupp, Roger] Univ Lausanne, Lausanne, Switzerland. RP Preusser, M (reprint author), Med Univ Vienna, Dept Med 1, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM Matthias.preusser@meduniwien.ac.at OI Preusser, Matthias/0000-0003-3541-2315 FU Genentech; GlaxoSmithKline; Roche FX M.P. has received travel support (scientific meetings), research support (unrestricted grants) and lecture honoraria by Roche. N.U.L. has received consultancy honoraria by GlaxoSmithKline and has received grants by Genentech and GlaxoSmithKline. D.S. has attended compensated advisory boards and received honoraria as part of its speaker's bureau from Roche, Genentech, Amgen, Novartis, BMS, GSK and Merck. R.S. has received consultancy honoraria by Celgene, Roche, MSD/Merck, Merck Serono, and lecture honoraria by MSD/Merck&Co. A.S.B. has no conflicts of interest. NR 40 TC 14 Z9 14 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 2012 VL 25 IS 6 BP 786 EP 794 DI 10.1097/WCO.0b013e328359320d PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 040ZA UT WOS:000311364500022 PM 23108247 ER PT J AU Attard, SM Herring, AH Mayer-Davis, EJ Popkin, BM Meigs, JB Gordon-Larsen, P AF Attard, S. M. Herring, A. H. Mayer-Davis, E. J. Popkin, B. M. Meigs, J. B. Gordon-Larsen, P. TI Multilevel examination of diabetes in modernising China: what elements of urbanisation are most associated with diabetes? SO DIABETOLOGIA LA English DT Article DE China; Modernisation; Multilevel analysis; Nutrition transition; Type 2 diabetes ID HEALTH SYSTEM REFORM; BODY-MASS INDEX; NUTRITION TRANSITION; NONCOMMUNICABLE DISEASES; ECONOMIC-DEVELOPMENT; DEVELOPING-COUNTRY; PHYSICAL-ACTIVITY; CARE-SYSTEM; SAO-PAULO; TRENDS AB The purpose of this study was to examine the association between urbanisation-related factors and diabetes prevalence in China. Anthropometry, fasting blood glucose (FBG) and community-level data were collected for 7,741 adults (18-90 years) across 217 communities and nine provinces in the 2009 China Health and Nutrition Survey to examine diabetes (FBG a parts per thousand yen7.0 mmol/l or doctor diagnosis). Sex-stratified multilevel models, clustered at the community and province levels and controlling for individual-level age and household income were used to examine the association between diabetes and: (1) a multicomponent urbanisation measure reflecting overall modernisation and (2) 12 separate components of urbanisation (e.g., population density, employment, markets, infrastructure and social factors). Prevalent diabetes was higher in more-urbanised (men 12%; women 9%) vs less-urbanised (men 6%; women 5%) areas. In sex-stratified multilevel models adjusting for residential community and province, age and household income, there was a twofold higher diabetes prevalence in urban vs rural areas (men OR 2.02, 95% CI 1.47, 2.78; women, OR 1.94, 95% CI 1.35, 2.79). All urbanisation components were positively associated with diabetes, with variation across components (e.g. men, economic and income diversity, OR 1.42, 95% CI 1.20, 1.66; women, transportation infrastructure, OR 1.18, 95% CI 1.06, 1.32). Community-level variation in diabetes was comparatively greater for women (intraclass correlation [ICC] 0.03-0.05) vs men (ICC a parts per thousand currency sign0.01); province-level variation was greater for men (men 0.03-0.04; women 0.02). Diabetes prevention and treatment efforts are needed particularly in urbanised areas of China. Community economic factors, modern markets, communications and transportation infrastructure might present opportunities for such efforts. C1 [Herring, A. H.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Biostat, Chapel Hill, NC 27516 USA. [Attard, S. M.; Mayer-Davis, E. J.; Popkin, B. M.; Gordon-Larsen, P.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC 27516 USA. [Mayer-Davis, E. J.] Univ N Carolina, UNC Sch Med, Dept Med, Chapel Hill, NC 27516 USA. [Meigs, J. B.] Massachusetts Gen Hosp, Div Gen Med, Cambridge, MA USA. [Meigs, J. B.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Gordon-Larsen, P (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, 123 W Franklin St, Chapel Hill, NC 27516 USA. EM pglarsen@unc.edu OI popkin, barry/0000-0001-9495-9324 FU NIH: NHLBI [R01HL108427]; NIDDK [R21DK089306]; NIH: NICHD [R01-HD30880]; National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) [K24 DK080140]; NICHD-National Research Service Award (NRSA) [5T32DK007686-19]; Carolina Population Center [R24 HD050924] FX This work was supported by NIH: NHLBI (R01HL108427) and NIDDK (R21DK089306). NIH had no role in the design and conduct of the study, the collection, management, analysis and interpretation of the data or in the preparation, review or approval of the manuscript. This research uses data from the CHNS, funded by NIH: NICHD (R01-HD30880), although no direct support was received in the form of a grant for this analysis. J. B. Meigs is supported by National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) K24 DK080140. S. M. Attard is funded by NICHD-National Research Service Award (NRSA) (5T32DK007686-19). The authors are grateful to the Carolina Population Center (R24 HD050924) for general support. NR 38 TC 18 Z9 20 U1 8 U2 34 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 2012 VL 55 IS 12 BP 3182 EP 3192 DI 10.1007/s00125-012-2697-8 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 027VJ UT WOS:000310381800006 PM 22923063 ER PT J AU Stevens, RJ Ali, R Bankhead, CR Bethel, MA Cairns, BJ Camisasca, RP Crowe, FL Farmer, AJ Harrison, S Hirst, JA Home, P Kahn, SE McLellan, JH Perera, R Pluddemann, A Ramachandran, A Roberts, NW Rose, PW Schweizer, A Viberti, G Holman, RR AF Stevens, R. J. Ali, R. Bankhead, C. R. Bethel, M. A. Cairns, B. J. Camisasca, R. P. Crowe, F. L. Farmer, A. J. Harrison, S. Hirst, J. A. Home, P. Kahn, S. E. McLellan, J. H. Perera, R. Plueddemann, A. Ramachandran, A. Roberts, N. W. Rose, P. W. Schweizer, A. Viberti, G. Holman, R. R. TI Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials (vol 55, pg 2593, 2012) SO DIABETOLOGIA LA English DT Correction C1 [Stevens, R. J.; Bankhead, C. R.; Farmer, A. J.; Harrison, S.; Hirst, J. A.; McLellan, J. H.; Perera, R.; Plueddemann, A.; Roberts, N. W.; Rose, P. W.] Univ Oxford, Dept Primary Care Hlth Sci, Oxford OX2 6GG, England. [Ali, R.; Cairns, B. J.; Crowe, F. L.] Univ Oxford, Canc Epidemiol Unit, Oxford OX2 6GG, England. [Bethel, M. A.; Holman, R. R.] Univ Oxford, Diabet Trials Unit, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX2 6GG, England. [Camisasca, R. P.] Takeda Pharmaceut Co, TGRD Europe, London, England. [Home, P.] Newcastle Univ, Sch Med, ICM Diabet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Kahn, S. E.] Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. [Kahn, S. E.] Univ Washington, Seattle, WA 98195 USA. [Ramachandran, A.] Dr A Ramachandrans Diabet Hosp, India Diabet Res Fdn, Chennai, Tamil Nadu, India. [Schweizer, A.] Novartis Pharmaceut, Basel, Switzerland. [Viberti, G.] Kings Coll London, Metab Med Unit, Sch Med, London WC2R 2LS, England. RP Stevens, RJ (reprint author), Univ Oxford, Dept Primary Care Hlth Sci, Woodstock Rd, Oxford OX2 6GG, England. EM richard.stevens@phc.ox.ac.uk OI Roberts, Nia Wyn/0000-0002-1142-6440 NR 1 TC 4 Z9 4 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 2012 VL 55 IS 12 BP 3399 EP 3400 DI 10.1007/s00125-012-2740-9 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 027VJ UT WOS:000310381800030 ER PT J AU Talreja, JP Sethi, A Jamidar, PA Singh, SK Kwon, RS Siddiqui, UD Sawhney, M Bakhru, MR Gaidhane, M Kline, P Sauer, BG Kahaleh, M AF Talreja, Jayant P. Sethi, Amrita Jamidar, Priya A. Singh, Satish K. Kwon, Richard S. Siddiqui, Uzma D. Sawhney, Mandeep Bakhru, Mihir R. Gaidhane, Monica Kline, Pam Sauer, Bryan G. Kahaleh, Michel TI Interpretation of Probe-Based Confocal Laser Endomicroscopy of Indeterminate Biliary Strictures: Is There Any Interobserver Agreement? SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Probe-based confocal laser endomicroscopy; pCLE; Biliary stricture; Interobserver; Diagnostic accuracy ID PANCREATICOBILIARY STRICTURES; DIRECT VISUALIZATION; ERCP; CHOLANGIOSCOPY AB Probe-based confocal laser endomicroscopy (pCLE) has enabled in vivo histopathology by obtaining high resolution images of the mucosal layers of the gastrointestinal tract. For indeterminate bile duct strictures, biopsy, cytologic brushing and needle aspiration have low levels of diagnostic accuracy. The objective of this multi-center pilot study was to assess the interobserver agreement in interpretation of pCLE imaging. Twenty-five de-identified pCLE video clips of indeterminate biliary strictures were sent to 6 observers at 5 institutions. Miami Classification was used to standardize image interpretation. Seven variables were assessed for interobserver agreement using the Fleiss kappa statistic which included: presence of thick (> 20 mu m) or thin (< 20 mu m) dark or white bands, dark clumps, epithelium including glandular structures, interstitial fluorescein leakage, ease of interpretation, and final diagnosis. Based on operator experience, observers were categorized into 3 categories of experience (Category 1: 0-10; Category 2: 11-20; Category 3: > 21 cases). Upon stratification, Category 1 interobserver agreement ranged from "Poor" to "Fair" (kappa = 0.277, kappa = -0.079, kappa = -0.025, kappa = -0.066, kappa = 0.128, kappa = 0.088), and for the final diagnosis variable, the agreement was slight (kappa = 0.033). Category 2 and 3 interobserver agreement ranged from "Poor" to "Fair" (kappa = 0.211, kappa = 0.181, kappa = 0.347, kappa = 0.238, kappa = -0.050, kappa = 0.092), and for the final diagnosis variable, the agreement was slight (kappa = 0.195). The overall interobserver agreement for pCLE image interpretation in indeterminate biliary strictures ranges from poor to fair. Interpretation criteria as well as training require further standardization toward improving inter-rater reliability. C1 [Gaidhane, Monica; Kline, Pam; Kahaleh, Michel] Weill Cornell Med Coll, Dept Med, Div Gastroenterol & Hepatol, New York, NY 10065 USA. [Talreja, Jayant P.; Bakhru, Mihir R.; Sauer, Bryan G.] Univ Virginia, Dept Digest Hlth, Charlottesville, VA USA. [Sethi, Amrita] Columbia Univ, Dept Gastroenterol, Med Ctr, New York, NY USA. [Jamidar, Priya A.; Siddiqui, Uzma D.] Yale Univ, Dept Gastroenterol, New Haven, CT USA. [Singh, Satish K.] Boston Univ, Sch Med, Dept Gastroenterol, Boston, MA 02118 USA. [Kwon, Richard S.] Univ Michigan, Dept Gastroenterol, Ann Arbor, MI 48109 USA. [Sawhney, Mandeep] BIDMC, Dept Gastroenterol, Boston, MA USA. RP Kahaleh, M (reprint author), Weill Cornell Med Coll, Dept Med, Div Gastroenterol & Hepatol, New York, NY 10065 USA. EM mkahaleh@gmail.com RI Gaidhane, Monica/B-9414-2009 OI Gaidhane, Monica/0000-0001-6773-7080 NR 18 TC 16 Z9 16 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD DEC PY 2012 VL 57 IS 12 BP 3299 EP 3302 DI 10.1007/s10620-012-2338-6 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 043AF UT WOS:000311513900039 PM 22875310 ER PT J AU Marshall, DF Strutt, AM Williams, AE Simpson, RK Jankovic, J York, MK AF Marshall, D. F. Strutt, A. M. Williams, A. E. Simpson, R. K. Jankovic, J. York, M. K. TI Alternating verbal fluency performance following bilateral subthalamic nucleus deep brain stimulation for Parkinson's disease SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE deep brain stimulation; neuropsychology; Parkinson's disease; verbal fluency ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE IMPAIRMENT; PALLIDAL STIMULATION; LOCALIZATION; LESIONS; TASKS; MOOD AB Background and purpose Despite common occurrences of verbal fluency declines following bilateral subthalamic nucleus deep brain stimulation (STN-DBS) for the treatment of Parkinson's disease (PD), alternating fluency measures using cued and uncued paradigms have not been evaluated. Methods Twenty-three STN-DBS patients were compared with 20 non-surgical PD patients on a comprehensive neuropsychological assessment, including cued and uncued intradimensional (phonemic/phonemic and semantic/semantic) and extradimensional (phonemic/semantic) alternating fluency measures at baseline and 6-month follow-up. Results STN-DBS patients demonstrated a greater decline on the cued phonemic/phonemic fluency and the uncued phonemic/semantic fluency tasks compared to the PD patients. For STN-DBS patients, verbal learning and information processing speed accounted for a significant proportion of the variance in declines in alternating phonemic/phonemic and phonemic/semantic fluency scores, respectively, whilst only naming was related to uncued phonemic/semantic performance for the PD patients. Both groups were aided by cueing for the extradimensional task at baseline and follow-up, and the PD patients were also aided by cueing for the phonemic/phonemic task on follow-up. Conclusions These findings suggest that changes in alternating fluency are not related to disease progression alone as STN-DBS patients demonstrated greater declines over time than the PD patients, and this change was related to declines in information processing speed. C1 [Marshall, D. F.; Strutt, A. M.; Williams, A. E.; Jankovic, J.; York, M. K.] Baylor Coll Med, Dept Neurol, Parkinsons Dis & Movement Disorders Ctr, Houston, TX 77030 USA. [Simpson, R. K.] Methodist Hosp, Dept Neurosurg, Neurol Inst, Houston, TX 77030 USA. [York, M. K.] Parkinsons Dis Res Educ & Clin Ctr, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP York, MK (reprint author), Baylor Coll Med, Dept Neurol, Parkinsons Dis & Movement Disorders Ctr, 6550 Fannin,SM1801, Houston, TX 77030 USA. EM myork@bcm.edu FU NIH/NINDS FX The authors wish to thank the National Parkinson's Foundation and the patients who willingly gave their time to participate in this research project and Zack Dorsey for his help in final editing and revisions. Work was funded by an NIH/NINDS K23 grant (PI: York) and supported with resources from the Veterans' Affairs Office of Research and Development. NR 33 TC 12 Z9 12 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD DEC PY 2012 VL 19 IS 12 BP 1525 EP 1531 DI 10.1111/j.1468-1331.2012.03759.x PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 040AI UT WOS:000311290500009 PM 22632922 ER PT J AU Deng, XM Choi, HG Buhrlage, SJ Gray, NS AF Deng, Xianming Choi, Hwan Geun Buhrlage, Sara J. Gray, Nathanael S. TI Leucine-rich repeat kinase 2 inhibitors: a patent review (2006-2011) SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Review DE blood-brain barrier property; kinase selectivity; leucine-rich repeat kinase 2; LRRK2 G2019S mutation; LRRK2 inhibitors; Parkinson's disease ID DISEASE-ASSOCIATED MUTATIONS; PARKINSONS-DISEASE; CYTOPLASMIC LOCALIZATION; ANGIOGENESIS INHIBITOR; 14-3-3 BINDING; PHASE-I; LRRK2; POTENT; SELECTIVITY; DISCOVERY AB Introduction: Leucine-rich repeat kinase 2 (LRRK2) has received considerable attention since the discovery of LRRK2 mutations in families with dominantly inherited Parkinson's disease (PD) in 2004. The missense mutation G2019S is the most common LRRK2 mutation and has been identified in both familial and sporadic PD cases. The G2019S mutation enhances kinase activity suggesting that LRRK2 could be an attractive therapeutic target for PD and small-molecule ATP-competitive LRRK2 kinase inhibitors are one way to investigate this possibility. Areas covered: Currently, LRRK2 kinase inhibitors are being actively pursued by industry and academia. Herein, patents detailing the discovery of LRRK2 kinase inhibitors from 2006 through 2011 and the corresponding publications from 2006 through July of 2012 are summarized. Expert opinion: Wild-type and mutant forms of LRRK2 are currently being actively pursued as therapeutic targets for the potential treatment of PD. The increasing number of patent applications being filed for inhibitors of LRRK2 is a testament to this activity. Numerous distinct chemo-types have been reported as LRRK2 inhibitors with some demonstrating exceptional potency and selectivity for LRRK2 relative to other kinases. These compounds are being used as pharmacological 'tools' to elucidate the physiological and pathophysiological function of LRRK2 and it appears likely that some will be investigated for their potential therapeutic effects for the treatment of PD. C1 [Deng, Xianming] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China. [Choi, Hwan Geun; Buhrlage, Sara J.; Gray, Nathanael S.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Choi, Hwan Geun; Buhrlage, Sara J.; Gray, Nathanael S.] Harvard Univ, Dept Canc Biol, Sch Med, Boston, MA 02115 USA. RP Deng, XM (reprint author), Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China. EM xmdeng@xmu.edu.cn; nathanael_gray@dfci.harvard.edu FU NIH [P41 GM079575-03]; Michael J Fox foundation for Parkinson's disease research; Fundamental Research Funds for the Central Universities of China [2011121030]; 111 Project of Education of China [B06016] FX This work was supported by NIH grant P41 GM079575-03 (N. Gray), the Michael J Fox foundation for Parkinson's disease research (N. Gray), the Fundamental Research Funds for the Central Universities of China, project number 2011121030 (X. Deng) and 111 Project of Education of China, project number B06016 (X. Deng). NR 64 TC 11 Z9 11 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD DEC PY 2012 VL 22 IS 12 BP 1415 EP 1426 DI 10.1517/13543776.2012.729041 PG 12 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 041SB UT WOS:000311420400003 PM 23126385 ER PT J AU Aboutalebi, A Jessup, CJ North, PE Mihm, MC AF Aboutalebi, Amir Jessup, Chad J. North, Paula E. Mihm, Martin C., Jr. TI Histopathology of Vascular Anomalies SO FACIAL PLASTIC SURGERY LA English DT Article DE vascular anomaly; vascular malformation; infantile hemangioma; RICH/NICH; capillary malformation ID PORT-WINE STAIN; PAPILLARY ENDOTHELIAL HYPERPLASIA; KAPOSIFORM HEMANGIOENDOTHELIOMA; INFANTILE HEMANGIOMA; ARTERIOVENOUS-MALFORMATIONS; CONGENITAL HEMANGIOMAS; JUVENILE HEMANGIOMAS; CAPILLARY HEMANGIOMA; TIE2 RECEPTOR; INFANCY AB Vascular anomalies may be appropriately classified into two broad categories, vascular tumors and vascular malformations, which are distinguished by the presence of cellular proliferation in contrast to aberrations in morphogenesis, respectively. This system of classification is based upon histological features that may in large part be differentiating, but nevertheless, may show morphological overlap. Advances in immunopheno-typing allow for more precise diagnoses as well as further delineation of cell origins. In the discussion, we present the clinical, histological, and, when applicable, the immunophenotypic presentation of vascular anomalies commonly seen in infancy and early childhood. C1 [Mihm, Martin C., Jr.] Harvard Univ, Sch Med, Dept Dermatol & Pathol, Boston, MA 02115 USA. [Mihm, Martin C., Jr.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Aboutalebi, Amir] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02115 USA. [Jessup, Chad J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [North, Paula E.] Med Coll Wisconsin, Childrens Hosp Wisconsin, Dept Pathol & Lab Med, Div Pediat Pathol, Milwaukee, WI 53226 USA. RP Mihm, MC (reprint author), Harvard Univ, Sch Med, Dept Dermatol & Pathol, 41 Ave Louis Pasteur,Alumnae Hall,Room 317, Boston, MA 02115 USA. EM mmihm@partners.org NR 59 TC 6 Z9 6 U1 1 U2 6 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0736-6825 EI 1098-8793 J9 FACIAL PLAST SURG JI Facial Plast. Surg. PD DEC PY 2012 VL 28 IS 6 BP 545 EP 553 DI 10.1055/s-0032-1329929 PG 9 WC Surgery SC Surgery GA 044ZF UT WOS:000311663000002 PM 23188681 ER PT J AU Ortiz, AE Nelson, JS AF Ortiz, Arisa E. Nelson, J. Stuart TI Port-Wine Stain Laser Treatments and Novel Approaches SO FACIAL PLASTIC SURGERY LA English DT Article DE port-wine stains; capillary malformation; laser; selective photothermolysis; pulsed dye laser ID PULSED-DYE-LASER; ENDOTHELIAL GROWTH-FACTOR; PHOTODYNAMIC THERAPY; BLOOD-VESSELS; IN-VIVO; SELECTIVE PHOTOTHERMOLYSIS; CAPILLARY MALFORMATION; MULTILAYER TECHNIQUE; THERMAL RELAXATION; VASCULAR DAMAGE AB Background and Objectives Port-wine stains (PWSs) are capillary vascular malformations that are commonly resistant to treatment. Currently, the pulsed dye laser (PDL) is the treatment of choice. Multiple treatments are required and complete blanching after laser irradiation is rarely achieved. We review current therapeutic modalities for PWSs and recent developments for enhanced clearance. Study Design/Materials and Methods Relevant literature was reviewed including PDL modifications for improved efficacy, alternative laser devices for treatment-resistant PWSs, and the addition of agents to modulate the wound-healing response after laser irradiation. Results Although PDL is the treatment of choice for PWSs, increased understanding of interactions between PWSs and PDL has led to improvements in therapeutic outcome in terms of lesion blanching. Conclusions Preliminary evidence of combination therapy using antiangiogenic agents after laser irradiation appears promising and could lead to the development of a new standard of care for PWSs. C1 [Nelson, J. Stuart] Univ Calif Irvine, Beckman Laser Inst & Med Clin, Dept Surg, Irvine, CA 92612 USA. [Nelson, J. Stuart] Univ Calif Irvine, Beckman Laser Inst & Med Clin, Dept Biomed Engn, Irvine, CA 92612 USA. [Ortiz, Arisa E.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Nelson, JS (reprint author), Univ Calif Irvine, Beckman Laser Inst & Med Clin, Dept Surg, Irvine, CA 92612 USA. EM jsnelson@uci.edu FU NIAMS NIH HHS [R01 AR059244] NR 65 TC 15 Z9 17 U1 1 U2 9 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0736-6825 J9 FACIAL PLAST SURG JI Facial Plast. Surg. PD DEC PY 2012 VL 28 IS 6 BP 611 EP 620 DI 10.1055/s-0032-1329936 PG 10 WC Surgery SC Surgery GA 044ZF UT WOS:000311663000010 PM 23188689 ER PT J AU Adelstein, DJ Ridge, JA Brizel, DM Holsinger, FC Haughey, BH O'Sullivan, B Genden, EM Beitler, JJ Weinstein, GS Quon, H Chepeha, DB Ferris, RL Weber, RS Movsas, B Waldron, J Lowe, V Ramsey, S Manola, J Yueh, B Carey, TE Bekelman, JE Konski, AA Moore, E Forastiere, A Schuller, DE Lynn, J Ullmann, CD AF Adelstein, David J. Ridge, John A. Brizel, David M. Holsinger, F. Christopher Haughey, Bruce H. O'Sullivan, Brian Genden, Eric M. Beitler, Jonathan J. Weinstein, Gregory S. Quon, Harry Chepeha, Douglas B. Ferris, Robert L. Weber, Randal S. Movsas, Benjamin Waldron, John Lowe, Val Ramsey, Scott Manola, Judith Yueh, Bevan Carey, Thomas E. Bekelman, Justin E. Konski, Andre A. Moore, Eric Forastiere, Arlene Schuller, David E. Lynn, Jean Ullmann, Claudio Dansky TI Transoral resection of pharyngeal cancer: Summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6-7, 2011, Arlington, Virginia SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Review ID SQUAMOUS-CELL-CARCINOMA; QUALITY-OF-LIFE; LOCALLY ADVANCED HEAD; LYMPH-NODE METASTASES; STAGE OROPHARYNGEAL CANCER; UPPER AERODIGESTIVE TRACT; ADVANCED LARYNGEAL-CANCER; LASER MICROSURGERY TLM; LONG-TERM DYSPHAGIA; ROBOTIC SURGERY AB Recent advances now permit resection of many pharyngeal tumors through the open mouth, an approach that can greatly reduce the morbidity of surgical exposure. These transoral techniques are being rapidly adopted by the surgical community and hold considerable promise. On November 67, 2011, the National Cancer Institute sponsored a Clinical Trials Planning Meeting to address how to further investigate the use of transoral surgery, both in the good prognosis human papillomavirus (HPV)initiated oropharyngeal cancers, and in those with HPV-unrelated disease. The proceedings of this meeting are summarized. (c) 2012 Wiley Periodicals, Inc. Head Neck, 2012 C1 [Adelstein, David J.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Ridge, John A.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Brizel, David M.] Duke Canc Inst, Durham, NC USA. [Holsinger, F. Christopher; Weber, Randal S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Haughey, Bruce H.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. [O'Sullivan, Brian; Waldron, John] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Genden, Eric M.] Mt Sinai Sch Med, New York, NY USA. [Beitler, Jonathan J.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Weinstein, Gregory S.; Bekelman, Justin E.] Univ Penn, Philadelphia, PA 19104 USA. [Quon, Harry; Forastiere, Arlene] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Chepeha, Douglas B.; Carey, Thomas E.] Univ Michigan, Ann Arbor, MI 48109 USA. [Ferris, Robert L.] Univ Pittsburgh, Pittsburgh, PA USA. [Movsas, Benjamin] Henry Ford Hosp, Detroit, MI 48202 USA. [Lowe, Val; Moore, Eric] Mayo Clin, Rochester, MN USA. [Ramsey, Scott] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Manola, Judith] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yueh, Bevan] Univ Minnesota, Minneapolis, MN USA. [Konski, Andre A.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Schuller, David E.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Lynn, Jean; Ullmann, Claudio Dansky] NCI, Bethesda, MD 20892 USA. RP Adelstein, DJ (reprint author), Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. EM adelstd@ccf.org OI Yueh, Bevan/0000-0003-1380-1053; Ferris, Robert/0000-0001-6605-2071; Carey, Thomas/0000-0002-5202-7518 FU NCI NIH HHS [P30 CA016672] NR 119 TC 42 Z9 42 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD DEC PY 2012 VL 34 IS 12 BP 1681 EP 1703 DI 10.1002/hed.23136 PG 23 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 040AT UT WOS:000311291900001 PM 23015475 ER PT J AU Lin, FH Nummenmaa, A Witzel, T Polimeni, JR Zeffiro, TA Wang, FN Belliveau, JW AF Lin, Fa-Hsuan Nummenmaa, Aapo Witzel, Thomas Polimeni, Jonathan R. Zeffiro, Thomas A. Wang, Fu-Nien Belliveau, John W. TI Physiological noise reduction using volumetric functional magnetic resonance inverse imaging SO HUMAN BRAIN MAPPING LA English DT Article DE event-related; inverse imaging; Inl; visual; MRI; fMRI; neuroimaging; inverse solution ID MULTIVARIATE AUTOREGRESSIVE MODELS/; SURFACE-BASED ANALYSIS; HUMAN-BRAIN; CORTICAL SURFACE; ECHO-PLANAR; COORDINATE SYSTEM; IMPULSE-RESPONSE; BOLD SIGNAL; FMRI; MRI AB Physiological noise arising from a variety of sources can significantly degrade the detection of task-related activity in BOLD-contrast fMRI experiments. If whole head spatial coverage is desired, effective suppression of oscillatory physiological noise from cardiac and respiratory fluctuations is quite difficult without external monitoring, since traditional EPI acquisition methods cannot sample the signal rapidly enough to satisfy the Nyquist sampling theorem, leading to temporal aliasing of noise. Using a combination of high speed magnetic resonance inverse imaging (InI) and digital filtering, we demonstrate that it is possible to suppress cardiac and respiratory noise without auxiliary monitoring, while achieving whole head spatial coverage and reasonable spatial resolution. Our systematic study of the effects of different moving average (MA) digital filters demonstrates that a MA filter with a 2 s window can effectively reduce the variance in the hemodynamic baseline signal, thereby achieving 57%58% improvements in peak z-statistic values compared to unfiltered InI or spatially smoothed EPI data (FWHM = 8.6 mm). In conclusion, the high temporal sampling rates achievable with InI permit significant reductions in physiological noise using standard temporal filtering techniques that result in significant improvements in hemodynamic response estimation. Hum Brain Mapp 33:2815-2830, 2012. (c) 2011 Wiley Periodicals, Inc. C1 [Wang, Fu-Nien] Natl Tsing Hua Univ, Dept Biomed Engn & Environm Sci, Hsinchu, Taiwan. [Lin, Fa-Hsuan] Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. [Lin, Fa-Hsuan; Nummenmaa, Aapo; Polimeni, Jonathan R.; Belliveau, John W.] MGH HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Nummenmaa, Aapo] Aalto Univ, Sch Sci & Technol, Dept Biomed Engn & Computat Sci, Espoo, Finland. [Witzel, Thomas] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Zeffiro, Thomas A.] Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA USA. RP Wang, FN (reprint author), Natl Tsing Hua Univ, Dept Biomed Engn & Environm Sci, Hsinchu, Taiwan. EM fnwang@mx.nthu.edu.tw RI Lin, Fa-Hsuan/G-6988-2012; Witzel, Thomas/P-1402-2014; Polimeni, Jonathan/P-1395-2014 OI Lin, Fa-Hsuan/0000-0002-9539-1731; Polimeni, Jonathan/0000-0002-1348-1179 FU National Institutes of Health [R01DA14178, R01HD040712, R01NS-037462, P41RR14075, R01EB006847, R01EB000790, R21EB007298, R01MH083744]; National Center for Research Resources [97-2320-B-002-058-MY3]; National Science Council, Taiwan [98-2320-B-002-004-MY3]; National Health Research Institute, Taiwan [NHRI-EX99-9715EC]; Academy of Finland [127624] FX Contract grant sponsor: National Institutes of Health Grants; Contract grant numbers: R01DA14178, R01HD040712, R01NS-037462, P41RR14075, R01EB006847, R01EB000790, R21EB007298, R01MH083744; Contract grant sponsor: National Center for Research Resources; Contract grant number: 97-2320-B-002-058-MY3; Contract grant sponsor: National Science Council, Taiwan; Contract grant number: 98-2320-B-002-004-MY3; Contract grant sponsor: National Health Research Institute, Taiwan; Contract grant number: NHRI-EX99-9715EC; Contract grant sponsor: Academy of Finland; Contract grant number: 127624. NR 55 TC 12 Z9 12 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD DEC PY 2012 VL 33 IS 12 BP 2815 EP 2830 DI 10.1002/hbm.21403 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 033LU UT WOS:000310798800006 PM 21954026 ER PT J AU de Nijs, L Wolkoff, N Coumans, B Delgado-Escueta, AV Grisar, T Lakaye, B AF de Nijs, Laurence Wolkoff, Nathalie Coumans, Bernard Delgado-Escueta, Antonio V. Grisar, Thierry Lakaye, Bernard TI Mutations of EFHC1, linked to juvenile myoclonic epilepsy, disrupt radial and tangential migrations during brain development SO HUMAN MOLECULAR GENETICS LA English DT Article ID VOXEL-BASED MORPHOMETRY; DEVELOPING CEREBRAL-CORTEX; NEURONAL MIGRATION; GENERALIZED EPILEPSY; RNA INTERFERENCE; PROTEIN; NEOCORTEX; MYOCLONIN1/EFHC1; NUCLEOKINESIS; ABNORMALITIES AB Heterozygous mutations in Myoclonin1/EFHC1 cause juvenile myoclonic epilepsy (JME), the most common form of genetic generalized epilepsies, while homozygous F229L mutation is associated with primary intractable epilepsy in infancy. Heterozygous mutations in adolescent JME patients produce subtle malformations of cortical and subcortical architecture, whereas homozygous F229L mutation in infancy induces severe brain pathology and death. However, the underlying pathological mechanisms for these observations remain unknown. We had previously demonstrated that EFHC1 is a microtubule-associated protein (MAP) involved in cell division and radial migration during cerebral corticogenesis. Here, we show that JME mutations, including F229L, do not alter the ability of EFHC1 to colocalize with the centrosome and the mitotic spindle, but act in a dominant-negative manner to impair mitotic spindle organization. We also found that mutants EFHC1 expression disrupted radial and tangential migration by affecting the morphology of radial glia and migrating neurons. These results show how Myoclonin1/EFHC1 mutations disrupt brain development and potentially produce structural brain abnormalities on which epileptogenesis is established. C1 [de Nijs, Laurence; Wolkoff, Nathalie; Coumans, Bernard; Grisar, Thierry; Lakaye, Bernard] Univ Liege, GIGA Neurosci, B-4000 Liege, Belgium. [Delgado-Escueta, Antonio V.] VA Greater Los Angeles Healthcare Syst, Epilepsy Genet Genom Labs, Neurol & Res Serv, Los Angeles, CA USA. [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Lakaye, B (reprint author), Univ Liege, GIGA Neurosci, 1 Ave Hop, B-4000 Liege, Belgium. EM b.lakaye@ulg.ac.be OI Delgado-Escueta, Antonio V./0000-0002-1581-6999 FU Fonds de la Recherche Scientifique-FNRS [FRSM 3.4531.09]; Leon Fredericq Foundation; Fonds speciaux of the University of Liege [C-10/31, C-11/94]; NIH [5R01NS055057]; VA Merit Review grant FX This work was supported by the Fonds de la Recherche Scientifique-FNRS (FRSM 3.4531.09 to T. G. and B. L.); the Leon Fredericq Foundation (to L.d.N.) and the Fonds speciaux of the University of Liege (C-10/31 and C-11/94 to T. G and B. L.). L.d.N. and B. L. are, respectively, postdoctoral researcher and research associates at the Fonds de la Recherche Scientifique-FNRS. A. V. D.-E. is supported by NIH grant 5R01NS055057 and VA Merit Review grant. NR 44 TC 13 Z9 14 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 1 PY 2012 VL 21 IS 23 BP 5106 EP 5117 DI 10.1093/hmg/dds356 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 035SE UT WOS:000310967900007 PM 22926142 ER PT J AU Babacan, SD Ansorge, R Luessi, M Mataran, PR Molina, R Katsaggelos, AK AF Babacan, S. Derin Ansorge, Reto Luessi, Martin Ruiz Mataran, Pablo Molina, Rafael Katsaggelos, Aggelos K. TI Compressive Light Field Sensing SO IEEE TRANSACTIONS ON IMAGE PROCESSING LA English DT Article DE Bayesian methods; coded aperture; compressive sensing; computational photography; image reconstruction; light fields ID UNCERTAINTY PRINCIPLES; ARRAYS; RECONSTRUCTION; PHOTOGRAPHY; NOISE AB We propose a novel design for light field image acquisition based on compressive sensing principles. By placing a randomly coded mask at the aperture of a camera, incoherent measurements of the light passing through different parts of the lens are encoded in the captured images. Each captured image is a random linear combination of different angular views of a scene. The encoded images are then used to recover the original light field image via a novel Bayesian reconstruction algorithm. Using the principles of compressive sensing, we show that light field images with a large number of angular views can be recovered from only a few acquisitions. Moreover, the proposed acquisition and recovery method provides light field images with high spatial resolution and signal-to-noise-ratio, and therefore is not affected by limitations common to existing light field camera designs. We present a prototype camera design based on the proposed framework by modifying a regular digital camera. Finally, we demonstrate the effectiveness of the proposed system using experimental results with both synthetic and real images. C1 [Babacan, S. Derin] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. [Ansorge, Reto] Varian Med Syst, CH-5405 Baden, Switzerland. [Luessi, Martin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging,Dept Radiol, Boston, MA 02114 USA. [Ruiz Mataran, Pablo; Molina, Rafael] Univ Granada, Dept Ciencias Comp & Inteligencia Artificial, Granada 18010, Spain. [Katsaggelos, Aggelos K.] Northwestern Univ, Dept Elect Engn & Comp Sci, Evanston, IL 60208 USA. RP Babacan, SD (reprint author), Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. EM dbabacan@illinois.edu; reto.ansorge@gmx.ch; mluessi@nmr.mgh.harvard.edu; mataran@decsai.ugr.es; rms@decsai.ugr.es; aggk@eecs.northwestern.edu RI Molina Soriano, Rafael/B-1849-2012; Katsaggelos, Aggelos/B-7233-2009 OI Molina Soriano, Rafael/0000-0003-4694-8588; FU Beckman Institute's Post-Doctoral Fellowship; Ministerio de Ciencia e Innovacion [TIN2010-15137]; Spanish Research Program Consolider Ingenio: MIPRCV [CSD2007-00018]; Department of Energy [DE-NA0000457] FX Manuscript received March 29, 2011; revised June 12, 2012; accepted June 27, 2012. Date of publication July 25, 2012; date of current version November 14, 2012. This work was supported in part by the Beckman Institute's Post-Doctoral Fellowship, the Ministerio de Ciencia e Innovacion under Contract TIN2010-15137, the Spanish Research Program Consolider Ingenio 2010: MIPRCV under Grant CSD2007-00018, and the Department of Energy under Grant DE-NA0000457. Preliminary results of this paper appeared at the IEEE Conference on Image Processing, Cairo, Egypt, 2009 [2]. The associate editor coordinating the review of this manuscript and approving it for publication was Dr. Xin Li. NR 47 TC 22 Z9 24 U1 1 U2 31 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1057-7149 EI 1941-0042 J9 IEEE T IMAGE PROCESS JI IEEE Trans. Image Process. PD DEC PY 2012 VL 21 IS 12 BP 4746 EP 4757 DI 10.1109/TIP.2012.2210237 PG 12 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 040YQ UT WOS:000311363200006 PM 22851261 ER PT J AU Bodhankar, S Vandenbark, AA Offner, H AF Bodhankar, Sheetal Vandenbark, Arthur A. Offner, Halina TI Oestrogen treatment of experimental autoimmune encephalomyelitis requires 17 beta-oestradiol-receptor-positive B cells that up-regulate PD-1 on CD4(+) Foxp3(+) regulatory T cells SO IMMUNOLOGY LA English DT Article DE experimental autoimmune encephalomyelitis; multiple sclerosis; oestrogen and receptors; programmed death-1; programmed death ligand; regulatory B cells ID PREGNANCY HORMONE ESTRIOL; PROGRAMMED DEATH 1; MULTIPLE-SCLEROSIS; EXPRESSION; MICE; MODULATION; SEVERITY AB It is now well accepted that sex hormones have immunoregulatory activity and may prevent exacerbations in multiple sclerosis during pregnancy. Our previous studies demonstrated that oestrogen (17 beta-oestradiol; E2) protection against experimental autoimmune encephalomyelitis (EAE) is mediated mainly through oestrogen receptor-a (ERa) and the membrane receptor G-protein-coupled receptor 30 (GPR30) and is abrogated in the absence of B cells and the co-inhibitory receptor, Programmed Death-1 (PD-1). To critically evaluate the cell source of the E2 and PD-1 co-inhibitory pathways in EAE regulation, we assessed the requirement for ERs on transferred B cells and downstream effects on expression of PD-1/PD-ligand on CD4+ Foxp3+ regulatory T (Treg) cells in B-cell-replenished, E2-treated B-cell-deficient (mu MT-/-) mice with EAE. The results clearly demonstrated involvement of ERa and GPR30 on transferred B cells that mediated the protective E2 treatment effect on EAE and further showed an E2-mediated B-cell-dependent up-regulation of PD-1 on CD4+ Foxp3+ Treg cells. These findings identify regulatory B-cell populations as key players in potentiating Treg-cell activity during E2-mediated protection against EAE. C1 [Bodhankar, Sheetal; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA. [Bodhankar, Sheetal; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Vandenbark, Arthur A.] Dept Vet Affairs Med Ctr, Res Serv, Portland, OR USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. [Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU National Institutes of Health [NS045445]; National Multiple Sclerosis Society [RG3405-C-6]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX The authors thank Lisa Miller and Mary Chase for technical assistance, Danielle Galipeau for assistance in histology images, Zefora Alderman for assistance in preparing the figures and Eva Niehaus for assistance with manuscript preparation. This work was supported by National Institutes of Health grant NS045445 and National Multiple Sclerosis Society grant RG3405-C-6. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the Department of Veterans Affairs or the US Government. NR 26 TC 21 Z9 21 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2012 VL 137 IS 4 BP 282 EP 293 DI 10.1111/imm.12013 PG 12 WC Immunology SC Immunology GA 041HE UT WOS:000311389900002 PM 23039230 ER PT J AU Garber, JJ Takeshima, F Anton, IM Oyoshi, MK Lyubimova, A Kapoor, A Shibata, T Chen, F Alt, FW Geha, RS Leong, JM Snapper, SB AF Garber, John J. Takeshima, Fuminao Anton, Ines M. Oyoshi, Michiko K. Lyubimova, Anna Kapoor, Archana Shibata, Tomoyuki Chen, Feng Alt, Frederick W. Geha, Raif S. Leong, John M. Snapper, Scott B. TI Enteropathogenic Escherichia coli and Vaccinia Virus Do Not Require the Family of WASP-Interacting Proteins for Pathogen-Induced Actin Assembly SO INFECTION AND IMMUNITY LA English DT Article ID ALDRICH-SYNDROME PROTEIN; N-WASP; PEDESTAL FORMATION; ARP2/3 COMPLEX; DEFICIENCY REVEALS; EFFACING LESIONS; EFFECTORS TIR; HELA-CELLS; WIP; MOTILITY AB The human pathogens enteropathogenic Escherichia coli (EPEC) and vaccinia virus trigger actin assembly in host cells by activating the host adaptor Nck and the actin nucleation promoter neural Wiskott-Aldrich syndrome protein (N-WASP). EPEC translocates effector molecules into host cells via type III secretion, and the interaction between the translocated intimin receptor (Tir) and the bacterial membrane protein intimin stimulates Nck and N-WASP recruitment, leading to the formation of actin pedestals beneath adherent bacteria. Vaccinia virus also recruits Nck and N-WASP to generate actin tails that promote cell-to-cell spread of the virus. In addition to Nck and N-WASP, WASP-interacting protein (WIP) localizes to vaccinia virus tails, and inhibition of actin tail formation upon ectopic expression of WIP mutants led to the suggestion that WIP is required for this process. Similar studies of WIP mutants, however, did not affect the ability of EPEC to form actin pedestals, arguing against an essential role for WIP in EPEC-induced actin assembly. In this study, we demonstrate that Nck and N-WASP are normally recruited by vaccinia virus and EPEC in the absence of WIP, and neither WIP nor the WIP family members CR16 and WIRE/WICH are essential for pathogen induced actin assembly. In addition, although Nck binds EPEC Tir directly, N-WASP is required for its localization during pedestal formation. Overall, these data highlight similar pathogenic strategies shared by EPEC and vaccinia virus by demonstrating a requirement for both Nck and N-WASP, but not WIP or WIP family members in pathogen-induced actin assembly. C1 [Garber, John J.; Takeshima, Fuminao; Lyubimova, Anna; Kapoor, Archana; Shibata, Tomoyuki; Snapper, Scott B.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Garber, John J.; Takeshima, Fuminao; Lyubimova, Anna; Kapoor, Archana; Shibata, Tomoyuki; Snapper, Scott B.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Garber, John J.; Takeshima, Fuminao; Lyubimova, Anna; Kapoor, Archana; Shibata, Tomoyuki; Snapper, Scott B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Anton, Ines M.; Oyoshi, Michiko K.; Geha, Raif S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Garber, John J.; Snapper, Scott B.] Childrens Hosp, Div Gastroenterol Nutr, Boston, MA 02115 USA. [Garber, John J.; Snapper, Scott B.] Childrens Hosp, Ctr Inflammatory Bowel Dis Treatment & Res, Boston, MA 02115 USA. [Anton, Ines M.; Oyoshi, Michiko K.; Geha, Raif S.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Chen, Feng; Alt, Frederick W.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Leong, John M.] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Snapper, Scott B.] Brigham & Womens Hosp, Div Gastroenterol & Hepatol, Boston, MA 02115 USA. RP Snapper, SB (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM scott.snapper@childrens.harvard.edu RI Anton, Ines/G-6090-2015 FU National Institutes of Health [R01AI46454, P01HL059561, R01AI052354, F32DK088442]; Career Development Award from the Crohn's and Colitis Foundation of America; Harvard Digestive Disease Center [5P30DK034854] FX This study was supported by National Institutes of Health grants R01AI46454 (to J.M.L.), P01HL059561 (to R.S.G. and S.B.S.), R01AI052354 (to S.B.S.), and F32DK088442 (to J.J.G.), as well as a Career Development Award from the Crohn's and Colitis Foundation of America (to J.J.G.) and the Harvard Digestive Disease Center (5P30DK034854 to S.B.S. and J.J.G.). NR 55 TC 3 Z9 3 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2012 VL 80 IS 12 BP 4071 EP 4077 DI 10.1128/IAI.06148-11 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 036MQ UT WOS:000311030800002 PM 22966049 ER PT J AU Fukuta, Y Cunningham, CA Harris, PL Wagener, MM Muder, RR AF Fukuta, Yuriko Cunningham, Candace A. Harris, Patricia L. Wagener, Marilyn M. Muder, Robert R. TI Identifying the Risk Factors for Hospital-Acquired Methicillin-Resistant Staphylococcus aureus (MRSA) Infection among Patients Colonized with MRSA on Admission SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID INTENSIVE-CARE-UNIT; NASAL COLONIZATION; SURVEILLANCE AB BACKGROUND. Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in hospital-acquired infections. MRSA-colonized inpatients who may benefit from undergoing decolonization have not been identified. OBJECTIVE. To identify risk factors for MRSA infection among patients who are colonized with MRSA at hospital admission. DESIGN. A case-control study. SETTING. A 146-bed Veterans Affairs hospital. PARTICIPANTS. Case patients were those patients admitted from January 2003 to August 2011 who were found to be colonized with MRSA on admission and then developed MRSA infection. Control subjects were those patients admitted during the same period who were found to be colonized with MRSA on admission but who did not develop MRSA infection. METHODS. A retrospective review. RESULTS. A total of 75 case patients and 150 control subjects were identified. A stay in the intensive care unit (ICU) was the significant risk factor in univariate analysis (P < .001). Prior history of MRSA (P = .03), transfer from a nursing home (P = .002), experiencing respiratory failure (P < .001), and receipt of transfusion (P = .001) remained significant variables in multivariate analysis. Prior history of MRSA colonization or infection (P = .02), difficulty swallowing (P = .04), presence of an open wound (P = .002), and placement of a central line (P = .02) were identified as risk factors for developing MRSA infection for patients in the ICU. Duration of hospitalization, readmission rate, and mortality rate were significantly higher in case patients than in control subjects (P < .001, .001, and <.001, respectively). CONCLUSIONS. MRSA-colonized patients admitted to the ICU or admitted from nursing homes have a high risk of developing MRSA infection. These patients may benefit from undergoing decolonization. Infect Control Hosp Epidemiol 2012;33(12):1219-1225 C1 [Fukuta, Yuriko; Muder, Robert R.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. [Cunningham, Candace A.; Harris, Patricia L.; Muder, Robert R.] VA Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA USA. [Wagener, Marilyn M.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Muder, RR (reprint author), Univ Dr C, Pittsburgh, PA 15240 USA. EM robert.muder@med.va.gov NR 15 TC 13 Z9 14 U1 0 U2 10 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD DEC PY 2012 VL 33 IS 12 BP 1219 EP 1225 DI 10.1086/668420 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 037BP UT WOS:000311076300006 PM 23143359 ER EF