FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Rayess, H Wang, MB Srivatsan, ES AF Rayess, Hani Wang, Marilene B. Srivatsan, Eri S. TI Cellular senescence and tumor suppressor gene p16 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Review DE senescence; tumor suppressor gene p16 ID FACTOR-KAPPA-B; HISTONE METHYLTRANSFERASE ACTIVITY; POLYCOMB GROUP PROTEINS; P16(INK4A) EXPRESSION; SELF-RENEWAL; CYCLE ARREST; IN-VIVO; TRANSCRIPTIONAL REPRESSION; PREMATURE SENESCENCE; HETEROCHROMATIN FOCI AB Cellular senescence is an irreversible arrest of cell growth. Biochemical and morphological changes occur during cellular senescence, including the formation of a unique cellular morphology such as flattened cytoplasm. Function of mitochondria, endoplasmic reticulum and lysosomes are affected resulting in the inhibition of lysosomal and proteosomal pathways. Cellular senescence can be triggered by a number of factors including, aging, DNA damage, oncogene activation and oxidative stress. While the molecular mechanism of senescence involves p16 and p53 tumor suppressor genes and telomere shortening, this review is focused on the mechanism of p16 control. The p16-mediated senescence acts through the retinoblastoma (Rb) pathway inhibiting the action of the cyclin dependant kinases leading to G1 cell cycle arrest. Rb is maintained in a hypophosphorylated state resulting in the inhibition of transcription factor E2F1. Regulation of p16 expression is complex and involves epigenetic control and multiple transcription factors. PRC1 (Pombe repressor complex (1) and PRC2 (Pombe repressor complex (2) proteins and histone deacetylases play an important role in the promoter hypermethylation for suppressing p16 expression. While transcription factors YY1 and Id1 suppress p16 expression, transcription factors CTCF, Sp1 and Ets family members activate p16 transcription. Senescence occurs with the inactivation of suppressor elements leading to the enhanced expression of p16. C1 [Srivatsan, Eri S.] Univ Calif Los Angeles, David Geffen Sch Med, VAGLAHS, Dept Surg, Los Angeles, CA 90073 USA. [Rayess, Hani; Wang, Marilene B.; Srivatsan, Eri S.] VA Greater Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Rayess, Hani] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Wang, Marilene B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, Dept Surg, Los Angeles, CA 90073 USA. RP Srivatsan, ES (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VAGLAHS, Dept Surg, 11301 Wilshire Blvd,Bldg 304, Los Angeles, CA 90073 USA. EM esrivats@ucla.edu FU NIH [R21 CA116826-01]; VAGLAHS; West Los Angeles Surgical Education Research Center; Veterans Administration, Washington, DC FX Grant sponsor: NIH; Grant number: R21 CA116826-01; Grant sponsors: VAGLAHS, West Los Angeles Surgical Education Research Center, Veterans Administration, Washington, DC NR 122 TC 126 Z9 142 U1 5 U2 55 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 15 PY 2012 VL 130 IS 8 BP 1715 EP 1725 DI 10.1002/ijc.27316 PG 11 WC Oncology SC Oncology GA 897WV UT WOS:000300692300001 PM 22025288 ER PT J AU Caesar, I Gandy, S AF Caesar, Ina Gandy, Sam TI Evidence that an APOE epsilon 4 'double whammy' increases risk for Alzheimer's disease SO BMC MEDICINE LA English DT Editorial Material DE Alzheimer's disease; epilepsy; apolipoprotein; cerebral amyloidosis ID TEMPORAL-LOBE EPILEPSY; IMPROVES COGNITIVE PERFORMANCE; APOLIPOPROTEIN-E; HIPPOCAMPAL SCLEROSIS; SENILE PLAQUES; PEPTIDE; COG1410; POLYMORPHISMS; CONFUSION; INJURY AB Temporal lobe epilepsy (TLE) is associated with some of the same neuropathological features as those reported for early stages of typical Alzheimer's disease (AD). The APOE epsilon 4 allele is associated with a gene-dose-dependent increase in AD risk and in the severity of amyloid-beta (A beta) pathology. In a study published in the current BMC Medicine, Sue Griffin and colleagues studied markers of brain resilience in the amputated temporal lobes of TLE patients. They discovered compelling evidence that the APOE epsilon 3 isoform in TLE patients is apparently more neuroprotective from A beta toxicity than is the APOE epsilon 4 isoform, as shown by the reduced levels of neuronal damage, glial activation, and expression of IL-1 alpha in the APOE epsilon 3/epsilon 3 brains. This result points to a new property of APOE isoforms: not only are APOE epsilon 4 alleles associated with increased brain amyloid plaque burden, but these alleles are also apparently inferior to APOE epsilon 3 alleles in conveying resistance to A beta neurotoxicity. This 'double whammy' result opens up a new direction for studies aimed at elucidating the relevant neurobiological activities of APOE isoforms in the pathogenesis of AD. Please see related article: http://www.biomedcentral.com/1741-7015/10/35 C1 [Caesar, Ina; Gandy, Sam] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Caesar, Ina; Gandy, Sam] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Caesar, Ina; Gandy, Sam] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Caesar, Ina; Gandy, Sam] James J Peters VA Med Ctr, New York, NY 10468 USA. RP Caesar, I (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM ina.caesar@mssm.edu NR 30 TC 5 Z9 5 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD APR 13 PY 2012 VL 10 AR 36 DI 10.1186/1741-7015-10-36 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 945TK UT WOS:000304298800002 PM 22502767 ER PT J AU Melo, JA Ruvkun, G AF Melo, Justine A. Ruvkun, Gary TI Inactivation of Conserved C. elegans Genes Engages Pathogen- and Xenobiotic-Associated Defenses SO CELL LA English DT Article ID CAENORHABDITIS-ELEGANS; SIGNALING PATHWAY; MAPK PHOSPHATASE; IMMUNE-RESPONSE; STRESS-RESPONSE; PROTEIN; INFECTION; RNAI; KINASE; NEMATOPHILUM AB The nematode C. elegans is attracted to nutritious bacteria and is repelled by pathogens and toxins. Here we show that RNAi and toxin-mediated disruption of core cellular activities, including translation, respiration, and protein turnover, stimulate behavioral avoidance of normally attractive bacteria. RNAi of these and other essential processes induces expression of detoxification and innate immune effectors, even in the absence of toxins or pathogens. Disruption of core processes in non-neuronal tissues was sufficient to stimulate aversion behavior, revealing a neuroendocrine axis of control that additionally required serotonergic and Jnk kinase signaling pathways. We propose that surveillance pathways overseeing core cellular activities allow animals to detect invading pathogens that deploy toxins and virulence factors to undermine vital host functions. Variation in cellular surveillance and endocrine pathways controlling behavior, detoxification, and immunity selected by past toxin or microbial interactions could underlie aberrant responses to foods, medicines, and microbes. C1 [Melo, Justine A.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Melo, Justine A.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU Jane Coffin Childs Memorial Fund; Bank of America Charles King Trust; MGH; NIH [DK070147] FX We thank F. Ausubel, D. McEwan, R. Pukkila-Worley, E. Troemel, S. Curran, A. Frand, J. Kim, D. Kim, Y. Tabach, B. Cezairliyan, A. Jose, J. Gray, B. Shtonda, L. Avery, C. Bargmann, and D. Hopwood for helpful discussions, D. Shore for participation in stress reporter assays, E. O'Rourke and B. Samuel for assistance with pharyngeal pumping assays, and Rusty Howson for figure support. We thank the CGC, OMRF knockout consortium, National Bioresource Project of Japan, F. Ausubel, D. Kim, E. Troemel, J. Irazoqui, J. Kaplan, J. Kim, A. Soukas, L. Avery, and R. Losick for strains, and the C. elegans resource Wormbase. For sharing unpublished results, we thank F. Ausubel, D. Kim, E. Troemel, Y. Tabach, L. Avery, and S. Politz. Salary support for J. A. M. was provided by the Jane Coffin Childs Memorial Fund, the Bank of America Charles King Trust, and the MGH Fund for Medical Discovery. This work was funded by NIH grant DK070147. NR 42 TC 112 Z9 113 U1 1 U2 22 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD APR 13 PY 2012 VL 149 IS 2 BP 452 EP 466 DI 10.1016/j.cell.2012.02.050 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 926BF UT WOS:000302805600022 PM 22500807 ER PT J AU Sapp, E Valencia, A Li, XY Aronin, N Kegel, KB Vonsattel, JP Young, AB Wexler, N DiFiglia, M AF Sapp, Ellen Valencia, Antonio Li, Xueyi Aronin, Neil Kegel, Kimberly B. Vonsattel, Jean-Paul Young, Anne B. Wexler, Nancy DiFiglia, Marian TI Native Mutant Huntingtin in Human Brain EVIDENCE FOR PREVALENCE OF FULL-LENGTH MONOMER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IN MOUSE MODEL; INTRANUCLEAR INCLUSIONS; TRANSGENIC MICE; POLYGLUTAMINE REPEAT; WILD-TYPE; DISEASE; PROTEIN; FRAGMENTS; EXPRESSION; PROTEOLYSIS AB Huntington disease (HD) is caused by polyglutamine expansion in theNterminus of huntingtin (htt). Analysis of human postmortem brain lysates by SDS-PAGE and Western blot reveals htt as full-lengthandfragmented. HereweusedBlueNativePAGE(BNP) and Western blots to study native htt in human postmortem brain. Antisera against htt detected a single band broadly migrating at 575-850 kDa in control brain and at 650-885 kDa in heterozygous and Venezuelan homozygousHDbrains. Anti-polyglutamine antisera detected full-length mutant htt in HD brain. There was little htt cleavage even if lysates were pretreated with trypsin, indicating a property of native htt to resist protease cleavage. Asoluble mutant htt fragment of about 180 kDa was detected with anti-htt antibody Ab1 (htt-(1-17)) and increased when lysates were treated with denaturants (SDS, 8 M urea, DTT, or trypsin) before BNP. Wild-type htt was more resistant to denaturants. Based on migration of in vitro translated htt fragments, the 180-kDa segment terminated approximate to htt 670-880 amino acids. If second dimension SDSPAGE followed BNP, the 180-kDa mutant htt was absent, and 43-50 kDa htt fragments appeared. Brain lysates from two HD mouse models expressed native full-length htt; a mutant fragment formed if lysates were pretreated with 8 M urea + DTT. Native full-length mutant htt in embryonic HD140Q/140Q mouse primary neurons was intact during cell death and when cell lysates were exposed to denaturants before BNP. Thus, native mutant htt occurs in brain and primary neurons as a soluble full-length monomer. C1 [Sapp, Ellen; Valencia, Antonio; Li, Xueyi; Kegel, Kimberly B.; DiFiglia, Marian] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Sapp, Ellen; Valencia, Antonio; Li, Xueyi; Kegel, Kimberly B.; DiFiglia, Marian] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Aronin, Neil] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Aronin, Neil] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA. [Vonsattel, Jean-Paul] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Vonsattel, Jean-Paul] New York Presbyterian Hosp, New York, NY 10032 USA. [Vonsattel, Jean-Paul] Columbia Univ Coll Phys & Surg, New York Brain Bank, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. [Young, Anne B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Wexler, Nancy] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Wexler, Nancy] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Wexler, Nancy] Hereditary Dis Fdn, New York, NY 10032 USA. RP DiFiglia, M (reprint author), Massachusetts Gen Hosp E, Dept Neurol, 114 16th St,Rm 2002, Charlestown, MA 02129 USA. EM difiglia@helix.mgh.harvard.edu FU National Institutes of Health (NINDS) [38194]; National Institutes of Health (NIA) [P01-AG07232, R37-AG15473, P50-AG08702]; Huntington Disease Society of America Coalition for the Cure; UMass DERC [DIC 32520]; Iseman Fund; Louis and Rachel Rudin Foundation; Hereditary Disease Foundation; W. M. Keck Foundation FX This work was supported, in whole or in part, by National Institutes of Health Grants 38194 (NINDS; to N. A. and M. D.) and P01-AG07232, R37-AG15473, and P50-AG08702 (NIA; to J. P. V.). This work was also supported by the Huntington Disease Society of America Coalition for the Cure (to M. D.), the UMass DERC (DIC 32520) (to N. A.), The Iseman Fund, The Louis and Rachel Rudin Foundation (to J. P. V.), Hereditary Disease Foundation (to J. P. V. and N. W.), and the W. M. Keck Foundation (to A. B. Y. and N. W.). NR 52 TC 9 Z9 10 U1 0 U2 5 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 APR 13 PY 2012 VL 287 IS 16 BP 13487 EP 13499 DI 10.1074/jbc.M111.286609 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 927JO UT WOS:000302903700082 PM 22375012 ER PT J AU Tron, AE Arai, T Duda, DM Kuwabara, H Olszewski, JL Fujiwara, Y Bahamon, BN Signoretti, S Schulman, BA DeCaprio, JA AF Tron, Adriana E. Arai, Takehiro Duda, David M. Kuwabara, Hiroshi Olszewski, Jennifer L. Fujiwara, Yuko Bahamon, Brittany N. Signoretti, Sabina Schulman, Brenda A. DeCaprio, James A. TI The Glomuvenous Malformation Protein Glomulin Binds Rbx1 and Regulates Cullin RING Ligase-Mediated Turnover of Fbw7 SO MOLECULAR CELL LA English DT Article ID F-BOX PROTEIN; SCFFBW7 UBIQUITIN LIGASE; CYCLIN-E; SUBSTRATE RECOGNITION; DEPENDENT DEGRADATION; COP9 SIGNALOSOME; HUMAN CANCER; C-MYC; NEDD8; PHOSPHORYLATION AB Fbw7, a substrate receptor for Cul1-RING-ligase (CRL1), facilitates the ubiquitination and degradation of several proteins, including Cyclin E and c-Myc. In spite of much effort, the mechanisms underlying Fbw7 regulation are mostly unknown. Here, we show that Glomulin (Glmn), a protein found mutated in the vascular disorder glomuvenous malformation (GVM), binds directly to the RING domain of Rbx1 and inhibits its E3 ubiquitin ligase activity. Loss of Glmn in a variety of cells, tissues, and GVM lesions results in decreased levels of Fbw7 and increased levels of Cyclin E and c-Myc. The increased turnover of Fbw7 is dependent on CRL and proteasome activity, indicating that Glmn modulates the E3 activity of CRL1(Fbw7). These data reveal an unexpected functional connection between Glmn and Rbx1 and demonstrate that defective regulation of Fbw7 levels contributes to GVM. C1 [Tron, Adriana E.; Arai, Takehiro; Kuwabara, Hiroshi; DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Tron, Adriana E.; Arai, Takehiro; Kuwabara, Hiroshi; DeCaprio, James A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Bahamon, Brittany N.; Signoretti, Sabina] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Duda, David M.; Olszewski, Jennifer L.; Schulman, Brenda A.] St Jude Childrens Hosp, Dept Biol Struct, Memphis, TN 38105 USA. [Duda, David M.; Schulman, Brenda A.] St Jude Childrens Hosp, Howard Hughes Med Inst, Memphis, TN 38105 USA. [Fujiwara, Yuko] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Fujiwara, Yuko] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM james_decaprio@dfci.harvard.edu FU Pew Charitable Trust; International Human Frontier Science Program Organization; ALSAC; Public Health Service [5P30CA021765, RO1GM069530, RO1GM077053, RO1CA93804, RO1CA63113, PO1CA050661] FX We are grateful to Hideaki Tanami for help with generation of ES cells and Wenyi Wei for discussions and critical reading of the manuscript. We thank Roderick Bronson (DF/HCC Rodent Histopathology Core); Xiaoqiu Wu and Rosina Liz (DFCI Center for Molecular Oncologic Pathology) for histological analysis; Harry Kozakewich and John Mulliken (Vascular Anomalies Center, Children's Hospital/Harvard Medical School) for providing GVM specimens; and Yue Xiong (University of North Carolina School of Medicine) for providing plasmids. This work was supported in part by fellowships from the Pew Charitable Trust and the International Human Frontier Science Program Organization to A.E.T.; ALSAC and Public Health Service grants 5P30CA021765, RO1GM069530, and RO1GM077053 to B.A.S.; and RO1CA93804, RO1CA63113, and PO1CA050661 to J.A.D. B.A.S. is an Investigator of the Howard Hughes Medical Institute. NR 44 TC 18 Z9 18 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD APR 13 PY 2012 VL 46 IS 1 BP 67 EP 78 DI 10.1016/j.molcel.2012.02.005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 926NL UT WOS:000302838000009 PM 22405651 ER PT J AU Moslehi, J Libby, P AF Moslehi, Javid Libby, Peter TI You Can't Run From Inflammation Lower Extremity Ischemia, Hypoxia Signaling, and Macrophage Subtypes SO CIRCULATION RESEARCH LA English DT Editorial Material ID HYDROXYLASE; INHIBITION; DEFICIENCY C1 [Moslehi, Javid; Libby, Peter] Harvard Univ, Sch Med, Dept Med, Div Cardiovasc Med,Brigham & Womens Hosp, Boston, MA 02115 USA. [Moslehi, Javid] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. RP Libby, P (reprint author), Harvard Univ, Sch Med, Dept Med, Div Cardiovasc Med,Brigham & Womens Hosp, 77 Ave Louis Pasteur,NRB741, Boston, MA 02115 USA. EM plibby@rics.bwh.harvard.edu NR 13 TC 4 Z9 4 U1 0 U2 2 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 APR 13 PY 2012 VL 110 IS 8 BP 1045 EP 1046 DI 10.1161/RES.0b013e318255409e PG 2 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 925VM UT WOS:000302790000005 PM 22499897 ER PT J AU Kluk, MJ Chapuy, B Sinha, P Roy, A Dal Cin, P Neuberg, DS Monti, S Pinkus, GS Shipp, MA Rodig, SJ AF Kluk, Michael J. Chapuy, Bjoern Sinha, Papiya Roy, Alyssa Dal Cin, Paola Neuberg, Donna S. Monti, Stefano Pinkus, Geraldine S. Shipp, Margaret A. Rodig, Scott J. TI Immunohistochemical Detection of MYC-driven Diffuse Large B-Cell Lymphomas SO PLOS ONE LA English DT Article ID SET ENRICHMENT ANALYSIS; BURKITTS-LYMPHOMA; RITUXIMAB; GENE; TRANSLOCATION; PROGNOSIS; THERAPY; CHOP AB Diffuse large B cell lymphoma (DLBCL) is a clinically and genetically heterogeneous disease. A small subset of DLBCLs has translocations involving the MYC locus and an additional group has a molecular signature resembling Burkitt lymphoma (mBL). Presently, identification of such cases by morphology is unreliable and relies on cytogenetic or complex molecular methods such as gene transcriptional profiling. Herein, we describe an immunohistochemical (IHC) method for identifying DLBCLs with increased MYC protein expression. We tested 77 cases of DLBCL and identified 15 cases with high MYC protein expression (nuclear staining in >50% of tumor cells). All MYC translocation positive cases had increased MYC protein expression by this IHC assay. In addition, gene set enrichment analysis (GSEA) of the DLBCL transcriptional profiles revealed that tumors with increased MYC protein expression (regardless of underlying MYC translocation status) had coordinate upregulation of MYC target genes, providing molecular confirmation of the IHC results. We then generated a molecular classifier derived from the MYC IHC results in our cases and employed it to successfully classify mBLs from two previously reported independent case series, providing additional confirmation that the MYC IHC results identify clinically important subsets of DLBCLs. Lastly, we found that DLBCLs with high MYC protein expression had inferior overall survival when treated with R-CHOP. In conclusion, the IHC method described herein can be used to readily identify the biologically and clinically distinct cases of MYC-driven DLBCL, which represent a clinically significant subset of DLBCL cases due to their inferior overall survival. C1 [Kluk, Michael J.; Sinha, Papiya; Roy, Alyssa; Dal Cin, Paola; Pinkus, Geraldine S.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chapuy, Bjoern; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Monti, Stefano] Boston Univ, Div Computat Biomed, Boston, MA 02215 USA. RP Kluk, MJ (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM srodig@partners.org OI Monti, Stefano/0000-0002-9376-0660 FU NIH [PO1CA092625]; Lymphoma Target Testing Center of the Dana-Farber Cancer Institute; Stanley L. Robbins Memorial Research Fund Award FX This work was supported in part by NIH PO1CA092625, the Lymphoma Target Testing Center of the Dana-Farber Cancer Institute and the Stanley L. Robbins Memorial Research Fund Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 20 TC 69 Z9 72 U1 2 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 12 PY 2012 VL 7 IS 4 AR e33813 DI 10.1371/journal.pone.0033813 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TZ UT WOS:000305338600012 PM 22511926 ER PT J AU Kohane, IS McMurry, A Weber, G MacFadden, D Rappaport, L Kunkel, L Bickel, J Wattanasin, N Spence, S Murphy, S Churchill, S AF Kohane, Isaac S. McMurry, Andrew Weber, Griffin MacFadden, Douglas Rappaport, Leonard Kunkel, Louis Bickel, Jonathan Wattanasin, Nich Spence, Sarah Murphy, Shawn Churchill, Susanne TI The Co-Morbidity Burden of Children and Young Adults with Autism Spectrum Disorders SO PLOS ONE LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; ELECTRONIC MEDICAL-RECORDS; DISINTEGRATIVE PSYCHOSIS; INFANTILE-AUTISM; NEUROPSYCHIATRIC DISORDERS; RHEUMATOID-ARTHRITIS; DISCOVERY RESEARCH; DIABETES-MELLITUS; RISK; COMMUNITY AB Objectives: Use electronic health records Autism Spectrum Disorder (ASD) to assess the comorbidity burden of ASD in children and young adults. Study Design: A retrospective prevalence study was performed using a distributed query system across three general hospitals and one pediatric hospital. Over 14,000 individuals under age 35 with ASD were characterized by their comorbidities and conversely, the prevalence of ASD within these comorbidities was measured. The comorbidity prevalence of the younger (Age, 18 years) and older (Age 18-34 years) individuals with ASD was compared. Results: 19.44% of ASD patients had epilepsy as compared to 2.19% in the overall hospital population (95% confidence interval for difference in percentages 13.58-14.69%), 2.43% of ASD with schizophrenia vs. 0.24% in the hospital population (95% CI 1.89-2.39%), inflammatory bowel disease (IBD) 0.83% vs. 0.54% (95% CI 0.13-0.43%), bowel disorders (without IBD) 11.74% vs. 4.5% (95% CI 5.72-6.68%), CNS/cranial anomalies 12.45% vs. 1.19% (95% CI 9.41-10.38%), diabetes mellitus type I (DM1) 0.79% vs. 0.34% (95% CI 0.3-0.6%), muscular dystrophy 0.47% vs 0.05% (95% CI 0.26-0.49%), sleep disorders 1.12% vs. 0.14% (95% CI 0.79-1.14%). Autoimmune disorders (excluding DM1 and IBD) were not significantly different at 0.67% vs. 0.68% (95% CI 20.14-0.13%). Three of the studied comorbidities increased significantly when comparing ages 0-17 vs 1834 with p<0.001: Schizophrenia (1.43% vs. 8.76%), diabetes mellitus type I (0.67% vs. 2.08%), IBD (0.68% vs. 1.99%) whereas sleeping disorders, bowel disorders (without IBD) and epilepsy did not change significantly. Conclusions: The comorbidities of ASD encompass disease states that are significantly overrepresented in ASD with respect to even the patient populations of tertiary health centers. This burden of comorbidities goes well beyond those routinely managed in developmental medicine centers and requires broad multidisciplinary management that payors and providers will have to plan for. C1 [Kohane, Isaac S.; McMurry, Andrew; MacFadden, Douglas] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02114 USA. [Kohane, Isaac S.; McMurry, Andrew; Bickel, Jonathan] Childrens Hosp, Childrens Hosp Informat Program, Boston, MA 02115 USA. [Kohane, Isaac S.; Weber, Griffin; Murphy, Shawn; Churchill, Susanne] Brigham & Womens Hosp, Natl Ctr Biomed Comp I2b2, Boston, MA 02115 USA. [Weber, Griffin] Harvard Med Sch Informat Technol, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Rappaport, Leonard] Childrens Hosp, Ctr Dev Med, Boston, MA 02115 USA. [Kunkel, Louis] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Bickel, Jonathan] Childrens Hosp, Dept Informat Syst, Boston, MA 02115 USA. [Wattanasin, Nich; Murphy, Shawn] Partners Healthcare Syst Informat Technol, Boston, MA USA. [Spence, Sarah] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Murphy, Shawn] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kohane, IS (reprint author), Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02114 USA. EM Isaac_kohane@harvard.edu RI Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 FU CTSA award (National Institutes of Health/National Center for Research Resources) [NIH/NCRR 1UL1RR025758-01]; i2b2 National Center for Biomedical Computing [NIH/NLM U54 LM008748]; Conte Center for Computational System Genomics of Neuropsychiatric Phenotypes [NIH P50MH94267] FX This work was funded in part by the CTSA award (National Institutes of Health/National Center for Research Resources NIH/NCRR 1UL1RR025758-01) and the i2b2 National Center for Biomedical Computing (NIH/NLM U54 LM008748) and the Conte Center for Computational System Genomics of Neuropsychiatric Phenotypes (NIH P50MH94267). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 120 Z9 122 U1 5 U2 42 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 12 PY 2012 VL 7 IS 4 AR e33224 DI 10.1371/journal.pone.0033224 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TZ UT WOS:000305338600004 PM 22511918 ER PT J AU Mutua, G Sanders, E Mugo, P Anzala, O Haberer, JE Bangsberg, D Barin, B Rooney, JF Mark, D Chetty, P Fast, P Priddy, FH AF Mutua, Gaudensia Sanders, Eduard Mugo, Peter Anzala, Omu Haberer, Jessica E. Bangsberg, David Barin, Burc Rooney, James F. Mark, David Chetty, Paramesh Fast, Patricia Priddy, Frances H. TI Safety and Adherence to Intermittent Pre-Exposure Prophylaxis (PrEP) for HIV-1 in African Men Who Have Sex with Men and Female Sex Workers SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY VIRUS-INFECTION; ANTIRETROVIRAL THERAPY ADHERENCE; SUB-SAHARAN AFRICA; POSTEXPOSURE PROPHYLAXIS; IMMUNE-RESPONSES; RHESUS MACAQUES; RISK BEHAVIOR; SELF-REPORT; SUPPRESSION; PREVENTION AB Background: Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM) and female sex workers (FSW). Methods/Principal Findings: MSM and FSW were randomized to daily oral FTC/TDF or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral FTC/TDF or placebo in a 2: 1: 2: 1 ratio; volunteers were followed monthly for 4 months. Adherence was assessed with the medication event monitoring system (MEMS). Sexual activity data were collected via daily text message (SMS) queries and timeline followback interviews with a one-month recall period. Sixty-seven men and 5 women were randomized into the study. Safety was similar among all groups. Median MEMS adherence rates were 83% [IQR: 63-92] for daily dosing and 55% [IQR: 28-78] for fixed intermittent dosing (p = 0.003), while adherence to any post-coital doses was 26% [IQR: 14-50]. SMS response rates were low, which may have impaired measurement of post-coital dosing adherence. Acceptability of PrEP was high, regardless of dosing regimen. Conclusions/Significance: Adherence to intermittent dosing regimens, fixed doses, and in particular coitally-dependent doses, may be more difficult than adherence to daily dosing. However, intermittent dosing may still be appropriate for PrEP if intracellular drug levels, which correlate with prevention of HIV acquisition, can be attained with less than daily dosing and if barriers to adherence can be addressed. Additional drug level data, qualitative data on adherence barriers, and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more standard regimens. C1 [Mutua, Gaudensia; Anzala, Omu] Univ Nairobi, Kenya AIDS Vaccine Initiat, Nairobi, Kenya. [Sanders, Eduard; Mugo, Peter] Kenya Govt Med Res Ctr, Kilifi, Kenya. [Sanders, Eduard] Univ Oxford, Nuffield Dept Med, Headington, England. [Haberer, Jessica E.; Bangsberg, David] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Barin, Burc] EMMES Corp, Rockville, MD USA. [Rooney, James F.] Gilead Sci Inc, Foster City, CA 94404 USA. [Mark, David; Fast, Patricia; Priddy, Frances H.] Int AIDS Vaccine Initiat, New York, NY USA. [Chetty, Paramesh] Int AIDS Vaccine Initiat, Johannesburg, South Africa. RP Mutua, G (reprint author), Univ Nairobi, Kenya AIDS Vaccine Initiat, Nairobi, Kenya. EM fpriddy@iavi.org FU International AIDS Vaccine Initiative (IAVI); Gilead Sciences FX The study was funded and sponsored by the International AIDS Vaccine Initiative (IAVI). Support in the form of study medication was provided by Gilead Sciences. As the sponsor, IAVI reviewed and approved the study design, data collection and analysis, decision to publish and the manuscript. As Gilead Sciences employ James F. Rooney, they have participated in study design and preparation of the manuscript but played no role in data collection and analysis or decision to publish.; Burc Barin is employed by a commercial statistical group, The EMMES Corporation. James F. Rooney is employed by a commercial funder of this study, Gilead Sciences, which supplied the active drug and placebo tablets used in this study. Gilead Sciences developed and markets the drug, Truvada, used in this trial for HIV treatment. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. NR 41 TC 55 Z9 58 U1 2 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 12 PY 2012 VL 7 IS 4 AR e33103 DI 10.1371/journal.pone.0033103 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TZ UT WOS:000305338600002 PM 22511916 ER PT J AU Ho, HJ Lin, TI Chang, HH Haase, SB Huang, S Pyne, S AF Ho, Hsiu J. Lin, Tsung I. Chang, Hannah H. Haase, Steven B. Huang, Sui Pyne, Saumyadipta TI Parametric modeling of cellular state transitions as measured with flow cytometry SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 1st IEEE International Conference on Computational Advances in Bio and Medical Sciences (ICCABS) CY FEB 03-05, 2011 CL Orlando, FL SP IEEE ID MAXIMUM-LIKELIHOOD; EM ALGORITHM; MIXTURE; DISTRIBUTIONS; FRAMEWORK; ECM AB Background: Gradual or sudden transitions among different states as exhibited by cell populations in a biological sample under particular conditions or stimuli can be detected and profiled by flow cytometric time course data. Often such temporal profiles contain features due to transient states that present unique modeling challenges. These could range from asymmetric non-Gaussian distributions to outliers and tail subpopulations, which need to be modeled with precision and rigor. Results: To ensure precision and rigor, we propose a parametric modeling framework StateProfiler based on finite mixtures of skew t-Normal distributions that are robust against non-Gaussian features caused by asymmetry and outliers in data. Further, we present in StateProfiler a new greedy EM algorithm for fast and optimal model selection. The parsimonious approach of our greedy algorithm allows us to detect the genuine dynamic variation in the key features as and when they appear in time course data. We also present a procedure to construct a well-fitted profile by merging any redundant model components in a way that minimizes change in entropy of the resulting model. This allows precise profiling of unusually shaped distributions and less well-separated features that may appear due to cellular heterogeneity even within clonal populations. Conclusions: By modeling flow cytometric data measured over time course and marker space with StateProfiler, specific parametric characteristics of cellular states can be identified. The parameters are then tested statistically for learning global and local patterns of spatio-temporal change. We applied StateProfiler to identify the temporal features of yeast cell cycle progression based on knockout of S-phase triggering cyclins Clb5 and Clb6, and then compared the S-phase delay phenotypes due to differential regulation of the two cyclins. We also used StateProfiler to construct the temporal profile of clonal divergence underlying lineage selection in mammalian hematopoietic progenitor cells. C1 [Ho, Hsiu J.; Lin, Tsung I.] Natl Chung Hsing Univ, Dept Appl Math, Taichung 402, Taiwan. [Ho, Hsiu J.; Lin, Tsung I.] Natl Chung Hsing Univ, Inst Stat, Taichung 402, Taiwan. [Lin, Tsung I.] China Med Univ, Dept Publ Hlth, Taichung 404, Taiwan. [Chang, Hannah H.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pathol & Surg, Boston, MA 02115 USA. [Chang, Hannah H.] Harvard Univ, Program Biophys, Cambridge, MA 02139 USA. [Chang, Hannah H.] Harvard Univ, Sch Med, MD PhD Program, Boston, MA 02115 USA. [Haase, Steven B.] Duke Univ, Dept Biol, Durham, NC USA. [Huang, Sui] Univ Calgary, Inst Biocomplex & Informat, Calgary, AB T2N 1N4, Canada. [Pyne, Saumyadipta] Broad Inst MIT & Harvard Univ, Cambridge, MA 02142 USA. [Pyne, Saumyadipta] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Pyne, S (reprint author), Broad Inst MIT & Harvard Univ, Cambridge, MA 02142 USA. EM spyne@broad.mit.edu NR 28 TC 4 Z9 4 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD APR 12 PY 2012 VL 13 SU 5 AR S5 DI 10.1186/1471-2105-13-S5-S5 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 941BU UT WOS:000303938200005 PM 22537009 ER PT J AU McMillin, DW Delmore, J Negri, JM Vanneman, M Koyama, S Schlossman, RL Munshi, NC Laubach, J Richardson, PG Dranoff, G Anderson, KC Mitsiades, CS AF McMillin, Douglas W. Delmore, Jake Negri, Joseph M. Vanneman, Matthew Koyama, Shohei Schlossman, Robert L. Munshi, Nikhil C. Laubach, Jacob Richardson, Paul G. Dranoff, Glenn Anderson, Kenneth C. Mitsiades, Constantine S. TI Compartment-specific bioluminescence imaging platform for the high-throughput evaluation of antitumor immune function SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MULTIPLE-MYELOMA; IMMUNOMODULATORY DRUGS; THERAPY; CANCER; CELLS; LENALIDOMIDE; CYTOTOXICITY; THALIDOMIDE; EXPRESSION AB Conventional assays evaluating antitumor activity of immune effector cells have limitations that preclude their high-throughput application. We adapted the recently developed Compartment-Specific Bioluminescence Imaging (CS-BLI) technique to perform high-throughput quantification of innate antitumor activity and to show how pharmacologic agents (eg, lenalidomide, pomalidomide, bortezomib, and dexamethasone) and autologous BM stromal cells modulate that activity. CS-BLI-based screening allowed us to identify agents that enhance or inhibit innate antitumor cytotoxicity. Specifically, we identified compounds that stimulate immune effector cells against some tumor targets but suppressed their activity against other tumor cells. CS-BLI offers rapid, simplified, and specific evaluation of multiple conditions, including drug treatments and/or cocultures with stromal cells and highlights that immunomodulatory pharmacologic responses can be heterogeneous across different types of tumor cells. This study provides a framework to identify novel immunomodulatory agents and to prioritize compounds for clinical development on the basis of their effect on antitumor immunity. (Blood. 2012;119(15):e131-e138) C1 [Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [McMillin, Douglas W.; Delmore, Jake; Negri, Joseph M.; Schlossman, Robert L.; Munshi, Nikhil C.; Laubach, Jacob; Richardson, Paul G.; Anderson, Kenneth C.; Mitsiades, Constantine S.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [McMillin, Douglas W.; Delmore, Jake; Negri, Joseph M.; Vanneman, Matthew; Koyama, Shohei; Schlossman, Robert L.; Laubach, Jacob; Richardson, Paul G.; Dranoff, Glenn; Anderson, Kenneth C.; Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Munshi, Nikhil C.] Vet Affairs Boston Healthcare Syst, W Roxbury, MA USA. RP Mitsiades, CS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,HIM Bldg,Rm 346, Boston, MA 02215 USA. EM constantine_mitsiades@dfci.harvard.edu OI Koyama, Shohei/0000-0002-6897-9417 FU Chambers Medical Foundation; Steven Cobb Foundation; R. J. Corman Fund for Myeloma Research; Stepanian Fund for Myeloma Research; Department of Veterans Affairs [I01-BX001584]; National Institutes of Health [RO1-50947, RO1-124929, PO1-155258, PO-1-78378]; Dana-Farber Cancer Institute; Millennium; Celgene; Amgen Pharmaceuticals; AVEO Pharma; EMD Serono; Sunesis; Gloucester Pharmaceuticals; Johnson Johnson FX This work was supported in part by the Chambers Medical Foundation (C. S. M. and P. G. R.), the Steven Cobb Foundation (D. W. M. and C. S. M.), the R. J. Corman Fund for Myeloma Research (P. G. R. and C. S. M.), the Stepanian Fund for Myeloma Research (P. G. R. and C. S. M.), the Department of Veterans Affairs (Merit Review Award I01-BX001584 to N.C.M.), and from the National Institutes of Health (grant RO1-50947 to C. S. M. and K. C. A.; grants RO1-124929 and PO1-155258 to NCM; and grant PO-1-78378 to G. D. and K. C. A.). C. S. M. is supported by the "Dunkin Donuts Rising Stars" Program at the Dana-Farber Cancer Institute. Compounds libraries for screening were provided by the National Cancer Institute Developmental Therapeutics Program (http://dtp.cancer.gov/).; D. W. M. is an equity holder in Axios Biosciences. P. G. R. received honoraria from Millennium and Celgene. K. C. A. has received research grants and honoraria from Millennium and Celgene. P. G. R. has participated in advisory boards for Celgene, Millennium, and Johnson and Johnson. C. S. M. has received in the past consultant honoraria from Millennium Pharmaceuticals, Novartis Pharmaceuticals, Bristol-Myers Squibb, Merck & Co, Kosan Pharmaceuticals, Pharmion, and Celgene; licensing royalties from PharmaMar; and research funding from Amgen Pharmaceuticals, AVEO Pharma, EMD Serono, Sunesis, Gloucester Pharmaceuticals, and Johnson & Johnson. The remaining authors declare no competing financial interests. NR 23 TC 11 Z9 11 U1 0 U2 1 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 APR 12 PY 2012 VL 119 IS 15 BP E131 EP E138 DI 10.1182/blood-2011-04-348490 PG 8 WC Hematology SC Hematology GA 927OK UT WOS:000302917200001 PM 22289890 ER PT J AU Roe, AW Chelazzi, L Connor, CE Conway, BR Fujita, I Gallant, JL Lu, HD Vanduffel, W AF Roe, Anna W. Chelazzi, Leonardo Connor, Charles E. Conway, Bevil R. Fujita, Ichiro Gallant, Jack L. Lu, Haidong Vanduffel, Wim TI Toward a Unified Theory of Visual Area V4 SO NEURON LA English DT Review ID INFERIOR TEMPORAL CORTEX; FEATURE-BASED ATTENTION; FRONTAL EYE FIELD; STEREOSCOPIC DEPTH-PERCEPTION; FINE DISPARITY DISCRIMINATION; OVERLAPPING NEURAL SYSTEMS; VENTRAL OCCIPITAL CORTEX; COVERT SPATIAL ATTENTION; COLOR-SELECTIVE NEURONS; PRIMATE STRIATE CORTEX AB Visual area V4 is a midtier cortical area in the ventral visual pathway. It is crucial for visual object recognition and has been a focus of many studies on visual attention. However, there is no unifying view of V4's role in visual processing. Neither is there an understanding of how its role in feature processing interfaces with its role in visual attention. This review captures our current knowledge of V4, largely derived from electrophysiological and imaging studies in the macaque monkey. Based on recent discovery of functionally specific domains in V4, we propose that the unifying function of V4 circuitry is to enable selective extraction of specific functional domain-based networks, whether it be by bottom-up specification of object features or by top-down attentionally driven selection. C1 [Roe, Anna W.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. [Chelazzi, Leonardo] Univ Verona, Dept Neurol Neuropsychol Morphol & Motor Sci, I-37134 Verona, Italy. [Connor, Charles E.] Johns Hopkins Univ, Krieger Mind Brain Inst, Baltimore, MD 21218 USA. [Conway, Bevil R.] Wellesley Coll, Neurosci Program, Wellesley, MA 02481 USA. [Fujita, Ichiro] Osaka Univ, Grad Sch Frontier Biosci, Toyonaka, Osaka 5608531, Japan. [Fujita, Ichiro] Osaka Univ, Ctr Informat & Neural Networks, Toyonaka, Osaka 5608531, Japan. [Gallant, Jack L.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [Lu, Haidong] Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China. [Vanduffel, Wim] Harvard Univ, AA Martinos Ctr Biomed Imaging, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. [Vanduffel, Wim] KUK U Leuven Med Sch, Lab Neuro & Psychophysiol, B-3000 Louvain, Belgium. RP Roe, AW (reprint author), Vanderbilt Univ, Dept Psychol, 301 Wilson Hall, Nashville, TN 37240 USA. EM anna.roe@vanderbilt.edu RI Chelazzi, Leonardo/B-6084-2011 OI Chelazzi, Leonardo/0000-0001-8566-0611 FU NEI NIH HHS [R01 EY023322, R01 EY016711] NR 248 TC 61 Z9 61 U1 9 U2 63 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 12 PY 2012 VL 74 IS 1 BP 12 EP 29 DI 10.1016/j.neuron.2012.03.011 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 927FZ UT WOS:000302893800005 PM 22500626 ER PT J AU Poduri, A Evrony, GD Cai, X Elhosary, PC Beroukhinn, R Lehtinen, MK Hills, LB Heinzen, EL Hill, A Hil, RS Barry, BJ Bourgeois, BFD Riviello, JJ Barkovich, AJ Black, PM Ligon, KL Walsh, CA AF Poduri, Annapurna Evrony, Gilad D. Cai, Xuyu Elhosary, Princess Christina Beroukhinn, Rameen Lehtinen, Maria K. Hills, L. Benjamin Heinzen, Erin L. Hill, Anthony Hil, R. Sean Barry, Brenda J. Bourgeois, Blaise F. D. Riviello, James J. Barkovich, A. James Black, Peter M. Ligon, Keith L. Walsh, Christopher A. TI Somatic Activation of AKT3 Causes Hemispheric Developmental Brain Malformations SO NEURON LA English DT Article ID PROTEUS SYNDROME; CORPUS-CALLOSUM; MUTATION; GENE; PHENOTYPES; 1Q; CONSEQUENCES; MOSAICISM; EPILEPSY; DELETION AB Hemimegalencephaly (HMG) is a developmental brain disorder characterized by an enlarged, malformed cerebral hemisphere, typically causing epilepsy that requires surgical resection. We studied resected HMG tissue to test whether the condition might reflect somatic mutations affecting genes critical to brain development. We found that two out of eight HMG samples showed trisomy of chromosome 1q, which encompasses many genes, including AKT3, a gene known to regulate brain size. A third case showed a known activating mutation in AKT3 (c.49G -> A, creating p.E17K) that was not present in the patient's blood cells. Remarkably, the E17K mutation in AKT3 is exactly paralogous to E17K mutations in AKT1 and AKT2 recently discovered in somatic overgrowth syndromes. We show that AKT3 is the most abundant AKT paralog in the brain during neurogenesis and that phosphorylated AKT is abundant in cortical progenitor cells. Our data suggest that somatic mutations limited to the brain could represent an important cause of complex neurogenetic disease. C1 [Evrony, Gilad D.; Cai, Xuyu; Lehtinen, Maria K.; Hills, L. Benjamin; Hill, Anthony; Hil, R. Sean; Barry, Brenda J.; Walsh, Christopher A.] Childrens Hosp Boston, Div Genet, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Evrony, Gilad D.; Cai, Xuyu; Lehtinen, Maria K.; Hills, L. Benjamin; Hill, Anthony; Hil, R. Sean; Barry, Brenda J.; Walsh, Christopher A.] Childrens Hosp Boston, Howard Hughes Med Inst, Boston, MA 02115 USA. [Poduri, Annapurna; Elhosary, Princess Christina; Bourgeois, Blaise F. D.; Riviello, James J.] Childrens Hosp Boston, Dept Neurol, Boston, MA 02115 USA. [Lehtinen, Maria K.; Ligon, Keith L.] Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA. [Poduri, Annapurna; Bourgeois, Blaise F. D.; Riviello, James J.; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Evrony, Gilad D.; Cai, Xuyu] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. [Beroukhinn, Rameen] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Lehtinen, Maria K.; Ligon, Keith L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Beroukhinn, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Beroukhinn, Rameen] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Beroukhinn, Rameen; Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Beroukhinn, Rameen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Black, Peter M.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Beroukhinn, Rameen; Hil, R. Sean; Walsh, Christopher A.] 7 Cambridge Ctr, Broad Inst, Cambridge, MA 02142 USA. [Heinzen, Erin L.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27708 USA. [Barkovich, A. James] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Black, Peter M.] World Federat Neurosurg Soc, CH-1260 Nyon, Vaud, Switzerland. RP Walsh, CA (reprint author), Childrens Hosp Boston, Div Genet, Manton Ctr Orphan Dis Res, 300 Longwood Ave, Boston, MA 02115 USA. EM christopher.walsh@childrens.harvard.edu FU American Academy of Neurology; Milken Family Foundation; American Epilepsy Society; NINDS [K23NS069784, K99/R00, R00 NS072192, K08 NS047213, R01 NS35129, RO1 NS032457]; Shore Fellowship; NCI [P01 CA142536]; Sontag Foundation FX The authors thank the patients and families who have participated in this research. We thank Rona Carroll in the Brigham and Women's Hospital Department of Neurosurgery Tissue Bank, Abha Aggarwal in the Cytogenetics Laboratory at Brigham and Women's Hospital, Laura MacConaill and Levi Garraway at the Dana Farber Cancer Institute Oncomap Project, and Elizabeth Bundock, formerly of the CHB Department of Pathology. A.P. was supported by the American Academy of Neurology Clinical Research Training Fellowship, the Milken Family Foundation, the American Epilepsy Society, and the NINDS (K23NS069784). M.K.L. is supported by a Shore Fellowship and a K99/R00 from the NINDS (R00 NS072192). K.L.L. is supported by grants from NCI (P01 CA142536), NINDS (K08 NS047213), and the Sontag Foundation. C.A.W. is an Investigator at the Howard Hughes Medical Institute and is supported by grants from the NINDS (R01 NS35129 and RO1 NS032457). NR 36 TC 150 Z9 153 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 12 PY 2012 VL 74 IS 1 BP 41 EP 48 DI 10.1016/j.neuron.2012.03.010 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 927FZ UT WOS:000302893800007 PM 22500628 ER PT J AU Duan, ZF Li, X Huang, HX Yuan, W Zheng, SL Liu, XZ Zhang, Z Choy, E Harmon, D Mankin, H Hornicek, F AF Duan, Zhenfeng Li, Xin Huang, Haoxi Yuan, Wei Zheng, Shao-Liang Liu, Xianzhe Zhang, Zhan Choy, Edwin Harmon, David Mankin, Henry Hornicek, Francis TI Synthesis and Evaluation of (2-(4-Methoxyphenyl)-4-quinolinyl) (2-piperidinyl)methanol (NSC23925) Isomers To Reverse Multidrug Resistance in Cancer SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ABC TRANSPORTERS; IN-VITRO; INHIBITOR; EFFICACY; ASSAY; VIVO AB Development of multidrug resistance (MDR) during chemotherapy is a fundamental obstacle associated with cancer care. Prior studies have identified (2-(4-methoxyphenyl)-4-quinolinyl) (2-piperidinyl)methanol (5) (NSC23925) to be a small molecule agent that reverses MDR in cancer cells. We synthesized all four isomers of 5 and analyzed them by liquid chromatography-mass spectrometry (LCMS). Structure-activity relationships for reversing MDR were evaluated. Isomer 11 demonstrated the most potent activity. 11 reversed MDR in several drug-resistant cell lines expressing Pgp, including ovarian, breast, colon, uterine, and sarcoma cancer. 11 resensitized these cell lines to paclitaxel, doxorubicin, mitoxantrone, vincristine, and trabectedin with no effect on cell sensitivity to cisplatin, topotecan, and methotrexate. 11 significantly enhanced in vivo antitumor activity of paclitaxel in MDR xenograft models, without increasing the level of paclitaxel toxicity. In conclusion, 11 and derivatives of this compound may hold therapeutic value in the treatment of MDR-dependent cancers. C1 [Duan, Zhenfeng; Liu, Xianzhe; Zhang, Zhan; Choy, Edwin; Harmon, David; Mankin, Henry; Hornicek, Francis] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Li, Xin; Huang, Haoxi; Yuan, Wei] Chengdu ChemPartner Co Ltd, Chengdu 610041, Peoples R China. [Zheng, Shao-Liang] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Zhang, Zhan] Zhengzhou Univ, Affiliated Hosp 3, Zhengzhou, Peoples R China. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. EM duanz@helix.mgh.harvard.edu OI Choy, Edwin/0000-0001-9896-8084 FU Gattegno fund; Wechsler fund; Kenneth Stanton Fund; Sarcoma Foundation of America (SFA); National Cancer Institute (NCI)/National Institutes of Health (NIH) [UO1, CA 151452] FX This work was supported in part by grants from the Gattegno and Wechsler funds. Support has also been provided by the Kenneth Stanton Fund. Dr. Duan is supported, in part, through a grant from Sarcoma Foundation of America (SFA), a grant from National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1, CA 151452. NR 21 TC 17 Z9 17 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 12 PY 2012 VL 55 IS 7 BP 3113 EP 3121 DI 10.1021/jm300117u PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 923AT UT WOS:000302591100021 PM 22400811 ER PT J AU Schrappe, M Hunger, SP Pui, CH Saha, V Gaynon, PS Baruchel, A Conter, V Otten, J Ohara, A Versluys, AB Escherich, G Heyman, M Silverman, LB Horibe, K Mann, G Camitta, BM Harbott, J Riehm, H Richards, S Devidas, M Zimmermann, M AF Schrappe, Martin Hunger, Stephen P. Pui, Ching-Hon Saha, Vaskar Gaynon, Paul S. Baruchel, Andre Conter, Valentino Otten, Jacques Ohara, Akira Versluys, Anne Birgitta Escherich, Gabriele Heyman, Mats Silverman, Lewis B. Horibe, Keizo Mann, Georg Camitta, Bruce M. Harbott, Jochen Riehm, Hansjoerg Richards, Sue Devidas, Meenakshi Zimmermann, Martin TI Outcomes after Induction Failure in Childhood Acute Lymphoblastic Leukemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MINIMAL RESIDUAL DISEASE; STEM-CELL TRANSPLANTATION; PROGNOSTIC VALUE; COMPLETE REMISSION; SALVAGE THERAPY; AIEOP-BFM; T-CELL; CHILDREN; RISK; CHEMOTHERAPY AB BACKGROUND Failure of remission-induction therapy is a rare but highly adverse event in children and adolescents with acute lymphoblastic leukemia (ALL). METHODS We identified induction failure, defined by the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after 4 to 6 weeks of remission-induction therapy, in 1041 of 44,017 patients (2.4%) 0 to 18 years of age with newly diagnosed ALL who were treated by a total of 14 cooperative study groups between 1985 and 2000. We analyzed the relationships among disease characteristics, treatments administered, and outcomes in these patients. RESULTS Patients with induction failure frequently presented with high-risk features, including older age, high leukocyte count, leukemia with a T-cell phenotype, the Philadelphia chromosome, and 11q23 rearrangement. With a median follow-up period of 8.3 years (range, 1.5 to 22.1), the 10-year survival rate (+/- SE) was estimated at only 32 +/- 1%. An age of 10 years or older, T-cell leukemia, the presence of an 11q23 rearrangement, and 25% or more blasts in the bone marrow at the end of induction therapy were associated with a particularly poor outcome. High hyperdiploidy (a modal chromosome number >50) and an age of 1 to 5 years were associated with a favorable outcome in patients with precursor B-cell leukemia. Allogeneic stem-cell transplantation from matched, related donors was associated with improved outcomes in T-cell leukemia. Children younger than 6 years of age with precursor B-cell leukemia and no adverse genetic features had a 10-year survival rate of 72 +/- 5% when treated with chemotherapy only. CONCLUSIONS Pediatric ALL with induction failure is highly heterogeneous. Patients who have T-cell leukemia appear to have a better outcome with allogeneic stem-cell transplantation than with chemotherapy, whereas patients who have precursor B-cell leukemia without other adverse features appear to have a better outcome with chemotherapy. (Funded by Deutsche Krebshilfe and others.) C1 [Pui, Ching-Hon] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Pui, Ching-Hon] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Schrappe, Martin] Univ Kiel, Dept Pediat, Univ Med Ctr Schleswig Holstein, D-2300 Kiel, Germany. [Escherich, Gabriele] Univ Med Ctr Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany. [Harbott, Jochen] Univ Giessen, Dept Pediat Hematol & Oncol, Oncogenet Lab, Giessen, Germany. [Riehm, Hansjoerg; Zimmermann, Martin] Hannover Med Sch, Dept Pediat Hematol & Oncol, D-3000 Hannover, Germany. [Hunger, Stephen P.] Univ Colorado, Sch Med, Aurora, CO USA. [Hunger, Stephen P.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Hunger, Stephen P.] Childrens Hosp Colorado, Aurora, CO USA. [Saha, Vaskar] Univ Manchester, Manchester Acad Hlth Sci Ctr, Sch Canc, Childrens Canc Grp, Manchester, Lancs, England. [Richards, Sue] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Gaynon, Paul S.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Baruchel, Andre] Hop Robert Debre, Dept Pediat Hematoimmunol, F-75019 Paris, France. [Baruchel, Andre] Univ Paris Diderot, Paris, France. [Conter, Valentino] Univ Milano Bicocca, Pediat Clin, Osped San Gerardo, Monza, Italy. [Conter, Valentino] Osped Riuniti Bergamo, Dept Pediat, I-24100 Bergamo, Italy. [Otten, Jacques] Univ Ziekenhuis Brussel, Dept Pediat, Hematooncol Unit, Brussels, Belgium. [Ohara, Akira] Toho Univ, Dept Pediat 1, Tokyo, Japan. [Versluys, Anne Birgitta] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Versluys, Anne Birgitta] Dutch Childhood Oncol Grp, The Hague, Netherlands. [Heyman, Mats] Karolinska Inst, Astrid Lindgren Childrens Hosp, Childhood Canc Res Unit, Stockholm, Sweden. [Silverman, Lewis B.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Silverman, Lewis B.] Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. [Silverman, Lewis B.] Childrens Hosp Boston, Boston, MA USA. [Horibe, Keizo] Clin Res Ctr, Nagoya Med Ctr, Nagoya, Aichi, Japan. [Mann, Georg] Univ Med Sch, St Anna Childrens Hosp, Dept Pediat, Vienna, Austria. [Camitta, Bruce M.] Med Coll Wisconsin, Midwest Ctr Canc & Blood Disorders, Milwaukee, WI 53226 USA. [Camitta, Bruce M.] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. [Camitta, Bruce M.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Devidas, Meenakshi] Stat & Data Ctr, Childrens Oncol Grp, Gainesville, FL USA. [Devidas, Meenakshi] Univ Florida, Dept Biostat, Gainesville, FL USA. RP Pui, CH (reprint author), St Jude Childrens Hosp, Dept Oncol, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM ching-hon.pui@stjude.org FU Deutsche Krebshilfe; St. Anna Children's Cancer Research Institute, Austria; Deutsche Krebshilfe, Germany; Madeleine-Schickedanz-Kinderkrebsstiftung, Germany; Fordergemeinschaft Kinderkrebszentrum Hamburg, Germany; National Cancer Institute (NCI) [5PO1CA068484]; Assistance Publique-Hopitaux de Paris, INSERM, Institut Universitaire d'Hematologie and Centre de Recherche en Hematologie, Oncologie, et Pediatrie, France; American Lebanese Syrian Associated Charities; Medical Research Council, United Kingdom; Swedish Childhood Cancer Foundation; Danish Childhood Cancer Foundation; Norwegian Cancer Society; Fonds Cancer, Belgium; Ministry of Health, Labour, and Welfare, Japan; Children's Cancer Association of Japan; [CA13539]; [CA98543]; [CA98413]; [CA30969]; [CA29139]; [CA21765] FX Funded by Deutsche Krebshilfe and others.; Supported by St. Anna Children's Cancer Research Institute, Austria; Deutsche Krebshilfe, Germany; Madeleine-Schickedanz-Kinderkrebsstiftung, Germany; grants (CA13539, CA98543, and CA98413) to the Children's Cancer Group; Fordergemeinschaft Kinderkrebszentrum Hamburg, Germany; a grant (NCI 5PO1CA068484) from the National Cancer Institute to the Dana-Farber Cancer Institute; Assistance Publique-Hopitaux de Paris, INSERM, Institut Universitaire d'Hematologie and Centre de Recherche en Hematologie, Oncologie, et Pediatrie, France; grants (CA30969, CA29139, CA98543, and CA98413) to the Pediatric Oncology Group; a grant (CA21765) and funding from American Lebanese Syrian Associated Charities to St. Jude Children's Research Hospital; the Medical Research Council, United Kingdom; the Swedish Childhood Cancer Foundation; the Danish Childhood Cancer Foundation; the Norwegian Cancer Society; Fonds Cancer, Belgium; a Clinical Cancer Research grant from the Ministry of Health, Labour, and Welfare, Japan; and the Children's Cancer Association of Japan. NR 58 TC 78 Z9 84 U1 1 U2 9 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 APR 12 PY 2012 VL 366 IS 15 BP 1371 EP 1381 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 923GV UT WOS:000302608600001 PM 22494120 ER PT J AU Ledermann, J Harter, P Gourley, C Friedlander, M Vergote, I Rustin, G Scott, C Meier, W Shapira-Frommer, R Safra, T Matei, D Macpherson, E Watkins, C Carmichael, J Matulonis, U AF Ledermann, Jonathan Harter, Philipp Gourley, Charlie Friedlander, Michael Vergote, Ignace Rustin, Gordon Scott, Clare Meier, Werner Shapira-Frommer, Ronnie Safra, Tamar Matei, Daniela Macpherson, Euan Watkins, Claire Carmichael, James Matulonis, Ursula TI Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID POLY(ADP-RIBOSE) POLYMERASE; DNA-REPAIR; BRCA1; CHEMOTHERAPY; INHIBITION; TUMORS; TRIAL; DEFICIENT; AZD2281; CELLS AB BACKGROUND Olaparib (AZD2281) is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor that has shown antitumor activity in patients with high-grade serous ovarian cancer with or without BRCA1 or BRCA2 germline mutations. METHODS We conducted a randomized, double-blind, placebo-controlled, phase 2 study to evaluate maintenance treatment with olaparib in patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer who had received two or more platinum-based regimens and had had a partial or complete response to their most recent platinum-based regimen. Patients were randomly assigned to receive olaparib, at a dose of 400 mg twice daily, or placebo. The primary end point was progression-free survival according to the Response Evaluation Criteria in Solid Tumors guidelines. RESULTS Of 265 patients who underwent randomization, 136 were assigned to the olaparib group and 129 to the placebo group. Progression-free survival was significantly longer with olaparib than with placebo (median, 8.4 months vs. 4.8 months from randomization on completion of chemotherapy; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.25 to 0.49; P<0.001). Subgroup analyses of progression-free survival showed that, regardless of subgroup, patients in the olaparib group had a lower risk of progression. Adverse events more commonly reported in the olaparib group than in the placebo group (by more than 10% of patients) were nausea (68% vs. 35%), fatigue (49% vs. 38%), vomiting (32% vs. 14%), and anemia (17% vs. 5%); the majority of adverse events were grade 1 or 2. An interim analysis of overall survival (38% maturity, meaning that 38% of the patients had died) showed no significant difference between groups (hazard ratio with olaparib, 0.94; 95% CI, 0.63 to 1.39; P=0.75). CONCLUSIONS Olaparib as maintenance treatment significantly improved progression-free survival among patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer. Interim analysis showed no overall survival benefit. The toxicity profile of olaparib in this population was consistent with that in previous studies. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT00753545.) C1 [Ledermann, Jonathan] UCL, Inst Canc, UCL & UCL Hosp Comprehens Biomed Res Ctr, London W1T 4TJ, England. [Harter, Philipp] Kliniken Essen Mitte, Essen, Germany. [Meier, Werner] Evangel Krankenhaus, Dusseldorf, Germany. [Gourley, Charlie] Univ Edinburgh, Canc Res UK Ctr, Edinburgh, Midlothian, Scotland. [Friedlander, Michael] Prince Wales Hosp, Randwick, NSW 2031, Australia. [Scott, Clare] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Vergote, Ignace] Katholieke Univ Leuven, Louvain, Belgium. [Rustin, Gordon] Mt Vernon Hosp, Northwood HA6 2RN, Middx, England. [Macpherson, Euan; Watkins, Claire; Carmichael, James] AstraZeneca, Macclesfield, Cheshire, England. [Shapira-Frommer, Ronnie] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Safra, Tamar] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. [Matei, Daniela] Indiana Univ Sch Med, Indianapolis, IN USA. [Matulonis, Ursula] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ledermann, J (reprint author), UCL, Inst Canc, UCL & UCL Hosp Comprehens Biomed Res Ctr, 90 Tottenham Court Rd, London W1T 4TJ, England. EM j.ledermann@ctc.ucl.ac.uk RI friedlander, michael/G-3490-2013 OI friedlander, michael/0000-0002-6488-0604 FU AstraZeneca FX Supported by AstraZeneca. NR 34 TC 389 Z9 401 U1 5 U2 35 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 12 PY 2012 VL 366 IS 15 BP 1382 EP 1392 DI 10.1056/NEJMoa1105535 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 923GV UT WOS:000302608600002 PM 22452356 ER PT J AU Morrow, DA Braunwald, E Bonaca, MP Ameriso, SF Dalby, AJ Fish, MP Fox, KAA Lipka, LJ Liu, X Nicolau, JC Ophuis, AJO Paolasso, E Scirica, BM Spinar, J Theroux, P Wiviott, SD Strony, J Murphy, SA AF Morrow, David A. Braunwald, Eugene Bonaca, Marc P. Ameriso, Sebastian F. Dalby, Anthony J. Fish, Mary Polly Fox, Keith A. A. Lipka, Leslie J. Liu, Xuan Nicolau, Jose Carlos Ophuis, A. J. Oude Paolasso, Ernesto Scirica, Benjamin M. Spinar, Jindrich Theroux, Pierre Wiviott, Stephen D. Strony, John Murphy, Sabina A. CA TRA 2P-TIMI 50 Steering Comm Inves TI Vorapaxar in the Secondary Prevention of Atherothrombotic Events SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE CORONARY SYNDROMES; PROTEASE-ACTIVATED RECEPTORS; ANTITHROMBOTIC AGENTS; DOUBLE-BLIND; CLOPIDOGREL; SAFETY; TRIAL; ASPIRIN; STROKE; TOLERABILITY AB BACKGROUND Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.) C1 [Morrow, David A.; Braunwald, Eugene; Bonaca, Marc P.; Fish, Mary Polly; Scirica, Benjamin M.; Wiviott, Stephen D.; Murphy, Sabina A.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA. [Ameriso, Sebastian F.] FLENI, Neurol Res Inst, Buenos Aires, DF, Argentina. [Dalby, Anthony J.] Milpark Hosp, Johannesburg, South Africa. [Fox, Keith A. A.] Univ Edinburgh, Div Cardiovasc Res, Edinburgh, Midlothian, Scotland. [Lipka, Leslie J.; Liu, Xuan; Strony, John] Merck Res Labs, Rahway, NJ USA. [Nicolau, Jose Carlos] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil. [Ophuis, A. J. Oude] Canisius Wilhelmina Hosp, Nijmegen, Netherlands. [Paolasso, Ernesto] Inst Invest Clin Rosario, Rosario, Santa Fe, Argentina. [Spinar, Jindrich] Masaryk Univ, Univ Hosp Brno, Brno, Czech Republic. [Theroux, Pierre] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Theroux, Pierre] Univ Montreal, Montreal, PQ, Canada. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org RI ESPOSITO, Giovanni/F-2880-2010; Ponikowski, Piotr/O-6454-2015; WORNER, FERNANDO/A-6821-2010; Nicolau, Jose/E-1487-2012; Aroney, Constantine/A-7672-2013; Tanne, David/F-2560-2010; Hankey, Graeme /H-4968-2014; Chaves, Marcia/K-8353-2014; Kubica, Jacek/D-6906-2014; Faria Neto, Jose/G-7559-2012; Urina, Miguel/H-2605-2016; De Caterina, Raffaele/K-3857-2016; OI Vanhooren, Geert/0000-0001-6818-9346; Isasti, Guillermo/0000-0001-7262-8620; Fiszer, Urszula/0000-0002-9286-2454; Van de Werf, Frans/0000-0001-9479-7767; Welsh, Robert/0000-0003-2613-9142; Ayo-Martin, Oscar/0000-0002-3632-1696; ESPOSITO, Giovanni/0000-0003-0565-7127; Garcia-Moll, Xavier/0000-0001-7837-8378; Wuttig, Helge/0000-0003-1877-8905; Iversen, Helle Klingenberg/0000-0002-5880-6352; Danzi, Gian Battista/0000-0003-0897-8006; Ponikowski, Piotr/0000-0002-3391-7064; samson, yves/0000-0002-8080-1427; Aroney, Constantine/0000-0002-0908-7179; Tanne, David/0000-0002-6699-2220; Hankey, Graeme /0000-0002-6044-7328; Faria Neto, Jose/0000-0002-1397-0634; Urina, Miguel/0000-0001-6003-4622; De Caterina, Raffaele/0000-0003-1637-574X; Michel, GALINIER/0000-0003-1735-3390; Macleod, Malcolm Robert/0000-0001-9187-9839 FU Merck FX Supported by Merck. NR 18 TC 338 Z9 350 U1 7 U2 92 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 APR 12 PY 2012 VL 366 IS 15 BP 1404 EP 1413 DI 10.1056/NEJMoa1200933 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 923GV UT WOS:000302608600004 PM 22443427 ER PT J AU Channick, RN Lorenzo, ME Wu, CC Hoang, MP AF Channick, Richard N. Lorenzo, Mayra E. Wu, Carol C. Hoang, Mai P. TI Case 11-2012: A 60-Year-Old Man with Weakness, Rash, and Renal Failure Rocky Mountain spotted fever SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RICKETTSIA-RICKETTSII; RHABDOMYOLYSIS; IMMUNOPEROXIDASE; EHRLICHIOSIS; INFECTION; FEATURES; VIRUS C1 [Channick, Richard N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lorenzo, Mayra E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Wu, Carol C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Channick, Richard N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lorenzo, Mayra E.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Wu, Carol C.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Hoang, Mai P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Channick, RN (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 29 TC 0 Z9 0 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 12 PY 2012 VL 366 IS 15 BP 1434 EP 1443 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 923GV UT WOS:000302608600009 PM 22494124 ER PT J AU Kroshinsky, D AF Kroshinsky, Daniela TI Case 1-2012: A Man with Persistent Ulcers on the Hands REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kroshinsky, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 APR 12 PY 2012 VL 366 IS 15 BP 1450 EP 1450 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 923GV UT WOS:000302608600022 ER PT J AU Diekstra, FP Saris, CGJ van Rheenen, W Franke, L Jansen, RC van Es, MA van Vught, PWJ Blauw, HM Groen, EJN Horvath, S Estrada, K Rivadeneira, F Hofman, A Uitterlinden, AG Robberecht, W Andersen, PM Melki, J Meininger, V Hardiman, O Landers, JE Brown, RH Shatunov, A Shaw, CE Leigh, PN Al-Chalabi, A Ophoff, RA van den Berg, LH Veldink, JH AF Diekstra, Frank P. Saris, Christiaan G. J. van Rheenen, Wouter Franke, Lude Jansen, Ritsert C. van Es, Michael A. van Vught, Paul W. J. Blauw, Hylke M. Groen, Ewout J. N. Horvath, Steve Estrada, Karol Rivadeneira, Fernando Hofman, Albert Uitterlinden, Andre G. Robberecht, Wim Andersen, Peter M. Melki, Judith Meininger, Vincent Hardiman, Orla Landers, John E. Brown, Robert H., Jr. Shatunov, Aleksey Shaw, Christopher E. Leigh, P. Nigel Al-Chalabi, Ammar Ophoff, Roel A. van den Berg, Leonard H. Veldink, Jan H. TI Mapping of Gene Expression Reveals CYP27A1 as a Susceptibility Gene for Sporadic ALS SO PLOS ONE LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; GENOME-WIDE ASSOCIATION; CEREBROTENDINOUS XANTHOMATOSIS; HEXANUCLEOTIDE REPEAT; CROHNS-DISEASE; VARIANTS; RISK; TOOL; MUTATIONS; DIAGNOSIS AB Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS is considered to be a complex trait and genome-wide association studies (GWAS) have implicated a few susceptibility loci. However, many more causal loci remain to be discovered. Since it has been shown that genetic variants associated with complex traits are more likely to be eQTLs than frequency-matched variants from GWAS platforms, we conducted a two-stage genome-wide screening for eQTLs associated with ALS. In addition, we applied an eQTL analysis to finemap association loci. Expression profiles using peripheral blood of 323 sporadic ALS patients and 413 controls were mapped to genome-wide genotyping data. Subsequently, data from a two-stage GWAS (3,568 patients and 10,163 controls) were used to prioritize eQTLs identified in the first stage (162 ALS, 207 controls). These prioritized eQTLs were carried forward to the second sample with both gene-expression and genotyping data (161 ALS, 206 controls). Replicated eQTL SNPs were then tested for association in the second-stage GWAS data to find SNPs associated with disease, that survived correction for multiple testing. We thus identified twelve cis eQTLs with nominally significant associations in the second-stage GWAS data. Eight SNP-transcript pairs of highest significance (lowest p = 1.27 x 10(-51)) withstood multiple-testing correction in the second stage and modulated CYP27A1 gene expression. Additionally, we show that C9orf72 appears to be the only gene in the 9p21.2 locus that is regulated in cis, showing the potential of this approach in identifying causative genes in association loci in ALS. This study has identified candidate genes for sporadic ALS, most notably CYP27A1. Mutations in CYP27A1 are causal to cerebrotendinous xanthomatosis which can present as a clinical mimic of ALS with progressive upper motor neuron loss, making it a plausible susceptibility gene for ALS. C1 [Diekstra, Frank P.; Saris, Christiaan G. J.; van Rheenen, Wouter; van Es, Michael A.; van Vught, Paul W. J.; Blauw, Hylke M.; Groen, Ewout J. N.; van den Berg, Leonard H.; Veldink, Jan H.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands. [Franke, Lude; Jansen, Ritsert C.] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands. [Jansen, Ritsert C.] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Groningen Bioinformat Ctr, Haren, Netherlands. [Horvath, Steve] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Horvath, Steve] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biostat, Los Angeles, CA 90095 USA. [Estrada, Karol; Rivadeneira, Fernando; Hofman, Albert; Uitterlinden, Andre G.] Erasmus Univ, Dept Epidemiol & Biostat, Med Ctr Rotterdam, NL-3000 DR Rotterdam, Netherlands. [Robberecht, Wim] Katholieke Univ Leuven, Univ Hosp Leuven, Dept Neurol, Louvain, Belgium. [Robberecht, Wim] Katholieke Univ Leuven VIB, Neurobiol Lab, Vesalius Res Ctr, Louvain, Belgium. [Andersen, Peter M.] Umea Univ, Dept Clin Neurosci, Umea, Sweden. [Melki, Judith] Univ Paris, Bicetre Hosp, Dept Neuropediat, F-75252 Paris, France. [Meininger, Vincent] Univ Paris 06, Hop La Pitie Salpetriere, Dept Neurol, Paris, France. [Hardiman, Orla] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. [Hardiman, Orla] Trinity Coll Dublin, Dept Neurol, Dublin, Ireland. [Landers, John E.; Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. [Landers, John E.; Brown, Robert H., Jr.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Shatunov, Aleksey; Shaw, Christopher E.; Leigh, P. Nigel; Al-Chalabi, Ammar] Kings Coll London, MRC, Dept Clin Neurosci, Ctr Neurodegenerat Res,Inst Psychiat, London WC2R 2LS, England. [Ophoff, Roel A.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Med Genet, Utrecht, Netherlands. [Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA. RP Diekstra, FP (reprint author), Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands. EM j.h.veldink@umcutrecht.nl RI Al-Chalabi, Ammar/E-5361-2010; Jansen, Ritsert/C-1160-2013; Rivadeneira, Fernando/O-5385-2015; Groen, Ewout/L-5081-2016; Franke, Lude/P-7036-2016 OI Hardiman, Orla/0000-0003-2610-1291; Al-Chalabi, Ammar/0000-0002-4924-7712; Jansen, Ritsert/0000-0003-2977-9110; Rivadeneira, Fernando/0000-0001-9435-9441; Groen, Ewout/0000-0002-2330-9444; Franke, Lude/0000-0002-5159-8802 FU Prinses Beatrix Fonds (Kersten Foundation); VSB fonds; The Netherlands ALS Foundation; J.R. van Dijk; Adessium Foundation; Brain Foundation of The Netherlands; Thierry Latran Foundation; Netherlands Organization of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [050-060-810]; European Community [259867]; National Institutes of Health [IU19A1063603-01, 5P30CA016042-28, P50CA092131, DK072206]; Erasmus Medical Center; Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; The Muscular Dystrophy Association (USA); The Health Research Board of Ireland; The Irish Neurological Association Travel Award; The Irish Motor Neuron Disease Research Foundation; Swedish Brain Research Foundation; Hallstens Research Foundation; Swedish Medical Society; Bjorklund Foundation for ALS Research; Swedish Association; University of Leuven (Methusalem); Belgian Federal Science Policy Office [P6/43]; Association pour la Recherche sur la SLA; Association Reseau SLA Ile de France; ALS Therapy Alliance; Project ALS; Angel Fund; Pierre L. de Bourgknecht ALS Research Foundation; Al-Athel ALS Research Foundation; ALS Family Charitable Foundation; National Institute of Neurological Disorders and Stroke [NS050557] FX This work was supported by the Prinses Beatrix Fonds (Kersten Foundation); VSB fonds; The Netherlands ALS Foundation and J.R. van Dijk; and the Adessium Foundation to [LHB]. JHV is supported by the Brain Foundation of The Netherlands; and the Thierry Latran Foundation. The GWA study was funded by the Netherlands Organization of Scientific Research NWO Investments [grant numbers 175.010.2005.011, 911-03-012]; the Research Institute for Diseases in the Elderly (014-93-015; RIDE); and the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [project number 050-060-810]. In addition, the research leading to these results has received funding from the European Community's Health Seventh Framework Programme (FP7/2007-2013) [grant agreement number 259867]. SH is supported by National Institutes of Health [grant numbers IU19A1063603-01, 5P30CA016042-28, P50CA092131, and DK072206]. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); 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 Irish study was funded by The Muscular Dystrophy Association (USA); The Health Research Board of Ireland; The Irish Neurological Association Travel Award; and The Irish Motor Neuron Disease Research Foundation. In Sweden, this project was supported by the Swedish Brain Research Foundation; the Hallstens Research Foundation; the Swedish Medical Society; the Bjorklund Foundation for ALS Research; and the Swedish Association for the Neurologically Disabled to [PMA]. WR was supported by grants from the University of Leuven (Methusalem); and the Interuniversity Attraction Poles program P6/43 of the Belgian Federal Science Policy Office. In France, this study was funded by the Association pour la Recherche sur la SLA; and the Association Reseau SLA Ile de France. Support was also provided by the ALS Therapy Alliance; Project ALS; the Angel Fund; the Pierre L. de Bourgknecht ALS Research Foundation; the Al-Athel ALS Research Foundation; the ALS Family Charitable Foundation and the National Institute of Neurological Disorders and Stroke [NS050557].'' The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 24 Z9 24 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 11 PY 2012 VL 7 IS 4 AR e35333 DI 10.1371/journal.pone.0035333 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TP UT WOS:000305336600101 PM 22509407 ER PT J AU Vinegoni, C Feruglio, PF Razansky, D Gorbatov, R Ntziachristos, V Sbarbati, A Nahrendorf, M Weissleder, R AF Vinegoni, Claudio Feruglio, Paolo Fumene Razansky, Daniel Gorbatov, Rostic Ntziachristos, Vasilis Sbarbati, Andrea Nahrendorf, Matthias Weissleder, Ralph TI Mapping Molecular Agents Distributions in Whole Mice Hearts Using Born-Normalized Optical Projection Tomography SO PLOS ONE LA English DT Article ID FLUORESCENCE TOMOGRAPHY; MYOCARDIAL-INFARCTION; FIBER ORIENTATION; IN-VIVO; MICROSCOPY; EFFICIENCY; STRAIN; DEEP AB To date there is a lack of tools to map the spatio-temporal dynamics of diverse cells in experimental heart models. Conventional histology is labor intensive with limited coverage, whereas many imaging techniques do not have sufficiently high enough spatial resolution to map cell distributions. We have designed and built a high resolution, dual channel Born-normalized near-infrared fluorescence optical projection tomography system to quantitatively and spatially resolve molecular agents distribution within whole murine heart. We validated the use of the system in a mouse model of monocytes/macrophages recruitment during myocardial infarction. While acquired, data were processed and reconstructed in real time. Tomographic analysis and visualization of the key inflammatory components were obtained via a mathematical formalism based on left ventricular modeling. We observed extensive monocyte recruitment within and around the infarcted areas and discovered that monocytes were also extensively recruited into non-ischemic myocardium, beyond that of injured tissue, such as the septum. C1 [Vinegoni, Claudio; Feruglio, Paolo Fumene; Gorbatov, Rostic; Nahrendorf, Matthias; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Vinegoni, Claudio; Feruglio, Paolo Fumene; Gorbatov, Rostic; Nahrendorf, Matthias; Weissleder, Ralph] Harvard Univ, Sch Med, Richard B Simches Res Ctr, Boston, MA USA. [Vinegoni, Claudio] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Vinegoni, Claudio] Harvard Univ, Sch Med, Charlestown, MA USA. [Feruglio, Paolo Fumene; Sbarbati, Andrea] Univ Verona, Dept Neurol Neuropsychol Morphol & Movement Sci, I-37100 Verona, Italy. [Razansky, Daniel; Ntziachristos, Vasilis] Tech Univ Munich, Inst Biol & Med Imaging, Neuherberg, Germany. [Razansky, Daniel; Ntziachristos, Vasilis] Helmholtz Ctr Munich, Neuherberg, Germany. RP Vinegoni, C (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM cvinegoni@mgh.harvard.edu OI Razansky, Daniel/0000-0001-8676-0964 FU NIH [RO1EB006432] FX This work was supported by NIH grant no. RO1EB006432. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 3 Z9 3 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 11 PY 2012 VL 7 IS 4 AR e34427 DI 10.1371/journal.pone.0034427 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TP UT WOS:000305336600032 PM 22509302 ER PT J AU Holsen, LM Lee, JH Spaeth, SB Ogden, LA Klibanski, A Whitfield-Gabrieli, S Sloan, RP Goldstein, JM AF Holsen, Laura M. Lee, Jong-Hwan Spaeth, Sarah B. Ogden, Lauren A. Klibanski, Anne Whitfield-Gabrieli, Susan Sloan, Richard P. Goldstein, Jill M. TI Brain hypoactivation, autonomic nervous system dysregulation, and gonadal hormones in depression: A preliminary study SO NEUROSCIENCE LETTERS LA English DT Article DE Mood disorders; Autonomic nervous system; Sympathovagal balance; HPG-axis; Estrogen; Progesterone ID HEART-RATE-VARIABILITY; MENSTRUAL-CYCLE PHASE; HEALTHY-SUBJECTS; WOMEN; DISORDER; ANXIETY; PHOTOPLETHYSMOGRAPHY; MODULATION; CIRCUITRY; RESPONSES AB The comorbidity of major depressive disorder (MDD) and cardiovascular disease (CVD) is among the 10th leading cause of morbidity and mortality worldwide. Thus, understanding the co-occurrence of these disorders will have major public health significance. MDD is associated with an abnormal stress response, manifested in brain circuitry deficits, gonadal dysfunction, and autonomic nervous system CANS) dysregulation. Contribution of the relationships between these systems to the pathophysiology of MDD is not well understood. The objective of this preliminary study was to investigate, in parallel, relationships between HPG-axis functioning, stress response circuitry activation, and parasympathetic reactivity in healthy controls and women with MOD. Using fMRI with pulse oximetry [from which we calculated the high frequency (HF) component of R-R interval variability (HF-RRV), a measure of parasympathetic modulation] and hormone data, we studied eight women with recurrent MDD in remission and six controls during a stress response paradigm. We demonstrated that hypoactivations of hypothalamus, amygdala, hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and subgenual ACC were associated with lower parasympathetic cardiac modulation in MDD women. Estradiol and progesterone attenuated group differences in the effect of HF-RRV on hypoactivation in the amygdala, hippocampus, ACC, and OFC in MDD women. Findings have implications for understanding the relationship between mood, arousal, heart regulation, and gonadal hormones, and may provide insights into MOD and CVD risk comorbidity. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Goldstein, Jill M.] Brigham & Womens Hosp, OBC, Dept Psychiat, Boston, MA 02120 USA. [Holsen, Laura M.; Spaeth, Sarah B.; Ogden, Lauren A.; Goldstein, Jill M.] Dept Med, Div Womens Hlth, Boston, MA 02120 USA. [Holsen, Laura M.; Klibanski, Anne; Goldstein, Jill M.] Harvard Univ, Sch Med, Boston, MA 02120 USA. [Lee, Jong-Hwan] Korea Univ, Dept Brain & Cognit Engn, Seoul 136701, South Korea. [Klibanski, Anne] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. [Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Whitfield-Gabrieli, Susan; Goldstein, Jill M.] MGH & MIT Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sloan, Richard P.] Columbia Univ, Dept Psychiat, Med Ctr, New York, NY 10032 USA. [Sloan, Richard P.] New York State Psychiat Inst & Hosp, Div Behav Med, New York, NY 10032 USA. RP Goldstein, JM (reprint author), Brigham & Womens Hosp, OBC, Dept Psychiat, 3rd Flr,1620 Tremont St, Boston, MA 02120 USA. EM jill_goldstein@hms.harvard.edu FU National Institute of Health [P50 MH082679]; NIH NCRR-GCRC at Brigham [M01 RR02635]; Women's Hospital's General Clinical Research Center; World Class University through the National Research Foundation (NRF) of Korea; Ministry of Education, Science and Technology [R31-10008]; NRF grant of Korea [2011-0004794] FX This work was supported by grants from the National Institute of Health to J.M.G.: ORWH-NIMH P50 MH082679 and pilot funds for fMRI scans from NIH NCRR-GCRC M01 RR02635 at Brigham and Women's Hospital's General Clinical Research Center. Additional funding for support of Dr. Lee's effort is from the World Class University program through the National Research Foundation (NRF) of Korea, funded by the Ministry of Education, Science and Technology (R31-10008) and Basic Science Research Program, NRF grant of Korea (2011-0004794). We thank Drs. Tamara Gersh, Seung-Schik Yoo, and Matthew Jerram for help in earlier phases of the study, Harlyn Aizley, M.Ed. for clinical interviewing, and Jo-Ann Donatelli, Ph.D. for her contributions to diagnostic review. We also appreciate the input of Stuart Tobet, Ph.D. and Robert Handa, Ph.D. (Co-Pls on ORWH-NIMH P50 MH082679) for their comments on earlier drafts. NR 37 TC 18 Z9 18 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 11 PY 2012 VL 514 IS 1 BP 57 EP 61 DI 10.1016/j.neulet.2012.02.056 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 929PE UT WOS:000303077100013 PM 22395084 ER PT J AU Stefani, LC Torres, ILD de Souza, ICC Rozisky, JR Fregni, F Caumo, W AF Stefani, Luciana Cadore da Silva Torres, Iraci Lucena Custodio de Souza, Izabel Cristina Rozisky, Joanna Ripoll Fregni, Felipe Caumo, Wolnei TI BDNF as an effect modifier for gender effects on pain thresholds in healthy subjects SO NEUROSCIENCE LETTERS LA English DT Article DE Pain threshold; BDNF; Neuroplasticity; Pain ID NOXIOUS INHIBITORY CONTROLS; NEUROTROPHIC FACTOR BDNF; TEMPORAL SUMMATION; SEX-DIFFERENCES; MENSTRUAL-CYCLE; BRAIN; RATS; PERCEPTION; DEPRESSION; ANXIETY AB BDNF is an important marker of neuronal plasticity. It has also been associated with pain processing. Increased BDNF levels are observed in chronic pain syndromes. In order to understand the role of BDNF associated with other factors such as gender on experimental pain we aimed to determine whether experimental heat or pressure pain threshold is correlated with brain derived neurotrophic factor (BDNF) level, gender and age. Heat pain threshold and pressure pain threshold were measured in 49 healthy volunteers (27 females). The multivariate linear regression models (on heat and pressure pain thresholds) revealed a significant effect of gender (p = 0.001 for both models), serum BDNF (p < 0.004 for both models) and interaction between BDNF and gender (<0.001 for both models). In fact, when adjusting for BDNF levels and age, heat and pressure pain thresholds were significantly reduced in women as compared to men (p < 0.001 for both models). These effects were not observed when gender was analyzed alone. These finding suggests that experimental heat and pressure pain threshold is gender-related and BDNF dependent. In fact BDNF has a facilitatory effect on pain threshold in females but has an opposite effect in males; supporting the notion that BDNF is an effect modifier of the gender effects on pain threshold in healthy subjects. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Stefani, Luciana Cadore; da Silva Torres, Iraci Lucena; Custodio de Souza, Izabel Cristina; Rozisky, Joanna Ripoll; Caumo, Wolnei] Hosp Clin Porto Alegre, Lab Pain & Neuromodulat, BR-90035003 Bairro Rio Branco Porto, RS, Brazil. [Stefani, Luciana Cadore; da Silva Torres, Iraci Lucena; Custodio de Souza, Izabel Cristina; Rozisky, Joanna Ripoll; Caumo, Wolnei] Univ Fed Rio Grande do Sul, Sch Med, BR-90046900 Porto Alegre, RS, Brazil. [da Silva Torres, Iraci Lucena; Caumo, Wolnei] Univ Fed Rio Grande do Sul, Dept Pharmacol, Inst Ciencias Basicas Saude, BR-90046900 Porto Alegre, RS, Brazil. [Fregni, Felipe] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fregni, Felipe] Harvard Univ, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol,Med Sch, Boston, MA 02215 USA. RP Caumo, W (reprint author), Hosp Clin Porto Alegre, Lab Pain & Neuromodulat, Rua Ramiro Barcelos 2350, BR-90035003 Bairro Rio Branco Porto, RS, Brazil. EM lustefani@terra.com.br; iracitorres@gmail.com; belcustodio20@yahoo.com.br; joannarozisky@gmail.com; Fregni.Felipe@mgh.harvard.edu; caumo@cpovo.net RI Torres, iraci/G-6693-2012; Rozisky, Joanna/F-6584-2015 OI Torres, iraci/0000-0002-3081-115X; FU Committee for the Development of Higher Education Personnel - CAPES - PNPD/CAPES; National Council for Scientific and Technological Development - CNPq; Foundation of Support of Research at Rio Grande do Sul (FAPERGS); NIH [5R21DK081773-03] FX This research was supported by grants from the following Brazilian agencies: Committee for the Development of Higher Education Personnel - CAPES - PNPD/CAPES (for W.C and I.C.C.S), National Council for Scientific and Technological Development - CNPq (Dr. I.L.S. Torres, Dr. W. Caumo), and Foundation of Support of Research at Rio Grande do Sul (FAPERGS). F.F. is supported by NIH grant (5R21DK081773-03). NR 52 TC 9 Z9 9 U1 1 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 11 PY 2012 VL 514 IS 1 BP 62 EP 66 DI 10.1016/j.neulet.2012.02.057 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 929PE UT WOS:000303077100014 PM 22395087 ER PT J AU Watanabe, H Xia, D Kanekiyo, T Kelleher, RJ Shen, J AF Watanabe, Hirotaka Xia, Dan Kanekiyo, Takahisa Kelleher, Raymond J., III Shen, Jie TI Familial Frontotemporal Dementia-Associated Presenilin-1 c.548G > T Mutation Causes Decreased mRNA Expression and Reduced Presenilin Function in Knock-In Mice SO JOURNAL OF NEUROSCIENCE LA English DT Article ID GAMMA-SECRETASE ACTIVITY; ALZHEIMERS-DISEASE; ACNE INVERSA; CAENORHABDITIS-ELEGANS; SYNAPTIC PLASTICITY; CLINICAL PHENOTYPE; MISSENSE MUTATIONS; GENE-MUTATIONS; STEM-CELLS; BETA-APP AB Mutations in the presenilin-1 (PSEN1) gene are associated with familial Alzheimer's disease and frontotemporal dementia (FTD). Interestingly, neuropathological analysis of a Belgian FTD family carrying a PSEN1 c.548G> T mutation confirmed neurodegeneration in the absence of amyloid plaques. To investigate the impact of the c.548G> T mutation on presenilin-1 (PS1) function in vivo, we introduced this mutation into the genomic Psen1 locus. The resulting c.548G> T knock-in (KI) mice are viable but express markedly lower levels of Psen1 mRNA and protein in the brain. This reduction is due to production of aberrantly spliced transcripts lacking either exon 6 or exons 6 and 7 and their subsequent degradation via non-sense-mediated decay (NMD); inhibition of NMD by cycloheximide treatment stabilized these transcripts and restored the level of Psen1 mRNA in KI/KI brains. Interestingly, the reduction of Psen1 mRNA expression and the degradation of aberrant Psen1 splice products occur exclusively in the brain but not in other tissues. Consistent with decreased Psen1 expression, gamma-secretase activity was strongly reduced in the cerebral cortex of KI mice, as measured by de novo gamma-secretase-mediated cleavage of APP and Notch. Moreover, PS1 expressed from Psen1 cDNA carrying the c.548G> T mutation displayed normal gamma-secretase activity in cultured cells, indicating that the corresponding p.183G> V amino acid substitution does not affect gamma-secretase activity. Finally, Psen1 c.548G> T-KI/KI; Psen2(-/-) mice exhibited mild spatial memory deficits in the Morris water maze task. Together, our findings demonstrate that the c.548G> T mutation results in a brain-specific loss of presenilin function due to decreased Psen1 mRNA expression. C1 [Shen, Jie] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Program Neurosci,Dept Neurol, Boston, MA 02115 USA. [Xia, Dan; Kelleher, Raymond J., III] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA. [Kanekiyo, Takahisa] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Kelleher, Raymond J., III; Shen, Jie] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Shen, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Program Neurosci,Dept Neurol, 77 Ave Louis Pasteur,New Res Bldg 636E, Boston, MA 02115 USA. EM jshen@rics.bwh.harvard.edu FU National Institutes of Health [R01NS041783, RC2AG036614]; Alzheimer's Association FX This work was supported by National Institutes of Health Grants R01NS041783 and RC2AG036614 (to J.S.) and grants from the Alzheimer's Association (to R.J.K., J.S.). We thank H. Zhao and X. Zou for breeding and genotyping the mice, and other laboratory members for helpful discussions. We also thank T. Iwatsubo and T. Tomita for pTrcHis2A-C100-FmH and pTrcHis2A-N102-FmH plasmids, B. DeStrooper for Psen double-knock-out mouse embryonic fibroblasts, P. Davies for phospho-specific tau antibodies (PHF1 and CP13), and A. Takashima for total tau antibody (J.M.). NR 60 TC 8 Z9 8 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 11 PY 2012 VL 32 IS 15 BP 5085 EP 5096 DI 10.1523/JNEUROSCI.0317-12.2012 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 925WT UT WOS:000302793500007 PM 22496554 ER PT J AU Wang, J Ferruzzi, MG Ho, L Blount, J Janle, EM Gong, B Pan, Y Gowda, GAN Raftery, D Arrieta-Cruz, I Sharma, V Cooper, B Lobo, J Simon, JE Zhang, CF Cheng, A Qian, XJ Ono, K Teplow, DB Pavlides, C Dixon, RA Pasinetti, GM AF Wang, Jun Ferruzzi, Mario G. Ho, Lap Blount, Jack Janle, Elsa M. Gong, Bing Pan, Yong Gowda, G. A. Nagana Raftery, Daniel Arrieta-Cruz, Isabel Sharma, Vaishali Cooper, Bruce Lobo, Jessica Simon, James E. Zhang, Chungfen Cheng, Alice Qian, Xianjuan Ono, Kenjiro Teplow, David B. Pavlides, Constantine Dixon, Richard A. Pasinetti, Giulio M. TI Brain-Targeted Proanthocyanidin Metabolites for Alzheimer's Disease Treatment SO JOURNAL OF NEUROSCIENCE LA English DT Article ID MOUSE MODEL; SYNAPTIC PLASTICITY; TRANSGENIC MICE; INGESTION; BEHAVIOR; MEMORY AB While polyphenolic compounds have many health benefits, the potential development of polyphenols for the prevention/treatment of neurological disorders is largely hindered by their complexity as well as by limited knowledge regarding their bioavailability, metabolism, and bioactivity, especially in the brain. We recently demonstrated that dietary supplementation with a specific grape-derived polyphenolic preparation (GP) significantly improves cognitive function in a mouse model of Alzheimer's disease (AD). GP is comprised of the proanthocyanidin (PAC) catechin and epicatechin in monomeric (Mo), oligomeric, and polymeric forms. In this study, we report that following oral administration of the independent GP forms, only Mo is able to improve cognitive function and only Mo metabolites can selectively reach and accumulate in the brain at a concentration of similar to 400 nM. Most importantly, we report for the first time that a biosynthetic epicatechin metabolite, 3'-O-methyl-epicatechin-5-O-beta-glucuronide (3'-O-Me-EC-Gluc), one of the PAC metabolites identified in the brain following Mo treatment, promotes basal synaptic transmission and long-term potentiation at physiologically relevant concentrations in hippocampus slices through mechanisms associated with cAMP response element binding protein (CREB) signaling. Our studies suggest that select brain-targeted PAC metabolites benefit cognition by improving synaptic plasticity in the brain, and provide impetus to develop 3'-O-Me-EC-Gluc and other brain-targeted PAC metabolites to promote learning and memory in AD and other forms of dementia. C1 [Wang, Jun; Ho, Lap; Gong, Bing; Pan, Yong; Arrieta-Cruz, Isabel; Cheng, Alice; Qian, Xianjuan; Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Ferruzzi, Mario G.; Janle, Elsa M.; Cooper, Bruce; Lobo, Jessica] Purdue Univ, Dept Food Sci, W Lafayette, IN 47907 USA. [Ferruzzi, Mario G.; Janle, Elsa M.; Cooper, Bruce; Lobo, Jessica] Purdue Univ, Dept Food & Nutr, W Lafayette, IN 47907 USA. [Gowda, G. A. Nagana; Raftery, Daniel] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Blount, Jack; Sharma, Vaishali; Zhang, Chungfen; Dixon, Richard A.] Samuel Roberts Noble Fdn Inc, Div Plant Biol, Ardmore, OK 73401 USA. [Pavlides, Constantine] Rockefeller Univ, New York, NY 10021 USA. [Simon, James E.] Rutgers State Univ, Dept Plant Biol & Plant Pathol, New Brunswick, NJ 08901 USA. [Ono, Kenjiro; Teplow, David B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Ono, Kenjiro; Teplow, David B.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. [Ono, Kenjiro; Teplow, David B.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. [Wang, Jun; Ho, Lap] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu FU NIH [PO1AT004511, AG027818]; Department of Veterans Affairs; Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers at University of California Los Angeles; Samuel Roberts Noble Foundation FX This work was supported by grants from the NIH (PO1AT004511) and Department of Veterans Affairs to G.M.P., the Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers at University of California Los Angeles to D.B.T., NIH Grant AG027818 to D.B.T., and the Samuel Roberts Noble Foundation (R.A.D.). NR 20 TC 63 Z9 65 U1 3 U2 28 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 11 PY 2012 VL 32 IS 15 BP 5144 EP 5150 DI 10.1523/JNEUROSCI.6437-11.2012 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 925WT UT WOS:000302793500013 PM 22496560 ER PT J AU Bonjean, M Baker, T Bazhenov, M Cash, S Halgren, E Sejnowski, T AF Bonjean, Maxime Baker, Tanya Bazhenov, Maxim Cash, Sydney Halgren, Eric Sejnowski, Terrence TI Interactions between Core and Matrix Thalamocortical Projections in Human Sleep Spindle Synchronization SO JOURNAL OF NEUROSCIENCE LA English DT Article ID THALAMIC RETICULAR NUCLEUS; CORTICOTHALAMIC FEEDBACK; RELAY NEURONS; OSCILLATIONS; MODEL; MECHANISMS; CORTEX; WAVES; NETWORKS; SLICES AB Sleep spindles are bursts of 11-15 Hz that occur during non-rapid eye movement sleep. Spindles are highly synchronous across the scalp in the electroencephalogram (EEG) but have low spatial coherence and exhibit low correlation with the EEG when simultaneously measured in the magnetoencephalogram (MEG). We developed a computational model to explore the hypothesis that the spatial coherence spindles in the EEG is a consequence of diffuse matrix projections of the thalamus to layer 1 compared with the focal projections of the core pathway to layer 4 recorded in the MEG. Increasing the fanout of thalamocortical connectivity in the matrix pathway while keeping the core pathway fixed led to increased synchrony of the spindle activity in the superficial cortical layers in the model. In agreement with cortical recordings, the latency for spindles to spread from the core to the matrix was independent of the thalamocortical fanout but highly dependent on the probability of connections between cortical areas. C1 [Bonjean, Maxime; Baker, Tanya; Bazhenov, Maxim; Sejnowski, Terrence] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA. [Halgren, Eric] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. [Halgren, Eric] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Halgren, Eric] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Bonjean, Maxime; Bazhenov, Maxim; Sejnowski, Terrence] Univ Calif San Diego, Div Biol Sci, San Diego, CA 92103 USA. [Bazhenov, Maxim] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. [Bonjean, Maxime; Cash, Sydney] Harvard Univ, Sch Med, Boston, MA USA. [Bonjean, Maxime; Cash, Sydney] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Sejnowski, T (reprint author), Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA. EM terry@salk.edu FU National Institutes of Health; NIH-National Institute of Biomedical Imaging and Bioengineering [1R01EB009282-01]; Crick-Jacobs Center for Theoretical Neurobiology; Swartz Foundation; Howard Hughes Medical Institute; Salk Institute for Biological Studies; Division of Biological Sciences, University of California, San Diego; NIH-NINDS [1R01NS060870-01] FX This work was supported by the National Institutes of Health; NIH-National Institute of Biomedical Imaging and Bioengineering Grant 1R01EB009282-01 (T.S., E.H., M.Ba., and M.Bo.); the Crick-Jacobs Center for Theoretical Neurobiology and the Swartz Foundation (T.B.); the Howard Hughes Medical Institute; The Salk Institute for Biological Studies (T.S. and M.Bo.); the Division of Biological Sciences, University of California, San Diego (T.S. and M.Bo.); and NIH-NINDS Grant 1R01NS060870-01 (M.Ba.). NR 47 TC 28 Z9 28 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 11 PY 2012 VL 32 IS 15 BP 5250 EP 5263 DI 10.1523/JNEUROSCI.6141-11.2012 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 925WT UT WOS:000302793500024 PM 22496571 ER PT J AU Wu, HY Hudry, E Hashimoto, T Uemura, K Fan, ZY Berezovska, O Grosskreutz, CL Bacskai, BJ Hyman, BT AF Wu, Hai-Yan Hudry, Eloise Hashimoto, Tadafumi Uemura, Kengo Fan, Zhan-Yun Berezovska, Oksana Grosskreutz, Cynthia L. Bacskai, Brian J. Hyman, Bradley T. TI Distinct Dendritic Spine and Nuclear Phases of Calcineurin Activation after Exposure to Amyloid-beta Revealed by a Novel Fluorescence Resonance Energy Transfer Assay SO JOURNAL OF NEUROSCIENCE LA English DT Article ID HIPPOCAMPAL SYNAPTIC PLASTICITY; DEPENDENT PROTEIN-KINASE; LONG-TERM DEPRESSION; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; CALMODULIN; PHOSPHATASE; ACTIN; DEPHOSPHORYLATION; EXPRESSION AB Calcineurin (CaN) activation is critically involved in the regulation of spine morphology in response to oligomeric amyloid-beta (A beta) as well as in synaptic plasticity in normal memory, but no existing techniques can monitor the spatiotemporal pattern of CaN activity. Here, we use a spectral fluorescence resonance energy transfer approach to monitor CaN activation dynamics in real time with subcellular resolution. When oligomeric A beta derived from Tg2576 murine transgenic neurons or human AD brains were applied to wild-type murine primary cortical neurons, we observe a dynamic progression of CaN activation within minutes, first in dendritic spines, and then in the cytoplasm and, in hours, in the nucleus. CaN activation in spines leads to rapid but reversible morphological changes in spines and in postsynaptic proteins; longer exposure leads to NFAT (nuclear factor of activated T-cells) translocation to the nucleus and frank spine loss. These results provide a framework for understanding the role of calcineurin in synaptic alterations associated with AD pathogenesis. C1 [Wu, Hai-Yan; Hudry, Eloise; Hashimoto, Tadafumi; Uemura, Kengo; Fan, Zhan-Yun; Berezovska, Oksana; Bacskai, Brian J.; Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. [Grosskreutz, Cynthia L.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Hyman, BT (reprint author), MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org RI Hashimoto, Tadafumi/A-7723-2013 FU National Institutes of Health [AG08487, EB000768, EY13399, 1R01AG041507-01] FX This work was supported by National Institutes of Health Grants AG08487, EB000768, EY13399, and 1R01AG041507-01. We thank Dr. Jeffery D. Molkentin (Cincinnati Children's Hospital, Cincinnati, OH) for providing CaN constructs. We thank Daniel Joyner for primary neuron preparation. NR 51 TC 28 Z9 29 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 11 PY 2012 VL 32 IS 15 BP 5298 EP 5309 DI 10.1523/JNEUROSCI.0227-12.2012 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 925WT UT WOS:000302793500028 PM 22496575 ER PT J AU Korvala, J Juppner, H Makitie, O Sochett, E Schnabel, D Mora, S Bartels, CF Warman, ML Deraska, D Cole, WG Hartikka, H Ala-Kokko, L Mannikko, M AF Korvala, Johanna Jueppner, Harald Makitie, Outi Sochett, Etienne Schnabel, Dirk Mora, Stefano Bartels, Cynthia F. Warman, Matthew L. Deraska, Donald Cole, William G. Hartikka, Heini Ala-Kokko, Leena Mannikko, Minna TI Mutations in LRP5 cause primary osteoporosis without features of OI by reducing Wnt signaling activity SO BMC MEDICAL GENETICS LA English DT Article ID IDIOPATHIC JUVENILE OSTEOPOROSIS; RECEPTOR-RELATED PROTEIN-5; BONE-MASS; PSEUDOGLIOMA SYNDROME; MISSENSE MUTATIONS; GENE-EXPRESSION; MULTIPLE-MYELOMA; DENSITY; INHIBITION; BINDING AB Background: Primary osteoporosis is a rare childhood-onset skeletal condition whose pathogenesis has been largely unknown. We have previously shown that primary osteoporosis can be caused by heterozygous missense mutations in the Low-density lipoprotein receptor-related protein 5 (LRP5) gene, and the role of LRP5 is further investigated here. Methods: LRP5 was analyzed in 18 otherwise healthy children and adolescents who had evidence of osteoporosis (manifested as reduced bone mineral density i.e. BMD, recurrent peripheral fractures and/or vertebral compression fractures) but who lacked the clinical features of osteogenesis imperfecta (OI) or other known syndromes linked to low BMD. Also 51 controls were analyzed. Methods used in the genetic analyses included direct sequencing and multiplex ligation-dependent probe amplification (MLPA). In vitro studies were performed using luciferase assay and quantitative real-time polymerase chain reaction (qPCR) to examine the effect of two novel and three previously identified mutations on the activity of canonical Wnt signaling and on expression of tryptophan hydroxylase 1 (Tph1) and 5-hydroxytryptamine (5-Htr1b). Results: Two novel LRP5 mutations (c. 3446 T > A; p.L1149Q and c. 3553 G > A; p.G1185R) were identified in two patients and their affected family members. In vitro analyses showed that one of these novel mutations together with two previously reported mutations (p.C913fs, p.R1036Q) significantly reduced the activity of the canonical Wnt signaling pathway. Such reductions may lead to decreased bone formation, and could explain the bone phenotype. Gut-derived Lrp5 has been shown to regulate serotonin synthesis by controlling the production of serotonin rate-limiting enzyme, Tph1. LRP5 mutations did not affect Tph1 expression, and only one mutant (p. L1149Q) reduced expression of serotonin receptor 5-Htr1b (p < 0.002). Conclusions: Our results provide additional information on the role of LRP5 mutations and their effects on the development of juvenile-onset primary osteoporosis, and hence the pathogenesis of the disorder. The mutations causing primary osteoporosis reduce the signaling activity of the canonical Wnt signaling pathway and may therefore result in decreased bone formation. The specific mechanism affecting signaling activity remains to be resolved in future studies. C1 [Korvala, Johanna; Hartikka, Heini; Ala-Kokko, Leena; Mannikko, Minna] Univ Oulu, Oulu Ctr Cell Matrix Res, Oulu 90014, Finland. [Korvala, Johanna; Hartikka, Heini; Ala-Kokko, Leena; Mannikko, Minna] Univ Oulu, Dept Med Biochem & Mol Biol, Oulu 90014, Finland. [Jueppner, Harald] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA USA. [Makitie, Outi] Univ Helsinki, Childrens Hosp, Cent Hosp, Helsinki, Finland. [Makitie, Outi] Univ Helsinki, Helsinki, Finland. [Cole, William G.] Univ Toronto, Hosp Sick Children, Div Orthopaed Surg, Toronto, ON M5G 1X8, Canada. [Schnabel, Dirk] Charite, Otto Heubner Ctr Kinder & Jugendmed, Dept Pediat Endocrinol & Diabet, D-13353 Berlin, Germany. [Mora, Stefano] Ist Sci San Raffaele, Div Metab & Cardiovasc Sci, Lab Pediat Endocrinol, I-20132 Milan, Italy. [Bartels, Cynthia F.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. [Warman, Matthew L.] Childrens Hosp Boston, Orthopaed Res Labs, Boston, MA USA. [Deraska, Donald] Winchester Hosp, Dept Med, Winchester, MA USA. [Hartikka, Heini] N Karelia Cent Hosp, Dept Surg, Joensuu, Finland. [Ala-Kokko, Leena] Connect Tissue Gene Tests, Allentown, PA USA. [Makitie, Outi] Folkhalsan Res Ctr, Helsinki, Finland. RP Mannikko, M (reprint author), Univ Oulu, Oulu Ctr Cell Matrix Res, Oulu 90014, Finland. EM minna.mannikko@oulu.fi RI Mora, Sefano/B-2143-2013; OI Makitie, Outi/0000-0002-4547-001X FU Finnish Cultural Foundation; Academy of Finland; Alma and K.A. Snellman Foundation, Oulu, Finland; Olga and Vilho Linnamo Foundation; Orion-Farmos Research Foundation FX We would like to thank all the patients and their family members for participating in the study. We thank Antti Railo, Ph.D., Minna Komu, Ph.D., Mari Taipale, M. Sc. and Marja-Riitta Vaisanen, M.D., Ph.D., for their valuable help and advice in setting up the in vitro studies. Seppo Vainio, Prof., is acknowledged for providing the STF and beta-Gal-CMV constructs. Laboratory technicians Aira Erkkila and Helena Satulehto are thanked for their excellent technical assistance. The study was supported by grants from the Finnish Cultural Foundation (to MM, LAK and JK), the Academy of Finland (LAK), the Alma and K.A. Snellman Foundation, Oulu, Finland (JK), the Olga and Vilho Linnamo Foundation (JK) and the Orion-Farmos Research Foundation (JK). NR 52 TC 27 Z9 30 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD APR 10 PY 2012 VL 13 AR 26 DI 10.1186/1471-2350-13-26 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 945MD UT WOS:000304276900001 PM 22487062 ER PT J AU Myre, MA AF Myre, Michael A. TI Clues to gamma-secretase, huntingtin and Hirano body normal function using the model organism Dictyostelium discoideum SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Review DE Dictyostelium discoideum; Model organism; Neurodegeneration; Huntingtin; Presenilin; gamma-secretase; Hirano bodies; Neurotransmitter homologues ID FAMILIAL ALZHEIMERS-DISEASE; AMYLOID PRECURSOR PROTEIN; SIGNAL-TRANSDUCTION; PRESENILIN; BODIES; GENE; COMPLEX; NICASTRIN; NEURONS; PROTEOLYSIS AB Many neurodegenerative disorders, although related by their destruction of brain function, display remarkable cellular and/or regional pathogenic specificity likely due to a deregulated functionality of the mutant protein. However, neurodegenerative disease genes, for example huntingtin (HTT), the ataxins, the presenilins (PSEN1/PSEN2) are not simply localized to neurons but are ubiquitously expressed throughout peripheral tissues; it is therefore paramount to properly understand the earliest precipitating events leading to neuronal pathogenesis to develop effective long-term therapies. This means, in no unequivocal terms, it is crucial to understand the gene's normal function. Unfortunately, many genes are often essential for embryogenesis which precludes their study in whole organisms. This is true for HTT, the beta-amyloid precursor protein (APP) and presenilins, responsible for early onset Alzheimer's disease (AD). To better understand neurological disease in humans, many lower and higher eukaryotic models have been established. So the question arises: how reasonable is the use of organisms to study neurological disorders when the model of choice does not contain neurons? Here we will review the surprising, and novel emerging use of the model organism Dictyostelium discoideum, a species of soil-living amoeba, as a valuable biomedical tool to study the normal function of neurodegenerative genes. Historically, the evidence on the usefulness of simple organisms to understand the etiology of cellular pathology cannot be denied. But using an organism without a central nervous system to understand diseases of the brain? We will first introduce the life cycle of Dictyostelium, the presence of many disease genes in the genome and how it has provided unique opportunities to identify mechanisms of disease involving actin pathologies, mitochondrial disease, human lysosomal and trafficking disorders and host-pathogen interactions. Secondly, I will highlight recent studies on the function of HTT, presenilin gamma-secretase and Hirano bodies conducted in Dictyostelium. I will then outline the limitations and future directions in using Dictyostelium to study disease, and finally conclude that given the evolutionary conservation of genes between Dictyostelium and humans and the organisms' genetic tractability, that this system provides a fertile environment for discovering normal gene function related to neurodegeneration and will permit translational studies in higher systems. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Dept Neurol, Boston, MA 02114 USA. RP Myre, MA (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Dept Neurol, Boston, MA 02114 USA. EM myre@chgr.mgh.harvard.edu FU NINDS [NS032765]; Massachusetts HD Center Without Walls [NS016367]; Huntington's Disease Society of America Coalition for the Cure; CHDI Foundation FX MM was supported by grants NINDS NS032765, Massachusetts HD Center Without Walls NS016367, Huntington's Disease Society of America Coalition for the Cure, and the CHDI Foundation. NR 58 TC 5 Z9 5 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD APR 10 PY 2012 VL 19 AR 41 DI 10.1186/1423-0127-19-41 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 942JI UT WOS:000304039800001 PM 22489754 ER PT J AU Chen, XY Shah, D Kositratna, G Manstein, D Anderson, RR Wu, MX AF Chen, Xinyuan Shah, Dilip Kositratna, Garuna Manstein, Dieter Anderson, Richard R. Wu, Mei X. TI Facilitation of transcutaneous drug delivery and vaccine immunization by a safe laser technology SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE Laser; Transdermal patch; Vaccine; Drug; Transcutaneous delivery; Tape stripping ID INFLUENZA VACCINE; IMMUNE-RESPONSES; STRATUM-CORNEUM; HEPATITIS-B; SKIN; PATCH; PRETREATMENT; DISRUPTION; ANTIGEN; TOXIN AB Full-surface laser ablation has been shown to efficiently disrupt stratum corneum and facilitate transcutaneous drug delivery, but it is frequently associated with skin damage that hampers its clinic use. We show here that a safer ablative fractional laser (AFL) can sufficiently facilitate delivery of not only patch-coated hydrophilic drugs but also protein vaccines. AFL treatment generated an array of self renewable microchannels (MCs) in the skin, providing free paths for drug and vaccine delivery into the dermis while maintaining integrity of the skin by quick healing of the MCs. AFL was superior to tape stripping in transcutaneous drug and vaccine delivery as a much higher amount of sulforhodamine B (SRB), methylene blue (MB) or a model vaccine ovalbumin (OVA) was recovered from AFL-treated skin than tape-stripped skin or control skin after patch application. Following entry into the MCs, the drugs or OVA diffused quickly to the entire dermal tissue via the lateral surface of conical-shaped MCs. In contrast, a majority of the drugs and OVA remained on the skin surface, unable to penetrate into the dermal tissue in untreated control skin or tape stripping-treated skin. Strikingly, OVA delivered through the MCs was efficiently taken up by epidermal Langerhans cells and dermal dendritic cells in the vicinity of the MCs or transported to the draining lymph nodes, leading to a robust immune response, in sharp contrast to a weak, though significant, immune response elicited in tape stripping group or a basal immune response in control groups. These data support strongly that AFL is safe and sufficient for transcutaneous delivery of drugs and vaccines. (C) 2012 Elsevier B.V. All rights reserved. C1 [Chen, Xinyuan; Shah, Dilip; Kositratna, Garuna; Manstein, Dieter; Wu, Mei X.] Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Dermatol,Med Sch, Boston, MA 02114 USA. [Anderson, Richard R.; Wu, Mei X.] Harvard MIT Div Hlth Sci & Technol HST, Cambridge, MA USA. RP Wu, MX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Dermatol,Med Sch, 50 Blossom St,Edwards 222, Boston, MA 02114 USA. EM mwu2@partners.org FU National Institutes of Health [AI070785, AI089779, RC1 DA028378]; Bullock-Wellman Fellowship FX This work is supported in part by the National Institutes of Health grants AI070785, AI089779, and RC1 DA028378 (to M.X.W.), and Bullock-Wellman Fellowship (to X.Y.C). NR 36 TC 37 Z9 37 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD APR 10 PY 2012 VL 159 IS 1 BP 43 EP 51 DI 10.1016/j.jconrel.2012.01.002 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 938LG UT WOS:000303734400006 PM 22261281 ER PT J AU Jacobsen, PB Holland, JC Steensma, DP AF Jacobsen, Paul B. Holland, Jimmie C. Steensma, David P. TI Caring for the Whole Patient: The Science of Psychosocial Care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID COLLABORATIVE CARE; CANCER-PATIENTS; DEPRESSION; ONCOLOGY; TRIAL; INTERVENTIONS; METAANALYSIS; MANAGEMENT; PEOPLE C1 [Jacobsen, Paul B.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Holland, Jimmie C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jacobsen, PB (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. OI Steensma, David/0000-0001-5130-9284 NR 32 TC 28 Z9 29 U1 1 U2 9 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 APR 10 PY 2012 VL 30 IS 11 BP 1151 EP 1153 DI 10.1200/JCO.2011.41.4078 PG 3 WC Oncology SC Oncology GA 928PR UT WOS:000302995700001 PM 22412125 ER PT J AU Traeger, L Greer, JA Fernandez-Robles, C Temel, JS Pirl, WF AF Traeger, Lara Greer, Joseph A. Fernandez-Robles, Carlos Temel, Jennifer S. Pirl, William F. TI Evidence-Based Treatment of Anxiety in Patients With Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID QUALITY-OF-LIFE; POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; PATIENTS RECEIVING CHEMOTHERAPY; PROGRESSIVE MUSCLE-RELAXATION; COGNITIVE-BEHAVIOR THERAPY; BREAST-CANCER; DOUBLE-BLIND; PSYCHOEDUCATIONAL INTERVENTION; PSYCHOSOCIAL INTERVENTIONS AB Anxiety is a dynamic response to perceived threat that is common among patients with cancer and fluctuates at critical points in the disease trajectory. A substantial minority of patients may experience clinically significant anxiety resulting from a range of potential etiologic factors. This review summarizes evidence-based recommendations for treatment of anxiety in oncology settings. Recommendations are based on the nature and time course of anxiety and the results of meta-analyses, systematic reviews, and individual trials in cancer populations. The evidence-based literature supports the use of psychosocial and psychopharmacologic treatments to prevent or alleviate anxiety symptoms. Conclusions are tempered by study heterogeneity and methodologic limitations and a lack of trials that included patients with clinically significant anxiety. In oncology settings, accessibility and acceptability of evidence-based treatments vary, and patients may seek a variety of resources to manage cancer concerns. Treatment planning should incorporate contributing factors to anxiety and patient preferences for psychiatric care. C1 [Traeger, Lara] Massachusetts Gen Hosp, Ctr Canc, MGH Behav Med Serv, Boston, MA 02114 USA. RP Traeger, L (reprint author), Massachusetts Gen Hosp, Ctr Canc, MGH Behav Med Serv, 1 Bowdoin Sq,Suite 701, Boston, MA 02114 USA. EM ltraeger@partners.org FU Forest Pharmaceuticals FX Funding: William F. Pirl, Forest Pharmaceuticals NR 104 TC 31 Z9 31 U1 7 U2 27 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 APR 10 PY 2012 VL 30 IS 11 BP 1197 EP 1205 DI 10.1200/JCO.2011.39.5632 PG 9 WC Oncology SC Oncology GA 928PR UT WOS:000302995700006 PM 22412135 ER PT J AU Giugliano, RP AF Giugliano, Robert P. TI Relationships Among Race, Bleeding, and Mortality in Coronary Reperfusion SO CIRCULATION LA English DT Editorial Material DE Editorials; acute myocardial infarction; fibrinolysis; hemorrhage; primary percutaneous coronary intervention; race/ethnicity ID ACUTE MYOCARDIAL-INFARCTION; PLASMINOGEN-ACTIVATOR; TRIAL; THROMBOLYSIS; INTERVENTION; OUTCOMES; TRANSFUSION; THERAPY; RISK; COMPLICATIONS C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 1st Floor Off,350 Longwood Ave, Boston, MA 02115 USA. EM rgiugliano@partners.org NR 26 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 10 PY 2012 VL 125 IS 14 BP 1715 EP 1717 DI 10.1161/CIRCULATIONAHA.112.100032 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 925WR UT WOS:000302793300009 PM 22419698 ER PT J AU Do Kwon, Y Finzi, A Wu, XL Dogo-Isonagie, C Lee, LK Moore, LR Schmidt, SD Stuckey, J Yang, YP Zhou, TQ Zhu, J Vicic, DA Debnath, AK Shapiro, L Bewley, CA Mascola, JR Sodroski, JG Kwong, PD AF Do Kwon, Young Finzi, Andres Wu, Xueling Dogo-Isonagie, Cajetan Lee, Lawrence K. Moore, Lucas R. Schmidt, Stephen D. Stuckey, Jonathan Yang, Yongping Zhou, Tongqing Zhu, Jiang Vicic, David A. Debnath, Asim K. Shapiro, Lawrence Bewley, Carole A. Mascola, John R. Sodroski, Joseph G. Kwong, Peter D. TI Unliganded HIV-1 gp120 core structures assume the CD4-bound conformation with regulation by quaternary interactions and variable loops SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE conformational equilibrium; viral evasion; X-ray crystallography ID VIRAL MEMBRANE-FUSION; ENVELOPE GLYCOPROTEIN; NEUTRALIZATION SENSITIVITY; MONOCLONAL-ANTIBODIES; VIRUS; CD4; BINDING; REVEALS; ENTRY; ARCHITECTURE AB The HIV-1 envelope (Env) spike (gp120(3)/gp41(3)) undergoes considerable structural rearrangements to mediate virus entry into cells and to evade the host immune response. Engagement of CD4, the primary human receptor, fixes a particular conformation and primes Env for entry. The CD4-bound state, however, is prone to spontaneous inactivation and susceptible to antibody neutralization. How does unliganded HIV-1 maintain CD4-binding capacity and regulate transitions to the CD4-bound state? To define this mechanistically, we determined crystal structures of unliganded core gp120 from HIV-1 clades B, C, and E. Notably, all of these unliganded HIV-1 structures resembled the CD4-bound state. Conformational fixation with ligand selection and thermodynamic analysis of full-length and core gp120 interactions revealed that the tendency of HIV-1 gp120 to adopt the CD4-bound conformation was restrained by the V1/V2- and V3-variable loops. In parallel, we determined the structure of core gp120 in complex with the small molecule, NBD-556, which specifically recognizes the CD4-bound conformation of gp120. Neutralization by NBD-556 indicated that Env spikes on primary isolates rarely assume the CD4-bound conformation spontaneously, although they could do so when quaternary restraints were loosened. Together, the results suggest that the CD4-bound conformation represents a "ground state" for the gp120 core, with variable loop and quaternary interactions restraining unliganded gp120 from "snapping" into this conformation. A mechanism of control involving deformations in unliganded structure from a functionally critical state (e. g., the CD4-bound state) provides advantages in terms of HIV-1 Env structural diversity and resistance to antibodies and inhibitors, while maintaining elements essential for entry. C1 [Finzi, Andres; Sodroski, Joseph G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol,Div AIDS, Boston, MA 02115 USA. [Do Kwon, Young; Wu, Xueling; Schmidt, Stephen D.; Stuckey, Jonathan; Yang, Yongping; Zhou, Tongqing; Zhu, Jiang; Shapiro, Lawrence; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Sodroski, Joseph G.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Dogo-Isonagie, Cajetan; Bewley, Carole A.] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Lee, Lawrence K.] Victor Chang Cardiac Res Inst, Struct & Computat Biol Div, Darlinghurst, NSW 2010, Australia. [Moore, Lucas R.; Vicic, David A.] Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA. [Vicic, David A.] Univ Hawaii, Dept Chem, Honolulu, HI 96822 USA. [Debnath, Asim K.] New York Blood Ctr, Lindsley F Kimball Res Inst, Lab Mol Modeling & Drug Design, New York, NY 10065 USA. [Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. RP Sodroski, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol,Div AIDS, 44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu; pdkwong@nih.gov RI Kwon, Young Do/A-6957-2010; Zhou, Tongqing/A-6880-2010; Cheng, Yushao/E-6256-2011; Schmidt, Stephen/B-5398-2012 OI Zhou, Tongqing/0000-0002-3935-4637; FU National Institutes of Health (NIH); International AIDS Vaccine Initiative's Neutralizing Antibody Consortium; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38] FX We thank J. Hoxie, R. Sandier, I. A. Wilson, and members of the Structural Biology Section and Structural Bioinformatics Core, Vaccine Research Center, for discussions and comments on the manuscript. Support for this work was provided by the Intramural Research Program of the National Institutes of Health (NIH) and by grants from the NIH and from the International AIDS Vaccine Initiative's Neutralizing Antibody Consortium. Use of sector 22 (Southeast Region Collaborative Access Team) at the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science Contract W-31-109-Eng-38. NR 46 TC 117 Z9 117 U1 2 U2 30 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2012 VL 109 IS 15 BP 5663 EP 5668 DI 10.1073/pnas.1112391109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 922FX UT WOS:000302533500028 ER PT J AU Scarcelli, G Yun, SH AF Scarcelli, Giuliano Yun, Seok Hyun TI In vivo Brillouin optical microscopy of the human eye SO OPTICS EXPRESS LA English DT Article ID OCULAR RESPONSE ANALYZER; CRYSTALLINE LENS; ELASTIC PROPERTIES; SCATTERING; AGE; CORNEA; SPECTROSCOPY; BIOMECHANICS; PRESBYOPIA; TENSILE AB We report the first Brillouin measurement of the human eye in vivo. We constructed a Brillouin optical scanner safe for human use by employing continuous-wave laser light at 780 nm at a low power of 0.7 mW. With a single scan along the optic axis of the eye, the axial profile of Brillouin frequency shift was obtained with a pixel acquisition time of 0.4 s and axial resolution of about 60 mu m, showing the depth-dependent biomechanical properties in the cornea and lens. (C)2012 Optical Society of America C1 [Yun, Seok Hyun] Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BHX 6, Boston, MA 02114 USA. EM syun@hms.harvard.edu OI scarcelli, giuliano/0000-0002-1736-077X FU National Institutes of Health [R21EB008472, P41RR032042]; National Science of Foundation [CBET-0853773]; Department of Defense [FA9550-04-1-0079]; Center for Integration of Medical Innovation and Technology FX The authors thank Dr. Puoris'haag for help in writing the study protocol and Dr. Roberto Pineda at Massachusetts Eye and Ear Infirmary for performing the eye exams. This work was supported by the National Institutes of Health (R21EB008472, P41RR032042), National Science of Foundation (CBET-0853773), Department of Defense (FA9550-04-1-0079), and the Center for Integration of Medical Innovation and Technology. NR 25 TC 52 Z9 54 U1 0 U2 20 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD APR 9 PY 2012 VL 20 IS 8 BP 9197 EP 9202 DI 10.1364/OE.20.009197 PG 6 WC Optics SC Optics GA 926TT UT WOS:000302855500098 PM 22513631 ER PT J AU Bennett, GG Warner, ET Glasgow, RE Askew, S Goldman, J Ritzwoller, DP Emmons, KM Rosner, BA Colditz, GA AF Bennett, Gary G. Warner, Erica T. Glasgow, Russell E. Askew, Sandy Goldman, Julie Ritzwoller, Debra P. Emmons, Karen M. Rosner, Bernard A. Colditz, Graham A. CA Be Fit Be Well Study Investigators TI Obesity Treatment for Socioeconomically Disadvantaged Patients in Primary Care Practice SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BODY-MASS INDEX; NUTRITION EXAMINATION SURVEY; WEIGHT-LOSS MAINTENANCE; BLOOD-PRESSURE; LIFE-STYLE; AFRICAN-AMERICAN; UNITED-STATES; CARDIOVASCULAR RISK; ETHNIC DISPARITIES; CANCER PREVENTION AB Background: Few evidence-based weight loss treatment options exist for medically vulnerable patients in the primary care setting. Methods: We conducted a 2-arm, 24-month randomized effectiveness trial in 3 Boston community health centers (from February 1, 2008, through May 2, 2011). Participants were 365 obese patients receiving hypertension treatment (71.2% black, 13.1% Hispanic, 68.5% female, and 32.9% with less than a high school educational level). We randomized participants to usual care or a behavioral intervention that promoted weight loss and hypertension self-management using eHealth components. The intervention included tailored behavior change goals, self-monitoring, and skills training, available via a website or interactive voice response; 18 telephone counseling calls; primary care provider endorsement; 12 optional group support sessions; and links with community resources. Results: At 24 months, weight change in the intervention group compared with that in the usual care group was -1.03 kg (95% CI, -2.03 to -0.03 kg). Twenty-four-month change in body mass index (calculated as weight in kilograms divided by height in meters squared) in the intervention group compared with that in the usual care group was -0.38 (95% CI, -0.75 to -0.004). Intervention participants had larger mean weight losses during the 24 months compared with that in the usual care group (area under the receiver operating characteristic curve, -1.07 kg; 95% CI, -1.94 to -0.22). Mean systolic blood pressure was not significantly lower in the intervention arm compared with the usual care arm. Conclusion: The intervention produced modest weight losses, improved blood pressure control, and slowed systolic blood pressure increases in this high-risk, socio-economically disadvantaged patient population. C1 [Bennett, Gary G.; Askew, Sandy] Duke Univ, Duke Obes Prevent Program, Durham, NC 27708 USA. [Bennett, Gary G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27708 USA. [Bennett, Gary G.; Askew, Sandy] Duke Univ, Duke Global Hlth Inst, Durham, NC 27708 USA. [Warner, Erica T.; Colditz, Graham A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bennett, Gary G.; Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc, Boston, MA 02115 USA. [Bennett, Gary G.; Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Human Dev, Boston, MA 02115 USA. [Bennett, Gary G.; Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Hlth, Boston, MA 02115 USA. [Rosner, Bernard A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Rosner, Bernard A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bennett, Gary G.; Warner, Erica T.; Askew, Sandy; Goldman, Julie; Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Div Populat Sci, Boston, MA 02115 USA. [Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Ritzwoller, Debra P.] Kaiser Permanente, Inst Hlth Res, Denver, CO USA. [Colditz, Graham A.] Washington Univ, Sch Med, Div Publ Hlth Sci, Alvin J Siteman Canc Ctr,Dept Surg, St Louis, MO USA. RP Bennett, GG (reprint author), Duke Univ, Duke Obes Prevent Program, POB 90086, Durham, NC 27708 USA. EM gary.bennett@duke.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU National Heart, Lung, and Blood Institute [U01-HL087071]; National Cancer Institute [K22CA126992, K05CA124415-04] FX This work was supported in part by grant U01-HL087071 from the National Heart, Lung, and Blood Institute and grants K22CA126992 (Dr Bennett) and K05CA124415-04 (Dr Emmons) from the National Cancer Institute. NR 58 TC 67 Z9 68 U1 2 U2 28 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 9 PY 2012 VL 172 IS 7 BP 565 EP 574 DI 10.1001/archinternmed.2012.1 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 922NV UT WOS:000302555300006 PM 22412073 ER PT J AU Mou, F Praskova, M Xia, F Van Buren, D Hock, H Avruch, J Zhou, DW AF Mou, Fan Praskova, Maria Xia, Fan Van Buren, Denille Hock, Hanno Avruch, Joseph Zhou, Dawang TI The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL MIGRATION; LYMPHOCYTE MIGRATION; SIGNALING PATHWAY; OXIDATIVE-STRESS; GROWTH-CONTROL; PROTEIN DOCK2; EXPRESSION; EMIGRATION; MICE; RAC AB The Mst1 kinase is an important regulator of murine T cell adhesion, migration, proliferation, and apoptosis. In this study, we analyze mice lacking both Mst1 and Mst2 in hematopoietic cells. Compared with wild-type mice, these double knockout (DKO) mice exhibit a severe reduction in the number of mature T cells in the circulation and in secondary lymphoid organs (SLOs). CD4(+)CD8(-) and CD4(-)CD8(+) single-positive (SP) thymocytes in DKO mice resemble mature T cells of wild-type mice but undergo excessive apoptosis, and their egress from the thymus is reduced by >90%. Even when placed directly in the circulation, DKO SP thymocytes failed to enter SLOs. In SP thymocytes, deficiency of Mst1 and Mst2 abolished sphingosine-1 phosphate- and CCL21-induced Mob1 phosphorylation, Rac1 and RhoA GTP charging, and subsequent cell migration. When phosphorylated by Mst1 or Mst2, Mob1 binds and activates the Rac1 guanyl nucleotide exchanger Dock8, which is abundant in the thymus. Thus, the Mst1 and Mst2 kinases control Rho GTPase activation and the migratory responses of SP thymocytes. C1 [Mou, Fan; Praskova, Maria; Xia, Fan; Avruch, Joseph; Zhou, Dawang] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Mou, Fan; Praskova, Maria; Xia, Fan; Avruch, Joseph; Zhou, Dawang] Massachusetts Gen Hosp, Diabet Unit, Med Serv, Boston, MA 02114 USA. [Van Buren, Denille; Hock, Hanno] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Mou, Fan; Praskova, Maria; Xia, Fan; Van Buren, Denille; Hock, Hanno; Avruch, Joseph; Zhou, Dawang] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu; dwzhou@xmu.edu.cn OI Zhou, Dawang/0000-0002-9053-5249 FU Fundamental Research Funds for the Central Universities of China [2010111079]; Science Planning Program of Fujian Province [2009J1010]; [CA136567]; [DK17776]; [T32DK007028] FX This work was supported in part by the RO1 awards CA136567 (to J. Avruch) and DK17776 (to J. Avruch) and institutional funds. D. Zhou is supported by T32DK007028, the Fundamental Research Funds for the Central Universities of China (project number 2010111079), and the Science Planning Program of Fujian Province (2009J1010). NR 49 TC 58 Z9 60 U1 1 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 9 PY 2012 VL 209 IS 4 BP 741 EP 759 DI 10.1084/jem.20111692 PG 19 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 925SS UT WOS:000302782300009 PM 22412158 ER PT J AU von Bruhl, ML Stark, K Steinhart, A Chandraratne, S Konrad, I Lorenz, M Khandoga, A Tirniceriu, A Coletti, R Kollnberger, M Byrne, RA Laitinen, I Walch, A Brill, A Pfeiler, S Manukyan, D Braun, S Lange, P Riegger, J Ware, J Eckart, A Haidari, S Rudelius, M Schulz, C Echtler, K Brinkmann, V Schwaiger, M Preissner, KT Wagner, DD Mackman, N Engelmann, B Massberg, S AF von Bruehl, Marie-Luise Stark, Konstantin Steinhart, Alexander Chandraratne, Sue Konrad, Ildiko Lorenz, Michael Khandoga, Alexander Tirniceriu, Anca Coletti, Raffaele Koellnberger, Maria Byrne, Robert A. Laitinen, Iina Walch, Axel Brill, Alexander Pfeiler, Susanne Manukyan, Davit Braun, Siegmund Lange, Philipp Riegger, Julia Ware, Jerry Eckart, Annekathrin Haidari, Selgai Rudelius, Martina Schulz, Christian Echtler, Katrin Brinkmann, Volker Schwaiger, Markus Preissner, Klaus T. Wagner, Denisa D. Mackman, Nigel Engelmann, Bernd Massberg, Steffen TI Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DEEP-VEIN THROMBOSIS; GREEN FLUORESCENT PROTEIN; INFERIOR VENA-CAVA; TISSUE FACTOR; PULMONARY-EMBOLISM; TARGETED DELETION; MURINE MODEL; MOUSE MODEL; P-SELECTIN; FACTOR-XII AB Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of DVT in humans. We demonstrate by intravital two-photon and epifluorescence microscopy that blood monocytes and neutrophils crawling along and adhering to the venous endothelium provide the initiating stimulus for DVT development. Using conditional mutants and bone marrow chimeras, we show that intravascular activation of the extrinsic pathway of coagulation via tissue factor (TF) derived from myeloid leukocytes causes the extensive intraluminal fibrin formation characteristic of DVT. We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII (FXII) and by supporting its activation through the release of neutrophil extracellular traps (NETs). Correspondingly, neutropenia, genetic ablation of FXII, or disintegration of NETs each confers protection against DVT amplification. Platelets associate with innate immune cells via glycoprotein Ib alpha and contribute to DVT progression by promoting leukocyte recruitment and stimulating neutrophil-dependent coagulation. Hence, we identified a cross talk between monocytes, neutrophils, and platelets responsible for the initiation and amplification of DVT and for inducing its unique clinical features. C1 [von Bruehl, Marie-Luise; Stark, Konstantin; Steinhart, Alexander; Chandraratne, Sue; Konrad, Ildiko; Lorenz, Michael; Khandoga, Alexander; Tirniceriu, Anca; Coletti, Raffaele; Koellnberger, Maria; Byrne, Robert A.; Braun, Siegmund; Riegger, Julia; Eckart, Annekathrin; Haidari, Selgai; Schulz, Christian; Echtler, Katrin; Massberg, Steffen] Tech Univ Munich, Deutsch Herzzentrum, D-80333 Munich, Germany. [von Bruehl, Marie-Luise; Stark, Konstantin; Steinhart, Alexander; Chandraratne, Sue; Konrad, Ildiko; Lorenz, Michael; Khandoga, Alexander; Tirniceriu, Anca; Coletti, Raffaele; Koellnberger, Maria; Byrne, Robert A.; Braun, Siegmund; Riegger, Julia; Eckart, Annekathrin; Haidari, Selgai; Schulz, Christian; Echtler, Katrin; Massberg, Steffen] Tech Univ Munich, Med Klin 1, D-80333 Munich, Germany. [Laitinen, Iina; Schwaiger, Markus] Tech Univ Munich, Nukl Med Klin & Poliklin, Klinikum Rechts Isar, D-80333 Munich, Germany. [Rudelius, Martina] Tech Univ Munich, Inst Allgemeine Pathol & Pathol Anat, D-80333 Munich, Germany. [von Bruehl, Marie-Luise; Stark, Konstantin; Steinhart, Alexander; Chandraratne, Sue; Konrad, Ildiko; Lorenz, Michael; Khandoga, Alexander; Tirniceriu, Anca; Coletti, Raffaele; Koellnberger, Maria; Byrne, Robert A.; Riegger, Julia; Eckart, Annekathrin; Haidari, Selgai; Schulz, Christian; Echtler, Katrin; Massberg, Steffen] Munich Heart Alliance, Munich, Germany. [Walch, Axel] Helmholtz Zentrum Munchen, Deutsch Forsch Zentrum Umwelt & Gesundheit, Inst Pathol, D-85764 Neuherberg, Germany. [Brill, Alexander; Wagner, Denisa D.] Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. [Brill, Alexander; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Pfeiler, Susanne; Manukyan, Davit; Engelmann, Bernd] Univ Munich, Inst Klin Chem, D-81377 Munich, Germany. [Lange, Philipp] Univ Munich, Med Klin 1, D-81377 Munich, Germany. [Ware, Jerry] Univ Arkansas Med Sci, Dept Physiol & Biophys, Little Rock, AR 72205 USA. [Schulz, Christian] Kings Coll London, Ctr Mol & Cellular Biol Inflammat, London SE1 1UL, England. [Brinkmann, Volker] Max Planck Inst Infekt Biol, D-10117 Berlin, Germany. [Preissner, Klaus T.] Univ Giessen, Dept Biochem, D-35392 Giessen, Germany. [Mackman, Nigel] Univ N Carolina, Dept Med, Chapel Hill, NC 27514 USA. RP Massberg, S (reprint author), Tech Univ Munich, Deutsch Herzzentrum, D-80333 Munich, Germany. EM massberg@idi.harvard.edu RI Brinkmann, Volker/A-6015-2009; Schulz, Christian/J-8545-2012; Walch, Axel/B-4554-2012; OI Schulz, Christian/0000-0003-3878-7833; Walch, Axel/0000-0001-5578-4023; Mackman, Nigel/0000-0002-9170-7700; schwaiger, markus /0000-0002-2305-7144 FU DFG [Forschergruppe 923]; FP7 program (PRESTIGE); National Institutes of Health [HL006350]; National Heart, Lung, and Blood Institute of the National Institutes of Health [HL102101]; [SFB914] FX This study was supported by the SFB914 (S. Massberg and A. Khandoga), the DFG-Forschergruppe 923 (S. Massberg) and the FP7 program (PRESTIGE; S. Massberg), as well as the National Institutes of Health grant HL006350 (N. Mackman) and the National Heart, Lung, and Blood Institute of the National Institutes of Health grant HL102101 (D.D. Wagner). NR 60 TC 359 Z9 364 U1 10 U2 58 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 9 PY 2012 VL 209 IS 4 BP 819 EP 835 DI 10.1084/jem.20112322 PG 17 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 925SS UT WOS:000302782300014 PM 22451716 ER PT J AU Huang, WJ Pach, D Napadow, V Park, K Long, XY Neumann, J Maeda, Y Nierhaus, T Liang, FR Witt, CM AF Huang, Wenjing Pach, Daniel Napadow, Vitaly Park, Kyungmo Long, Xiangyu Neumann, Jane Maeda, Yumi Nierhaus, Till Liang, Fanrong Witt, Claudia M. TI Characterizing Acupuncture Stimuli Using Brain Imaging with fMRI - A Systematic Review and Meta-Analysis of the Literature SO PLOS ONE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CARPAL-TUNNEL-SYNDROME; IMPLICATED ACUPOINTS; ELECTROACUPUNCTURE STIMULATION; NEURONAL SPECIFICITY; CORTICAL ACTIVATIONS; MANUAL ACUPUNCTURE; PLACEBO ANALGESIA; SHAM ACUPUNCTURE; HEALTHY-SUBJECTS AB Background: The mechanisms of action underlying acupuncture, including acupuncture point specificity, are not well understood. In the previous decade, an increasing number of studies have applied fMRI to investigate brain response to acupuncture stimulation. Our aim was to provide a systematic overview of acupuncture fMRI research considering the following aspects: 1) differences between verum and sham acupuncture, 2) differences due to various methods of acupuncture manipulation, 3) differences between patients and healthy volunteers, 4) differences between different acupuncture points. Methodology/Principal Findings: We systematically searched English, Chinese, Korean and Japanese databases for literature published from the earliest available up until September 2009, without any language restrictions. We included all studies using fMRI to investigate the effect of acupuncture on the human brain (at least one group that received needle-based acupuncture). 779 papers were identified, 149 met the inclusion criteria for the descriptive analysis, and 34 were eligible for the meta-analyses. From a descriptive perspective, multiple studies reported that acupuncture modulates activity within specific brain areas, including somatosensory cortices, limbic system, basal ganglia, brain stem, and cerebellum. Meta-analyses for verum acupuncture stimuli confirmed brain activity within many of the regions mentioned above. Differences between verum and sham acupuncture were noted in brain response in middle cingulate, while some heterogeneity was noted for other regions depending on how such meta-analyses were performed, such as sensorimotor cortices, limbic regions, and cerebellum. Conclusions: Brain response to acupuncture stimuli encompasses a broad network of regions consistent with not just somatosensory, but also affective and cognitive processing. While the results were heterogeneous, from a descriptive perspective most studies suggest that acupuncture can modulate the activity within specific brain areas, and the evidence based on meta-analyses confirmed some of these results. More high quality studies with more transparent methodology are needed to improve the consistency amongst different studies. C1 [Huang, Wenjing; Pach, Daniel; Witt, Claudia M.] Charite Univ Med Ctr, Inst Social Med Epidemiol & Hlth Econ, Berlin, Germany. [Huang, Wenjing; Liang, Fanrong] Chengdu Univ Tradit Chinese Med, Chengdu, Peoples R China. [Witt, Claudia M.] Univ Maryland, Sch Med, Ctr Integrat Med, Baltimore, MD 21201 USA. [Napadow, Vitaly; Maeda, Yumi] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Napadow, Vitaly; Maeda, Yumi] Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. [Park, Kyungmo] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea. [Nierhaus, Till] Berlin Neuroimaging Ctr, Berlin, Germany. [Nierhaus, Till] Charite, Dept Neurol, Berlin, Germany. [Long, Xiangyu; Neumann, Jane; Nierhaus, Till] Max Planck Inst Human Cognit & Brain Sci, Leipzig, Germany. [Neumann, Jane] Univ Leipzig, Med Ctr, IFB Adipos Dis, Leipzig, Germany. RP Huang, WJ (reprint author), Charite Univ Med Ctr, Inst Social Med Epidemiol & Hlth Econ, Berlin, Germany. EM claudia.witt@charite.de FU Carstens Foundation; Chinese Scholarship Council FX Funding provided by Carstens Foundation and Chinese Scholarship Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 168 TC 86 Z9 91 U1 6 U2 30 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 9 PY 2012 VL 7 IS 4 AR e32960 DI 10.1371/journal.pone.0032960 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955JO UT WOS:000305014500007 PM 22496739 ER PT J AU Arjomandi, M Haight, T Sadeghi, N Redberg, R Gold, WM AF Arjomandi, Mehrdad Haight, Thaddeus Sadeghi, Nasrat Redberg, Rita Gold, Warren M. TI Reduced Exercise Tolerance and Pulmonary Capillary Recruitment with Remote Secondhand Smoke Exposure SO PLOS ONE LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; CABIN AIR-QUALITY; ACUTE CORONARY SYNDROMES; DIFFUSING-CAPACITY; FLIGHT ATTENDANTS; SINGLE EXHALATION; CARBON-MONOXIDE; POSITION PAPER; DISEASE; ASSOCIATION AB Rationale: Flight attendants who worked on commercial aircraft before the smoking ban in flights (pre-ban FAs) were exposed to high levels of secondhand smoke (SHS). We previously showed never-smoking pre-ban FAs to have reduced diffusing capacity (Dco) at rest. Methods: To determine whether pre-ban FAs increase their Dco and pulmonary blood flow ((Q) over dotc) during exercise, we administered a symptom-limited supine-posture progressively increasing cycle exercise test to determine the maximum work (watts) and oxygen uptake ((V) over doto(2)) achieved by FAs. After 30 min rest, we then measured Dco and (Q) over dotc at 20, 40, 60, and 80 percent of maximum observed work. Results: The FAs with abnormal resting Dco achieved a lower level of maximum predicted work and (V) over doto(2) compared to those with normal resting Dco (mean +/- SEM; 88.7 +/- 2.9 vs. 102.5 +/- 3.1% predicted (V) over doto(2); p = 0.001). Exercise limitation was associated with the FAs' FEV1 (r = 0.33; p = 0.003). The Dco increased less with exercise in those with abnormal resting Dco (mean +/- SEM: 1.36 +/- 0.16 vs. 1.90 +/- 0.16 ml/min/mmHg per 20% increase in predicted watts; p = 0.020), and amongst all FAs, the increase with exercise seemed to be incrementally lower in those with lower resting Dco. Exercise-induced increase in (Q) over dotc was not different in the two groups. However, the FAs with abnormal resting Dco had less augmentation of their Dco with increase in (Q) over dotc during exercise (mean +/- SEM: 0.93 +/- 0.06 vs. 1.47 +/- 0.09 ml/min/mmHg per L/min; p<0.0001). The Dco during exercise was inversely associated with years of exposure to SHS in those FAs with >= 10 years of pre-ban experience (r = -0.32; p = 0.032). Conclusions: This cohort of never-smoking FAs with SHS exposure showed exercise limitation based on their resting Dco. Those with lower resting Dco had reduced pulmonary capillary recruitment. Exposure to SHS in the aircraft cabin seemed to be a predictor for lower Dco during exercise. C1 [Arjomandi, Mehrdad; Redberg, Rita; Gold, Warren M.] Univ Calif San Francisco, Flight Attendants Med Res Inst, Ctr Excellence, San Francisco, CA 94143 USA. [Gold, Warren M.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Arjomandi, Mehrdad; Gold, Warren M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Arjomandi, Mehrdad; Redberg, Rita] San Francisco VA Med Ctr, San Francisco, CA USA. [Haight, Thaddeus] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Sadeghi, Nasrat] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. RP Arjomandi, M (reprint author), Univ Calif San Francisco, Flight Attendants Med Res Inst, Ctr Excellence, San Francisco, CA 94143 USA. EM mehrdad.arjomandi@ucsf.edu FU The Flight Attendants Medical Research Institute; The National Institutes of Health [K23 HL083099]; Northern California Institute for Research and Education; University of California San Francisco Cardiovascular Research Institute FX Funding provided by The Flight Attendants Medical Research Institute, The National Institutes of Health (K23 HL083099), Northern California Institute for Research and Education and the University of California San Francisco Cardiovascular Research Institute Faculty Development Funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 2 Z9 2 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 6 PY 2012 VL 7 IS 4 AR e34393 DI 10.1371/journal.pone.0034393 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955JA UT WOS:000305012700031 PM 22493689 ER PT J AU Wagers, AJ AF Wagers, Amy J. TI The Stem Cell Niche in Regenerative Medicine SO CELL STEM CELL LA English DT Review ID HUMAN HEMATOPOIETIC STEM; HUMAN SOMATIC-CELLS; BONE-MARROW NICHE; PROGENITOR CELLS; MOTOR-NEURONS; PARKINSONS-DISEASE; DEFINED FACTORS; SELF-RENEWAL; MUSCLE; PLURIPOTENT AB Stem cells are fundamental units for achieving regenerative therapies, which leads naturally to a theoretical and experimental focus on these cells for therapeutic screening and intervention. A growing body of data in many tissue systems indicates that stem cell function is critically influenced by extrinsic signals derived from the microenvironment, or "niche." In this vein, the stem cell niche represents a significant, and largely untapped, entry point for therapeutic modulation of stem cell behavior. This Perspective will discuss how the niche influences stem cells in homeostasis, in the progression of degenerative and malignant diseases, and in therapeutic strategies for tissue repair. C1 [Wagers, Amy J.] Howard Hughes Med Inst, Boston, MA 02215 USA. [Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Boston, MA 02215 USA. [Wagers, Amy J.] Joslin Diabet Ctr, Cambridge, MA 02215 USA. RP Wagers, AJ (reprint author), Howard Hughes Med Inst, 7 Divin Ave, Boston, MA 02215 USA. EM amy.wagers@joslin.harvard.edu NR 84 TC 87 Z9 89 U1 6 U2 52 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD APR 6 PY 2012 VL 10 IS 4 BP 362 EP 369 DI 10.1016/j.stem.2012.02.018 PG 8 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 929QA UT WOS:000303079400006 PM 22482502 ER PT J AU Mou, HM Zhao, R Sherwood, R Ahfeldt, T Lapey, A Wain, J Sicilian, L Izvolsky, K Musunuru, K Cowan, C Rajagopal, J AF Mou, Hongmei Zhao, Rui Sherwood, Richard Ahfeldt, Tim Lapey, Allen Wain, John Sicilian, Leonard Izvolsky, Konstantin Musunuru, Kiran Cowan, Chad Rajagopal, Jayaraj TI Generation of Multipotent Lung and Airway Progenitors from Mouse ESCs and Patient-Specific Cystic Fibrosis iPSCs SO CELL STEM CELL LA English DT Article ID EMBRYONIC STEM-CELLS; DIRECTED DIFFERENTIATION; RESPIRATORY EPITHELIUM; GENETIC MODIFIERS; ENDODERM; MORPHOGENESIS; FOREGUT; MODEL; BMP; EXPRESSION AB Deriving lung progenitors from patient-specific pluripotent cells is a key step in producing differentiated lung epithelium for disease modeling and transplantation. By mimicking the signaling events that occur during mouse lung development, we generated murine lung progenitors in a series of discrete steps. Definitive endoderm derived from mouse embryonic stem cells (ESCs) was converted into foregut endoderm, then into replicating Nkx2.1+ lung endoderm, and finally into multipotent embryonic lung progenitor and airway progenitor cells. We demonstrated that precisely-timed BMP, FGF, and WNT signaling are required for NKX2.1 induction. Mouse ESC-derived Nkx2.1+ progenitor cells formed respiratory epithelium (tracheospheres) when transplanted subcutaneously into mice. We then adapted this strategy to produce disease-specific lung progenitor cells from human Cystic Fibrosis induced pluripotent stem cells (iPSCs), creating a platform for dissecting human lung disease. These disease-specific human lung progenitors formed respiratory epithelium when subcutaneously engrafted into immunodeficient mice. C1 [Mou, Hongmei; Zhao, Rui; Ahfeldt, Tim; Wain, John; Izvolsky, Konstantin; Musunuru, Kiran; Cowan, Chad; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Mou, Hongmei; Zhao, Rui; Sicilian, Leonard; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Internal Med, Boston, MA 02114 USA. [Lapey, Allen; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Pulm Unit, Dept Pediat, Boston, MA 02114 USA. [Wain, John] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sherwood, Richard; Musunuru, Kiran] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Ahfeldt, Tim; Musunuru, Kiran; Cowan, Chad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Musunuru, Kiran; Cowan, Chad; Rajagopal, Jayaraj] Holyoke Ctr, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Rajagopal, J (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM jrajagopal@partners.org RI Zhao, Rui/J-7110-2014; Ahfeldt, Tim/E-2935-2017 FU Harvard Stem Cell Institute; NIH-NHLBI [P30] FX The work in this manuscript was supported by a Harvard Stem Cell Institute Seed Grant and an NIH-NHLBI Early Career Research New Faculty (P30) award to J.R. We thank Drs. William Anderson and Darrell Kotton for reading this manuscript and for their critical comments. We also wish to extend our thanks to all of the members of the Rajagopal Laboratory for their reading of the text, their constructive criticisms and comments, and valuable discussion and support. NR 57 TC 114 Z9 114 U1 4 U2 48 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD APR 6 PY 2012 VL 10 IS 4 BP 385 EP 397 DI 10.1016/j.stem.2012.01.018 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 929QA UT WOS:000303079400008 PM 22482504 ER PT J AU Longmire, TA Ikonomou, L Hawkins, F Christodoulou, C Cao, YX Jean, JC Kwok, LW Mou, HM Rajagopal, J Shen, SS Dowton, AA Serra, M Weiss, DJ Green, MD Snoeck, HW Ramirez, MI Kotton, DN AF Longmire, Tyler A. Ikonomou, Laertis Hawkins, Finn Christodoulou, Constantina Cao, Yuxia Jean, J. C. Kwok, Letty W. Mou, Hongmei Rajagopal, Jayaraj Shen, Steven S. Dowton, Anne A. Serra, Maria Weiss, Daniel J. Green, Michael D. Snoeck, Hans-Willem Ramirez, Maria I. Kotton, Darrell N. TI Efficient Derivation of Purified Lung and Thyroid Progenitors from Embryonic Stem Cells SO CELL STEM CELL LA English DT Article ID DEFINITIVE ENDODERM; II CELLS; EPITHELIAL-CELLS; IPS CELLS; IN-VITRO; MOUSE; DIFFERENTIATION; FOREGUT; MORPHOGENESIS; PROTEIN AB Two populations of Nicx2-1+ progenitors in the developing foregut endoderm give rise to the entire postnatal lung and thyroid epithelium, but little is known about these cells because they are difficult to isolate in a pure form. We demonstrate here the purification and directed differentiation of primordial lung and thyroid progenitors derived from mouse embryonic stem cells (ESCs). Inhibition of TGF beta and BMP signaling, followed by combinatorial stimulation of BMP and FGF signaling, can specify these cells efficiently from definitive endodermal precursors. When derived using Nkx2-1(GFP) knockin reporter ESCs, these progenitors can be purified for expansion in culture and have a transcriptome that overlaps with developing lung epithelium. Upon induction, they can express a broad repertoire of markers indicative of lung and thyroid lineages and can recellularize a 3D lung tissue scaffold. Thus, we have derived a pure population of progenitors able to recapitulate the developmental milestones of lung/thyroid development. C1 [Longmire, Tyler A.; Ikonomou, Laertis; Hawkins, Finn; Christodoulou, Constantina; Cao, Yuxia; Jean, J. C.; Kwok, Letty W.; Dowton, Anne A.; Serra, Maria; Ramirez, Maria I.; Kotton, Darrell N.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Shen, Steven S.] Boston Univ, Sch Med, Sect Computat Biomed, Boston, MA 02118 USA. [Shen, Steven S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Longmire, Tyler A.; Ikonomou, Laertis; Hawkins, Finn; Christodoulou, Constantina; Cao, Yuxia; Jean, J. C.; Kwok, Letty W.; Dowton, Anne A.; Serra, Maria; Ramirez, Maria I.; Kotton, Darrell N.] Boston Univ, Ctr Regenerat Med CReM, Boston, MA 02118 USA. [Mou, Hongmei; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Shen, Steven S.] NYU, Sch Med, Ctr Hlth Informat & Bioinformat, New York, NY 10016 USA. [Shen, Steven S.] NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. [Shen, Steven S.] NYU, Sch Med, Dept Med, New York, NY 10016 USA. [Weiss, Daniel J.] Univ Vermont, Coll Med, Vermont Lung Ctr, Burlington, VT 05405 USA. [Green, Michael D.; Snoeck, Hans-Willem] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. [Longmire, Tyler A.; Ikonomou, Laertis; Hawkins, Finn; Christodoulou, Constantina; Cao, Yuxia; Jean, J. C.; Kwok, Letty W.; Dowton, Anne A.; Serra, Maria; Ramirez, Maria I.; Kotton, Darrell N.] Boston Med Ctr, Boston, MA 02118 USA. RP Kotton, DN (reprint author), Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. EM dkotton@bu.edu RI Ikonomou, Laertis/D-4579-2009; OI Ikonomou, Laertis/0000-0003-0993-6713; Hawkins, Finn/0000-0002-2246-6448; Shen, Steven/0000-0001-7725-1260; Kotton, Darrell/0000-0002-9604-8476 FU NIH [PO1 HL047049-16A1, 1RC2HL101535-01, 1R01 HL095993-01, 1R01 HL108678, T32 HL007035, R01 HL111574]; USAMRRA; Alpha-1 Foundation; ARC from Evans Center for Interdisciplinary Research at Boston University; ATS/ChILD Foundation FX We thank Paul Gadue for supplying the TV8-Puro gene targeting vector; Raul Mostoslavsky for assistance with Southern blotting techniques; Susan Guttentag for DCI+K media protocols; and Mary C. Williams, Wellington V. Cardoso, Bess P. Rosen, George Murphy, Gustavo Mostoslavsky, and Jerome Brody for insightful manuscript editing. For technical support, we thank Dr. Yuriy Alekseyev, Sherry Zang, and Dr. Gang Liu for microarray processing; Dr. Jining Lu and Avrum Spira for bioinformatics analysis assistance; and John M. Wallis for lung slice culture technical support. D.N.K. is supported by NIH PO1 HL047049-16A1, 1RC2HL101535-01, 1R01 HL095993-01, 1R01 HL108678, a USAMRRA Award, an Alpha-1 Foundation Award, and an ARC award from the Evans Center for Interdisciplinary Research at Boston University. T.A.L. is supported by NIH training grant T32 HL007035. L.I. is supported by R01 HL111574 and an ATS/ChILD Foundation Award. The authors have no conflicts of interest to declare. NR 57 TC 124 Z9 126 U1 4 U2 36 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD APR 6 PY 2012 VL 10 IS 4 BP 398 EP 411 DI 10.1016/j.stem.2012.01.019 PG 14 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 929QA UT WOS:000303079400009 PM 22482505 ER PT J AU Heidel, FH Bullinger, L Feng, ZH Wang, Z Neff, TA Stein, L Kalaitzidis, D Lane, SW Armstrong, SA AF Heidel, Florian H. Bullinger, Lars Feng, Zhaohui Wang, Zhu Neff, Tobias A. Stein, Lauren Kalaitzidis, Demetrios Lane, Steve W. Armstrong, Scott A. TI Genetic and Pharmacologic Inhibition of beta-Catenin Targets Imatinib-Resistant Leukemia Stem Cells in CML SO CELL STEM CELL LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; COMPLETE MOLECULAR REMISSION; ABL TYROSINE KINASE; HEMATOPOIETIC STEM; COLORECTAL-CANCER; PHILADELPHIA-CHROMOSOME; SIGNALING PATHWAY; CD34(+) CELLS; COLON-CANCER AB A key characteristic of hematopoietic stem cells (HSCs) is the ability to self-renew. Genetic deletion of beta-catenin during fetal HSC development leads to impairment of self-renewal while beta-catenin is dispensable in fully developed adult HSCs. Whether beta-catenin is required for maintenance of fully developed CML leukemia stem cells (LSCs) is unknown. Here, we use a conditional mouse model to show that deletion of beta-catenin after CML initiation does not lead to a significant increase in survival. However, deletion of beta-catenin synergizes with imatinib (IM) to delay disease recurrence after imatinib discontinuation and to abrogate CML stem cells. These effects can be mimicked by pharmacologic inhibition of beta-catenin via modulation of prostaglandin signaling. Treatment with the cyclooxygenase inhibitor indomethacin reduces beta-catenin levels and leads to a reduction in LSCs. In conclusion, inhibiting beta-catenin by genetic inactivation or pharmacologic modulation is an effective combination therapy with imatinib and targets CML stem cells. C1 [Heidel, Florian H.; Bullinger, Lars; Feng, Zhaohui; Wang, Zhu; Neff, Tobias A.; Stein, Lauren; Kalaitzidis, Demetrios; Lane, Steve W.; Armstrong, Scott A.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Heidel, Florian H.; Bullinger, Lars; Feng, Zhaohui; Wang, Zhu; Neff, Tobias A.; Stein, Lauren; Kalaitzidis, Demetrios; Armstrong, Scott A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Heidel, Florian H.; Bullinger, Lars; Feng, Zhaohui; Wang, Zhu; Neff, Tobias A.; Stein, Lauren; Kalaitzidis, Demetrios; Armstrong, Scott A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Heidel, Florian H.] Univ Magdeburg, Univ Hosp, Dept Hematol Oncol, F-39120 Magdeburg, Germany. [Bullinger, Lars] Univ Hosp Ulm, Dept Hematol Oncol, D-89081 Ulm, Germany. [Lane, Steve W.] Queensland Inst Med Res, Herston, Qld 4006, Australia. [Armstrong, Scott A.] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Armstrong, SA (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM scott.armstrong@childrens.harvard.edu RI Lane, Steven/C-3215-2012; OI Lane, Steven/0000-0002-8050-6209; Neff, Tobias/0000-0002-0188-8393 FU Deutsche Krebshilfe [DKH D/08/00661]; NCI [CA66996]; German Research Foundation [BU 1339/3-1] FX This work was supported by a Mildred-Scheel grant (DKH D/08/00661, Deutsche Krebshilfe to F.H.H.) and an NCI grant (#CA66996 to S.A.A.). S.A.A. is a Leukemia and Lymphoma Society Scholar, and L.B. was supported in part by the German Research Foundation (Heisenberg-Stipendium BU 1339/3-1). NR 56 TC 97 Z9 106 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD APR 6 PY 2012 VL 10 IS 4 BP 412 EP 424 DI 10.1016/j.stem.2012.02.017 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 929QA UT WOS:000303079400010 PM 22482506 ER PT J AU Mediouni, S Watkins, JD Pierres, M Bole, A Loret, EP Baillat, G AF Mediouni, Sonia Watkins, Jennifer D. Pierres, Michel Bole, Angelique Loret, Erwann P. Baillat, Gilbert TI A Monoclonal Antibody Directed against a Conformational Epitope of the HIV-1 Trans-activator (Tat) Protein Neutralizes Cross-clade SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELLS; APOPTOSIS; GLYCOPROTEIN; COMBINATION; PERSISTENCE; INFECTION; VARIANTS; THERAPY; DEFINES AB The identification of a neutralizing mAb against extracellular HIV-1 transactivator of transcription (Tat) is important for the development of an efficient HIV-1 treatment. Tat plays an essential role in HIV-1 pathogenesis, not only for HIV-1 replication but also as an extracellular toxin able to disrupt the immune system. We showed previously that immunization of rabbits with Tat Oyi, a variant cloned from an African woman who did not develop AIDS following HIV-1 infection, raised antibodies able to recognize different Tat variants. We carried out mice immunization with Tat Oyi and selected a mAb named 7G12, which had the capacity to cross-recognize heterologous Tat variants by a common three-dimensional epitope. These results highlighted that Tat variants were able to acquire a structure, in contrast to a number of studies showing Tat as an unfolded protein. mAb 7G12 also had the capacity to neutralize the biological activities of these Tat variants by blocking the cellular uptake of extracellular Tat. This is the first study using Tat Oyi to produce a mAb able to neutralize effectively activities of extracellular Tats from different HIV-1 subtypes. This mAb has an important potential in therapeutic passive immunization and could help HIV-1 infected patients to restore their immunity. C1 [Mediouni, Sonia; Loret, Erwann P.; Baillat, Gilbert] Univ Aix Marseille 2, Fac Pharm, Equipe Rech Technol 2011, F-13385 Marseille 5, France. [Watkins, Jennifer D.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02215 USA. [Pierres, Michel; Bole, Angelique] Univ Mediterranee UNIVMED UM631, Ctr Immunol Marseille Luminy, INSERM, CNRS,UMR S613,UMR 6102, F-13288 Marseille 9, France. RP Loret, EP (reprint author), Univ Aix Marseille 2, Fac Pharm, Equipe Rech Technol 2011, 27 BD Jean Moulin, F-13385 Marseille 5, France. EM erwann.loret@univmed.fr; gilbert.baillat@univmed.fr NR 47 TC 5 Z9 5 U1 0 U2 6 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 APR 6 PY 2012 VL 287 IS 15 BP 11942 EP 11950 DI 10.1074/jbc.M111.319863 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 925SR UT WOS:000302782200033 PM 22362765 ER PT J AU Palsgaard, J Emanuelli, B Winnay, JN Sumara, G Karsenty, G Kahn, CR AF Palsgaard, Jane Emanuelli, Brice Winnay, Jonathon N. Sumara, Grzegorz Karsenty, Gerard Kahn, C. Ronald TI Cross-talk between Insulin and Wnt Signaling in Preadipocytes ROLE OF WNT CO-RECEPTOR LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN-5 (LRP5) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-CATENIN; GLUCOSE-METABOLISM; DIABETES-MELLITUS; OXIDATIVE STRESS; PROTEIN-5 LRP5; ADIPOGENESIS; PATHWAY; PHOSPHORYLATION; CELLS; POLYMORPHISMS AB Disturbed Wnt signaling has been implicated in numerous diseases, including type 2 diabetes and the metabolic syndrome. In the present study, we have investigated cross-talk between insulin and Wnt signaling pathways using preadipocytes with and without knockdown of the Wnt co-receptors LRP5 and LRP6 and with and without knock-out of insulin and IGF-1 receptors. We find that Wnt stimulation leads to phosphorylation of insulin signaling key mediators, including Akt, GSK3 beta, and ERK1/2, although with a lower fold stimulation and slower time course than observed for insulin. These Wnt effects are insulin/IGF-1 receptor-dependent and are lost in insulin/IGF-1 receptor double knock-out cells. Conversely, in LRP5 knockdown preadipocytes, insulin-induced phosphorylation of IRS1, Akt, GSK3 beta, and ERK1/2 is highly reduced. This effect is specific to insulin, as compared with IGF-1, stimulation and appears to be due to an inducible interaction between LRP5 and the insulin receptor as demonstrated by co-immunoprecipitation. These data demonstrate that Wnt and insulin signaling pathways exhibit cross-talk at multiple levels. Wnt induces phosphorylation of Akt, ERK1/2, and GSK3 beta, and this is dependent on insulin/IGF-1 receptors. Insulin signaling also involves the Wnt co-receptor LRP5, which has a positive effect on insulin signaling. Thus, altered Wnt and LRP5 activity can serve as modifiers of insulin action and insulin resistance in the pathophysiology of diabetes and metabolic syndrome. C1 [Palsgaard, Jane; Emanuelli, Brice; Winnay, Jonathon N.; Kahn, C. Ronald] Harvard Univ, Joslin Diabet Ctr, Sch Med, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. [Sumara, Grzegorz; Karsenty, Gerard] Columbia Univ, Dept Genet & Dev, Sch Med, New York, NY 10032 USA. RP Kahn, CR (reprint author), Harvard Univ, Joslin Diabet Ctr, Sch Med, Sect Integrat Physiol & Metab, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu RI Emanuelli, Brice/M-2097-2016 FU National Institutes of Health [DK31036, DK33201, DK55545]; Novo Nordisk STAR FX * This work was supported, in whole or in part, by National Institutes of Health Grants DK31036, DK33201, and DK55545.; 1 Supported by a Novo Nordisk STAR International postdoctoral fellowship. NR 57 TC 29 Z9 31 U1 1 U2 9 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 APR 6 PY 2012 VL 287 IS 15 BP 12016 EP 12026 DI 10.1074/jbc.M111.337048 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 925SR UT WOS:000302782200039 PM 22337886 ER PT J AU Simini, F Gonzalez, MC Maritan, A Barabasi, AL AF Simini, Filippo Gonzalez, Marta C. Maritan, Amos Barabasi, Albert-Laszlo TI A universal model for mobility and migration patterns SO NATURE LA English DT Article ID INTERVENING OPPORTUNITIES; NETWORKS; CITIES; GROWTH; TRADE AB Introduced in its contemporary form in 1946 (ref. 1), but with roots that go back to the eighteenth century(2), the gravity law(1,3,4) is the prevailing framework with which to predict population movement(3,5,6), cargo shipping volume(7) and inter-city phone calls(8,9), as well as bilateral trade flows between nations(10). Despite its widespread use, it relies on adjustable parameters that vary from region to region and suffers from known analytic inconsistencies. Here we introduce a stochastic process capturing local mobility decisions that helps us analytically derive commuting and mobility fluxes that require as input only information on the population distribution. The resulting radiation model predicts mobility patterns in good agreement with mobility and transport patterns observed in a wide range of phenomena, from long-term migration patterns to communication volume between different regions. Given its parameter-free nature, the model can be applied in areas where we lack previous mobility measurements, significantly improving the predictive accuracy of most of the phenomena affected by mobility and transport processes(11-23). C1 [Simini, Filippo; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Simini, Filippo; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys Biol & Comp Sci, Boston, MA 02115 USA. [Simini, Filippo; Maritan, Amos] Univ Padua, Dipartimento Fis G Galilei, CNISM, I-35131 Padua, Italy. [Simini, Filippo; Maritan, Amos] Ist Nazl Fis Nucl, I-35131 Padua, Italy. [Simini, Filippo] Budapest Univ Technol & Econ, Inst Phys, H-1111 Budapest, Hungary. [Gonzalez, Marta C.] MIT, Dept Civil & Environm Engn, Cambridge, MA 02139 USA. [Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Barabasi, AL (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. EM amos.maritan@pd.infn.it; alb@neu.edu RI Gonzalez, Marta/E-9456-2011 OI Gonzalez, Marta/0000-0002-8482-0318 FU Cariparo foundation; Network Science Collaborative Technology Alliance; US Army Research Laboratory [W911NF-09-2-0053]; Office of Naval Research [N000141010968]; Defense Threat Reduction Agency [WMD BRBAA07-J-2-0035, BRBAA08-Per4-C-2-0033]; James S. McDonnell Foundation 21st Century Initiative in Studying Complex Systems FX We thank J. P. Bagrow, A. Fava, F. Giannotti, Y.-R. Lin, J. Menche, Z. Neda, D. Pedreschi, D. Wang, G. Wilkerson and D. Bauer for many discussions, and N. Ferguson for prompting us to look into the gravity law. A.M. and F.S. acknowledge the Cariparo foundation for financial support. This work was supported by the Network Science Collaborative Technology Alliance sponsored by the US Army Research Laboratory under Agreement Number W911NF-09-2-0053; the Office of Naval Research under Agreement Number N000141010968; the Defense Threat Reduction Agency awards WMD BRBAA07-J-2-0035 and BRBAA08-Per4-C-2-0033; and the James S. McDonnell Foundation 21st Century Initiative in Studying Complex Systems. NR 30 TC 225 Z9 245 U1 18 U2 173 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 5 PY 2012 VL 484 IS 7392 BP 96 EP 100 DI 10.1038/nature10856 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 919QN UT WOS:000302343400041 PM 22367540 ER PT J AU Baselga, J Benyunes, MC Swain, SM AF Baselga, Jose Benyunes, Mark C. Swain, Sandra M. TI Pertuzumab plus Trastuzumab in Metastatic Breast Cancer REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Benyunes, Mark C.] Genentech Inc, San Francisco, CA 94080 USA. [Swain, Sandra M.] MedStar Washington Hosp Ctr, Washington, DC USA. RP Baselga, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM jbaselga@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 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 APR 5 PY 2012 VL 366 IS 14 BP 1349 EP 1350 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 919QJ UT WOS:000302343000019 ER PT J AU Seabury, S Chandra, A Lakdawalla, D Jena, AB AF Seabury, Seth Chandra, Amitabh Lakdawalla, Darius Jena, Anupam B. TI Defense Costs of Medical Malpractice Claims SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Seabury, Seth] RAND, Santa Monica, CA USA. [Chandra, Amitabh] Harvard Univ, Cambridge, MA 02138 USA. [Lakdawalla, Darius] Univ So Calif, Los Angeles, CA USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Seabury, S (reprint author), RAND, Santa Monica, CA USA. EM jena.anupam@mgh.harvard.edu OI Lakdawalla, Darius/0000-0001-5934-8042 NR 3 TC 11 Z9 11 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 5 PY 2012 VL 366 IS 14 BP 1354 EP 1356 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 919QJ UT WOS:000302343000028 PM 22475613 ER PT J AU Oral, E Beckos, CG Muratoglu, OK AF Oral, Ebru Beckos, Christine Godleski Muratoglu, Orhun K. TI Homogenization in supercritical carbon dioxide enhances the diffusion of vitamin E in ultrahigh-molecular-weight polyethylene SO JOURNAL OF APPLIED POLYMER SCIENCE LA English DT Article DE crosslinking; implant; polyethylene (PE); polymer blends ID HAP-PAUL-AWARD; ALPHA-TOCOPHEROL; FREE-RADICALS; MECHANICAL-PROPERTIES; FATIGUE RESISTANCE; IRRADIATED UHMWPE; FLUID EXTRACTION; ACETABULAR CUPS; WEAR-RESISTANCE; CROSS-LINKING AB Vitamin E stabilization of radiation-crosslinked ultrahigh-molecular-weight polyethylene (UHMWPE) joint implants was successfully introduced to improve long-term oxidation resistance. Current clinically available vitamin E stabilized UHMWPE implants were prepared by the postirradiation diffusion of vitamin E into 100-kGy-irradiated UHMWPE by a two-step process, which included doping in pure vitamin E at an elevated temperature below the melting point followed by an annealing step at an elevated temperature in inert gas to homogenize the antioxidant throughout components of desired thickness. We hypothesized that the diffusion of vitamin E could be enhanced with supercritical carbon dioxide (SC-CO2) during homogenization without an increase in the surface vitamin E concentration, which would thus result in faster homogenization. Our hypothesis tested positive; crosslinked UHMWPE doped with vitamin E at 120 degrees C and homogenized in SC-CO2 at 10-12 MPa had a greater penetration of vitamin E than those homogenized in inert gas. We attributed the faster diffusion of vitamin E in irradiated UHMWPE in SC-CO2 to the dissolution of vitamin E in the supercritical fluid and a rate of diffusion that was closer to that of the supercritical fluid in the polymer. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012 C1 [Oral, Ebru; Beckos, Christine Godleski; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St,GRJ 1231, Boston, MA 02114 USA. EM omuratoglu@partners.org FU National Institutes of Health [AR051142]; Zimmer, Inc. FX Contract grant sponsor: National Institutes of Health; contract grant number: AR051142.; Contract grant sponsor: Zimmer, Inc. NR 39 TC 3 Z9 3 U1 1 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8995 J9 J APPL POLYM SCI JI J. Appl. Polym. Sci. PD APR 5 PY 2012 VL 124 IS 1 BP 518 EP 524 DI 10.1002/app.34882 PG 7 WC Polymer Science SC Polymer Science GA 869YW UT WOS:000298637300061 ER PT J AU O'Seaghdha, CM Hwang, SJ Vasan, RS Larson, MG Hoffmann, U Wang, TJ Fox, CS AF O'Seaghdha, Conall M. Hwang, Shih-Jen Vasan, Ramachandran S. Larson, Martin G. Hoffmann, Udo Wang, Thomas J. Fox, Caroline S. TI Correlation of renin angiotensin and aldosterone system activity with subcutaneous and visceral adiposity: the framingham heart study SO BMC ENDOCRINE DISORDERS LA English DT Article ID BODY-MASS INDEX; ESSENTIAL-HYPERTENSION; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; TISSUE COMPARTMENTS; SERUM ALDOSTERONE; RISK-FACTORS; OBESITY; ADULTS; DIET AB Background: Animal studies suggest that local adipocyte-mediated activity of the renin-angiotensin-aldosterone system (RAAS) contributes to circulating levels, and may promote the development of obesity-related hypertension in rodents. Methods: We examined relations of systemic RAAS activity, as assessed by circulating plasma renin activity (PRA), serum aldosterone level, and aldosterone: renin ratio (ARR), with specific regional adiposity measures in a large, community-based sample. Third Generation Framingham Heart Study participants underwent multidetector computed tomography assessment of SAT and VAT volumes during Exam 1 (2002 and 2005). PRA and serum aldosterone were measured after approximately 10 minutes of supine rest; results were log-transformed for analysis. Correlation coefficients between log-transformed RAAS measures and adiposity measurements were calculated, adjusted for age and sex. Partial correlations between log-transformed RAAS measures and adiposity measurements were also calculated, adjusted for standard CVD risk factors. Results: Overall, 992 women and 897 men were analyzed (mean age 40 years; 7% hypertension; 3% diabetes). No associations were observed with SAT (renin r = 0.04, p = 0.1; aldosterone r = -0.01, p = 0.6) or VAT (renin r = 0.03, p = 0.2; aldosterone r = -0.03, p = 0.2). Similar results were observed for ARR, in sex-stratified analyses, and for BMI and waist circumference. Non-significant partial correlations were also observed in models adjusted for standard cardiovascular risk factors. Conclusions: Regional adiposity measures were not associated with circulating measures of RAAS activity in this large population-based study. Further studies are required to determine whether adipocyte-derived RAAS components contribute to systemic RAAS activity in humans. C1 [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Vasan, Ramachandran S.; Larson, Martin G.; Wang, Thomas J.; Fox, Caroline S.] Nat Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA USA. [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [O'Seaghdha, Conall M.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [O'Seaghdha, Conall M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Fox, CS (reprint author), Nat Heart Lung & Blood Inst, Framingham Heart Study, 73 Mt Wayte Ave Suite 2, Framingham, MA USA. EM foxca@nhlbi.nih.gov OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; [R01-HL-086875] FX The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (N01-HC-25195). Dr. Wang is supported by R01-HL-086875. NR 42 TC 12 Z9 12 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6823 J9 BMC ENDOCR DISORD JI BMC Endocr. Disord. PD APR 4 PY 2012 VL 12 AR 3 DI 10.1186/1472-6823-12-3 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 943AN UT WOS:000304092900001 PM 22475205 ER PT J AU Ruan, GX Kazlauskas, A AF Ruan, Guo-Xiang Kazlauskas, Andrius TI Axl is essential for VEGF-A-dependent activation of PI3K/Akt SO EMBO JOURNAL LA English DT Article DE angiogenesis; Axl; PI3K; VEGF-A; VEGFR-2 ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; SRC-FAMILY KINASES; VASCULAR-PERMEABILITY; MACULAR DEGENERATION; SIGNAL-TRANSDUCTION; TUMOR ANGIOGENESIS; PDGF RECEPTOR; CELLS; CANCER AB Herein, we report that vascular endothelial growth factor A (VEGF-A) engages the PI3K/Akt pathway by a previously unknown mechanism that involves three tyrosine kinases. Upon VEGF-A-dependent activation of VEGF receptor-2 (VEGFR-2), and subsequent TSAd-mediated activation of Src family kinases (SFKs), SFKs engage the receptor tyrosine kinase Axl via its juxtamembrane domain to trigger ligand-independent autophosphorylation at a pair of YXXM motifs that promotes association with PI3K and activation of Akt. Other VEGF-A-mediated signalling pathways are independent of Axl. Interfering with Axl expression or function impairs VEGF-A- but not bFGF-dependent migration of endothelial cells. Similarly, Axl null mice respond poorly to VEGF-A-induced vascular permeability or angiogenesis, whereas other agonists induce a normal response. These results elucidate the mechanism by which VEGF-A activates PI3K/Akt, and identify previously unappreciated potential therapeutic targets of VEGF-A-driven processes. The EMBO Journal (2012) 31, 1692-1703. doi: 10.1038/emboj.2012.21; Published online 10 February 2012 C1 [Ruan, Guo-Xiang; Kazlauskas, Andrius] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. RP Kazlauskas, A (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst,Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA. EM ak@eri.harvard.edu FU Juvenile Diabetes Research Foundation (JDRF) [12008905, 32009560, 102011367]; NIH [EY016385] FX We would like to thank Drs Lena Claesson-Welsh and Xiujuan Li (Uppsala University, Sweden) for advice on TSAd experiments. We appreciate the suggestions and input from the following members of the Kazlauskas laboratory: Sarah Melissa P Jacob, Hetian Lei, Steven Pennock, Kevin Conway, Ruta Motiejunaite, Jorge Aranda, Eun Young Park and Magdalena Staniszewska. This work was supported by Juvenile Diabetes Research Foundation (JDRF) grant 12008905 (to AK), NIH grant EY016385 (to AK), JDRF postdoctoral fellowship 32009560 (to GXR) and JDRF advanced postdoctoral fellowship 102011367 (to GXR). NR 54 TC 52 Z9 55 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD APR 4 PY 2012 VL 31 IS 7 BP 1692 EP 1703 DI 10.1038/emboj.2012.21 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 923RJ UT WOS:000302636100009 PM 22327215 ER PT J AU Hrkach, J Von Hoff, D Ali, MM Andrianova, E Auer, J Campbell, T De Witt, D Figa, M Figueiredo, M Horhota, A Low, S McDonnell, K Peeke, E Retnarajan, B Sabnis, A Schnipper, E Song, JJ Song, YH Summa, J Tompsett, D Troiano, G Hoven, TV Wright, J LoRusso, P Kantoff, PW Bander, NH Sweeney, C Farokhzad, OC Langer, R Zale, S AF Hrkach, Jeffrey Von Hoff, Daniel Ali, Mir Mukkaram Andrianova, Elizaveta Auer, Jason Campbell, Tarikh De Witt, David Figa, Michael Figueiredo, Maria Horhota, Allen Low, Susan McDonnell, Kevin Peeke, Erick Retnarajan, Beadle Sabnis, Abhimanyu Schnipper, Edward Song, Jeffrey J. Song, Young Ho Summa, Jason Tompsett, Douglas Troiano, Greg Hoven, Tina Van Geen Wright, Jim LoRusso, Patricia Kantoff, Philip W. Bander, Neil H. Sweeney, Christopher Farokhzad, Omid C. Langer, Robert Zale, Stephen TI Preclinical Development and Clinical Translation of a PSMA-Targeted Docetaxel Nanoparticle with a Differentiated Pharmacological Profile SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID POLYMER HYBRID NANOPARTICLES; LIPID-LIKE MATERIALS; DRUG-DELIVERY; MEMBRANE ANTIGEN; CANCER-THERAPY; IN-VIVO; PEG NANOPARTICLES; PROSTATE-CANCER; SOLID TUMORS; SURFACE AB We describe the development and clinical translation of a targeted polymeric nanoparticle (TNP) containing the chemotherapeutic docetaxel (DTXL) for the treatment of patients with solid tumors. DTXL-TNP is targeted to prostate-specific membrane antigen, a clinically validated tumor antigen expressed on prostate cancer cells and on the neovasculature of most nonprostate solid tumors. DTXL-TNP was developed from a combinatorial library of more than 100 TNP formulations varying with respect to particle size, targeting ligand density, surface hydrophilicity, drug loading, and drug release properties. Pharmacokinetic and tissue distribution studies in rats showed that the NPs had a blood circulation half-life of about 20 hours and minimal liver accumulation. In tumor-bearing mice, DTXL-TNP exhibited markedly enhanced tumor accumulation at 12 hours and prolonged tumor growth suppression compared to a solvent-based DTXL formulation (sb-DTXL). In tumor-bearing mice, rats, and nonhuman primates, DTXL-TNP displayed pharmacokinetic characteristics consistent with prolonged circulation of NPs in the vascular compartment and controlled release of DTXL, with total DTXL plasma concentrations remaining at least 100-fold higher than sb-DTXL for more than 24 hours. Finally, initial clinical data in patients with advanced solid tumors indicated that DTXL-TNP displays a pharmacological profile differentiated from sb-DTXL, including pharmacokinetics characteristics consistent with preclinical data and cases of tumor shrinkage at doses below the sb-DTXL dose typically used in the clinic. C1 [Farokhzad, Omid C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Nanomed & Biomat, Boston, MA 02115 USA. [Farokhzad, Omid C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol, Boston, MA 02115 USA. [Hrkach, Jeffrey; Ali, Mir Mukkaram; Andrianova, Elizaveta; Auer, Jason; Campbell, Tarikh; De Witt, David; Figa, Michael; Figueiredo, Maria; Horhota, Allen; Low, Susan; McDonnell, Kevin; Peeke, Erick; Retnarajan, Beadle; Sabnis, Abhimanyu; Schnipper, Edward; Song, Jeffrey J.; Song, Young Ho; Summa, Jason; Tompsett, Douglas; Troiano, Greg; Hoven, Tina Van Geen; Wright, Jim; Zale, Stephen] BIND Biosci Inc, Cambridge, MA 02139 USA. [Von Hoff, Daniel] Scottsdale Healthcare, TGen Clin Res Serv, Phoenix, AZ 85004 USA. [LoRusso, Patricia] Karmanos Canc Inst, Detroit, MI 48201 USA. [Kantoff, Philip W.; Sweeney, Christopher] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02215 USA. [Bander, Neil H.] Weill Cornell Med Coll, New York, NY 10065 USA. [Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Farokhzad, OC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Nanomed & Biomat, Boston, MA 02115 USA. EM ofarokhzad@zeus.bwh.harvard.edu; rlanger@mit.edu; szale@bindbio.com FU NCI [HHSN261200700060C]; National Institute of Standards and Technology [70NANB7H7021] FX BIND received funding from NCI Small Business Innovation Research Contract No. HHSN261200700060C and National Institute of Standards and Technology Advanced Technology Program Award No. 70NANB7H7021. NR 49 TC 274 Z9 275 U1 29 U2 223 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 4 PY 2012 VL 4 IS 128 AR 128ra39 DI 10.1126/scitranslmed.3003651 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 925AP UT WOS:000302732700002 PM 22491949 ER PT J AU Baron, R Saito, H Gori, F AF Baron, Roland Saito, Hiroaki Gori, Francesca TI Bone Cells Crosstalk: Noncanonical Roring in the Wnt SO CELL METABOLISM LA English DT Editorial Material ID ACTIVATION AB It is well established that canonical Wnt signaling in bone regulates bone mass. Much less is known about the role of noncanonical Wnt signaling. Maeda and colleagues now report in Nature Medicine that Wnt5a-Ror2 crosstalk between bone cells enhances bone resorption, thereby negatively regulating skeletal homeostasis (Maeda et al., 2012). C1 [Baron, Roland; Saito, Hiroaki; Gori, Francesca] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Baron, Roland; Gori, Francesca] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Baron, Roland; Saito, Hiroaki; Gori, Francesca] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Baron, R (reprint author), Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. EM roland_baron@hsdm.harvard.edu NR 9 TC 3 Z9 4 U1 0 U2 4 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 APR 4 PY 2012 VL 15 IS 4 BP 415 EP 417 DI 10.1016/j.cmet.2012.03.014 PG 3 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 922CC UT WOS:000302523400002 PM 22482722 ER PT J AU Zarse, K Schmeisser, S Groth, M Priebe, S Beuster, G Kuhlow, D Guthke, R Platzer, M Kahn, CR Ristow, M AF Zarse, Kim Schmeisser, Sebastian Groth, Marco Priebe, Steffen Beuster, Gregor Kuhlow, Doreen Guthke, Reinhard Platzer, Matthias Kahn, C. Ronald Ristow, Michael TI Impaired Insulin/IGF1 Signaling Extends Life Span by Promoting Mitochondrial L-Proline Catabolism to Induce a Transient ROS Signal SO CELL METABOLISM LA English DT Article ID DIFFERENTIAL EXPRESSION ANALYSIS; AGING CAENORHABDITIS-ELEGANS; OXIDATIVE STRESS; DIETARY RESTRICTION; GENE-EXPRESSION; C-ELEGANS; SACCHAROMYCES-CEREVISIAE; CALORIC RESTRICTION; HYDROGEN-PEROXIDE; FACTOR SKN-1 AB Impaired insulin and IGF-1 signaling (illS) in C. elegans daf-2 mutants extends life span more than 2-fold. Constitutively, illS increases mitochondrial activity and reduces reactive oxygen species (ROS) levels. By contrast, acute impairment of daf-2 in adult C. elegans reduces glucose uptake and transiently increases ROS. Consistent with the concept of mitohormesis, this ROS signal causes an adaptive response by inducing ROS defense enzymes (SOD, catalase), culminating in ultimately reduced ROS levels despite increased mitochondrial activity. Inhibition of this ROS signal by antioxidants reduces illS-mediated longevity by up to 60%. Induction of the ROS signal requires AAK-2 (AMPK), while PMK-1 (p38) and SKN-1 (NRF-2) are needed for the retrograde response. IIIS upregulates mitochondrial L-proline catabolism, and impairment of the latter impairs the life span-extending capacity of illS while L-proline supplementation extends C. elegans life span. Taken together, illS promotes L-proline metabolism to generate a ROS signal for the adaptive induction of endogenous stress defense to extend life span. C1 [Zarse, Kim; Schmeisser, Sebastian; Beuster, Gregor; Kuhlow, Doreen; Ristow, Michael] Univ Jena, Inst Nutr, Dept Human Nutr, D-07743 Jena, Germany. [Zarse, Kim; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02215 USA. [Schmeisser, Sebastian] Fritz Lipmann Inst, Leibniz Inst Age Res, Leibniz Grad Sch Aging, D-07745 Jena, Germany. [Groth, Marco; Platzer, Matthias] Fritz Lipmann Inst, Leibniz Inst Age Res, Genome Anal Grp, D-07745 Jena, Germany. [Priebe, Steffen; Guthke, Reinhard] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Syst Biol & Bioinformat Grp, D-07745 Jena, Germany. [Kuhlow, Doreen; Ristow, Michael] German Inst Human Nutr Potsdam Rehbrucke, Dept Clin Nutr, D-14558 Nuthetal, Germany. RP Ristow, M (reprint author), Univ Jena, Inst Nutr, Dept Human Nutr, D-07743 Jena, Germany. EM mristow@mristow.org RI Ristow, Michael/O-9858-2014; Zarse, Kim/D-2133-2016 OI Ristow, Michael/0000-0003-2109-2453; Zarse, Kim/0000-0003-2542-6123 FU National Institutes of Health (NIH) [DK31036, DK33201]; National Center for Research Resources (NCRR); German Ministry for Education and Research (Bundesministerium fur Bildung und Forschung) [BMBF 0315581] FX C. elegans strains used in this work were provided by the Caenorhabditis Genetics Center (University of Minnesota), which is funded by the National Institutes of Health (NIH) National Center for Research Resources (NCRR). The authors thank Cynthia Kenyon for the RNAi construct against daf-2 (Dillin et al., 2002). The excellent technical assistance of Ivonne Heinze, Beate Laube, Annett Muller, and Waltraud Scheiding, as well as the excellent secretarial assistance of Mandy Schalowski, is gratefully acknowledged. This work is part of the research program of the Jena Centre for Systems Biology of Ageing (JenAge) funded by the German Ministry for Education and Research (Bundesministerium fur Bildung und Forschung; support code BMBF 0315581), and has been additionally funded by NIH grants DK31036 and DK33201 to C.R.K. Funding for this project was denied by the German Research Association (Deutsche Forschungsgemeinschaft, DFG), grant application number RI 1976/3-1. NR 73 TC 144 Z9 152 U1 5 U2 41 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD APR 4 PY 2012 VL 15 IS 4 BP 451 EP 465 DI 10.1016/j.cmet.2012.02.013 PG 15 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 922CC UT WOS:000302523400008 PM 22482728 ER PT J AU Blattler, SM Cunningham, JT Verdeguer, F Chim, H Haas, W Liu, HF Romanino, K Ruegg, MA Gygi, SP Shi, Y Puigserver, P AF Blaettler, Sharon M. Cunningham, John T. Verdeguer, Francisco Chim, Helen Haas, Wilhelm Liu, Huifei Romanino, Klaas Rueegg, Markus A. Gygi, Steven P. Shi, Yang Puigserver, Pere TI Yin Yang 1 Deficiency in Skeletal Muscle Protects against Rapamycin-Induced Diabetic-like Symptoms through Activation of Insulin/IGF Signaling SO CELL METABOLISM LA English DT Article ID MTOR COMPLEX 1; CELL-GROWTH; LIFE-SPAN; LIPID-METABOLISM; ADIPOSE-TISSUE; MICE LACKING; CANCER; DOWNSTREAM; RESISTANCE; MELLITUS AB Rapamycin and its derivatives are mTOR inhibitors used in tissue transplantation and cancer therapy. A percentage of patients treated with these inhibitors develop diabetic-like symptoms, but the molecular mechanisms are unknown. We show here that chronic rapamycin treatment in mice led to insulin resistance with suppression of insulin/IGF signaling and genes associated within this pathway, such as Igf1-2, Irs1-2, and Akt1-3. Importantly, skeletal muscle-specific YY1 knockout mice were protected from rapamycin-induced diabetic-like symptoms. This protection was caused by hyperactivation of insulin/IGF signaling with increased gene expression in this cascade that, in contrast to wild-type mice, was not suppressed by rapamycin. Mechanistically, rapamycin induced YY1 dephosphorylation and recruitment to promoters of insulin/IGF genes, which promoted interaction with the polycomb protein-2 corepressor. This was associated with H3K27 trimethylation leading to decreased gene expression and insulin signaling. These results have implications for rapamycin action in human diseases and biological processes such as longevity. C1 [Blaettler, Sharon M.; Cunningham, John T.; Verdeguer, Francisco; Chim, Helen; Puigserver, Pere] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Blaettler, Sharon M.; Cunningham, John T.; Verdeguer, Francisco; Chim, Helen; Haas, Wilhelm; Liu, Huifei; Gygi, Steven P.; Shi, Yang; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. [Romanino, Klaas; Rueegg, Markus A.] Univ Basel, Biozentrum, Dept Neurobiol, CH-4056 Basel, Switzerland. RP Puigserver, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. EM pere_puigserver@dfci.harvard.edu OI Cunningham, John/0000-0001-6490-4533 FU Swiss National Science Foundation; NIH/NIDDK [RO1 DK081418]; Muscular Dystrophy Association [MDA202237] FX We would like to thank members of the Puigserver lab for advice and fruitful discussions, Christine Chin for technical assistance, Benjamin Szlyk for assistance in the creation of the figures, Eric Olson for the myogenin CRE mice, Markus Schubert for the IRS2-driven luciferase construct, Nathanael Gray for Torin 2, and Owen McGuinness for interpretation of the clamp experiments. These studies were supported by a postdoctoral fellowship from the Swiss National Science Foundation (S.M.B.) and by the NIH/NIDDK RO1 DK081418 grant and Muscular Dystrophy Association MDA202237 (P.P.). NR 57 TC 43 Z9 44 U1 0 U2 3 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 APR 4 PY 2012 VL 15 IS 4 BP 505 EP 517 DI 10.1016/j.cmet.2012.03.008 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 922CC UT WOS:000302523400012 PM 22482732 ER PT J AU Loewenstein, G Volpp, KG Asch, DA AF Loewenstein, George Volpp, Kevin G. Asch, David A. TI Incentives in Health Different Prescriptions for Physicians and Patients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Loewenstein, George] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Loewenstein, George; Volpp, Kevin G.; Asch, David A.] Univ Penn, Penn CMU Roybal Ctr Behav Econ & Hlth P30, Philadelphia, PA 19104 USA. [Loewenstein, George; Volpp, Kevin G.; Asch, David A.] Univ Penn, Leonard Davis Inst Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Asch, David A.] Univ Penn, Dept Med, Wharton Sch, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Asch, David A.] Univ Penn, Dept Hlth Care Management, Wharton Sch, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Asch, David A.] Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. [Volpp, Kevin G.; Asch, David A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Loewenstein, G (reprint author), Carnegie Mellon Univ, 5000 Forbes Ave,BP 319D, Pittsburgh, PA 15213 USA. EM gl20@andrew.cmu.edu OI Asch, David/0000-0002-7970-286X FU NIA NIH HHS [P30 AG034546] NR 10 TC 10 Z9 10 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 4 PY 2012 VL 307 IS 13 BP 1375 EP 1376 DI 10.1001/jama.2012.387 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 919AY UT WOS:000302294200021 PM 22474198 ER PT J AU Sauer, AJ Newton-Cheh, C AF Sauer, Andrew J. Newton-Cheh, Christopher TI Clinical and Genetic Determinants of Torsade de Pointes Risk SO CIRCULATION LA English DT Review DE death, sudden; genetics; genome-wide association studies; long QT syndrome; torsades de pointes ID LONG-QT SYNDROME; SUDDEN CARDIAC DEATH; VENTRICULAR SYSTOLIC DYSFUNCTION; POTENTIAL DURATION PROLONGATION; REDUCES TRANSMURAL DISPERSION; ELECTROCARDIOGRAPHIC T-WAVE; ACUTE MYOCARDIAL-INFARCTION; FEMALE RABBIT HEART; INTERVAL DURATION; END INTERVAL C1 [Newton-Cheh, Christopher] Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res,Sch Med, Boston, MA 02114 USA. [Sauer, Andrew J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. RP Newton-Cheh, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res,Sch Med, 185 Cambridge St,CPZN 5-242, Boston, MA 02114 USA. EM cnewtoncheh@chgr.mgh.harvard.edu OI Sauer, Andrew/0000-0002-9268-2795 FU National Institutes of Health [HL080025, HL098283]; Doris Duke Charitable Foundation; Burroughs Wellcome Fund FX Dr Newton-Cheh was supported by the National Institutes of Health (HL080025, HL098283), the Doris Duke Charitable Foundation, and the Burroughs Wellcome Fund. NR 119 TC 31 Z9 32 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 APR 3 PY 2012 VL 125 IS 13 BP 1684 EP 1694 DI 10.1161/CIRCULATIONAHA.111.080887 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 922OS UT WOS:000302557900019 PM 22474311 ER PT J AU Werner, RM AF Werner, Rachel M. TI Will Using Medicare Data to Rate Doctors Benefit Patients? SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID PAY-FOR-PERFORMANCE; REPORT CARDS; QUALITY C1 [Werner, Rachel M.] Univ Penn, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Werner, RM (reprint author), Univ Penn, 1230 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rwerner@upenn.edu NR 16 TC 4 Z9 4 U1 1 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 3 PY 2012 VL 156 IS 7 BP 532 EP U1500 DI 10.7326/0003-4819-156-7-201204030-00396 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 921GP UT WOS:000302466400007 PM 22331620 ER PT J AU Frelinger, AL Lee, RD Mulford, DJ Wu, JT Nudurupati, S Nigam, A Brooks, JK Bhatt, DL Michelson, AD AF Frelinger, Andrew L., III Lee, Ronald D. Mulford, Darcy J. Wu, Jingtao Nudurupati, Sai Nigam, Anu Brooks, Julie K. Bhatt, Deepak L. Michelson, Alan D. TI A Randomized, 2-Period, Crossover Design Study to Assess the Effects of Dexlansoprazole, Lansoprazole, Esomeprazole, and Omeprazole on the Steady-State Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Volunteers SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE clopidogrel; drug-drug interaction; pharmacology; platelets; proton pump inhibitor; thrombosis ID CONSENSUS AB Objectives The aim of this study was to assess the effects of different proton pump inhibitors (PPIs) on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel. Background Metabolism of clopidogrel requires cytochrome P450s (CYPs), including CYP2C19. However, PPIs may inhibit CYP2C19, potentially reducing the effectiveness of clopidogrel. Methods A randomized, open-label, 2-period, crossover study of healthy subjects (n = 160, age 18 to 55 years, homozygous for CYP2C19 extensive metabolizer genotype, confined, standardized diet) was conducted. Clopidogrel 75 mg with or without a PPI (dexlansoprazole 60 mg, lansoprazole 30 mg, esomeprazole 40 mg, or, as a positive control to maximize potential interaction and demonstrate assay sensitivity, omeprazole 80 mg) was given daily for 9 days. Pharmacokinetics and pharmacodynamics were assessed on days 9 and 10. Pharmacodynamic end-points were vasodilator-stimulated phosphoprotein P2Y(12) platelet reactivity index, maximal platelet aggregation to 5 and 20 mu mol/l adenosine diphosphate, and VerifyNow P2Y(12) platelet response units. Results Pharmacokinetic and pharmacodynamic responses with omeprazole demonstrated assay sensitivity. The area under the curve for clopidogrel active metabolite decreased significantly with esomeprazole but not with dexlansoprazole or lansoprazole. Similarly, esomeprazole but not dexlansoprazole or lansoprazole significantly reduced the effect of clopidogrel on vasodilator-stimulated phosphoprotein platelet reactivity index. All PPIs decreased the peak plasma concentration of clopidogrel active metabolite (omeprazole > esomeprazole > lansoprazole > dexlansoprazole) and showed a corresponding order of potency for effects on maximal platelet aggregation and platelet response units. Conclusions Generation of clopidogrel active metabolite and inhibition of platelet function were reduced less by the coadministration of dexlansoprazole or lansoprazole with clopidogrel than by the coadministration of esomeprazole or omeprazole. These results suggest that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of dexlansoprazole or lansoprazole rather than esomeprazole or omeprazole. (A Study of the Effects of Multiple Doses of Dexlansoprazole, Lansoprazole, Omeprazole or Esomeprazole on the Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Participants; NCT00942175) (J Am Coll Cardiol 2012;59:1304-11) (C) 2012 by the American College of Cardiology Foundation C1 [Frelinger, Andrew L., III; Nigam, Anu; Brooks, Julie K.; Michelson, Alan D.] Harvard Univ, Childrens Hosp Boston, Dana Farber Canc Inst, Sch Med,Div Hematol Oncol,Ctr Platelet Res Studie, Boston, MA 02115 USA. [Lee, Ronald D.; Mulford, Darcy J.; Wu, Jingtao; Nudurupati, Sai] Takeda Global Res & Dev Ctr Inc, Deerfield, IL USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Frelinger, AL (reprint author), Harvard Univ, Childrens Hosp Boston, Dana Farber Canc Inst, Sch Med,Div Hematol Oncol,Ctr Platelet Res Studie, Karp 07212,300 Longwood Ave, Boston, MA 02115 USA. EM andrew.frelinger@childrens.harvard.edu FU Takeda Global Research & Development Center, Inc.; Takeda Global Research & Development Center; Arena Pharmaceuticals; GLSynthesis; Eli Lilly/Daiichi Sankyo; Sanofi Aventis/Bristol-Myers Squibb; Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; Medicines Company FX This study was sponsored by Takeda Global Research & Development Center, Inc. In addition, this study was funded in part by a research grant from Takeda Global Research & Development Center to Children's Hospital Boston (Alan D. Michelson, principal investigator). Drs. Frelinger and Michelson have been principal investigators or co-investigators on research grants to the University of Massachusetts Medical School, Children's Hospital Boston, or both from Arena Pharmaceuticals, GLSynthesis, Eli Lilly/Daiichi Sankyo, and Sanofi Aventis/Bristol-Myers Squibb; and have been consultants to Eli Lilly/Daiichi Sankyo and PLx Pharma. Drs. Lee, Mulford, Wu, and Nudurupati are employees of Takeda Global Research & Development Center, Inc. Dr. Bhatt has received honoraria from WebMD; research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company; and is a research collaborator with PLx Pharma and Takeda and served as the Chair of the COGENT trial. Dr. Michelson has been a member of the data safety monitoring boards of clinical trials sponsored by Eli Lilly/Daiichi Sankyo and Sanofi Aventis/Bristol-Myers Squibb. All other authors have reported that they have no relationship relevant to the contents of this paper to disclose. NR 5 TC 56 Z9 61 U1 0 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 3 PY 2012 VL 59 IS 14 BP 1304 EP 1311 DI 10.1016/j.jacc.2011.12.024 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916ZD UT WOS:000302140800008 PM 22464259 ER PT J AU Cohen-Adad, J Polimeni, JR Helmer, KG Benner, T McNab, JA Wald, LL Rosen, BR Mainero, C AF Cohen-Adad, J. Polimeni, J. R. Helmer, K. G. Benner, T. McNab, J. A. Wald, L. L. Rosen, B. R. Mainero, C. TI T-2* mapping and B-o orientation-dependence at 7 T reveal cyto- and myeloarchitecture organization of the human cortex SO NEUROIMAGE LA English DT Article DE Ultra-high field MRI; Cytoarchitecture; Myeloarchitecture; T-2*; Susceptibility ID HUMAN CEREBRAL-CORTEX; HUMAN AUDITORY-CORTEX; MAGNETIC-RESONANCE IMAGES; HIGH-RESOLUTION MRI; IN-VIVO; HUMAN BRAIN; MULTIPLE-SCLEROSIS; LECITHIN MEMBRANES; FIBER ORIENTATION; SIGNAL INTENSITY AB Ultra-high field MRI (>= 7 T) has recently shown great sensitivity to depict patterns of tissue microarchitecture. Moreover, recent studies have demonstrated a dependency between T-2* and orientation of white matter fibers with respect to the main magnetic field B-o. In this study we probed the potential of T-2* mapping at 7 T to provide new markers of cortical architecture. We acquired multi-echo measurements at 7 T and mapped T-2* over the entire cortex of eight healthy individuals using surface-based analysis. B-o dependence was tested by computing the angle theta(z) between the normal of the surface and the direction of B-o, then fitting T-2* (theta(z)) using model from the literature. Average T-2* in the cortex was 32.20 +/- 1.35 ms. Patterns of lower T-2* were detected in the sensorimotor, visual and auditory cortices, likely reflecting higher myelin content. Significantly lower T-2* was detected in the left hemisphere of the auditory region (p<0.005), suggesting higher myelin content, in accordance with previous investigations. B-o orientation dependence was detected in some areas of the cortex, the strongest being in the primary motor cortex (Delta R-2* = 4.10 Hz). This study demonstrates that quantitative T-2* measures at 7 T MRI can reveal patterns of cytoarchitectural organization of the human cortex in vivo and that B-o orientation dependence can probe the coherency and orientation of gray matter fibers in the cortex, shedding light into the potential use of this type of contrast to characterize cyto-/myeloarchitecture and to understand the pathophysiology of diseases associated with changes in iron and/or myelin concentration. (c) 2012 Elsevier Inc. All rights reserved. C1 [Cohen-Adad, J.; Polimeni, J. R.; Helmer, K. G.; Benner, T.; McNab, J. A.; Wald, L. L.; Rosen, B. R.; Mainero, C.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Cohen-Adad, J.; Polimeni, J. R.; Helmer, K. G.; Benner, T.; McNab, J. A.; Wald, L. L.; Rosen, B. R.; Mainero, C.] Harvard Univ, Sch Med, Boston, MA USA. [Wald, L. L.] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Cohen-Adad, J (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Bldg 149,13th St, Charlestown, MA 02129 USA. EM jcohen@nmr.mgh.harvard.edu RI Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009 OI Polimeni, Jonathan/0000-0002-1348-1179; FU National Multiple Sclerosis Society [FG 1892A1/1, 4281-RG-A-1]; National Center for Research Resources [P41-RR14075]; NCRR BIRN Morphometric [BIRN002, U24 RR021382]; NIH [U01MH093765] FX We thank Drs. Doug Greve, Bruce Fischl and Kawin Setsompop for helpful discussions and Dr. Boris Keil for helping with the 7 T coil. This work was supported by the National Multiple Sclerosis Society [FG 1892A1/1 to J.C-A], [Grant 4281-RG-A-1 to C.M.]. by the National Center for Research Resources [P41-RR14075, and the NCRR BIRN Morphometric, Project BIRN002, U24 RR021382] and by the NIH [Human Connectome Project, U01MH093765]. NR 85 TC 45 Z9 45 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 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD APR 2 PY 2012 VL 60 IS 2 BP 1006 EP 1014 DI 10.1016/j.neuroimage.2012.01.053 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 932ED UT WOS:000303272300018 PM 22270354 ER PT J AU Entis, JJ Doerga, P Barrett, LF Dickerson, BC AF Entis, Jonathan J. Doerga, Priya Barrett, Lisa Feldman Dickerson, Bradford C. TI A reliable protocol for the manual segmentation of the human amygdala and its subregions using ultra-high resolution MRI SO NEUROIMAGE LA English DT Article DE Amygdala; Segmentation; MRI; Subnuclei; Parcellation ID HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; CENTRAL NUCLEUS; FACIAL EXPRESSIONS; IN-VIVO; AUTOMATED SEGMENTATION; CORTICAL SURFACE; HIPPOCAMPAL-FORMATION; VOLUME MEASUREMENTS; COORDINATE SYSTEM AB The measurement of the volume of the human amygdala in vivo has received increasing attention over the past decade, but existing methods face several challenges. First, due to the amorphous appearance of the amygdala and the difficulties in interpreting its boundaries, it is common for protocols to omit sizable sections of the rostral and dorsal regions of the amygdala comprising parts of the basolateral complex (BL) and central nucleus (Ce), respectively. Second, segmentation of the amgydaloid complex into separate subdivisions is challenging due to the resolution of routinely acquired images and the lack of standard protocols. Recent advances in technology have made ultra-high resolution MR images available, and in this study we provide a detailed segmentation protocol for manually tracing the whole amygdala that incorporates a greater portion of the rostral and dorsal sections with techniques illustrated in detail to maximize reproducibility. In addition, we propose a geometrically-based protocol for segmenting the amygdala into four component subregions of interest (sROI), which correspond largely to amygdala subnuclear divisions: the BL sROI, centromedial (CM) sROI, basomedial (BM) sROI, and the amygdaloid cortical (ACo) sROI. We performed an intra- and inter-rater reliability study of our methods in 10 adults (5 young adults and 5 older adults). The results indicate that both protocols can be implemented with a high degree of reliability (the majority of intra-rater and inter-rater correlations were >0.81). This protocol should aid further research into the alterations in amygdala anatomy, connectivity, and function that accompany normal aging and pathology associated with neuropsychiatric disorders. (c) 2012 Elsevier Inc. All rights reserved. C1 [Entis, Jonathan J.] Boston Coll, Dept Psychol, Chestnut Hill, MA 02167 USA. [Dickerson, Bradford C.] Massachusetts Alzheimers Dis Res Ctr, Frontotemporal Disorders Unit, Charlestown, MA USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA. [Barrett, Lisa Feldman; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Doerga, Priya] Vrije Univ Amsterdam, Dept Anat & Neurosci, Amsterdam, Netherlands. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Dickerson, BC (reprint author), 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM entisj@mail.bc.edu; p.n.doerga@student.vu.n1; l.barrett@neu.edu; bradd@nmr.mgh.harvard.edu FU National Institute on Aging [R01 AG029840, AG030311]; Alzheimer's Association; National Institutes of Health [DP1OD003312] FX This work was supported by grants from the National Institute on Aging (R01 AG029840) and the Alzheimer's Association to Dr. Brad Dickerson and from the National Institutes of Health Director's Pioneer Award (DP1OD003312) and a National Institute on Aging grant (AG030311) to Lisa Feldman Barrett. The authors thank Michael Brickhouse for excellent technical assistance. NR 81 TC 24 Z9 24 U1 3 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 2 PY 2012 VL 60 IS 2 BP 1226 EP 1235 DI 10.1016/j.neuroimage.2011.12.073 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 932ED UT WOS:000303272300039 PM 22245260 ER PT J AU Thompson, B Villeneuve, MY Casanova, C Hess, RF AF Thompson, B. Villeneuve, M. Y. Casanova, C. Hess, R. F. TI Abnormal cortical processing of pattern motion in amblyopia: Evidence from fMRI SO NEUROIMAGE LA English DT Article DE Amblyopia; Motion; MT; V5; Plaid; Dorsal Stream ID VISUAL AREA MT; PERCEPTION FOLLOWING LESIONS; SUPERIOR TEMPORAL SULCUS; PURSUIT EYE-MOVEMENTS; GLOBAL MOTION; STRABISMIC AMBLYOPIA; OPTIC FLOW; BINOCULAR INTERACTION; EXTRASTRIATE CORTEX; RECEPTIVE-FIELDS AB Converging evidence from human psychophysics and animal neurophysiology indicates that amblyopia is associated with abnormal function of area MT, a motion sensitive region of the extrastriate visual cortex. In this context, the recent finding that amblyopic eyes mediate normal perception of dynamic plaid stimuli was surprising, as neural processing and perception of plaids has been closely linked to MT function. One intriguing potential explanation for this discrepancy is that the amblyopic eye recruits alternative visual brain areas to support plaid perception. This is the hypothesis that we tested. We used functional magnetic resonance imaging (fMRI) to measure the response of the amblyopic visual cortex and thalamus to incoherent and coherent motion of plaid stimuli that were perceived normally by the amblyopic eye. We found a different pattern of responses within the visual cortex when plaids were viewed by amblyopic as opposed to non-amblyopic eyes. The non-amblyopic eyes of amblyopes and control eyes differentially activated the hMT + complex when viewing incoherent vs. coherent plaid motion, consistent with the notion that this region is centrally involved in plaid perception. However, for amblyopic eye viewing, hMT + activation did not vary reliably with motion type. In a sub-set of our participants with amblyopia we were able to localize MT and MST within the larger hMT + complex and found a lack of plaid motion selectivity in both sub-regions. The response of the pulvinar and ventral V3 to plaid stimuli also differed under amblyopic vs. non-amblyopic eye viewing conditions, however the response of these areas did vary according to motion type. These results indicate that while the perception of the plaid stimuli was constant for both amblyopic and non-amblyopic viewing, the network of neural areas that supported this perception was different. (c) 2012 Elsevier Inc. All rights reserved. C1 [Thompson, B.] Univ Auckland, Dept Optometry & Vis Sci, Auckland 1142, New Zealand. [Thompson, B.; Hess, R. F.] McGill Univ, Royal Victoria Hosp, Dept Ophthalmol, McGill Vis Res, Montreal, PQ H3A 1A1, Canada. [Villeneuve, M. Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Martinos Ctr, Boston, MA USA. [Villeneuve, M. Y.] McGill Univ, Montreal Neurol Inst, Dept Neurol, Montreal, PQ H3A 2B4, Canada. [Villeneuve, M. Y.] McGill Univ, Montreal Neurol Inst, Dept Neurosurg, Montreal, PQ H3A 2B4, Canada. [Casanova, C.] Univ Montreal, Ecole Optometrie, Lab Nurosci Vis, Montreal, PQ H3C 3J7, Canada. RP Thompson, B (reprint author), Univ Auckland, Dept Optometry & Vis Sci, Private Bag 92019, Auckland 1142, New Zealand. EM b.thompson@auckland.ac.nz RI Hess, Robert/A-5624-2008 FU CIHR [MOP-14825, MOP-53346]; FRSQ FX This work was supported by the CIHR grants MOP-14825 to CC and MOP-53346 to RFH and a FRSQ reseau en sante de la vision grant to CC and RFH. NR 73 TC 21 Z9 21 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 2 PY 2012 VL 60 IS 2 BP 1307 EP 1315 DI 10.1016/j.neuroimage.2012.01.078 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 932ED UT WOS:000303272300046 PM 22285220 ER PT J AU Brown, TI Ross, RS Tobyne, SM Stern, CE AF Brown, Thackery I. Ross, Robert S. Tobyne, Sean M. Stern, Chantal E. TI Cooperative interactions between hippocampal and striatal systems support flexible navigation SO NEUROIMAGE LA English DT Article DE fMRI; Memory; Hippocampus; Caudate; Human; Disambiguation ID MEDIAL TEMPORAL-LOBE; MONKEY ORBITOFRONTAL CORTEX; STOP-SIGNAL TASK; PREFRONTAL CORTEX; BASAL-GANGLIA; CAUDATE-NUCLEUS; OVERLAPPING SEQUENCES; RESPONSE-INHIBITION; EPISODIC MEMORY; WORKING-MEMORY AB Research in animals and humans has demonstrated that the hippocampus is critical for retrieving distinct representations of overlapping sequences of information. There is recent evidence that the caudate nucleus and orbitofrontal cortex are also involved in disambiguation of overlapping spatial representations. The hippocampus and caudate are functionally distinct regions, but both have anatomical links with the orbitofrontal cortex. The present study used an fMRI-based functional connectivity analysis in humans to examine the functional relationship between the hippocampus, caudate, and orbitofrontal cortex when participants use contextual information to navigate well-learned spatial routes which share common elements. Participants were trained outside the scanner to navigate virtual mazes from a first-person perspective. Overlapping condition mazes began and ended at distinct locations, but converged in the middle to share some hallways with another maze. Non-overlapping condition mazes did not share any hallways with any other maze. Successful navigation through the overlapping hallways required contextual information identifying the current navigational route to guide the appropriate response for a given trial. Results revealed greater functional connectivity between the hippocampus, caudate, and orbitofrontal cortex for overlapping mazes compared to non-overlapping mazes. The current findings suggest that the hippocampus and caudate interact with prefrontal structures cooperatively for successful contextually dependent navigation. (c) 2012 Elsevier Inc. All rights reserved. C1 [Brown, Thackery I.; Ross, Robert S.; Tobyne, Sean M.; Stern, Chantal E.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Brown, Thackery I.; Ross, Robert S.; Tobyne, Sean M.; Stern, Chantal E.] Boston Univ, Silvio O Conte Ctr Memory & Brain, Boston, MA 02215 USA. [Brown, Thackery I.; Ross, Robert S.; Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Stern, CE (reprint author), Ctr Memory & Brain, 2 Cummington St, Boston, MA 02215 USA. EM chantal@bu.edu OI Ross, Robert/0000-0002-3987-881X; Tobyne, Sean/0000-0001-5985-7920 FU National Institutes of Health [P50 MH071702, P50 MH094263]; Office of Naval Research Multidisciplinary University Research Initiative [ONR MURI N00014-10-1-0936]; National Center for Research Resources [P41RR14075] FX This work was supported by the National Institutes of Health Grants P50 MH071702 and P50 MH094263, Office of Naval Research Multidisciplinary University Research Initiative grant ONR MURI N00014-10-1-0936, and National Center for Research Resources Grant P41RR14075. Research was conducted at the Cognitive Neuroimaging Lab, Center for Memory and Brain, Boston University (Boston, MA), and the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School (Charlestown, MA). We would like to thank Dr. Rissman for generously sharing his functional connectivity scripts with us. NR 82 TC 28 Z9 28 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 2 PY 2012 VL 60 IS 2 BP 1316 EP 1330 DI 10.1016/j.neuroimage.2012.01.046 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 932ED UT WOS:000303272300047 PM 22266411 ER PT J AU Sarkka, S Solin, A Nummenmaa, A Vehtari, A Auranen, T Vanni, S Lin, FH AF Sarkka, Simo Solin, Arno Nummenmaa, Aapo Vehtari, Aki Auranen, Toni Vanni, Simo Lin, Fa-Hsuan TI Dynamic retrospective filtering of physiological noise in BOLD fMRI: DRIFTER SO NEUROIMAGE LA English DT Article DE Functional magnetic resonance imaging; Physiological noise; Kalman filter; RTS smoother; Interacting multiple models; Bayesian inference ID FUNCTIONAL MRI; BALLOON MODEL; FLUCTUATIONS; RESPONSES; OXYGENATION; SIGNAL; REDUCTION; ARTIFACTS; IMPACT AB In this article we introduce the DRIFTER algorithm, which is a new model based Bayesian method for retrospective elimination of physiological noise from functional magnetic resonance imaging (fMRI) data. In the method, we first estimate the frequency trajectories of the physiological signals with the interacting multiple models (IMM) filter algorithm. The frequency trajectories can be estimated from external reference signals, or if the temporal resolution is high enough, from the fMRI data. The estimated frequency trajectories are then used in a state space model in combination of a Kalman filter (KF) and Rauch-Tung-Striebel (RTS) smoother, which separates the signal into an activation related cleaned signal, physiological noise, and white measurement noise components. Using experimental data, we show that the method outperforms the RETROICOR algorithm if the shape and amplitude of the physiological signals change over time. (c) 2012 Elsevier Inc. All rights reserved. C1 [Sarkka, Simo; Solin, Arno; Nummenmaa, Aapo; Vehtari, Aki; Lin, Fa-Hsuan] Aalto Univ, Dept Biomed Engn & Computat Sci, Espoo, Finland. [Nummenmaa, Aapo; Lin, Fa-Hsuan] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Auranen, Toni; Vanni, Simo] Aalto Univ, Low Temp Lab, Adv Magnet Imaging Ctr, Espoo, Finland. [Vanni, Simo] Aalto Univ, Low Temp Lab, Brain Res Unit, Espoo, Finland. [Lin, Fa-Hsuan] Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. RP Sarkka, S (reprint author), POB 12200, Aalto 00076, Finland. EM simo.sarkka@aalto.fi RI Sarkka, Simo/E-7747-2012; Solin, Arno/G-6859-2012; Vehtari, Aki/A-7584-2008; Vanni, Simo/B-9590-2013; Lin, Fa-Hsuan/G-6988-2012; Auranen, Toni/J-7137-2012 OI Vehtari, Aki/0000-0003-2164-9469; Solin, Alexei/0000-0002-6277-3506; Lin, Fa-Hsuan/0000-0002-9539-1731; FU United States National Institutes of Health (NIH) [R01HD040712, R01NS037462, R01NS048279, P41RR014075, R01MH083744, R21DC010060, R21EB007298]; National Science Council, Taiwan [NSC 98-2320-B-002-004-MY3, NSC 100-2325-B-002-046]; National Health Research Institute, Taiwan [NHRI-EX100-9715EC]; Academy of Finland [124698, 125349, 127624, 129670, 218054, 218248]; National Center for Research Resources FX This work was supported by grants from the United States National Institutes of Health (NIH) (R01HD040712, R01NS037462, R01NS048279, P41RR014075, R01MH083744, R21DC010060, R21EB007298, National Center for Research Resources), National Science Council, Taiwan (NSC 98-2320-B-002-004-MY3, NSC 100-2325-B-002-046), National Health Research Institute, Taiwan (NHRI-EX100-9715EC), and Academy of Finland (124698, 125349, 127624, 129670, 218054, 218248, and the FiDiPro program). We thank Marita Kattelus for assistance in the conduct of the experimental study. NR 40 TC 25 Z9 25 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 2 PY 2012 VL 60 IS 2 BP 1517 EP 1527 DI 10.1016/j.neuroimage.2012.01.067 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 932ED UT WOS:000303272300062 PM 22281675 ER PT J AU Linskey, K Lewandrowski, K AF Linskey, K. Lewandrowski, K. TI The role of B-type natriuretic peptide testing in patients with acute coronary syndromes SO MINERVA CARDIOANGIOLOGICA LA English DT Review DE Natriuretic peptide, brain; Pro-brain natriuretic peptide; Acute coronary syndrome; Heart failure ID ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; C-REACTIVE PROTEIN; RISK STRATIFICATION; ARTERY-DISEASE; CHEST-PAIN; TROPONIN-T; SYSTOLIC FUNCTION; PROGNOSTIC VALUE; PLASMA-LEVELS AB B-type (brain) natriuretic peptide (BNP) is a cardiac hormone whose measurement can be helpful in a variety of clinical settings, but has been most extensively studied in patients with heart failure and acute coronary syndrome (ACS). The value of both BNP and its N-terminal fragment, NT-proBNP, as independent prognostic biomarkers in ACS is supported by data from a number of clinical trials. BNP/NT-proBNP levels can predict death and subsequent development of heart failure, but not recurrent ischemic events. BNP may also be helpful as an aid in establishing the diagnosis of ACS in patients presenting with chest pain. The role of BNP in determining treatment has not yet been defined, though patients with high levels may derive more benefit from invasive management and from treatment with ranolazine. The National Academy of Clinical Biochemists (NACB) guidelines state that measurement of BNP/NT-proBNP may be useful in prognosis for ACS patients, but do not yet recommend its routine use, naming a number of other issues that need to be resolved in the use of this marker. Age- and gender-related decision limits should be determined, and cutoff levels of BNP/NT-proBNP corresponding to low, intermediate, and high risk patients should be ascertained. Additional evidence regarding the impact of BNP/NT-proBNP levels on treatment strategy in ACS patients will be helpful in further defining the role of B-type natriuretic peptide testing in the acute coronary syndromes. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Gray 5 Chem, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 33 TC 1 Z9 2 U1 0 U2 2 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0026-4725 J9 MINERVA CARDIOANGIOL JI Minerva Cardioangiol. PD APR PY 2012 VL 60 IS 2 BP 175 EP 182 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 097LR UT WOS:000315476100006 PM 22495166 ER PT J AU Xie, AL AF Xie, Ailiang TI Effect of sleep on breathing - Why recurrent apneas are only seen during sleep SO JOURNAL OF THORACIC DISEASE LA English DT Article ID RESPIRATORY MUSCLE; LUNG-VOLUME; REM-SLEEP; VENTILATION; WAKEFULNESS; THRESHOLD; MECHANICS; AROUSAL; PATTERN; ONSET C1 [Xie, Ailiang] Univ Wisconsin, Dept Med, Madison, WI USA. [Xie, Ailiang] William S Middleton Mem Vet Adm Med Ctr, Pulm Physiol Lab, Madison, WI 53705 USA. RP Xie, AL (reprint author), William S Middleton Mem Vet Adm Med Ctr, Pulm Physiol Lab, 2500 Overlook Terrace, Madison, WI 53705 USA. EM axie@facstaff.wisc.edu NR 26 TC 0 Z9 0 U1 0 U2 0 PU PIONEER BIOSCIENCE PUBL CO PI HONG KONG PA 9A GOLD SHINE TOWER, 346-348 QUEEN'S RD CENTRAL, SHEUNG WAN, HONG KONG, 00000, PEOPLES R CHINA SN 2072-1439 J9 J THORAC DIS JI J. Thorac. Dis. PD APR PY 2012 VL 4 IS 2 BP 194 EP 197 DI 10.3978/j.issn.2072-1439.2011.04.04 PG 4 WC Respiratory System SC Respiratory System GA 087UR UT WOS:000314789900014 PM 22833825 ER PT J AU Davis, KC Schraufnagel, TJ Jacques-Tiura, AJ Norris, J George, WH Kiekel, PA AF Davis, Kelly Cue Schraufnagel, Trevor J. Jacques-Tiura, Angela J. Norris, Jeanette George, William H. Kiekel, Preston A. TI Childhood Sexual Abuse and Acute Alcohol Effects on Men's Sexual Aggression Intentions SO PSYCHOLOGY OF VIOLENCE LA English DT Article DE childhood sexual abuse; alcohol; sexual aggression; cognitive distortions; condom use resistance ID ASSAULT PERPETRATION; IMPLICIT THEORIES; COLLEGE-STUDENTS; RISK BEHAVIOR; VIOLENCE; IMPACT; SAMPLE; MALES; RAPE; EXPECTANCIES AB Although research has established childhood sexual abuse (CSA) as a risk factor for men's perpetration of sexual aggression, there has been little investigation of the factors undergirding this association. This study represents one of the first to use a laboratory-based sexual aggression analogue coupled with an alcohol administration protocol to investigate the pathways through which CSA and alcohol influence men's self-reported sexual aggression intentions. Method: After completing background questionnaires, male social drinkers (N = 220) were randomly assigned to a control, placebo, low alcohol dose or high alcohol dose condition. Following beverage consumption, participants read a sexual scenario in which the female partner refused to have unprotected sexual intercourse, after which they completed dependent measures. Results: Path analysis indicated that men with a CSA history and intoxicated men perceived the female character as more sexually aroused and reported stronger sexual entitlement cognitions, both of which were in turn associated with greater condom use resistance and higher sexual aggression intentions. Exploratory analyses revealed that intoxication moderated the effects of CSA history on sexual entitlement cognitions, such that sexual entitlement cognitions were highest for men who had a CSA history and consumed alcohol. Conclusions: Findings suggest that CSA history may facilitate sexual assault perpetration through its effects on in-the-moment cognitions and that these effects may be exacerbated by alcohol intoxication. C1 [Davis, Kelly Cue] Univ Washington, Sch Social Work, Seattle, WA 98105 USA. [Schraufnagel, Trevor J.] Univ Washington, Seattle, WA 98105 USA. [Schraufnagel, Trevor J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Jacques-Tiura, Angela J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA. [Norris, Jeanette; Kiekel, Preston A.] Univ Washington, Alcohol & Drug Abuse Inst, Seattle, WA 98105 USA. [George, William H.] Univ Washington, Dept Psychol, Seattle, WA 98105 USA. RP Davis, KC (reprint author), Univ Washington, Sch Social Work, Box 354900, Seattle, WA 98105 USA. EM kcue@uw.edu FU NIAAA NIH HHS [R01 AA014512, R01 AA017608-01A2, R21 AA016283-01A1, R21 AA016283, R01 AA017608] NR 44 TC 15 Z9 15 U1 2 U2 20 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 2152-0828 J9 PSYCHOL VIOLENCE JI Psychol. Violence PD APR PY 2012 VL 2 IS 2 SI SI BP 179 EP 193 DI 10.1037/a0027185 PG 15 WC Psychology, Clinical; Criminology & Penology; Family Studies SC Psychology; Criminology & Penology; Family Studies GA 087EX UT WOS:000314745200007 PM 22754720 ER PT J AU Johnson, KA Fox, NC Sperling, RA Klunk, WE AF Johnson, Keith A. Fox, Nick C. Sperling, Reisa A. Klunk, William E. TI Brain Imaging in Alzheimer Disease SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID MILD COGNITIVE IMPAIRMENT; PITTSBURGH COMPOUND-B; POSITRON-EMISSION-TOMOGRAPHY; TEMPORAL-LOBE ATROPHY; RESTING-STATE NETWORKS; CEREBROSPINAL-FLUID MARKERS; CEREBRAL GLUCOSE-METABOLISM; APOLIPOPROTEIN-E EPSILON-4; NONDEMENTED OLDER-ADULTS; PARIETAL MEMORY NETWORK AB Imaging has played a variety of roles in the study of Alzheimer disease (AD) over the past four decades. Initially, computed tomography (CT) and then magnetic resonance imaging (MRI) were used diagnostically to rule out other causes of dementia. More recently, a variety of imaging modalities including structural and functional MRI and positron emission tomography (PET) studies of cerebral metabolism with fluoro-deoxy-D-glucose (FDG) and amyloid tracers such as Pittsburgh Compound-B (PiB) have shown characteristic changes in the brains of patients with AD, and in prodromal and even presymptomatic states that can help rule-in the AD pathophysiological process. No one imaging modality can serve all purposes as each have unique strengths and weaknesses. These modalities and their particular utilities are discussed in this article. The challenge for the future will be to combine imaging biomarkers to most efficiently facilitate diagnosis, disease staging, and, most importantly, development of effective disease-modifying therapies. C1 [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Brigham & Womens Hosp, Boston, MA 02114 USA. [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Brigham & Womens Hosp, Boston, MA 02114 USA. [Fox, Nick C.] UCL, UCL Inst Neurol, Dementia Res Ctr, London WC1N 3AR, England. [Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Ctr Alzheimer Res & Treatment,Med Sch, Boston, MA 02115 USA. [Klunk, William E.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Klunk, William E.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. RP Klunk, WE (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. EM klunkwe@upmc.edu RI Fox, Nick/B-1319-2009; OI Fox, Nick/0000-0002-6660-657X; Klunk, William/0000-0001-5512-0251 FU Medical Research Council [G0601846, G0801306] NR 230 TC 83 Z9 88 U1 4 U2 27 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 APR PY 2012 VL 2 IS 4 AR a006213 DI 10.1101/cshperspect.a006213 PG 23 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 080XH UT WOS:000314277000009 PM 22474610 ER PT J AU Suter, MJ Lam, S Brenner, M AF Suter, Melissa J. Lam, Stephen Brenner, Matthew TI Optical techniques in pulmonary medicine SO EXPERT REVIEW OF RESPIRATORY MEDICINE LA English DT Article AB Optical Techniques in Pulmonary Medicine. SPIE photonics West Moscone Center San Fransisco, CA, USA, 21 January 2012 There is ongoing interest in the emerging field of pulmonary photonic-based diagnostics. Potential clinical need areas that are being actively investigated at this time include airway and peripheral lung cancer diagnostics, pulmonary parenchymal and interstitial disorders, alveolar structure function, inhalation injury, ciliary function analysis, asthma and obstructive lung diseases. C1 [Brenner, Matthew] UC Irvine Med Ctr, Orange, CA 92868 USA. [Suter, Melissa J.] Harvard Univ, Sch Med, Pulm & Crit Care Unit, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lam, Stephen] British Columbia Canc Agcy, Canc Imaging Dept, Vancouver, BC V5Z 1L3, Canada. [Brenner, Matthew] Beckman Laser Inst & Med Clin, Irvine, CA 92612 USA. RP Brenner, M (reprint author), UC Irvine Med Ctr, 101 City Dr S,City Tower,Suite 400,ZOT Code 4095, Orange, CA 92868 USA. EM mbrenner@uci.edu FU NinePoint Medical FX MJ Suter receives research support from NinePoint Medical. NinePoint Medical has a licensing arrangement with Massachusetts General Hospital. MJ Suter has the right to receive royalty payments from NinePoint Medical. M Brenner is a co-investigator on an SBIR Phase II Grant with OCT Medical, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 19 TC 0 Z9 0 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-6348 J9 EXPERT REV RESP MED JI Expert Rev. Respir. Med. PD APR PY 2012 VL 6 IS 2 BP 143 EP 145 DI 10.1586/ERS.12.11 PG 3 WC Respiratory System SC Respiratory System GA 056RK UT WOS:000312508600009 PM 22455486 ER PT J AU Sgubin, D Wakimoto, H Kanai, R Rabkin, SD Martuza, RL AF Sgubin, Donatella Wakimoto, Hiroaki Kanai, Ryuichi Rabkin, Samuel D. Martuza, Robert L. TI Oncolytic Herpes Simplex Virus Counteracts the Hypoxia-Induced Modulation of Glioblastoma Stem-Like Cells SO STEM CELLS TRANSLATIONAL MEDICINE LA English DT Article DE Gene transfer; Glioma; Herpes simplex virus; Cancer stem cells; Hypoxia ID TUMOR INITIATING CELLS; INDUCIBLE FACTORS; GENE-EXPRESSION; TRANSCRIPTION FACTOR; MALIGNANT GLIOMAS; MARKER CD133; KINASE PERK; CANCER; ACTIVATION; PHOSPHORYLATION AB Glioblastoma (GBM), a fatal malignant brain tumor, contains abundant hypoxic regions that provide a "niche" to promote both the maintenance and enrichment of glioblastoma stem-like cells (GSCs) and confer resistance to chemo- and radiotherapy. Since GSCs, with an ability to resist conventional therapies, may be responsible for tumor recurrence, targeting GSCs located in such a hypoxic environment may be critical to improving the therapeutic outcome for GBM patients. Oncolytic viral therapies have been tested in the clinic as a promising therapeutic approach for GBM. In this study, we analyzed and compared the therapeutic effects of oncolytic herpes simplex virus (oHSV) type 1 G47 Delta (gamma 34.5(-)ICP6(-)LacZ(+)alpha 47(-)) in patient-derived GSCs under normoxia (21% oxygen) and hypoxia (1% oxygen). GSCs cultured in hypoxia showed an increased ability to form neurospheres and expressed higher levels of the putative stem cell marker CD133 compared with GSCs cultured in normoxia. G47 Delta exhibited a comparable ability to infect, replicate, and kill GSCs in normoxia and hypoxia in vitro. Importantly, G47 Delta could counteract hypoxia-mediated enhancement of the stem-like properties of GSCs, inhibiting their self-renewal and stem cell marker expression. Using orthotopic human GSC xenografts in mice, we demonstrated that intratumoral injection of G47 Delta Us11fluc, a newly developed G47 Delta derivative that expresses firefly luciferase driven by a true late viral promoter, led to an equivalent frequency of viral infection and replication in hypoxic and non-hypoxic tumor areas. These findings suggest that oHSV G47 Delta represents a promising therapeutic strategy to target and kill GSCs, not only in normoxic areas of GBM but also within the hypoxic niche. STEM CELLS TRANSLATIONAL MEDICINE 2012;1:322-332 C1 [Sgubin, Donatella; Wakimoto, Hiroaki; Kanai, Ryuichi; Rabkin, Samuel D.; Martuza, Robert L.] Massachusetts Gen Hosp, Brain Tumor Res Ctr, Dept Neurosurg, Boston, MA 02114 USA. [Sgubin, Donatella; Wakimoto, Hiroaki; Kanai, Ryuichi; Rabkin, Samuel D.; Martuza, Robert L.] Harvard Univ, Sch Med, Boston, MA USA. [Sgubin, Donatella] Univ Padua, Dept Neurosurg, Padua, Italy. RP Wakimoto, H (reprint author), Massachusetts Gen Hosp, Brain Tumor Res Ctr, Dept Neurosurg, Simches Res Bldg,CPZN 3800,185 Cambridge St, Boston, MA 02114 USA. EM hwakimoto@patners.org FU NIH [NS032677]; University of Padova FX We thank Prof. Pierluigi Longatti (University of Padova) for grant support (to D.S.). This work was supported in part by NIH Grant NS032677 (to R.L.M.). NR 51 TC 14 Z9 15 U1 0 U2 6 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 2157-6564 J9 STEM CELL TRANSL MED JI Stem Cells Transl. Med. PD APR PY 2012 VL 1 IS 4 BP 322 EP 332 DI 10.5966/sctm.2011-0035 PG 11 WC Cell & Tissue Engineering SC Cell Biology GA 057NZ UT WOS:000312571600012 PM 23197811 ER PT J AU Fleming, AJ Chi, SN AF Fleming, Adam J. Chi, Susan N. TI Brain Tumors in Children SO CURRENT PROBLEMS IN PEDIATRIC AND ADOLESCENT HEALTH CARE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; LOW-GRADE GLIOMA; GERM-CELL TUMORS; CHOROID-PLEXUS CARCINOMA; PRIMITIVE NEUROECTODERMAL TUMORS; HIGH-DOSE CHEMOTHERAPY; CONFORMAL RADIATION-THERAPY; TERATOID RHABDOID TUMOR; VON-HIPPEL-LINDAU; CANCER GROUP C1 [Fleming, Adam J.; Chi, Susan N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Neurooncol,Dept Pediat, Boston, MA 02115 USA. RP Fleming, AJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Neurooncol,Dept Pediat, 44 Binney St, Boston, MA 02115 USA. OI Fleming, Adam/0000-0002-7194-3220 NR 143 TC 21 Z9 21 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-5442 J9 CURR PROB PEDIATR AD JI Curr. Probl. Pediatr. Adolesc. Health Care PD APR PY 2012 VL 42 IS 4 BP 80 EP 103 DI 10.1016/j.cppeds.2011.12.002 PG 24 WC Pediatrics SC Pediatrics GA 052AD UT WOS:000312169200002 PM 22433905 ER PT J AU Yeh, RW Rosenfield, K Zelevinsky, K Mauri, L Sakhuja, R Shivapour, DM Lovett, A Weiner, BH Jacobs, AK Normand, SLT AF Yeh, Robert W. Rosenfield, Kenneth Zelevinsky, Katya Mauri, Laura Sakhuja, Rahul Shivapour, Daniel M. Lovett, Ann Weiner, Bonnie H. Jacobs, Alice K. Normand, Sharon-Lise T. TI Sources of Hospital Variation in Short-Term Readmission Rates After Percutaneous Coronary Intervention SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE performance measures; percutaneous coronary intervention; outcomes research ID ACUTE MYOCARDIAL-INFARCTION; 30-DAY READMISSION; HEART-FAILURE; CARE; STENTS; COHORT AB Background-Risk-standardized all-cause 30-day readmission rates (RSRRs) after percutaneous coronary intervention (PCI) have been endorsed as a national measure of hospital quality. Little is known about variation in the performance of hospitals on this measure, and whether high hospital rates of readmission after PCI are due to modifiable deficiencies in quality of care has not been assessed. Methods and Results-We estimated 30-day, all-cause RSRRs for all nonfederal PCI-performing hospitals in Massachusetts, adjusted for clinical and angiographic variables, between 2005 and 2008. We assessed if differences in race, insurance type, and PCI and post-PCI characteristics, including procedural complications and discharge characteristics, could explain variation between hospitals using nested hierarchical logistic regression models. Of 36 060 patients undergoing PCI at 24 hospitals and surviving to discharge, 4469 (12.4%) were readmitted within 30 days of discharge. Hospital RSRRs ranged from 9.5% to 17.9%, with 8 of 24 hospitals being identified as outliers (4 lower than expected and 4 higher than expected). Differences in race, insurance, PCI, and post-PCI factors accounted for 10.4% of the between- hospital variance in RSRRs. Conclusions-We observed wide variation in hospital 30-day all-cause RSRRs after PCI, most of which could not be explained by identifiable differences in procedural and postprocedural factors. A better understanding of etiologies of hospital variation is necessary to determine whether this measure is an actionable assessment of hospital quality, and, if so, how hospitals might improve their performance. (Circ Cardiovasc Interv. 2012;5:227-236.) C1 [Yeh, Robert W.; Rosenfield, Kenneth; Shivapour, Daniel M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02114 USA. [Zelevinsky, Katya; Lovett, Ann; Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02114 USA. [Mauri, Laura] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02114 USA. [Sakhuja, Rahul] Wellmont CVA Heart Inst, Kingsport, TN USA. [Weiner, Bonnie H.] St Vincent Hosp, Worcester, MA 01604 USA. [Jacobs, Alice K.] Boston Med Ctr, Cardiol Sect, Dept Med, Boston, MA USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02114 USA. RP Yeh, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, GRB8-843,55 Fruit St, Boston, MA 02114 USA. EM ryeh@partners.org FU Massachusetts Department of Public Health; American Heart Association [12CRP9010016]; Abbott Vascular; Bard Peripheral Vascular; Consulting/Advisory Board: Abbott Vascular; Angioguard (Cordis); Boston Scientific Corp; Complete Conference Manager; Harvard Clinical Research Institute; Equity: Lumen Biomedical; Medical Stimulation Corp; VIVA Physicians Association; Abbott; Boston Scientific; Cordis; Medtronic; Eli Lilly; Daiichi Sankyo; Bristol Myers Squibb; Sanofi-Aventis FX Data analysis was supported by funding from the Massachusetts Department of Public Health. Dr Yeh was supported in part by a grant from the American Heart Association (12CRP9010016).; Dr Rosenfield reports the following disclosures: Research grant: Abbott Vascular, Bard Peripheral Vascular; Consulting/Advisory Board: Abbott Vascular, Angioguard (Cordis), Boston Scientific Corp, Complete Conference Manager, Harvard Clinical Research Institute; Equity: Lumen Biomedical, Medical Stimulation Corp, and VIVA Physicians Association. Dr Mauri receives institutional research support from Abbott, Boston Scientific, Cordis, Medtronic, Eli Lilly, Daiichi Sankyo, Bristol Myers Squibb, and Sanofi-Aventis and has consulted for Cordis and Medtronic. Dr Jacobs reports being the site principal investigator for a registry sponsored by Abbott. NR 22 TC 18 Z9 18 U1 0 U2 2 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 APR PY 2012 VL 5 IS 2 BP 227 EP 236 DI 10.1161/CIRCINTERVENTIONS.111.967638 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 045OF UT WOS:000311705400016 PM 22438431 ER PT J AU Chowdhury, D AF Chowdhury, Dipanjan TI MicroRNAs in DNA Damaging Cancer Therapy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Chowdhury, Dipanjan] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303122 ER PT J AU Gandhi, CR Huang, C Stolz, DB AF Gandhi, Chandrashekhar R. Huang, Chao Stolz, Donna B. TI Endotoxin-stimulated hepatic stellate cells promote survival of hepatocytes in endotoxemia by inducing endoplasmic reticulum stress and autophagy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Gandhi, Chandrashekhar R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gandhi, Chandrashekhar R.; Huang, Chao; Stolz, Donna B.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305297 ER PT J AU Gooch, JL Ecelbarger, C Reddy, RN Tsukerman, S Madsen, K AF Gooch, Jennifer L. Ecelbarger, Carolyn Reddy, Ramesh N. Tsukerman, Susanna Madsen, Kirsten TI Impaired kidney function and anatomy in dietarily-rescued calcineurin (alpha isoform) knockout mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Gooch, Jennifer L.; Reddy, Ramesh N.] Emory Univ, Atlanta, GA 30322 USA. [Gooch, Jennifer L.] US Dept Vet Affairs, Decatur, GA USA. [Madsen, Kirsten] Univ So Denmark, Dept Cardiovasc & Renal Res, Odense, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306327 ER PT J AU Green, A Jacques, PF Rogers, GT Meigs, JB McKeown, NM AF Green, Angela Jacques, Paul F. Rogers, Gail T. Meigs, James B. McKeown, Nicola M. TI Association between sugar-sweetened beverage consumption and the metabolically healthy obese phenotype SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Green, Angela] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Jacques, Paul F.; Rogers, Gail T.; McKeown, Nicola M.] Tufts Univ, USDA HNRCA, Boston, MA 02111 USA. [Jacques, Paul F.; McKeown, Nicola M.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305832 ER PT J AU Gruionu, G Munn, LL AF Gruionu, Gabriel Munn, Lance L. TI Novel Laser Microsurgery and Imaging Techniques for the Longitudinal Study of Structural Adaptation of Microvascular Networks SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304744 ER PT J AU Hahn, WC AF Hahn, William C. TI Functional genomics to decipher cancer dependencies and mechanisms SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300066 ER PT J AU Ho, L Bloom, PA Vega, JG Pasinetti, GM AF Ho, Lap Bloom, Patricia A. Vega, Joan Griffiths Pasinetti, Giulio Maria TI Exploring The Molecular Mechanisms Underlying The Efficacy of Mindfulness Based Stress Reduction In Alleviating Psychological Stress in Alzheimer's Disease Caregivers SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Ho, Lap; Bloom, Patricia A.; Vega, Joan Griffiths; Pasinetti, Giulio Maria] Mt Sinai Sch Med, New York, NY USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Geriatr Res Ctr, Bronx, NY USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Educ Ctr, Bronx, NY USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Clin Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 2 U2 28 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306109 ER PT J AU Hruby, A Ngwa, JS Meigs, JB Nettleton, JA McKeown, NM AF Hruby, Adela Ngwa, Julius S. Meigs, James B. Nettleton, Jennifer A. McKeown, Nicola M. CA CHARGE Nutr Working Grp TI Meta-analysis of interaction between dietary magnesium intake and genetic risk variants on diabetes phenotypes in the CHARGE Consortium SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Hruby, Adela; McKeown, Nicola M.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Hruby, Adela; McKeown, Nicola M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Ngwa, Julius S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Nettleton, Jennifer A.; CHARGE Nutr Working Grp] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300935 ER PT J AU Janiszewska, M Suva, ML Houtkooper, RH Clement-Schatlo, V Stamenkovic, I AF Janiszewska, Michalina Suva, Mario-Luca Houtkooper, Riekelt H. Clement-Schatlo, Virginie Stamenkovic, Ivan TI The RNA-binding protein Imp2 regulates oxidative phosporylation that is key to glioblastoma cancer stem cell maintenance SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Janiszewska, Michalina; Stamenkovic, Ivan] Univ Lausanne, Lausanne, Switzerland. [Suva, Mario-Luca] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Houtkooper, Riekelt H.] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland. [Clement-Schatlo, Virginie] Univ Geneva, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305169 ER PT J AU Knable, LA Wang, J Ferruzzi, MG Vempati, P Freire, D Gong, B Pasinetti, GM AF Knable, Lindsay Alexis Wang, Jun Ferruzzi, Mario G. Vempati, Prashant Freire, Daniele Gong, Bing Pasinetti, Giulio Maria TI Nasal Spray of Bioactive Polyphenol Metabolites as a Novel Therapy for Alzheimer's Disease and Other Forms of Dementia SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Knable, Lindsay Alexis; Wang, Jun; Vempati, Prashant; Freire, Daniele; Gong, Bing; Pasinetti, Giulio Maria] Mt Sinai Sch Med, New York, NY USA. [Wang, Jun; Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Ferruzzi, Mario G.] Purdue Univ, W Lafayette, IN 47907 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306428 ER PT J AU Liao, S Bazou, D Cheng, G Munn, LL AF Liao, Shan Bazou, Despina Cheng, Gang Munn, Lance L. TI Perivascular cell dynamics during wrapping-and-tapping anastomosis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Liao, Shan; Bazou, Despina; Cheng, Gang; Munn, Lance L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305682 ER PT J AU Lin, GN Field, J Neuberg, D Nathan, D Linden, J AF Lin, Gene Field, Joshua Neuberg, Donna Nathan, David Linden, Joel TI The adenosine A(2A) receptor agonist regadenoson decreases activation of invariant NKT cells in human sickle cell subjects SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Lin, Gene; Linden, Joel] La Jolla Inst Allergy & Immunol, La Jolla, CA USA. [Field, Joshua] Blood Ctr Wisconsin, Milwaukee, WI USA. [Neuberg, Donna; Nathan, David] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303652 ER PT J AU Londono, D Diego, C AF Londono, Diana Diego, Cadavid TI Interleukin 10 prevents apoptosis of brain endothelium during bacteremia SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Londono, Diana; Diego, Cadavid] Massachusetts Gen Hosp, Chalestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711307223 ER PT J AU Londono, D Diego, C AF Londono, Diana Diego, Cadavid TI Immune System Adaptation to Rapid Changes in Bacteremia SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Londono, Diana] Massachusetts Gen Hosp, Chalestown, MA USA. [Diego, Cadavid] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711307231 ER PT J AU McKeown, NM Ma, YY Rogers, G Meigs, J Fontes, J Jacques, P AF McKeown, Nicola Mary Ma, YiYi Rogers, Gail Meigs, James Fontes, Joao Jacques, Paul TI Whole grain intake is associated with inflammatory markers in the Framingham Offspring Study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [McKeown, Nicola Mary; Ma, YiYi; Rogers, Gail; Jacques, Paul] Tufts Univ, JM USDA HNRCA, Boston, MA 02111 USA. [McKeown, Nicola Mary; Ma, YiYi; Jacques, Paul] Gerald J & Dorothy R Friedman Sch Nutr Sci & Poli, Boston, MA USA. [Meigs, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fontes, Joao] Boston Univ, Sch Med, Dept Cardiovasc Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302230 ER PT J AU Melton, DW Gelfond, J Chen, YX McManus, L Shireman, P AF Melton, David Wayne Gelfond, Jonathan Chen, Yongxin McManus, Linda Shireman, Paula TI Unique microRNA expression patterns associated with macrophage infiltration following skeletal muscle injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Melton, David Wayne; Gelfond, Jonathan; Chen, Yongxin; McManus, Linda; Shireman, Paula] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Melton, David Wayne; Chen, Yongxin; Shireman, Paula] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304810 ER PT J AU Murray, DR Valente, AJ Siebenlist, U Chandrasekar, B AF Murray, David R. Valente, Anthony J. Siebenlist, Ulrich Chandrasekar, Bysani TI CIKS is critical mediator of isoproterenol/beta-AR induced cardiomyocyte hypertrophy in vitro and in vivo SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Murray, David R.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Valente, Anthony J.] Univ Texas HSC, San Antonio, TX USA. [Siebenlist, Ulrich] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. [Chandrasekar, Bysani] SLVHCS, New Orleans, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304479 ER PT J AU Pasinetti, GM Gordon, W Dams-O'Connor, K Zhao, W Ho, L AF Pasinetti, Giulio Maria Gordon, Wayne Dams-O'Connor, Kristen Zhao, Wei Ho, Lap TI Traumatic Brain Injury (TBI) Induces Down-Regulation of Olfactory Receptors That Are Ectopically Expressed In The Brain: Implications In TBI-Mediated Tauopathy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Pasinetti, Giulio Maria; Gordon, Wayne; Dams-O'Connor, Kristen] Mt Sinai Sch Med, New York, NY USA. [Pasinetti, Giulio Maria; Zhao, Wei; Ho, Lap] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306514 ER PT J AU Roy, A Khadem, S Donnelly, BF Gong, F Pastor-Soler, NM Chang, YPC Subramanya, AR AF Roy, Ankita Khadem, Shaheen Donnelly, Bridget F. Gong, Fan Pastor-Soler, Nuria M. Chang, Y. P. Christy Subramanya, Arohan R. TI Alternatively spliced PY cassette exons in WNK1 enhance sensitivity to aldosterone via the E3 ubiquitin ligase Nedd4-2 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Roy, Ankita; Khadem, Shaheen; Donnelly, Bridget F.; Gong, Fan; Pastor-Soler, Nuria M.; Subramanya, Arohan R.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Chang, Y. P. Christy] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Subramanya, Arohan R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305462 ER PT J AU Salinardi, T Batra, P Das, SK Robinson, L Lichtenstein, AH Deckersbach, T Roberts, S AF Salinardi, Taylor Batra, Payal Das, Sai Krupa Robinson, Lisa Lichtenstein, Alice H. Deckersbach, Thilo Roberts, Susan TI A Worksite-based Weight Loss Intervention for Obesity Prevention SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Salinardi, Taylor; Batra, Payal; Das, Sai Krupa; Robinson, Lisa; Roberts, Susan] John Mayer USDA, Energy Metab Lab, Human Nutr Res Ctr Aging, Boston, MA USA. [Lichtenstein, Alice H.] John Mayer USDA, Cardiovasc Nutr Lab, Human Nutr Res Ctr Aging, Boston, MA USA. [Deckersbach, Thilo] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Deckersbach, Thilo] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304797 ER PT J AU Schultz, K Boyd, J Byrd, JP McKenney, M Chawla, A Alloosh, M Teague, S Sacks, H Sturek, M AF Schultz, Kyle Boyd, Jack Byrd, James Patrick McKenney, Mikaela Chawla, Aarti Alloosh, Mouhamad Teague, Shawn Sacks, Harold Sturek, Michael TI Surgical excision of coronary epicardial adipose tissue provides evidence for its role in coronary artery disease SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Schultz, Kyle; Boyd, Jack; Byrd, James Patrick; McKenney, Mikaela; Chawla, Aarti; Alloosh, Mouhamad; Teague, Shawn; Sturek, Michael] Indiana Univ Sch Med, Indianapolis, IN USA. [Sacks, Harold] VA Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302588 ER PT J AU Shalhoub, PJ Brancato, SJ Foecking, EM Fargo, KN AF Shalhoub, Philip J. Brancato, Sam J. Foecking, Eileen M. Fargo, Keith N. TI A bilateral pudendal nerve injury model in male rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Shalhoub, Philip J.; Brancato, Sam J.] Loyola Univ Chicago, Stritch Sch Med, Dept Urol, Maywood, IL USA. [Foecking, Eileen M.] Loyola Univ Chicago, Stritch Sch Med, Dept Otolaryngol, Maywood, IL USA. [Fargo, Keith N.] Loyola Univ Chicago, Stritch Sch Med, Dept Mol Pharmacol & Therapeut, Maywood, IL USA. [Foecking, Eileen M.; Fargo, Keith N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res & Dev Serv, Hines, IL 60141 USA. RI Brancato, Sam/K-3266-2014 OI Brancato, Sam/0000-0002-3760-5818 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305870 ER PT J AU Shi, Y Alpatov, R Wagner, U Nakamoto-Kinoshita, M Ye, Z Luu, Y Armache, KJ Simon, MD Stuetzer, A Greer, EL Wang, ZB Hu, GQ Wu, FZ Xu, C Beavers, WN Guo, YH Bian, CB Morrison, PT Vakoc, CR Min, JR Fischle, W Kingston, RE Zhao, KJ Ren, B Warren, ST AF Shi, Yang Alpatov, Roman Wagner, Ulrich Nakamoto-Kinoshita, Mika Ye, Zhen Luu, Ying Armache, Karim J. Simon, Matthew D. Stuetzer, Alexandra Greer, Eric L. Wang, Zhibin Hu, Gang-Qing Wu, Feizhen Xu, Chao Beavers, William N. Guo, Yahong Bian, Chuanbing Morrison, Paul T. Vakoc, Christopher R. Min, Jinrong Fischle, Wolfgang Kingston, Robert E. Zhao, Keji Ren, Bing Warren, Stephen T. TI The fragile X mental retardation protein FMRP plays a role in the DNA damage response SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Shi, Yang; Alpatov, Roman; Greer, Eric L.] Childrens Hosp, Boston, MA 02115 USA. [Shi, Yang; Alpatov, Roman; Greer, Eric L.] Harvard Univ, Sch Med, Boston, MA USA. [Wagner, Ulrich; Ye, Zhen; Luu, Ying; Ren, Bing] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. [Nakamoto-Kinoshita, Mika; Warren, Stephen T.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. [Nakamoto-Kinoshita, Mika; Warren, Stephen T.] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA. [Nakamoto-Kinoshita, Mika; Warren, Stephen T.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. [Armache, Karim J.; Simon, Matthew D.; Kingston, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stuetzer, Alexandra; Fischle, Wolfgang] Max Planck Inst Biol Chem, Gottingen, Germany. [Wang, Zhibin; Hu, Gang-Qing; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Wu, Feizhen] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China. [Xu, Chao; Guo, Yahong; Bian, Chuanbing; Min, Jinrong] Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada. [Beavers, William N.; Morrison, Paul T.] Dana Farber Canc Inst, Mol Biol Core Facil, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711307045 ER PT J AU Song, JW Munn, LL AF Song, Jonathan W. Munn, Lance L. TI Biomechanical Determinants of Endothelial Sprouting and Morphogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RI Munn, Lance/L-3950-2016; Song, Jonathan/C-1922-2013 OI Munn, Lance/0000-0003-0698-7232; Song, Jonathan/0000-0002-6991-5298 NR 0 TC 0 Z9 0 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303228 ER PT J AU Soto-Pina, AE Rani, S Franklin, C Hinojosa-Laborde, C Strong, R AF Soto-Pina, Alexandra Estela Rani, Sheela Franklin, Cynthia Hinojosa-Laborde, Carmen Strong, Randy TI Investigating the contribution of the adrenal medulla and sympathetic nerves in the regulation of dexamethasone-induced hypertension SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Soto-Pina, Alexandra Estela; Rani, Sheela; Franklin, Cynthia; Hinojosa-Laborde, Carmen; Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Soto-Pina, Alexandra Estela; Rani, Sheela; Strong, Randy] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301533 ER PT J AU Stanford, KI Middelbeek, RJW An, D Townsend, KL Markan, KR Hitchcox, KM Hellbach, K Hirshman, MF Goodyear, LJ AF Stanford, Kristin I. Middelbeek, Roeland J. W. An, Ding Townsend, Kristy L. Markan, Kathleen R. Hitchcox, Kristen M. Hellbach, Katharina Hirshman, Michael F. Goodyear, Laurie J. TI A Novel Role for Adipose Tissue in Exercise-Induced Improvements in Glucose Homeostasis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Stanford, Kristin I.; Middelbeek, Roeland J. W.; An, Ding; Townsend, Kristy L.; Markan, Kathleen R.; Hitchcox, Kristen M.; Hellbach, Katharina; Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303171 ER PT J AU Sutherland, KM Bentley, T LaFemina, M Ho, G Hirsch, J Frank, J AF Sutherland, Katherine Marie Bentley, Trevor LaFemina, Michael Ho, Gwen Hirsch, Jan Frank, James TI Claudin-4 interacts with the small GTPase Rap1 and accelerates epithelial repair SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Sutherland, Katherine Marie; LaFemina, Michael; Ho, Gwen; Hirsch, Jan; Frank, James] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sutherland, Katherine Marie; LaFemina, Michael; Hirsch, Jan; Frank, James] San Francisco VA Med Ctr, San Francisco, CA USA. [Bentley, Trevor] No Calif Inst Res & Educ, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306237 ER PT J AU Turman, M Soberman, R AF Turman, Melissa Soberman, Roy TI Nanoclusters of biosynthetic enzymes define the supramolecular organization of leukotriene synthesis on nuclear membranes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Turman, Melissa; Soberman, Roy] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711307202 ER PT J AU Vedovelli, L Rothermel, JT Finberg, KE Wagner, CA Brown, D Paunescu, TG AF Vedovelli, Luca Rothermel, John T. Finberg, Karin E. Wagner, Carsten A. Brown, Dennis Paunescu, Teodor G. TI Subunit-specific regulation of V-ATPase expression in purified intercalated cells from B1-deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Vedovelli, Luca; Rothermel, John T.; Brown, Dennis; Paunescu, Teodor G.] Mass Gen Hosp, Ctr Syst Biol, Prog Memb Biol, Boston, MA USA. [Vedovelli, Luca; Rothermel, John T.; Brown, Dennis; Paunescu, Teodor G.] Mass Gen Hosp, Div Nephrol, Boston, MA USA. [Vedovelli, Luca; Rothermel, John T.; Brown, Dennis; Paunescu, Teodor G.] Harvard Univ, Sch Med, Boston, MA USA. [Finberg, Karin E.] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27706 USA. [Wagner, Carsten A.] Zurich Ctr Integrat Human Physiol, Zurich, Switzerland. [Wagner, Carsten A.] Univ Zurich, Inst Physiol, Zurich, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300549 ER PT J AU Vempati, P Gong, B Zhao, W Wang, J Devi, LA Pasinetti, GM AF Vempati, Prashant Gong, Bing Zhao, Wei Wang, Jun Devi, Lakshmi A. Pasinetti, Giulio M. TI Complement-derived anaphylatoxin, C5a-mediated signaling pathway is a novel pharmacological target for IVIG-regulated humoral immunotherapy in Alzheimer's Disease SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Vempati, Prashant; Gong, Bing; Zhao, Wei; Wang, Jun; Devi, Lakshmi A.; Pasinetti, Giulio M.] Mt Sinai Sch Med, New York, NY USA. [Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Educ & Clin Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306159 ER PT J AU Walensky, LD AF Walensky, Loren David TI Dissecting the BCL-2 family interaction network with stapled peptides: mechanistic insights and pharmacologic opportunities SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Walensky, Loren David] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303944 ER PT J AU Wang, HZ Porter, L Sarwar, Z McManus, LM Shireman, PK AF Wang, Hanzhou Porter, Laurel Sarwar, Zaheer McManus, Linda M. Shireman, Paula K. TI Proinflammatory macrophage ablation in CD11b-diphtheria toxin receptor (DTR) transgenic mice impairs skeletal muscle regeneration SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Wang, Hanzhou; Porter, Laurel; Sarwar, Zaheer; McManus, Linda M.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Shireman, Paula K.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 2 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302344 ER PT J AU Wang, J Ferruzzi, M Janle, EM Tang, CY Gong, B Varghese, M Ho, L Pasinetti, GM AF Wang, Jun Ferruzzi, Mario Janle, Elsa M. Tang, Cheuk Ying Gong, Bing Varghese, Merina Ho, Lap Pasinetti, Giulio M. TI Systems Biology Evaluation of Combi-Phenol on Metabolic Syndrome-Induced Brain Dysfunction SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Wang, Jun; Tang, Cheuk Ying; Gong, Bing; Varghese, Merina; Ho, Lap; Pasinetti, Giulio M.] Mt Sinai Sch Med, New York, NY USA. [Wang, Jun; Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Ferruzzi, Mario; Janle, Elsa M.] Purdue Univ, W Lafayette, IN 47907 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305741 ER PT J AU Wardlow, RD Choi, SH McMillan, B Blacklow, SC AF Wardlow, Robert D., II Choi, Sung Hee McMillan, Brian Blacklow, Stephen C. TI Structure and function of E3 ubiquitin ligase mindbomb RING domain SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Wardlow, Robert D., II] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. [Choi, Sung Hee; McMillan, Brian; Blacklow, Stephen C.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304095 ER PT J AU Wick, MJ Loomis, ZL Hersh, LB Dempsey, EC AF Wick, Marilee J. Loomis, Zoe L. Hersh, Louis B. Dempsey, Edward C. TI Mechanisms that decrease human Neprilysin gene expression in cigarette smoke-induced pulmonary vascular disease SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Wick, Marilee J.; Loomis, Zoe L.; Dempsey, Edward C.] Univ Colorado, Cardiovasc Pulm Res Lab, Aurora, CO USA. [Wick, Marilee J.; Loomis, Zoe L.; Dempsey, Edward C.] Denver VAMC, Denver, CO USA. [Hersh, Louis B.] Univ Kentucky, Lexington, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303596 ER PT J AU Chen, LF Qin, FN Deng, XM Avruch, J Zhou, DW AF Chen, Lanfen Qin, Funiu Deng, Xianming Avruch, Joseph Zhou, Dawang TI Hippo pathway in intestinal homeostasis and tumorigenesis SO PROTEIN & CELL LA English DT Review DE Hippo/Mst1/2; YAP/Yorkie; intestinal stem cells ID STEM-CELL PROLIFERATION; YES-ASSOCIATED PROTEIN; TUMOR-SUPPRESSOR PATHWAY; SELF-RENEWAL; PROMOTES APOPTOSIS; COLORECTAL-CANCER; DROSOPHILA MIDGUT; GROWTH-CONTROL; SIZE-CONTROL; ORGAN SIZE AB The Hippo pathway plays a crucial role in controlling organ size by inhibiting cell proliferation and promoting cell death. Recent findings implicate that this pathway is involved in the process of intestinal regeneration and tumorigenesis. Here we summarize current studies for the function of the Hippo signaling pathway in intestinal homeostasis, regeneration and tumorigenesis, and the crosstalk between the Hippo signaling pathway and other major signaling pathways, i.e. Wnt, Notch and Jak/Stat signaling pathways in intestinal compartment. C1 [Chen, Lanfen; Qin, Funiu; Deng, Xianming; Zhou, Dawang] Xiamen Univ, State Key Lab Stress Cell Biol, Sch Life Sci, Xiamen 361005, Peoples R China. [Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Avruch, Joseph] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Chen, LF (reprint author), Xiamen Univ, State Key Lab Stress Cell Biol, Sch Life Sci, Xiamen 361005, Peoples R China. EM chenlanfen@xmu.edu.cn; dwzhou@xmu.edu.cn RI han, jing/A-2527-2015; Chen, Lanfen/B-7975-2016; OI Chen, Lanfen/0000-0002-9413-1284; Zhou, Dawang/0000-0002-9053-5249 FU China's 1000 Young Talents Program; 111 Project of The Ministration of Education of China [B06016]; Fundamental Research Funds for the Central Universities of China [2010111079]; National Natural Science Foundation of China [81101503]; Natural Science Foundation of Fujian [2011J05096]; RO1 awards [CA136567, DK17776] FX DZ was supported by grants from the China's 1000 Young Talents Program, the 111 Project of The Ministration of Education of China (No. B06016), the Fundamental Research Funds for the Central Universities of China (No. 2010111079), National Natural Science Foundation of China (Grant No. 81101503) and Natural Science Foundation of Fujian (No. 2011J05096). JA was in part supported by the RO1 awards CA136567 (JA), DK17776 (JA) and institutional funds. The authors have no financial conflicts to disclose. NR 51 TC 8 Z9 9 U1 1 U2 18 PU HIGHER EDUCATION PRESS PI BEIJING PA SHATANHOU ST 55, BEIJING 100009, PEOPLES R CHINA SN 1674-800X J9 PROTEIN CELL JI Protein Cell PD APR PY 2012 VL 3 IS 4 BP 305 EP 310 DI 10.1007/s13238-012-2913-9 PG 6 WC Cell Biology SC Cell Biology GA 029WK UT WOS:000310527600008 PM 22492181 ER PT J AU Etzrodt, M Cortez-Retamozo, V Newton, A Zhao, J Ng, A Wildgruber, M Romero, P Wurdinger, T Xavier, R Geissmann, F Meylan, E Nahrendorf, M Swirski, FK Baltimore, D Weissleder, R Pittet, MJ AF Etzrodt, Martin Cortez-Retamozo, Virna Newton, Andita Zhao, Jimmy Ng, Aylwin Wildgruber, Moritz Romero, Pedro Wurdinger, Thomas Xavier, Ramnik Geissmann, Frederic Meylan, Etienne Nahrendorf, Matthias Swirski, Filip K. Baltimore, David Weissleder, Ralph Pittet, Mikael J. TI Regulation of Monocyte Functional Heterogeneity by miR-146a and Relb SO CELL REPORTS LA English DT Article ID DENDRITIC CELLS; IMMUNE-SYSTEM; MACROPHAGES; SUBSETS; DIFFERENTIATION; INFLAMMATION; EXPRESSION; MICRORNAS; INFECTION; RISE AB Monocytes serve as a central defense system against infection and injury but can also promote pathological inflammatory responses. Considering the evidence that monocytes exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. We identified a microRNA (miRNA), miR-146a, which is differentially regulated both in mouse (Ly-6C(hi)/Ly-6C(lo)) and human (CD14(hi)/CD14(lo)CD16(+)) monocyte subsets. The single miRNA controlled the amplitude of the Ly-6C(hi) monocyte response during inflammatory challenge whereas it did not affect Ly-6C(lo) cells. miR-146a-mediated regulation was cell-intrinsic and depended on Relb, a member of the noncanonical NF-kappa B/Rel family, which we identified as a direct miR-146a target. These observations not only provide mechanistic insights into the molecular events that regulate responses mediated by committed monocyte precursor populations but also identify targets for manipulating Ly-6C(hi) monocyte responses while sparing Ly-6C(lo) monocyte activity. C1 [Etzrodt, Martin; Cortez-Retamozo, Virna; Newton, Andita; Wildgruber, Moritz; Nahrendorf, Matthias; Swirski, Filip K.; Weissleder, Ralph; Pittet, Mikael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Ng, Aylwin; Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Ng, Aylwin; Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Zhao, Jimmy; Baltimore, David] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Romero, Pedro] Ludwig Ctr Canc Res, CH-1005 Lausanne, Switzerland. [Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, NL-1080 Amsterdam, Netherlands. [Geissmann, Frederic] Kings Coll London, Ctr Mol & Cellular Biol Inflammat, London SE1 1UL, England. [Meylan, Etienne] Ecole Polytech Fed Lausanne, Swiss Inst Expt Canc Res, CH-1015 Lausanne, Switzerland. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Pittet, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. EM mpittet@mgh.harvard.edu RI Etzrodt, Martin/P-3325-2015; OI Etzrodt, Martin/0000-0003-1928-3904; geissmann, frederic/0000-0001-5029-2468 FU American Association for Cancer Research Centennial Predoctoral Fellowship; Boehringer Ingelheim Fonds; National Institutes of Health [NIH-R01 AI084880, P30 DK043351] FX The authors thank Mike Waring, Andrew Cosgrove, and Adam Chicoine (Ragon Institute of MGH, MIT, and Harvard) for cell sorting; Borja Saez (Harvard Medical School), Patrick Stern, and David Feldser (MIT) for help with retroviral gene transfer. Charles Vanderburg and Anna Krichevsky (Harvard Medical School) for help with analytical RNA techniques; and Yoshiko Iwamoto and Joshua Dunham (MGH Center for Systems Biology) for help with immunofluorescence staining and imaging. M.E. is part of the International PhD program "Cancer and Immunology" at the University of Lausanne, Switzerland and was supported by the American Association for Cancer Research Centennial Predoctoral Fellowship and the Boehringer Ingelheim Fonds. This work was supported in part by National Institutes of Health grants NIH-R01 AI084880 (to M.J.P.) and P30 DK043351 (to M.J.P. and R.X.). D.B. is a director and chairman of the scientific advisory board of Regulus Therapeutics, a biotech company developing miRNA-based drugs. NR 28 TC 48 Z9 48 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REPORTS JI Cell Reports PD APR PY 2012 VL 1 IS 4 BP 317 EP 324 DI 10.1016/j.celrep.2012.02.009 PG 8 WC Cell Biology SC Cell Biology GA 019BN UT WOS:000309712000004 PM 22545247 ER PT J AU Sacks, DB Arnold, M Bakris, GL Bruns, DE Horvath, AR Kirkman, MS Lemmark, A Metzger, BE Nathan, DM AF Sacks, David B. Arnold, Mark Bakris, George L. Bruns, David E. Horvath, Andrea Rita Kirkman, M. Sue Lemmark, Ake Metzger, Boyd E. Nathan, David M. TI Practice Guides of the Clinical Laboratory Guides and recommendations for the diagnosis and treatment of Diabetes Mellitus Chapters 1-6 SO ACTA BIOQUIMICA CLINICA LATINOAMERICANA LA Spanish DT Article ID IMPAIRED FASTING GLUCOSE; NUTRITION EXAMINATION SURVEY; COST-EFFECTIVENESS ANALYSIS; NEAR-INFRARED SPECTROSCOPY; LONG-TERM COMPLICATIONS; CRITICALLY-ILL PATIENTS; PATHOLOGISTS Q-PROBES; BLOOD-GLUCOSE; PLASMA-GLUCOSE; QUALITY SPECIFICATIONS C1 [Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Arnold, Mark] Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. [Bakris, George L.] Univ Chicago, Dept Med, Hypertens Dis Unit, Sect Endocrinol Diabet & Metab, Chicago, IL 60637 USA. [Bruns, David E.] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. [Horvath, Andrea Rita] Univ Sydney, Screening & Test Evaluat Program, Sch Publ Hlth, SEALS Dept Clin Chem,Prince Wales Hosp, Sydney, NSW 2006, Australia. [Kirkman, M. Sue] Amer Diabet Assoc, Alexandria, VA USA. [Lemmark, Ake] Lund Univ, Dept Clin Sci, CRC, Skane Univ Hosp Malmo, Malmo, Sweden. [Metzger, Boyd E.] Northwestern Univ, Div Endocrinol, Feinberg Sch Med, Chicago, IL 60611 USA. [Nathan, David M.] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nathan, David M.] Harvard Univ, Sch Med, Ctr Diabet, Boston, MA USA. RP Sacks, DB (reprint author), NIH, Dept Lab Med, Bldg 10, Bethesda, MD 20892 USA. NR 191 TC 0 Z9 0 U1 0 U2 2 PU FEDERACION BIOQUIMICA PROVINCIA BUENOS AIRES PI LA PLATA, BUENOS AIRES PA CALLE 6, NO. 1344, 1900 LA PLATA, BUENOS AIRES, ARGENTINA SN 0325-2957 EI 1851-6114 J9 ACTA BIOQUIM CLIN L JI Acta Bioquim. Clin. Latinoam. PD APR-JUN PY 2012 VL 46 IS 2 BP 303 EP 336 PG 34 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 015DR UT WOS:000309426200014 ER PT J AU Klionsky, DJ Abdalla, FC Abeliovich, H Abraham, RT Acevedo-Arozena, A Adeli, K Agholme, L Agnello, M Agostinis, P Aguirre-Ghiso, JA Ahn, HJ Ait-Mohamed, O Ait-Si-Ali, S Akematsu, T Akira, S Al-Younes, HM Al-Zeer, MA Albert, ML Albin, RL Alegre-Abarrategui, J Aleo, MF Alirezaei, M Almasan, A Almonte-Becerril, M Amano, A Amaravadi, R Amarnath, S Amer, AO Andrieu-Abadie, N Anantharam, V Ann, DK Anoopkumar-Dukie, S Aoki, H Apostolova, N Arancia, G Aris, JP Asanuma, K Asare, NYO Ashida, H Askanas, V Askew, DS Auberger, P Baba, M Backues, SK Baehrecke, EH Bahr, BA Bai, XY Bailly, Y Baiocchi, R Baldini, G Balduini, W Ballabio, A Bamber, BA Bampton, ETW Banhegyi, G Bartholomew, CR Bassham, DC Bast, RC Batoko, H Bay, BH Beau, I Bechet, DM Begley, TJ Behl, C Behrends, C Bekri, S Bellaire, B Bendall, LJ Benetti, L Berliocchi, L Bernardi, H Bernassola, F Besteiro, S Bhatia-Kissova, I Bi, XN Biard-Piechaczyk, M Blum, JS Boise, LH Bonaldo, P Boone, DL Bornhauser, BC Bortoluci, KR Bossis, I Bost, F Bourquin, JP Boya, P Boyer-Guittaut, M Bozhkov, PV Brady, NR Brancolini, C Brech, A Brenman, JE Brennand, A Bresnick, EH Brest, P Bridges, D Bristol, ML Brookes, PS Brown, EJ Brumell, JH Brunetti-Pierri, N Brunk, UT Bulman, DE Bultman, SJ Bultynck, G Burbulla, LF Bursch, W Butchar, JP Buzgariu, W Bydlowski, SP Cadwell, K Cahova, M Cai, DS Cai, JY Cai, Q Calabretta, B Calvo-Garrido, J Camougrand, N Campanella, M Campos-Salinas, J Candi, E Cao, LZ Caplan, AB Carding, SR Cardoso, SM Carew, JS Carlin, CR Carmignac, V Carneiro, LAM Carra, S Caruso, RA Casari, G Casas, C Castino, R Cebollero, E Cecconi, F Celli, J Chaachouay, H Chae, HJ Chai, CY Chan, DC Chan, EY Chang, RCC Che, CM Chen, CC Chen, GC Chen, GQ Chen, M Chen, Q Chen, SSL Chen, WL Chen, X Chen, XM Chen, XQ Chen, YG Chen, YY Chen, YQ Chen, YJ Chen, ZX Cheng, A Cheng, CHK Cheng, Y Cheong, H Cheong, JH Cherry, S Chess-Williams, R Cheung, ZH Chevet, E Chiang, HL Chiarelli, R Chiba, T Chin, LS Chiou, SH Chisari, FV Cho, CH Cho, DH Choi, AMK Choi, D Choi, KS Choi, ME Chouaib, S Choubey, D Choubey, V Chu, CT Chuang, TH Chueh, SH Chun, T Chwae, YJ Chye, ML Ciarcia, R Ciriolo, MR Clague, MJ Clark, RSB Clarke, PGH Clarke, R Codogno, P Coller, HA Colombo, MI Comincini, S Condello, M Condorelli, F Cookson, MR Coppens, GHCI Corbalan, R Cossart, P Costelli, P Costes, S Coto-Montes, A Couve, E Coxon, FP Cregg, JM Crespo, JL Cronje, MJ Cuervo, AM Cullen, JJ Czaja, MJ D'Amelio, M Darfeuille-Michaud, A Davids, LM Davies, FE De Felici, M de Groot, JF de Haan, CAM De Martino, L De Milito, A De Tata, V Debnath, J Degterev, A Dehay, B Delbridge, LMD Demarchi, F Deng, YZ Dengjel, J Dent, P Denton, D Deretic, V Desai, SD Devenish, RJ Di Gioacchino, M Di Paolo, G Di Pietro, C Diaz-Araya, G Diaz-Laviada, I Diaz-Meco, MT Diaz-Nido, J Dikic, I Dinesh-Kumar, SP Ding, WX Distelhorst, CW Diwan, A Djavaheri-Mergny, M Dokudovskaya, S Dong, Z Dorsey, FC Dosenko, V Dowling, JJ Doxsey, S Dreux, M Drew, ME Duan, QH Duchosal, MA Duff, K Dugail, I Durbeej, M Duszenko, M Edelstein, CL Edinger, AL Egea, G Eichinger, L Eissa, NT Ekmekcioglu, S El-Deiry, WS Elazar, Z Elgendy, M Ellerby, LM Eng, KE Engelbrecht, AM Engelender, S Erenpreisa, J Escalante, R Esclatine, A Eskelinen, EL Espert, L Espina, V Fan, HZ Fan, J Fan, QW Fan, Z Fang, SY Fang, YQ Fanto, M Fanzani, A Farkas, T Farre, JC Faure, M Fechheimer, M Feng, CG Feng, J Feng, QL Feng, YJ Fesus, L Feuer, R Figueiredo-Pereira, ME Fimia, GM Fingar, DC Finkbeiner, S Finkel, T Finley, KD Fiorito, F Fisher, EA Fisher, PB Flajolet, M Florez-McClure, ML Florio, S Fon, EA Fornai, F Fortunato, F Fotedar, R Fowler, DH Fox, HS Franco, R Frankel, LB Fransen, M Fuentes, JM Fueyo, J Fujii, J Fujisaki, K Fujita, E Fukuda, M Furukawa, RH Gaestel, M Gailly, P Gajewska, M Galliot, B Galy, V Ganesh, S Ganetzky, B Ganley, IG Gao, FB Gao, GF Gao, JM Garcia, L Garcia-Manero, G Garcia-Marcos, M Garmyn, M Gartel, AL Gatti, E Gautel, M Gawriluk, TR Gegg, ME Geng, JF Germain, M Gestwicki, JE Gewirtz, DA Ghavami, S Ghosh, P Giammarioli, AM Giatromanolaki, AN Gibson, SB Gilkerson, RW Ginger, ML Ginsberg, HN Golab, J Goligorsky, MS Golstein, P Gomez-Manzano, C Goncu, E Gongora, C Gonzalez, CD Gonzalez, R Gonzalez-Estevez, C Gonzalez-Polo, RA Gonzalez-Rey, E Gorbunov, NV Gorski, S Goruppi, S Gottlieb, RA Gozuacik, D Granato, GE Grant, GD Green, KN Gregorc, A Gros, F Grose, C Grunt, TW Gual, P Guan, JL Guan, KL Guichard, SM Gukovskaya, AS Gukovsky, I Gunst, J Gustafsson, AB Halayko, AJ Hale, AN Halonen, SK Hamasaki, M Han, F Han, T Hancock, MK Hansen, M Harada, H Harada, M Hardt, SE Harper, JW Harris, AL Harris, J Harris, SD Hashimoto, M Haspel, JA Hayashi, S Hazelhurst, LA He, CC He, YW Hebert, MJ Heidenreich, KA Helfrich, MH Helgason, GV Henske, EP Herman, B Herman, PK Hetz, C Hilfiker, S Hill, JA Hocking, LJ Hofman, P Hofmann, TG Hohfeld, J Holyoake, TL Hong, MH Hood, DA Hotamisligil, GS Houwerzijl, EJ Hoyer-Hansen, M Hu, BR Hu, CAA Hu, HM Hua, Y Huang, CH Huang, J Huang, SB Huang, WP Huber, TB Huh, WK Hung, TH Hupp, TR Hur, GM Hurley, JB Hussain, SNA Hussey, PJ Hwang, JJ Hwang, SM Ichihara, A Ilkhanizadeh, S Inoki, K Into, T Iovane, V Iovanna, JL Ip, NY Isaka, Y Ishida, H Isidoro, C Isobe, K Iwasaki, A Izquierdo, M Izumi, Y Jaakkola, PM Jaattela, M Jackson, GR Jackson, WT Janji, B Jendrach, M Jeon, JH Jeung, EB Jiang, H Jiang, HC Jiang, JX Jiang, M Jiang, Q Jiang, XJ Jiang, XJ Jimenez, A Jin, MY Jin, SK Joe, CO Johansen, T Johnson, DE Johnson, GVW Jones, NL Joseph, B Joseph, SK Joubert, AM Juhasz, G Juillerat-Jeanneret, L Jung, CH Jung, YK Kaarniranta, K Kaasik, A Kabuta, T Kadowaki, M Kagedal, K Kamada, Y Kaminskyy, VO Kampinga, HH Kanamori, H Kang, C Kang, KB Kang, KI Kang, R Kang, YA Kanki, T Kanneganti, TD Kanno, H Kanthasamy, AG Kanthasamy, A Karantza, V Kaushal, GP Kaushik, S Kawazoe, Y Ke, PY Kehrl, JH Kelekar, A Kerkhoff, C Kessel, DH Khalil, H Kiel, JAKW Kiger, AA Kihara, A Kim, DR Kim, DH Kim, DH Kim, EK Kim, HR Kim, JS Kim, JH Kim, JC Kim, JK Kim, PK Kim, SW Kim, YS Kim, Y Kimchi, A Kimmelman, AC King, JS Kinsella, TJ Kirkin, V Kirshenbaum, LA Kitamoto, K Kitazato, K Klein, L Klimecki, WT Klucken, J Knecht, E Ko, BCB Koch, JC Koga, H Koh, JY Koh, YH Koike, M Komatsu, M Kominami, E Kong, HJ Kong, WJ Korolchuk, VI Kotake, Y Koukourakis, MI Flores, JBK Kovacs, AL Kraft, C Krainc, D Kraemer, H Kretz-Remy, C Krichevsky, AM Kroemer, G Krueger, R Krut, O Ktistakis, NT Kuan, CY Kucharczyk, R Kumar, A Kumar, R Kumar, S Kundu, M Kung, HJ Kurz, T Kwon, HJ La Spada, AR Lafont, F Lamark, T Landry, J Lane, JD Lapaquette, P Laporte, JF Laszlo, L Lavandero, S Lavoie, JN Layfield, R Lazo, PA Le, WD Le Cam, L Ledbetter, DJ Lee, AJX Lee, BW Lee, GM Lee, J Lee, JH Lee, M Lee, MS Lee, SH Leeuwenburgh, C Legembre, P Legouis, R Lehmann, M Lei, HY Lei, QY Leib, DA Leiro, J Lemasters, JJ 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Gaestel, Matthias Gailly, Philippe Gajewska, Malgorzata Galliot, Brigitte Galy, Vincent Ganesh, Subramaniam Ganetzky, Barry Ganley, Ian G. Gao, Fen-Biao Gao, George F. Gao, Jinming Garcia, Lorena Garcia-Manero, Guillermo Garcia-Marcos, Mikel Garmyn, Marjan Gartel, Andrei L. Gatti, Evelina Gautel, Mathias Gawriluk, Thomas R. Gegg, Matthew E. Geng, Jiefei Germain, Marc Gestwicki, Jason E. Gewirtz, David A. Ghavami, Saeid Ghosh, Pradipta Giammarioli, Anna M. Giatromanolaki, Alexandra N. Gibson, Spencer B. Gilkerson, Robert W. Ginger, Michael L. Ginsberg, Henry N. Golab, Jakub Goligorsky, Michael S. Golstein, Pierre Gomez-Manzano, Candelaria Goncu, Ebru Gongora, Celine Gonzalez, Claudio D. Gonzalez, Ramon Gonzalez-Estevez, Cristina Gonzalez-Polo, Rosa Ana Gonzalez-Rey, Elena Gorbunov, Nikolai V. Gorski, Sharon Goruppi, Sandro Gottlieb, Roberta A. Gozuacik, Devrim Granato, Giovanna Elvira Grant, Gary D. Green, Kim N. Gregorc, Ales Gros, Frederic Grose, Charles Grunt, Thomas W. Gual, Philippe Guan, Jun-Lin Guan, Kun-Liang Guichard, Sylvie M. Gukovskaya, Anna S. Gukovsky, Ilya Gunst, Jan Gustafsson, Asa B. Halayko, Andrew J. Hale, Amber N. Halonen, Sandra K. Hamasaki, Maho Han, Feng Han, Ting Hancock, Michael K. Hansen, Malene Harada, Hisashi Harada, Masaru Hardt, Stefan E. Harper, J. Wade Harris, Adrian L. Harris, James Harris, Steven D. Hashimoto, Makoto Haspel, Jeffrey A. Hayashi, Shin-ichiro Hazelhurst, Lori A. He, Congcong He, You-Wen Hebert, Marie-Josee Heidenreich, Kim A. Helfrich, Miep H. Helgason, Gudmundur V. Henske, Elizabeth P. Herman, Brian Herman, Paul K. Hetz, Claudio Hilfiker, Sabine Hill, Joseph A. Hocking, Lynne J. Hofman, Paul Hofmann, Thomas G. Hoehfeld, Joerg Holyoake, Tessa L. Hong, Ming-Huang Hood, David A. Hotamisligil, Goekhan S. Houwerzijl, Ewout J. Hoyer-Hansen, Maria Hu, Bingren Hu, Chien-An A. Hu, Hong-Ming Hua, Ya Huang, Canhua Huang, Ju Huang, Shengbing Huang, Wei-Pang Huber, Tobias B. Huh, Won-Ki Hung, Tai-Ho Hupp, Ted R. Hur, Gang Min Hurley, James B. Hussain, Sabah N. A. Hussey, Patrick J. Hwang, Jung Jin Hwang, Seungmin Ichihara, Atsuhiro Ilkhanizadeh, Shirin Inoki, Ken Into, Takeshi Iovane, Valentine Iovanna, Juan L. Ip, Nancy Y. Isaka, Yoshitaka Ishida, Hiroyuki Isidoro, Ciro Isobe, Ken-ichi Iwasaki, Akiko Izquierdo, Marta Izumi, Yotaro Jaakkola, Panu M. Jaattela, Marja Jackson, George R. Jackson, William T. Janji, Bassam Jendrach, Marina Jeon, Ju-Hong Jeung, Eui-Bae Jiang, Hong Jiang, Hongchi Jiang, Jean X. Jiang, Ming Jiang, Qing Jiang, Xuejun Jiang, Xuejun Jimenez, Alberto Jin, Meiyan Jin, Shengkan Joe, Cheol O. Johansen, Terje Johnson, Daniel E. Johnson, Gail V. W. Jones, Nicola L. Joseph, Bertrand Joseph, Suresh K. Joubert, Annie M. Juhasz, Gabor Juillerat-Jeanneret, Lucienne Jung, Chang Hwa Jung, Yong-Keun Kaarniranta, Kai Kaasik, Allen Kabuta, Tomohiro Kadowaki, Motoni Kagedal, Katarina Kamada, Yoshiaki Kaminskyy, Vitaliy O. Kampinga, Harm H. Kanamori, Hiromitsu Kang, Chanhee Kang, Khong Bee Kang, Kwang Il Kang, Rui Kang, Yoon-A Kanki, Tomotake Kanneganti, Thirumala-Devi Kanno, Haruo Kanthasamy, Anumantha G. Kanthasamy, Arthi Karantza, Vassiliki Kaushal, Gur P. Kaushik, Susmita Kawazoe, Yoshinori Ke, Po-Yuan Kehrl, John H. Kelekar, Ameeta Kerkhoff, Claus Kessel, David H. Khalil, Hany Kiel, Jan A. K. W. Kiger, Amy A. Kihara, Akio Kim, Deok Ryong Kim, Do-Hyung Kim, Dong-Hou Kim, Eun-Kyoung Kim, Hyung-Ryong Kim, Jae-Sung Kim, Jeong Hun Kim, Jin Cheon Kim, John K. Kim, Peter K. Kim, Seong Who Kim, Yong-Sun Kim, Yonghyun Kimchi, Adi Kimmelman, Alec C. King, Jason S. Kinsella, Timothy J. Kirkin, Vladimir Kirshenbaum, Lorrie A. Kitamoto, Katsuhiko Kitazato, Kaio Klein, Ludger Klimecki, Walter T. Klucken, Jochen Knecht, Erwin Ko, Ben C. B. Koch, Jan C. Koga, Hiroshi Koh, Jae-Young Koh, Young Ho Koike, Masato Komatsu, Masaaki Kominami, Eiki Kong, Hee Jeong Kong, Wei-Jia Korolchuk, Viktor I. Kotake, Yaichiro Koukourakis, Michael I. Flores, Juan B. Kouri Kovacs, Attila L. Kraft, Claudine Krainc, Dimitri Kraemer, Helmut Kretz-Remy, Carole Krichevsky, Anna M. Kroemer, Guido Krueger, Rejko Krut, Oleg Ktistakis, Nicholas T. Kuan, Chia-Yi Kucharczyk, Roza Kumar, Ashok Kumar, Raj Kumar, Sharad Kundu, Mondira Kung, Hsing-Jien Kurz, Tino Kwon, Ho Jeong La Spada, Albert R. Lafont, Frank Lamark, Trond Landry, Jacques Lane, Jon D. Lapaquette, Pierre Laporte, Jocelyn F. Laszlo, Lajos Lavandero, Sergio Lavoie, Josee N. Layfield, Robert Lazo, Pedro A. Le, Weidong Le Cam, Laurent Ledbetter, Daniel J. Lee, Alvin J. X. Lee, Byung-Wan Lee, Gyun Min Lee, Jongdae Lee, Ju-Hyun Lee, Michael Lee, Myung-Shik Lee, Sug Hyung Leeuwenburgh, Christiaan Legembre, Patrick Legouis, Renaud Lehmann, Michael Lei, Huan-Yao Lei, Qun-Ying Leib, David A. Leiro, Jose Lemasters, John J. Lemoine, Antoinette Lesniak, Maciej S. Lev, Dina Levenson, Victor V. Levine, Beth Levy, Efrat Li, Faqiang Li, Jun-Lin Li, Lian Li, Sheng Li, Weijie Li, Xue-Jun Li, Yan-bo Li, Yi-Ping Liang, Chengyu Liang, Qiangrong Liao, Yung-Feng Liberski, Pawel P. Lieberman, Andrew Lim, Hyunjung J. Lim, Kah-Leong Lim, Kyu Lin, Chiou-Feng Lin, Fu-Cheng Lin, Jian Lin, Jiandie D. Lin, Kui Lin, Wan-Wan Lin, Weei-Chin Lin, Yi-Ling Linden, Rafael Lingor, Paul Lippincott-Schwartz, Jennifer Lisanti, Michael P. Liton, Paloma B. Liu, Bo Liu, Chun-Feng Liu, Kaiyu Liu, Leyuan Liu, Qiong A. Liu, Wei Liu, Young-Chau Liu, Yule Lockshin, Richard A. Lok, Chun-Nam Lonial, Sagar Loos, Benjamin Lopez-Berestein, Gabriel Lopez-Otin, Carlos Lossi, Laura Lotze, Michael T. Low, Peter Lu, Binfeng Lu, Bingwei Lu, Bo Lu, Zhen Luciano, Frederic Lukacs, Nicholas W. Lund, Anders H. Lynch-Day, Melinda A. Ma, Yong Macian, Fernando MacKeigan, Jeff P. Macleod, Kay F. Madeo, Frank Maiuri, Luigi Maiuri, Maria Chiara Malagoli, Davide Malicdan, May Christine V. Malorni, Walter Man, Na Mandelkow, Eva-Maria Manon, Stephen Manov, Irena Mao, Kai Mao, Xiang Mao, Zixu Marambaud, Philippe Marazziti, Daniela Marcel, Yves L. Marchbank, Katie Marchetti, Piero Marciniak, Stefan J. Marcondes, Mateus Mardi, Mohsen Marfe, Gabriella Marino, Guillermo Markaki, Maria Marten, Mark R. Martin, Seamus J. Martinand-Mari, Camille Martinet, Wim Martinez-Vicente, Marta Masini, Matilde Matarrese, Paola Matsuo, Saburo Matteoni, Raffaele Mayer, Andreas Mazure, Nathalie M. McConkey, David J. McConnell, Melanie J. McDermott, Catherine McDonald, Christine McInerney, Gerald M. McKenna, Sharon L. McLaughlin, BethAnn McLean, Pamela J. McMaster, Christopher R. McQuibban, G. Angus Meijer, Alfred J. Meisler, Miriam H. Melendez, Alicia Melia, Thomas J. Melino, Gerry Mena, Maria A. Menendez, Javier A. Menna-Barreto, Rubem F. S. Menon, Manoj B. Menzies, Fiona M. Mercer, Carol A. Merighi, Adalberto Merry, Diane E. Meschini, Stefania Meyer, Christian G. Meyer, Thomas F. Miao, Chao-Yu Miao, Jun-Ying Michels, Paul A. M. Michiels, Carine Mijaljica, Dalibor Milojkovic, Ana Minucci, Saverio Miracco, Clelia Miranti, Cindy K. Mitroulis, Ioannis Miyazawa, Keisuke Mizushima, Noboru Mograbi, Baharia Mohseni, Simin Molero, Xavier Mollereau, Bertrand Mollinedo, Faustino Momoi, Takashi Monastyrska, Iryna Monick, Martha M. Monteiro, Mervyn J. Moore, Michael N. Mora, Rodrigo Moreau, Kevin Moreira, Paula I. Moriyasu, Yuji Moscat, Jorge Mostowy, Serge Mottram, Jeremy C. Motyl, Tomasz Moussa, Charbel E. -H. Mueller, Sylke Muenger, Karl Muenz, Christian Murphy, Leon O. Murphy, Maureen E. Musaro, Antonio Mysorekar, Indira Nagata, Eiichiro Nagata, Kazuhiro Nahimana, Aimable Nair, Usha Nakagawa, Toshiyuki Nakahira, Kiichi Nakano, Hiroyasu Nakataogawa, Hitoshi Nanjundan, Meera Naqvi, Naweed I. Narendra, Derek P. Narita, Masashi Navarro, Miguel Nawrocki, Steffan T. Nazarko, Taras Y. Nemchenko, Andriy Netea, Mihai G. Neufeld, Thomas P. Ney, Paul A. Nezis, Ioannis P. Huu Phuc Nguyen Nie, Daotai Nishino, Ichizo Nislow, Corey Nixon, Ralph A. Noda, Takeshi Noegel, Angelika A. Nogalska, Anna Noguchi, Satoru Notterpek, Lucia Novak, Ivana Nozaki, Tomoyoshi Nukina, Nobuyuki Nuernberger, Thorsten Nyfeler, Beat Obara, Keisuke Oberley, Terry D. Oddo, Salvatore Ogawa, Michinaga Ohashi, Toya Okamoto, Koji Oleinick, Nancy L. Oliver, F. Javier Olsen, Laura J. Olsson, Stefan Opota, Onya Osborne, Timothy F. Ostrander, Gary K. Otsu, Kinya Ou, Jing-hsiung James Ouimet, Mireille Overholtzer, Michael Ozpolat, Bulent Paganetti, Paolo Pagnini, Ugo Pallet, Nicolas Palmer, Glen E. Palumbo, Camilla Pan, Tianhong Panaretakis, Theocharis Pandey, Udai Bhan Papackova, Zuzana Papassideri, Issidora Paris, Irmgard Park, Junsoo Park, Ohkmae K. Parys, Jan B. Parzych, Katherine R. Patschan, Susann Patterson, Cam Pattingre, Sophie Pawelek, John M. Peng, Jianxin Perlmutter, David H. Perrotta, Ida Perry, George Pervaiz, Shazib Peter, Matthias Peters, Godefridus J. Petersen, Morten Petrovski, Goran Phang, James M. Piacentini, Mauro Pierre, Philippe Pierrefite-Carle, Valerie Pierron, Gerard Pinkas-Kramarski, Ronit Piras, Antonio Piri, Natik Platanias, Leonidas C. Poeggeler, Stefanie Poirot, Marc Poletti, Angelo Poues, Christian Pozuelo-Rubio, Mercedes Praetorius-Ibba, Mette Prasad, Anil Prescott, Mark Priault, Muriel Produit-Zengaffinen, Nathalie Progulske-Fox, Ann Proikas-Cezanne, Tassula Przedborski, Serge Przyklenk, Karin Puertollano, Rosa Puyal, Julien Qian, Shu-Bing Qin, Liang Qin, Zheng-Hong Quaggin, Susan E. Raben, Nina Rabinowich, Hannah Rabkin, Simon W. Rahman, Irfan Rami, Abdelhaq Ramm, Georg Randall, Glenn Randow, Felix Rao, V. Ashutosh Rathmell, Jeffrey C. Ravikumar, Brinda Ray, Swapan K. Reed, Bruce H. Reed, John C. Reggiori, Fulvio Regnier-Vigouroux, Anne Reichert, Andreas S. Reiners, John J., Jr. Reiter, Russel J. Ren, Jun Revuelta, Jose L. Rhodes, Christopher J. Ritis, Konstantinos Rizzo, Elizete Robbins, Jeffrey Roberge, Michel Roca, Hernan Roccheri, Maria C. Rocchi, Stephane Rodemann, H. Peter de Cordoba, Santiago Rodriguez Rohrer, Baerbel Roninson, Igor B. Rosen, Kirill Rost-Roszkowska, Magdalena M. Rouis, Mustapha Rouschop, Kasper M. A. Rovetta, Francesca Rubin, Brian P. Rubinsztein, David C. Ruckdeschel, Klaus Rucker, Edmund B., III Rudich, Assaf Rudolf, Emil Ruiz-Opazo, Nelson Russo, Rossella Rusten, Tor Erik Ryan, Kevin M. Ryter, Stefan W. Sabatini, David M. Sadoshima, Junichi Saha, Tapas Saitoh, Tatsuya Sakagami, Hiroshi Sakai, Yasuyoshi Salekdeh, Ghasem Hoseini Salomoni, Paolo Salvaterra, Paul M. Salvesen, Guy Salvioli, Rosa Sanchez, Anthony M. J. Sanchez-Alcazar, Jose A. Sanchez-Prieto, Ricardo Sandri, Marco Sankar, Uma Sansanwal, Poonam Santambrogio, Laura Saran, Shweta Sarkar, Sovan Sarwal, Minnie Sasakawa, Chihiro Sasnauskiene, Ausra Sass, Miklos Sato, Ken Sato, Miyuki Schapira, Anthony H. V. Scharl, Michael Schaetzl, Hermann M. 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Xi, Zhijun Xia, Pu Xiao, Gengfu Xie, Zhiping Xie, Zhonglin Xu, Da-zhi Xu, Jianzhen Xu, Liang Xu, Xiaolei Yamamoto, Ai Yamamoto, Akitsugu Yamashina, Shunhei Yamashita, Michiaki Yan, Xianghua Yanagida, Mitsuhiro Yang, Dun-Sheng Yang, Elizabeth Yang, Jin-Ming Yang, Shi Yu Yang, Wannian Yang, Wei Yuan Yang, Zhifen Yao, Meng-Chao Yao, Tso-Pang Yeganeh, Behzad Yen, Wei-Lien Yin, Jia-jing Yin, Xiao-Ming Yoo, Ook-Joon Yoon, Gyesoon Yoon, Seung-Yong Yorimitsu, Tomohiro Yoshikawa, Yuko Yoshimori, Tamotsu Yoshimoto, Kohki You, Ho Jin Youle, Richard J. Younes, Anas Yu, Li Yu, Long Yu, Seong-Woon Yu, Wai Haung Yuan, Zhi-Min Yue, Zhenyu Yun, Cheol-Heui Yuzaki, Michisuke Zabirnyk, Olga Silva-Zacarin, Elaine Zacks, David Zacksenhaus, Eldad Zaffaroni, Nadia Zakeri, Zahra Zeh, Herbert J., III Zeitlin, Scott O. Zhang, Hong Zhang, Hui-Ling Zhang, Jianhua Zhang, Jing-Pu Zhang, Lin Zhang, Long Zhang, Ming-Yong Zhang, Xu Dong Zhao, Mantong Zhao, Yi-Fang Zhao, Ying Zhao, Zhizhuang J. Zheng, Xiaoxiang Zhivotovsky, Boris Zhong, Qing Zhou, Cong-Zhao Zhu, Changlian Zhu, Wei-Guo Zhu, Xiao-Feng Zhu, Xiongwei Zhu, Yuangang Zoladek, Teresa Zong, Wei-Xing Zorzano, Antonio Zschocke, Juergen Zuckerbraun, Brian TI Guidelines for the use and interpretation of assays for monitoring autophagy SO AUTOPHAGY LA English DT Review DE autolysosome; autophagosome; flux; LC3; lysosome; phagophore; stress; vacuole ID ACTIVATED PROTEIN-KINASE; CHAPERONE-MEDIATED AUTOPHAGY; PROGRAMMED CELL-DEATH; ISOLATED RAT HEPATOCYTES; STARVATION-INDUCED AUTOPHAGY; VACUOLE TARGETING PATHWAY; GLUCAGON-INDUCED AUTOPHAGY; BREAST-CANCER CELLS; BETAINE HOMOCYSTEINE METHYLTRANSFERASE; ENDOPLASMIC-RETICULUM STRESS AB In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. 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[Amer, Amal O.; Drew, Mark E.] Ohio State Univ, Dept Internal Med, Dept Microbial Infect & Immun, Ctr Microbial Interface Biol, Columbus, OH 43210 USA. [Amer, Amal O.] Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. [Andrieu-Abadie, Nathalie; Poirot, Marc] Univ Toulouse 3, INSERM, UMR1037, F-31062 Toulouse, France. [Anantharam, Vellareddy; Kanthasamy, Anumantha G.; Kanthasamy, Arthi] Iowa State Univ, Dept Biomed Sci, Iowa Ctr Adv Neurotoxicol, Ames, IA USA. [Ann, David K.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Pharmacol, Duarte, CA USA. [Anoopkumar-Dukie, Shailendra; Grant, Gary D.] Griffith Univ, Griffith Hlth Inst, Gold Coast, Australia. [Anoopkumar-Dukie, Shailendra; Grant, Gary D.] Griffith Univ, Sch Pharm, Gold Coast, Australia. [Aoki, Hiroshi; Apostolova, Nadezda] Niigata Univ, Brain Res Inst, Dept Neurosurg, Niigata 95021, Japan. Univ Valencia, Fac Med, Dept Farmacol, Valencia, Spain. [Arancia, Giuseppe; Condello, Maria; Meschini, Stefania] Italian Natl Inst Hlth, Technol & Hlth Dept, Ultrastruct Methods Innovat Canc Therapies Unit, Rome, Italy. [Aris, John P.] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL USA. [Asanuma, Katsuhiko; Tomino, Yasuhiko] Juntendo Univ, Fac Med, Dept Internal Med, Div Nephrol, Tokyo, Japan. [Asare, Nana Y. O.] Norwegian Inst Publ Hlth, Dept Chem Toxicol, Oslo, Norway. [Ashida, Hisashi] Kyoto Univ, Grad Sch Biostudies, Kyoto, Japan. [Nogalska, Anna] Univ So Calif, Keck Sch Med, Dept Neurol, USC Neuromuscular Ctr, Los Angeles, CA 90033 USA. [Askew, David S.] Univ Cincinnati, Coll Med, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA. [Bost, Frederic; Luciano, Frederic] Univ Nice Sophia Antipolis, INSERM, Ctr Mediterraneen Med Mol C3M, U1065, Nice, France. [Baba, Misuzu] Kogakuin Univ, Sci & Technol Res Inst, Collaborat Open Res Ctr, Tokyo, Japan. [Baehrecke, Eric H.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA USA. [Bahr, Ben A.] Univ N Carolina Pembroke, William C Friday Lab, Biotechnol Res & Training Ctr, Pembroke, NC USA. [Bai, Xue-Yuan; Chen, Xiangmei] Chinese Peoples Liberat Army Gen Hosp, State Key Lab Kidney Dis, Dept Nephrol, Beijing, Peoples R China. [Bailly, Yannick] Univ Strasbourg, INCI CNRS UPR 3212, Strasbourg, France. [Baiocchi, Robert] Ohio State Univ, Div Hematol, Columbus, OH 43210 USA. [Baldini, Giulia] Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. [Balduini, Walter] Univ Urbino Carlo Bo, Dept Biomol Sci, Urbino, Italy. [Ballabio, Andrea; Brunetti-Pierri, Nicola; Settembre, Carmine] Telethon Inst Genet & Med TIGEM, Naples, Italy. [Ballabio, Andrea; Brunetti-Pierri, Nicola; Settembre, Carmine] Univ Naples Federico II, Dept Pediat, Naples, Italy. [Ballabio, Andrea; Settembre, Carmine] Baylor Coll Med, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA. [Bamber, Bruce A.] Univ Toledo, Dept Biol Sci, Toledo, OH 43606 USA. [Bampton, Edward T. W.; Melino, Gerry] Univ Leicester, MRC, Toxicol Unit, Leicester, Leics, England. [Banhegyi, Gabor] Semmelweis Univ, Dept Med Chem Mol Biol & Pathobiochem, H-1085 Budapest, Hungary. [Bassham, Diane C.] Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA USA. [Bast, Robert C., Jr.; Fan, Zhen; Lopez-Berestein, Gabriel; Lu, Zhen; Ozpolat, Bulent] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Batoko, Henri] Catholic Univ Louvain, Inst Life Sci, UCL ISV, B-3000 Louvain, Belgium. [Bay, Boon-Huat] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Anat, Singapore 117595, Singapore. [Beau, Isabelle; Esclatine, Audrey] INSERM, UMR S984, Chatenay Malabry, France. [Beau, Isabelle; Esclatine, Audrey] Univ Paris 11, Chatenay Malabry, France. [Bechet, Daniel M.] INRA, UMR 1019, Unite Nutr Humaine, Clermont Ferrand, France. [Bechet, Daniel M.] Univ Auvergne, CRNH, Clermont Ferrand, France. [Begley, Thomas J.] SUNY Albany, Coll Nanoscale Sci & Engn, Albany, NY 12222 USA. [Behl, Christian] Johannes Gutenberg Univ Mainz, Inst Pathobiochem, Univ Med Ctr, Mainz, Germany. [Behrends, Christian; Dikic, Ivan] Goethe Univ Frankfurt, Sch Med, Inst Biochem 2, Frankfurt, Germany. [Bekri, Soumeya] Univ Rouen, Rouen Univ Hosp, Lab Biochim Med, Rouen, France. [Bekri, Soumeya] Univ Rouen, NeoVasc EA 4309, Rouen, France. [Bellaire, Bryan] Iowa State Univ, Ames, IA USA. [Bendall, Linda J.] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Westmead, NSW 2145, Australia. [Benetti, Luca] Merck Mfg Div, West Point, PA USA. [Berliocchi, Laura] Magna Graecia Univ Catanzaro, Dept Hlth Sci, Catanzaro, Italy. [Bernardi, Henri; Sanchez, Anthony M. J.] Univ Montpellier I, INRA, Dynam Musculaire & Metab UMR866, Montpellier, France. [Bernassola, Francesca; Marfe, Gabriella; Palumbo, Camilla] Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, Rome, Italy. [Besteiro, Sebastien] Univ Montpellier 2, CNRS, DIMNP, UMR5235, Montpellier, France. [Bhatia-Kissova, Ingrid] Comenius Univ, Dept Biochem, Bratislava, Slovakia. [Bi, Xiaoning] Western Univ Hlth Sci, Pomona, CA USA. [Biard-Piechaczyk, Martine; Espert, Lucile] CNRS, Ctr Etud Agents Pathogenes & Biotechnol Sante, UM1, UM2, Montpellier, France. [Blum, Janice S.] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. [Boise, Lawrence H.; Lonial, Sagar; Sun, Shi-Yong] Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA USA. [Bonaldo, Paolo; Sandri, Marco] Univ Padua, Dept Biomed Sci, Padua, Italy. [Boone, David L.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Bornhauser, Beat C.; Bourquin, Jean-Pierre] Univ Zurich, Univ Childrens Hosp, Dept Oncol, Zurich, Switzerland. [Bortoluci, Karina R.] Univ Fed Sao Paulo, Dept Biol Sci, Sao Paulo, Brazil. [Bortoluci, Karina R.] Univ Fed Sao Paulo, Cellular & Mol Therapy Ctr, Sao Paulo, Brazil. [Begley, Thomas J.] Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA. [Boya, Patricia] CSIC, CIB, Ctr Invest Biol, Dept Cell Proliferat & Dev, Madrid, Spain. [Boyer-Guittaut, Michael] Univ Franche Comte, Biochim Lab, EA3922, UFR Sci & Tech,IFR133, F-25030 Besancon, France. [Bozhkov, Peter V.] Swedish Univ Agr Sci, Uppsala BioCtr, Dept Plant Biol & Forest Genet, Uppsala, Sweden. [Brady, Nathan R.] Heidelberg Univ, German Canc Res Ctr DKFZ, Heidelberg, Germany. [Brady, Nathan R.] Heidelberg Univ, Fac Med, Heidelberg, Germany. [Brancolini, Claudio] Univ Udine, Dipartment Sci Med & Biol, I-33100 Udine, Italy. [Brech, Andreas; Nezis, Ioannis P.; Rusten, Tor Erik; Stenmark, Harald] Univ Oslo, Ctr Canc Biomed, Oslo, Norway. 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[Burbulla, Lena F.] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany. [Burbulla, Lena F.] DZNE, German Ctr Neurodegenerat Dis, Tubingen, Germany. [Bursch, Wilfried] Med Univ Vienna, Inst Canc Res, Div Oncol, Dept Med 1, Vienna, Austria. [Butchar, Jonathan P.] Ohio State Univ, Dept Internal Med, Div Pulm Allergy Crit Care & Sleep Med, Columbus, OH 43210 USA. [Buzgariu, Wanda; Galliot, Brigitte] Univ Geneva, Dept Genet & Evolut, Geneva, Switzerland. [Bydlowski, Sergio P.] Univ Sao Paulo, Sch Med, Lab Genet & Mol Hematol, Sao Paulo, Brazil. [Cadwell, Ken] NYU, Sch Med, Dept Microbiol, Skirball Inst Biomol Med, New York, NY 10016 USA. [Cahova, Monika; Papackova, Zuzana] Inst Clin & Expt Med, Dept Metab & Diabet, Prague, Czech Republic. [Cai, Dongsheng] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10467 USA. [Cai, Jiyang] Vanderbilt Univ, Vanderbilt Eye Inst, Nashville, TN USA. 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[Candi, Eleonora] Univ Roma Tor Vergata, Dept Biochem, Rome, Italy. [Cao, Lizhi] Cent S Univ, Xiangya Hosp, Dept Pediat, Changsha, Hunan, Peoples R China. [Caplan, Allan B.] Univ Idaho, Dept Plant Soil & Entomol Sci, Moscow, ID 83843 USA. [Carding, Simon R.] Univ E Anglia, Fac Hlth, Norwich Sch Med, GI Tract Programme,Inst Food Res, Norwich NR4 7TJ, Norfolk, England. [Carding, Simon R.] Univ E Anglia, Fac Hlth, Norwich Sch Med, Dept Mucosal Immunol, Norwich NR4 7TJ, Norfolk, England. [Cardoso, Sandra M.; Moreira, Paula I.] Univ Coimbra, Fac Med, Coimbra, Portugal. [Cardoso, Sandra M.; Moreira, Paula I.] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Carew, Jennifer S.; Nawrocki, Steffan T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol Oncol, San Antonio, TX 78229 USA. [Carlin, Cathleen R.] Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA. [Carmignac, Virgine; Durbeej, Madeleine] Lund Univ, Dept Expt Med Sci, Muscle Biol Unit, Lund, Sweden. [Carneiro, Leticia A. M.] Univ Fed Rio de Janeiro, Inst Microbiol, BR-21941 Rio De Janeiro, Brazil. [Carra, Serena] Univ Modena & Reggio Emilia, Dept Med Biosci, Modena, Italy. [Carra, Serena; Kampinga, Harm H.] Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Groningen, Netherlands. [Caruso, Rosario A.] Univ Messina, Dept Human Pathol, Messina, Italy. [Casari, Giorgio] Univ Vita Salute San Raffaele, Milan, Italy. [Casari, Giorgio] Ist Sci San Raffaele, I-20132 Milan, Italy. [Casas, Caty] Univ Autonoma Barcelona, Dept Cell Biol Physiol & Immunol, Inst Neurosci, E-08193 Barcelona, Spain. [Castino, Roberta; Isidoro, Ciro] Univ Piemonte Orientale, Dept Hlth Sci, Novara, Italy. [Cebollero, Eduardo; Reggiori, Fulvio] Univ Med Ctr Utrecht, Dept Cell Biol, Utrecht, Netherlands. [Cebollero, Eduardo; Reggiori, Fulvio] Univ Med Ctr Utrecht, Inst Biomembranes, Utrecht, Netherlands. [Cebollero, Eduardo] Univ Med Ctr Utrecht, Dept Biochem & Cell Biol, Utrecht, Netherlands. [Cecconi, Francesco] IRCCS Santa Lucia Fdn, Rome, Italy. [Cecconi, Francesco; Ciriolo, Maria R.; Piacentini, Mauro] Univ Roma Tor Vergata, Dept Biol, Dulbecco Telethon Inst, I-00173 Rome, Italy. [Celli, Jean] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. [Chaachouay, Hassan; Rodemann, H. Peter] Univ Tubingen, Dept Radiat Oncol, Div Radiat Biol & Mol Environm Res, Tubingen, Germany. [Chae, Han-Jung] Chonbuk Univ, Sch Med, Cardiovasc Res Inst, Chonbuk, South Korea. [Chae, Han-Jung] Chonbuk Univ, Dept Pharmacol, Chonbuk, South Korea. [Chai, Chee-Yin] Kaohsiung Med Univ Hosp, Dept Pathol, Kaohsiung, Taiwan. [Chan, David C.] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Chan, Edmond Y.; Coppens, Graham H. Coombs Isabelle] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow, Lanark, Scotland. [Chang, Raymond Chuen-Chung] Univ Hong Kong, Li Ka Shing Fac Med, Dept Anat, Lab Neurodegenerat Dis, Hong Kong, Hong Kong, Peoples R China. [Che, Chi-Ming; Lok, Chun-Nam; Sy, Lai-King] Univ Hong Kong, Dept Chem, Hong Kong, Hong Kong, Peoples R China. [Chen, Ching-Chow; Lin, Wan-Wan] Natl Taiwan Univ, Coll Med, Dept Pharmacol, Taipei 10764, Taiwan. [Chen, Guang-Chao; Yang, Wei Yuan] Acad Sinica, Inst Biol Chem, Taipei, Taiwan. [Chen, Guo-Qiang] Shanghai Jiao Tong Univ, Sch Med, Key Lab Cell Differentiat & Apoptosis, Chinese Minist Educ, Shanghai 200030, Peoples R China. [Chen, Min; Wang, Jin] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Chen, Quan] Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing, Peoples R China. [Chen, Quan] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China. [Chen, Steve S. -L.; Ke, Po-Yuan; Lin, Yi-Ling] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Chen, WenLi] S China Normal Univ, MOE Key Lab Laser Life Sci, Guangzhou, Guangdong, Peoples R China. [Chen, WenLi] S China Normal Univ, Inst Laser Life Sci, Guangzhou, Guangdong, Peoples R China. [Chen, Xi] Zhejiang Univ, Sch Med, Childrens Hosp, Hangzhou 310003, Zhejiang, Peoples R China. [Chen, Xiequn] Fourth Mil Med Univ, Xijing Hosp, Dept Hematol, Xian 710032, Peoples R China. [Chen, Ye-Guang; Liu, Yule; Yu, Li] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China. [Chen, Yingyu] Peking Univ, Dept Immunol, Ctr Human Dis Genom, Beijing 100871, Peoples R China. [Chen, Yongqiang; Guan, Jun-Lin; Towns, Roberto; Wiley, John W.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Chen, Yu-Jen] Mackay Mem Hosp, Dept Radiat Oncol, Taipei, Taiwan. [Chen, Zhixiang] Purdue Univ, Dept Bot & Plant Pathol, W Lafayette, IN 47907 USA. [Cheng, Alan] Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40292 USA. [Cheng, Christopher H. K.] Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. [Cheng, Yan; Wang, Hong-Gang; Yang, Jin-Ming] Penn State Univ, Coll Med, Penn State Hershey Canc Inst, Dept Pharmacol, Hershey, PA USA. [Cheong, Heesun; Thompson, Craig B.] Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10021 USA. [Cheong, Jae-Ho] Yonsei Univ, Coll Med, Dept Surg, Seoul, South Korea. [Cherry, Sara] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Chess-Williams, Russ] Bond Univ, Fac Hlth Sci & Med, Southport, Qld 4229, Australia. [Cheung, Zelda H.] Univ Hong Kong, Li Ka Shing Fac Med, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. [Chevet, Eric] Univ Bordeaux Segalen, Bordeaux, France. [Chevet, Eric] INSERM, U1053, Bordeaux, France. [Chiang, Hui-Ling] Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA USA. [Chiba, Tomoki] Univ Tsukuba, Grad Sch Life & Environm Sci, Ibaraki, Japan. [Chin, Lih-Shen; Li, Lian; Mao, Zixu] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. [Chiou, Shih-Hwa] Natl Yang Ming Univ, Sch Med, Inst Pharmacol, Taipei 112, Taiwan. [Cho, Chi Hin] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. [Cho, Dong-Hyung] Kyung Hee Univ, Grad Sch EW Med Sci, Yongin, South Korea. [Choi, Augustine M. K.; Haspel, Jeffrey A.; Henske, Elizabeth P.; Nakahira, Kiichi; Ryter, Stefan W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Choi, DooSeok] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea. [Choi, Kyeong Sook] Ajou Univ, Sch Med, Inst Med Sci, Suwon 441749, South Korea. [Choi, Mary E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Renal Div, Boston, MA 02115 USA. [Chouaib, Salem] Inst Gustave Roussy, INSERM, U753 PR1, F-94805 Villejuif, France. [Choubey, Divaker] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA. [Choubey, Vinay; Kaasik, Allen] Univ Tartu, Dept Pharmacol, EE-50090 Tartu, Estonia. [Chu, Charleen T.; Rabinowich, Hannah] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Chu, Charleen T.] Univ Pittsburgh, Sch Med, Ctr Neurosci, Pittsburgh, PA USA. [Chuang, Tsung-Hsien] Natl Hlth Res Inst, Immunol Res Ctr, Miaoli Cty, Taiwan. [Chueh, Sheau-Huei] Natl Def Med Ctr, Dept Biochem, Taipei, Taiwan. [Chun, Taehoon; Park, Ohkmae K.] Korea Univ, Sch Life Sci & Biotechnol, Seoul, South Korea. [Chwae, Yong-Joon] Ajou Univ, Sch Med, Dept Microbiol, Suwon 441749, South Korea. [Chye, Mee-Len] Univ Hong Kong, Sch Biol Sci, Pokfulam, Hong Kong, Peoples R China. [Ciarcia, Roberto; Florio, Salvatore; Granato, Giovanna Elvira] Univ Naples Federico II, Dept Struct Funct & Biol Technol, Naples, Italy. [Ciriolo, Maria R.] IRCCS San Raffaele, Rome, Italy. [Clague, Michael J.] Univ Liverpool, Physiol Lab, Inst Translat Med, Liverpool L69 3BX, Merseyside, England. [Clark, Robert S. B.] Safar Ctr Resuscitat Res, Pittsburgh, PA USA. [Clarke, Peter G. H.; Puyal, Julien] Univ Lausanne, Dept Biol Cellulaire & Morphol, Lausanne, Switzerland. [Clarke, Robert; Saha, Tapas] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA. [Codogno, Patrice] Univ Paris S, INSERM, U984, Paris, France. [Coller, Hilary A.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. [Colombo, Maria I.] Univ Nacl Cuyo, CONICET, Inst Histol & Embriol, Lab Biol Celular & Mol, RA-5500 Mendoza, Argentina. [Comincini, Sergio] Univ Pavia, Dept Genet & Microbiol, I-27100 Pavia, Italy. [Condorelli, Fabrizio] Univ Piemonte Orientale, Fac Pharm, Novara, Italy. [Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, NIH, Bethesda, MD 20892 USA. [Corbalan, Ramon] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Cossart, Pascale] Pontificia Univ Catolica Chile, Fac Med, Dept Enfermedades Cardiovasc, Santiago, Chile. [Costelli, Paola] Inst Pasteur, Unite Interact Bacteries Cellules, Paris, France. [Costelli, Paola] INSERM, INRA, U604, USC2020, Paris, France. [Costes, Safia] Univ Turin, Dept Expt Med & Oncol, Turin, Italy. [Coto-Montes, Ana] Univ Calif Los Angeles, David Geffen Sch Med, Larry Hillblom Islet Res Ctr, Los Angeles, CA 90095 USA. [Couve, Eduardo] Univ Oviedo, Dept Morfol & Biol Celular, Oviedo, Spain. [Coxon, Fraser P.] Univ Valparaiso, Fac Ciencias, Dept Biol & Cs Ambientales, Valparaiso, Chile. [Cregg, James M.; Helfrich, Miep H.; Hocking, Lynne J.] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland. [Crespo, Jose L.] Keck Grad Inst Appl Sci, Claremont, CA USA. [Cronje, Marianne J.] Univ Seville, CSIC, Inst Bioquim Vegetal Fotosintesis, Seville, Spain. Univ Johannesburg, Dept Biochem, Johannesburg, South Africa. [Kaushik, Susmita] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10467 USA. [Kaushik, Susmita; Koga, Hiroshi] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10467 USA. [D'Amelio, Marcello; Kaushik, Susmita; Koga, Hiroshi] Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Bronx, NY 10467 USA. Univ Iowa, Dept Surg, Iowa City, IA 52242 USA. [D'Amelio, Marcello] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. Santa Lucia Fdn, European Ctr Brain Res, Expt Neurol Unit, Rome, Italy. Univ Campus Biomed, Rome, Italy. [Cuervo, Ana Maria; Darfeuille-Michaud, Arlette] INRA, USC 2018, Clermont Ferrand, France. [Cuervo, Ana Maria; Darfeuille-Michaud, Arlette] Univ Auvergne, INSERM, UMR 1071, Clermont Ferrand, France. [Cullen, Joseph J.; Davids, Lester M.] Univ Cape Town, Dept Human Biol, ZA-7925 Cape Town, South Africa. [Czaja, Mark J.; Davies, Faith E.] Inst Canc Res, Div Mol Pathol, Sutton, Surrey, England. [Czaja, Mark J.; Davies, Faith E.] Royal Marsden Hosp, Sutton, Surrey, England. [De Felici, Massimo] Univ Roma Tor Vergata, Dept Publ Hlth & Cell Biol, Rome, Italy. [de Groot, John F.; Fueyo, Juan; Gomez-Manzano, Candelaria; Jiang, Hong] Univ Texas Houston, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [de Haan, Cornelis A. M.; Monastyrska, Iryna] Univ Utrecht, Dept Infect Dis & Immunol, Div Virol, Utrecht, Netherlands. [De Martino, Luisa; Fiorito, Filomena; Iovane, Valentine; Pagnini, Ugo] Univ Naples Federico II, Dept Pathol & Anim Hlth, Naples, Italy. [De Milito, Angelo; Joseph, Bertrand; Panaretakis, Theocharis] Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden. [De Tata, Vincenzo] Univ Pisa, Sch Med, Dept Expt Pathol, I-56100 Pisa, Italy. [Debnath, Jayanta] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Degterev, Alexei] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. [Dehay, Benjamin] Univ Bordeaux Segalen, Inst Malad Neurodegenerat, CNRS, UMR 5293, Bordeaux, France. [Delbridge, Lea M. D.] Univ Melbourne, Dept Physiol, Parkville, Vic 3052, Australia. [Demarchi, Francesca; Schneider, Claudio] Lab Nazl Consorzio Interuniv, Trieste, Italy. [Deng, Yi Zhen; Naqvi, Naweed I.] Natl Univ Singapore, Temasek Life Sci Lab, Fungal Pathobiol Grp, Singapore 117548, Singapore. [Dengjel, Joen] Freiburg Inst Adv Studies FRIAS, Sch Life Sci LifeNet, Freiburg, Germany. [Dent, Paul] Virginia Commonwealth Univ, Sch Med, VCU Massey Canc Ctr, Dept Neurosurg,VCU Inst Moleular Med, Richmond, VA USA. [Denton, Donna] SA Pathol, Ctr Canc Biol, Adelaide, SA, Australia. [Denton, Donna] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA, Australia. [Deretic, Vojo] Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Desai, Shyamal D.] Louisiana State Univ, Hlth Sci Ctr, Sch Med, Dept Biochem & Mol Biol, New Orleans, LA USA. [Devenish, Rodney J.; Mijaljica, Dalibor; Prescott, Mark; Ramm, Georg] Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic 3004, Australia. 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[Duan, Qiuhong] Huazhong Univ Techol & Sci, Tongji Med Coll, Dept Biochem & Mol Biol, Wuhan, Hubei, Peoples R China. [Duchosal, Michel A.] Univ Lausanne Hosp, Div Hematol, Lausanne, Switzerland. [Duchosal, Michel A.] Univ Lausanne Hosp, Cent Lab Hematol, Lausanne, Switzerland. [Dugail, Isabelle; Maiuri, Maria Chiara] INSERM, Ctr Rech Cordeliers, Paris, France. [Dugail, Isabelle] Univ Paris 06, Paris, France. [Duszenko, Michael] Univ Tubingen, Dept Biochem, Tubingen, Germany. [Edelstein, Charles L.] Univ Colorado Denver, Div Renal Dis & Hypertens, Aurora, CO USA. [Edinger, Aimee L.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA. [Egea, Gustavo] Univ Barcelona, Fac Med, IDIBAPS, Dept Biol Celular Inmunol & Neurociencias, Barcelona 7, Spain. [Eichinger, Ludwig; Noegel, Angelika A.] Univ Cologne, Fac Med, Inst Biochem 1, D-50931 Cologne, Germany. [Eissa, N. Tony; Lin, Weei-Chin] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Ekmekcioglu, Suhendan] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [El-Deiry, Wafik S.] Penn State Coll Med, Penn State Hershey Med Ctr, Dept Med Hematol Oncol, Lab Translat Oncol & Expt Canc Therapeut, Hershey, PA USA. [Elazar, Zvulun] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. [Elgendy, Mohamed; Minucci, Saverio] Univ Milan, European Inst Oncol, Milan, Italy. [Elgendy, Mohamed; Minucci, Saverio] Univ Milan, Dept Biomol Sci & Biotechnol, Milan, Italy. [Ellerby, Lisa M.] Buck Inst Res Aging, Novato, CA USA. [Eng, Kai Er; McInerney, Gerald M.] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [Engelbrecht, Anna-Mart; Loos, Benjamin] Univ Stellenbosch, Dept Physiol Sci, ZA-7600 Stellenbosch, South Africa. [Engelender, Simone] Technion Israel Inst Technol, Bruce Rappaport Fac Med, Dept Pharmacol, IL-31096 Haifa, Israel. [Erenpreisa, Jekaterina] Latvian Biomed Res & Study Ctr, Riga, Latvia. [Eskelinen, Eeva-Liisa] Univ Helsinki, Dept Biosci, Helsinki, Finland. [Espina, Virginia] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA. [Fan, Huizhou] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Physiol & Biophys, Piscataway, NJ 08854 USA. [Fan, Jia] Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Shanghai 200433, Peoples R China. [Fan, Qi-Wen; Ilkhanizadeh, Shirin; Weiss, William A.] Univ Calif San Francisco, Dept Neurol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Fan, Qi-Wen; Ilkhanizadeh, Shirin; Weiss, William A.] Univ Calif San Francisco, Dept Pediat, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Fan, Qi-Wen; Ilkhanizadeh, Shirin; Weiss, William A.] Univ Calif San Francisco, Dept Neurol Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Fan, Qi-Wen; Ilkhanizadeh, Shirin; Weiss, William A.] Univ Calif San Francisco, Brain Tumor Res Ctr, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Fang, Shengyun; Monteiro, Mervyn J.] Univ Maryland, Ctr Biomed Engn & Technol BioMET, Baltimore, MD 21201 USA. [Fang, Shengyun] Univ Maryland, Dept Physiol, Baltimore, MD 21201 USA. [Fang, Yongqi] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China. [Fanto, Manolis] Kings Coll London, MRC, Ctr Dev Neurobiol, London, England. [Farkas, Thomas; Jaattela, Marja] Danish Canc Soc, Res Ctr, Copenhagen, Denmark. [Farre, Jean-Claude; Nazarko, Taras Y.] Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA. [Faure, Mathias] Univ Lyon 1, F-69365 Lyon, France. [Faure, Mathias] Univ Lyon, INSERM, U851, Lyon, France. [Fechheimer, Marcus; Furukawa, Ruth H.] Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA. [Feng, Carl G.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Feng, Jian] SUNY Buffalo, Dept Physiol & Biophys, Buffalo, NY 14260 USA. [Feng, Qili] S China Normal Univ, Sch Life Sci, Guangdong Prov Key Lab Biotechnol Plant Dev, Guangzhou, Guangdong, Peoples R China. [Feng, Youji] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Dept Obstet & Gynecol, Shanghai 200030, Peoples R China. [Fesues, Laszlo] Univ Debrecen, Res Ctr Mol Med, Hungarian Acad Sci, Res Grp,Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. [Fesues, Laszlo] Univ Debrecen, Res Ctr Mol Med, Hungarian Acad Sci, Res Grp,Dept Apoptosis & Genom, H-4012 Debrecen, Hungary. [Feuer, Ralph] San Diego State Univ, Dept Biol, Cell & Mol Biol Joint Doctoral Program, San Diego, CA 92182 USA. [Figueiredo-Pereira, Maria E.] CUNY, Hunter Coll, Dept Biol Sci, New York, NY 10021 USA. [Fimia, Gian Maria] IRCCS L Spallanzani, Natl Inst Infect Dis, Rome, Italy. [Fingar, Diane C.; Guan, Jun-Lin; Han, Ting; Lin, Jiandie D.] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI USA. [Finkbeiner, Steven] Univ Calif San Francisco, Gladstone Inst, Taube Koret Ctr Huntingtons Dis, San Francisco, CA 94143 USA. [Finkbeiner, Steven] Univ Calif San Francisco, Hellman Alzheimers Dis Program, San Francisco, CA 94143 USA. [Finkel, Toren] NHLBI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Finley, Kim D.; Gottlieb, Roberta A.] San Diego State Univ, Biosci Ctr, San Diego, CA 92182 USA. [Fisher, Edward A.] NYU, Sch Med, Dept Med, New York, NY USA. [Fisher, Edward A.] NYU, Sch Med, Dept Cell Biol, Marc & Ruti Bell Program Vasc Biol, New York, NY 10016 USA. [Fisher, Paul B.] Virginia Commonwealth Univ, Sch Med, VCU Inst Moleular Med, Dept Human & Mol Genet,VCU Massey Canc Ctr, Richmond, VA USA. [Flajolet, Marc; Tian, Yuan] Rockefeller Univ, Lab Mol & Cellular Neurosci, New York, NY 10021 USA. [Florez-McClure, Maria L.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Fon, Edward A.] McGill Univ, Dept Neurol & Neurosurg, McGill Parkinson Program, Montreal Neurol Inst, Montreal, PQ, Canada. [Fornai, Francesco] Univ Pisa, Dept Human Morphol & Appl Biol, Pisa, Italy. [Fornai, Francesco] IRCCS Neuromed, Pozzilli, Italy. [Fortunato, Franco] Univ Heidelberg Hosp, Dept Surg, Res Lab, Heidelberg, Germany. [Fox, Howard S.] Univ Nebraska, Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE USA. [Franco, Rodrigo] Univ Nebraska, Sch Vet Med & Biomed Sci, Lincoln, NE USA. [Franco, Rodrigo] Univ Nebraska, Redox Biol Ctr, Lincoln, NE USA. [Frankel, Lisa B.; Lund, Anders H.] Univ Copenhagen, Biotech Res & Innovat Ctre, Copenhagen, Denmark. [Fransen, Marc] Katholieke Univ Leuven, Dept Mol & Cellular Med, Louvain, Belgium. [Fuentes, Jose M.; Gonzalez-Polo, Rosa Ana] Univ Extremadura, Dept Bioquim & Biol Mol Genet, EU Enfermeria, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Caceres, Spain. [Fujii, Jun] Kyushu Univ, Grad Sch Med Sci, Dept Bacteriol, Kagoshima, Japan. [Fujisaki, Kozo; Umemiya-Shirafuji, Rika] Kyushu Univ, Dept Frontier Vet Med, Lab Emerging Infect Dis, Kagoshima, Japan. [Fujita, Eriko] Jichi Med Univ, Dept Pediat, Shimotsuke, Tochigi, Japan. [Fukuda, Mitsunori] Tohoku Univ, Grad Sch Life Sci, Dept Dev Biol & Neurosci, Sendai, Miyagi 980, Japan. [Gaestel, Matthias; Menon, Manoj B.] Hannover Med Sch, Inst Physiol Chem, D-3000 Hannover, Germany. [Gailly, Philippe] Univ Louvain, Lab Cell Physiol, Brussels, Belgium. [Gajewska, Malgorzata; Motyl, Tomasz] Warsaw Univ Life Sci, Fac Vet Med, Dept Physiol Sci, Warsaw, Poland. [Galy, Vincent] Univ Paris 06, CNRS, UMR 7622, Paris, France. [Ganesh, Subramaniam] Indian Inst Technol, Dept Biol Sci & Bioengn, Kanpur 208016, Uttar Pradesh, India. [Ganetzky, Barry] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. [Ganley, Ian G.] Univ Dundee, Coll Life Sci, MRC, Prot Phosphorylat Unit, Dundee, Scotland. [Gao, Fen-Biao] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. [Gao, George F.] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China. [Gao, Jinming] UT SW Med Ctr, Dallas, TX USA. [Garcia, Lorena; Lavandero, Sergio] Univ Chile, Fac Med, Santiago 7, Chile. [Garcia, Lorena; Lavandero, Sergio] Univ Chile, Fac Ciencias Quim & Farmaceut, Ctr Estudios Mol Celula, Santiago 7, Chile. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Garcia-Marcos, Mikel] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. [Garmyn, Marjan] Katholieke Univ Leuven, Dept Oncol, Dermatol Lab, Louvain, Belgium. [Gartel, Andrei L.] Univ Illinois, Dept Med, Chicago, IL USA. [Gatti, Evelina; Golstein, Pierre; Pierre, Philippe] Univ Aix Marseille 2, Ctr Immunol Marseille Luminy, INSERM, UM2,U1104, F-13284 Marseille 07, France. [Gatti, Evelina; Golstein, Pierre; Pierre, Philippe] CNRS, UMR7280, Marseille, France. [Gautel, Mathias] Kings Coll London, Randall Div Cell & Mol Biophys, London WC2R 2LS, England. [Gautel, Mathias] Kings Coll London, Div Cardiovasc, London WC2R 2LS, England. [Gawriluk, Thomas R.; Hale, Amber N.; Ledbetter, Daniel J.; Rucker, Edmund B., III] Univ Kentucky, Dept Biol, Lexington, KY USA. [Gegg, Matthew E.; Schapira, Anthony H. V.] UCL, Inst Neurol, Dept Clin Neurosci, London, England. [Geng, Jiefei; Harper, J. Wade] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Germain, Marc; Slack, Ruth S.] Univ Ottawa, Dept Cellular Mol Med, Ottawa, ON, Canada. [Gestwicki, Jason E.; Lieberman, Andrew; Lukacs, Nicholas W.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Ghavami, Saeid; Halayko, Andrew J.; Kirshenbaum, Lorrie A.; Yeganeh, Behzad] Univ Manitoba, Dept Physiol, Manitoba Inst Child Hlth, Winnipeg, MB R3T 2N2, Canada. [Ghosh, Pradipta; Lee, Jongdae] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Giammarioli, Anna M.; Malorni, Walter] Ist Super Sanita, Dept Therapeut Res & Med Evaluat, I-00161 Rome, Italy. [Giatromanolaki, Alexandra N.; Sivridis, Efthimios] Democritus Univ Thrace, Dept Pathol, Alexandroupolis, Greece. [Giatromanolaki, Alexandra N.; Sivridis, Efthimios] Univ Gen Hosp Alexandroupolis, Alexandroupolis, Greece. [Gibson, Spencer B.] Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB, Canada. [Gilkerson, Robert W.; Przedborski, Serge; Sulzer, David; Yamamoto, Ai] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Ginger, Michael L.] Univ Lancaster, Sch Hlth & Med, Lancaster, England. [Ginsberg, Henry N.; Tabas, Ira] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. [Golab, Jakub] Med Univ Warsaw, Dept Immunol, Warsaw, Poland. [Goligorsky, Michael S.] New York Med Coll, Renal Res Inst, Valhalla, NY 10595 USA. [Gomez-Manzano, Candelaria] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. [Goncu, Ebru] Ege Univ, Fac Sci, Dept Biol, Izmir, Turkey. [Gongora, Celine; Le Cam, Laurent; Legouis, Renaud; Pattingre, Sophie] Univ Montpellier I, INSERM, Inst Rech Cancerol Montpellier, U896, Montpellier, France. [Gonzalez, Claudio D.; Vaccaro, Maira I.] Univ Buenos Aires, Dept Pathophysiol, Sch Pharm & Biochem, Buenos Aires, DF, Argentina. [Gonzalez, Ramon] CSIC UR CAR, Inst Ciencias Vino, Logrono, Spain. [Gonzalez-Estevez, Cristina] Univ Nottingham, Queens Med Ctr, Ctr Genet & Genom, Dept Dev Genet & Gene Control, Nottingham NG7 2RD, England. [Gorbunov, Nikolai V.] Uniformed Serv Univ Hlth Sci, Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20814 USA. [Gorski, Sharon] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada. [Goruppi, Sandro] Tufts Univ, Sch Med, Tufts Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. [Goruppi, Sandro] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Gozuacik, Devrim] Sabanci Univ, Biol Sci & Bioengn Program, Istanbul, Turkey. [Green, Kim N.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA. [Gregorc, Ales] Agr Inst Slovenia, Ljubljana, Slovenia. [Gros, Frederic] Univ Strasbourg, CNRS, Strasbourg, France. [Grose, Charles] Univ Iowa, Dept Pediat, Childrens Hosp, Iowa City, IA 52242 USA. [Grunt, Thomas W.] Med Univ Vienna, Ctr Comprehens Canc, Dept Med 1, Signaling Networks Program,Div Oncol, Vienna, Austria. [Guan, Kun-Liang] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [Guan, Kun-Liang] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Gukovskaya, Anna S.; Gukovsky, Ilya] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Gunst, Jan; Van den Berghe, Greet; Vanhorebeek, Ilse] Katholieke Univ Leuven, Dept & Lab Intens Care Med, Louvain, Belgium. [Gustafsson, Asa B.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA. [Halayko, Andrew J.] Univ Manitoba, Manitoba Inst Child Hlth, Dept Internal Med, Winnipeg, MB, Canada. [Halonen, Sandra K.] Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA. [Hamasaki, Maho; Noda, Takeshi; Yoshimori, Tamotsu] Osaka Univ, Dept Genet, Grad Sch Med, Osaka, Japan. [Han, Feng] Zhejiang Univ, Inst Pharmacol,Toxicol & Biochem Pharmaceut, Hangzhou 310003, Zhejiang, Peoples R China. [Hancock, Michael K.] Life Technol, Discovery & ADMET TOX Syst, Madison, WI USA. [Harada, Hisashi] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Oral & Craniofacial Mol Biol, Richmond, VA USA. [Harada, Masaru] Univ Occupat & Environm Hlth, Sch Med, Dept Internal Med 3, Kitakyushu, Fukuoka 807, Japan. [Hardt, Stefan E.] Heidelberg Univ, Dept Cardiol Angiol & Pulmol, Heidelberg, Germany. [Harris, Adrian L.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Mol Oncol Labs,Dept Oncol, Oxford OX3 9DU, England. [Harris, James] Trinity Coll Dublin, Sch Biochem & Immunol, Immunol Res Ctr, Dublin, Ireland. [Harris, Steven D.] Univ Nebraska, Ctr Plant Sci Innovat, Lincoln, NE USA. [Hashimoto, Makoto] Tokyo Metropolitan Inst Med Sci, Div Sensory & Motor Syst, Tokyo 113, Japan. [Haspel, Jeffrey A.] VA Boston Healthcare Syst, Boston, MA USA. [Hayashi, Shin-ichiro] Natl Cerebral & Cardiovasc Ctr, Div Hypertens & Nephrol, Osaka, Japan. [Hayashi, Shin-ichiro] Gifu Univ, Grad Sch Med, Dept Cell Signalling, Gifu, Japan. [Hazelhurst, Lori A.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [He, Congcong; Levine, Beth; Terada, Lance S.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [He, Congcong; Levine, Beth; Terada, Lance S.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [He, You-Wen; Rathmell, Jeffrey C.; Taylor, Gregory A.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA. [Hebert, Marie-Josee] CRCHUM, Dept Nephrol, Montreal, PQ, Canada. [Heidenreich, Kim A.] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO USA. [Helgason, Gudmundur V.; Holyoake, Tessa L.] Univ Glasgow, Inst Canc Sci, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland. [Herman, Brian; Reiter, Russel J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Herman, Paul K.] Ohio State Univ, Dept Mol Genet, Columbus, OH 43210 USA. [Hetz, Claudio] Univ Chile, Fac Med, ICBM, Biomed Neurosci Inst, Santiago 7, Chile. [Hilfiker, Sabine; Navarro, Miguel] CSIC, IPBLN, Inst Parasitol & Biomed Lopez Neyra, Dept Mol Biol, Granada, Spain. [Hill, Joseph A.; Lavandero, Sergio; Nemchenko, Andriy] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA. [Hofmann, Thomas G.] DKFZ ZMBH Alliance, German Canc Res Ctr, Cellular Senescence Grp A210, Heidelberg, Germany. [Hoehfeld, Joerg] Univ Bonn, Inst Cell Biol, Bonn, Germany. [Hong, Ming-Huang] Sun Yat Sen Univ, GCP Ctr, Guangzhou 510275, Guangdong, Peoples R China. [Hood, David A.] York Univ, Sch Kinesiol & Hlth Sci, Toronto, ON M3J 2R7, Canada. [Hotamisligil, Goekhan S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Houwerzijl, Ewout J.] Univ Med Ctr Groningen, Dept Internal Med, NL-9713 AV Groningen, Netherlands. [Hoyer-Hansen, Maria] LEO Pharma AS, Dept Mol Biomed, Ballerup, Denmark. [Hu, Bingren] Univ Maryland, Sch Med, Shock Trauma & Anesthesiol Res Ctr, Baltimore, MD 21201 USA. [Hu, Chien-An A.] Univ New Mexico, Sch Med, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA. [Hu, Hong-Ming] Providence Portland Med Ctr, Earle A Chiles Res Inst, Lab Canc Immunobiol, Portland, OR USA. [Hua, Ya] Univ Michigan, Dept Neurosurg, Ann Arbor, MI 48109 USA. [Huang, Canhua; Liu, Bo] Sichuan Univ, State Key Lab Biotherapy, Chengdu 610064, Peoples R China. [Huang, Shengbing; Sinicrope, Frank A.] Mayo Clin, Dept Med, Rochester, MN USA. [Huang, Shengbing; Sinicrope, Frank A.] Mayo Canc Ctr, Rochester, MN USA. [Huang, Wei-Pang] Natl Taiwan Univ, Dept Life Sci, Taipei 10764, Taiwan. [Huang, Wei-Pang] Natl Taiwan Univ, Inst Zool, Taipei 10764, Taiwan. [Huber, Tobias B.] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, D-79106 Freiburg, Germany. [Huber, Tobias B.] Univ Hosp Freiburg, Div Renal, Freiburg, Germany. [Huh, Won-Ki] Seoul Natl Univ, Sch Biol Sci, Seoul, South Korea. [Huh, Won-Ki] Seoul Natl Univ, Res Ctr Funct Cellul, Seoul, South Korea. [Hung, Tai-Ho] Chang Gung Mem Hosp, Dept Obstet & Gynecol, Taipei 10591, Taiwan. [Hupp, Ted R.] Univ Edinburgh, Dept Expt Canc Res, Inst Genet & Mol Med, Cell Signalling Unit, Edinburgh, Midlothian, Scotland. [Hur, Gang Min] Chungnam Natl Univ, Coll Med, Dept Pharmacol, Infect Signaling Network,Res Ctr, Taejon, South Korea. [Hurley, James B.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Hussain, Sabah N. A.] McGill Univ, Crit Care Dept, Montreal, PQ, Canada. [Hussey, Patrick J.] Univ Durham, Sch Biol & Biomed Sci, Durham, England. [Hwang, Jung Jin] Univ Ulsan, Coll Med, Inst Innovat Canc Res, Seoul, South Korea. [Hwang, Jung Jin] Asan Med Ctr, Seoul, South Korea. [Hwang, Seungmin] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Ichihara, Atsuhiro] Tokyo Womens Med Univ, Dept Med 2, Tokyo, Japan. [Inoki, Ken] Univ Michigan, Sch Med, Dept Internal Med, Div Nephrol, Ann Arbor, MI USA. [Inoki, Ken] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI USA. [Into, Takeshi] Asahi Univ, Sch Dent, Dept Oral Microbiol, Div Oral Infect & Hlth Sci, Mizuho, Japan. [Iovanna, Juan L.] Univ Aix Marseille 2, Marseille, France. [Iovanna, Juan L.] INSERM, U624, F-13258 Marseille, France. [Ip, Nancy Y.] Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China. [Ip, Nancy Y.] Hong Kong Univ Sci & Technol, State Key Lab Mol Neurosci, Hong Kong, Hong Kong, Peoples R China. [Isaka, Yoshitaka] Osaka Univ, Grad Sch Med, Dept Geriatr Med & Nephrol, Suita, Osaka, Japan. [Ishida, Hiroyuki] Tohoku Univ, Grad Sch Agr Sci, Dept Appl Plant Sci, Sendai, Miyagi 980, Japan. [Isobe, Ken-ichi] Nagoya Univ, Grad Sch Med, Dept Immunol, Nagoya, Aichi 4648601, Japan. [Iwasaki, Akiko] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Izumi, Yotaro] Keio Univ, Sch Med, Divs Gen Thorac Surg, Tokyo, Japan. [Jaakkola, Panu M.] Univ Turku, Ctr Biotechnol, Turku, Finland. [Jackson, George R.] Univ Texas Med Branch, Dept Neurol, Galveston, TX USA. 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[Koukourakis, Michael I.] Democritus Univ Thrace, Dept Radiotherapy Oncol, Alexandroupolis, Greece. Univ Vienna, Max Perutz Labs, Vienna, Austria. [McLean, Pamela J.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA. Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. Univ Lyon 1, CNRS, Ctr Genet & Physiol Mol & Cellulaire, UMR5534, F-69365 Lyon, France. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. Univ Paris 05, Fac Med, Paris, France. Univ Cologne, Inst Med Microbiol Immunol & Hyg, D-50931 Cologne, Germany. Babraham Inst, Signaling Program, Cambridge, England. Cincinnati Childrens Hosp Res Fdn, Div Dev Biol, Cincinnati, OH USA. [Zoladek, Teresa] Polish Acad Sci, Inst Biochem & Biophys, Warsaw, Poland. Univ Louisville, Sch Med, Dept Anat Sci & Neurobiol, Louisville, KY 40292 USA. Commonwealth Med Coll, Dept Basic Sci, Scranton, PA USA. St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. Univ Calif Davis, Ctr Canc, Dept Biochem & Mol Med, Sacramento, CA 95817 USA. Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biotechnol, Seoul, South Korea. Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. [Spector, Stephen A.] Rady Childrens Hosp, San Diego, CA USA. [Lafont, Frank] Univ Lille Nord France, INSERM, Inst Pasteur Lille, Ctr Infect & Immun Lille,CNRS,UMR8204,U1019, Lille, France. [Landry, Jacques; Lavoie, Josee N.] Univ Laval, Canc Res Ctr, Quebec City, PQ G1K 7P4, Canada. [Lane, Jon D.] Univ Bristol, Sch Biochem, Bristol, Avon, England. [Lapaquette, Pierre] Inst Pasteur, INSERM, Nucl Org & Oncogenesis Unit, U993, F-75724 Paris, France. [Laporte, Jocelyn F.] Univ Strasbourg, CNRS, INSERM, Dept Translat Med,IGBMC,U964,UMR7104, Illkirch Graffenstaden, France. [Layfield, Robert] Univ Nottingham, Queens Med Ctr, Sch Biomed Sci, Nottingham NG7 2RD, England. [Lazo, Pedro A.; Mollinedo, Faustino] Univ Salamanca, CSIC, Inst Biol Mol & Celular Canc, E-37008 Salamanca, Spain. [Le, Weidong; Legembre, Patrick] Shanghai Jiao Tong Univ, Chinese Acad Sci, Sch Med, Inst Hlth Sci, Shanghai 200030, Peoples R China. [Le, Weidong; Legembre, Patrick; Li, Sheng] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China. [Lee, Alvin J. X.; Swanton, Charles] Canc Res UK London Res Inst, Translat Canc Therapeut Lab, London, England. [Lee, Byung-Wan] Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea. [Lee, Ju-Hyun; Levy, Efrat; Nixon, Ralph A.; Yang, Dun-Sheng] NYU, Sch Med, Nathan S Kline Inst Psychiat Res, Dept Psychiat, Orangeburg, NY USA. [Lee, Michael] Univ Incheon, Div Life Sci, Inchon, South Korea. 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[Malagoli, Davide] Univ Modena & Reggio Emilia, Dept Biol, Modena, Italy. [Malicdan, May Christine V.] NHGRI, Med Genet Branch & UDP Translat Med, NIH, Bethesda, MD 20892 USA. [Malorni, Walter] San Raffaele Sulmona Inst, Laquila, Italy. [Man, Na; Zhou, Cong-Zhao] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Anhui, Peoples R China. [Man, Na; Zhou, Cong-Zhao] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China. [Mandelkow, Eva-Maria; Wang, Yipeng] CAESAR Res Ctr, Bonn, Germany. [Mandelkow, Eva-Maria; Wang, Yipeng] DZNE German Ctr Neurodegenerat Dis, Bonn, Germany. [Manov, Irena] Technion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, Pediat Res & Electron Microscopy Unit, Haifa, Israel. [Mao, Xiang] Nanjing Agr Univ, Coll Vet Med, Nanjing, Jiangsu, Peoples R China. [Mao, Zixu] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Marambaud, Philippe] Feinstein Inst Med Res, Manhasset, NY USA. 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Linden, Rafael/0000-0003-3287-336X; Meyer, Thomas F./0000-0002-6120-8679; Wang, Xuejun/0000-0001-9267-1343; Diaz-Nido, Javier/0000-0002-0927-7925; Andrieu-Abadie, Nathalie/0000-0003-2698-1970; Golstein, Pierre/0000-0003-1750-3483; Yoshimoto, Kohki/0000-0003-3948-3751; Gonzalez, Ramon/0000-0001-7388-1660; Poletti, Angelo/0000-0002-8883-0468; Poirot, Marc/0000-0002-5711-6624; Schapira, Anthony/0000-0002-3018-3966; Codogno, Patrice/0000-0002-5492-3180; Kanki, Tomotake/0000-0001-9646-5379; Juhasz, Gabor/0000-0001-8548-8874; Velasco, Guillermo/0000-0002-1994-2386; Johnson, David/0000-0001-5491-3460; Wu, William K.K./0000-0002-5662-5240; Tavernarakis, Nektarios/0000-0002-5253-1466; Votruba, Marcela/0000-0002-7680-9135; van Grunsven, Leo/0000-0002-0990-7034; Bast, Robert/0000-0003-4621-8462; Smith, Duncan /0000-0002-6592-9852; Yang, Shi Yu/0000-0001-8517-9238; Stork, Bjorn/0000-0002-4167-7806; Skulachev, Vladimir/0000-0003-4886-2243; Perry, George/0000-0002-6547-0172; Marino, Guillermo/0000-0003-1960-1677; Bridges, Dave/0000-0002-5334-972X; King, Jason/0000-0003-0596-4506; Kim, Do-Hyung/0000-0002-2924-4370; Korolchuk, Viktor/0000-0002-4071-592X; Mottram, Jeremy/0000-0001-5574-3766; Marazziti, Daniela/0000-0002-1582-9271; SIMONE, Cristiano/0000-0002-2628-7658; Galliot, Brigitte/0000-0001-7596-8284; Gozuacik, Devrim/0000-0001-7739-2346; Fallon, Brian/0000-0003-1797-9713; Paris, Irmgard/0000-0003-2331-7513; legembre, patrick/0000-0001-6649-8049; Parys, Jan/0000-0002-3591-4967; HUANG, WEI-PANG/0000-0001-8410-6555; Marciniak, Stefan/0000-0001-8472-7183; Ryan, Kevin M./0000-0002-1059-9681; Marten, Mark/0000-0002-1863-8956; Brunetti-Pierri, Nicola/0000-0002-6895-8819; Almasan, Alex/0000-0002-8916-6650; Zhang, Xu Dong/0000-0001-9457-8003; Lee, Ju-hyun/0000-0002-0280-8375; Balduini, Walter/0000-0001-8438-9559; Mograbi, Baharia/0000-0002-1025-3429; Frankel, Lisa/0000-0001-7249-3607; Khalil, Hany/0000-0001-9738-4087; malorni, walter/0000-0002-1223-7000; Hocking, Lynne J/0000-0002-2414-2826; Rouschop, Kasper/0000-0002-4208-5415; Condorelli, Fabrizio/0000-0002-9943-0857; Engelbrecht, Anna-Mart/0000-0003-1469-0148; Palumbo, Camilla/0000-0001-5087-7140; Panaretakis, Theocharis/0000-0001-5754-6950; LIANG, CHENGYU/0000-0001-6082-2143; D'Amelio, Marcello/0000-0001-6526-1832; Bozhkov, Peter/0000-0002-8819-3884; Van der Klei, Ida J./0000-0001-7165-9679; Sinclair, David/0000-0002-9936-436X; De Felici, Massimo/0000-0001-8479-8264; Wang, Xinglong/0000-0001-8657-0159; Russo, Rossella/0000-0001-8758-6523; CASARI, Giorgio/0000-0002-0115-8980; gatti, evelina/0000-0002-0667-0799; Whitworth, Alexander/0000-0002-1154-6629; Grant, Gary/0000-0002-2574-5442; Berliocchi, Laura/0000-0002-3014-1838; FORNAI, FRANCESCO/0000-0002-3883-5084; Skop, Vojtech/0000-0002-4685-4429; SETTEMBRE, Carmine/0000-0002-5829-8589; Zhou, Cong-Zhao/0000-0002-6881-7151; CHEN, CHING-CHOW/0000-0002-7810-0939; Batoko, Henri/0000-0002-8256-519X; Hofman, Paul/0000-0003-0431-9353; pierre, philippe/0000-0003-0863-8255; Ganley, Ian/0000-0003-1481-9407; Ko, Ben Chi Bun/0000-0003-2027-5899; Fox, Howard/0000-0003-2032-374X; McInerney, Gerald/0000-0003-2257-7241; Low, Peter/0000-0003-2450-7087; De Milito, Angelo/0000-0003-2591-2914; Leiro Vidal, Jose Manuel/0000-0001-6963-515X; Chisari, Francis/0000-0002-4832-1044; Isidoro, Ciro/0000-0002-5494-3034; BRANCOLINI, Claudio/0000-0002-6597-5373; Lavandero, Sergio/0000-0003-4258-1483; holyoake, tessa/0000-0002-0608-6066; Kramer, Helmut/0000-0002-1167-2676; Gaestel, Matthias/0000-0002-4944-4652; Cadwell, Ken/0000-0002-5860-0661; Simon, Hans-Uwe/0000-0002-9404-7736; Espina, Virginia/0000-0001-5080-5972; Lingor, Paul/0000-0001-9362-7096; Jung, Yong-Keun/0000-0002-9686-3120; Hwang, Seungmin/0000-0003-0846-5462; Clague, Michael/0000-0003-3355-9479; Scorrano, Luca/0000-0002-8515-8928; Demarchi, Francesca/0000-0003-1565-3162; Ruiz-Opazo, Nelson/0000-0001-8234-1332; Zhivotovsky, Boris/0000-0002-2238-3482; Deretic, Vojo/0000-0002-3624-5208; COTO-MONTES, ANA/0000-0002-6609-6258; Lund, Anders/0000-0002-7407-3398; Marambaud, Philippe/0000-0002-8983-1497; BALLABIO, Andrea/0000-0003-1381-4604; YUN, Cheol-Heui/0000-0002-0041-2887; Wu, Daocheng/0000-0002-6183-539X; Simonsen, Anne/0000-0003-4711-7057; Tonges, Lars/0000-0001-6621-144X; Liton, Paloma/0000-0002-1440-3762; Subauste, Carlos/0000-0002-5602-1439; Cecconi, Francesco/0000-0002-5614-4359; Kanneganti, Thirumala-Devi/0000-0002-6395-6443; Mostowy, Serge/0000-0002-7286-6503; Munger, Karl/0000-0003-3288-9935; Nakano, Hiroyasu/0000-0003-4843-1427; Bultynck, Geert/0000-0002-5968-4828; Ginger, Michael/0000-0002-9643-8482; Bechet, Daniel/0000-0002-3812-8099; Lin, Wan Wan/0000-0002-3207-734X; Kehrl, John/0000-0002-6526-159X; Macian, Fernando/0000-0003-2666-035X; Carding, Simon/0000-0002-2383-9701; Piras, Antonio/0000-0003-3052-1715; Harris, Adrian/0000-0003-1376-8409; Egea, Gustavo/0000-0001-5242-150X; MATTEONI, RAFAELE/0000-0002-0314-5948; Kaminskyy, Vitaliy/0000-0002-8151-5270; /0000-0003-3505-3674; Wouters, Bradly/0000-0002-8187-592X; Kaarniranta, Kai/0000-0003-2600-8679; Kabuta, Tomohiro/0000-0002-3058-2596; Jaattela, Marja/0000-0001-5950-7111; Kumar, Sharad/0000-0001-7126-9814; Weiss, William/0000-0003-2230-9132; Tschan, Mario P./0000-0001-5897-3647; Zacks, David/0000-0001-8592-5165; Nishino, Ichizo/0000-0001-9452-112X; Chen, Quan/0000-0001-7539-8728; Kim, Yonghyun/0000-0001-6344-1258; Zhu, Wei-Guo/0000-0001-8385-6581; Merighi, Adalberto/0000-0002-1140-3556; Schiaffino, Stefano/0000-0002-5607-6421 FU National Institutes of Health Public Health Service [GM53396] FX In a rapidly expanding and highly dynamic field such as autophagy, it is possible that some authors who should have been included on this manuscript have been missed. D.J.K. extends his apologies to researchers in the field of autophagy who, due to oversight or any other reason, could not be included. This work was supported by National Institutes of Health Public Health Service grant GM53396 to D.J.K. Due to space and other limitations, it is not possible to include all other sources of financial support. NR 884 TC 1731 Z9 1809 U1 275 U2 2273 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PD APR PY 2012 VL 8 IS 4 BP 445 EP 544 DI 10.4161/auto.19496 PG 100 WC Cell Biology SC Cell Biology GA 960QQ UT WOS:000305403400002 PM 22966490 ER PT J AU Jaber, N Dou, ZX Lin, RZ Zhang, JH Zong, WX AF Jaber, Nadia Dou, Zhixun Lin, Richard Z. Zhang, Jianhua Zong, Wei-Xing TI Mammalian PIK3C3/VPS34 The key to autophagic processing in liver and heart SO AUTOPHAGY LA English DT Editorial Material DE VPS34; PIK3C3; autophagy; endocytosis; PtdIns3K; PtdIns3P; liver; heart; cancer AB PIK3C3/Vps34 is the class III PtdIns3K that is evolutionarily conserved from yeast to mammals. Its central role in mammalian autophagy has been suggested through the use of pharmacological inhibitors and the study of its binding partners. However, the precise role of PIK3C3 in mammals is not clear. Using mouse strains that allow tissue-specific deletion of PIK3C3, we have described an essential role of PIK3C3 in regulating autophagy, and liver and heart function. C1 [Jaber, Nadia; Dou, Zhixun; Zong, Wei-Xing] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. [Lin, Richard Z.] SUNY Stony Brook, Dept Physiol & Biophys, Stony Brook, NY 11794 USA. [Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Lin, Richard Z.] Northport VA Med Ctr, Northport, NY USA. [Zhang, Jianhua] Birmingham VA Med Ctr, Birmingham, AL USA. RP Zong, WX (reprint author), SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. EM wzong@notes.cc.sunysb.edu RI Lin, Richard/J-1754-2014; OI Lin, Richard/0000-0002-3473-7276; Zhang, Jianhua/0000-0002-2128-9574 FU NCI NIH HHS [R01 CA129536, R01 CA136754]; NIDDK NIH HHS [R01 DK062722]; NIGMS NIH HHS [R01 GM097355] NR 0 TC 10 Z9 10 U1 0 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD APR PY 2012 VL 8 IS 4 BP 707 EP 708 DI 10.4161/auto.19627 PG 2 WC Cell Biology SC Cell Biology GA 960QQ UT WOS:000305403400020 PM 22498475 ER PT J AU Saifu, HN Asch, SM Goetz, MB Smith, JP Graber, CJ Schaberg, D Sun, BC AF Saifu, Hemen N. Asch, Steven M. Goetz, Matthew Bidwell Smith, Jason P. Graber, Christopher J. Schaberg, Dennis Sun, Benjamin C. TI Evaluation of Human Immunodeficiency Virus and Hepatitis C Telemedicine Clinics SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID RANDOMIZED-TRIAL; CARE; VETERANS; POPULATION AB Background: Geographical barriers to subspecialty care may prevent optimal care of patients living in rural areas. We assess the impact of human immunodeficiency virus (HIV) and hepatitis C telemedicine consultation on patient-oriented outcomes in a rural Veterans Affairs population. Methods: This was a pre- and post-intervention study comparing telemedicine with in-person subspecialty clinic visits for HIV and hepatitis C. Eligible patients resided in 2 rural catchment areas. The primary binary outcome was clinic completion. We estimated a logistic regression model with patient-level fixed effects. This approach controls for the clustering of visits by patient, uses each patient's in-person clinic experience as an internal control group, and eliminates confounding by person-level factors. We also surveyed patients to assess satisfaction and patient-perceived reductions in health visit-related time. Results: There were 43 patients who accounted for 94 telemedicine visits and 128 in-person visits. Clinic completion rates were higher for telemedicine (76%) than for in-person visits (61%). In regression analyses, telemedicine was strongly predictive of clinic completion (OR 2.2; 95% confidence interval [CI]: 1.0-4.7). The adjusted effect of telemedicine on clinic completion rate was 13% (95% CI: 12-13). Of the 30 patients (70%) who completed the survey, more than 95% rated telemedicine at the highest level of satisfaction and preferred telemedicine to in-person clinic visits. Patients reported a significant reduction in health visit-related time (median 340 minutes, interquartile range 250-440), mostly due to decreased travel time. Conclusions: HIV and hepatitis C telemedicine clinics are associated with improved access, high patient satisfaction, and reduction in health visit-related time. (Am J Manag Care. 2012;18(4):207-212) C1 [Saifu, Hemen N.; Asch, Steven M.; Goetz, Matthew Bidwell; Smith, Jason P.; Graber, Christopher J.; Schaberg, Dennis; Sun, Benjamin C.] VA Greater Los Angeles Hlth Syst, Dept Med, Los Angeles, CA USA. [Asch, Steven M.; Goetz, Matthew Bidwell; Graber, Christopher J.; Sun, Benjamin C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Sun, Benjamin C.] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. RP Saifu, HN (reprint author), Off 3246,Mail Stop 111G,Bldg 500,Wing 3E,11301 Wi, Los Angeles, CA 90073 USA. EM Hemen.Saifu@va.gov OI Goetz, Matthew/0000-0003-4542-992X FU VA grant [RRP 09-127]; VA HIV/Hepatitis Quality Enhancement Research Initiative FX This study was supported by VA grant RRP 09-127 and the VA HIV/Hepatitis Quality Enhancement Research Initiative. NR 17 TC 9 Z9 9 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 APR PY 2012 VL 18 IS 4 BP 207 EP 212 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 001EK UT WOS:000308443000003 PM 22554009 ER PT J AU Sistrom, C McKay, NL Weilburg, JB Atlas, SJ Ferris, TG AF Sistrom, Chris McKay, Niccie L. Weilburg, Jeffrey B. Atlas, Steven J. Ferris, Timothy G. TI Determinants of Diagnostic Imaging Utilization in Primary Care SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID ZERO-INFLATED POISSON; SMALL-AREA VARIATIONS; PHYSICIANS; SERVICES; PATIENT; TOMOGRAPHY; REGRESSION; PATTERNS AB Objectives: To examine patient and physician factors affecting utilization of diagnostic imaging in primary care. Data Sources/Study Setting: Patient-level data from a large academic group practice over the period July 1, 2007, through June 30,2009. Study Design: This is a retrospective cohort study of 85,277 patients cared for by 148 primary care physicians (PCPs). The dependent variable is the number of outpatient imaging exams ordered by each patient's PCP over the study period. Independent variables include 17 patient factorsdescribing both clinical need and demographic characteristics and 7 physician factors. Data Collection: Data were collected from the electronic medical record and associated administrative databases. Principal Findings: Patient factors having a statistically significant effect on both the probability race, more than 10 medications, congestive heart failure, diabetes, hypertension, other problems, visits to the PCP, visits to specialists, and imaging exams ordered by specialists. For physician factors, experience, gender, and having another degree were statistically significant in both portions of the model. Conclusions: Both patient and physician factors have a substantial effect on primary care outpatient diagnostic imaging utilization. Several of these significantly influence both the probability that any images will be ordered and the intensity (number) of imaging. C1 [Sistrom, Chris] Univ Florida, Ctr Hlth, Dept Radiol, Gainesville, FL 32610 USA. [McKay, Niccie L.] Univ Florida, Dept Hlth Serv Res, Gainesville, FL 32610 USA. [Weilburg, Jeffrey B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Atlas, Steven J.; Ferris, Timothy G.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Sistrom, C (reprint author), Univ Florida, Ctr Hlth, Dept Radiol, POB 100374, Gainesville, FL 32610 USA. EM sistrc@radiology.ufl.edu NR 28 TC 5 Z9 5 U1 4 U2 8 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 APR PY 2012 VL 18 IS 4 BP E135 EP E142 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 001EK UT WOS:000308443000007 PM 22554039 ER PT J AU Coglianese, EE Wang, TJ AF Coglianese, Erin E. Wang, Thomas J. TI Clinical Monitoring of Stage B Heart Failure: Echocardiography SO HEART FAILURE CLINICS LA English DT Article DE Stage B heart failure; Heart failure; Echocardiography; Left ventricular systolic dysfunction ID VENTRICULAR SYSTOLIC DYSFUNCTION; ASSOCIATION TASK-FORCE; ASYMPTOMATIC PATIENTS; AMERICAN-COLLEGE; DIASTOLIC DYSFUNCTION; NATRIURETIC PEPTIDE; PRACTICE GUIDELINES; ACC/AHA GUIDELINES; DIABETES-MELLITUS; EJECTION FRACTION AB Estimates of the prevalence of asymptomatic left ventricular systolic dysfunction (LVSD) vary widely depending on the study sample and definition of LVSD. Subtle reductions in LV systolic or diastolic function are now detectable with newer echocardiographic measures, which can influence estimates of the burden of stage B heart failure (HF). If the definition is broadened to include diastolic filling abnormalities, the estimated prevalence of stage B HF increases dramatically. This article reviews the rationale for echocardiographic screening for stage B HF, describes currently available measures of cardiac structure and function, and assesses the potential role of echocardiography in selected subgroups. C1 [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Coglianese, Erin E.] Loyola Univ Hlth Syst, Div Cardiol, Maywood, IL 60514 USA. RP Wang, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, GRB-800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org NR 68 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7136 J9 HEART FAIL CLIN JI Heart Fail. Clin. PD APR PY 2012 VL 8 IS 2 BP 169 EP + DI 10.1016/j.hfc.2011.11.007 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 988ML UT WOS:000307495000003 PM 22405658 ER PT J AU West, TW Hess, C Cree, BAC AF West, Timothy W. Hess, Christopher Cree, Bruce A. C. TI Acute Transverse Myelitis: Demyelinating, Inflammatory, and Infectious Myelopathies SO SEMINARS IN NEUROLOGY LA English DT Article DE myelitis; myelopathy; demyelinating; inflammatory ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY SJOGRENS-SYNDROME; CENTRAL-NERVOUS-SYSTEM; ACUTE DISSEMINATED ENCEPHALOMYELITIS; ANGIOTENSIN-CONVERTING ENZYME; POLYMERASE-CHAIN-REACTION; VARICELLA-ZOSTER-VIRUS; NEUROMYELITIS-OPTICA; MULTIPLE-SCLEROSIS; CEREBROSPINAL-FLUID AB Acute transverse myelitis is a rare neurologic condition that has an estimated incidence of up to 3 per 100,000 patient years (0.003%). Although rare, acute transverse myelitis can have devastating neurologic effects with up to two-thirds of patients having a moderate to severe degree of residual disability. The term acute transverse myelitis was previously reserved for idiopathic cases, but currently is used to encompass the general clinical syndrome, whether or not the cause is known. Once adequate neuroimaging has ruled out a compressive etiology, and a lumbar puncture has demonstrated signs of inflammation within the cerebrospinal fluid, a workup of causes for an acute transverse myelitis must be undertaken. Determining the etiology of transverse myelitis can be challenging because there are autoimmune, inflammatory, and infectious diseases associated with acute transverse myelitis. The authors discuss an approach to acute transverse myelitis including clinical symptoms, neuroimaging, and biomarkers that may aid the clinician in diagnosis. C1 [West, Timothy W.] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Las Vegas, NV 89106 USA. [Hess, Christopher] San Francisco VA Med Ctr, Div Neuroradiol, UCSF Dept Radiol & Biomed Imaging, San Francisco, CA USA. [Cree, Bruce A. C.] Univ Calif San Francisco, Dept Neurol, Div Clin Neurol, Multiple Sclerosis Ctr, San Francisco, CA USA. RP West, TW (reprint author), Cleveland Clin, Lou Ruvo Ctr Brain Hlth, 888 W Bonneville Ave, Las Vegas, NV 89106 USA. EM westt3@ccf.org OI Hess, Christopher/0000-0002-5132-5302 NR 150 TC 13 Z9 15 U1 0 U2 16 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 EI 1098-9021 J9 SEMIN NEUROL JI Semin. Neurol. PD APR PY 2012 VL 32 IS 2 BP 97 EP 113 DI 10.1055/s-0032-1322586 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA 987NC UT WOS:000307423200002 PM 22961185 ER PT J AU Ganguly, K Abrams, GM AF Ganguly, Karunesh Abrams, Gary M. TI Management of Chronic Myelopathy Symptoms and Activities of Daily Living SO SEMINARS IN NEUROLOGY LA English DT Article DE myelopathy; spinal cord injury; spasticity; pain ID SPINAL-CORD-INJURY; PLACEBO-CONTROLLED TRIAL; NEUROPATHIC PAIN; AUTONOMIC DYSREFLEXIA; HETEROTOPIC OSSIFICATION; INPATIENT REHABILITATION; MULTIPLE-SCLEROSIS; BOTULINUM TOXIN; SPASTICITY; EPIDEMIOLOGY AB Many disorders can injure the spinal cord resulting in long-term chronic myelopathy. Spinal cord dysfunction influences the homeostasis of multiple organ systems ranging from the heart or lung to the integument, thus presenting a wide variety of challenges for medical management. Although most of our knowledge about the consequences of myelopathies derives from the study of traumatic spinal cord injuries, similar complications occur in myelopathies of all etiologies. The authors survey some of the important clinical issues that the general neurologist needs to consider in caring for patients with chronic spinal cord disease. C1 [Ganguly, Karunesh; Abrams, Gary M.] Univ Calif San Francisco, Dept Neurol, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Abrams, Gary M.] Univ Calif San Francisco, Dept Rehabil Serv, San Francisco, CA 94121 USA. RP Abrams, GM (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM Gary.Abrams@ucsf.edu NR 66 TC 0 Z9 0 U1 0 U2 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD APR PY 2012 VL 32 IS 2 BP 161 EP 168 DI 10.1055/s-0032-1322582 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 987NC UT WOS:000307423200008 PM 22961191 ER PT J AU Kyriakis, JM Avruch, J AF Kyriakis, John M. Avruch, Joseph TI MAMMALIAN MAPK SIGNAL TRANSDUCTION PATHWAYS ACTIVATED BY STRESS AND INFLAMMATION: A 10-YEAR UPDATE SO PHYSIOLOGICAL REVIEWS LA English DT Review ID TUMOR-NECROSIS-FACTOR; N-TERMINAL KINASE; JUN NH2-TERMINAL KINASE; GERMINAL CENTER KINASE; TOLL-LIKE RECEPTORS; T-CELL-ACTIVATION; HEMATOPOIETIC PROGENITOR KINASE; EMBRYONIC CARDIOVASCULAR DEVELOPMENT; PATTERN-RECOGNITION RECEPTORS; STE20-RELATED PROTEIN-KINASE AB Kyriakis JM, Avruch J. Mammalian MAPK Signal Transduction Pathways Activated by Stress and Inflammation: A 10-Year Update. Physiol Rev 92: 689-737, 2012; doi:10.1152/physrev.00028.2011.-The mammalian stress-activated families of mitogen-activated protein kinases (MAPKs) were first elucidated in 1994, and by 2001, substantial progress had been made in identifying the architecture of the pathways upstream of these kinases as well as in cataloguing candidate substrates. This information remains largely sound. Nevertheless, an informed understanding of the physiological and pathophysiological roles of these kinases remained to be accomplished. In the past decade, there has been an explosion of new work using RNAi in cells, as well as transgenic, knockout and conditional knockout technology in mice that has provided valuable insight into the functions of stress-activated MAPK pathways. These findings have important implications in our understanding of organ development, innate and acquired immunity, and diseases such as atherosclerosis, tumorigenesis, and type 2 diabetes. These new developments bring us within striking distance of the development and validation of novel treatment strategies. Herein we first summarize the molecular components of the mammalian stress-regulated MAPK pathways and their regulation as described thus far. We then review some of the in vivo functions of these pathways. C1 [Kyriakis, John M.] Tufts Med Ctr, Mol Cardiol Res Inst, Dept Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Med Serv, Diabet Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kyriakis, JM (reprint author), Tufts Med Ctr, Mol Cardiol Res Inst, Dept Med, 800 Washington St,Box 8486, Boston, MA 02111 USA. EM jkyriakis@tuftsmedicalcenter.org NR 350 TC 316 Z9 336 U1 10 U2 83 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 EI 1522-1210 J9 PHYSIOL REV JI Physiol. Rev. PD APR PY 2012 VL 92 IS 2 BP 689 EP 737 DI 10.1152/physrev.00028.2011 PG 49 WC Physiology SC Physiology GA 976EC UT WOS:000306562500006 PM 22535895 ER PT J AU Birkbak, NJ Wang, ZGC Kim, JY Eklund, AC Li, QY Tian, RY Bowman-Colin, C Li, Y Greene-Colozzi, A Iglehart, JD Tung, N Ryan, PD Garber, JE Silver, DP Szallasi, Z Richardson, AL AF Birkbak, Nicolai J. Wang, Zhigang C. Kim, Ji-Young Eklund, Aron C. Li, Qiyuan Tian, Ruiyang Bowman-Colin, Christian Li, Yang Greene-Colozzi, April Iglehart, J. Dirk Tung, Nadine Ryan, Paula D. Garber, Judy E. Silver, Daniel P. Szallasi, Zoltan Richardson, Andrea L. TI Telomeric Allelic Imbalance Indicates Defective DNA Repair and Sensitivity to DNA-Damaging Agents SO CANCER DISCOVERY LA English DT Article ID FRAGILE-SITE STABILITY; BREAST-CANCER CELLS; COPY NUMBER; HOMOLOGOUS RECOMBINATION; GENETIC INSTABILITY; OVARIAN-CARCINOMA; HUMAN GENOME; BRCA1; RESISTANCE; MUTATIONS AB DNA repair competency is one determinant of sensitivity to certain chemotherapy drugs, such as cisplatin. Cancer cells with intact DNA repair can avoid the accumulation of genome damage during growth and also can repair platinum-induced DNA damage. We sought genomic signatures indicative of defective DNA repair in cell lines and tumors and correlated these signatures to platinum sensitivity. The number of subchromosomal regions with allelic imbalance extending to the telomere (N-tAI) predicted cisplatin sensitivity in vitro and pathologic response to preoperative cisplatin treatment in patients with triple-negative breast cancer (TNBC). In serous ovarian cancer treated with platinum-based chemotherapy, higher levels of N-tAI forecast a better initial response. We found an inverse relationship between BRCA1 expression and N-tAI in sporadic TNBC and serous ovarian cancers without BRCA1 or BRCA2 mutation. Thus, accumulation of telomeric allelic imbalance is a marker of platinum sensitivity and suggests impaired DNA repair. SIGNIFICANCE: Mutations in BRCA genes cause defects in DNA repair that predict sensitivity to DNA damaging agents, including platinum; however, some patients without BRCA mutations also benefit from these agents. N-tAI, a genomic measure of unfaithfully repaired DNA, may identify cancer patients likely to benefit from treatments targeting defective DNA repair. Cancer Discov; 2(4); 366-75. (c) 2012 AACR. C1 [Birkbak, Nicolai J.; Wang, Zhigang C.; Li, Qiyuan; Tian, Ruiyang; Bowman-Colin, Christian; Li, Yang; Greene-Colozzi, April; Iglehart, J. Dirk; Garber, Judy E.; Silver, Daniel P.; Richardson, Andrea L.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Birkbak, Nicolai J.; Eklund, Aron C.; Li, Qiyuan; Szallasi, Zoltan] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Wang, Zhigang C.; Kim, Ji-Young; Iglehart, J. Dirk; Silver, Daniel P.; Richardson, Andrea L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Szallasi, Zoltan] Harvard MIT Div Hlth Sci & Technol CHIP HST, Childrens Hosp Informat Program, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. [Kim, Ji-Young] CHA Univ, Sch Med, Seoul, South Korea. [Ryan, Paula D.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Richardson, AL (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Smith 936A, Boston, MA 02215 USA. EM arichardson@partners.org RI Tian, Ruiyang/E-5023-2012; OI Eklund, Aron Charles/0000-0003-0861-1001; Szallasi, Zoltan/0000-0001-5395-7509 FU Dana-Farber/Harvard SPORE in Breast Cancer [CA089393]; Dana-Farber/Harvard Cancer Center Support Grant [5 P30 CA06516]; V Foundation for Cancer Research; Breast Cancer Research Foundation; The Danish Council for Independent Research Medical Sciences (FSS); Cogan Family Foundation FX This work is partly supported by the Dana-Farber/Harvard SPORE in Breast Cancer, grant number CA089393, by an Avon supplement to 5 P30 CA06516 Dana-Farber/Harvard Cancer Center Support Grant, and by the V Foundation for Cancer Research. J.E. Garber, N. Tung, Z.C. Wang. J.D. Iglehart, Z. Szallasi, and A.L. Richardson are supported by the Breast Cancer Research Foundation. N.J. Birkbak, A.C. Eklund, Q. Li, and Z. Szallasi are supported by The Danish Council for Independent Research Medical Sciences (FSS). D.P. Silver gratefully acknowledges support of the Cogan Family Foundation. NR 45 TC 68 Z9 68 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD APR PY 2012 VL 2 IS 4 BP 366 EP 375 DI 10.1158/2159-8290.CD-11-0206 PG 10 WC Oncology SC Oncology GA 973BP UT WOS:000306327000030 PM 22576213 ER PT J AU Ekblad, S Mollica, RF AF Ekblad, Solvig Mollica, Richard F. TI Scandinavia 9/11-lessons learnt and ways forward SO EUROPEAN JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Ekblad, Solvig] Karolinska Inst, Dept LIME, SE-17177 Stockholm, Sweden. [Mollica, Richard F.] Massachusetts Gen Hosp, Harvard Program Refugee Trauma, Cambridge, MA USA. RP Ekblad, S (reprint author), Karolinska Inst, Dept LIME, Berzeliusvag 3, SE-17177 Stockholm, Sweden. EM Solvig.Ekblad@ki.se NR 3 TC 0 Z9 0 U1 0 U2 4 PU EUROPEAN JOURNAL OF PSYCHIATRY PI ZARAGOZA PA FAC MED, DEPT PSYCHIATRY PROF A LOBO, DOMINGO MIRAL S-N, 50009 ZARAGOZA, SPAIN SN 0213-6163 J9 EUR J PSYCHIAT JI Eur. J. Psychiat. PD APR-JUN PY 2012 VL 26 IS 2 BP 135 EP 137 PG 3 WC Psychiatry SC Psychiatry GA 970SY UT WOS:000306153800007 ER PT J AU Patti, JA AF Patti, John A. TI ACR CHAIR'S MEMO Radiology's Golden Opportunity SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Patti, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM jpatti@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2012 VL 9 IS 4 BP 223 EP 223 DI 10.1016/j.jacr.2012.02.025 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 961FM UT WOS:000305449600001 PM 22469366 ER PT J AU Campigotto, F Neuberg, D Zwicker, JI AF Campigotto, Federico Neuberg, Donna Zwicker, Jeffrey I. TI Accounting for death as a competing risk in cancer-associated thrombosis studies SO THROMBOSIS RESEARCH LA English DT Article; Proceedings Paper CT 6th International Conference on Thrombosis and Hemostasis Issues in Cancer CY APR 20-22, 2012 CL Bergamo, ITALY DE Competing risk model; Cumulative incidence function; Cancer-associated thrombosis ID CUMULATIVE INCIDENCE AB In recent years, clinical investigation in the field of cancer-associated thrombosis has identified a number of potential biomarkers to predict the risk of developing a thrombotic event. Similarly, large randomized clinical trials have demonstrated the benefit of low molecular weight heparins in the treatment as well as prevention of venous thromboembolic events (VTE) in cancer patients. However, the most common statistical methodology to evaluate the occurrence of VTE has been the Kaplan-Meier approach. When used to estimate the cumulative incidence of VTE in cancer studies, the Kaplan-Meier method over-estimates the cumulative incidence function due to failure to account for death as a competing risk for the development of VTE. A more appropriate statistical estimate of cumulative incidence of VTE in cancer studies is the competing risk model. This review describes the theoretical and mathematical basis for estimating the cumulative incidence function by the competing risk model for the analysis of VTE outcomes in cancer-associated thrombosis. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Campigotto, Federico; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Zwicker, Jeffrey I.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hemostasis Thrombosis, Boston, MA 02215 USA. [Zwicker, Jeffrey I.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. RP Campigotto, F (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM campigotto.federico@jimmy.harvard.edu FU NHLBI NIH HHS [K23HL84052] NR 3 TC 8 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD APR PY 2012 VL 129 SU 1 BP S85 EP S87 PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 964EO UT WOS:000305676800018 PM 22682141 ER PT J AU Burstein, R Strassman, A Moskowitz, M AF Burstein, Rami Strassman, Andrew Moskowitz, Michael TI Can cortical spreading depression activate central trigeminovascular neurons without peripheral input? Pitfalls of a new concept SO CEPHALALGIA LA English DT Editorial Material ID MIGRAINE; MODEL; AURA; PAIN C1 [Burstein, Rami; Strassman, Andrew] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Moskowitz, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Burstein, R (reprint author), Beth Israel Deaconess Med Ctr, CLS 649,3 Blackfan Circle, Boston, MA 02215 USA. EM rburstei@bidmc.harvard.edu FU NINDS NIH HHS [P01 NS035611, R01 NS069847, R37 NS079678] NR 13 TC 8 Z9 9 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD APR PY 2012 VL 32 IS 6 BP 509 EP 511 DI 10.1177/0333102411436262 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 951DP UT WOS:000304701300011 PM 22345633 ER PT J AU Trimarchi, S Tolenaar, JL Tsai, TT Froehlich, J Pegorer, M Upchurch, GR Fattori, R Sundt, TM Isselbacher, EM Nienaber, CA Rampoldi, V Eagle, KA AF Trimarchi, S. Tolenaar, J. L. Tsai, T. T. Froehlich, J. Pegorer, M. Upchurch, G. R., Jr. Fattori, R. Sundt, T. M., III Isselbacher, E. M. Nienaber, C. A. Rampoldi, V. Eagle, K. A. TI Influence of clinical presentation on the outcome of acute B aortic dissection: evidences from IRAD SO JOURNAL OF CARDIOVASCULAR SURGERY LA English DT Article DE Aortic diseases; Aorta; Outcome assessment (Health Care) ID INTERNATIONAL REGISTRY; FOLLOW-UP; MANAGEMENT; SURGERY; THERAPY; DETERMINANTS; DIAGNOSIS AB Aim. In-hospital outcome of acute type B dissection (ABAD) is strongly related to preoperative aortic conditions. In order to clarify the influence of the clinical presentation on the outcome, we analyzed the patients of the International Registry of Acute Aortic Dissection (IRAD). All patients affected by complicated ABAD, enrolled in the IRAD from 1996-2004, were included. Complications were defined as the presence of shock, periaortic hematoma, spinal cord ischemia, preoperative mesenteric ischemia/infarction, acute renal failure, limb ischemia, recurrent pain, refractory pain or refractory hypertension (group I). All other patients were categorized as uncomplicated (group II). A comprehensive analysis was performed of all clinical variables in relation to in-hospital outcome. Results. The overall in-hospital mortality among 550 patients was 12.4%. Mortality in group I (250 patients) was 20.0 %, compared to 6.1% in group II (300 patients) (P<0.001). Univariate predictors of ABAD complications were Marfan syndrome, abrupt onset of pain, migrating pain, any focal neurological deficits, need for higher number of diagnostic examinations and use of magnetic resonance and/or aortogram, abdominal vessels involvement at aortogram, larger descending aortic diameter, especially >6 cm, pleural effusion, and widened mediastinum on chest Xray. Univariate predictors of a non complicated status were normal chest X-ray and medical management. In group I, in-hospital mortality following surgical and endovascular intervention were 28.6% and 10.1% (P=0.006), respectively. Independent predictors of overall in-hospital mortality included age >70 years, female gender, ECG showing ischemia, preoperative acute renal failure, preoperative limb ischemia, peri-aortic hematoma, and surgical management. The only independent variable protective for mortality was magnetic resonance as diagnostic test. Conclusion. ABAD is a heterogeneous disease that produces dissimilar clinical subsets, each of which can have specific clinical signs, management and in hospital results. In IRAD ABAD uncomplicated patients, medical therapy was associated with best hospital outcome, while endovascular interventions were associated with better results than surgery when invasive treatments were required. Although selection bias may be possible, and irrespective of treatments, knowledge of significant risk factors for mortality may contribute to a better management and a more defined risk-assessment in patients affected by ABAD. C1 [Trimarchi, S.; Tolenaar, J. L.; Pegorer, M.; Rampoldi, V.] Univ Milan, Policlin San Donato IRCCS, Thorac Aort Res Ctr, I-20097 San Donato Milanese, Italy. [Tsai, T. T.] Univ Colorado, Denver, CO 80202 USA. [Froehlich, J.; Eagle, K. A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Upchurch, G. R., Jr.] Univ Virginia, Charlottesville, VA USA. [Fattori, R.] Univ Bologna, Bologna, Italy. [Sundt, T. M., III; Isselbacher, E. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nienaber, C. A.] Univ Rostock, Rostock, Germany. RP Trimarchi, S (reprint author), Univ Milan, IRCCS Policlin San Donato, Thorac Aort Res Ctr, Piazza Malan 2, I-20097 San Donato Milanese, Italy. EM santi.trimarchi@unimi.it RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 FU University of Michigan Faculty Group Practice, W.L.Gore; Varbedian Fund for Aortic Research FX This study was supported by the University of Michigan Faculty Group Practice, W.L.Gore and the Varbedian Fund for Aortic Research. NR 25 TC 21 Z9 22 U1 0 U2 5 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0021-9509 J9 J CARDIOVASC SURG JI J. Cardiovasc. Surg. PD APR PY 2012 VL 53 IS 2 BP 161 EP 168 PG 8 WC Cardiac & Cardiovascular Systems; Surgery; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Surgery GA 955SD UT WOS:000305040300004 PM 22456637 ER PT J AU Suri, P Hunter, DJ Rainville, J Guermazi, A Katz, JN AF Suri, Pradeep Hunter, David J. Rainville, James Guermazi, Ali Katz, Jeffrey N. TI Quantitative assessment of abdominal aortic calcification and associations with lumbar intervertebral disc height loss: the Framingham Study SO SPINE JOURNAL LA English DT Article DE Intervertebral disc; Degeneration; Vascular diseases; Lumbar; Spine ID LOW-BACK-PAIN; CORONARY-ARTERY; RADIOGRAPHIC FEATURES; COMPUTED-TOMOGRAPHY; VASCULAR-DISEASE; DEGENERATION; SPINE; CONSEQUENCES; VARIABILITY; PROGRESSION AB BACKGROUND CONTEXT: Vascular disease has been proposed as a risk factor for disc height loss (DHL). PURPOSE: To examine the relationship between quantitative measures of abdominal aortic calcifications (AACs) as a marker of vascular disease, and DHL, on computed tomography (CT). STUDY DESIGN: Cross-sectional study in a community-based population. PATIENT SAMPLE: Four hundred thirty-five participants from the Framingham Heart Study. OUTCOME MEASURES: Quantitative AAC scores assessed by CT were grouped as tertiles of "no" (reference), "low," and "high" calcification. Disc height loss was evaluated on CT reformations using a four-grade scale. For analytic purposes, DHL was dichotomized as moderate DHL of at least one level at L2-S1 versus less than moderate or no DHL. METHODS: We examined the association of AAC and DHL using logistic regression before and after adjusting for cardiovascular risk factors and before and after adjusting for age, sex, and body mass index (BMI). RESULTS: In crude analyses, low AAC (odds ratio [OR], 2.05 [1.27-3.30]; p = .003) and high AAC (OR, 2.24 [1.38-3.62]; p = .001) were strongly associated with DHL, when compared with the reference group of no AAC. Diabetes, hypercholesterolemia, hypertension, and smoking were not associated with DHL and did not attenuate the observed relationship between AAC and DHL. Adjustment for age, sex, and BMI markedly attenuated the associations between DHL and low AAC (OR, 1.20 [0.69-2.09]; p = .51) and high AAC (OR, 0.74 [0.36-1.53]; p = .42). CONCLUSIONS: Abdominal aortic calcification was associated with DHL in this community-based population. This relationship was independent of cardiovascular risk factors. However, the association of AAC with DHL was explained by the effects of age, sex, and BMI. Published by Elsevier Inc. C1 [Suri, Pradeep] VA Boston Healthcare Syst, Div PM&R, Boston, MA 02130 USA. [Suri, Pradeep; Rainville, James] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02115 USA. [Suri, Pradeep] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Suri, Pradeep; Hunter, David J.; Rainville, James] New England Baptist Hosp, Dept Orthoped, Div Res, Boston, MA 02120 USA. [Hunter, David J.] Univ Sydney, No Clin Sch, Dept Med, Sydney, NSW 2006, Australia. [Guermazi, Ali] Boston Univ, Sch Med, Dept Radiol, Boston, MA 02118 USA. [Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy,Dept Med, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. RP Suri, P (reprint author), VA Boston Healthcare Syst, Div PM&R, 150 S Huntington Ave, Boston, MA 02130 USA. EM pradeep.suri@va.gov RI Hunter, David/A-4622-2010 OI Hunter, David/0000-0003-3197-752X FU NIH [K12 HD 01097]; GE Healthcare; National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-25195]; Boston University [N01-HC-25195]; Rehabilitation Medicine Scientist Training Program (RMSTP); New England Baptist Hospital; NIH/NIAMS [K24 AR 02123, P60 AR 47782]; ARC FX PS: Nothing to disclose. DJH: Royalties: DonJoy (B); Consulting: NicOx (B); Board of Directors: OARSI (Nonfinancial); Research Support (Staff/Materials): Chief of research (A); Grants: NIH, AF, ACR (F). JR: Nothing to disclose. AG: Consulting: Merck Serono (C, Paid directly to institution/employer), Novartis (C, Paid directly to institution/employer), Genzyme (C, Paid directly to institution/employer), Stryker (C, Paid directly to institution/employer); Grants: GE Healthcare (C, Paid directly to institution/employer). JNK: Nothing to disclose.; The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195). This manuscript was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or conclusions of the Framingham Heart Study or the NHLBI. Dr Suri and this research were funded by the Rehabilitation Medicine Scientist Training Program (RMSTP), the National Institutes of Health (K12 HD 01097), and a Research Funding Award from New England Baptist Hospital. Dr Katz is funded in part by NIH/NIAMS K24 AR 02123 and P60 AR 47782. Dr Hunter is funded by an ARC future fellowship. NR 38 TC 7 Z9 7 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 J9 SPINE J JI Spine Journal PD APR PY 2012 VL 12 IS 4 BP 315 EP 323 DI 10.1016/j.spinee.2012.03.033 PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 952QS UT WOS:000304807900010 PM 22561175 ER PT J AU Hussey, EP Smolinsky, JG Piryatinsky, I Budson, AE Ally, BA AF Hussey, Erin P. Smolinsky, John G. Piryatinsky, Irene Budson, Andrew E. Ally, Brandon A. TI Using Mental Imagery to Improve Memory in Patients With Alzheimer Disease Trouble Generating or Remembering the Mind's Eye? SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE mental imagery; visual imagery; recognition memory; cognitive rehabilitation ID MILD COGNITIVE IMPAIRMENT; RANDOMIZED CONTROLLED-TRIAL; NURSING-HOME PLACEMENT; VISUAL-IMAGERY; OLDER-ADULTS; RECOGNITION MEMORY; DEMENTIA; BLIND; BRAIN; ACTIVATION AB This study was conducted to understand whether patients with mild Alzheimer disease (AD) could use general or self-referential mental imagery to improve their recognition of visually presented words. Experiment 1 showed that, unlike healthy controls, patients generally did not benefit from either type of imagery. To help determine whether the patients' inability to benefit from mental imagery at encoding was due to poor memory or due to an impairment in mental imagery, participants performed 4 imagery tasks with varying imagery and cognitive demands. Experiment 2 showed that patients successfully performed basic visual imagery, but degraded semantic memory, coupled with visuospatial and executive functioning deficits, impaired their ability to perform more complex types of imagery. Given that patients with AD can perform basic mental imagery, our results suggest that episodic memory deficits likely prevent AD patients from storing or retrieving general mental images generated during encoding. Overall, the results of both experiments suggest that neurocognitive deficits do not allow patients with AD to perform complex mental imagery, which may be most beneficial to improving memory. However, our data also suggest that intact basic mental imagery and rehearsal could possibly be helpful if used in a rehabilitation multisession intervention approach. C1 [Hussey, Erin P.; Ally, Brandon A.] Vanderbilt Univ, Dept Neurol, Nashville, TN 37232 USA. [Smolinsky, John G.] Bedford Vet Adm Hosp, Geriatr Res Educ Clin Ctr, Ctr Translat Cognit Neurosci, Bedford, MA USA. [Piryatinsky, Irene] Brown Univ, Dept Psychol, Providence, RI 02912 USA. [Budson, Andrew E.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Dept Neurol, Boston, MA 02118 USA. [Budson, Andrew E.] Boston Univ, Sch Med, Boston Univ Alzheimers Dis Ctr, Boston, MA 02118 USA. [Ally, Brandon A.] Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. [Ally, Brandon A.] Vanderbilt Univ, Dept Physiol, Nashville, TN USA. RP Ally, BA (reprint author), Vanderbilt Univ, Dept Neurol, Med Ctr N A0118,1161 21st Ave S, Nashville, TN 37232 USA. EM brandon.ally@vanderbilt.edu OI Ally, Brandon/0000-0002-6034-7968 FU National Institute on Aging [K23 AG031925, R01 AG038471, R01 AG025815] FX Supported by National Institute on Aging Grants K23 AG031925 and R01 AG038471 to B.A.A. and R01 AG025815 to A.E.B. NR 80 TC 9 Z9 10 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD APR-JUN PY 2012 VL 26 IS 2 BP 124 EP 134 DI 10.1097/WAD.0b013e31822e0f73 PG 11 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 948UC UT WOS:000304527100005 PM 21946012 ER PT J AU Cubeddu, RJ Lago, R Horvath, SA Vignola, PA O'Neill, W Palacios, IF AF Cubeddu, Roberto J. Lago, Rodrigo Horvath, Sofia A. Vignola, Paul A. O'Neill, William Palacios, Igor F. TI Use of the Impella 2.5 system alone, after and in combination with an intra-aortic balloon pump in patients with cardiogenic shock: case description and review of the literature SO EUROINTERVENTION LA English DT Review DE angiography; angioplasty; coronary flow ID ACUTE MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; VENTRICULAR ASSIST DEVICE; HIGH-RISK PATIENTS; INITIAL CLINICAL-EXPERIENCE; BLOOD-FLOW; PRIMARY ANGIOPLASTY; CARDIAC-ARREST; COUNTERPULSATION; SUPPORT AB Cardiogenic shock remains a serious complication of acute myocardial infarction as it is associated with very poor prognosis. Despite the historical clinical benefits of the intra-aortic balloon pump (IABP), in some patients additional mechanical cardiac support is necessary. The recent introduction of the percutaneous Impella (R) 2.5 mechanical circulatory support system (Abiomed Inc., Danvers, MA, USA) represents a major advancement and has been used in these circumstances. Nevertheless, the data supporting the use of this technology alone, after, or in combination with the IABP in patients with cardiogenic shock is limited and the clinical benefits remain unproven. We herein provide an updated comprehensive overview of the literature supporting the use of the Impella 2.5 system compared to the use of IABP in patients with cardiogenic shock. We also discuss the potential role for combination therapy for a patient with refractory shock. We describe a case in which an IABP was used as a bail-out strategy to provide additional haemodynamic support in a patient with refractory cardiogenic shock after the Impella 2.5 system was in place. In selected cases of refractory cardiogenic shock, the use of combined therapy with both the the Impella 2.5 and IABP can provide enhanced circulatory support and could be considered an option to maintain haemodynamic support in these patients. C1 [Cubeddu, Roberto J.; Horvath, Sofia A.; Vignola, Paul A.] Aventura Hosp & Med Ctr, Aventura, FL 33180 USA. [Lago, Rodrigo; Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [O'Neill, William] Univ Miami, Miami, FL USA. RP Cubeddu, RJ (reprint author), Aventura Hosp & Med Ctr, 20900 Biscayne Blvd, Aventura, FL 33180 USA. EM rjcubeddu@gmail.com NR 42 TC 6 Z9 6 U1 0 U2 2 PU EUROPA EDITION PI TOULOUSE CEDEX 6 PA 5, RUE SAINT-PANTALEON, BP 61508, TOULOUSE CEDEX 6, 31015, FRANCE SN 1774-024X J9 EUROINTERVENTION JI EuroIntervention PD APR PY 2012 VL 7 IS 12 BP 1453 EP 1460 DI 10.4244/EIJV7I12A226 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 948PO UT WOS:000304515300013 PM 22522555 ER PT J AU Kotton, CN AF Kotton, Camille Nelson TI Optimizing the immunogenicity of pandemic H1N1 2009 influenza vaccine in adult organ transplant patients SO EXPERT REVIEW OF VACCINES LA English DT Article DE adjuvant; H1N1 influenza; immunocompromised host; transplant; vaccine ID KIDNEY-TRANSPLANT; DIALYSIS PATIENTS; RECIPIENTS; EFFICACY; ANTIBODY AB Pandemic H1N1 influenza presented a significant threat to vulnerable immunocompromised hosts. Vaccination provided the best method of prevention, both for individuals and for herd immunity. Numerous studies have shown that the antibody response to pandemic H1N1 2009 influenza vaccine in adult organ transplant patients is diminished compared with normal hosts. Techniques to improve response to influenza vaccination, including multiple doses, use of adjuvants, different delivery methods and doses have been investigated in transplant patients. The recent article in Transplant International by Felldin et al. evaluating the humoral immune response to two serial doses of pandemic H1N1 2009 influenza vaccine in adult organ transplant recipients is reviewed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. EM ckotton@partners.org NR 17 TC 1 Z9 1 U1 0 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD APR PY 2012 VL 11 IS 4 BP 423 EP 426 DI 10.1586/ERV.12.19 PG 4 WC Immunology SC Immunology GA 950YU UT WOS:000304688600013 PM 22551028 ER PT J AU Kim, Y Higgins, JM Dasari, RR Suresh, S Park, Y AF Kim, Youngchan Higgins, John M. Dasari, Ramachandra R. Suresh, Subra Park, YongKeun TI Anisotropic light scattering of individual sickle red blood cells SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE red blood cell; sickle cell disease; light scattering; quantitative phase microscopy ID DIFFRACTION PHASE; MEMBRANE; MICROSCOPY; SPECTROSCOPY; ERYTHROCYTES; HEMOGLOBIN; DISEASE AB We present the anisotropic light scattering of individual red blood cells (RBCs) from a patient with sickle cell disease (SCD). To measure light scattering spectra along two independent axes of elongated-shaped sickle RBCs with arbitrary orientation, we introduce the anisotropic Fourier transform light scattering (aFTLS) technique and measured both the static and dynamic anisotropic light scattering. We observed strong anisotropy in light scattering patterns of elongated-shaped sickle RBCs along its major axes using static aFTLS. Dynamic aFTLS analysis reveals the significantly altered biophysical properties in individual sickle RBCs. These results provide evidence that effective viscosity and elasticity of sickle RBCs are significantly different from those of the healthy RBCs. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.4.040501] C1 [Kim, Youngchan; Park, YongKeun] Korea Adv Inst Sci & Technol, Dept Phys, Taejon 305701, South Korea. [Higgins, John M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Higgins, John M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Higgins, John M.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Dasari, Ramachandra R.] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. [Suresh, Subra] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. RP Park, Y (reprint author), Korea Adv Inst Sci & Technol, Dept Phys, Taejon 305701, South Korea. EM yk.park@kaist.ac.kr RI Park, YongKeun/B-9017-2009; Kim, Youngchan/I-5224-2014 OI Kim, Youngchan/0000-0002-5724-3949 FU KAIST [N10110038, N10110048, G04100075]; Korean Ministry of Education, Science and Technology (MEST) [2009-0087691 (BRL)]; National Research Foundation [NRF-2011-355-c00039]; National Institutes of Health [P41-RR02594-18-24, R01HL094270, DK083242]; POSCO TJ Park FX This work was supported by KAIST (N10110038, N10110048, G04100075), the Korean Ministry of Education, Science and Technology (MEST) Grant No. 2009-0087691 (BRL), National Research Foundation (NRF-2011-355-c00039), and the National Institutes of Health (P41-RR02594-18-24, R01HL094270, and DK083242). YKP acknowledges support from POSCO TJ Park Fellowship. NR 25 TC 21 Z9 21 U1 0 U2 13 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 APR PY 2012 VL 17 IS 4 AR 040501 DI 10.1117/1.JBO.17.4.040501 PG 3 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 946UL UT WOS:000304382900001 PM 22559667 ER PT J AU Gewirtz, H AF Gewirtz, Henry TI PET measurement of adenosine stimulated absolute myocardial blood flow for physiological assessment of the coronary circulation SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Review DE PET; absolute myocardial blood flow; ischemic heart disease; adenosine ID POSITRON-EMISSION-TOMOGRAPHY; ISCHEMIC-HEART-DISEASE; CARDIAC SYNDROME-X; ARTERY-DISEASE; MICROVASCULAR DYSFUNCTION; HIBERNATING MYOCARDIUM; MULTIVESSEL EVALUATION; PRESSURE MEASUREMENTS; FUNCTIONAL SEVERITY; STENOSIS SEVERITY AB Considerable awareness has been raised of late of the need to reduce radiation exposure and control costs of x-ray and radionuclide imaging procedures. PET/CT cameras are now widely available and in conjunction with appropriate radionuclides and commercially available software make quantitative measurement of absolute MBF feasible for routine clinical practice. Quantitative measurement of absolute MBF under condition of coronary vasodilation permits independent assessment of the functional status of each of the three major coronary perfusion zones and so obviates the need for rest MBF determination in the great majority of cases. Coronary microvascular function also may be assessed in this same way. Thus, the stress-only protocol with quantitative PET measurement of MBF provides essential information required for clinical decision making related to need for catheterization and intervention for patients with known or suspected ischemic heart disease. Moreover, the single PET determination of maximal MBF in contrast to the usual rest/stress procedure addresses both safety and cost concerns. The present review focuses on: (1) quantitative PET measurements of myocardial blood flow for physiological assessment of the coronary circulation and (2) the value and potential limitations of performing stress only imaging in the clinical context. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med,Cardiac Unit Yawkey 5E, Boston, MA 02114 USA. RP Gewirtz, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med,Cardiac Unit Yawkey 5E, Boston, MA 02114 USA. EM hgewirtz@partners.org FU FluoroPharma, Inc. FX Research grant from FluoroPharma, Inc. NR 62 TC 7 Z9 7 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD APR PY 2012 VL 19 IS 2 BP 347 EP 354 DI 10.1007/s12350-011-9510-9 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 947CJ UT WOS:000304403900020 PM 22231036 ER PT J AU Jeon, Y Sarma, K Lee, JT AF Jeon, Yesu Sarma, Kavitha Lee, Jeannie T. TI New and Xisting regulatory mechanisms of X chromosome inactivation SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID FACULTATIVE HETEROCHROMATIN FORMATION; ES CELL-DIFFERENTIATION; LONG NONCODING RNA; DOSAGE COMPENSATION; SAF-A; CHROMATIN-STRUCTURE; UP-REGULATION; LINKED GENES; STEM-CELLS; MOUSE AB Equalization of X linked gene expression is necessary in mammalian cells due to the presence of two X chromosomes in females and one in males. To achieve this, all female cells inactivate one of the two X chromosomes during development. This process, termed X chromosome inactivation (XCI), is a quintessential epigenetic phenomenon and involves a complex interplay between noncoding RNAs and protein factors. Progress in this area of study has consequently resulted in new approaches to study epigenetics and regulatory RNA function. Here we will discuss recent developments in the field that have advanced our understanding of XCI and its regulatory mechanisms. C1 [Jeon, Yesu; Sarma, Kavitha; Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU National Institute of Health [F32-GM090765, RO1-GM58839, RO1-GM090278] FX We thank members of the lab for valuable discussions. We have highlighted only papers published in 2010-2011 related to mechanisms of XCI regulation and apologize to colleagues whose work could not be cited due to space limitations. This work was supported by National Institute of Health Grants F32-GM090765 (to K.S.), RO1-GM58839, and RO1-GM090278 (to J.T.L.). J.T.L. is an investigator of the Howard Hughes Medical Institute. NR 84 TC 45 Z9 46 U1 2 U2 11 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 2012 VL 22 IS 2 BP 62 EP 71 DI 10.1016/j.gde.2012.02.007 PG 10 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 946FX UT WOS:000304338000002 PM 22424802 ER PT J AU Sayegh, RR Madsen, KA Adler, JD Johnson, MA Mathews, MK AF Sayegh, Rony R. Madsen, Kimberly A. Adler, Jason D. Johnson, Mary A. Mathews, Michaela K. TI Response to TASER electronic control devices and eye injuries SO DOCUMENTA OPHTHALMOLOGICA LA English DT Letter C1 [Sayegh, Rony R.; Madsen, Kimberly A.; Johnson, Mary A.; Mathews, Michaela K.] Univ Maryland, Sch Med, Dept Ophthalmol & Visual Sci, Baltimore, MD 21201 USA. [Sayegh, Rony R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Adler, Jason D.] Univ Maryland, Sch Med, Dept Emergency Med, Baltimore, MD 21201 USA. RP Mathews, MK (reprint author), Univ Maryland, Sch Med, Dept Ophthalmol & Visual Sci, Baltimore, MD 21201 USA. EM mmath002@umaryland.edu RI Sayegh, Rony/G-8777-2013 OI Sayegh, Rony/0000-0002-0119-4201 FU NEI NIH HHS [K08 EY016357] NR 6 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0012-4486 J9 DOC OPHTHALMOL JI Doc. Ophthalmol. PD APR PY 2012 VL 124 IS 2 BP 161 EP 162 DI 10.1007/s10633-012-9311-8 PG 2 WC Ophthalmology SC Ophthalmology GA 946ZY UT WOS:000304397600010 PM 22262232 ER PT J AU Kumar, N Spofford, IS Thompson, CC AF Kumar, Nitin Spofford, Inbar S. Thompson, Christopher C. TI Health Care Utilization Comparison of Direct Endoscopic Necrosectomy Versus Percutaneous Catheter Drainage for Management of Walled-off Pancreatic Necrosis SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT Digestive Disease Week (DDW) CY MAY 19-22, 2012 CL San Diego, CA C1 [Kumar, Nitin; Spofford, Inbar S.; Thompson, Christopher C.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Spofford, Inbar S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thompson, Christopher C.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2012 VL 75 IS 4 SU S BP 129 EP 130 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 946CU UT WOS:000304328000090 ER PT J AU Kumar, N Spofford, IS Thompson, CC AF Kumar, Nitin Spofford, Inbar S. Thompson, Christopher C. TI Endoscopic Versus Surgical Necrosectomy for Management of Walled-off Pancreatic Necrosis: A Health Care Utilization Comparison SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT Digestive Disease Week (DDW) CY MAY 19-22, 2012 CL San Diego, CA C1 [Kumar, Nitin; Spofford, Inbar S.; Thompson, Christopher C.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Thompson, Christopher C.] Harvard Univ, Sch Med, Boston, MA USA. [Spofford, Inbar S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2012 VL 75 IS 4 SU S BP 130 EP 130 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 946CU UT WOS:000304328000091 ER PT J AU Shin, EJ Topazian, M Syngal, S Saltzman, JR Lee, JH Farrell, JJ Goggins, MG Canto, MI AF Shin, Eun Ji Topazian, Mark Syngal, Sapna Saltzman, John R. Lee, Jeffrey H. Farrell, James J. Goggins, Michael G. Canto, Marcia I. TI Radial Versus Linear and Second Look Endoscopic Ultrasound (EUS) Improved Detection of Pancreatic Lesions: A Randomized Tandem Study SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT Digestive Disease Week (DDW) CY MAY 19-22, 2012 CL San Diego, CA C1 [Shin, Eun Ji; Goggins, Michael G.; Canto, Marcia I.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Topazian, Mark] Mayo Clin, Rochester, MN USA. [Syngal, Sapna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Saltzman, John R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Lee, Jeffrey H.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Farrell, James J.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2012 VL 75 IS 4 SU S BP 131 EP 131 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 946CU UT WOS:000304328000093 ER PT J AU Canto, MI Anandasabapathy, S Brugge, WR Falk, GW Dunbar, KB Woods, KE Almario, JAN Schell, U Goetz, M Kiesslich, R AF Canto, Marcia I. Anandasabapathy, Sharmila Brugge, William R. Falk, Gary W. Dunbar, Kerry B. Woods, Kevin E. Almario, Jose Antonio N. Schell, Ursula Goetz, Martin Kiesslich, Ralf TI In Vivo Endoscope-Based Confocal Laser Endomicroscopy (eCLE) Improves Detection of Unlocalized Barrett's Esophagus-Related Neoplasia Over High Resolution White Light Endoscopy: an International Multicenter Randomized Controlled Trial SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT Digestive Disease Week (DDW) CY MAY 19-22, 2012 CL San Diego, CA C1 [Canto, Marcia I.; Almario, Jose Antonio N.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Anandasabapathy, Sharmila] Mt Sinai Sch Med, New York, NY USA. [Brugge, William R.; Woods, Kevin E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Falk, Gary W.] Univ Penn, Philadelphia, PA 19104 USA. [Dunbar, Kerry B.] VA N Texas Hlth Care Syst, Gastroenterol, Dallas, TX USA. [Schell, Ursula; Goetz, Martin; Kiesslich, Ralf] Johannes Gutenberg Univ Mainz, Mainz, Germany. NR 0 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2012 VL 75 IS 4 SU S BP 174 EP 174 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 946CU UT WOS:000304328000207 ER PT J AU Reynolds, JA Sedarat, A Oliva, I Tatishchev, S Pisegna, JR Farrell, JJ AF Reynolds, Justin A. Sedarat, Alireza Oliva, Irma Tatishchev, Sergei Pisegna, Joseph R. Farrell, James J. TI Incremental Value of EUS-FNA Compared With CT/MRI in the Management of Pancreatic Neuroendocrine Tumors (pNETs): Defining the Pivotal Role of EUS-FNA SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT Digestive Disease Week (DDW) CY MAY 19-22, 2012 CL San Diego, CA C1 [Reynolds, Justin A.; Sedarat, Alireza; Farrell, James J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Oliva, Irma; Tatishchev, Sergei] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. [Pisegna, Joseph R.] VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2012 VL 75 IS 4 SU S BP 184 EP 184 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 946CU UT WOS:000304328001022 ER PT J AU Yoon, WJ Daglilar, E Brugge, WR AF Yoon, Won Jae Daglilar, Ebubekir Brugge, William R. TI Cystic Pancreatic Neuroendocrine Neoplasms: Results of Endoscopic Ultrasound-Guided Fine Needle Aspiration Fluid Analysis SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT Digestive Disease Week (DDW) CY MAY 19-22, 2012 CL San Diego, CA C1 [Yoon, Won Jae; Daglilar, Ebubekir; Brugge, William R.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2012 VL 75 IS 4 SU S BP 194 EP 194 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 946CU UT WOS:000304328001053 ER PT J AU Kumar, N Spofford, IS Conwell, D Thompson, CC AF Kumar, Nitin Spofford, Inbar S. Conwell, Darwin Thompson, Christopher C. TI Direct Endoscopic Necrosectomy Versus Percutaneous Catheter Drainage for Management of Walled-off Pancreatic Necrosis: A Retrospective Cohort Study SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT Digestive Disease Week (DDW) CY MAY 19-22, 2012 CL San Diego, CA C1 [Kumar, Nitin; Spofford, Inbar S.; Conwell, Darwin; Thompson, Christopher C.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Conwell, Darwin; Thompson, Christopher C.] Harvard Univ, Sch Med, Boston, MA USA. [Spofford, Inbar S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2012 VL 75 IS 4 SU S BP 317 EP 317 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 946CU UT WOS:000304328001418 ER PT J AU Somsouk, M Ng, SW Kornfield, R McQuaid, KR Lampiris, H Inadomi, JM AF Somsouk, Ma Ng, Susie W. Kornfield, Rachel McQuaid, Kenneth R. Lampiris, Harry Inadomi, John M. TI Colorectal Neoplasia in HIV-Infected Individuals During Screening and Surveillance Colonoscopy SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT Digestive Disease Week (DDW) CY MAY 19-22, 2012 CL San Diego, CA C1 [Somsouk, Ma; Ng, Susie W.; Kornfield, Rachel; McQuaid, Kenneth R.; Lampiris, Harry] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Somsouk, Ma] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [McQuaid, Kenneth R.; Lampiris, Harry] San Francisco VA Med Ctr, San Francisco, CA USA. [Inadomi, John M.] Univ Washington, Sch Med, Seattle, WA USA. RI Inadomi, John/A-6221-2014 OI Inadomi, John/0000-0001-6776-8661 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2012 VL 75 IS 4 SU S BP 344 EP 344 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 946CU UT WOS:000304328001495 ER PT J AU Azoulay, L Gralnek, IM Provenzale, D Talley, J Griffin, JM AF Azoulay, Leor Gralnek, Ian M. Provenzale, Dawn Talley, Jennifer Griffin, Joan M. TI Evaluating the Impact of Health Literacy on Knowledge, Attitudes, and Beliefs Toward Colorectal Cancer (CRC) and CRC Screening in Veterans. The Value Study: Veterans as Leaders in Understanding and Education SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT Digestive Disease Week (DDW) CY MAY 19-22, 2012 CL San Diego, CA C1 [Azoulay, Leor] Technion Israel Inst Technol, Israel Sch Med TEAMS, Haifa, Israel. [Gralnek, Ian M.] Rambam Med Ctr, Haifa, Israel. [Provenzale, Dawn] Durham VA Med Ctr, Durham, NC USA. [Provenzale, Dawn] Duke Univ, Durham, NC USA. [Talley, Jennifer] W Los Angles VA Med Ctr, Ctr Outcomes Res & Educ CORE, Los Angeles, CA USA. [Griffin, Joan M.] Minneappolis VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Griffin, Joan M.] Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2012 VL 75 IS 4 SU S BP 346 EP 346 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 946CU UT WOS:000304328001500 ER PT J AU Ma, QF AF Ma, Qiufu TI Population coding of somatic sensations SO NEUROSCIENCE BULLETIN LA English DT Review DE developmental neurobiology; dorsal root ganglion; pain pathways; itch; spinal dorsal horn ID LAMINA-I NEURONS; UNDERLYING NEUROPATHIC PAIN; SUPERFICIAL DORSAL-HORN; HISTAMINE-INDUCED ITCH; C-FIBER AFFERENTS; SPINAL-CORD; NERVE INJURY; MECHANICAL HYPERALGESIA; CENTRAL SENSITIZATION; GABAERGIC INHIBITION AB The somatic sensory system includes a variety of sensory modalities, such as touch, pain, itch, and temperature sensitivity. The coding of these modalities appears to be best explained by the population-coding theory, which is composed of the following features. First, an individual somatic sensory afferent is connected with a specific neural circuit or network (for simplicity, a sensory-labeled line), whose isolated activation is sufficient to generate one specific sensation under normal conditions. Second, labeled lines are interconnected through local excitatory and inhibitory interneurons. As a result, activation of one labeled line could modulate, or provide gate control of, another labeled line. Third, most sensory fibers are polymodal, such that a given stimulus placed onto the skin often activates two or multiple sensory-labeled lines; crosstalk among them is needed to generate one dominant sensation. Fourth and under pathological conditions, a disruption of the antagonistic interaction among labeled lines could open normally masked neuronal pathways, and allow a given sensory stimulus to evoke a new sensation, such as pain evoked by innocuous mechanical or thermal stimuli and itch evoked by painful stimuli. As a result of this, some sensory fibers operate along distinct labeled lines under normal versus pathological conditions. Thus, a better understanding of the neural network underlying labeled line crosstalk may provide new strategies to treat chronic pain and itch. C1 [Ma, Qiufu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ma, Qiufu] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Ma, QF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Qiufu_Ma@dfci.harvard.edu FU NIH from NIDCR [R01DE018025]; NINDS, USA [R01NS047710] FX This work was supported by NIH grants from NIDCR (R01DE018025) and NINDS (R01NS047710), USA. NR 100 TC 23 Z9 24 U1 1 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1673-7067 J9 NEUROSCI BULL JI Neurosci. Bull. PD APR PY 2012 VL 28 IS 2 SI SI BP 91 EP 99 DI 10.1007/s12264-012-1201-2 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 947WH UT WOS:000304463800002 PM 22466120 ER PT J AU Paucar, M Winnberg, E Walker, R Svenningsson, P AF Paucar, Martin Winnberg, Elisabeth Walker, Ruth Svenningsson, Per TI A case of Huntington disease like-1 with long disease duration SO PRION LA English DT Meeting Abstract C1 [Paucar, Martin] Karolinska Hosp Huddinge, Stockholm, Sweden. [Winnberg, Elisabeth] Ersta Nursing Sch, Inst Nursing Sci, Stockholm, Sweden. [Walker, Ruth] James Peters Vet Med Affair Ctr, Dept Neurol, Bronx, NY USA. [Svenningsson, Per] Ctr Mol Med, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 J9 PRION JI Prion PD APR-JUN PY 2012 VL 6 SU S BP 132 EP 133 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 944WK UT WOS:000304234300275 ER PT J AU O'Neil-Pirozzi, T Glenn, M Goldstein, R Strangman, G AF O'Neil-Pirozzi, Therese Glenn, Mel Goldstein, Richard Strangman, Gary TI A Controlled Treatment Study of a Novel Group Intervention for Memory Impairment SO BRAIN INJURY LA English DT Meeting Abstract C1 [O'Neil-Pirozzi, Therese] Northeastern Univ, Boston, MA 02115 USA. [Glenn, Mel; Goldstein, Richard] Spaulding Rehabil Hosp, Boston, MA USA. [Strangman, Gary] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD APR-MAY PY 2012 VL 26 IS 4-5 MA 0143 BP 369 EP 370 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 943EZ UT WOS:000304104600118 ER PT J AU Nicholas, C McLaren, D Gawrysiak, M Rogers, B Dougherty, J Nash, M AF Nicholas, Christopher McLaren, Donald Gawrysiak, Michael Rogers, Baxter Dougherty, John Nash, Michael TI Functional neuroimaging in a pediatric case of impaired awareness SO BRAIN INJURY LA English DT Meeting Abstract C1 [Nash, Michael] Univ Tennessee, Dept Psychol, Knoxville, TN 37996 USA. [Dougherty, John] Univ Tennessee, Med Ctr, Knoxville, TN USA. [Nicholas, Christopher] Henry M Jackson Fdn, Minneapolis VA Med Ctr, Minneapolis, MN USA. [McLaren, Donald] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gawrysiak, Michael] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Rogers, Baxter] Vanderbilt Univ, Dept Radiol & Radiol Sci, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD APR-MAY PY 2012 VL 26 IS 4-5 MA 0480 BP 551 EP 552 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 943EZ UT WOS:000304104600436 ER PT J AU Cabrera, J Norman, R AF Cabrera, Juan Norman, Rocio TI Post-Traumatic Attention Disorder in the chronic mild Traumatic Brain Injury Population: A Case Study using Direct Attention Training and methylphenidate SO BRAIN INJURY LA English DT Meeting Abstract C1 [Cabrera, Juan; Norman, Rocio] Dept Vet Affairs, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD APR-MAY PY 2012 VL 26 IS 4-5 MA 0525 BP 577 EP 578 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 943EZ UT WOS:000304104600480 ER PT J AU Brenner, L Homaifar, B Bahraini, N Lott, S Harwood, J Schneider, A Nagamoto, H AF Brenner, Lisa Homaifar, Beeta Bahraini, Nazanin Lott, Shea Harwood, Jeri Schneider, Alexandra Nagamoto, Herbert TI Executive Dysfunction and Suicide in United States Veterans SO BRAIN INJURY LA English DT Meeting Abstract C1 [Brenner, Lisa; Homaifar, Beeta; Bahraini, Nazanin; Lott, Shea; Schneider, Alexandra] Educ & Clin Ctr MIRECC, VISN Mental Illness Res 19, Denver, CO USA. [Harwood, Jeri] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA. [Nagamoto, Herbert] Denver VA Med Ctr, Mental Hlth Serv, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD APR-MAY PY 2012 VL 26 IS 4-5 MA 0705 BP 675 EP 676 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 943EZ UT WOS:000304104600652 ER PT J AU Arciniegas, DB Frey, KL Wortzel, HS Wagner, PJ Newman, J Anderson, CA AF Arciniegas, David B. Frey, Kimberly L. Wortzel, Hal S. Wagner, Peter J. Newman, Jody Anderson, C. Alan TI Norm-Adjusted Mini-Mental State Examination and Frontal Assessment Battery Scores Predict Inpatient Rehabilitation Outcomes after Traumatic Brain Injury SO BRAIN INJURY LA English DT Meeting Abstract C1 [Arciniegas, David B.; Frey, Kimberly L.; Wagner, Peter J.; Newman, Jody; Anderson, C. Alan] Univ Colorado, Denver Sch Med, Neurobehav Disorders Program, Dept Psychiat, Aurora, CO USA. [Arciniegas, David B.; Frey, Kimberly L.; Wagner, Peter J.; Newman, Jody; Anderson, C. Alan] Univ Colorado, Denver Sch Med, Neurobehav Disorders Program, Dept Neurol, Aurora, CO USA. [Wortzel, Hal S.] Denver Vet Affairs Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 19, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD APR-MAY PY 2012 VL 26 IS 4-5 MA 0768 BP 709 EP 710 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 943EZ UT WOS:000304104600712 ER PT J AU Wilkinson, CW Peskind, ER Colasurdo, EA Pagulayan, KF Shofer, JB AF Wilkinson, Charles W. Peskind, Elaine R. Colasurdo, Elizabeth A. Pagulayan, Kathleen F. Shofer, Jane B. TI Prevalence and Characteristics of Chronic Pituitary Dysfunction after Blast-related Mild Traumatic Brain Injury SO BRAIN INJURY LA English DT Meeting Abstract C1 [Wilkinson, Charles W.; Peskind, Elaine R.; Colasurdo, Elizabeth A.; Pagulayan, Kathleen F.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Shofer, Jane B.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD APR-MAY PY 2012 VL 26 IS 4-5 MA 0804 BP 732 EP 732 PG 1 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 943EZ UT WOS:000304104600748 ER PT J AU Arciniegas, DB Wortzel, HS Wagner, PJ Frey, KL Anderson, CA AF Arciniegas, David B. Wortzel, Hal S. Wagner, Peter J. Frey, Kimberly L. Anderson, C. Alan TI Clock Drawing Performance Predicts Inpatient Rehabilitation Outcomes after Traumatic Brain Injury SO BRAIN INJURY LA English DT Meeting Abstract C1 [Arciniegas, David B.; Wagner, Peter J.; Frey, Kimberly L.; Anderson, C. Alan] Univ Colorado, Denver Sch Med, Neurobehav Disorders Program, Dept Psychiat, Aurora, CO USA. [Arciniegas, David B.; Wagner, Peter J.; Frey, Kimberly L.; Anderson, C. Alan] Univ Colorado, Denver Sch Med, Dept Neurol, Aurora, CO USA. [Wortzel, Hal S.] Denver Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr VISN 19, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD APR-MAY PY 2012 VL 26 IS 4-5 MA 0832 BP 748 EP 749 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 943EZ UT WOS:000304104600774 ER PT J AU Pasinetti, G Gordon, W Ho, L Zhao, W AF Pasinetti, Giulio Gordon, Wayne Ho, Lap Zhao, Wei TI Role of Olfactory Receptor in Traumatic Brain Injury-Associated Tauopathy SO BRAIN INJURY LA English DT Meeting Abstract C1 [Gordon, Wayne; Ho, Lap; Zhao, Wei] Mt Sinai Sch Med, New York, NY USA. [Pasinetti, Giulio] James J Peters VA Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD APR-MAY PY 2012 VL 26 IS 4-5 MA 0835 BP 750 EP 750 PG 1 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 943EZ UT WOS:000304104600777 ER PT J AU Carlson, K O'Neil, ME Ensley, M Tun, SM Hutson, L Storzbach, D AF Carlson, Kathleen O'Neil, Maya Elin Ensley, Megan Tun, Saw-Myo Hutson, Lee Storzbach, Daniel TI Associations between Post-concussive Symptoms and Psychosocial Problems Endorsed by United States Veterans of the Iraq and Afghanistan Wars SO BRAIN INJURY LA English DT Meeting Abstract C1 [Carlson, Kathleen; O'Neil, Maya Elin; Ensley, Megan; Tun, Saw-Myo; Hutson, Lee; Storzbach, Daniel] Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD APR-MAY PY 2012 VL 26 IS 4-5 MA 0885 BP 779 EP 780 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 943EZ UT WOS:000304104600826 ER PT J AU d'Othee, BJ Walker, TG Marota, JJ Waltman, AC Greenfield, AJ Koizumi, J AF d'Othee, Bertrand Janne Walker, T. Gregory Marota, John J. Waltman, Arthur C. Greenfield, Alan J. Koizumi, Jun TI Splenic Venous Congestion after Balloon-Occluded Retrograde Transvenous Obliteration of Gastric Varices SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Letter ID NATURAL-HISTORY; PORTAL-HYPERTENSION; FUNDAL VARICES; SCLEROTHERAPY; HEMODYNAMICS; ESOPHAGEAL; SHUNT; CT C1 [d'Othee, Bertrand Janne] Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, Div Vasc & Intervent Radiol, Baltimore, MD 21021 USA. [d'Othee, Bertrand Janne; Walker, T. Gregory; Waltman, Arthur C.; Greenfield, Alan J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Marota, John J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anaesthesiol, Boston, MA 02114 USA. [Koizumi, Jun] Univ Tokyo, Sch Med, Dept Diagnost Radiol, Tokyo 113, Japan. RP d'Othee, BJ (reprint author), Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, Div Vasc & Intervent Radiol, 22 S Greene St, Baltimore, MD 21021 USA. EM bjannedothee@umm.edu NR 20 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD APR PY 2012 VL 35 IS 2 BP 434 EP 438 DI 10.1007/s00270-011-0160-8 PG 5 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 943XY UT WOS:000304162400031 ER PT J AU Bandyopadhyay, M Rohrer, B AF Bandyopadhyay, Mausumi Rohrer, Baerbel TI Matrix Metalloproteinase Activity Creates Pro-Angiogenic Environment in Primary Human Retinal Pigment Epithelial Cells Exposed to Complement SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CHOROIDAL NEOVASCULAR MEMBRANES; ACTIVATED PROTEIN-KINASE; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; BRUCHS MEMBRANE; ALTERNATIVE PATHWAY; TARGETED INHIBITOR; DRUSEN FORMATION; ATTACK COMPLEX; MOUSE MODEL AB PURPOSE. Mechanistic studies have shown that inflammation, complement activation, extracellular matrix (ECM) turnover, growth factor imbalance, and oxidative stress are fundamental components of age-related macular degeneration (AMD). Matrix metalloproteinases (MMPs) mediate ECM turnover but also process various bioactive molecules. Here, we tested whether complement attack on RPE monolayers changes MMP secretion and activation, thereby altering the availability of growth factors in the extracellular space. METHODS. Human embryonic RPE monolayers with stable transepithelial resistance (TER) were established. Complement activation was induced with H2O2 and normal human serum. MMP-2/9, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) protein, and mRNA levels were analyzed by Western blotting, ELISA, and real-time PCR; activity of MMP-2/9 by gelatin zymography. RESULTS. Complement activation resulted in a loss of TER, which required transient membrane attack complex formation, activation of the alternative pathway, and VEGF secretion and signaling. Despite the generation of reactive oxygen species, cellular integrity or intracellular adenosine triphosphate (ATP) levels were unaffected. However, expression of MMP-2/9 and their protease activity was elevated. Inhibition of MMP-2/9 activity increased PEDF and decreased VEGF levels in the apical and basal supernatants but had no effect on their expression levels. VEGF levels in the supernatant correlated with the level TER reduction. CONCLUSIONS. These studies suggest that complement activation, by altering the expression and activation of MMPs, has the ability to generate a proangiogenic environment by altering the balance between VEGF and PEDF. Our findings link reported results that have been associated with AMD pathogenesis; oxidative stress; complement activation; VEGF/PEDF ratio; and MMP activity. (Invest Ophthalmol Vis Sci. 2012;53:1953-1961) DOI:10.1167/iovs.11-8638 C1 [Bandyopadhyay, Mausumi; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Storm Eye Inst, Charleston, SC 29425 USA. [Rohrer, Baerbel] Med Univ S Carolina, Div Res, Dept Neurosci, Charleston, SC 29425 USA. [Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. RP Rohrer, B (reprint author), Med Univ S Carolina, Dept Ophthalmol, Storm Eye Inst, 167 Ashley Ave,SEI 511, Charleston, SC 29425 USA. EM rohrer@musc.edu FU National Institutes of Health [R01EY019320, C06 RR015455]; Department of Veterans Affairs [I01 RX000444]; Foundation Fighting Blindness; Research to Prevent Blindness, New York, New York (RPB) FX Supported in part by the National Institutes of Health Grant R01EY019320; Department of Veterans Affairs Grant I01 RX000444; Foundation Fighting Blindness; and an unrestricted grant to MUSC from Research to Prevent Blindness, New York, New York (RPB). BR is a Research to Prevent Blindness Olga Keith Wiess Scholar. Animal studies were conducted in a facility constructed with support from the National Institutes of Health Grant C06 RR015455. NR 71 TC 24 Z9 24 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 APR PY 2012 VL 53 IS 4 BP 1953 EP 1961 DI 10.1167/iovs.11-8638 PG 9 WC Ophthalmology SC Ophthalmology GA 937PC UT WOS:000303669400032 PM 22408008 ER PT J AU Peppi, M Landa, M Sewell, WF AF Peppi, Marcello Landa, Melissa Sewell, William F. TI Cochlear Kainate Receptors SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE immunohistochemistry; AMPA; mouse; hearing; auditory nerve; neurotransmitter; pharmacology ID CELL RIBBON SYNAPSE; AFFERENT SYNAPSES; AMPA RECEPTORS; ION CHANNELS; EXPRESSION; RAT; PHARMACOLOGY; ANTAGONISTS; SUBUNITS; POTENT AB Synaptic transmission between the cochlear hair cell and its afferent fiber is mediated by glutamate receptors. While kainate receptors are known to be present in the spiral ganglion, little is known of their distribution or functional role. We have detected all five kainate receptor subunits in the mouse cochlea with quantitative RT-PCR and with immunohistochemistry. We observed kainate receptors on afferent terminals co-localized with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors at the afferent synapse. Individual terminals innervating a single hair cell varied in their ratios of AMPA to kainate receptor immunoreactivity. Infusion of the mouse cochlea via the scala tympani with UBP296, a recently developed antagonist with high specificity for the GluK1 kainate receptor (compared to the AMPA receptor), reduced the compound action potential and elevated auditory neural thresholds without affecting the distortion product otoacoustic emission thresholds. Thus, the pharmacological evidence suggests that kainate receptors may contribute to the response to transmitter released from the hair cell during acoustic stimulation. It is plausible that afferent transmission at this synapse is mediated by a mix of AMPA and kainate receptors. C1 [Sewell, William F.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Eaton Peabody Lab, Boston, MA 02114 USA. [Sewell, William F.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sewell, WF (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM wfs@epl.meei.harvard.edu FU NIDCD [DC00767] FX The work was supported by the NIDCD (grant # DC00767). We thank M. C. Brown and M. C. Liberman for comments and critiques of the manuscript. NR 22 TC 6 Z9 6 U1 0 U2 6 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 APR PY 2012 VL 13 IS 2 BP 199 EP 208 DI 10.1007/s10162-011-0309-9 PG 10 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 940MH UT WOS:000303893200004 PM 22231646 ER PT J AU Chambers, AR Hancock, KE Maison, SF Liberman, MC Polley, DB AF Chambers, Anna R. Hancock, Kenneth E. Maison, Stephane F. Liberman, M. Charles Polley, Daniel B. TI Sound-Evoked Olivocochlear Activation in Unanesthetized Mice SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE olivocochlear; corticofugal; arousal; attention; anesthesia; contralateral reflex; outer hair cell ID PRODUCT OTOACOUSTIC EMISSIONS; AWAKE GUINEA-PIGS; INFERIOR COLLICULUS; AUDITORY-CORTEX; FINE-STRUCTURE; EFFERENT ACTIVATION; DISTORTION PRODUCTS; COCHLEAR EFFERENT; ACOUSTIC INJURY; BRAIN-STEM AB Genetic tools available for the mouse make it a powerful model to study the modulation of cochlear function by descending control systems. Suppression of distortion product otoacoustic emission (DPOAE) amplitude by contralateral acoustic stimulation (CAS) provides a robust tool for noninvasively monitoring the strength of descending modulation, yet investigations in mice have been performed infrequently and only under anesthesia, a condition likely to reduce olivocochlear activation. Here, we characterize the contralateral olivocochlear reflex in the alert, unanesthetized mouse. Head-fixed mice were restrained between two closed acoustic systems, while an artifact rejection protocol minimized contamination from self-generated sounds and movements. In mice anesthetized with pentobarbital, ketamine or urethane, CAS at 80 dB SPL evoked, on average, a <1-dB change in DPOAE amplitude. In contrast, the mean CAS-induced DPOAE suppression in unanesthetized mice was nearly 8 dB. Experiments in mice with targeted deletion of the alpha 9 subunit of the nicotinic acetylcholine receptor confirmed the contribution of the medial olivocochlear efferents to this phenomenon. These findings demonstrate the utility of the CAS assay in the unanesthetized mouse and highlight the adverse effects of anesthesia when probing the functional status of descending control pathways within the auditory system. C1 [Chambers, Anna R.; Hancock, Kenneth E.; Maison, Stephane F.; Liberman, M. Charles; Polley, Daniel B.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Chambers, Anna R.; Polley, Daniel B.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Hancock, Kenneth E.; Maison, Stephane F.; Liberman, M. Charles; Polley, Daniel B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Chambers, AR (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Anna_Chambers@meei.harvard.edu OI Polley, Daniel/0000-0002-5120-2409 FU NIDCD [P30 DC5029, R01 DC0188, R01 DC09836, R03 DC09488] FX We are grateful to Dr. Douglas Vetter for generously sharing his alpha 9-null and wild-type mice with us, to Drs. John Guinan, Jeremiah Cohen and Nao Uchida for helpful advice, and to Sara Anastas and John Thompson for animal care and technical assistance. Financial support was provided by NIDCD grants: P30 DC5029 (MCL), R01 DC0188 (MCL), R01 DC09836 (DBP), and R03 DC09488 (DBP). NR 56 TC 19 Z9 19 U1 0 U2 5 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 APR PY 2012 VL 13 IS 2 BP 209 EP 217 DI 10.1007/s10162-011-0306-z PG 9 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 940MH UT WOS:000303893200005 PM 22160753 ER PT J AU Jiao, JJ Kang, JX Tan, R Wang, JD Zhang, Y AF Jiao, Jingjing Kang, Jing X. Tan, Rui Wang, Jingdong Zhang, Yu TI Multiplex time-reducing quantitative polymerase chain reaction assay for determination of telomere length in blood and tissue DNA SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Multiplex qPCR; Time-reducing; Telomere length; Genomic DNA; Cancer ID PCR AMPLIFICATION; CELLS; CANCER; DISEASE; MOUSE; ATTRITION; BIOMARKER; BETAINE; MICE AB In this paper we describe a multiplex time-reducing quantitative polymerase chain reaction (qPCR) method for determination of telomere length. This multiplex qPCR assay enables two pairs of primers to simultaneously amplify telomere and single copy gene (albumin) templates, thus reducing analysis time and labor compared with the previously established singleplex assay. The chemical composition of the master mix and primers for the telomere and albumin were systematically optimized. The thermal cycling program was designed to ensure complete separation of the melting processes of the telomere and albumin. Semi-log standard curves of DNA concentration versus cycle threshold (C (t)) were established, with a linear relationship over an 81-fold DNA concentration range. The well-performed intra-assay (RSD range 2.4-4.7%) and inter-assay (RSD range: 3.1-5.0%) reproducibility were demonstrated to ensure measurement stability. Using wild-type, Lewis lung carcinoma and H22 liver carcinoma C57BL/6 mouse models, significantly different telomere lengths among different DNA samples were not observed in wild-type mice. However, the relative telomere lengths of the tumor DNA in the two strains of tumor-bearing mice were significantly shorter than the lengths in the surrounding non-tumor DNA of tumor-bearing mice and the tissue DNA of wild-type mice. These results suggest that the shortening of telomere lengths may be regarded as an important indicator for cancer control and prevention. Quantification of telomere lengths was further confirmed by the traditional Southern blotting method. This method could be successfully used to reduce the time needed for rapid, precise measurement of telomere lengths in biological samples. ' C1 [Zhang, Yu] Zhejiang Univ, Dept Food Sci & Nutr, Coll Biosyst Engn & Food Sci, Hangzhou 310058, Zhejiang, Peoples R China. [Jiao, Jingjing; Kang, Jing X.; Wang, Jingdong] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jiao, Jingjing; Kang, Jing X.; Wang, Jingdong] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tan, Rui] SW Jiaotong Univ, Sch Life Sci & Engn, Chengdu 610031, Sichuan, Peoples R China. RP Zhang, Y (reprint author), Zhejiang Univ, Dept Food Sci & Nutr, Coll Biosyst Engn & Food Sci, 866 Yuhangtang Rd, Hangzhou 310058, Zhejiang, Peoples R China. EM y_zhang@zju.edu.cn NR 42 TC 2 Z9 2 U1 1 U2 13 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD APR PY 2012 VL 403 IS 1 BP 157 EP 166 DI 10.1007/s00216-012-5783-3 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 912YY UT WOS:000301839700010 PM 22327932 ER PT J AU Feil, DG Zhu, CW Sultzer, DL AF Feil, Denise G. Zhu, Carolyn W. Sultzer, David L. TI The relationship between cognitive impairment and diabetes self-management in a population-based community sample of older adults with Type 2 diabetes SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Diabetes mellitus; Cognitive impairment; Self-management; Comorbidity; Health behaviors ID MEDICATION ADHERENCE; GLYCEMIC CONTROL; PRACTICE GUIDELINES; ALZHEIMERS-DISEASE; HEMOGLOBIN A(1C); DEMENTIA; MELLITUS; HEALTH; PREVALENCE; DECLINE AB Although nearly one-third of older diabetics are cognitively impaired, their diabetes management remains poorly understood. To examine the relationship between cognitive impairment and diabetes self-management in a population-based community sample of older adults with Type 2 diabetes. Cross-sectional observational analysis. 1,398 persons with diabetes, aged 60 years or older, who responded to the 2003 Health and Retirement Study Diabetes Survey. We conducted logistic regressions on the effects of cognitive impairment on respondents' self-management ability after controlling for diabetes comorbidities, demographics, and clinical characteristics. Participants with greater cognitive impairment were less likely to adhere to exercise (Adjusted Odds ratio [AOR] = 0.725 and 0.712 for moderate and severe cognitive impairment, both P < 0.05), and to diet (AOR = 0.906 and 0.618 for moderate and severe cognitive impairment, both P < 0.01). Cognitive impairment is associated with worse self-care and may pose challenges to diabetic older persons, notably in diet and exercise. Cognitive screening may be indicated in this high risk group. C1 [Feil, Denise G.; Sultzer, David L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Greater Los Angeles VA Healthcare Syst, W LA Vet Hlth Care Ctr, Los Angeles, CA 90073 USA. [Zhu, Carolyn W.] Mt Sinai Sch Med, JJP VA Med Ctr, New York, NY USA. RP Feil, DG (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Greater Los Angeles VA Healthcare Syst, W LA Vet Hlth Care Ctr, 11301 Wilshire Blvd,Bldg 401 116 AE, Los Angeles, CA 90073 USA. EM denise.feil@va.gov NR 60 TC 19 Z9 22 U1 4 U2 23 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD APR PY 2012 VL 35 IS 2 BP 190 EP 199 DI 10.1007/s10865-011-9344-6 PG 10 WC Psychology, Clinical SC Psychology GA 940BP UT WOS:000303865300008 PM 21503710 ER PT J AU Pevnick, JM Claver, M Dobalian, A Asch, SM Stutman, HR Tomines, A Fu, P AF Pevnick, Joshua M. Claver, Maria Dobalian, Aram Asch, Steven M. Stutman, Harris R. Tomines, Alan Fu, Paul, Jr. TI Provider Stakeholders' Perceived Benefit from a Nascent Health Information Exchange: A Qualitative Analysis SO JOURNAL OF MEDICAL SYSTEMS LA English DT Article DE Medical informatics; Community networks; Health policy; Qualitative research; Organizational case studies; Community based participatory research ID SANTA-BARBARA; CARE; PRIVACY; SYSTEMS AB We sought to better understand the perceived costs and benefits of joining a nascent health information exchange (HIE) from the perspective of potential provider organization participants. We therefore conducted semi-structured interviews with organizational representatives. Interview transcriptions were thematically coded, and coded text was subsequently aggregated to summarize the breadth and depth of responses. Although no respondents expected HIE to result in net financial benefit to their organization, all respondents recognized some potential benefits, and some respondents expected HIE to result in overall organizational benefit. Disproportionate benefit was expected for the poorest, sickest patients. Many respondents had concerns about HIE increasing the risk of data security breaches, and these concerns were most pronounced at larger organizations. We found little evidence of organizational concern regarding loss of patients to other organizations or publication of unfavorable quality data. If HIE's greatest benefactors are indeed the poorest, sickest patients, our current health care financing environment will make it difficult to align HIE costs with benefits. To sustain HIE, state and federal governments may need to consider ongoing subsidies. Furthermore, these governments will need to ensure that policies regulating data exchange have sufficient nationwide coordination and liability limitations that the perceived organizational risks of joining HIEs do not outweigh perceived benefits. HIE founders can address organizational concerns by attempting to coordinate HIE policies with those of their largest founding organizations, particularly for data security policies. Early HIE development and promotional efforts should not only focus on potential benefits, but should also address organizational concerns. C1 [Pevnick, Joshua M.] Cedars Sinai Med Ctr, Dept Med, Div Gen Internal Med, Los Angeles, CA 90048 USA. [Claver, Maria] Calif State Univ Long Beach, Long Beach, CA 90840 USA. [Dobalian, Aram; Asch, Steven M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dobalian, Aram; Tomines, Alan; Fu, Paul, Jr.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Asch, Steven M.] RAND Hlth, Los Angeles, CA USA. [Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Stutman, Harris R.] Mem Care Hlth Syst, Miller Childrens Hosp, Long Beach, CA USA. [Tomines, Alan; Fu, Paul, Jr.] Harbor UCLA Med Ctr, Div Gen & Emergency Pediat, Torrance, CA 90509 USA. [Tomines, Alan; Fu, Paul, Jr.] Los Angeles Biomed Res Inst, Torrance, CA USA. RP Pevnick, JM (reprint author), Cedars Sinai Med Ctr, Dept Med, Div Gen Internal Med, 8700 Beverly Blvd,Room B220, Los Angeles, CA 90048 USA. EM jpevnick@gmail.com FU Office of the National Coordinator for Health Information Technology; Department of Veterans Affairs FX This study was funded by the Office of the National Coordinator for Health Information Technology. This work was also supported by a health services research and development fellowship from the Department of Veterans Affairs (to JMP). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of their employers, including the Department of Veterans Affairs and the United States government. NR 14 TC 10 Z9 10 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0148-5598 J9 J MED SYST JI J. Med. Syst. PD APR PY 2012 VL 36 IS 2 BP 601 EP 613 DI 10.1007/s10916-010-9524-x PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 939PS UT WOS:000303825500026 PM 20703673 ER PT J AU Berra, L Pinciroli, R Panigada, M Zanella, A Cressoni, M Bassi, GL AF Berra, L. Pinciroli, R. Panigada, M. Zanella, A. Cressoni, M. Bassi, G. Li CA Gravity-VAP Network TI Alternative approaches to ventilator associated pneumonia prevention. The authors reply SO MINERVA ANESTESIOLOGICA LA English DT Letter ID TRACHEAL INTUBATION; COLONIZATION; ASPIRATION; POSITION; GRAVITY C1 [Berra, L.; Pinciroli, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Panigada, M.; Cressoni, M.] Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Intens Care Unit, Milan, Italy. [Zanella, A.] Osped Azienda Osped San Gerardo, Monza, Italy. [Bassi, G. Li] Hosp Clin Barcelona, Resp Crit Care Unit, Barcelona, Spain. RP Berra, L (reprint author), Massachusetts Gen Hosp, White 434B,55 Fruit St, Boston, MA 02114 USA. EM lberra@partners.org RI Cressoni, Massimo/B-7315-2017; Panigada, Mauro/K-4650-2014; OI Cressoni, Massimo/0000-0002-0089-2905; Panigada, Mauro/0000-0003-4841-9794; zanella, Alberto/0000-0002-2967-2527 NR 7 TC 0 Z9 0 U1 0 U2 1 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0375-9393 J9 MINERVA ANESTESIOL JI Minerva Anestesiol. PD APR PY 2012 VL 78 IS 4 BP 509 EP 510 PG 2 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA 939FB UT WOS:000303791900019 ER PT J AU Ries, ML McLaren, DG Bendlin, BB GuofanXu Rowley, HA Birn, R Kastman, EK Sager, MA Asthana, S Johnson, SC AF Ries, Michele L. McLaren, Donald G. Bendlin, Barbara B. GuofanXu Rowley, Howard A. Birn, Rasmus Kastman, Erik K. Sager, Mark A. Asthana, Sanjay Johnson, Sterling C. TI Medial prefrontal functional connectivity-Relation to memory self-appraisal accuracy in older adults with and without memory disorders SO NEUROPSYCHOLOGIA LA English DT Article DE Alzheimer's disease; Mild cognitive impairment; Anosognosia; Self-appraisal; fMRI; Functional connectivity ID MILD COGNITIVE IMPAIRMENT; STAGE ALZHEIMERS-DISEASE; FRONTOTEMPORAL LOBAR DEGENERATION; NEURODEGENERATIVE-DISEASE; CAREGIVER BURDEN; DEMENTIA; AWARENESS; ANOSOGNOSIA; CORTEX; NETWORKS AB It is tentatively estimated that 25% of people with early Alzheimer's disease (AD) show impaired awareness of disease-related changes in their own cognition. Research examining both normative self-awareness and altered awareness resulting from brain disease or injury points to the central role of the medial prefrontal cortex (MPFC) in generating accurate self-appraisals. The current project builds on this work - examining changes in MPFC functional connectivity that correspond to impaired self-appraisal accuracy early in the AD time course. Our behavioral focus was self-appraisal accuracy for everyday memory function, and this was measured using the Memory Function Scale of the Memory Awareness Rating Scale - an instrument psychometrically validated for this purpose. Using regression analysis of data from people with healthy memory (n = 12) and people with impaired memory due to amnestic mild cognitive impairment or early AD (n = 12), we tested the hypothesis that altered MPFC functional connectivity - particularly with other cortical midline structures and dorsolateral prefrontal cortex - explains variation in memory self-appraisal accuracy. We spatially constrained (i.e., explicitly masked) our regression analyses to those regions that work in conjunction with the MPFC to evoke self-appraisals in a normative group. This empirically derived explicit mask was generated from the result of a psychophysiological interaction analysis of fMRI self-appraisal task data in a separate, large group of cognitively healthy individuals. Results of our primary analysis (i.e., the regression of memory self-appraisal accuracy on MPFC functional connectivity) were generally consistent with our hypothesis: people who were less accurate in making memory self-appraisals showed attenuated functional connectivity between the MPFC seed region and proximal areas within the MPFC (including subgenual anterior cingulate cortex), bilateral dorsolateral prefrontal cortex, bilateral caudate, and left posterior hippocampus. Contrary to our expectations, MPFC functional connectivity with the posterior cingulate was not significantly related to accuracy of memory self-appraisals. Results reported here corroborate findings of variable memory self-appraisal accuracy during the earliest emergence of AD symptoms and reveal alterations in MPFC functional connectivity that correspond to impaired memory self-appraisal. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Ries, Michele L.; Bendlin, Barbara B.; GuofanXu; Kastman, Erik K.; Asthana, Sanjay; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. [Ries, Michele L.; Bendlin, Barbara B.; GuofanXu; Rowley, Howard A.; Birn, Rasmus; Kastman, Erik K.; Sager, Mark A.; Asthana, Sanjay; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Madison, WI 53705 USA. [McLaren, Donald G.] Edith Nourse Rogers Mem Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, Bedford, MA 01730 USA. [McLaren, Donald G.] Massachusetts Gen Hosp, Ctr Biomed Imaging, Dept Neurol & Athinoula A Martinos, Boston, MA 02114 USA. [McLaren, Donald G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ries, ML (reprint author), Wisconsin Alzheimers Dis Res Ctr, 600 Highland Ave,J5-1 Mezzanine,Mail Code 2420, Madison, WI 53792 USA. EM mlr@medicine.wisc.edu RI Kastman, Erik/N-6645-2016; OI Kastman, Erik/0000-0001-7221-9042; Bendlin, Barbara/0000-0002-0580-9875; McLaren, Donald/0000-0002-0566-4610; Johnson, Sterling/0000-0002-8501-545X FU National Center for Research Resources (NCRR), National Institutes of Health (NIH) [1UL1RR025011]; CTSA; NIH [R01AG21155, R01AG027161]; Wisconsin Alzheimer's Disease Research Center (NIH) [P50AG033514] FX The authors gratefully acknowledge the study participants who generously gave their time and effort to make this project possible. We also thank Caitlin Cleary, Robbie Kattappuram, Amy Hawley, Kelli Hellenbrand, Sara Pladziewicz, and Jennifer Oh for their dedicated work in participant recruitment and execution of the study procedures. This work was supported by grant 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources (NCRR), National Institutes of Health (NIH). Michele Ries' contributions to this paper were supported through the CTSA grant - both as a Clinical Scholar and through a pilot grant that funded acquisition of data used in the primary analysis. Acquisition of data used in the explicit mask was made possible by support through NIH grants R01AG21155 (PI: Sterling Johnson) and R01AG027161 (PI: Mark Sager). We also acknowledge facilities and resources provided through the Wisconsin Alzheimer's Disease Research Center (NIH grant P50AG033514; PI: Sanjay Asthana) and the Geriatric Research Education and Clinical Center (GRECC) of the William S. Middleton Memorial Veterans Hospital (GRECC manuscript number 2011-10). NR 76 TC 16 Z9 16 U1 2 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD APR PY 2012 VL 50 IS 5 BP 603 EP 611 DI 10.1016/j.neuropsychologia.2011.12.014 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 941HS UT WOS:000303954900006 PM 22230228 ER PT J AU Stevenson, W Cheng, SF Dastjerdi, MH Ferrari, G Dana, R AF Stevenson, William Cheng, Sheng-Fu Dastjerdi, Mohammad H. Ferrari, Giulio Dana, Reza TI Corneal Neovascularization and the Utility of Topical VEGF Inhibition: Ranibizumab (Lucentis) Vs Bevacizumab (Avastin) SO OCULAR SURFACE LA English DT Article DE angiogenesis; bevacizumab; cornea; corneal angiogenic privilege; hemangiogenesis; lymphangiogenesis; neovascularization; ranibizumab; vascular endothelial growth factor; VEGF ID ENDOTHELIAL GROWTH-FACTOR; EPITHELIUM-DERIVED FACTOR; STEM-CELL DEFICIENCY; SMOOTH-MUSCLE-CELLS; NEUTROPHIL-DIRECTED ANGIOGENESIS; BASEMENT-MEMBRANE ZONES; NECROSIS-FACTOR-ALPHA; PHOTODYNAMIC THERAPY; ARGON-LASER; LIPID KERATOPATHY AB Corneal avascularity is necessary for the preservation of optimal vision. The cornea maintains a dynamic balance between pro- and antiangiogenic factors that allows it to remain avascular under normal homeostatic conditions; however, corneal avascularity can be compromised by pathologic conditions that negate the cornea's "angiogenic privilege." The clinical relevance of corneal neovascularization has long been recognized, but management of this condition has been hindered by a lack of safe and effective therapeutic modalities. Herein, the etiology, epidemiology, pathogenesis, and treatment of corneal neovascularization are reviewed. Additionally, the authors' recent findings regarding the clinical utility of topical ranibizumab (Lucentis (R)) and bevacizumab (Avastin (R)) in the treatment of corneal neovascularization are summarized. These findings clearly indicate that ranibizumab and bevacizumab are safe and effective treatments for corneal neovascularization when appropriate precautions are observed. Although direct comparisons are not conclusive, the results suggest that ranibizumab may be modestly superior to bevacizumab in terms of both onset of action and degree of efficacy. In order to justify the increased cost of ranibizumab, it will be necessary to demonstrate meaningful treatment superiority in a prospective, randomized, head-to-head comparison study. C1 [Stevenson, William; Cheng, Sheng-Fu; Dastjerdi, Mohammad H.; Dana, Reza] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Ferrari, Giulio] GB Bietti Eye Fdn, Rome, Italy. RP Dana, R (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu RI ferrari, giulio/J-9260-2016 OI ferrari, giulio/0000-0001-6474-9908 FU NIH [EY-12963, EY-19098] FX Supported in part by NIH grants EY-12963 (RD) and EY-19098 (RD). NR 264 TC 39 Z9 44 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1542-0124 EI 1937-5913 J9 OCUL SURF JI Ocul. Surf. PD APR PY 2012 VL 10 IS 2 BP 67 EP 83 PG 17 WC Ophthalmology SC Ophthalmology GA 937FB UT WOS:000303643300003 PM 22482468 ER PT J AU Sullivan, DA Hammitt, KM Schaumberg, DA Sullivan, BD Begley, CG Gjorstrup, P Garrigue, JS Nakamura, M Quentric, Y Barabino, S Dalton, M Novack, GD AF Sullivan, David A. Hammitt, Katherine M. Schaumberg, Debra A. Sullivan, Benjamin D. Begley, Carolyn G. Gjorstrup, Per Garrigue, Jean-Sebastien Nakamura, Masatsugu Quentric, Yann Barabino, Stefano Dalton, Michelle Novack, Gary D. TI Report of the TFOS/ARVO Symposium on Global Treatments for try Eye Disease: An Unmet Need SO OCULAR SURFACE LA English DT Article DE clinical trials; dry eye disease; drug development; Tear Film & Ocular Surface Society ID QUALITY-OF-LIFE; TEAR BREAK-UP; DRY EYE; SJOGRENS-SYNDROME; WORKSHOP 2007; KERATOCONJUNCTIVITIS SICCA; UTILITY-ASSESSMENT; DIAGNOSTIC-TESTS; IMPACT; SUBCOMMITTEE AB In September 2010, a Symposium in Florence, Italy, was held to address the unmet need for global treatments for dry eye disease (DED). It was sponsored by The Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and co-sponsored by the Association for Research in Vision & Ophthalmology (www.arvo.org). The Symposium objectives were two-fold: first, to discuss accepted and emerging clinical endpoints of DED with regulatory experts from around the world; and second, to consider how to improve clinical trials of treatments for DED. The Symposium focused on the personal and collective burden of DED, as well as the developmental and regulatory challenges associated with generating new DED therapeutics. This article provides a synopsis of many of the presentations, discussions and recommendations of this Symposium. C1 [Sullivan, David A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Sullivan, David A.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Hammitt, Katherine M.] Sjogrens Syndrome Fdn, Bethesda, MD USA. [Schaumberg, Debra A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sullivan, Benjamin D.] TearLab Corp, San Diego, CA USA. [Begley, Carolyn G.] Indiana Univ, Sch Optometry, Bloomington, IN USA. [Gjorstrup, Per] Resolvyx Pharmaceut, Bedford, MA USA. [Garrigue, Jean-Sebastien] Novagali Pharma, Evry, France. [Nakamura, Masatsugu] Santen Pharmaceut Co, Nara, Japan. [Quentric, Yann] Iris Pharma, La Gaude, France. [Barabino, Stefano] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Clin Oculist, Genoa, Italy. [Dalton, Michelle] Dalton & Associates, Reading, PA USA. [Novack, Gary D.] Pharma Log, San Rafael, CA USA. RP Sullivan, DA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM david.sullivan@schepens.harvard.edu FU Tear Film & Ocular Surface Society FX This Symposium was supported financially by the Tear Film & Ocular Surface Society. NR 44 TC 23 Z9 23 U1 0 U2 1 PU ETHIS COMMUNICATINS, INC PI NEW YORK PA 75 MAIDEN LANE, STE 408, NEW YORK, NY 10038 USA SN 1542-0124 J9 OCUL SURF JI Ocul. Surf. PD APR PY 2012 VL 10 IS 2 BP 108 EP 116 PG 9 WC Ophthalmology SC Ophthalmology GA 937FB UT WOS:000303643300006 PM 22482471 ER PT J AU Connolly, RM Bardia, A AF Connolly, Roisin M. Bardia, Aditya TI Trastuzumab for Small HER-2+ Breast Cancer: Small Tumor, Big Decision SO ONCOLOGIST LA English DT Editorial Material ID ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; RECEPTOR; TAMOXIFEN; SURVIVAL; THERAPY AB A 53-year-old postmenopausal woman was found to have a new area of microcalcification at the 10 o'clock position of her right breast during a routine screening mammogram. Ultrasound-guided core biopsy revealed a grade 2 invasive ductal carcinoma, estrogen receptor (ER) + (90%), progesterone receptor positive (20%), and human epidermal growth factor receptor (HER)-2+ (3+ by immunohistochemistry). Aright breast lumpectomy and sentinel node biopsy were performed. The invasive tumor measured 0.7 cm, no lymphovascular space invasion was identified, surgical margins were uninvolved, and the sentinel lymph nodes were negative for tumor. She was evaluated postoperatively in the medical oncology clinic to discuss an adjuvant treatment strategy. The question for our colleagues is: should she be offered adjuvant chemotherapy and trastuzumab prior to adjuvant radiation and 5 years of hormonal therapy? C1 [Connolly, Roisin M.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Bardia, Aditya] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Cambridge, MA 02138 USA. RP Connolly, RM (reprint author), Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 24 TC 1 Z9 1 U1 1 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD APR PY 2012 VL 17 IS 4 BP 508 EP 511 DI 10.1634/theoncologist.2012-0077 PG 4 WC Oncology SC Oncology GA 940FA UT WOS:000303874200008 PM 22491004 ER PT J AU Sheth, SA Kwon, CS Barker, FG AF Sheth, Sameer A. Kwon, Churl-Su Barker, Fred G., II TI The Art of Management Decision Making: From Intuition to Evidence-based Medicine SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Vestibular schwannoma; Acoustic neuroma; Evidence-based medicine; Conservative management; Microsurgery; Radiosurgery; Radiation therapy ID FRACTIONATED STEREOTACTIC RADIOTHERAPY; QUALITY-OF-LIFE; ACOUSTIC NEUROMA RADIOSURGERY; GAMMA-KNIFE RADIOSURGERY; VESTIBULAR SCHWANNOMA SURGERY; LONG-TERM OUTCOMES; CONSERVATIVE MANAGEMENT; HEARING PRESERVATION; SINGLE-INSTITUTION; FOLLOW-UP AB This article summarizes available evidence on various management options for vestibular schwannoma as they relate to the decision-making strategies used in selection. After a brief consideration of individual options, the literature directly comparing two or more management options is examined, noting the level of evidence supporting their claims. A discussion of the strategies developed to guide decision making follows. The article closes with a summary of the evidence-based findings and suggestions for further research. The focus is on management of sporadic, unilateral vestibular schwannomas, because patients with neurofibromatosis type 2 pose different management problems best discussed separately. C1 [Barker, Fred G., II] Massachusetts Gen Hosp, Brain Tumor Ctr, Dept Neurosurg, Boston, MA 02114 USA. [Barker, Fred G., II] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Dept Neurosurg, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM barker@helix.mgh.harvard.edu NR 70 TC 6 Z9 6 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 0030-6665 EI 1557-8259 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD APR PY 2012 VL 45 IS 2 BP 333 EP + DI 10.1016/j.otc.2012.01.001 PG 20 WC Otorhinolaryngology SC Otorhinolaryngology GA 941HL UT WOS:000303954200009 PM 22483820 ER PT J AU Terry, AR Plotkin, SR AF Terry, Anna R. Plotkin, Scott R. TI Chemotherapy: Present and Future SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Vestibular schwannoma; Neurofibromatosis type 2; Growth factor inhibition; Erlotinib; Bevacizumab ID VESTIBULAR SCHWANNOMA GROWTH; NATURAL-HISTORY CONSORTIUM; NEUROFIBROMATOSIS TYPE-2; ACOUSTIC NEUROMA; TUMOR-GROWTH; CONSERVATIVE MANAGEMENT; HEARING PRESERVATION; RESPONSE CRITERIA; PHASE-II; BEVACIZUMAB AB Vestibular schwannomas (VS) are among the most common benign tumors of the central nervous system. Bilateral VS are the hallmark of neurofibromatosis type II, commonly leading to complete deafness and cranial nerve deficits as a result of tumor progression or treatment with surgery or radiation. Effective medical therapies are needed to address tumor progression and treatment-related morbidity. This article reviews the standard therapies for VS, summarizes the molecular biology of these tumors, and describes potential targets for chemotherapeutic agents. The article also defines and recommends the use of specific clinical end points in future drug trials, describes previous and current experience with anti-VEGF and anti-EGFR agents, and delineates areas of future research. C1 [Plotkin, Scott R.] Massachusetts Gen Hosp, Pappas Ctr Neuro Oncol, Dept Neurol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Terry, Anna R.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neuro Oncol, Dept Neurol, YAW 9E,55 Fruit St, Boston, MA 02114 USA. EM splotkin@partners.org FU PTC Therapeutics FX Dr Plotkin receives research support from PTC Therapeutics. Dr Terry has no conflicts of interest to disclose. NR 60 TC 2 Z9 2 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 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD APR PY 2012 VL 45 IS 2 BP 471 EP + DI 10.1016/j.otc.2011.12.013 PG 17 WC Otorhinolaryngology SC Otorhinolaryngology GA 941HL UT WOS:000303954200017 PM 22483828 ER PT J AU Peterson, VM Castro, CM Lee, H Weissleder, R AF Peterson, Vanessa M. Castro, Cesar M. Lee, Hakho Weissleder, Ralph TI Orthogonal Amplification of Nanoparticles for Improved Diagnostic Sensing SO ACS NANO LA English DT Article DE nanoparticles; targeting; orthogonal chemistry; tetrazine; NMR; diagnostics; cancer ID CIRCULATING TUMOR-CELLS; MAGNETIC NANOPARTICLES; CANCER-CELLS; RESONANCE; MARKERS AB There remains an ongoing need for fast, highly sensitive, and quantitative technologies that can detect and profile rare cells in freshly harvested samples. Recent developments in nanomaterial-based detection platforms provide advantages over traditional approaches in terms of signal sensitivity, stability, and the possibility for performing multiplexed measurements. Here, we describe a bioorthogonal, nanoparticle amplification technique capable of rapid augmentation of detection sensitivities by up to 1-2 orders of magnitude over current methods. This improvement in sensitivity was achieved by (i) significantly reducing background noise arising from nonspecific nanoparticle binding, (ii) increasing nanomaterial binding through orthogonal rounds of amplification, and (iii) implementing a cleavage step to improve assay robustness. The developed method allowed sensitive detection and molecular profiling of scant tumor cells directly in unpurified human clinical samples such as ascites. With Its high sensitivity and simplified assay steps, this technique will likely have broad utility in nanomaterial-based diagnostics. C1 [Peterson, Vanessa M.; Castro, Cesar M.; Lee, Hakho; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Peterson, Vanessa M.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU Merck; DOD [W81XWH-11-1-0706]; [U54CA151884]; [R01EB010011]; [2R01EB004626]; [HHSN268201000044C]; [2-P50-CA86355]; [K12CA087723] FX The authors thank T. Reiner and J. Klubnik for synthesizing the TCO precursor, S. Hilderbrand, M. Karver, and S. Agasti for synthesizing the tetrazine precursor, N. Sergeyev for synthesizing cross-linked dextran iron oxide nanoparticles, J. Dunham with imaging, and C. Min, B. Marinelli, and R. Gorbatov for help with NMR measurements. We especially thank J. Haun, G. Thurber, M. Liong, K. Prather, and R. Langer for many helpful discussions, and Y. Fisher-Jeffes for review of the manuscript. V.P. was supported in part by a Merck Educational Assistance Fellowship. This work was funded in part by U54CA151884, R01EB010011, 2R01EB004626, HHSN268201000044C, 2-P50-CA86355, K12CA087723, and DOD W81XWH-11-1-0706. NR 33 TC 19 Z9 20 U1 3 U2 48 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD APR PY 2012 VL 6 IS 4 BP 3506 EP 3513 DI 10.1021/nn300536y PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 929XP UT WOS:000303099300076 PM 22424443 ER PT J AU Borgen, L Kalra, MK Laerum, F Hachette, IW Fredriksson, CH Sandborg, M Smedby, O AF Borgen, Lars Kalra, Mannudeep K. Laerum, Frode Hachette, Isabelle W. Fredriksson, Carina H. Sandborg, Michael Smedby, Orjan TI Application of adaptive non-linear 2D and 3D postprocessing filters for reduced dose abdominal CT SO ACTA RADIOLOGICA LA English DT Article DE Abdomen/GI; CT; pancreas; adults; computer applications; radiation safety ID NOISE-REDUCTION FILTERS; OPTIMIZED RECONSTRUCTION ALGORITHM; MULTIDETECTOR COMPUTED-TOMOGRAPHY; IMAGE QUALITY; LIVER-LESIONS; IMPROVEMENT; ABDOMEN; PELVIS; MSCT AB Background: Abdominal computed tomography (an is a frequently performed imaging procedure, resulting in considerable radiation doses to the patient population. Postprocessing filters are one of several dose reduction measures that might help to reduce radiation doses without loss of image quality. Purpose: To assess and compare the effect of two- and three-dimensional (2D, 3D) non-linear adaptive filters on reduced dose abdominal CT images. Material and Methods: Two baseline abdominal CT image series with a volume computer tomography dose index (CTDI (vol)) of 12 mGy and 6 mGy were acquired for 12 patients. Reduced dose images were postprocessed with 2D and 3D filters. Six radiologists performed blinded randomized, side-by-side image quality assessments. Objective noise was measured. Data were analyzed using visual grading regression and mixed linear models. Results: All image quality criteria were rated as superior for 3D filtered images compared to reduced dose baseline and 2D filtered images (P < 0.01). Standard dose images had better image quality than reduced dose 3D filtered images (P < 0.01), but similar image noise. For patients with body mass index (BMI) < 30 kg/m(2) however, 3D filtered images were rated significantly better than normal dose images for two image criteria (P < 0.05), while no significant difference was found for the remaining three image criteria (P > 0.05). There were no significant variations of objective noise between standard dose and 2D or 3D filtered images. Conclusion: The quality of 3D filtered reduced dose abdominal CT images is superior compared to reduced dose unfiltered and 2D filtered images. For patients with BMI < 30 kg/m(2), 3D filtered images are comparable to standard dose images. C1 [Borgen, Lars] Drammen & Buskerud Univ Coll, Drammen Hosp, Dept Radiol, Drammen, Norway. [Kalra, Mannudeep K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp Imaging, Boston, MA USA. [Laerum, Frode] Akershus Univ Hosp, Dept Radiol, Lorenskog, Norway. [Hachette, Isabelle W.; Fredriksson, Carina H.] ContextVision AB, Linkoping, Sweden. [Sandborg, Michael] Linkoping Univ, Cty Council Ostergotland, Fac Hlth Sci, Dept Med Phys,IMH, Linkoping, Sweden. [Sandborg, Michael; Smedby, Orjan] Ctr Med Image Sci & Visualizat, Linkoping, Sweden. [Smedby, Orjan] Linkoping Univ, Dept Radiol, Linkoping, Sweden. RP Borgen, L (reprint author), Drammen & Buskerud Univ Coll, Drammen Hosp, Dept Radiol, Drammen, Norway. EM lars.borgen@vestreviken.no FU Norwegian Radiological Society; Radiological Society of North America; GE Healthcare FX LB received research funding from the Norwegian Radiological Society. PATH and CF are employees of Context Vision Inc., Linkoping, Sweden. MK has received research grants from the Radiological Society of North America and GE Healthcare. The remaining authors, OS, MS, and FL have no pertinent disclosures and had complete access to the study data and the manuscript. NR 25 TC 8 Z9 8 U1 0 U2 3 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0284-1851 J9 ACTA RADIOL JI Acta Radiol. PD APR PY 2012 VL 53 IS 3 BP 335 EP 342 DI 10.1258/ar.2011.110563 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 935XU UT WOS:000303556300017 PM 22362136 ER PT J AU Bedoya, CA Mimiaga, MJ Beauchamp, G Donnell, D Mayer, KH Safren, SA AF Bedoya, C. Andres Mimiaga, Mathew J. Beauchamp, Geetha Donnell, Deborah Mayer, Kenneth H. Safren, Steven A. TI Predictors of HIV Transmission Risk Behavior and Seroconversion Among Latino Men Who have Sex with Men in Project EXPLORE SO AIDS AND BEHAVIOR LA English DT Article DE Hispanic/Latino; MSM; HIV prevention; AIDS/HIV; High-risk sexual behavior; Substance use ID UNPROTECTED ANAL INTERCOURSE; BASE-LINE DATA; UNITED-STATES; BISEXUAL MEN; DRUG-USE; INTERVENTION; GAY; INFECTION; PREVENTION; MSM AB In the US, Latino MSM are disproportionately affected by HIV, yet there is a paucity of data for this risk group. To this end, we examined data on Latino and non-Latino white MSM who participated across six cities in a 2-year randomized behavioral intervention study-Project EXPLORE. At baseline, Latinos reported significantly more serodiscordant unprotected anal intercourse (SDUA) than non-Latinos. Longitudinal predictors of SDUA included marijuana, poppers, amphetamines and heavy drinking, as well as lower self-efficacy, poorer communication skills, weaker safe-sex norms and more enjoyment of risky sex. For HIV infection, Latinos had significantly higher seroconversion rate over follow-up than non-Latinos. Longitudinal predictors of seroconversion among Latinos included poppers and SDUA. Intervention effects did not significantly differ between Latino and non-Latinos. Findings support HIV intervention work with Latino MSM that includes skills training/counseling to address attitudes about safe sex and impact of substance use on HIV-risk behavior and acquisition. C1 [Bedoya, C. Andres] MGH Behav Med Serv, Boston, MA 02114 USA. [Bedoya, C. Andres; Mimiaga, Mathew J.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Bedoya, C. Andres; Mimiaga, Mathew J.; Mayer, Kenneth H.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Beauchamp, Geetha; Donnell, Deborah] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent SCHARP, Seattle, WA 98104 USA. [Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. RP Bedoya, CA (reprint author), MGH Behav Med Serv, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM abedoya@partners.org FU NCI NIH HHS [N01 CA035176]; NIAID NIH HHS [N01 AI045200, N01 AI45200, U01 AI046749, U01 AI047995, U01 AI048040, U01 AI47995, U01 AI48040, U01 AI48016, 5 U01 AI46749, N01 AI35176, U01 AI047981, U01 AI048016, U01 AI47981]; NIDA NIH HHS [R01 DA018603, R01DA018603]; NIMH NIH HHS [K24 MH094214] NR 37 TC 18 Z9 18 U1 0 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD APR PY 2012 VL 16 IS 3 BP 608 EP 617 DI 10.1007/s10461-011-9911-4 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 935GS UT WOS:000303507700014 PM 21390540 ER PT J AU Skeer, MR Mimiaga, MJ Mayer, KH O'Cleirigh, C Covahey, C Safren, SA AF Skeer, Margie R. Mimiaga, Matthew J. Mayer, Kenneth H. O'Cleirigh, Conall Covahey, Charles Safren, Steven A. TI Patterns of Substance Use Among a Large Urban Cohort of HIV-Infected Men Who Have Sex With Men in Primary Care SO AIDS AND BEHAVIOR LA English DT Article DE HIV/AIDS; Men who have sex with men; Alcohol; Drugs; HIV clinic ID BASE-LINE DATA; RISK BEHAVIORS; POSITIVE MEN; HEALTH; METHAMPHETAMINE; PSYCHOPATHOLOGY; EXPLORE; AIDS; INTERVENTION; ASSOCIATION AB The present study sought to identify characteristics of HIV-infected MSM that are associated with the use of specific substances and substance abuse in general. Participants were 503 HIV-infected MSM who were receiving primary care. A self-assessment and medical records were used to obtain information about past 3-month alcohol and drug use and abuse, and demographics, HIV-disease stage and treatment, sexual risk, and mental health. Associations of these four domains with substance use and abuse outcomes were examined using hierarchical block-stepwise multivariable logistic regression. Substance use and abuse in the sample was high. Transmission risk behavior was significantly associated with over half of the outcomes. The associations of demographic and HIV-disease stage and treatment variables varied by substance, and mental health problems contributed differentially to almost every outcome. These findings should be considered for designing, implementing, and evaluating substance use programming for HIV-infected MSM. C1 [Skeer, Margie R.; Mimiaga, Matthew J.; Mayer, Kenneth H.; O'Cleirigh, Conall; Covahey, Charles; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Skeer, Margie R.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Mimiaga, Matthew J.; O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Providence, RI USA. RP Skeer, MR (reprint author), Fenway Hlth, Fenway Inst, 1340 Boylston St, Boston, MA 02215 USA. EM mskeer@fenwayhealth.org FU NIMH NIH HHS [K24 MH094214, R01 MH068746, 5R01MH068746-05] NR 35 TC 23 Z9 23 U1 0 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD APR PY 2012 VL 16 IS 3 BP 676 EP 689 DI 10.1007/s10461-011-9880-7 PG 14 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 935GS UT WOS:000303507700022 PM 21234666 ER PT J AU Lorizio, W Wu, AHB Beattie, MS Rugo, H Tchu, S Kerlikowske, K Ziv, E AF Lorizio, Wendy Wu, Alan H. B. Beattie, Mary S. Rugo, Hope Tchu, Simone Kerlikowske, Karla Ziv, Elad TI Clinical and biomarker predictors of side effects from tamoxifen SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Tamoxifen; Side effects; Predictors; Biomarkers; Endoxifen; Breast cancer treatment ID QUALITY-OF-LIFE; SURGICAL ADJUVANT BREAST; MENOPAUSAL HOT FLASHES; CYP2D6 GENOTYPE; ESTROGEN-RECEPTOR; CANCER PREVENTION; JAPANESE-AMERICAN; RISK-FACTORS; WOMEN; SYMPTOMS AB Tamoxifen decreases breast cancer recurrence, mortality, and breast cancer risk in high-risk women. Despite these proven benefits, tamoxifen use is often limited due to side effects. We identified predictors of tamoxifen-induced side effects based on clinical variables and serum tamoxifen metabolite biomarkers in a cross-sectional study of patients taking tamoxifen. We enrolled 241 women and collected data on demographics, tamoxifen use and side effects, as well as potential clinical and serum predictors. We used logistic regression models and adjusted for age, body mass index, ethnicity, education, prior post-menopausal hormone therapy (HT), tamoxifen duration, and endoxifen levels to identify factors associated with side effects. Common tamoxifen attributed side effects were hot flashes (64%), vaginal dryness (35%), sleep problems (36%), weight gain (6%), and depression, irritability or mood swings (6%). In multi-variate models, tamoxifen duration, age, prior post-menopausal HT, and endoxifen levels all predicted side effects. Women who had been on tamoxifen for > 12 months were less likely to report side effects (OR 0.15, 95% CI 0.04-0.58) or severe side effects (OR 0.05, 95% CI 0.005-0.58) compared to women on tamoxifen for < 12 months. Compared to women younger than 50, women who were age 60-70 and older than 70 were less likely to report side effects (OR 0.22, 95% CI 0.03-1.35; OR 0.13, 95% CI 0.01-0.99; respectively). Women who previously took post-menopausal HT were more likely to report severe side effects. Women with higher endoxifen levels were more likely to report side effects (OR 1.67, 95% CI 1.01-2.77 per standard deviation increase in endoxifen). Clinicians should consider closely monitoring adherence in women taking tamoxifen, especially in younger women, and women who previously took HT. The association between endoxifen levels and side effects is consistent with the data that suggest that endoxifen is the most highly active metabolite of tamoxifen. C1 [Lorizio, Wendy; Ziv, Elad] UCSF Helen Diller Family Canc Res Bldg, San Francisco, CA 94158 USA. [Lorizio, Wendy; Beattie, Mary S.; Ziv, Elad] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA. [Lorizio, Wendy] Univ Calif San Francisco, Dept Med, Div Clin Pharmacol & Expt Therapeut, San Francisco, CA USA. [Lorizio, Wendy; Beattie, Mary S.; Rugo, Hope; Ziv, Elad] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Wu, Alan H. B.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Wu, Alan H. B.; Tchu, Simone] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Beattie, Mary S.; Ziv, Elad] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Beattie, Mary S.; Ziv, Elad] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Beattie, Mary S.; Rugo, Hope] UCSF Med Ctr Mt Zion, San Francisco, CA 94143 USA. [Rugo, Hope] Univ Calif San Francisco, Dept Med, Div Hematol & Oncol, San Francisco, CA USA. [Tchu, Simone] Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. [Kerlikowske, Karla] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA 94121 USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Med & Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Lorizio, W (reprint author), UCSF Helen Diller Family Canc Res Bldg, 1450 3rd St,Room 289,Box 3116, San Francisco, CA 94158 USA. EM wlorizio@hotmail.com RI Ziv, Elad/L-5396-2014 FU National Institute of General Medical Sciences (NIGMS); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [T32 GM007546]; University of California San Francisco; California Breast Cancer Research Program (CBCRP) [14OB-0166]; National Cancer Institute (NCI) [P50 CA58207]; Center for Translational and Policy Research in Personalized Medicine (TRANSPERS) National Institutes of Health/National Cancer Institute (NIH/NCI) [P01 CA130818-02A1] FX This work was supported by the National Institute of General Medical Sciences (NIGMS) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Award T32 GM007546, University of California San Francisco, Clinical Pharmacology Fellowship Training Program (W. Lorizio); California Breast Cancer Research Program (CBCRP) Grant 14OB-0166 (E. Ziv); National Cancer Institute (NCI) Grant P50 CA58207 funded UCSF Breast SPORE; the Center for Translational and Policy Research in Personalized Medicine (TRANSPERS) National Institutes of Health/National Cancer Institute (NIH/NCI) Grant P01 CA130818-02A1 (M. S. Beattie), and materials and instrumentation for the AmpliChip CYP450 Test were donated by Roche Molecular Systems, Inc. We thank Viktoriya Krepkiy (Ziv Lab) for helping with participants and administrative support. NR 55 TC 31 Z9 31 U1 1 U2 5 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 APR PY 2012 VL 132 IS 3 SI SI BP 1107 EP 1118 DI 10.1007/s10549-011-1893-4 PG 12 WC Oncology SC Oncology GA 933RL UT WOS:000303379800033 PM 22207277 ER PT J AU Fu, H Kesari, S Cai, J AF Fu, Hui Kesari, Santosh Cai, Jun TI Tcf7l2 is Tightly Controlled During Myelin Formation SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE Tcf7l2; Myelin formation; Demyelinating diseases; Wnt; Beta-catenin; Olig2 ID OLIGODENDROCYTE DIFFERENTIATION; TRANSCRIPTION FACTOR; MULTIPLE-SCLEROSIS; CNS MYELINATION; SPINAL-CORD; CATENIN; OLIG2; REMYELINATION; NKX2.2; BRAIN AB Recent, studies have shown that Tcf7l2, an important transcription factor in Wnt pathway, plays critical roles in oligodendrocyte development. In this article we report a study showing that Tcf7l2 is under tight regulation during myelin formation. We have found that during early development, Tcf7l2 mRNA appears much earlier than the protein, suggesting a regulation at the translational level. We induced demyelination in a mouse model by a dietary toxin, where remyelination followed after a few weeks, and found that Tcf7l2 protein was expressed specifically during the active remyelination phase. Similarly, in human patients with demyelination diseases, Tcf7l2 protein expression was specifically promoted in regions undergoing active remyelination. During remyelination, Tcf7l2 was only expressed in non-dividing oligodendrocyte precursors and was associated with modest levels of nuclear beta-catenin. We also documented that Tcf7l2 could form protein complex with Olig2, but not with Olig1. Our data showed that during myelin formation, Tcf7l2/beta-catenin is regulated temporally, spatially, and also at levels of expression. These data suggest a key role for Tcf7l2 in myelination/remyelination processes via a tightly controlled activation of Wnt/beta-catenin pathway and the interaction with Olig2. C1 [Fu, Hui] Nanchang Univ, Basic Med Coll, Dept Physiol, Nanchang 330006, Jiangxi, Peoples R China. [Fu, Hui] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Kesari, Santosh] UC San Diego, Moores Canc Ctr, Dept Neurosci, Div Neurooncol, La Jolla, CA 92093 USA. [Cai, Jun] Univ Louisville, Sch Med, Kosair Childrens Hosp Res Inst, Dept Pediat, Louisville, KY 40202 USA. RP Fu, H (reprint author), Nanchang Univ, Basic Med Coll, Dept Physiol, Nanchang 330006, Jiangxi, Peoples R China. EM hueyfu@yahoo.com; skesari@ucsd.edu; j0cai002@louisville.edu RI Fu, Hui/C-2881-2011; Kesari, Santosh/E-8461-2013 OI Fu, Hui/0000-0003-0252-6009; FU National Natural Science Foundation of China [30860131]; NIH [R01NS059893, 2P20RR017702-061A1] FX This research was supported by National Natural Science Foundation of China Grant NO 30860131 and NIH grant R01NS059893, NIH 2P20RR017702-061A1. NR 29 TC 14 Z9 15 U1 0 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD APR PY 2012 VL 32 IS 3 BP 345 EP 352 DI 10.1007/s10571-011-9778-y PG 8 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 934AE UT WOS:000303409700003 PM 22160878 ER PT J AU Leung, DT Chowdhury, F Calderwood, SB Qadri, F Ryan, ET AF Leung, Daniel T. Chowdhury, Fahima Calderwood, Stephen B. Qadri, Firdausi Ryan, Edward T. TI Immune responses to cholera in children SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Review DE children; cholera; memory B cells; mucosal immunity; oral cholera vaccines ID ENTEROTOXIGENIC ESCHERICHIA-COLI; VACCINE FIELD-TRIAL; SUBUNIT-WHOLE CELL; MEMORY B-CELL; VIBRIOCIDAL ANTIBODY-RESPONSE; INFECTION-DERIVED IMMUNITY; RURAL EAST PAKISTAN; ENDEMIC CHOLERA; CVD 103-HGR; INFLAMMATORY MEDIATORS AB Cholera is a severe acute dehydrating diarrheal disease caused by Vibrio cholerae O1 or O139 infection, and is associated with significant mortality and morbidity globally. Although young children bear a high burden of the disease, currently available oral vaccines give a lower efficacy and shorter duration of protection in this group than in adults. According to the studies of natural infection, young children achieve comparable systemic anti-V cholerae antigen-specific antibody, gut-homing antibody-secreting cell and memory B-cell responses as adults. Studies on innate and cell-mediated immune responses are lacking in children, and may offer important insights into differences in vaccine efficacy. The impact of host factors such as malnutrition, genetics and coinfection with other pathogens also remains to be fully defined. C1 [Leung, Daniel T.; Chowdhury, Fahima; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, Dhaka 1000, Bangladesh. [Leung, Daniel T.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Leung, Daniel T.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Leung, DT (reprint author), Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, GPO Box 128, Dhaka 1000, Bangladesh. EM dleung@partners.org OI leung, daniel/0000-0001-8401-0801 FU International Centre for Diarrhoeal Disease Research, NIH, including the National Institute of Allergy & Infectious Diseases [AI058935, U01 AI077883]; Fogarty International Center, a Harvard Initiative for Global Health [TW005572]; American Society for Tropical Medicine & Hygiene/Burroughs Wellcome Fund FX This work was supported by grants from the International Centre for Diarrhoeal Disease Research, NIH, including the National Institute of Allergy & Infectious Diseases (AI058935 to SB Calderwood and ET Ryan, U01 AI077883 to ET Ryan); an American Recovery and Reinvestment Act Post-doctoral Fellowship in Global Infectious Diseases (TW005572 to DT Leung) from the Fogarty International Center, a Harvard Initiative for Global Health Post-doctoral Fellowship in Global Infectious Diseases (DT Leung), and a Post-doctoral Fellowship in Tropical Infectious Diseases from the American Society for Tropical Medicine & Hygiene/Burroughs Wellcome Fund (DT Leung). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 105 TC 16 Z9 16 U1 5 U2 13 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD APR PY 2012 VL 10 IS 4 BP 435 EP 444 DI 10.1586/ERI.12.23 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 937AF UT WOS:000303630700011 PM 22512753 ER PT J AU Lamb, AN Rosenfeld, JA Neill, NJ Talkowski, ME Blumenthal, I Girirajan, S Keelean-Fuller, D Fan, Z Pouncey, J Stevens, C Mackay-Loder, L Terespolsky, D Bader, PI Rosenbaum, K Vallee, SE Moeschler, JB Ladda, R Sell, S Martin, J Ryan, S Jones, MC Moran, R Shealy, A Madan-Khetarpal, S McConnell, J Surti, U Delahaye, A Heron-Longe, B Pipiras, E Benzacken, B Passemard, S Verloes, A Isidor, B Le Caignec, C Glew, GM Opheim, KE Descartes, M Eichler, EE Morton, CC Gusella, JF Schultz, RA Ballif, BC Shaffer, LG AF Lamb, Allen N. Rosenfeld, Jill A. Neill, Nicholas J. Talkowski, Michael E. Blumenthal, Ian Girirajan, Santhosh Keelean-Fuller, Debra Fan, Zheng Pouncey, Jill Stevens, Cathy Mackay-Loder, Loren Terespolsky, Deborah Bader, Patricia I. Rosenbaum, Kenneth Vallee, Stephanie E. Moeschler, John B. Ladda, Roger Sell, Susan Martin, Judith Ryan, Shawnia Jones, Marilyn C. Moran, Rocio Shealy, Amy Madan-Khetarpal, Suneeta McConnell, Juliann Surti, Urvashi Delahaye, Andree Heron-Longe, Benedicte Pipiras, Eva Benzacken, Brigitte Passemard, Sandrine Verloes, Alain Isidor, Bertrand Le Caignec, Cedric Glew, Gwen M. Opheim, Kent E. Descartes, Maria Eichler, Evan E. Morton, Cynthia C. Gusella, James F. Schultz, Roger A. Ballif, Blake C. Shaffer, Lisa G. TI Haploinsufficiency of SOX5 at 12p12.1 is associated with developmental delays with prominent language delay, behavior problems, and mild dysmorphic features SO HUMAN MUTATION LA English DT Article DE SOX5; developmental delay; intragenic deletion; behavior problems; microarray ID LACTICO-DEHYDROGENASE-B; SHORT ARM; MICRODELETION SYNDROME; INTERSTITIAL DELETION; CHROMOSOME 12P; HUMAN-DISEASE; ACTIVE GENES; HUMAN GENOME; HISTONE H3; LONG FORM AB SOX5 encodes a transcription factor involved in the regulation of chondrogenesis and the development of the nervous system. Despite its important developmental roles, SOX5 disruption has yet to be associated with human disease. We report one individual with a reciprocal translocation breakpoint within SOX5, eight individuals with intragenic SOX5 deletions (four are apparently de novo and one inherited from an affected parent), and seven individuals with larger 12p12 deletions encompassing SOX5. Common features in these subjects include prominent speech delay, intellectual disability, behavior abnormalities, and dysmorphic features. The phenotypic impact of the deletions may depend on the location of the deletion and, consequently, which of the three major SOX5 protein isoforms are affected. One intragenic deletion, involving only untranslated exons, was present in a more mildly affected subject, was inherited from a healthy parent and grandparent, and is similar to a deletion found in a control cohort. Therefore, some intragenic SOX5 deletions may have minimal phenotypic effect. Based on the location of the deletions in the subjects compared to the controls, the de novo nature of most of these deletions, and the phenotypic similarities among cases, SOX5 appears to be a dosage-sensitive, developmentally important gene. Hum Mutat 33:728740, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Lamb, Allen N.; Rosenfeld, Jill A.; Neill, Nicholas J.; Schultz, Roger A.; Ballif, Blake C.; Shaffer, Lisa G.] PerkinElmer Inc, Signature Genom Labs, Spokane, WA 99207 USA. [Talkowski, Michael E.; Blumenthal, Ian; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Talkowski, Michael E.; Gusella, James F.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Talkowski, Michael E.; Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Talkowski, Michael E.; Morton, Cynthia C.; Gusella, James F.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Girirajan, Santhosh] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Keelean-Fuller, Debra; Fan, Zheng] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. [Keelean-Fuller, Debra; Fan, Zheng] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. [Pouncey, Jill; Stevens, Cathy] Univ Tennessee, Coll Med, Dept Pediat, Chattanooga, TN USA. [Mackay-Loder, Loren; Terespolsky, Deborah] Credit Valley Hosp, Div Genet, Dept Lab Med, Mississauga, ON, Canada. [Bader, Patricia I.] Parkview Hosp, Cytogenet Lab, Ft Wayne, IN USA. [Rosenbaum, Kenneth] Childrens Natl Med Ctr, Dept Genet & Metab, Washington, DC 20010 USA. [Vallee, Stephanie E.; Moeschler, John B.] Dartmouth Hitchcock Med Ctr, Dept Pediat, Lebanon, NH 03766 USA. [Ladda, Roger; Sell, Susan] Penn State Hershey Childrens Hosp, Penn State Milton S Hershey Med Ctr, Dept Pediat, Hershey, PA USA. [Martin, Judith; Ryan, Shawnia] Providence Sacred Heart Hosp, Dept Pediat, Providence Genet Clin, Spokane, WA USA. [Jones, Marilyn C.] Univ Calif San Diego, Dept Pediat, Rady Childrens Hosp, San Diego, CA 92103 USA. [Moran, Rocio; Shealy, Amy] Cleveland Clin, Genom Med Inst, Cleveland, OH 44106 USA. [Madan-Khetarpal, Suneeta; McConnell, Juliann] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Div Med Genet, Pittsburgh, PA 15213 USA. [Surti, Urvashi] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Delahaye, Andree; Pipiras, Eva; Benzacken, Brigitte] Hop Jean Verdier, AP HP, Serv Histol Embryol & Cytogenet, Bondy, France. [Delahaye, Andree; Pipiras, Eva; Benzacken, Brigitte] Univ Paris 13, UFR SMBH, Bobigny, France. [Delahaye, Andree; Pipiras, Eva; Benzacken, Brigitte; Passemard, Sandrine; Verloes, Alain] INSERM, U676, Paris, France. [Heron-Longe, Benedicte] Hop Jean Verdier, AP HP, Serv Pediat, Consultat Neuropediat, Bondy, France. [Benzacken, Brigitte; Passemard, Sandrine; Verloes, Alain] Hop Robert Debre, AP HP, Dept Genet, F-75019 Paris, France. [Passemard, Sandrine; Verloes, Alain] Univ Paris Diderot, Univ Paris 07, Paris, France. [Passemard, Sandrine] Hop Robert Debre, AP HP, Serv Neurol Pediat, F-75019 Paris, France. [Isidor, Bertrand; Le Caignec, Cedric] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France. [Glew, Gwen M.] Univ Washington, Sch Med, Dept Pediat, Seattle Childrens Hosp,Div Dev Med, Seattle, WA 98195 USA. [Opheim, Kent E.] Seattle Childrens Hosp, Dept Labs, Seattle, WA USA. [Descartes, Maria] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Morton, Cynthia C.] Harvard Univ, Sch Med, Boston, MA USA. RP Shaffer, LG (reprint author), PerkinElmer Inc, Signature Genom Labs, 2820 N Astor St, Spokane, WA 99207 USA. EM lisa.shaffer@perkinelmer.com RI Le Caignec, Cedric/K-8467-2015; Isidor, Bertrand/L-2435-2015; OI Le Caignec, Cedric/0000-0002-0598-653X; Isidor, Bertrand/0000-0001-6480-126X; , Alain/0000-0003-4819-0264 FU NIH [GM061354, HD065286, F32MH087123] FX Contract grant sponsors: NIH; GM061354 (DGAP; C. C. M); HD065286 (J.F.G.); F32MH087123 (M.E.T.). NR 57 TC 24 Z9 26 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD APR PY 2012 VL 33 IS 4 BP 728 EP 740 DI 10.1002/humu.22037 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 906IP UT WOS:000301338900021 PM 22290657 ER PT J AU Menon, LG Pratt, J Yang, HW Black, PM Sorensen, GA Carroll, RS AF Menon, Lata G. Pratt, John Yang, Hong Wei Black, Peter M. Sorensen, Gregory A. Carroll, Rona S. TI Imaging of human mesenchymal stromal cells: homing to human brain tumors SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Glioblastoma; Human bone marrow mesenchymal stromal cells; Gene therapy; Ferumoxide; Magnetic resonance imaging ID NEURAL STEM-CELLS; IRON-OXIDE NANOPARTICLES; IN-VIVO TRACKING; GLIOMA MODEL; ADJUVANT TEMOZOLOMIDE; TRANSFECTION AGENTS; MALIGNANT GLIOMAS; GENE-EXPRESSION; THERAPY; MRI AB Human mesenchymal stromal cells (hMSC) can be used as a drug delivery vehicle for the treatment of GBM. However, tracking the migration and distribution of these transplanted cells is necessary to interpret therapeutic efficacy. We compared three labeling techniques for their ability to track the migration of transplanted hMSC in an orthotopic mouse xenograft model. hMSC were labeled with three different imaging tags (fluorescence, luciferase or ferumoxide) for imaging by fluorescence, bioluminescence or magnetic resonance imaging (MRI), respectively. hMSC were labeled for all imaging modalities without the use of transfection agents. The labeling efficacy of the tags was confirmed, followed by in vitro and in vivo migration assays to track hMSC migration towards U87 glioma cells. Our results confirmed that the labeled hMSC retained their migratory ability in vitro, similar to unlabeled hMSC. In addition, labeled hMSC migrated towards the U87 tumor site, demonstrating their retention of tumor tropism. hMSC tumor tropism was confirmed by all three imaging modalities; however, MRI provides both real time assessment and the high resolution needed for clinical studies. Our findings suggest that ferumoxide labeling of hMSC is feasible, does not alter their migratory ability and allows detection by MRI. Non invasive tracking of transplanted therapeutic hMSC in the brain will allow further development of human cell based therapies. C1 [Menon, Lata G.; Yang, Hong Wei; Black, Peter M.; Carroll, Rona S.] Harvard Univ, Sch Med, Dept Neurosurg, Brigham & Womens Hosp, Boston, MA 02115 USA. [Pratt, John; Sorensen, Gregory A.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Pratt, John; Sorensen, Gregory A.] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. RP Carroll, RS (reprint author), Harvard Univ, Sch Med, Dept Neurosurg, Brigham & Womens Hosp, 221 Longwood Ave,Rm 121, Boston, MA 02115 USA. EM rcarroll@rics.bwh.harvard.edu FU Brain Science Foundation (BSF); Harvard Catalyst Grant; US Public Health Service [T32 CA009502] FX We are grateful to Dr. Mark Johnson in the Department of Neurosurgery, Brigham and Women's Hospital, (BWH) for reviewing the manuscript and expert technical advice. We thank Veronica Shi and Enzo Martinelli for the help with staining and cryosectioning. We would like to thank Dr. Myriam Armant, Center for Human Cell Therapy (at the Immune Disease Institute) for help with flow cytometry analysis of hMSC. We are thankful to Dr. Christian Farrar (A. A. Martinos Center for Biomedical Imaging) for helping us with MRI studies. We also would like to thank Dr Xiaoyin Xu, BICOR-Functional and Molecular Imaging Center at BWH, for his help with luciferase imaging experiments. This study was supported by grants from by Brain Science Foundation (BSF) to L. G. M.; Harvard Catalyst Grant to P. M. B., R. S. C., A. G. S and L. G. M., and by the US Public Health Service (T32 CA009502) to A.G.S. NR 48 TC 13 Z9 14 U1 0 U2 23 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD APR PY 2012 VL 107 IS 2 BP 257 EP 267 DI 10.1007/s11060-011-0754-7 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 934TG UT WOS:000303469000005 PM 22081298 ER PT J AU Goldlust, SA Cavaliere, R Newton, HB Hsu, M DeAngelis, LM Batchelor, TT Gilbert, MR Lassman, AB AF Goldlust, Samuel A. Cavaliere, Robert Newton, Herbert B. Hsu, Meier DeAngelis, Lisa M. Batchelor, Tracy T. Gilbert, Mark R. Lassman, Andrew B. TI Bevacizumab for glioblastoma refractory to vascular endothelial growth factor receptor inhibitors SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Glioma; Glioblastoma; Bevacizumab; Tyrosine kinase inhibitor; Vascular endothelial growth factor ID RECURRENT GLIOBLASTOMA; PHASE-III; TRIAL; PROGRESSION; CEDIRANIB; THERAPY AB Glioblastoma (GBM) is a highly vascular tumor dependent on angiogenesis through the vascular endothelial growth factor (VEGF) signaling cascade. Inhibition of VEGF signaling is an important therapeutic strategy. We report our experience with bevacizumab (BEV), a VEGF targeting antibody, following failure of a VEGF receptor targeting tyrosine kinase inhibitor (TKI). We retrospectively identified patients treated on clinical trials with VEGFR-TKIs for recurrent GBM followed by BEV at next recurrence. Survival was estimated by the Kaplan-Meier method. Fourteen patients were identified (six women; median age 57). All received VEGFR-TKIs (sunitinib 11, cediranib 2, sorafenib 1) then BEV at next recurrence. There were no radiographic responses to VEGFR-TKIs; best response was stable disease in 50% (7/14). Patients received BEV alone (21%, 3/14) or in combination with chemotherapy (79%, 11/14). On BEV, 29% (4/14) had a partial response, and 36% (5/14) stabilized. Of evaluable patients, 42% (5/12) had neurological improvement and 56% (5/9) reduced corticosteroid requirement. Median survival on BEV was 7.8 months (95% CI 4.0-15.8), median progression-free survival (PFS) was 4.0 months (95% CI 1.6-10.5), and the 6-month PFS rate was 29% (95% CI 9-52). Our radiographic and survival outcomes with BEV following progression after VEGFR-TKIs are similar to data from studies of BEV as initial salvage therapy, although our sample size was small. Prior exposure to VEGFR-TKIs may not preclude response to BEV, but sensitivity to BEV may be lower following more robust VEGFR inhibition. C1 [Goldlust, Samuel A.; DeAngelis, Lisa M.; Lassman, Andrew B.] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10021 USA. [Cavaliere, Robert; Newton, Herbert B.] Ohio State Univ, Med Ctr, Dardinger Neurooncol Ctr, Columbus, OH 43210 USA. [Cavaliere, Robert; Newton, Herbert B.] James Canc Hosp, Columbus, OH USA. [Hsu, Meier] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Goldlust, Samuel A.; DeAngelis, Lisa M.; Lassman, Andrew B.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. RP Lassman, AB (reprint author), Columbia Univ, Dept Neurol, Div Neurooncol, Med Ctr, New York, NY 10027 USA. EM abl7@columbia.edu RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 FU Schering-Plough; Genentech/Roche; Millennium; AstraZeneca; Pfizer; Medscape; Genentech; Merck; Keryx; Merck Co. FX This study was not funded by a grant or other external source. SAG, RC, and MH report no disclosures. HBN received honoraria as a speaker and/or advisor from Schering-Plough, UCB Pharma, Genentech, Eisai, and research support from Schering-Plough. LMD received research support from and consulted for Genentech/Roche. TTB consulted for Genentech/Roche and Amgen and receives research funding from Millennium, AstraZeneca, and Pfizer; received honoraria from Merck, Educational Concepts, and Medscape; and receives royalties from UpToDate, Inc. MRG served on advisory boards for Genentech and Merck; received travel funding from Medscape; is an Editor for Current Oncology Reports; receives Royalties from Oxford University Press, received honoraria from Merck, Genentech, National Brain Tumor Society, Medscape, and IMER; and receives research support from Genentech and Merck. ABL consulted for and received honoraria from Schering Corp. and Merck & Co,; consulted for Bristol-Myers Squibb, Campus Bio, Cephalon, Eisai, Genentech/Roche, GlaxoSmithKline, Imclone, and Sigma Tau; and formerly served on a Speaker's Bureau for Merck & Co. (formerly Schering Corp.); and received research support from Genentech/Roche, Keryx, and Merck & Co. (formerly Schering Corp.). NR 12 TC 9 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD APR PY 2012 VL 107 IS 2 BP 407 EP 411 DI 10.1007/s11060-011-0768-1 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 934TG UT WOS:000303469000022 PM 22203237 ER PT J AU Mercier, F Guiot, MC Bojanowski, MW AF Mercier, Francois Guiot, Marie-Christine Bojanowski, Michel W. TI Treatment of chordoma with imatinib complicated by intracranial hemorrhage: a case showing dissociation between biological effect and therapeutic outcome SO JOURNAL OF NEURO-ONCOLOGY LA English DT Letter ID MESYLATE C1 [Mercier, Francois] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Guiot, Marie-Christine] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Bojanowski, Michel W.] Ctr Hosp Univ Montreal, Montreal, PQ, Canada. RP Mercier, F (reprint author), Massachusetts Gen Hosp, 185 Cambridge St, Boston, MA 02114 USA. EM francois.mercier@mail.mcgill.ca NR 3 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD APR PY 2012 VL 107 IS 2 BP 435 EP 437 DI 10.1007/s11060-011-0767-2 PG 3 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 934TG UT WOS:000303469000026 PM 22120582 ER PT J AU Gaudet, S Spencer, SL Chen, WW Sorger, PK AF Gaudet, Suzanne Spencer, Sabrina L. Chen, William W. Sorger, Peter K. TI Exploring the Contextual Sensitivity of Factors that Determine Cell-to-Cell Variability in Receptor-Mediated Apoptosis SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID TRAIL-INDUCED APOPTOSIS; SINGLE-CELL; GENE-EXPRESSION; CASPASE ACTIVATION; PROTEIN-LEVELS; TRANSCRIPTOME; SYSTEMS; MODELS; BCL-2; DEATH AB Stochastic fluctuations in gene expression give rise to cell-to-cell variability in protein levels which can potentially cause variability in cellular phenotype. For TRAIL (TNF-related apoptosis-inducing ligand) variability manifests itself as dramatic differences in the time between ligand exposure and the sudden activation of the effector caspases that kill cells. However, the contribution of individual proteins to phenotypic variability has not been explored in detail. In this paper we use feature-based sensitivity analysis as a means to estimate the impact of variation in key apoptosis regulators on variability in the dynamics of cell death. We use Monte Carlo sampling from measured protein concentration distributions in combination with a previously validated ordinary differential equation model of apoptosis to simulate the dynamics of receptor-mediated apoptosis. We find that variation in the concentrations of some proteins matters much more than variation in others and that precisely which proteins matter depends both on the concentrations of other proteins and on whether correlations in protein levels are taken into account. A prediction from simulation that we confirm experimentally is that variability in fate is sensitive to even small increases in the levels of Bcl-2. We also show that sensitivity to Bcl-2 levels is itself sensitive to the levels of interacting proteins. The contextual dependency is implicit in the mathematical formulation of sensitivity, but our data show that it is also important for biologically relevant parameter values. Our work provides a conceptual and practical means to study and understand the impact of cell-to-cell variability in protein expression levels on cell fate using deterministic models and sampling from parameter distributions. C1 [Gaudet, Suzanne] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Gaudet, Suzanne] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Gaudet, Suzanne] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Spencer, Sabrina L.; Chen, William W.; Sorger, Peter K.] Harvard Univ, Sch Med, Dept Syst Biol, Ctr Cell Decis Proc, Boston, MA USA. RP Gaudet, S (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM suzanne_gaudet@dfci.harvard.edu; peter_sorger@hms.harvard.edu OI SPENCER, SABRINA/0000-0002-5798-3007 FU NIH [CA139980, GM68762] FX This work was supported by NIH grants CA139980 to PKS and SG and GM68762 to PKS (http://www.nih.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 33 Z9 33 U1 1 U2 8 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 APR PY 2012 VL 8 IS 4 AR e1002482 DI 10.1371/journal.pcbi.1002482 PG 15 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 934JM UT WOS:000303440400034 PM 22570596 ER PT J AU Radford, EJ Isganaitis, E Jimenez-Chillaron, J Schroeder, J Molla, M Andrews, S Didier, N Charalambous, M McEwen, K Marazzi, G Sassoon, D Patti, ME Ferguson-Smith, AC AF Radford, Elizabeth J. Isganaitis, Elvira Jimenez-Chillaron, Josep Schroeder, Joshua Molla, Michael Andrews, Simon Didier, Nathalie Charalambous, Marika McEwen, Kirsten Marazzi, Giovanna Sassoon, David Patti, Mary-Elizabeth Ferguson-Smith, Anne C. TI An Unbiased Assessment of the Role of Imprinted Genes in an Intergenerational Model of Developmental Programming SO PLOS GENETICS LA English DT Article ID LOW-BIRTH-WEIGHT; TRANSGENERATIONAL INHERITANCE; METHYLATION IMPRINTS; MATERNAL-BEHAVIOR; OOCYTE GROWTH; FETAL-GROWTH; MOUSE; EXPRESSION; MICE; LIFE AB Environmental factors during early life are critical for the later metabolic health of the individual and of future progeny. In our obesogenic environment, it is of great socioeconomic importance to investigate the mechanisms that contribute to the risk of metabolic ill health. Imprinted genes, a class of functionally mono-allelic genes critical for early growth and metabolic axis development, have been proposed to be uniquely susceptible to environmental change. Furthermore, it has also been suggested that perturbation of the epigenetic reprogramming of imprinting control regions (ICRs) may play a role in phenotypic heritability following early life insults. Alternatively, the presence of multiple layers of epigenetic regulation may in fact protect imprinted genes from such perturbation. Unbiased investigation of these alternative hypotheses requires assessment of imprinted gene expression in the context of the response of the whole transcriptome to environmental assault. We therefore analyse the role of imprinted genes in multiple tissues in two affected generations of an established murine model of the developmental origins of health and disease using microarrays and quantitative RT-PCR. We demonstrate that, despite the functional mono-allelicism of imprinted genes and their unique mechanisms of epigenetic dosage control, imprinted genes as a class are neither more susceptible nor protected from expression perturbation induced by maternal undernutrition in either the F1 or the F2 generation compared to other genes. Nor do we find any evidence that the epigenetic reprogramming of ICRs in the germline is susceptible to nutritional restriction. However, we propose that those imprinted genes that are affected may play important roles in the foetal response to undernutrition and potentially its long-term sequelae. We suggest that recently described instances of dosage regulation by relaxation of imprinting are rare and likely to be highly regulated. C1 [Radford, Elizabeth J.; Charalambous, Marika; McEwen, Kirsten; Ferguson-Smith, Anne C.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge, England. [Isganaitis, Elvira; Jimenez-Chillaron, Josep; Schroeder, Joshua; Molla, Michael; Patti, Mary-Elizabeth] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Isganaitis, Elvira; Jimenez-Chillaron, Josep; Schroeder, Joshua; Molla, Michael; Patti, Mary-Elizabeth] Harvard Univ, Sch Med, Boston, MA USA. [Andrews, Simon] Babraham Inst, Bioinformat Grp, Cambridge, England. [Didier, Nathalie; Marazzi, Giovanna; Sassoon, David] INSERM, Myol Grp, UMR S 787, Paris, France. [Didier, Nathalie; Marazzi, Giovanna; Sassoon, David] Univ Paris 06, Paris, France. RP Radford, EJ (reprint author), Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge, England. EM mary.elizabeth.patti@joslin.harvard.edu; afsmith@mole.bio.cam.ac.uk OI Charalambous, Marika/0000-0002-1684-5783 FU Medical Research Council FX This work was supported by the Medical Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 70 TC 52 Z9 52 U1 1 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2012 VL 8 IS 4 BP 41 EP 53 AR e1002605 DI 10.1371/journal.pgen.1002605 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 934KA UT WOS:000303441800003 PM 22511876 ER PT J AU Montgomery, TA Rim, YS Zhang, C Dowen, RH Phillips, CM Fischer, SEJ Ruvkun, G AF Montgomery, Taiowa A. Rim, Young-Soo Zhang, Chi Dowen, Robert H. Phillips, Carolyn M. Fischer, Sylvia E. J. Ruvkun, Gary TI PIWI Associated siRNAs and piRNAs Specifically Require the Caenorhabditis elegans HEN1 Ortholog henn-1 SO PLOS GENETICS LA English DT Article ID ARGONAUTE2 PAZ DOMAIN; C-ELEGANS; RNA INTERFERENCE; INTERACTING RNAS; CHROMOSOME SEGREGATION; 3'-END RECOGNITION; ENDOGENOUS SIRNAS; STRUCTURAL BASIS; 3' TERMINI; GENE AB Small RNAs-including piRNAs, miRNAs., and endogenous siRNAs-bind Argonaute proteins to form RNA silencing complexes that target coding genes, transposons, and aberrant RNAs. To assess the requirements for endogenous siRNA formation and activity in Caenorhabditis elegans, we developed a GFP-based sensor for the endogenous siRNA 22G siR-1 one of a set of abundant siRNAs processed from a precursor RNA mapping to the X chromosome, the X-cluster. Silencing of the sensor is also dependent on the partially complementary, unlinked 26G siR-O7 siRNA. We show that 26G siR-O7 acts in trans to initiate 22G siRNA formation from the X-cluster. The presence of several mispairs between 26G siR-O7 and the X-cluster mRNA, as well as mutagenesis of the siRNA sensor, indicates that siRNA target recognition is permissive to a degree of mispairing. From a candidate reverse genetic screen, we identified several factors required for 22G siR-1 activity, including the chromatin factors mes-4 and gfl-1, the Argonaute ergo-1, and the 3' methyltransferase henn-1. Quantitative RT-PCR of small RNAs in a henn-1 mutant and deep sequencing of methylated small RNAs indicate that siRNAs and piRNAs that associate with PIWI clade Argonautes are methylated by HENN-1, while siRNAs and miRNAs that associate with non-PIWI clade Argonautes are not. Thus, PIWI-class Argonaute proteins are specifically adapted to associate with methylated small RNAs in C. elegans. C1 [Montgomery, Taiowa A.; Rim, Young-Soo; Zhang, Chi; Dowen, Robert H.; Phillips, Carolyn M.; Fischer, Sylvia E. J.; Ruvkun, Gary] Harvard Univ, Dept Mol Biol, Massachusetts Gen Hosp, Dept Genet,Med Sch, Boston, MA 02115 USA. RP Montgomery, TA (reprint author), Harvard Univ, Dept Mol Biol, Massachusetts Gen Hosp, Dept Genet,Med Sch, Boston, MA 02115 USA. EM ruvkun@molbio.mgh.harvard.edu RI Phillips, Carolyn/E-8305-2011; OI Phillips, Carolyn/0000-0002-6228-6468; Montgomery, Taiowa/0000-0001-7857-3253 FU National Institute of Health [GM44619]; Damon Runyon Cancer Research Foundation [DRG-2029-09, DRG1988-08] FX This work is supported by National Institute of Health (GM44619) and Damon Runyon Cancer Research Foundation (DRG-2029-09 and DRG1988-08). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 41 Z9 46 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2012 VL 8 IS 4 BP 72 EP 83 AR e1002616 DI 10.1371/journal.pgen.1002616 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 934KA UT WOS:000303441800005 PM 22536158 ER PT J AU Chahrour, MH Yu, TW Lim, ET Ataman, B Coulter, ME Hill, RS Stevens, CR Schubert, CR Greenberg, ME Gabriel, SB Walsh, CA AF Chahrour, Maria H. Yu, Timothy W. Lim, Elaine T. Ataman, Bulent Coulter, Michael E. Hill, R. Sean Stevens, Christine R. Schubert, Christian R. Greenberg, Michael E. Gabriel, Stacey B. Walsh, Christopher A. CA ARRA Autism Sequencing TI Whole-Exome Sequencing and Homozygosity Analysis Implicate Depolarization-Regulated Neuronal Genes in Autism SO PLOS GENETICS LA English DT Article ID LOWE-SYNDROME; SPECTRUM DISORDERS; MENTAL-RETARDATION; MUTATIONS; DISEASE; GENETICS; REVEALS; LINKAGE; LOCI; CONSANGUINITY AB Although autism has a clear genetic component, the high genetic heterogeneity of the disorder has been a challenge for the identification of causative genes. We used homozygosity analysis to identify probands from nonconsanguineous families that showed evidence of distant shared ancestry, suggesting potentially recessive mutations. Whole-exome sequencing of 16 probands revealed validated homozygous, potentially pathogenic recessive mutations that segregated perfectly with disease in 4/16 families. The candidate genes (UBE3B, CLTCL1, NCKAP5L, ZNF18) encode proteins involved in proteolysis, GTPase-mediated signaling, cytoskeletal organization, and other pathways. Furthermore, neuronal depolarization regulated the transcription of these genes, suggesting potential activity-dependent roles in neurons. We present a multidimensional strategy for filtering whole-exome sequence data to find candidate recessive mutations in autism, which may have broader applicability to other complex, heterogeneous disorders. C1 [Chahrour, Maria H.; Yu, Timothy W.; Coulter, Michael E.; Hill, R. Sean; Schubert, Christian R.; Walsh, Christopher A.] Childrens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Chahrour, Maria H.; Yu, Timothy W.; Hill, R. Sean; Schubert, Christian R.; Walsh, Christopher A.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Chahrour, Maria H.; Yu, Timothy W.; Hill, R. Sean; Schubert, Christian R.; Walsh, Christopher A.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Chahrour, Maria H.; Yu, Timothy W.; Schubert, Christian R.; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Chahrour, Maria H.; Yu, Timothy W.; Lim, Elaine T.; Stevens, Christine R.; Schubert, Christian R.; Gabriel, Stacey B.; Walsh, Christopher A.] Broad Inst Massachusetts Inst Technol & Harvard U, Program Med & Populat Genet, Cambridge, MA USA. [Yu, Timothy W.; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Lim, Elaine T.] Harvard Univ, Biol & Biomed Sci Program, Boston, MA 02115 USA. [Lim, Elaine T.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ataman, Bulent; Greenberg, Michael E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Chahrour, MH (reprint author), Childrens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. EM christopher.walsh@childrens.harvard.edu OI Chahrour, Maria/0000-0002-3174-1480; Yu, Timothy/0000-0003-2988-7701 FU National Institute of Health (NIH) [T32 NS007473-12, T32 NS007484-08, T32 NS007473-11, T32 NS007484-11, NS028829, R01MH089208, R01 MH089025, R01 MH089004, R01 MH089482, P50 HD055751, R01 MH057881, R01 MH061009]; Harvard-MIT Health Sciences and Technology; Beth Israel Deaconess Medical Center; Pfizer; Merck; Nancy Lurie Marks Junior Faculty; Alice and Joseph Brooks Fund; National Institute of Mental Health [R01 MH083565, 1RC2MH089952]; Nancy Lurie Marks Foundation; Simons Foundation; Autism Consortium; Manton Center for Orphan Disease Research; ARRA [1RC2MH089952]; NHGRI; Intellectual and Developmental Disabilities Research Centers (CHB DDRC) [P30 HD18655] FX MH Chahrour was supported by a National Institute of Health (NIH) T32 grant (T32 NS007473-12). TW Yu was supported by a NIH T32 grant (T32 NS007484-08), the Clinical Investigator Training Program at Harvard-MIT Health Sciences and Technology, and Beth Israel Deaconess Medical Center in collaboration with Pfizer and Merck, and the Nancy Lurie Marks Junior Faculty MeRIT Fellowship. B Ataman was supported by Alice and Joseph Brooks Fund. CR Schubert was supported by two NIH T32 grants (T32 NS007473-11 and T32 NS007484-11). Research was supported by grants from the National Institute of Mental Health (R01 MH083565; 1RC2MH089952) to CA Walsh, the Nancy Lurie Marks Foundation, the Simons Foundation, the Autism Consortium, the Manton Center for Orphan Disease Research, and a NIH grant to ME Greenberg (NS028829). Sequencing at the Broad Institute was supported by the ARRA Grand Opportunities grant 1RC2MH089952. Genotyping at the Broad Institute was supported by NHGRI. Genotyping at Children's Hospital Boston was supported by the Intellectual and Developmental Disabilities Research Centers (CHB DDRC, P30 HD18655). Exome sequencing as part of the ARRA Autism Sequencing Consortium was directly supported by NIH grants R01MH089208 (MJD), R01 MH089025 (JDB), R01 MH089004 (GDS), and R01 MH089482 (JSS) and was supported in part by NIH grants P50 HD055751 (EHC), R01 MH057881 (BD), and R01 MH061009 (JSS). CA Walsh is an Investigator of the Howard Hughes Medical Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 81 Z9 84 U1 2 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2012 VL 8 IS 4 BP 236 EP 244 AR e1002635 DI 10.1371/journal.pgen.1002635 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 934KA UT WOS:000303441800017 PM 22511880 ER PT J AU Manichaikul, A Palmas, W Rodriguez, CJ Peralta, CA Divers, J Guo, XQ Chen, WM Wong, QN Williams, K Kerr, KF Taylor, KD Tsai, MY Goodarzi, MO Sale, MM Diez-Roux, AV Rich, SS Rotter, JI Mychaleckyj, JC AF Manichaikul, Ani Palmas, Walter Rodriguez, Carlos J. Peralta, Carmen A. Divers, Jasmin Guo, Xiuqing Chen, Wei-Min Wong, Quenna Williams, Kayleen Kerr, Kathleen F. Taylor, Kent D. Tsai, Michael Y. Goodarzi, Mark O. Sale, Michele M. Diez-Roux, Ana V. Rich, Stephen S. Rotter, Jerome I. Mychaleckyj, Josyf C. TI Population Structure of Hispanics in the United States: The Multi-Ethnic Study of Atherosclerosis SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; GENETIC-VARIATION; GENOTYPE DATA; PATTERNS; SCANS; RISK; LOCI; ACCULTURATION; INFERENCE; VARIANTS AB Using similar to 60,000 SNPs selected for minimal linkage disequilibrium, we perform population structure analysis of 1,374 unrelated Hispanic individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with self-identification corresponding to Central America (n=93), Cuba (n=50), the Dominican Republic (n=203), Mexico (n=708), Puerto Rico (n=192), and South America (n=111). By projection of principal components (PCs) of ancestry to samples from the HapMap phase III and the Human Genome Diversity Panel (HGDP), we show the first two PCs quantify the Caucasian, African, and Native American origins, while the third and fourth PCs bring out an axis that aligns with known South-to-North geographic location of HGDP Native American samples and further separates MESA Mexican versus Central/South American samples along the same axis. Using k-means clustering computed from the first four PCs, we define four subgroups of the MESA Hispanic cohort that show close agreement with self-identification, labeling the clusters as primarily Dominican/Cuban, Mexican, Central/South American, and Puerto Rican. To demonstrate our recommendations for genetic analysis in the MESA Hispanic cohort, we present pooled and stratified association analysis of triglycerides for selected SNPs in the LPL and TRIB1 gene regions, previously reported in GWAS of triglycerides in Caucasians but as yet unconfirmed in Hispanic populations. We report statistically significant evidence for genetic association in both genes, and we further demonstrate the importance of considering population substructure and genetic heterogeneity in genetic association studies performed in the United States Hispanic population. C1 [Manichaikul, Ani; Chen, Wei-Min; Sale, Michele M.; Rich, Stephen S.; Mychaleckyj, Josyf C.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22903 USA. [Manichaikul, Ani; Chen, Wei-Min] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA. [Palmas, Walter] Columbia Univ, Dept Med, New York, NY USA. [Rodriguez, Carlos J.] Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Winston Salem, NC 27103 USA. [Rodriguez, Carlos J.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol, Winston Salem, NC USA. [Peralta, Carmen A.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA. [Peralta, Carmen A.] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. [Divers, Jasmin] Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. [Guo, Xiuqing; Taylor, Kent D.; Goodarzi, Mark O.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Wong, Quenna; Williams, Kayleen; Kerr, Kathleen F.] Univ Washington, Dept Biostat, Sch Publ Hlth, Seattle, WA 98195 USA. [Tsai, Michael Y.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Sale, Michele M.] Univ Virginia, Dept Med, Charlottesville, VA USA. [Sale, Michele M.] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA. [Diez-Roux, Ana V.] Univ Michigan, Dept Epidemiol, Ctr Social Epidemiol & Populat Hlth, Ann Arbor, MI 48109 USA. RP Manichaikul, A (reprint author), Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22903 USA. EM amanicha@virginia.edu RI Kerr, Kathleen/A-2893-2013; OI Manichaikul, Ani/0000-0002-5998-795X FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-95159, N01-HC-95169, RR-024156, N02-HL-6-4278]; United States Environmental Protection Agency (EPA); MESA Air investigators [RD83169701]; MESA investigators; [R01HL071051]; [R01HL071205]; [R01HL071250]; [R01HL071251]; [R01HL071252]; [R01HL071258]; [R01HL071259] FX MESA and the MESA SHARe project are conducted and supported by contracts N01-HC-95159 through N01-HC-95169 and RR-024156 from the National Heart, Lung, and Blood Institute (NHLBI). MESA Air is conducted and supported by the United States Environmental Protection Agency (EPA) in collaboration with MESA Air investigators, with support provided by grant RD83169701. Funding for MESA SHARe genotyping was provided by NHLBI Contract N02-HL-6-4278. MESA Family is conducted and supported in collaboration with MESA investigators; support is provided by grants and contracts R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258, R01HL071259. The authors thank the participants of the MESA study, the Coordinating Center, MESA investigators, and study staff for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. The NHLBI was involved in design and data collection of the MESA Study. The funders had no role in performing the analyses presented in this paper, nor in the decision to publish or in preparation of the manuscript. NR 35 TC 34 Z9 34 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2012 VL 8 IS 4 BP 285 EP 298 AR e1002640 DI 10.1371/journal.pgen.1002640 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 934KA UT WOS:000303441800021 PM 22511882 ER PT J AU Wiggs, JL Yapan, BL Hauser, MA Kane, JH Allingham, RR Olson, LM Abdrabou, W Fan, BJ Wang, DY Brodeur, W Budenz, DL Caprioli, J Crenshaw, A Crooks, K DelBono, E Doheny, KF Friedman, DS Gaasterland, D Gaasterland, T Laurie, C Lee, RK Lichter, PR Loomis, S Liu, YT Medeiros, FA McCarty, C Mirel, D Moroi, SE Musch, DC Realini, A Rozsa, FW Schuman, JS Scott, K Singh, K Stein, JD Trager, EH VanVeldhuisen, P Vollrath, D Wollstein, G Yoneyama, S Zhang, K Weinreb, RN Ernst, J Kellis, M Masuda, T Zack, D Richards, JE Pericak-Vance, M Pasquale, LR Haines, JL AF Wiggs, Janey L. Yapan, Brian L. Hauser, Michael A. Kane, Jae H. Allingham, R. Rand Olson, Lana M. Abdrabou, Wael Fan, Bao J. Wang, Dan Y. Brodeur, Wendy Budenz, Donald L. Caprioli, Joseph Crenshaw, Andrew Crooks, Kristy DelBono, Elizabeth Doheny, Kimberly F. Friedman, David S. Gaasterland, Douglas Gaasterland, Terry Laurie, Cathy Lee, Richard K. Lichter, Paul R. Loomis, Stephanie Liu, Yutao Medeiros, Felipe A. McCarty, Cathy Mirel, Daniel Moroi, Sayoko E. Musch, David C. Realini, Anthony Rozsa, Frank W. Schuman, Joel S. Scott, Kathleen Singh, Kuldev Stein, Joshua D. Trager, Edward H. VanVeldhuisen, Paul Vollrath, Douglas Wollstein, Gadi Yoneyama, Sachiko Zhang, Kang Weinreb, Robert N. Ernst, Jason Kellis, Manolis Masuda, Tomohiro Zack, Don Richards, Julia E. Pericak-Vance, Margaret Pasquale, Louis R. Haines, Jonathan L. TI Common Variants at 9p21 and 8q22 Are Associated with Increased Susceptibility to Optic Nerve Degeneration in Glaucoma SO PLOS GENETICS LA English DT Article ID OPEN-ANGLE GLAUCOMA; GENOME-WIDE ASSOCIATION; NORMAL-TENSION GLAUCOMA; RECEPTOR-RELATED PROTEIN; RETINAL GENE-EXPRESSION; US CAUCASIAN POPULATION; INTRAOCULAR-PRESSURE; DISEASE; MODULATION; NUMBER AB Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95%CI 0.63-0.75], p = 1.86 x 10(-18)), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95%CI 1.21-1.43], p = 3.87 x 10(-11)). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95% Cl 0.50-0.67], p = 1.17 x 10(-12)) and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95% Cl 0.53-0.72], p = 8.88 x 10(-10)). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95% Cl 0.41-0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95% Cl 0.54-1.06], p = 0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). These results suggest that neuro-protective therapies targeting TGFbeta signaling could be effective for multiple forms of glaucoma. C1 [Wiggs, Janey L.; Abdrabou, Wael; Fan, Bao J.; Wang, Dan Y.; DelBono, Elizabeth; Loomis, Stephanie; Pasquale, Louis R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Yapan, Brian L.; Olson, Lana M.; Haines, Jonathan L.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA. [Hauser, Michael A.; Allingham, R. Rand; Crooks, Kristy; Liu, Yutao] Duke Univ, Sch Med, Durham, NC USA. [Kane, Jae H.; Loomis, Stephanie; Pasquale, Louis R.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kane, Jae H.; Loomis, Stephanie; Pasquale, Louis R.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Brodeur, Wendy; Crenshaw, Andrew; Mirel, Daniel; Ernst, Jason; Kellis, Manolis] Broad Inst Harvard & Massachusetts Inst Technol, Boston, MA USA. [Budenz, Donald L.] Univ N Carolina, Dept Ophthalmol, Sch Med, Durham, NC USA. [Caprioli, Joseph] Univ Calif Los Angeles, Dept Ophthalmol, Los Angeles, CA USA. [Doheny, Kimberly F.] Johns Hopkins Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA. [Friedman, David S.; Masuda, Tomohiro; Zack, Don] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. [Gaasterland, Douglas] Eye Doctors Washington DC, Washington, DC USA. [Gaasterland, Terry] Univ Calif San Diego, Inst Genom Med, San Diego, CA 92103 USA. [Gaasterland, Terry] Univ Calif San Diego, Div Marine Biol Res, San Diego, CA 92103 USA. [Laurie, Cathy] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Lee, Richard K.] Univ Miami, Dept Ophthalmol, Miami, FL USA. [Lichter, Paul R.; Moroi, Sayoko E.; Musch, David C.; Rozsa, Frank W.; Scott, Kathleen; Stein, Joshua D.; Trager, Edward H.; Yoneyama, Sachiko; Richards, Julia E.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Medeiros, Felipe A.; Zhang, Kang; Weinreb, Robert N.] Univ Calif San Diego, Dept Ophthalmol, San Diego, CA 92103 USA. [McCarty, Cathy] Essentia Inst Rural Hlth, Duluth, MN USA. [Musch, David C.; Yoneyama, Sachiko; Richards, Julia E.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Realini, Anthony] W Virginia Univ, Dept Ophthalmol, Sch Med, Morgantown, WV 26506 USA. [Schuman, Joel S.; Wollstein, Gadi] Univ Pittsburgh, Dept Ophthalmol, Pittsburgh, PA 15260 USA. [Singh, Kuldev] Stanford Univ, Dept Ophthalmol, Palo Alto, CA 94304 USA. [VanVeldhuisen, Paul] EMMES Corp, Rockville, MD USA. [Vollrath, Douglas] Stanford Univ, Dept Genet, Palo Alto, CA 94304 USA. [Ernst, Jason; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Pericak-Vance, Margaret] Univ Miami, Sch Med, Dept Human Genet, Miami, FL USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. EM janey_wiggs@meei.harvard.edu RI Schuman, Joel/K-7304-2012; Haines, Jonathan/C-3374-2012 OI Rozsa, Frank/0000-0002-1378-7020; Caprioli, Joseph/0000-0002-2383-7263; Zack, Don/0000-0002-7966-1973; Fan, Baojian/0000-0002-6851-2737; Schuman, Joel/0000-0002-8885-3766; FU National Eye Institute [HG005259-01, 3R01EY015872-05S1, 3R01EY019126-02S1]; National Institutes of Health [HHSN268200782096C, EY015543, EY006827, HL73042, HL073389, EY13315, CA87969, CA49449, CA55075, EY009149, HG004608, EY008208, EY015473]; GENEVA [HG004728, U01-HG004424]; Harvard Glaucoma Center for Excellence; Margolis Fund; Glaucoma Research Foundation; American Health Assistance Foundation; Glaucoma Foundation; Research to Prevent Blindness; Center for Inherited Disease Research (CIDR); National Institutes of Health. [EY012118, EY015682, EY011671, EY09580, EY013178, RR015574, EY015872, EY010886, EY009847, EY011008, EY144428, EY144448, EY18660, T32EY021453]; [RC1HG005334]; [U54HG004570] FX This work was supported by the following: Genotyping services for the NEIGHBOR study were provided by the Center for Inherited Disease Research (CIDR) and were supported by the National Eye Institute through grant HG005259-01 (JL Wiggs). Additionally, CIDR is funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. Genotyping for the GLAUGEN dataset at the Broad Institute was supported by GENEVA project grant HG004728 (LR Pasquale) and U01-HG004424 (Broad Institute). Genotype data cleaning and analysis for the GLAUGEN study was supported by U01 HG004446 (C Laurie). Collecting and processing samples for the NEIGHBOR dataset was supported by the National Eye Institute through ARRA grants 3R01EY015872-05S1 (JL Wiggs) and 3R01EY019126-02S1 (MA Hauser). Support for ENCODE was provided through grants RC1HG005334 and U54HG004570. Funding for the collection of cases and controls was provided by NIH grants: EY015543 (RR Allingham), EY006827 (D Gaasterland); HL73042, HL073389, EY13315 (MA Hauser); CA87969 (JH Kang), CA49449 (JH Kang), CA55075 (JH Kang), EY009149 (PR Lichter), HG004608 (C McCarty), EY008208 (FA Medeiros), EY015473 (LR Pasquale), EY012118 (M Pericak-Vance), EY015682 (A Realini), EY011671 (JE Richards), EY09580 (JE Richards), EY013178 (JS Schuman), RR015574, EY015872 (JL Wiggs), EY010886 (JL Wiggs), EY009847 (JL Wiggs), EY011008, EY144428 (K Zhang), EY144448 (K Zhang), EY18660 (K Zhang). We also thank the staff of the Vanderbilt Computational Genomics Core for their help in collating and analyzing these data and the University of Washington and Duke ENCODE groups for making DNase data available pre-publication. JL Wiggs and LR Pasquale are also supported by the Harvard Glaucoma Center for Excellence and the Margolis Fund. BL Yaspan was supported in part by NIH grant T32EY021453. Y Liu is supported by the Glaucoma Research Foundation, American Health Assistance Foundation, and the Glaucoma Foundation. JL Wiggs, LR Pasquale, DC Musch, and JE Richards are supported by Research to Prevent Blindness. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 100 Z9 101 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2012 VL 8 IS 4 BP 413 EP 424 AR e1002654 DI 10.1371/journal.pgen.1002654 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 934KA UT WOS:000303441800031 PM 22570617 ER PT J AU Keller, MC Simonson, MA Ripke, S Neale, BM Gejman, PV Howrigan, DP Lee, SH Lencz, T Levinson, DF Sullivan, PF AF Keller, Matthew C. Simonson, Matthew A. Ripke, Stephan Neale, Ben M. Gejman, Pablo V. Howrigan, Daniel P. Lee, Sang Hong Lencz, Todd Levinson, Douglas F. Sullivan, Patrick F. CA Schizophrenia Psychiat Genome Wide TI Runs of Homozygosity Implicate Autozygosity as a Schizophrenia Risk Factor SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; INBREEDING DEPRESSION; GENOTYPE IMPUTATION; COMPLEX DISEASES; CONSANGUINITY; POPULATIONS; SUSCEPTIBILITY; METAANALYSIS; PREVALENCE; MARRIAGES AB Autozygosity occurs when two chromosomal segments that are identical from a common ancestor are inherited from each parent. This occurs at high rates in the offspring of mates who are closely related (inbreeding), but also occurs at lower levels among the offspring of distantly related mates. Here, we use runs of homozygosity in genome-wide SNP data to estimate the proportion of the autosome that exists in autozygous tracts in 9,388 cases with schizophrenia and 12,456 controls. We estimate that the odds of schizophrenia increase by similar to 17% for every 1% increase in genome-wide autozygosity. This association is not due to one or a few regions, but results from many autozygous segments spread throughout the genome, and is consistent with a role for multiple recessive or partially recessive alleles in the etiology of schizophrenia. Such a bias towards recessivity suggests that alleles that increase the risk of schizophrenia have been selected against over evolutionary time. C1 [Keller, Matthew C.; Simonson, Matthew A.; Howrigan, Daniel P.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. [Keller, Matthew C.; Simonson, Matthew A.; Howrigan, Daniel P.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Ripke, Stephan; Neale, Ben M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ripke, Stephan; Neale, Ben M.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Ripke, Stephan; Neale, Ben M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Gejman, Pablo V.] N Shore Univ Hlth Syst, Dept Psychiat & Behav Sci, Evanston, IL USA. [Gejman, Pablo V.] Univ Chicago, Dept Psychiat & Behav Sci, Chicago, IL 60637 USA. [Lee, Sang Hong] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Lencz, Todd] N Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp Div, Dept Psychiat, Div Res, Glen Oaks, NY USA. [Lencz, Todd] Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA. [Lencz, Todd] Yeshiva Univ, Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY USA. [Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Sullivan, Patrick F.] Karolinska Inst, Dept Dept Med Epidemiol & Biostatist, Stockholm, Sweden. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. RP Keller, MC (reprint author), Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. EM matthew.c.keller@gmail.com RI Lee, Sang Hong/A-2569-2011; Ingason, Andres/G-6817-2012; Cahn , Wiepke /B-5743-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Myin-Germeys, Inez /L-5106-2014; Mattheisen, Manuel/B-4949-2012; Melle, Ingrid /B-4858-2011; Lencz, Todd/J-3418-2014; McQuillin, Andrew/C-1623-2008; OI Zammit, Stanley/0000-0002-2647-9211; lichtenstein, paul/0000-0003-3037-5287; Bruggeman, Richard/0000-0002-3238-8471; Agartz, Ingrid/0000-0002-9839-5391; Nothen, Markus/0000-0002-8770-2464; Andreassen, Ole A./0000-0002-4461-3568; Lee, Sang Hong/0000-0001-9701-2718; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Mattheisen, Manuel/0000-0002-8442-493X; Melle, Ingrid /0000-0002-9783-548X; Lencz, Todd/0000-0001-8586-338X; McQuillin, Andrew/0000-0003-1567-2240; Bergen, Sarah/0000-0002-5888-0034; KELLER, MATTHEW/0000-0002-6075-9882; Myin-Germeys, Inez/0000-0002-3731-4930 FU National Institutes of Health; National Institute of Mental Health [MH085812, MH61675, MH085520] FX This study was supported by grants from the National Institutes of Health and the National Institute of Mental Health (grants MH085812 to MCK, MH61675 to DFL, and MH085520 to SPGWASC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 39 Z9 39 U1 4 U2 21 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2012 VL 8 IS 4 BP 425 EP 435 AR e1002656 DI 10.1371/journal.pgen.1002656 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 934KA UT WOS:000303441800032 PM 22511889 ER PT J AU Ranjbar, S Jasenosky, LD Chow, N Goldfeld, AE AF Ranjbar, Shahin Jasenosky, Luke D. Chow, Nancy Goldfeld, Anne E. TI Regulation of Mycobacterium tuberculosis-Dependent HIV-1 Transcription Reveals a New Role for NFAT5 in the Toll-Like Receptor Pathway SO PLOS PATHOGENS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NF-KAPPA-B; LONG TERMINAL REPEAT; NECROSIS-FACTOR-ALPHA; ADAPTIVE IMMUNE-RESPONSE; ENHANCER-BINDING PROTEIN; GENE-EXPRESSION; PROINFLAMMATORY CYTOKINES; PRODUCTIVE INFECTION; ALVEOLAR MACROPHAGES AB Tuberculosis (TB) disease in HIV co-infected patients contributes to increased mortality by activating innate and adaptive immune signaling cascades that stimulate HIV-1 replication, leading to an increase in viral load. Here, we demonstrate that silencing of the expression of the transcription factor nuclear factor of activated T cells 5 (NFAT5) by RNA interference (RNAi) inhibits Mycobacterium tuberculosis (MTb)-stimulated HIV-1 replication in co-infected macrophages. We show that NFAT5 gene and protein expression are strongly induced by MTb, which is a Toll-like receptor (TLR) ligand, and that an intact NFAT5 binding site in the viral promoter of R5-tropic HIV-1 subtype B and subtype C molecular clones is required for efficent induction of HIV-1 replication by MTb. Furthermore, silencing by RNAi of key components of the TLR pathway in human monocytes, including the downstream signaling molecules MyD88, IRAK1, and TRAF6, significantly inhibits MTb-induced NFAT5 gene expression. Thus, the innate immune response to MTb infection induces NFAT5 gene and protein expression, and NFAT5 plays a crucial role in MTb regulation of HIV-1 replication via a direct interaction with the viral promoter. These findings also demonstrate a general role for NFAT5 in TLR- and MTb-mediated control of gene expression. C1 [Ranjbar, Shahin; Jasenosky, Luke D.; Chow, Nancy; Goldfeld, Anne E.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Ranjbar, Shahin; Jasenosky, Luke D.; Chow, Nancy; Goldfeld, Anne E.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Ranjbar, Shahin] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Goldfeld, Anne E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Ranjbar, S (reprint author), Childrens Hosp, Immune Dis Inst, 300 Longwood Ave, Boston, MA 02115 USA. EM goldfeld@idi.harvard.edu FU NIH [AI065285, GM076685]; HU Center for AIDS Research [P30 AI 060354] FX This work was funded by grants from the NIH (AI065285 and GM076685) to AEG and HU Center for AIDS Research (P30 AI 060354) to SR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 77 TC 16 Z9 18 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2012 VL 8 IS 4 AR e1002620 DI 10.1371/journal.ppat.1002620 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 934KY UT WOS:000303444200017 PM 22496647 ER PT J AU Allen, AM Pawlicki, T Dong, L Fourkal, E Buyyounouski, M Cengel, K Plastaras, J Bucci, MK Yock, TI Bonilla, L Price, R Harris, EE Konski, AA AF Allen, Aaron M. Pawlicki, Todd Dong, Lei Fourkal, Eugene Buyyounouski, Mark Cengel, Keith Plastaras, John Bucci, Mary K. Yock, Torunn I. Bonilla, Luisa Price, Robert Harris, Eleanor E. Konski, Andre A. TI An evidence based review of proton beam therapy: The report of ASTRO's emerging technology committee SO RADIOTHERAPY AND ONCOLOGY LA English DT Review DE Proton beam therapy; Radiation therapy; Evidence based guidelines ID CELL LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; RADIATION-THERAPY; UVEAL MELANOMA; SKULL BASE; CONSERVATIVE TREATMENT; RADIOTHERAPY; PHOTON; MALIGNANCIES; IRRADIATION AB Proton beam therapy (PBT) is a novel method for treating malignant disease with radiotherapy. The purpose of this work was to evaluate the state of the science of PBT and arrive at a recommendation for the use of PBT. The emerging technology committee of the American Society of Radiation Oncology (ASTRO) routinely evaluates new modalities in radiotherapy and assesses the published evidence to determine recommendations for the society as a whole. In 2007, a Proton Task Force was assembled to evaluate the state of the art of PBT. This,report reflects evidence collected up to November 2009. Data was reviewed for PBT in central nervous system tumors, gastrointestinal malignancies, lung, head and neck, prostate, and pediatric tumors. Current data do not provide sufficient evidence to recommend PBT in lung cancer, head and neck cancer, GI malignancies, and pediatric non-CNS malignancies. In hepatocellular carcinoma and prostate cancer and there is evidence for the efficacy of PBT but no suggestion that it is superior to photon based approaches. In pediatric CNS malignancies PBT appears superior to photon approaches but more data is needed. In large ocular melanomas and chordomas, we believe that there is evidence for a benefit of PBT over photon approaches. PBT is an important new technology in radiotherapy. Current evidence provides a limited indication for PBT. More robust prospective clinical trials are needed to determine the appropriate clinical setting for PBT. (C) 2012 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 103 (2012) 8-11 C1 [Allen, Aaron M.] Tel Aviv Univ, Rabin Med Ctr, Davidoff Ctr, Petah Tiqwa, Israel. [Pawlicki, Todd] Univ Calif San Diego, La Jolla, CA 92093 USA. [Dong, Lei; Bucci, Mary K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fourkal, Eugene; Buyyounouski, Mark; Price, Robert] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Cengel, Keith; Plastaras, John] Univ Penn, Philadelphia, PA 19104 USA. [Yock, Torunn I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, Eleanor E.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Konski, Andre A.] Wayne State Univ, Med Ctr, Detroit, MI 48202 USA. RP Allen, AM (reprint author), Tel Aviv Univ, Rabin Med Ctr, Davidoff Ctr, Petah Tiqwa, Israel. EM Aarona2@clalit.org.il OI Harris, Eleanor/0000-0002-7529-7473; Dong, Lei/0000-0003-2623-3198 NR 51 TC 82 Z9 82 U1 4 U2 36 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD APR PY 2012 VL 103 IS 1 BP 8 EP 11 DI 10.1016/j.radonc.2012.02.001 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 934ZE UT WOS:000303485600003 PM 22405807 ER PT J AU Efstathiou, JA Paly, JJ Lu, HM Athar, BS Moteabbed, M Niemierko, A Adams, JA Bekelman, JE Shipley, WU Zietman, AL Paganetti, H AF Efstathiou, Jason A. Paly, Jonathan J. Lu, Hsiao-Ming Athar, Basit S. Moteabbed, Maryam Niemierko, Andrzej Adams, Judith A. Bekelman, Justin E. Shipley, William U. Zietman, Anthony L. Paganetti, Harald TI Adjuvant radiation therapy for early stage seminoma: Proton versus photon planning comparison and modeling of second cancer risk SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Testicular cancer; Seminoma; Radiation therapy; Second cancers; Protons ID I TESTICULAR SEMINOMA; RANDOMIZED-TRIAL; RADIOTHERAPY; FERTILITY; SURVIVORS; VOLUME; BOMB AB Purpose: Given concerns of excess malignancies following adjuvant radiation for seminoma, we evaluated photon and proton beam therapy (PBT) treatment plans to assess dose distributions to organs at risk and model rates of second cancers. Materials and methods: Ten stage I seminoma patients who were treated with conventional para-aortic AP-PA photon radiation to 25.5 Gy at Massachusetts General Hospital had PBT plans generated (APPA, PA alone). Dose differences to critical organs were examined. Risks of second primary malignancies were calculated. Results: PBT plans were superior to photons in limiting dose to organs at risk. PBT decreased dose by 46% (8.2 Gy) and 64% (10.2 Gy) to the stomach and large bowel, respectively (p < 0.01). Notably, PBT was found to avert 300 excess second cancers among 10,000 men treated at a median age of 39 and surviving to 75 (p < 0.01). Conclusions: In this study, the use of protons provided a favorable dose distribution with an ability to limit unnecessary exposure to critical normal structures in the treatment of early-stage seminoma. It is expected that this will translate into decreased acute toxicity and reduced risk of second cancers, for which prospective studies are warranted. (C) 2012 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 103 (2012) 12-17 C1 [Efstathiou, Jason A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Bekelman, Justin E.] Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Efstathiou, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org NR 30 TC 15 Z9 15 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD APR PY 2012 VL 103 IS 1 BP 12 EP 17 DI 10.1016/j.radonc.2012.01.012 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 934ZE UT WOS:000303485600004 PM 22391053 ER PT J AU Hong, TS Tome, WA Harari, PM AF Hong, Theodore S. Tome, Wolfgang A. Harari, Paul M. TI Heterogeneity in head and neck IMRT target design and clinical practice SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE IMRT; Head and neck; Target design; CTV definition; Contouring ID INTENSITY-MODULATED RADIOTHERAPY; PAROTID-SPARING IRRADIATION; SQUAMOUS-CELL CARCINOMA; RADIATION-THERAPY BOOST; ORAL-CAVITY; CANCER; PATTERNS; FAILURE; DELINEATION; XEROSTOMIA AB Purpose: To assess patterns of H&N IMRT practice with particular emphasis on elective target delineation. Materials and methods: Twenty institutions with established H&N IMRT expertise were solicited to design clinical target volumes for the identical H&N cancer case. To limit contouring variability, a primary tonsil GTV and ipsilateral level II node were pre-contoured. Participants were asked to accept this GTV, and contour their recommended CTV and PTV. Dose prescriptions, contouring time, and recommendations regarding chemotherapy were solicited. Results: All 20 institutions responded. Remarkable heterogeneity in H&N IMRT design and practice was identified. Seventeen of 20 centers recommended treatment of bilateral necks whereas 3/20 recommended treatment of the ipsilateral neck only. The average CTV volume was 250 cm(3) (range 37-676 cm(3)). Although there was high concordance in coverage of ipsilateral neck levels II and III, substantial variation was identified for levels I, V. and the contralateral neck. Average CTV expansion was 4.1 mm (range 0-15 mm). Eight of 20 centers recommended chemotherapy (cisplatin), whereas 12/20 recommended radiation alone. Responders prescribed on average 69 and 68 Gy to the tumor and metastatic node GTV, respectively. Average H&N target volume contouring time was 102.5 min (range 60-210 min). Conclusion: This study identifies substantial heterogeneity in H&N IMRT target definition, prescription, neck treatment, and use of chemotherapy among practitioners with established H&N IMRT expertise. These data suggest that continued efforts to standardize and simplify the H&N IMRT process are desirable for the safe and effective global advancement of H&N IMRT practice. (C) 2012 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 103 (2012) 92-98 C1 [Harari, Paul M.] Univ Wisconsin, Dept Human Oncol, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Ctr Canc, Boston, MA 02114 USA. [Tome, Wolfgang A.] Univ Wisconsin, Dept Med Phys, Madison, WI 53792 USA. [Tome, Wolfgang A.] Univ Wisconsin, Dept Biomed Engn, Madison, WI 53792 USA. RP Harari, PM (reprint author), Univ Wisconsin, Dept Human Oncol, Sch Med & Publ Hlth, Madison, WI 53792 USA. EM harari@humonc.wisc.edu RI Tome, Wolfgang/P-5443-2016 OI Tome, Wolfgang/0000-0003-1586-8091 FU NIH [5-PO1 CA88960-02] FX We sincerely thank the personnel from 20 participating centers (Appendix) who devoted their time and expertise to this study. We also thank Julie Thomas who coordinated communications with participating centers and facilitated data collection. Supported in part by NIH Grant #5-PO1 CA88960-02. NR 30 TC 23 Z9 23 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD APR PY 2012 VL 103 IS 1 BP 92 EP 98 DI 10.1016/j.radonc.2012.02.010 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 934ZE UT WOS:000303485600017 PM 22405806 ER PT J AU Nebergall, A Bragdon, C Antonellis, A Karrholm, J Branemark, R Berlin, O Malchau, H AF Nebergall, Audrey Bragdon, Charles Antonellis, Anne Karrholm, Johan Branemark, Rickard Berlin, Orjan Malchau, Henrik TI Stable fixation of an osseointegated implant system for above-the-knee amputees Titel RSA and radiographic evaluation of migration and bone remodeling in 55 cases SO ACTA ORTHOPAEDICA LA English DT Article ID TRANS-FEMORAL AMPUTATION; TOTAL HIP-ARTHROPLASTY; QUALITY-OF-LIFE; TRANSFEMORAL AMPUTATION; PROSTHESES; REHABILITATION; CONSEQUENCES; REPLACEMENT; SOCKET AB Background and purpose Rehabilitation of patients with transfemoral amputations is particularly difficult due to problems in using standard socket prostheses. We wanted to assess long-term fixation of the osseointegrated implant system (OPRA) using radiostereometric analysis (RSA) and periprosthetic bone remodeling. Methods 51 patients with transfemoral amputations (55 implants) were enrolled in an RSA study. RSA and plain radiographs were scheduled at 6 months and at 1, 2, 5, 7, and 10 years after surgery. RSA films were analyzed using UmRSA software. Plain radiographs were graded for bone resorption, cancellization, cortical thinning, and trabecular streaming or buttressing in specifically defined zones around the implant. Results At 5 years, the median (SE) migration of the implant was -0.02 (0.06) mm distally. The rotational movement was 0.42 (0.32) degrees around the longitudinal axis. There was no statistically significant difference in median rotation or migration at any follow-up time. Cancellization of the cortex (plain radiographic grading) appeared in at least 1 zone in over half of the patients at 2 years. However, the prevalence of cancellization had decreased by the 5-year follow-up. Interpretation The RSA analysis for the OPRA system indicated stable fixation of the implant. The periprosthetic bone remodeling showed similarities with changes seen around uncemented hip stems. The OPRA system is a new and promising approach for addressing the challenges faced by patients with transfemoral amputations. C1 [Nebergall, Audrey; Bragdon, Charles; Antonellis, Anne; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Karrholm, Johan; Branemark, Rickard; Berlin, Orjan] Sahlgrens Univ Hosp, Gothenburg, Sweden. RP Malchau, H (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. EM hmalchau@partners.org NR 24 TC 20 Z9 21 U1 1 U2 6 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1745-3674 J9 ACTA ORTHOP JI Acta Orthop. PD APR PY 2012 VL 83 IS 2 BP 121 EP 128 DI 10.3109/17453674.2012.678799 PG 8 WC Orthopedics SC Orthopedics GA 931TR UT WOS:000303242700005 PM 22489885 ER PT J AU Kim, JS Kim, BK Jang, IK Shin, DH Ko, YG Choi, D Hong, MK Cho, YK Nam, CW Hur, SH Choi, JH Song, YB Hahn, JY Choi, SH Gwon, HC Jang, Y AF Kim, Jung-Sun Kim, Byeong-Kuk Jang, Ik-Kyung Shin, Dong-Ho Ko, Young-Guk Choi, Donghoon Hong, Myeong-Ki Cho, Yun-Kyeong Nam, Chang-Wook Hur, Seung-Ho Choi, Jin-Ho Song, Young Bin Hahn, Joo Yong Choi, Seung Hyuk Gwon, Hyeon Cheol Jang, Yangsoo TI ComparisOn of neointimal coVerage betwEen zotaRolimus-eluting stent and everolimus-eluting stent using Optical Coherence Tomography (COVER OCT) SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY-DISEASE; VASCULAR-RESPONSE; STRUT COVERAGE; DRUG-RELEASE; BARE-METAL; IMPLANTATION; RESOLUTE; SYSTEM; TRIAL; THROMBOSIS AB Background Data on strut surface coverage of second-generation drug-eluting stents (DES) are limited. We investigated stent strut coverage of resolute zotarolimus-eluting stent (ZES-R) or everolimus-eluting stent (EES) at 9 months after implantation using optical coherence tomography (OCT). Methods ComparisOn of neointimal coVerage betwEen zotaRolimus-eluting stent and everolimus-eluting stent using Optical Coherence Tomography (COVER OCT) is a prospective, randomized, multicenter trial comparing ZES-R to EES using OCT at 9 months after stent implantation. The primary end point was the rate of stent strut coverage at 9 months. Results A total of 51 patients were randomized to receive either ZES-R (ZES-R group) or EES (EES group), and 47 stents (24 ZES-R and 23 EES) in 44 of 51 patients were evaluated by OCT both immediately after stent implantation and at 9 months. The neointimal thickness was not significantly different between the 2 groups at 9 months (ZES-R vs EES: 139 +/- 58 vs 124 +/- 42 mu m, P = .31). The mean percentages of uncovered stent struts were 3.3% for ZES-R versus 3.4% for EES at 9 months (P = .51). The proportions of malapposed struts immediately after stent implantation (P = .89) and at 9-month follow-up (P = .34) were 0.8% and 0.7% for ZES-R versus 1.0% and 0.1% for EES, respectively. Thrombi were documented in 1 stent (1 [4.2%] in ZES-R vs 0 [0%] in EES). Conclusion According to the sequential OCT evaluation, ZES-R and EES showed comparable neointimal thickness and the rate of uncovered stent strut at 9 months after stent implantation. (Am Heart J 2012; 163:601-7.) C1 [Kim, Jung-Sun; Kim, Byeong-Kuk; Shin, Dong-Ho; Ko, Young-Guk; Choi, Donghoon; Hong, Myeong-Ki; Jang, Yangsoo] Yonsei Univ, Div Cardiol, Yonsei Cardiovasc Ctr, Coll Med, Seoul 120752, South Korea. [Kim, Jung-Sun; Kim, Byeong-Kuk; Shin, Dong-Ho; Ko, Young-Guk; Choi, Donghoon; Hong, Myeong-Ki] Yonsei Univ, Div Cardiol, Severance Biomed Sci Inst, Seoul 120752, South Korea. [Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Cho, Yun-Kyeong; Nam, Chang-Wook; Hur, Seung-Ho] Keimyung Univ, Dongsan Med Ctr, Taegu, South Korea. [Choi, Jin-Ho; Song, Young Bin; Hahn, Joo Yong; Choi, Seung Hyuk; Gwon, Hyeon Cheol] Sungkyunkwan Univ, Div Cardiol, Samsung Med Ctr, Coll Med, Seoul, South Korea. RP Jang, Y (reprint author), Yonsei Univ, Div Cardiol, Yonsei Cardiovasc Ctr, Coll Med, 250 Seongsanno, Seoul 120752, South Korea. EM jangys1212@yuhs.ac OI Choi, Seung-Hyuk/0000-0002-0304-6317; Hur, Seung-Ho/0000-0002-3895-1915 NR 21 TC 23 Z9 25 U1 0 U2 3 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 APR PY 2012 VL 163 IS 4 BP 601 EP 607 DI 10.1016/j.ahj.2011.10.016 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 930AD UT WOS:000303106800021 PM 22520526 ER PT J AU Ayotte, BJ Hausmann, LRM Whittle, J Kressin, NR AF Ayotte, Brian J. Hausmann, Leslie R. M. Whittle, Jeff Kressin, Nancy R. TI The relationship between perceived discrimination and coronary artery obstruction SO AMERICAN HEART JOURNAL LA English DT Article ID CARDIOVASCULAR-DISEASE; HEART-DISEASE; AFRICAN-AMERICANS; RACIAL-DISCRIMINATION; BLOOD-PRESSURE; CHRONIC STRESS; TRAIT ANXIETY; HEALTH; WOMEN; CORTISOL AB Background Chronic stressors such as perceived discrimination might underlie race disparities in cardiovascular disease. This study focused on the relationship between perceived discrimination and risk of severe coronary obstruction while also accounting for multiple psychosocial variables and clinical factors. Methods Data from 793 (629 white and 164 black) male veterans with positive nuclear imaging studies were analyzed. Participants were categorized as being at low/moderate or high risk for severe coronary obstruction based on results of their nuclear imaging studies. Hierarchical logistic regression models were tested separately for blacks and whites. The first step of the models included clinical factors. The second step included the psychosocial variables of optimism, religiosity, negative affect, and social support. The final step included perceived discrimination. Results Perceived discrimination was positively related to risk of severe obstruction among blacks but not among whites after controlling for clinical and psychosocial variables. Similar results were found in patients who underwent coronary angiography (n = 311). Conclusions Perceived discrimination was associated with risk of severe coronary obstruction among black male veterans and could be an important target for future interventions. (Am Heart J 2012;163:677-83.) C1 [Ayotte, Brian J.] Univ Massachusetts Dartmouth, Dept Psychol, N Dartmouth, MA 02747 USA. [Hausmann, Leslie R. M.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hausmann, Leslie R. M.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Whittle, Jeff] Clement J Zablocki VA Med Ctr, Primary Care Div, Milwaukee, WI USA. [Whittle, Jeff] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Kressin, Nancy R.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Ayotte, BJ (reprint author), Univ Massachusetts Dartmouth, Dept Psychol, N Dartmouth, MA 02747 USA. EM bayotte@umassd.edu OI Kressin, Nancy/0000-0003-2767-4286 NR 38 TC 5 Z9 5 U1 2 U2 10 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 APR PY 2012 VL 163 IS 4 BP 677 EP 683 DI 10.1016/j.ahj.2012.01.006 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 930AD UT WOS:000303106800029 PM 22520534 ER PT J AU Magnani, JW Moser, CB Murabito, JM Nelson, KP Fontes, JD Lubitz, SA Sullivan, LM Ellinor, PT Benjamin, EJ AF Magnani, Jared W. Moser, Carlee B. Murabito, Joanne M. Nelson, Kerrie P. Fontes, Joao D. Lubitz, Steven A. Sullivan, Lisa M. Ellinor, Patrick T. Benjamin, Emelia J. TI Age of natural menopause and atrial fibrillation: The Framingham Heart Study SO AMERICAN HEART JOURNAL LA English DT Article ID C-REACTIVE PROTEIN; CARDIOVASCULAR RISK-FACTORS; POSTMENOPAUSAL WOMEN; CARDIAC ELECTROPHYSIOLOGY; GENDER-DIFFERENCES; ESTROGEN-RECEPTOR; DISEASE RISK; MORTALITY; FAILURE; HYPERTENSION AB Background Early menopausal age is associated with risk of cardiovascular events including myocardial infraction, stroke, and increased mortality. Relations between menopausal age and atrial fibrillation (AF) have not been investigated. We examined the association between menopausal age and AF. Methods Framingham Heart Study women >= 60 years old without prevalent AF and natural menopause were followed up for 10 years or until incident AF. Menopausal age was modeled as a continuous variable and by categories (<45, 45-53, and >53 years). We used Cox proportional hazards regression to determine associations between menopausal age and AF risk. Results In 1,809 Framingham women (2,662 person-examinations, mean baseline age 71.4 +/- 7.6 years, menopausal age 49.8 +/- 3.6 years), there were 273 unique participants with incident AF. We did not identify a significant association between the SD of menopausal age (3.6 years) and AF (hazard ratio [HR] per SD 0.94, 95% CI 0.83-1.06; P = .29). In a multivariable model with established risk factors for AF, menopausal age was not associated with incident AF (HR per SD 0.97, 95% CI 0.86-1.09; P = .60). Examining categorical menopausal age, earlier menopausal age (<45 years) was not significantly associated with increased AF risk compared with older menopausal age >53 years (HR 1.20, 95% CI 0.74-1.94; P = .52) or menopausal age 45 to 53 years (HR 1.38, 95% CI 0.93-2.04; P = .11). Conclusion In our moderate-sized, community-based sample, we did not identify menopausal age as significantly increasing AF risk. However, future larger studies will need to examine whether there is a small effect of menopausal age on AF risk. (Am Heart J 2012;163:729-34.) C1 [Magnani, Jared W.] Boston Univ, Sch Med, Sect Cardiovasc Med, Dept Med, Boston, MA 02118 USA. [Magnani, Jared W.; Murabito, Joanne M.; Fontes, Joao D.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Magnani, Jared W.; Murabito, Joanne M.; Fontes, Joao D.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Moser, Carlee B.; Nelson, Kerrie P.; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Murabito, Joanne M.] Boston Univ, Gen Internal Med Sect, Dept Med, Boston, MA 02215 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, Dept Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu OI Murabito, Joanne/0000-0002-0192-7516; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU American Heart Association [09FTF219028]; NIH [HL092577, RO1AG028321, RC1-HL01056, 1R01HL102214, 5R21DA027021, 1RO1HL104156, 1K24HL105780, 6R01-NS17950, N01-HC25195]; Evans Center for Interdisciplinary Biomedical Research ARC FX Dr. Magnani is supported by American Heart Association Award 09FTF219028. This work was supported by grants from the NIH to Drs. Benjamin and Ellinor (HL092577), Dr. Benjamin (RO1AG028321, RC1-HL01056, 1R01HL102214) and Dr. Ellinor (5R21DA027021, 1RO1HL104156, 1K24HL105780) and 6R01-NS17950, N01-HC25195. This work was partially supported by the Evans Center for Interdisciplinary Biomedical Research ARC on "Atrial Fibrillation at Boston University (http://www.bumc.bu.edu/evanscenteribr/). NR 47 TC 4 Z9 4 U1 1 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 APR PY 2012 VL 163 IS 4 BP 729 EP 734 DI 10.1016/j.ahj.2012.01.010 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 930AD UT WOS:000303106800036 PM 22520541 ER PT J AU Zamani, P Ganz, P Libby, P Sutradhar, SC Rifai, N Nicholls, SJ Nissen, SE Kinlay, S AF Zamani, Payman Ganz, Peter Libby, Peter Sutradhar, Santosh C. Rifai, Nader Nicholls, Stephen J. Nissen, Steven E. Kinlay, Scott CA CAMELOT Study Investigators TI Relationship of antihypertensive treatment to plasma markers of vascular inflammation and remodeling in the Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis study SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; INTRAVASCULAR ULTRASOUND OBSERVATIONS; INTERLEUKIN-1 RECEPTOR ANTAGONIST; RANDOMIZED CONTROLLED-TRIAL; LIPID-LOWERING THERAPY; BLOOD-PRESSURE; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA AB Background Antihypertensive agents lower the risk of cardiovascular events, but whether they affect pathways important in inflammation and plaque remodeling in atherosclerosis is uncertain. We assessed whether 2 commonly used antihypertensive agents affected plasma biomarkers reflecting specific inflammatory and remodeling processes over 2 years in the Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) study. Methods The study was a randomized controlled trial of 2 antihypertensives (amlodipine and enalapril) compared with placebo in patients with coronary artery disease and diastolic blood pressure less than 100 mm Hg. In 196 subjects who had baseline and 2-year intravascular coronary ultrasound examinations, we measured plasma interleukin 18, interleukin 1 receptor antagonist, matrix metalloproteinase 9, neopterin, and C-reactive protein. Results for both treatment groups were pooled and compared with placebo. Results Antihypertensive treatment with either agent significantly lowered diastolic blood pressure (-4.7 vs placebo 1.3 mm Hg, P = .002) and progression of coronary atheroma (. percent atheroma volume 0.6 vs placebo 2.1, P = .031). Antihypertensive therapy did not affect plasma biomarkers of inflammation or plaque remodeling in the 135 subjects with baseline and 2-year biomarker samples. Progression in percent atheroma volume was significantly less in subjects taking statins at baseline (-2.5%, P = .0008). Conclusions In patients with coronary artery disease and well-controlled risk factors, antihypertensive therapy lowered blood pressure and progression of coronary atherosclerosis but did not affect plasma biomarkers of inflammation and remodeling. Antihypertensives may decrease atheroma progression by mechanisms other than those reflected by these plasma biomarkers. (Am Heart J 2012;163:735-40.) C1 [Kinlay, Scott] VA Boston Healthcare Syst, Div Cardiovasc, W Roxbury, MA 02132 USA. [Libby, Peter; Kinlay, Scott] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Libby, Peter; Rifai, Nader; Kinlay, Scott] Harvard Univ, Sch Med, Boston, MA USA. [Zamani, Payman] Univ Calif San Diego, Div Cardiovasc, San Diego, CA 92103 USA. [Ganz, Peter] Univ Calif San Francisco, Div Cardiovasc, San Francisco, CA 94143 USA. [Sutradhar, Santosh C.] Pfizer Inc, New York, NY USA. [Rifai, Nader] Childrens Hosp, Boston, MA 02115 USA. [Nicholls, Stephen J.; Nissen, Steven E.] Case Western Reserve Univ, Cleveland Clin Fdn, Cleveland Clin, Lerner Sch Med, Cleveland, OH 44106 USA. RP Kinlay, S (reprint author), VA Boston Healthcare Syst, Div Cardiovasc, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM scott.kinlay@va.org NR 37 TC 6 Z9 6 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 APR PY 2012 VL 163 IS 4 BP 735 EP 740 DI 10.1016/j.ahj.2011.12.008 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 930AD UT WOS:000303106800037 PM 22520542 ER PT J AU Boyce, RD Handler, SM Karp, JF Hanlon, JT AF Boyce, Richard D. Handler, Steven M. Karp, Jordan F. Hanlon, Joseph T. TI Age-Related Changes in Antidepressant Pharmacokinetics and Potential Drug-Drug Interactions: A Comparison of Evidence-Based Literature and Package Insert Information SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY LA English DT Article DE aged; antidepressants; drug interactions; drug product package inserts; pharmacokinetics ID HEALTHY MALE-SUBJECTS; CIMETIDINE INTERACTION; CLINICAL PHARMACOKINETICS; ELDERLY PATIENTS; STEADY-STATE; NORTRIPTYLINE PHARMACOKINETICS; PSYCHOTROPIC MEDICATIONS; CYTOCHROME P4502D6; POOR METABOLIZERS; IMPAIRS CLEARANCE AB Background: Antidepressants are among the most commonly prescribed psychotropic agents for older patients. Little is known about the best source of pharmacotherapy information to consult about key factors necessary to safely prescribe these medications to older patients. Objective: The Objective of this study was to synthesize and contrast information in the package insert (PI) with information found in the scientific literature about age-related changes of antidepressants in systemic clearance and potential pharmacokinetic drug drug interactions (DDIs). Methods: A comprehensive search of two databases (MEDLINE and EMBASE from January 1, 1975 to September 30, 2011) with the use of a combination of search terms (antidepressants, pharmacokinetics, and drug interactions) was conducted to identify relevant English language articles. This information was independently reviewed by two researchers and synthesized into tables. These same two researchers examined the most up-to-date PIs for the 26 agents available at the time of the study to abstract quantitative information about age-related decline in systemic clearance and potential DDIs. The agreement between the two information sources was tested with K statistics. Results: The literature reported age-related clearance changes for 13 antidepressants, whereas the PIs only had evidence about 4 antidepressants (kappa < 0.4). Similarly, the literature identified 45 medications that could potentially interact with a specific antidepressant, whereas the PIs only provided evidence about 12 potential medication antidepressant DDIs (kappa < 0.4). Conclusion: The evidence-based literature compared with PIs is the most complete pharmacotherapy information source about both age-related clearance changes and pharmacokinetic DDIs with antidepressants. Future rigorously designed observational studies are needed to examine the combined risk of antidepressants with age-related decline in clearance and potential DDIs on important health outcomes such as falls and fractures in older patients. (Am J Geriatr Pharmacother. 2012;10:139-150) (C) 2012 Elsevier HS Journals, Inc. All rights reserved. C1 [Boyce, Richard D.; Handler, Steven M.; Hanlon, Joseph T.] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA 15213 USA. [Boyce, Richard D.; Handler, Steven M.; Hanlon, Joseph T.] Univ Pittsburgh, Geriatr Pharmaceut Outcomes & Geroinformat Res &, Pittsburgh, PA 15213 USA. [Handler, Steven M.; Hanlon, Joseph T.] Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15213 USA. [Handler, Steven M.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Handler, Steven M.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Karp, Jordan F.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Karp, Jordan F.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Pharm & Therapeut, Sch Pharm, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. RP Hanlon, JT (reprint author), Univ Pittsburgh, Dept Biomed Informat, 3471 5th Ave,Kaufman Bldg,Suite 500, Pittsburgh, PA 15213 USA. EM jth14@pitt.edu OI Handler, Steven/0000-0002-3940-3224 FU Agency for Healthcare Research and Quality [K12HS019461, R01HS018721, R01 HS017695]; National Institute on Aging [K07AG033174, P30AG024827, T32 AG021885, R01AG034056, R56AG0207017, AG033575]; National Institute of Nursing Research [R01 NR010135]; National Center for Research Resources [KL2 RR024154, 3 UL1 RR024153-04S4]; Department of Veterans Affairs Health Services Research [IIR-06-062] FX We thank Subashan Perera, PhD, for his help calculating the kappa statistics. Dr. Richard Boyce received support from the Agency for Healthcare Research and Quality (grant K12HS019461). Additional support for the co-authors was provided by the Agency for Healthcare Research and Quality (grants R01HS018721 and R01 HS017695), National Institute on Aging (grants K07AG033174, P30AG024827, T32 AG021885, R01AG034056, R56AG0207017, and AG033575), National Institute of Nursing Research (grant R01 NR010135), National Center for Research Resources (grants KL2 RR024154 and 3 UL1 RR024153-04S4), and Department of Veterans Affairs Health Services Research (grant IIR-06-062). The content is solely the responsibility of the authors and does not represent the official views of the Agency for Healthcare Research and Quality or any of the other funding sources. NR 109 TC 9 Z9 9 U1 0 U2 0 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 APR PY 2012 VL 10 IS 2 BP 139 EP 150 DI 10.1016/j.amjopharm.2012.01.001 PG 12 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 930MC UT WOS:000303142500007 PM 22285509 ER PT J AU Weng, YC Sonni, A Labelle-Dumais, C de Leau, M Kauffman, WB Jeanne, M Biffi, A Greenberg, SM Rosand, J Gould, DB AF Weng, Yi-Chinn Sonni, Akshata Labelle-Dumais, Cassandre de Leau, Michelle Kauffman, W. Berkeley Jeanne, Marion Biffi, Alessandro Greenberg, Steven M. Rosand, Jonathan Gould, Douglas B. TI COL4A1 mutations in patients with sporadic late-onset intracerebral hemorrhage SO ANNALS OF NEUROLOGY LA English DT Article ID COLLAGEN-IV A1; CAENORHABDITIS-ELEGANS; HANAC SYNDROME; STROKE; DYSGENESIS; ANGIOPATHY; STABILITY; DEFECTS; DISEASE; BRAIN AB Objective: Mutations in the type IV collagen alpha 1 gene (COL4A1) cause dominantly inherited cerebrovascular disease. We seek to determine the extent to which COL4A1 mutations contribute to sporadic, nonfamilial, intracerebral hemorrhages (ICHs). Methods: We sequenced COL4A1 in 96 patients with sporadic ICH. The presence of putative mutations was tested in 145 ICH-free controls. The effects of rare coding variants on COL4A1 biosynthesis were compared to previously validated mutations that cause porencephaly, small vessel disease, and hereditary angiopathy, nephropathy, aneurysms, and cramps (HANAC) syndrome. Results: We identified 2 rare nonsynonymous variants in ICH patients that were not detected in controls, 2 rare nonsynonymous variants in controls that were not detected in patients, and 2 common nonsynonymous variants that were detected in patients and controls. No variant found in controls affected COL4A1 biosynthesis. Both variants (COL4A1(P352L) and COL4A1(R538G)) found only in patients changed conserved amino acids and impaired COL4A1 secretion much like mutations that cause familial cerebrovascular disease. Interpretation: This is the first assessment of the broader role for COL4A1 mutations in the etiology of ICH beyond a contribution to rare and severe familial cases and the first functional evaluation of the biosynthetic consequences of an allelic series of COL4A1 mutations that cause cerebrovascular disease. We identified 2 putative mutations in 96 patients with sporadic ICH and showed that these and other previously validated mutations inhibit secretion of COL4A1. Our data support the hypothesis that increased intracellular accumulation of COL4A1, decreased extracellular COL4A1, or both, contribute to sporadic cerebrovascular disease and ICH. ANN NEUROL 2012; 71: 470-477 C1 [Weng, Yi-Chinn; Labelle-Dumais, Cassandre; de Leau, Michelle; Kauffman, W. Berkeley; Jeanne, Marion; Gould, Douglas B.] UCSF Sch Med, Inst Human Genet, Dept Ophthalmol, San Francisco, CA USA. [Weng, Yi-Chinn; Labelle-Dumais, Cassandre; de Leau, Michelle; Kauffman, W. Berkeley; Jeanne, Marion; Gould, Douglas B.] UCSF Sch Med, Inst Human Genet, Dept Anat, San Francisco, CA USA. [Sonni, Akshata; Biffi, Alessandro; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Biffi, Alessandro; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Rosand, Jonathan] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. RP Gould, DB (reprint author), 10 Koret Way,Rm K235, San Francisco, CA 94122 USA. EM GouldD@vision.ucsf.edu FU American Heart Association [0830165N]; NIH [NINDS R01NS059727]; Larry L. Hillblom Foundation [2007-A-010-SUP]; Research to Prevent Blindness; Hersenstichcting [K08.85]; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775010N]; National Eye Institute [EY02162] FX This research was supported by grants from the American Heart Association (0830165N to D. B. G.), NIH (NINDS R01NS059727 to S. M. G. and J.R.), Larry L. Hillblom Foundation (2007-A-010-SUP D. B. G. for Y.C.W.), Research to Prevent Blindness (D. B. G. for W. B. K.), American Heart Association (D. B. G. for C. L. D.), Hersenstichcting (K08.85 M. dL.), American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775010N to A. B.), National Eye Institute (EY02162), and Research To Prevent Blindness Unrestricted Grant (to UCSF Department of Ophthalmology). NR 37 TC 37 Z9 39 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 APR PY 2012 VL 71 IS 4 BP 470 EP 477 DI 10.1002/ana.22682 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 929CW UT WOS:000303039800007 PM 22522439 ER PT J AU Friedman, J Roze, E Abdenur, JE Chang, R Gasperini, S Saletti, V Wali, GM Eiroa, H Neville, B Felice, A Parascandalo, R Zafeiriou, DI Arrabal-Fernandez, L Dill, P Eichler, FS Echenne, B Gutierrez-Solana, LG Hoffmann, GF Hyland, K Kusmierska, K Tijssen, MAJ Lutz, T Mazzuca, M Penzien, J Poll-The, BT Sykut-Cegielska, J Szymanska, K Thony, B Blau, N AF Friedman, Jennifer Roze, Emmanuel Abdenur, Jose E. Chang, Richard Gasperini, Serena Saletti, Veronica Wali, Gurusidheshwar M. Eiroa, Hernan Neville, Brian Felice, Alex Parascandalo, Ray Zafeiriou, Dimitrios I. Arrabal-Fernandez, Luisa Dill, Patricia Eichler, Florian S. Echenne, Bernard Gutierrez-Solana, Luis G. Hoffmann, Georg F. Hyland, Keith Kusmierska, Katarzyna Tijssen, Marina A. J. Lutz, Thomas Mazzuca, Michel Penzien, Johann Bwee Tien Poll-The Sykut-Cegielska, Jolanta Szymanska, Krystyna Thoeny, Beat Blau, Nenad TI Sepiapterin reductase deficiency: A Treatable Mimic of Cerebral Palsy SO ANNALS OF NEUROLOGY LA English DT Article ID DOPA-RESPONSIVE DYSTONIA; CYCLOHYDROLASE-I GENE; TETRAHYDROBIOPTERIN DEFICIENCIES; HYPERPHENYLALANINEMIA; HYPERSOMNIA; DISORDERS; MUTATIONS; SIBLINGS; FEATURES; REGION AB Objective: Sepiapterin reductase deficiency (SRD) is an under-recognized levodopa-responsive disorder. We describe clinical, biochemical, and molecular findings in a cohort of patients with this treatable condition. We aim to improve awareness of the phenotype and available diagnostic and therapeutic strategies to reduce delayed diagnosis or misdiagnosis, optimize management, and improve understanding of pathophysiologic mechanisms. Methods: Forty-three individuals with SRD were identified from 23 international medical centers. The phenotype and treatment response were assessed by chart review using a detailed standardized instrument and by literature review for cases for which records were unavailable. Results: In most cases, motor and language delays, axial hypotonia, dystonia, weakness, oculogyric crises, and diurnal fluctuation of symptoms with sleep benefit become evident in infancy or childhood. Average age of onset is 7 months, with delay to diagnosis of 9.1 years. Misdiagnoses of cerebral palsy (CP) are common. Most patients benefit dramatically from levodopa/carbidopa, often with further improvement with the addition of 5-hydroxytryptophan. Cerebrospinal fluid findings are distinctive. Diagnosis is confirmed by mutation analysis and/or enzyme activity measurement in cultured fibroblasts. Interpretation: Common, clinical findings of SRD, aside from oculogyric crises and diurnal fluctuation, are nonspecific and mimic CP with hypotonia or dystonia. Patients usually improve dramatically with treatment. Consequently, we recommend consideration of SRD not only in patients with levodopa-responsive motor disorders, but also in patients with developmental delays with axial hypotonia, and patients with unexplained or atypical presumed CP. Biochemical investigation of cerebrospinal fluid is the preferred method of initial investigation. Early diagnosis and treatment are recommended to prevent ongoing brain dysfunction. ANN NEUROL 2012; 71: 520-530 C1 [Friedman, Jennifer] Rady Childrens Hosp, San Diego, CA 92123 USA. [Friedman, Jennifer] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Friedman, Jennifer] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Roze, Emmanuel] Salpetriere Hosp, APHP, Dept Neurol, Paris, France. [Roze, Emmanuel] Salpetriere Hosp, INSERM, UMRS 975, Paris, France. [Roze, Emmanuel] Salpetriere Hosp, CNRS CRICM 7225, Paris, France. [Abdenur, Jose E.; Chang, Richard] Childrens Hosp Orange Cty, Orange, CA 92668 USA. [Gasperini, Serena] Univ Florence, Anna Meyer Childrens Hosp, Pediat Neurol Unit, Dept Neurosci, Florence, Italy. [Gasperini, Serena] Univ Florence, Anna Meyer Childrens Hosp, Metab & Neuromuscular Disorders Unit, Dept Neurosci, Florence, Italy. [Saletti, Veronica] IRCCS Fdn, Carlo Besta Neurol Inst, Dev Neurol Unit, Milan, Italy. [Wali, Gurusidheshwar M.] Neurospecial Ctr, Belgaum, India. [Eiroa, Hernan] Hosp Pediat JP Garrahan, Serv Errores Congenitos Metab, Buenos Aires, DF, Argentina. [Neville, Brian] UCL, Inst Child Hlth, Neurosci Unit, London, England. [Felice, Alex] Univ Malta, Fac Med & Surg, Dept Physiol & Biochem, Mol Genet Lab, Msida, Malta. [Parascandalo, Ray] Mater Hosp, Dept Pediat, Valletta, Malta. [Zafeiriou, Dimitrios I.] Aristotle Univ Thessaloniki, Dept Pediat 1, GR-54006 Thessaloniki, Greece. [Arrabal-Fernandez, Luisa] Virgen de las Nieves Hosp, Dept Pediat, Granada, Spain. [Dill, Patricia] Univ Childrens Hosp, Div Pediat Neurol & Dev Med, Basel, Switzerland. [Eichler, Florian S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Child Neurol, Boston, MA USA. [Echenne, Bernard] Gui de Chauliac Hosp, Dept Pediat Neurol, Montpellier, France. [Gutierrez-Solana, Luis G.] Hosp Infantil Univ Nino Jesus, Secc Neurol, Madrid, Spain. [Hoffmann, Georg F.; Lutz, Thomas; Blau, Nenad] Univ Childrens Hosp Heidelberg, Heidelberg, Germany. [Hyland, Keith] Med Neurogenet, Atlanta, GA USA. [Kusmierska, Katarzyna] Childrens Mem Hlth Inst, Dept Biochem & Expt Med, Lab Metab Disorders, Warsaw, Poland. [Tijssen, Marina A. J.] Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands. [Mazzuca, Michel] Univ Lyon 1, INSERM, U1028, CNRS,UMR5292,Lyon Neurosci Res Ctr,Brain Dynam &, Lyon, France. [Mazzuca, Michel] Hosp Civils Lyon, Hop Edouard Herriot, Serv Audiol & Exporat Orofaciales, Lyon, France. [Penzien, Johann] Klin Kinder & Jugendliche, Augsburg, Germany. [Bwee Tien Poll-The] Univ Amsterdam, Acad Med Ctr, Dept Pediat Neurol, NL-1105 AZ Amsterdam, Netherlands. [Sykut-Cegielska, Jolanta] Childrens Mem Hlth Inst, Dept Metab Dis, Warsaw, Poland. [Szymanska, Krystyna] Polish Acad Sci, Mossakowski Med Res Ctr, Dept Expt & Clin Neuropathol, Warsaw, Poland. [Thoeny, Beat; Blau, Nenad] Univ Childrens Hosp Zurich, Div Clin Chem & Biochem, Zurich, Switzerland. [Thoeny, Beat; Blau, Nenad] Zurich Ctr Integrat Human Physiol, Zurich, Switzerland. RP Friedman, J (reprint author), Rady Childrens Hosp, 8010 Frost St,Suite 400, San Diego, CA 92123 USA. EM jrfriedman@rchsd.org RI Zafeiriou, Dimitrios/N-2641-2013 OI Zafeiriou, Dimitrios/0000-0003-2187-9299 FU Swiss National Science Foundation [31003A-119982/2]; INSERM (COS-SEC); AP-HP (DRC-PHRC); Dystonia Coalition (Pilot project); Ipsen Pharmaceuticals; Merz Pharmaceuticals; EC plan 6; Esmee Fairbairn Foundation; Sanofi; Prinses Beatrix Fonds; STW Technology Foundation; BioMarin Pharmaceutical; Merck Serono FX This study was funded in part by the Swiss National Science Foundation grant No. 31003A-119982/2 (to N.B. and B. T.). The funding source had no role in study design; collection, analysis, or interpretation of the data; or writing of the report.; J.F.: consultancy, BioMarin Pharmaceuticals. E. R.: board membership, Orkyn, Ipsen Pharmaceuticals, and Merz Pharmaceuticals; grants/grants pending, INSERM (COS-SEC), AP-HP (DRC-PHRC), Dystonia Coalition (Pilot project), Ipsen Pharmaceuticals, and Merz Pharmaceuticals; travel expenses, Teva Pharmaceuticals, Dystonia Coalition, Dystonia Medical Research Foundation, Movement Disorders Society, World Federation of Neurology Association of Parkinsonism and Related Disorders, Bachmann and Strauss Foundation. B. N.: grants/grants pending, EC plan 6, Esmee Fairbairn Foundation; speaking fees, Sanofi; royalties, pending for buccal midazolam with Special Products Ltd; travel expenses, Sanofi. K. H.: Vice President of Medical Neurogenetics, a company that provides biochemical and molecular testing for sepiapterin reductase deficiency. M.A.J.T.: grants/grants pending, Prinses Beatrix Fonds, STW Technology Foundation, Ipsen Pharmaceuticals. N. B.: grants, BioMarin Pharmaceutical, Merck Serono; speaking fees, Merck Serono. NR 33 TC 39 Z9 41 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2012 VL 71 IS 4 BP 520 EP 530 DI 10.1002/ana.22685 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 929CW UT WOS:000303039800012 PM 22522443 ER PT J AU Viswanathan, A Greenberg, SM AF Viswanathan, Anand Greenberg, Steven M. TI Cerebral amyloid angiopathy in the elderly Reply SO ANNALS OF NEUROLOGY LA English DT Letter C1 [Viswanathan, Anand] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Trials Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Viswanathan, A (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2012 VL 71 IS 4 BP 586 EP 586 DI 10.1002/ana.23564 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 929CW UT WOS:000303039800020 ER PT J AU Brown, JE Fominaya, C Christensen, KJ McConnell, SA Lamp, KC AF Brown, Jack E. Fominaya, Cory Christensen, Keith J. McConnell, Scott A. Lamp, Kenneth C. TI Daptomycin Experience in Critical Care Patients: Results from a Registry SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE bacteremia; daptomycin; Enterococcus faecium; intensive care; sepsis; Staphylococcus aureus ID SEVERE SEPSIS; VANCOMYCIN; OUTCOMES; THERAPY; NEPHROTOXICITY; INFECTIONS; PATHOGENS; SAFETY AB BACKGROUND: Vancomycin is often the drug of choice in critically ill patients with gram-positive infections, although circumstances often prevent its use. In these situations, clinicans are frequently left with limited data regarding alternative agents. OBJECTIVE: To describe patients with reported sepsis receiving daptomycin in a critical care unit. METHODS: This multicenter, noncomparative, noninterventional study identified patients in critical care units, using the Cubicin Outcomes Registry and Experience (CORE) 2005-2009 registry. A descriptive account of patient characteristics, infectious etiology, outcomes at the end of daptomycin therapy, and 30-day mortality is reported. Nonevaluable patients were excluded from the efficacy analysis but included in the safety analysis. RESULTS: We identified 128 patients, 98 (77%) of whom were evaluable for efficacy. Patient characteristics for the efficacy population were 55 (56%) males, 30 (31%) aged 66 years or older, 38 (39%) had creatinine clearance less than 30 mL/min, and 27 (28%) were on dialysis. Common underlying diseases included acute or chronic renal failure 44 (45%), hypertension 40 (41%), and diabetes 27 (28%). Seventy-two (73%) patients were bacteremic. The most common pathogens found were methicillin-resistant Staphylococcus aureus (32%), vancomycin-resistant Enterococcus faecium (21%), and coagulase-negative staphylococci (20%). Prior to daptomycin, antibiotics were used in 84 (86%) patients, most commonly vancomycin (65/84; 77%). The median (range) initial daptomycin dose was 6 mg/kg (3-10) and duration of 10 days (1-58). Overall success rate was 70% (31% cured; 39% improved). Twelve adverse events possibly related to daptomycin were reported in 9 of 128 (7%) patients in the safety population; 4 of these in 4 (3%) patients were serious. The mortality rate within 30 days of completing daptomycin was 42 of 128 (33%) patients. CONCLUSIONS: These data provide preliminary results on the use of daptomycin in critically ill patients with complicated conditions. Controlled studies are needed to best evaluate daptomycin use in these patients. C1 [Lamp, Kenneth C.] Cubist Pharmaceut Inc, Registry Res, Lexington, MA USA. [Brown, Jack E.] SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Buffalo, NY 14260 USA. [Brown, Jack E.] Univ Rochester, Sch Med, Buffalo, NY USA. [Fominaya, Cory] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Christensen, Keith J.] Creighton Univ, Sch Pharm & Hlth Profess, Omaha, NE 68178 USA. [McConnell, Scott A.] Cubist Pharmaceut Inc, Sci Training & Operat, Omaha, NE USA. RP Lamp, KC (reprint author), Cubist Pharmaceut Inc, Registry Res, Lexington, MA USA. EM kenneth.lamp@cubist.com FU Cubist Pharmaceuticals FX This study was funded by Cubist Pharmaceuticals, of which Dr. Brown was an employee at the time of the study, Dr. Christensen has received honoraria for consultant work with Cubist Pharmaceuticals; and Drs. McConnell and Lamp are employees of and own stock in Cubist Pharmaceuticals. NR 16 TC 4 Z9 4 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD APR PY 2012 VL 46 IS 4 BP 495 EP 502 DI 10.1345/aph.1Q490 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 930XE UT WOS:000303177300004 PM 22454446 ER PT J AU Vassy, JL Meigs, JB AF Vassy, Jason L. Meigs, James B. TI Is Genetic testing useful to predict type 2 diabetes? SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE type 2 diabetes genetics; risk prediction models; genotype risk scores ID GENOME-WIDE ASSOCIATION; IMPAIRED GLUCOSE-TOLERANCE; LARGE-SCALE ASSOCIATION; FASTING GLUCOSE; RISK PREDICTION; TCF7L2 GENE; SUSCEPTIBILITY LOCI; INSULIN-RESISTANCE; PHYSICAL-ACTIVITY; LIFE-STYLE AB The early identification of individuals at risk for type 2 diabetes (T2D) enables prevention. Recent genome-wide association studies (GWAS) have added at least 40 genetic variants to the list of already well characterized T2D risk predictors, including family history, obesity, and elevated fasting plasma glucose levels. Although these variants can significantly predict T2D alone and as a part of genotype risk scores, they do not yet offer clinical discrimination beyond that achieved with common clinical measurements. Future progress on at least two research fronts may improve the predictive performance of genotype information. First, expanded GWAS efforts in non-European populations will allow targeted sequencing of risk loci and the identification of true causal variants. Second, studies with longer prediction time horizons may demonstrate that genotype information performs better than clinical risk predictors over a longer period of the life course. At present, however, genetic testing cannot be recommended for clinical 120 risk prediction in adults. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Vassy, Jason L.; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Vassy, Jason L.; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Vassy, Jason L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Vassy, JL (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jvassy@partners.org; jmeigs@partners.org FU NIH from the Health Resources and Services Administration [T32 HP12706]; NIH; NIDDK [K24 DK080140, R01 DK078616] FX JLV is supported by NIH National Research Service Award grant T32 HP12706 from the Health Resources and Services Administration and the NIH Loan Repayment Program (NIDDK). JBM is supported by NIDDK K24 DK080140 and R01 DK078616. The sponsors had no role in the collection, analysis, or interpretation of data or in the writing of this manuscript. NR 81 TC 29 Z9 30 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-690X J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD APR PY 2012 VL 26 IS 2 BP 189 EP 201 DI 10.1016/j.beem.2011.09.002 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 932KI UT WOS:000303289600007 PM 22498248 ER PT J AU Bhutta, HY Deelman, T Rhoads, DB Tavakkolizadeh, A AF Bhutta, H. Y. Deelman, T. Rhoads, D. B. Tavakkolizadeh, A. TI Disruption of eating patterns and intestinal glucose sensing in obesity-induced diabetes SO BRITISH JOURNAL OF SURGERY LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Academic-and-Research-Surgery CY JAN 04-05, 2012 CL Univ Nottingham Med Sch, Nottingham, ENGLAND SP Soc Acad & Res Surg HO Univ Nottingham Med Sch C1 [Bhutta, H. Y.; Deelman, T.; Tavakkolizadeh, A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rhoads, D. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bhutta, H. Y.; Deelman, T.; Rhoads, D. B.; Tavakkolizadeh, A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD APR PY 2012 VL 99 SU 4 BP 4 EP 4 PG 1 WC Surgery SC Surgery GA 930PP UT WOS:000303151900011 ER PT J AU Vacanti, JP AF Vacanti, J. P. TI Tissue engineering and the road to whole organs SO BRITISH JOURNAL OF SURGERY LA English DT Editorial Material ID TRANSPLANTATION C1 Massachusetts Gen Hosp, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Lab Tissue Engn & Organ Fabricat, 55 Fruit St,Warren 1151, Boston, MA 02114 USA. EM jvacanti@partners.org NR 9 TC 15 Z9 16 U1 1 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD APR PY 2012 VL 99 IS 4 BP 451 EP 453 DI 10.1002/bjs.7819 PG 3 WC Surgery SC Surgery GA 930PA UT WOS:000303150400002 PM 22287115 ER PT J AU Lee, NG Xue, H Lerner, LB AF Lee, Nora G. Xue, Hui Lerner, Lori B. TI Trends and attitudes in surgical management of benign prostatic hyperplasia SO CANADIAN JOURNAL OF UROLOGY LA English DT Article DE benign prostatic hyperplasia; surgical techniques; technology ID LASER AB Introduction: Surgical management of benign prostatic hyperplasia (BPH) has changed over the past 15 years with newer techniques emerging such as laser therapy that can be used with anticoagulation, an increasing issue with modern patients. We sought to evaluate current trends in procedure utilization based on age, location, type of practice, and experience. We also hoped to determine what factors influence surgeons' decisions to choose or reject particular surgical techniques. Methods and materials: A 90-item on-line survey was sent via electronic mail to the American Urological Association (AUA), Veterans Administration, Society for Government Service Urologists, and Endourological Society. Data concerning utilization of 12 BPH surgical techniques were analyzed and compared to the surgeons' demographics using categorical data analysis and logistic regression. Results: Of approximately 5500 urologists contacted, 600 urologists replied with 570 currently performing BPH surgery. The two procedures that continue to be utilized by urologists are open prostatectomy (OP) at 78% and monopolar trans urethral resection of prostate (TURP) at 73%. When stratified by urologist age and year of residency completion, there were no differences in procedure utilization. There were no differences in types of procedures utilized between AUA sections except in the Northeastern AUA section which utilized less monopolar TURP and the New York section which utilized less photoselective vaporization (PVP). Higher volume surgeons were more likely to perform holmium laser enucleation of the prostate (HoLEP), diode laser vaporization of the prostate, holmium laser ablation of the prostate (HoLAP), and thulium laser ablation. There were no trends for low volume surgeons. There were no differences in types of procedures performed in full time academic versus non-academic settings except for robotic prostatectomy and button TURP which were utilized more often in academic settings. Urologists were more likely to accept a technique that produces good clinical outcomes, is safe in practice, and minimally invasive. Urologists reject procedures most frequently due to preference for another technique or lack of training/equipment. Interestingly, reimbursement/cost issues were never reported as primary reasons for acceptance/rejection of any approach. Conclusions: Change in technology has led urologists to change their approach to surgical treatment of BPH. OP and monopolar TURP are still the procedures utilized by most urologists, however, laser therapy is emerging as a commonly used technique. As more high-risk patients are treated, laser therapies may become a more popularized technique. Further larger scale studies evaluating surgeon attitudes might clarify how changing technology influences practice patterns. C1 [Lee, Nora G.] Boston Univ, Med Ctr, Dept Urol, Boston, MA USA. [Xue, Hui] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. [Lerner, Lori B.] Vet Affairs Boston Healthcare Syst, Dept Urol, Boston, MA USA. RP Lerner, LB (reprint author), VA Boston Healthcare Syst, Dept Surg, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 9 TC 13 Z9 16 U1 1 U2 4 PU CANADIAN J UROLOGY PI ST LAURENT PA 2330 WARD ST, STE 604, ST LAURENT, QUEBEC H4M 2V6, CANADA SN 1195-9479 J9 CAN J UROL JI Can. J. Urol. PD APR PY 2012 VL 19 IS 2 BP 6170 EP 6175 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 932KQ UT WOS:000303290400005 PM 22512959 ER PT J AU Lee, JE Wei, EK Fuchs, CS Hunter, DJ Lee, IM Selhub, J Stampfer, MJ Willett, WC Ma, J Giovannucci, E AF Lee, Jung Eun Wei, Esther K. Fuchs, Charles S. Hunter, David J. Lee, I-Min Selhub, Jacob Stampfer, Meir J. Willett, Walter C. Ma, Jing Giovannucci, Edward TI Plasma folate, methylenetetrahydrofolate reductase (MTHFR), and colorectal cancer risk in three large nested case-control studies SO CANCER CAUSES & CONTROL LA English DT Article DE Folate; Methylenetetrahydrofolate reductase (MTHFR); Colorectal cancer ID UNMETABOLIZED FOLIC-ACID; COMMON MUTATION; DIETARY-FOLATE; PUBLIC-HEALTH; COLON-CANCER; FORTIFICATION; METAANALYSIS; ADENOMA; GENE; HOMOCYSTEINE AB Few prospective studies have examined the associations between blood levels of folate, in conjunction with methylenetetrahydrofolate reductase (MTHFR) polymorphisms, and colorectal cancer. We evaluated the associations between plasma folate, MTHFR C677T, and A1298C, and colorectal cancer in three large prospective studies: the Nurses' Health Study, the Health Professionals Follow-up Study, and the Physicians' Health Study. A total of 602 incident cases were identified and individually matched to controls who provided blood specimens. We used conditional logistic regression to calculate the relative risk (RR) and 95% confidence interval (95% CI) and then pooled the estimates using a random effects model. We found a lower risk of colorectal cancer among participants with low plasma folate levels: compared with the lowest quartile, RRs (95% CIs) for each successively higher quartile of plasma folate levels were 1.55 (1.14-2.11), 1.37 (1.00-1.88), and 1.47 (1.07-2.01; P for trend = 0.10). For the MTHFR polymorphisms, RRs (95% CIs) were 0.62 (0.44-0.90) for 677TT versus CC/CT and 0.68 (0.31-1.51) for 1298CC versus AC/AA, and these lower-risk genotypes were associated with lower circulating plasma folate levels. When we partitioned the variation in plasma folate levels, variation due to folate intake was not positively associated with colorectal cancer risk. We found that low plasma folate levels were associated with lower risk of colorectal cancer. The reasons underlying a lower risk of colorectal cancer with low plasma folate levels require elucidation because plasma folate levels can reflect dietary intake, genetic influences, and other factors. C1 [Wei, Esther K.; Fuchs, Charles S.; Hunter, David J.; Stampfer, Meir J.; Willett, Walter C.; Ma, Jing; Giovannucci, Edward] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Lee, Jung Eun] Sookmyung Womens Univ, Dept Food & Nutr, Seoul, South Korea. [Wei, Esther K.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hunter, David J.; Lee, I-Min; Stampfer, Meir J.; Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Lee, I-Min] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Selhub, Jacob] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA. RP Giovannucci, E (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM edward.giovannucci@channing.harvard.edu OI Lee, Jung Eun/0000-0003-1141-878X FU National Cancer Institute [CA87969, CA55075, CA42182, CA34944, CA40360, CA97193]; National Heart, Lung, and Blood Institute [HL26490, HL34595]; Prevent Cancer Foundation FX Our study is supported by National Cancer Institute CA87969, CA55075, CA42182, CA34944, CA40360, and CA97193, National Heart, Lung, and Blood Institute HL26490 and HL34595, and Prevent Cancer Foundation. The sponsors of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. NR 34 TC 22 Z9 22 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 2012 VL 23 IS 4 BP 537 EP 545 DI 10.1007/s10552-012-9911-3 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 931QE UT WOS:000303233600002 PM 22367721 ER PT J AU Schernhammer, ES Giobbie-Hurder, A Gantman, K Savoie, J Scheib, R Parker, LM Chen, WY AF Schernhammer, E. S. Giobbie-Hurder, A. Gantman, K. Savoie, J. Scheib, R. Parker, L. M. Chen, W. Y. TI A randomized controlled trial of oral melatonin supplementation and breast cancer biomarkers SO CANCER CAUSES & CONTROL LA English DT Article DE Melatonin; aMT6s; Estradiol; IGF; Postmenopausal; Breast cancer ID PREMENOPAUSAL WOMEN; ESTRADIOL; TAMOXIFEN; CHEMOTHERAPY; HYPOTHESIS; THERAPY; GROWTH; SLEEP; RISK AB We examined compliance with and the effects of melatonin supplementation on breast cancer biomarkers (estradiol, insulin-like growth factor I (IGF-1), insulin-like growth factor-binding protein 3 (IGFBP-3), and the IGF-1/IGFBP-3 ratio) in postmenopausal breast cancer survivors. In a double-blind, placebo-controlled study, postmenopausal women with a prior history of stages 0-III breast cancer who had completed active cancer treatment (including hormonal therapy) were randomly assigned to either 3 mg oral melatonin (n = 48) or placebo daily for 4 months. Plasma samples were collected at baseline and after the completion of the intervention. The primary endpoints were compliance and change in estradiol and IGF-1/IGFBP-3 levels. Ninety-five women were randomized (48 to melatonin and 47 to placebo). Eighty-six women (91%) completed the study and provided pre- and postintervention bloods. Melatonin was well tolerated without any grade 3/4 toxicity and compliance was high (89.5%). Overall, among postmenopausal women with a prior history of breast cancer, a 4-month course of 3 mg melatonin daily did not influence circulating estradiol, IGF-1, or IGFBP-3 levels. Compliance was comparable between the two groups. Short-term melatonin treatment did not influence the estradiol and IGF-1/IGBBP-3 levels. Effects of longer courses of melatonin among premenopausal women are unknown. Low baseline estradiol levels in our study population may have hindered the ability to detect any further estradiol-lowering effects of melatonin. C1 [Schernhammer, E. S.; Chen, W. Y.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Schernhammer, E. S.] Harvard Univ, Sch Med, Boston, MA USA. [Schernhammer, E. S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Schernhammer, E. S.] LBI ACR CTO, Vienna, Austria. [Schernhammer, E. S.] ACR ITR VIEnna CEADDP, Vienna, Austria. [Giobbie-Hurder, A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gantman, K.; Savoie, J.; Scheib, R.; Parker, L. M.; Chen, W. Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Schernhammer, ES (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM eva.schernhammer@channing.harvard.edu FU National Institutes of Cancer, USA [R03 CA123597]; NIH FX This study was supported by a grant from the National Institutes of Cancer, USA (grant No R03 CA123597 "A Pilot Trial of Oral Melatonin Supplementation in Breast Cancer Survivors," PI Schernhammer). Because in the United States melatonin is sold as a dietary supplement and not as a drug and the endpoints were biomarkers, no trial registration number was assigned to this NIH-funded study. The funding source had no role in the design or analysis of the study or in the decision to submit the manuscript for publication. We are grateful to the participants of this trial, as well as to the staff at the Dana-Farber Cancer Institute that helped facilitate the trial's conduct. NR 29 TC 7 Z9 8 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 2012 VL 23 IS 4 BP 609 EP 616 DI 10.1007/s10552-012-9927-8 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 931QE UT WOS:000303233600009 PM 22370698 ER PT J AU Nagler, RH Puleo, E Sprunck-Harrild, K Emmons, KM AF Nagler, Rebekah H. Puleo, Elaine Sprunck-Harrild, Kim Emmons, Karen M. TI Internet use among childhood and young adult cancer survivors who smoke: implications for cessation interventions SO CANCER CAUSES & CONTROL LA English DT Article DE Childhood cancer survival; Smoking cessation; Internet-based interventions; Internet use ID TRENDS SURVEY HINTS; HEALTH INFORMATION; ADOLESCENT CANCER; CYBERINFRASTRUCTURE; PARTNERSHIP AB Objective To identify patterns of Internet use among childhood and young adult cancer survivors who smoke. Methods Baseline assessment data were collected from 2005 to 2008 for the Partnership for Health-2 (PFH-2) study, a web-based smoking cessation intervention for childhood and young adult cancer survivors. Participants were surveyed about their Internet access and use. Sociodemographic, clinical, and psychosocial data also were collected. Results Internet access and use was widespread among PFH-2 participants. However, older, less-educated, and female survivors reported less frequent Internet use, even when they had access to the Internet at home and/or at work. These associations were significant in multivariable analyses. Conclusions Although the digital divide is narrowing, Internet use and engagement remains socially patterned. web-based prevention interventions are a promising method of reaching this geographically dispersed, high-risk population, but certain subgroups-particularly older and lower socioeconomic status survivors-might be missed by this approach. C1 [Nagler, Rebekah H.; Sprunck-Harrild, Kim; Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Nagler, Rebekah H.; Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Puleo, Elaine] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. RP Nagler, RH (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave,LW 601, Boston, MA 02215 USA. EM rebekah_nagler@dfci.harvard.edu FU National Cancer Institute (NCI) [5 R01-CA106914-05, K05-CA124415, 5 R25-CA057711-17] FX This research was supported by grants 5 R01-CA106914-05 and K05-CA124415 from the National Cancer Institute (NCI). Funding support for the lead author was also provided through NCI by the Harvard Education Program in Cancer Prevention and Control (5 R25-CA057711-17). The authors would like to thank Nancy Klockson for her assistance in manuscript preparation, as well as the participating survivorship programs: St. Jude Children's Research Hospital, Memorial Sloan Kettering Cancer Center, Princess Margaret Hospital, The Hospital for Sick Children, and Dana-Farber Cancer Institute/Partners HealthCare. NR 27 TC 7 Z9 7 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 2012 VL 23 IS 4 BP 647 EP 652 DI 10.1007/s10552-012-9926-9 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 931QE UT WOS:000303233600013 PM 22370697 ER PT J AU Poon, H Chang, MH Fung, HB AF Poon, Henry Chang, Mei H. Fung, Horatio B. TI Ceftaroline Fosamil: A Cephalosporin With Activity Against Methicillin-Resistant Staphylococcus Aureus SO CLINICAL THERAPEUTICS LA English DT Review DE ceftaroline; cephalosporin; community-acquired pneumonia; methicillin-resistant Staphylococcus aureus; skin and skin structure infections ID IN-VITRO ACTIVITY; COMMUNITY-ACQUIRED PNEUMONIA; SKIN-STRUCTURE INFECTIONS; RABBIT ENDOCARDITIS MODEL; GRAM-NEGATIVE PATHOGENS; SOFT-TISSUE INFECTIONS; COMPLICATED SKIN; VANCOMYCIN-INTERMEDIATE; STREPTOCOCCUS-PNEUMONIAE; ANTIMICROBIAL ACTIVITY AB Background: Ceftaroline is a cephalosporin with expanded gram-positive activity recently approved for clinical uses by the US Food and Drug Administration. Objective: This article provides an overview of the in vitro and in vivo activities, mechanism of action, pharmacologic and pharmacokinetic properties, clinical efficacy, and tolerability of ceftaroline. Methods: Relevant information was identified through a search of Pub Med (1990 April 2011), EM-BASE (1990 April 2011), International Pharmaceutical Abstracts (1970 April 2011), and Google Scholar using the key words ceftaroline, PPI-0903, PPI-0903M, T-91825, and TAK-599. A review of the reference lists of identified articles, a search of the US Food and Drug Administration Web site, and posters and abstracts from scientific meetings yielded additional publications. Results: In vitro, ceftaroline exhibits activity against most aerobic gram-positive isolates, common aerobic gram-negative respiratory pathogens, and some gram-positive anaerobes. The MIC range for most Staphylococcus aureus isolates, including vancomycin-resistant strains was between <= 0.008 and 4 mu g/mL. In Phase III studies (CANVAS 1 and CANVAS 2), ceftaroline was found to be noninferior to vancomycin + aztreonam for the treatment of complicated skin and skin-structure infections, with a clinical cure rate of 91.6% among clinically evaluable patients (ceftaroline versus vancomycin + aztreonam: difference, -1.1; 95% CI, -4.2 to 2.0; P = NS). Ceftaroline's efficacy has also been assessed for the treatment of community-acquired pneumonia in 2 Phase III studies (FOCUS 1 and FOCUS 2) and was equivalent to ceftriaxone, with cure rates of 84.3% and 77.7%, respectively, among clinically evaluable patients in the combined analysis (ceftaroline versus ceftriaxone: difference, 6.7; 95% CI, 1.6 to 11.8). The recommended dosage for patients 18 years and older is 600 mg IV every 12 hours. Dosage adjustment is necessary in patients with renal impairment (creatinine clearance <= 50 mL/min). The pharmacokinetic properties of ceftaroline in patients with hepatic impairments are currently unavailable. Ceftaroline appeared to be well tolerated generally. The most frequently (>3%) reported adverse events were nausea, headaches, diarrhea, pruritus, rash, and insomnia; all were usually mild to moderate, self-limiting, and of little clinical significance. Conclusions: Ceftaroline is a cephalosporin with broad gram-positive activity, including Methicillin-resistant S aureus and vancomycin-resistant S aureus. Its gram-negative activity includes common respiratory pathogens and members of the Enterobacteriaceae. Clinical trials have reported that ceftaroline was noninferior to ceftriaxone, and vancomycin + aztreonam for the treatment of community-acquired pneumonia and complicated skin and skin-structure infections, respectively. (Clin Ther. 2012;34:743-765) Published by Elsevier HS Journals, Inc. C1 [Poon, Henry; Chang, Mei H.; Fung, Horatio B.] James J Peters Vet Affairs Med Ctr, Serv Pharm, Bronx, NY 10468 USA. RP Poon, H (reprint author), James J Peters Vet Affairs Med Ctr, Serv Pharm, 130 W Kingsbridge Rd 119, Bronx, NY 10468 USA. EM Henry.Poon@VA.gov NR 89 TC 17 Z9 19 U1 1 U2 12 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD APR PY 2012 VL 34 IS 4 BP 743 EP 765 DI 10.1016/j.clinthera.2012.02.025 PG 23 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 931KZ UT WOS:000303220100002 PM 22444785 ER PT J AU Kapoor, R Elston, DM AF Kapoor, Roger Elston, Dirk M. TI What's Eating You? The Sticktight Flea (Echidnophaga gallinacea) SO CUTIS LA English DT Editorial Material ID NEW-MEXICO; DOGS; FLORIDA; ECTOPARASITES; INFESTATION; CATS C1 [Kapoor, Roger] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Elston, Dirk M.] Geisinger Med Ctr, Dept Dermatol, Danville, PA 17822 USA. [Elston, Dirk M.] Geisinger Med Ctr, Dept Pathol, Danville, PA 17822 USA. RP Elston, DM (reprint author), Ackerman Acad Dermatopathol, 145 E 32nd St,10th Floor, New York, NY 10016 USA. EM delston@dermpathdiagnostics.com NR 11 TC 1 Z9 1 U1 0 U2 2 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 0011-4162 J9 CUTIS JI Cutis PD APR PY 2012 VL 89 IS 4 BP 157 EP 158 PG 2 WC Dermatology SC Dermatology GA 932EJ UT WOS:000303272900003 PM 22611740 ER PT J AU Le, DE Bragadeesh, T Zhao, Y Wang, YG Zha, DG Kaul, S AF Le, D. Elizabeth Bragadeesh, Thanjavur Zhao, Yan Wang, Yue-Gang Zha, Daogang Kaul, Sanjiv TI Detection of coronary stenosis with myocardial contrast echocardiography using regadenoson, a selective adenosine A(2A) receptor agonist SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING LA English DT Article DE Regadenoson; Stress testing; Myocardial contrast echocardiography ID EMISSION COMPUTED-TOMOGRAPHY; PHARMACOLOGICAL STRESS ECHOCARDIOGRAPHY; ARTERY-DISEASE; DIPYRIDAMOLE-STRESS; CONSCIOUS DOGS; BLOOD-FLOW; ULTRASOUND CONTRAST; PROGNOSTIC VALUE; PERFUSION; SAFETY AB Aims Regadenoson is comparable to adenosine in pharmacologic radionuclide stress tests but has not been studied with stress myocardial contrast echocardiography. This study assessed the haemodynamic profile and ability of regadenoson, a novel selective A(2A) receptor agonist, to detect coronary artery stenosis during myocardial contrast echocardiography. Methods and results Myocardial contrast echocardiography was performed to measure myocardial blood volume, myocardial blood flow velocity, and total regional myocardial blood flow before and after administration of regadenoson (5 mu g kg(-1), 10 s bolus) in 10 open-chest dogs with mild-to-moderate coronary stenosis that was not flow limiting at rest. Regadenoson decreased blood pressure but did not change heart rate. It increased coronary blood flow significantly (P < 0.05) for 30 min, which was attenuated in proportion to coronary stenosis severity. Whereas myocardial blood volume maximally increased by 0.5-0.75-fold in the control region, it did not change in the region supplied by the non-flow limiting stenosis. Perfusion defects were visually and quantitatively detectable for as long as 10 min after administration of regadenoson. No arrhythmias were noted with regadenoson either prior to or during myocardial contrast echocardiography. Conclusion Regadenoson can be used as a vasodilator stress agent with myocardial contrast echocardiography to detect the presence of physiologically significant coronary stenosis. The optimum time for image acquisition was 3-10 min after drug administration. C1 [Le, D. Elizabeth] Portland VA Med Ctr, Portland, OR USA. [Le, D. Elizabeth; Bragadeesh, Thanjavur; Zhao, Yan; Kaul, Sanjiv] Oregon Hlth & Sci Univ, Div Cardiovasc Med, Portland, OR 97239 USA. [Wang, Yue-Gang; Zha, Daogang] So Med Univ, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China. RP Le, DE (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,P3CAR, Portland, OR USA. EM lee@ohsu.edu FU Cardiovascular Therapeutics (Palo Alto, CA, USA); Bracco Research SA (Geneva, Switzerland); Philips Ultrasound (Andover, MA, USA); Portland Veterans Affairs Medical Center (Portland, OR, USA); Nanfang Hospital of Southern Medical University (GuangZhou, China); National Natural Science Foundation of China FX Supported in part by grants from Cardiovascular Therapeutics (Palo Alto, CA, USA), Bracco Research SA (Geneva, Switzerland), and Philips Ultrasound (Andover, MA, USA). D.E.L. also received support from the Portland Veterans Affairs Medical Center (Portland, OR, USA). Y.-G.W. and D.Z. were supported by Nanfang Hospital of Southern Medical University (GuangZhou, China) and the National Natural Science Foundation of China. NR 39 TC 3 Z9 3 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2047-2404 J9 EUR HEART J-CARD IMG JI Eur. Heart J.-Cardiovasc. Imaging PD APR PY 2012 VL 13 IS 4 BP 298 EP 308 DI 10.1093/ejechocard/jer232 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 931NS UT WOS:000303227200005 PM 22067143 ER PT J AU Weber, GF Rosenberg, R Murphy, JE zum Buschenfelde, CM Friess, H AF Weber, Georg F. Rosenberg, Robert Murphy, Janet E. zum Bueschenfelde, Christian Meyer Friess, Helmut TI Multimodal treatment strategies for locally advanced rectal cancer SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE adjuvant therapy; locally advanced rectal cancer; multimodal treatment strategies; neoadjuvant therapy; prognostic factors; quality of life; staging; surgery ID TOTAL MESORECTAL EXCISION; TOTAL PELVIC EXENTERATION; ADVANCED COLORECTAL-CANCER; QUALITY-OF-LIFE; COMBINED-MODALITY THERAPY; HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY; CIRCUMFERENTIAL RESECTION MARGIN; POSITRON-EMISSION-TOMOGRAPHY; HOSPITAL PROCEDURE VOLUME; RNA EXPRESSION LEVELS AB This review outlines the important multimodal treatment issues associated with locally advanced rectal cancer. Changes to chemotherapy and radiation schema, as well as modern surgical approaches, have led to a revolution in the management of this disease but the morbidity and mortality remains high. Adequate treatment is dependent on precise preoperative staging modalities. Advances in staging via endorectal ultrasound, computed tomography, M RI and PET have improved pretreatment triage and management. Important prognostic factors and their impact for this disease are under investigation. Here we discuss the different treatment options including modern tumor-related surgical approaches, neoadjuvant as well as adjuvant therapies. Further clinical progress will largely depend on the broader implementation of multidisciplinary treatment strategies following the principles of evidence-based medicine. C1 [Weber, Georg F.; Murphy, Janet E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Rosenberg, Robert] Kantonsspital, Dept Surg, Baden, Switzerland. [zum Bueschenfelde, Christian Meyer] Asklepios Klin Altona, Dept Med, Hamburg, Germany. [Friess, Helmut] Tech Univ Munich, Klinikum Rechts Isar, Dept Surg, D-8000 Munich, Germany. RP Weber, GF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM weber.georg@mgh.harvard.edu NR 132 TC 5 Z9 6 U1 0 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD APR PY 2012 VL 12 IS 4 BP 481 EP 494 DI 10.1586/ERA.12.3 PG 14 WC Oncology SC Oncology GA 931OI UT WOS:000303228800013 PM 22500685 ER PT J AU Spain, RI George, RJS Salarian, A Mancini, M Wagner, JM Horak, FB Bourdette, D AF Spain, R. I. George, R. J. St. Salarian, A. Mancini, M. Wagner, J. M. Horak, F. B. Bourdette, D. TI Body-worn motion sensors detect balance and gait deficits in people with multiple sclerosis who have normal walking speed SO GAIT & POSTURE LA English DT Article DE Gait; Postural balance; Multiple sclerosis; Outcome measurement; Rehabilitation ID DISABILITY STATUS SCALE; TIMED 25-FOOT WALK; FUNCTIONAL COMPOSITE; CLINICAL DISABILITY; TRUNK ACCELEROMETRY; IMPAIRMENT; STABILIZATION; SYSTEM; IMPACT; MS AB While balance and gait limitations are hallmarks of multiple sclerosis (MS), standard stopwatch-timed measures practical for Use in the clinic are insensitive in minimally affected patients. This prevents early detection and intervention for mobility problems. The study sought to determine if body-worn sensors could detect differences in balance and gait between people with MS with normal walking speeds and healthy controls. Thirty-one MS and twenty-eight age- and sex-matched control subjects were tested using body-worn sensors both during quiet stance and gait (Timed Up and Go test, TUG). Results were compared to stopwatch-timed measures. Stopwatch durations of the TUG and Timed 25 Foot Walk tests were not significantly different between groups. However, during quiet stance with eyes closed, people with MS had significantly greater sway acceleration amplitude than controls (p = 0.02). During gait, people with MS had greater trunk angular range of motion in roll (medio-lateral flexion, p = 0.017) and yaw (axial rotation, p = 0.026) planes. Turning duration through 180 degrees was also longer in MS (p = 0.031). Thus, body-worn motion sensors detected mobility differences between MS and healthy controls when traditional timed tests could not. This portable technology provides objective and quantitative mobility data previously not obtainable in the clinic, and may prove a useful outcome measure for early mobility changes in MS. Published by Elsevier B.V. C1 [Spain, R. I.; Bourdette, D.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, MS Ctr ExcellenceWest, Portland, OR 97239 USA. [Spain, R. I.; Bourdette, D.] Oregon Hlth & Sci Univ, Neurol Serv, Portland, OR 97239 USA. [Spain, R. I.; George, R. J. St.; Mancini, M.; Horak, F. B.; Bourdette, D.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Salarian, A.] Oregon Hlth & Sci Univ, Balance Disorders Lab, Beaverton, OR USA. [Wagner, J. M.] St Louis Univ, Dept Phys Therapy & Athlet Training, St Louis, MO 63103 USA. RP Spain, RI (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, MS Ctr ExcellenceWest, Mail Code CR120 3181,SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM spainr@ohsu.edu RI Salarian, Arash/E-8311-2016 OI Salarian, Arash/0000-0001-7332-0062 FU National MS Society; Medical Research Foundation of Oregon; Oregon Clinical and Translational Research Institute (OCTRI); National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1 RR024140]; NIH Roadmap for Medical Research; VA Rehabilitation Research & Development service FX Mr. Joshua Adams is acknowledged for his assistance with data collection. Dr. Spain received grant support for this project from the National MS Society Mentor Based Post-doctoral Fellowship in Rehabilitation, and the Medical Research Foundation of Oregon Early Clinical Investigator Award. This publication was made possible with support from the Oregon Clinical and Translational Research Institute (OCTRI), grant number UL1 RR024140 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Dr. Spain is a Career Development Award recipient from the VA Rehabilitation Research & Development service. NR 30 TC 66 Z9 66 U1 4 U2 22 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD APR PY 2012 VL 35 IS 4 BP 573 EP 578 DI 10.1016/j.gaitpost.2011.11.026 PG 6 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 931ON UT WOS:000303229300009 PM 22277368 ER PT J AU Brooks, VL Cassaglia, PA Zhao, D Goldman, RK AF Brooks, Virginia L. Cassaglia, Priscila A. Zhao, Ding Goldman, Robert K. TI Baroreflex Function in Females: Changes With the Reproductive Cycle and Pregnancy SO GENDER MEDICINE LA English DT Review DE 3 alpha-OH-DHP; baroreflex sensitivity; sympathetic nerve activity; insulin; hemorrhage ID OBESE ZUCKER RATS; SYMPATHETIC-NERVE ACTIVITY; CONSCIOUS RABBITS; MENSTRUAL-CYCLE; BRAIN INSULIN; HEART-RATE; CHRONOTROPIC BAROREFLEXES; ESTROUS-CYCLE; SENSITIVITY; REFLEX AB This review briefly describes the changes in baroreflex function that occur during female reproductive life, specifically during the reproductive cycle and pregnancy. The sensitivity or gain of baroreflex control of heart rate and sympathetic activity fluctuates during the reproductive cycle, reaching a peak when gonadal hormone levels increase, during the follicular phase in women and proestrus in rats. The increase in baroreflex sensitivity (BRS) is likely mediated by estrogen because ovariectomy in rats eliminates the BRS increase, the cyclic profile of changes in BRS mirror the changes in estrogen, and estrogen acts in the brainstem to increase BRS. In contrast, pregnancy depresses both BRS and the maximal level of sympathetic activity and heart rate evoked by severe hypotension. The decrease in BRS may be mediated by a reduction in the actions of insulin in the arcuate nucleus to support the baroreflex. In addition, increased levels of the neurosteroid progesterone metabolite 3 alpha-OH-DHP act downstream in the rostral ventrolateral medulla to suppress maximal baroreflex increases in sympathetic activity. Consequently, these changes in baroreflex function impair blood pressure regulation in the presence of hypotensive challenges such as orthostasis and hemorrhage, a common event during delivery. As a result, peripartum hemorrhage is a major cause of human maternal death. (Gend Med. 2012;9:61-67) (C) 2012 Elsevier HS Journals, Inc. All rights reserved. C1 [Brooks, Virginia L.; Cassaglia, Priscila A.; Zhao, Ding] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Zhao, Ding] Hebei Med Univ, Sch Pharm, Shijiazhuang, Peoples R China. [Goldman, Robert K.] Portland VA Med Ctr, Dept Surg, Portland, OR USA. RP Brooks, VL (reprint author), Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, L-334,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM brooksv@ohsu.edu FU National Institutes of Health [HL088552]; American Heart Association [09GRNT2060630] FX This work was supported in part by grant HL088552 from the National Institutes of Health and by Grant-in-Aid 09GRNT2060630 from the American Heart Association. All authors contributed to the writing of the manuscript and also contributed to the design, conduct, or analysis of aspects of the research from the authors' lab described in this review. NR 45 TC 11 Z9 12 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 1550-8579 J9 GENDER MED JI Gend. Med. PD APR PY 2012 VL 9 IS 2 BP 61 EP 67 DI 10.1016/j.genm.2012.02.004 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 930WZ UT WOS:000303176700001 PM 22483197 ER PT J AU Kassambara, A Hose, D Moreaux, J Walker, BA Protopopov, A Reme, T Pellestor, F Pantesco, V Jauch, A Morgan, G Goldschmidt, H Klein, B AF Kassambara, Alboukadel Hose, Dirk Moreaux, Jerome Walker, Brian A. Protopopov, Alexei Reme, Thierry Pellestor, Franck Pantesco, Veronique Jauch, Anna Morgan, Gareth Goldschmidt, Hartmut Klein, Bernard TI Genes with a spike expression are clustered in chromosome (sub)bands and spike (sub)bands have a powerful prognostic value in patients with multiple myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE spike (sub)bands; myeloma; molecular biology; survival; prognosis ID IN-SITU HYBRIDIZATION; STEM-CELL TRANSPLANTATION; RISK-ADAPTED TREATMENT; HUMAN CANCER GENES; MOLECULAR CLASSIFICATION; PROLIFERATION; TRANSLOCATION; MUTATIONS; SUBGROUPS; LINES AB Background Genetic abnormalities are common in patients with multiple myeloma, and may deregulate gene products involved in tumor survival, proliferation, metabolism and drug resistance. In particular, translocations may result in a high expression of targeted genes (termed spike expression) in tumor cells. We identified spike genes in multiple myeloma cells of patients with newly-diagnosed myeloma and investigated their prognostic value. Design and Methods Genes with a spike expression in multiple myeloma cells were picked up using box plot probe set signal distribution and two selection filters. Results In a cohort of 206 newly diagnosed patients with multiple myeloma, 2587 genes/expressed sequence tags with a spike expression were identified. Some spike genes were associated with some transcription factors such as MAF or MMSET and with known recurrent translocations as expected. Spike genes were not associated with increased DNA copy number and for a majority of them, involved unknown mechanisms. Of spiked genes, 36.7% clustered significantly in 149 out of 862 documented chromosome (sub) bands, of which 53 had prognostic value (35 bad, 18 good). Their prognostic value was summarized with a spike band score that delineated 23.8% of patients with a poor median overall survival (27.4 months versus not reached, P<0.001) using the training cohort of 206 patients. The spike band score was independent of other gene expression profiling-based risk scores, t(4; 14), or del17p in an independent validation cohort of 345 patients. Conclusions We present a new approach to identify spike genes and their relationship to patients' survival. C1 [Klein, Bernard] CHU Montpellier, Inst Rech Biotherapie, Hop St Eloi, F-34285 Montpellier 5, France. [Kassambara, Alboukadel; Moreaux, Jerome; Reme, Thierry; Pellestor, Franck; Pantesco, Veronique; Klein, Bernard] INSERM, U1040, Montpellier, France. [Hose, Dirk; Jauch, Anna; Goldschmidt, Hartmut] Univ Klinikum Heidelberg, Med Klin 5, Heidelberg, Germany. [Hose, Dirk; Jauch, Anna; Goldschmidt, Hartmut] Natl Ctr Tumorerkrankungen, Heidelberg, Germany. [Walker, Brian A.; Morgan, Gareth] Inst Canc Res, Sect Haematooncol, London SW3 6JB, England. [Pellestor, Franck; Klein, Bernard] Univ Montpellier I, UFR Med, Montpellier, France. [Protopopov, Alexei] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Klein, B (reprint author), CHU Montpellier, Inst Rech Biotherapie, Hop St Eloi, Av Augustin Fliche, F-34285 Montpellier 5, France. EM bernard.klein@inserm.fr RI Walker, Brian/A-4984-2013; OI Walker, Brian/0000-0002-8615-6254; Moreaux, Jerome/0000-0002-5717-3207 FU ICMJE; Biological Research Centre at the Royal Marsden Hospital; Ligue Nationale Contre le Cancer (equipe labellisee), Paris, France; ARC (France); EU (OVERMYR); Hopp-Foundation, Germany; University of Heidelberg, Germany; National Centre for Tumor Diseases, Heidelberg, Germany; Tumorzentrum Heidelberg/Mannheim, Germany; Deutsche Krebshilfe, Bonn, Germany; Deutsche Forschungsgemeinschaft, Bonn, Germany FX Financial and other disclosures provided by the authors using the ICMJE (www.icmje.org) Uniform Format for Disclosure of Competing Interests are also available at www.haematologica.org.; we acknowledge the support of the Biological Research Centre at the Royal Marsden Hospital.; this work was supported by grants from the Ligue Nationale Contre le Cancer (equipe labellisee), Paris, France, from ARC (France), EU FP7 (OVERMYR), the Hopp-Foundation, Germany, the University of Heidelberg, Germany, the National Centre for Tumor Diseases, Heidelberg, Germany, the Tumorzentrum Heidelberg/Mannheim, Germany, the Deutsche Krebshilfe, Bonn, Germany, and the Deutsche Forschungsgemeinschaft, Bonn, Germany. We thank the Microarray Core Facility of IRB (http://irb.montp.inserm.fr/en/index.php?page=Plateau&IdEquipe=6) and the cytometry platform of the Institute of Research in Biotherapy (http://irb.montp.inserm.fr/en/index.php?page=Plateau&IdEquipe=3, Montpellier Rio Imaging). NR 46 TC 20 Z9 21 U1 0 U2 4 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD APR PY 2012 VL 97 IS 4 BP 622 EP 630 DI 10.3324/haematol.2011.046821 PG 9 WC Hematology SC Hematology GA 931TG UT WOS:000303241600026 PM 22102711 ER PT J AU Battinelli, EM Murphy, DL Connors, JM AF Battinelli, Elisabeth M. Murphy, Devon L. Connors, Jean M. TI Venous Thromboembolism Overview SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Deep vein thrombosis; Pulmonary embolism; Anticoagulation ID DEEP-VEIN THROMBOSIS; ORAL ANTICOAGULANT-THERAPY; MOLECULAR-WEIGHT HEPARIN; INTENSITY WARFARIN THERAPY; D-DIMER; PULMONARY-EMBOLISM; 1ST EPISODE; AIR-TRAVEL; ATRIAL-FIBRILLATION; SUPERFICIAL THROMBOPHLEBITIS AB This article gives a general overview of venous thromboembolism (VTE). Pathophysiology, presentation, diagnosis, and initial management of VTE are briefly reviewed. More difficult management problems are reviewed in greater depth, including duration of anticoagulation, treatment of superficial venous thrombosis, and controversies surrounding bridging therapy, with a brief review of currently available new oral anticoagulants. C1 [Battinelli, Elisabeth M.; Murphy, Devon L.; Connors, Jean M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Battinelli, EM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol,Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM ebattinelli@partners.org NR 99 TC 6 Z9 8 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2012 VL 26 IS 2 BP 345 EP + DI 10.1016/j.hoc.2012.02.010 PG 24 WC Oncology; Hematology SC Oncology; Hematology GA 932GZ UT WOS:000303279900009 PM 22463831 ER PT J AU Bianchi, G Ghobrial, IM AF Bianchi, Giada Ghobrial, Irene M. TI Does My Patient with a Serum Monoclonal Spike have Multiple Myeloma? SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Monoclonal spike; MGUS; Multiple myeloma; Progression ID UNDETERMINED SIGNIFICANCE MGUS; INDEPENDENT RISK-FACTOR; PLASMA-CELL DISORDERS; LIGHT-CHAIN RATIO; EXTRAMEDULLARY PLASMACYTOMA; STAGING SYSTEM; RENAL-FAILURE; UNITED-STATES; WORKING GROUP; FOLLOW-UP AB A monoclonal spike on serum protein electrophoresis is a frequent finding in the general population and pathognomonic of a plasma cell dyscrasia. In otherwise healthy individuals, it is diagnostic of two asymptomatic, premalignant conditions called monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) which carry a lifelong risk of progression to multiple myeloma (MM) or related malignancy. This article discusses the criteria for diagnosis of MGUS, SMM, and MM; current recommendations for follow-up and risk factors for progression to MM of patients with MGUS and SMM; and diagnostic evaluation of suspected MM transformation. C1 [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bianchi, Giada] Mayo Clin, Dept Internal Med, Rochester, MN 55905 USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM Irene_Ghobrial@DFCI.HARVARD.EDU FU NCI NIH HHS [R01 CA125690, R01 CA133799-01A1, R01 CA133799, R01 CA125690-01A2] NR 55 TC 2 Z9 3 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2012 VL 26 IS 2 BP 383 EP + DI 10.1016/j.hoc.2012.02.009 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 932GZ UT WOS:000303279900011 PM 22463833 ER PT J AU Motyckova, G Steensma, DP AF Motyckova, Gabriela Steensma, David P. TI Why Does My Patient Have Lymphadenopathy or Splenomegaly? SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Lymphadenopathy; Splenomegaly; Differential diagnosis; Hematological malignancy ID CORE-NEEDLE-BIOPSY; MEDIASTINAL LYMPH-NODES; CERVICAL LYMPHADENOPATHY; DIFFERENTIAL-DIAGNOSIS; MALIGNANT-LYMPHOMA; PALPABLE SPLEENS; SONOGRAPHY; HEAD; NECK; CT AB Lymph node or spleen enlargement may be innocent or the first sign of a serious disorder. Lymphadenopathy and splenomegaly can be found in symptomatic or asymptomatic patients. Lymph node enlargement in a single region or multiple sites can be seen in various diseases, including infections, noninfectious inflammatory conditions, or malignancies; a similar differential diagnosis applies to splenomegaly, but splenomegaly can also be caused by vascular abnormalities and hemolysis. Frequently, lymphadenopathy is detected incidentally during screening examinations or imaging procedures. This review focuses on causes of lymphadenopathy and splenomegaly and an appropriate diagnostic approach to patients with lymphadenopathy or splenomegaly. C1 [Steensma, David P.] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02215 USA. RP Steensma, DP (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Suite D1B30,450 Brookline Ave, Boston, MA 02215 USA. EM david_steensma@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284 NR 70 TC 7 Z9 8 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2012 VL 26 IS 2 BP 395 EP + DI 10.1016/j.hoc.2012.02.005 PG 15 WC Oncology; Hematology SC Oncology; Hematology GA 932GZ UT WOS:000303279900012 PM 22463834 ER PT J AU Foret, MM Scult, M Wilcher, M Chudnofsky, R Malloy, L Hasheminejad, N Park, ER AF Foret, Megan M. Scult, Matthew Wilcher, Marilyn Chudnofsky, Rana Malloy, Laura Hasheminejad, Nicole Park, Elyse R. TI Integrating a relaxation response-based curriculum into a public high school in Massachusetts SO JOURNAL OF ADOLESCENCE LA English DT Article DE Curriculum; Emotional health; Mental health; Stress management; Relaxation response ID ACADEMIC-PERFORMANCE; PERCEIVED STRESS; ANXIETY; STUDENTS; HEALTH; INTERVENTIONS; ADOLESCENTS; CHILDREN; SUICIDE; SCALE AB Academic and societal pressures result in U.S. high school students feeling stressed. Stress management and relaxation interventions may help students increase resiliency to stress and overall well-being. The objectives of this study were to examine the feasibility (enrollment, participation and acceptability) and potential effectiveness (changes in perceived stress, anxiety, self-esteem, health-promoting behaviors, and locus of control) of a relaxation response (RR)-based curriculum integrated into the school day for high school students. The curriculum included didactic instruction, relaxation exercises, positive psychology, and cognitive restructuring. The intervention group showed significantly greater improvements in levels of perceived stress, state anxiety, and health-promoting behaviors when compared to the wait list control group. The intervention appeared most useful for girls in the intervention group. The results suggest that several modifications may increase the feasibility of using this potentially effective intervention in high schools. (C) 2011 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved. C1 [Foret, Megan M.; Scult, Matthew; Wilcher, Marilyn; Chudnofsky, Rana; Malloy, Laura; Hasheminejad, Nicole; Park, Elyse R.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. RP Park, ER (reprint author), Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM epark@partners.org OI Scult, Matthew/0000-0001-5554-8186 FU NCCDPHP CDC HHS [R01DP000339] NR 48 TC 5 Z9 5 U1 0 U2 12 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0140-1971 J9 J ADOLESCENCE JI J. Adolesc. PD APR PY 2012 VL 35 IS 2 BP 325 EP 332 DI 10.1016/j.adolescence.2011.08.008 PG 8 WC Psychology, Developmental SC Psychology GA 929YF UT WOS:000303100900008 PM 21893336 ER PT J AU Guzzardi, MA Habib, N Kitsberg, D Uygun, K Trippler, M Timm, J Friedman, N Nahmias, Y AF Guzzardi, M. A. Habib, N. Kitsberg, D. Uygun, K. Trippler, M. Timm, J. Friedman, N. Nahmias, Y. TI TRANSCRIPTIONAL-METABOLIC REPROGRAMMING OF HCV-INFECTION FROM PRIMARY HUMAN HEPATOCYTES CO-CULTURES TO CLINICAL SAMPLES SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 18-22, 2012 CL Barcelona, SPAIN SP European Assoc Study Liver (EASL) C1 [Guzzardi, M. A.; Habib, N.; Kitsberg, D.; Friedman, N.; Nahmias, Y.] Hebrew Univ Jerusalem, Jerusalem, Israel. [Uygun, K.; Nahmias, Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Trippler, M.; Timm, J.] Univ Hosp Essen, Essen, Germany. EM ynahmias@gmail.com RI Friedman, Nir/H-9692-2012; Nahmias, Yaakov/H-4725-2013; Guzzardi, Maria-Angela/K-1389-2016 OI Friedman, Nir/0000-0002-9678-3550; Guzzardi, Maria-Angela/0000-0001-9574-5088 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2012 VL 56 SU 2 MA 862 BP S336 EP S336 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931TD UT WOS:000303241301421 ER PT J AU Hoshida, Y Villanueva, A Sangiovanni, A Sole, M Hur, C Andersson, KL Chung, RT Gould, J Kojima, K Gupta, S Taylor, B Crenshaw, A Gabriel, S Minguez, B Iavarone, M Friedman, SL Colombo, M Llovet, JM Golub, T AF Hoshida, Y. Villanueva, A. Sangiovanni, A. Sole, M. Hur, C. Andersson, K. L. Chung, R. T. Gould, J. Kojima, K. Gupta, S. Taylor, B. Crenshaw, A. Gabriel, S. Minguez, B. Iavarone, M. Friedman, S. L. Colombo, M. Llovet, J. M. Golub, T. TI PROGNOSTIC GENE-EXPRESSION SIGNATURE FOR HEPATITIS C-RELATED EARLY-STAGE LIVER CIRRHOSIS SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 18-22, 2012 CL Barcelona, SPAIN SP European Assoc Study Liver (EASL) C1 [Hoshida, Y.; Gould, J.; Kojima, K.; Gupta, S.; Taylor, B.; Crenshaw, A.; Gabriel, S.; Golub, T.] Broad Inst Harvard & MIT, Boston, MA USA. [Hoshida, Y.; Golub, T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Villanueva, A.; Llovet, J. M.] Hosp Clin Barcelona, IDIBAPS, Lab Reserca Translac Oncol Hepat, Barcelona, Spain. [Sangiovanni, A.; Iavarone, M.; Colombo, M.] Univ Milan, Fdn Ca Granda IRCCS Osped Maggiore Policlin, Div Gastroenterol, Milan, Italy. [Sole, M.] Hosp Clin Barcelona, Dept Pathol, Barcelona, Spain. [Hur, C.; Andersson, K. L.; Chung, R. T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Minguez, B.] Hosp Univ Vall dHebron, Liver Unit, Dept Med, Barcelona, Spain. [Friedman, S. L.; Llovet, J. M.] Mt Sinai Sch Med, Dept Liver Dis, New York, NY USA. EM hoshida@broadinstitute.org RI Minguez, Beatriz/N-4456-2014 OI Minguez, Beatriz/0000-0002-7276-9666 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2012 VL 56 SU 2 MA 716 BP S283 EP S283 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931TD UT WOS:000303241301276 ER PT J AU Hu, W Nevzorova, YA Haas, U Moro, N Sicinski, P Barbacid, M Trautwein, C Liedtke, C AF Hu, W. Nevzorova, Y. A. Haas, U. Moro, N. Sicinski, P. Barbacid, M. Trautwein, C. Liedtke, C. TI CDK2-DEFICIENT HEPATOCYTES REQUIRE NON-CANONICAL FUNCTIONS OF CYCLIN E1 FOR EFFICIENT LIVER REGENERATION IN MICE SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 18-22, 2012 CL Barcelona, SPAIN SP European Assoc Study Liver (EASL) C1 [Hu, W.; Nevzorova, Y. A.; Haas, U.; Moro, N.; Trautwein, C.; Liedtke, C.] Rhein Westfal TH Aachen, Dept Med 3, Univ Hosp Aachen, Aachen, Germany. [Sicinski, P.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Barbacid, M.] CNIO, Madrid, Spain. EM whu@ukaachen.de NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2012 VL 56 SU 2 MA 61 BP S27 EP S27 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931TD UT WOS:000303241300062 ER PT J AU Kim, AY Levant, E Reyor, LL Chung, RT Nahmias, Y AF Kim, A. Y. Levant, E. Reyor, L. L. Chung, R. T. Nahmias, Y. TI CLINICAL STUDY: METABOLIC INHIBITION OF VLDL AND ASSOCIATED HCV PRODUCTION BY A SINGLE ORAL DOSE OF NARINGENIN NANOCOMPLEX SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 18-22, 2012 CL Barcelona, SPAIN SP European Assoc Study Liver (EASL) C1 [Kim, A. Y.; Reyor, L. L.; Chung, R. T.; Nahmias, Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Levant, E.; Nahmias, Y.] Hebrew Univ Jerusalem, Jerusalem, Israel. EM ynahmias@gmail.com RI Nahmias, Yaakov/H-4725-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2012 VL 56 SU 2 MA 1196 BP S474 EP S474 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931TD UT WOS:000303241302303 ER PT J AU Lopez-Vicario, C Titos, E Gonzalez-Periz, A Rius, B Moran-Salvador, E Garcia-Alonso, V Cofan, M Kang, JX Arroyo, V Claria, J AF Lopez-Vicario, C. Titos, E. Gonzalez-Periz, A. Rius, B. Moran-Salvador, E. Garcia-Alonso, V. Cofan, M. Kang, J. X. Arroyo, V. Claria, J. TI FAT-1 TRANSGENIC MICE EXPRESSING AN OMEGA-3 FATTY ACID DESATURASE ARE PROTECTED FROM STEATOHEPATITIS SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 18-22, 2012 CL Barcelona, SPAIN SP European Assoc Study Liver (EASL) C1 [Lopez-Vicario, C.; Titos, E.; Gonzalez-Periz, A.; Rius, B.; Moran-Salvador, E.; Garcia-Alonso, V.; Claria, J.] Univ Barcelona, Dept Biochem & Mol Genet, Hosp Clin, CIBERehd, Barcelona, Spain. [Kang, J. X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Lipid Med & Technol, Boston, MA USA. [Arroyo, V.] Univ Barcelona, Liver Unit, Hosp Clin, CIBERehd, Barcelona, Spain. EM lopezvicario@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2012 VL 56 SU 2 MA 1225 BP S486 EP S486 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931TD UT WOS:000303241302332 ER PT J AU Cao, SG McMillin, DW Tamayo, G Delmore, J Mitsiades, CS Clardy, J AF Cao, Shugeng McMillin, Douglas W. Tamayo, Giselle Delmore, Jake Mitsiades, Constantine S. Clardy, Jon TI Inhibition of Tumor Cells Interacting with Stromal Cells by Xanthones Isolated from a Costa Rican Penicillium sp. SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID ENDOPHYTIC FUNGUS; MOULD METABOLITES; PHOMOXANTHONE-A; CONSTITUTION; PIGMENTS; DIMERS AB CR1642D, an endophytic isolate of Penicillium sp. collected from a Costa Rican rainforest, was identified through a high-throughput approach to identify natural products with enhanced antitumor activity in the context of tumor stromal interactions. Bioassay-guided separation led to the identification of five xanthones (1-5) from CR1642D. The structures of the xanthone dimer penexanthone A (1) and monomer penexanthone B (2) were elucidated on the basis of spectroscopic analyses, including 2D NMR experiments. All of the compounds were tested against a panel of tumor cell lines in the presence and absence of bone marrow stromal cells. Compound 3 was the most active, with IC50 values of 1-17 mu M, and its activity was enhanced 2-fold against tumor cell line RPMI8226 in the presence of stromal cells (IC50 1.2 mu M, but 2.4 mu M without stromal cells). C1 [McMillin, Douglas W.; Delmore, Jake; Mitsiades, Constantine S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cao, Shugeng; Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Tamayo, Giselle] Inst Nacl Biodiversidad INBio, Unidad Estrateg Bioprospecc, Santo Domingo De Heredia, Costa Rica. RP Mitsiades, CS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM constantine_mitsiades@dfci.harvard.edu; Clardy@hms.harvard.edu RI Tamayo, Giselle/J-3609-2015 OI Tamayo, Giselle/0000-0002-4912-8895 FU NIH [U01 TW007404, R01 CA050947] FX This work was generously supported by NIH U01 TW007404 (J.C.) and NIH R01 CA050947 (C.S.M.). We thank J. A. V. D. Blodgett for taking the photo and helping deposit the DNA sequence in GenBank. NR 18 TC 17 Z9 17 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD APR PY 2012 VL 75 IS 4 BP 793 EP 797 DI 10.1021/np2009863 PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 931LD UT WOS:000303220500045 PM 22458669 ER PT J AU Hassija, CM Jakupcak, M Maguen, S Shipherd, JC AF Hassija, Christina M. Jakupcak, Matthew Maguen, Shira Shipherd, Jillian C. TI The Influence of combat and interpersonal trauma on PTSD, depression, and alcohol misuse in U.S. Gulf War and OEF/OIF women veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; GENDER-DIFFERENCES; SEXUAL ASSAULT; MENTAL-HEALTH; FEMALE VETERANS; SYMPTOMS; CARE; VALIDATION; MILITARY; ABUSE AB The present study evaluated the impact of combat and interpersonal trauma exposure in a sample of 115 U.S. women veterans from Gulf War I and the Iraq and Afghanistan wars on 3 postdeployment trauma-related mental health outcomes: posttraumatic stress disorder symptoms (PSS), depressive symptom severity (DSS), and alcohol misuse. Patients presenting for healthcare services at a Veterans Affairs postdeployment health specialty clinic completed screening questionnaires that assessed combat exposure, lifetime interpersonal trauma history of childhood neglect, physical, or sexual abuse, and adult sexual and physical assault. In a regression model, combat exposure was the only significant independent variable associated with PSS, DSS, and alcohol misuse (beta = .42, .27 and B = 1.58, respectively) even after adding lifetime interpersonal assault exposure to the model. Results highlight the negative effects of combat exposure on treatment-seeking women veterans' postdeployment mental health. Incorporating combat exposure into routine screening procedures for Gulf War and Iraq and Afghanistan war women veterans can aid in mental health treatment planning. C1 [Hassija, Christina M.; Jakupcak, Matthew] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Hassija, Christina M.] Univ Wyoming, Dept Psychol, Laramie, WY 82071 USA. [Jakupcak, Matthew] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Maguen, Shira] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Maguen, Shira] San Francisco VA Med Ctr, San Francisco, CA USA. [Shipherd, Jillian C.] VA Boston Healthcare Syst, Boston, MA USA. [Shipherd, Jillian C.] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Shipherd, Jillian C.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. RP Hassija, CM (reprint author), VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM chassija@stanford.edu NR 17 TC 24 Z9 24 U1 1 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2012 VL 25 IS 2 BP 216 EP 219 DI 10.1002/jts.21686 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 929DN UT WOS:000303041500015 PM 22522738 ER PT J AU Cho, HJ Sigmund, EE Song, YQ AF Cho, Hyung Joon Sigmund, Eric E. Song, Yiqiao TI Magnetic Resonance Characterization of Porous Media Using Diffusion through Internal Magnetic Fields SO MATERIALS LA English DT Review DE gradients; susceptibility; diffusion; decay due to diffusion in the internal field (DDIF); porous media; trabecular bone ID TO-VOLUME RATIO; TRABECULAR BONE; IN-VIVO; SPIN-ECHO; SUSCEPTIBILITY CONTRAST; TRANSVERSE-RELAXATION; TUMOR ANGIOGENESIS; PORE SIZES; NMR; GRADIENT AB When a porous material is inserted into a uniform magnetic field, spatially varying fields typically arise inside the pore space due to susceptibility contrast between the solid matrix and the surrounding fluid. As a result, direct measurement of the field variation may provide a unique opportunity to characterize the pore geometry. The sensitivity of nuclear magnetic resonance (NMR) to inhomogeneous field variations through their dephasing effects on diffusing spins is unique and powerful. Recent theoretical and experimental research sheds new light on how to utilize susceptibility-induced internal field gradients to quantitatively probe the microstructure of porous materials. This article reviews ongoing developments based on the stimulated echo-pulse sequence to extend the characterization of porous media using both spatially resolved and unresolved susceptibility-induced internal gradients that operate on a diffusing-spin ensemble. C1 [Cho, Hyung Joon] Ulsan Natl Inst Sci & Technol, Sch Nanobiosci & Chem Engn, Ulsan 689798, South Korea. [Sigmund, Eric E.] NYU, Dept Radiol, New York, NY 10016 USA. [Song, Yiqiao] Schlumberger Doll Res Ctr, Cambridge, MA 02139 USA. [Song, Yiqiao] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02215 USA. RP Cho, HJ (reprint author), Ulsan Natl Inst Sci & Technol, Sch Nanobiosci & Chem Engn, Ulsan 689798, South Korea. EM hjcho@unist.ac.kr; eric.sigmund@nyumc.org; ysong@nmr.mgh.harvard.edu RI Sigmund, Eric/E-1981-2013; Cho, HyungJoon/F-1423-2010 OI Sigmund, Eric/0000-0001-6783-3611; FU National Research Foundation of Korea; Korean government [2011-0000886, 2011-0005711] FX This work was supported in part by a grant from the National Research Foundation of Korea, which is funded by the Korean government (Nos. 2011-0000886 and 2011-0005711). NR 68 TC 7 Z9 7 U1 2 U2 36 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1996-1944 J9 MATERIALS JI Materials PD APR PY 2012 VL 5 IS 4 BP 590 EP 616 DI 10.3390/ma5040590 PG 27 WC Materials Science, Multidisciplinary SC Materials Science GA 932AV UT WOS:000303262300004 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI Adolf Butenandt-Nobel Prize for Chemistry SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN 55905 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shampo, MA (reprint author), Mayo Clin, Rochester, MN 55905 USA. OI Steensma, David/0000-0001-5130-9284 NR 0 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD APR PY 2012 VL 87 IS 4 BP E27 EP E27 DI 10.1016/j.mayocp.2011.12.019 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 930OC UT WOS:000303147700002 PM 22469359 ER PT J AU Min, CH Lee, HR Kim, CH Lee, SB AF Min, Chul Hee Lee, Han Rim Kim, Chan Hyeong Lee, Se Byeong TI Development of array-type prompt gamma measurement system for in vivo range verification in proton therapy SO MEDICAL PHYSICS LA English DT Article DE proton beam; prompt gamma; distal dose edge; radiation measurement; Monte Carlo simulation ID MONTE-CARLO; BEAM; PET; SIMULATION; RAYS AB Purpose: In vivo range verification is one of the most important parts of proton therapy to fully utilize its benefits delivering high radiation dose to tumor, while sparing the normal tissue with the so-called Bragg peak. Currently, however, range verification method is not used in clinics. The purpose of the present study is to optimize and evaluate the configuration of an array-type prompt gamma measurement system on determining distal dose edge for in vivo range verification of proton therapy. Methods: To effectively measure the prompt gammas against the background gammas, the Monte Carlo simulations with the MCNPX code were employed in optimizing the configuration of the measurement system, and the Monte Carlo method was also used to understand the effect of the background gammas, mainly neutron capture gammas, in the measured gamma distribution. To reduce the effect of the background gammas, the optimized energy window of 4-10 MeV in measuring the prompt gammas was employed. A parameterized source was used to maximize computation speed in the optimization study. A simplified test measurement system, using only one detector moving from one measurement location to the next, was constructed and applied to therapeutic proton beams of 80-220 MeV. For accurate determination of the distal dose edge, the sigmoidal curve-fitting method was applied to the measured distributions of the prompt gammas, and then, the location of the half-value between the maximum and minimum value in the curve-fitting was determined as the distal dose edge and compared with the beam range assessed by the proton dose distribution. Results: The parameterized source term employed in optimization process improved the calculation speed by up to similar to 300 times. The optimization study indicates that an array-type measurement system with 3, 2, 2, and 150 mm for scintillator thickness, slit width, septal thickness, and slit length, respectively, can effectively measure the prompt gamma distributions minimizing the contribution of background gammas. The present results show that a few hundred counts of prompt gammas can be easily obtained by measuring 10 s at each measurement location for proton beams of similar to 4 nA. The distal dose edges determined by the prompt gamma distribution are 5.45, 14.73, and 27.74 cm for proton beams of 5.17 (80 MeV), 14.99 (150 MeV), and 27.38 (220 MeV) cm, respectively. Conclusions: The results show that the array-type measurement system can measure prompt gamma distributions from a therapeutic proton beam within a short measurement time, and that the distal dose edge can be determined within a few millimeters of error without using any sophisticated analysis. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.3694098] C1 [Lee, Han Rim; Kim, Chan Hyeong] Hanyang Univ, Dept Nucl Engn, Seoul 133791, South Korea. [Min, Chul Hee] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Min, Chul Hee] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lee, Se Byeong] Natl Canc Ctr, Proton Therapy Ctr, Goyang 410769, Gyeonggi, South Korea. RP Kim, CH (reprint author), Hanyang Univ, Dept Nucl Engn, 17 Haengdang Dong, Seoul 133791, South Korea. EM chkim@hanyang.ac.kr FU National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [2010-0028913, 2010-0018572] FX This research was supported by National Nuclear R&D Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (Nos. 2010-0028913 and 2010-0018572). NR 21 TC 41 Z9 41 U1 0 U2 7 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 APR PY 2012 VL 39 IS 4 BP 2100 EP 2107 DI 10.1118/1.3694098 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 919ZY UT WOS:000302371900039 PM 22482631 ER PT J AU Ashizawa, T Perlman, S Gomez, C Wilmot, G Schmahmann, J Ying, S Zesiewicz, T Paulson, H Shakkottai, V Bushara, K Mazzoni, P Kuo, SH Pulst, S Figueroa, K Xia, GB Krischer, J Cuthbertson, D Holbert, AR Ferguson, J Galpern, W Subramony, S AF Ashizawa, Tetsuo Perlman, Susan Gomez, Christopher Wilmot, George Schmahmann, Jeremy Ying, Sarah Zesiewicz, Theresa Paulson, Henry Shakkottai, Vikram Bushara, Khalaf Mazzoni, Pietro Kuo, Sheng-Han Pulst, Stefan Figueroa, Karla Xia, Guangbin Krischer, Jeffrey Cuthbertson, David Holbert, Amy Roberts Ferguson, John Galpern, Wendy Subramony, S. TI Clinical Characteristics of Spinocerebellar Ataxias 1, 2, 3 and 6 SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Ashizawa, Tetsuo] Univ Florida, McKnight Brain Inst UF, Gainesville, FL USA. [Perlman, Susan] Univ Calif Los Angeles, Sherman Oaks, CA USA. [Gomez, Christopher] Univ Chicago, Chicago, IL 60637 USA. [Wilmot, George] Emory Univ, Atlanta, GA 30322 USA. [Zesiewicz, Theresa; Krischer, Jeffrey; Cuthbertson, David; Holbert, Amy Roberts] Univ S Florida, Tampa, FL USA. [Pulst, Stefan; Figueroa, Karla] Univ Utah, Salt Lake City, UT USA. [Paulson, Henry; Shakkottai, Vikram] Univ Michigan, Ann Arbor, MI 48109 USA. [Schmahmann, Jeremy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ying, Sarah] Jons Hopkins Univ, Baltimore, MD USA. [Bushara, Khalaf] Univ Minnesota, Minneapolis, MN USA. [Mazzoni, Pietro; Kuo, Sheng-Han] Columbia Univ, New York, NY USA. [Ferguson, John] NIH, Off Rare Dis, Bethesda, MD 20892 USA. [Galpern, Wendy] NINDS, Bethesda, MD 20892 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S12002 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204804266 ER PT J AU Atassi, N Lee, A Chang, J Macklin, E Cudkowicz, M AF Atassi, Nazem Lee, Alexandra Chang, Judith Macklin, Eric Cudkowicz, Merit TI Delays in Diagnosing Amyotrophic Lateral Sclerosis SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Atassi, Nazem; Lee, Alexandra; Chang, Judith; Cudkowicz, Merit] Massachusetts Gen Hosp, Charlestown, MA USA. [Macklin, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P03174 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801305 ER PT J AU Auriel, E Gurol, E Ayers, A Schwab, K Vashkevich, A Rosand, J Viswanathan, A Greenberg, S AF Auriel, Eitan Gurol, Edip Ayers, Alison Schwab, Kristin Vashkevich, Anastasia Rosand, Jonathan Viswanathan, Anand Greenberg, Steven TI Ongoing Microinfarction in Patients with Intracerebral Hemorrhage SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Auriel, Eitan; Gurol, Edip; Ayers, Alison; Vashkevich, Anastasia; Rosand, Jonathan; Viswanathan, Anand; Greenberg, Steven] Harvard Univ, Sch Med, Boston, MA USA. [Auriel, Eitan; Gurol, Edip; Ayers, Alison; Schwab, Kristin; Vashkevich, Anastasia; Viswanathan, Anand; Greenberg, Steven] Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. [Schwab, Kristin] Harvard Univ, Sch Med, Newburyport, MA USA. [Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S23002 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801551 ER PT J AU Bellande, B Winicur, Z Gallo, B Turner, M Saulino, M Heath, S Bennett, S Nelson, ME Reese, C Larson, A Dawidowicz, S Boche, J Cox, K AF Bellande, Bruce Winicur, Zev Gallo, Bruno Turner, Michael Saulino, Michael Heath, Susan Bennett, Susan Nelson, Mary Elizabeth Reese, Cynthia Larson, Andrea Dawidowicz, Suzanne Boche, Jamie Cox, Kathleen TI Competency-Based Curricula in DBS and ITB Therapies for Movement Disorders SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Bellande, Bruce] DWA Healthcare Commun Grp, Indianapolis, IN USA. [Cox, Kathleen] DWA Healthcare Commun Grp, Med Sci & Educ Div, Carmel, IN USA. [Gallo, Bruno] Univ Miami, Miami, FL USA. [Turner, Michael] Goodman Campbell Brain & Spine, Indianapolis, IN USA. [Saulino, Michael] MossRehab, Elkins Pk, PA USA. [Heath, Susan] San Francisco VA Med Ctr, San Francisco, CA USA. [Bennett, Susan] SUNY Buffalo, Buffalo, NY 14260 USA. [Nelson, Mary Elizabeth] PM&R Med Coll Wisconsin, Milwaukee, WI USA. [Reese, Cynthia; Larson, Andrea; Dawidowicz, Suzanne; Boche, Jamie] Medtronic, Minneapolis, MN 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P06022 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803369 ER PT J AU Brashear, A Cook, J Amponsah, A Hill, D Snively, B Light, L Suerken, C McCall, WV Boggs, N Stacy, M Ozelius, L Sweadner, K AF Brashear, Allison Cook, Jared Amponsah, Alethea Hill, Deborah Snively, Beverly Light, Laney Suerken, Cynthia McCall, W. Vaughn Boggs, Niki Stacy, Mark Ozelius, Laurie Sweadner, Kathleen TI Psychiatric and Neurocognitive Morbidity in Rapid-Onset Dystonia Parkinsonism SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Brashear, Allison; Cook, Jared; Amponsah, Alethea; Snively, Beverly; Light, Laney; McCall, W. Vaughn; Boggs, Niki] Wake Forest Sch Med, Winston Salem, NC USA. [Hill, Deborah] Neurol Wake Forest Baptist Hlth, Winston Salem, NC USA. [Suerken, Cynthia] Biostat Sci Wake Forest Baptist Hlth, Winston Salem, NC USA. [Stacy, Mark] Duke Univ, Durham, NC USA. [Ozelius, Laurie] Mt Sinai Hosp, New York, NY 10029 USA. [Sweadner, Kathleen] 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P01225 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800305 ER PT J AU Butovsky, O Siddiqui, S Gabriely, G Lanser, A Dake, B Gopal, M Doykan, C Wu, P Lawson, R Berry, J Krichevsky, A Cudkowicz, M Weiner, H AF Butovsky, Oleg Siddiqui, Shafiuddin Gabriely, Galina Lanser, Amanda Dake, Ben Gopal, Murugaiyan Doykan, Camille Wu, Pauline Lawson, Robert Berry, James Krichevsky, Anna Cudkowicz, Merit Weiner, Howard TI Identification of a Unique miRNA Signature in CD14(+)/CD16(-) Blood-Monocytes in ALS Subjects Identical to That Observed in SOD Mice SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Butovsky, Oleg; Gopal, Murugaiyan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. [Lawson, Robert; Berry, James] Harvard Univ, Sch Med, Neurol Clin Trial Unit, Charlestown, MA USA. [Cudkowicz, Merit] Harvard Univ, Sch Med, Neurol Clin Trial Unit, Massachusetts Gen Hosp, Charlestown, MA 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN92002 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803087 ER PT J AU Butovsky, O Siddiqui, S Gabriely, G Lanser, A Dake, B Gopal, M Doykan, C Wu, P Lawson, R Berry, J Krichevsky, A Cudkowicz, M Weiner, H AF Butovsky, Oleg Siddiqui, Shafiuddin Gabriely, Galina Lanser, Amanda Dake, Ben Gopal, Murugaiyan Doykan, Camille Wu, Pauline Lawson, Robert Berry, James Krichevsky, Anna Cudkowicz, Merit Weiner, Howard TI Identification of a Unique miRNA Signature in CD14(+)/CD16(-) Blood-Monocytes in ALS Subjects Identical to That Observed in SOD Mice SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Butovsky, Oleg] Harvard Univ, Brigham & Womens Hosp, Sch Med, Neurol Ctr Neurol Dis, Boston, MA 02115 USA. [Siddiqui, Shafiuddin; Gabriely, Galina; Lanser, Amanda; Dake, Ben; Doykan, Camille; Wu, Pauline] Brigham & Womens Hosp, Neurol Ctr Neurol Dis, Boston, MA 02115 USA. [Gopal, Murugaiyan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. [Krichevsky, Anna] Neurol Ctr Neurol Dis, Boston, MA USA. [Cudkowicz, Merit] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trial Unit, Charlestown, MA 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P05167 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802401 ER PT J AU Cai, XM Han, S Chou, S AF Cai, Xuemei Han, Steve Chou, Sherry TI Small but Consequential: A Case of Deep Intracerebral Hemorrhage (ICH) Caused by Distal Lenticulostriate Artery Aneurysm SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Cai, Xuemei; Chou, Sherry] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Han, Steve] Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA USA. RI Chou, Sherry/G-5779-2015 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P05218 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802464 ER PT J AU Chheda, M Wen, P Hochberg, F Chi, A Drappatz, J Yang, D Eichler, A Beroukhim, R Norden, A Gerstner, E Batchelor, T AF Chheda, Milan Wen, Patrick Hochberg, Fred Chi, Andrew Drappatz, Jan Yang, Daniel Eichler, April Beroukhim, Rameen Norden, Andrew Gerstner, Elizabeth Batchelor, Tracy TI Phase I Trial of Vandetanib Plus Sirolimus in Adults with Recurrent Glioblastoma SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Chheda, Milan] Mem Sloan Kettering Canc Ctr, Neurol & Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Wen, Patrick; Beroukhim, Rameen; Norden, Andrew] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Wen, Patrick; Beroukhim, Rameen; Norden, Andrew] Dana Farber Canc Inst, Dept Neurol, Boston, MA 02115 USA. [Wen, Patrick; Beroukhim, Rameen; Norden, Andrew] Brigham & Womens Canc Ctr, Boston, MA USA. [Hochberg, Fred; Chi, Andrew; Yang, Daniel; Eichler, April; Gerstner, Elizabeth; Batchelor, Tracy] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hochberg, Fred; Chi, Andrew; Yang, Daniel; Eichler, April; Gerstner, Elizabeth; Batchelor, Tracy] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Drappatz, Jan] Univ Pittsburgh, Neurooncol Program, Pittsburgh, PA 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P04180 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802290 ER PT J AU Chiquete, E Ruiz-Sandoval, J Rodriguez-Balaguer, R Magana-Zamora, L Saniger-Alba, M Gonzalez-Duarte, A Garcia-Ramos, G Ramos, A Steg, PG Bhatt, D Cantu-Brito, C AF Chiquete, Erwin Ruiz-Sandoval, Jose Rodriguez-Balaguer, Rainier Magana-Zamora, Lucia Saniger-Alba, Maria Gonzalez-Duarte, Alejandra Garcia-Ramos, Guillermo Ramos, Alma Steg, Philippe Gabriel Bhatt, Deepak Cantu-Brito, Carlos TI Four-Year Changing Patterns in Prescription of Anti-Atherothrombotic Drugs in the Latin American Cohort of the Worldwide Reduction of Atherothrombosis for Continued Health (REACH) Registry SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Chiquete, Erwin; Rodriguez-Balaguer, Rainier; Magana-Zamora, Lucia; Gonzalez-Duarte, Alejandra; Garcia-Ramos, Guillermo; Cantu-Brito, Carlos] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico. [Ruiz-Sandoval, Jose] Hosp Civil Guadalajara, Guadalajara, Jalisco, Mexico. [Saniger-Alba, Maria] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico. [Ramos, Alma] Clin Res Sanofi, Mexico City, DF, Mexico. [Steg, Philippe Gabriel] Hop Univ Paris Nord Val de Seine, AP HP, Hop Bichat, F-75877 Paris, France. [Steg, Philippe Gabriel] Univ Paris Diderot, Paris, France. [Bhatt, Deepak] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak] Harvard Univ, Sch Med, Boston, MA USA. RI Gonzalez-Duarte, Alejandra/N-3097-2013 OI Gonzalez-Duarte, Alejandra/0000-0002-2434-9560 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P01039 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800163 ER PT J AU David, W Oaklander, AL Pan, J Novak, P Brown, R Eichler, F AF David, William Oaklander, Anne Louise Pan, Jessica Novak, Peter Brown, Robert Eichler, Florian TI Neurophysiology and Intraepidermal Nerve Fiber Density in Hereditary Sensory and Autonomic Neuropathy Type 1 (HSAN1) SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [David, William; Oaklander, Anne Louise; Pan, Jessica; Eichler, Florian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Novak, Peter; Brown, Robert] Univ Massachusetts, Worcester, MA 01605 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P03202 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801468 ER PT J AU Davis, M Smith, C Sheehy, C Batish, SD Swanson, P Bird, T AF Davis, Marie Smith, Corrine Sheehy, Connor Batish, Sat Dev Swanson, Phillip Bird, Thomas TI Novel Mutations in Ataxia Telangiectasia and AOA2 Associated with Prolonged Survival SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Davis, Marie; Smith, Corrine; Sheehy, Connor; Swanson, Phillip] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Batish, Sat Dev] Athena Diagnost Inc, Worcester, MA USA. [Bird, Thomas] VA Puget Sound, Seattle, WA 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P05028 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803004 ER PT J AU Domoto-Reilly, K Negreira, A Brickhouse, M Sapolsky, D Dickerson, B AF Domoto-Reilly, Kimiko Negreira, Alyson Brickhouse, Michael Sapolsky, Daisy Dickerson, Bradford TI The Prodromal Phase of Frontotemporal Lobar Degeneration: Mild Cognitive Impairment of the FTLD Type SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Domoto-Reilly, Kimiko] Massachusetts Gen Hosp, Brookline, MA USA. [Negreira, Alyson; Brickhouse, Michael; Sapolsky, Daisy; Dickerson, Bradford] Massachusetts Gen Hosp, Charlestown, MA 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P07165 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803518 ER PT J AU Edlow, B Copen, W Glenn, M Greenberg, S Greer, D Wu, ON AF Edlow, Brian Copen, William Glenn, Mel Greenberg, Steven Greer, David Wu, Ona TI Diffusion Tensor Imaging Detects Neuronal Recovery after Traumatic Axonal Injury SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Edlow, Brian; Copen, William; Greenberg, Steven; Wu, Ona] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Edlow, Brian] Brigham & Womens Hosp, Boston, MA 02115 USA. [Glenn, Mel] Spaulding Rehabil Hosp, Boston, MA USA. [Greer, David] Yale New Haven Med Ctr, New Haven, CT 06504 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P06252 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803267 ER PT J AU Edlow, B Takahashi, E Cummings, P Klein, J Haynes, R Wu, O Greer, D Greenberg, S Kinney, H Folkerth, R AF Edlow, Brian Takahashi, Emi Cummings, Peter Klein, Joshua Haynes, Robin Wu, Ona Greer, David Greenberg, Steven Kinney, Hannah Folkerth, Rebecca TI Advanced MRI Neural Network Analysis for Determining the Neuroanatomic Basis of Traumatic Coma SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Edlow, Brian; Klein, Joshua; Folkerth, Rebecca] Brigham & Womens Hosp, Boston, MA 02115 USA. [Takahashi, Emi; Haynes, Robin; Kinney, Hannah] Childrens Hosp Boston, Boston, MA USA. [Cummings, Peter] Massachusetts Med Examiner, Boston, MA USA. [Wu, Ona; Greenberg, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greer, David] Yale New Haven Med Ctr, New Haven, CT 06504 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S47007 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803137 ER PT J AU Edlow, B Takahashi, E Cummings, P Klein, J Haynes, R Wu, O Greer, D Greenberg, S Kinney, H Folkerth, R AF Edlow, Brian Takahashi, Emi Cummings, Peter Klein, Joshua Haynes, Robin Wu, Ona Greer, David Greenberg, Steven Kinney, Hannah Folkerth, Rebecca TI Advanced MRI Neural Network Analysis for Determining the Neuroanatomic Basis of Traumatic Coma SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Edlow, Brian; Wu, Ona; Greenberg, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Edlow, Brian; Klein, Joshua; Folkerth, Rebecca] Brigham & Womens Hosp, Boston, MA 02115 USA. [Takahashi, Emi; Haynes, Robin; Kinney, Hannah] Childrens Hosp Boston, Boston, MA USA. [Greer, David] Yale New Haven Med Ctr, New Haven, CT 06504 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN31004 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800065 ER PT J AU Erten-Lyons, D Woltjer, R Dodge, H Silbert, L Kramer, P Kaye, J AF Erten-Lyons, Deniz Woltjer, Randall Dodge, Hiroko Silbert, Lisa Kramer, Patricia Kaye, Jeffrey TI Neuropathological Basis of Age-Associated Brain Atrophy SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Erten-Lyons, Deniz] Portland VA Med Ctr, Portland, OR USA. [Woltjer, Randall; Silbert, Lisa; Kramer, Patricia; Kaye, Jeffrey] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Dodge, Hiroko] Oregon Hlth & Sci Univ, Plymouth, MI 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P05053 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802412 ER PT J AU Fehnel, C Ayres, A Rost, N AF Fehnel, Corey Ayres, Alison Rost, Natalia TI Cocaine Use Is Associated with Ischemic Stroke among Well-Educated White Males SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Fehnel, Corey; Ayres, Alison; Rost, Natalia] 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P06224 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803249 ER PT J AU Feng, WN Sidorov, E Schlaug, G AF Feng, Wayne Sidorov, Evgeny Schlaug, Gottfried TI Absence of Upper Limb Movement within 72 Hours after Acute Ichemic Stroke Predicts Spasticity at 3 Months SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Feng, Wayne] Univ S Carolina, Charleston, SC USA. [Sidorov, Evgeny] Univ Oklahoma, Oklahoma City, OK USA. [Schlaug, Gottfried] Beth Israsel Deaconess Med Ctr, 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA PD2001 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800504 ER PT J AU Fox, M Pascual-Leone, A AF Fox, Michael Pascual-Leone, Alvaro TI Intrinsic Functional Connectivity with the Subgenual Cingulate Predicts Clinical Efficacy of TMS Targets for Depression SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Fox, Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Gen Hosp, Brookline, MA USA. [Pascual-Leone, Alvaro] Harvard Univ, Sch Med, Boston, MA USA. [Pascual-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P01.188 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800218 ER PT J AU Hammond, S Drappatz, J Lee, E Muzikansky, A Weiss, S Kesari, S Wong, E Fadul, C Norden, A Beroukhim, R Alexander, B Ruland, S Ciampa, A Lafrankie, D Doherty, L McCluskey, C Smith, K Gerard, M Wen, P AF Hammond, Samantha Drappatz, Jan Lee, Eudocia Muzikansky, Alona Weiss, Stephanie Kesari, Santosh Wong, Eric Fadul, Camilo Norden, Andrew Beroukhim, Rameen Alexander, Brian Ruland, Sandra Ciampa, Abigail Lafrankie, Debra Doherty, Lisa McCluskey, Christine Smith, Katrina Gerard, Mary Wen, Patrick TI Interim Analysis of a Randomized Placebo-Controlled Pilot Trial of Armodafinil for Fatigue in Patients with Malignant Gliomas Undergoing Radiotherapy with or without Standard Chemotherapy Treatment SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Hammond, Samantha; Ruland, Sandra; Ciampa, Abigail; Lafrankie, Debra; Doherty, Lisa; McCluskey, Christine; Smith, Katrina; Gerard, Mary] Dana Farber Canc Inst, Boston, MA 02115 USA. [Drappatz, Jan] Univ Virginia, Pittsburgh, PA USA. [Lee, Eudocia; Norden, Andrew; Beroukhim, Rameen; Wen, Patrick] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weiss, Stephanie; Alexander, Brian] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kesari, Santosh] Moores UCSD Canc Ctr, La Jolla, CA USA. [Wong, Eric] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Fadul, Camilo] Dartmouth Coll, Lebanon, NH USA. RI Kesari, Santosh/E-8461-2013 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P07104 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204804090 ER PT J AU Han, SD Gruhl, J Beckett, L Dodge, H Stricker, N Farias, S Mungas, D AF Han, S. Duke Gruhl, Jonathan Beckett, Laurel Dodge, Hiroko Stricker, Nikki Farias, Sarah Mungas, Dan TI Beta Amyloid, Tau, Neuroimaging, and Cognition: Sequence Modeling of Biomarkers for Alzheimer's Disease SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Han, S. Duke] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Gruhl, Jonathan] Univ Washington, Seattle, WA 98195 USA. [Beckett, Laurel] UC Davis, Davis, CA USA. [Dodge, Hiroko] Oregon Hlth & Sci Univ, Plymouth, MI USA. [Stricker, Nikki] VA Boston Healthcare Syst, Jamaica Plain, MA USA. [Farias, Sarah; Mungas, Dan] UC Davis, Sacramento, CA 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA PD1005 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800123 ER PT J AU Harel, N Song, KH Tang, X Spungen, A Strittmatter, S AF Harel, Noam Song, Kang Ho Tang, Xin Spungen, Ann Strittmatter, Stephen TI A Hebbian Approach to Retraining Spared Circuits after Spinal Cord Injury SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Harel, Noam] Mt Sinai Sch Med, Bronx, NY USA. [Song, Kang Ho; Tang, Xin; Strittmatter, Stephen] Yale Univ, New Haven, CT USA. [Spungen, Ann] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY USA. RI Strittmatter, Stephen/F-5739-2011 OI Strittmatter, Stephen/0000-0001-8188-3092 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P02005 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801123 ER PT J AU Helenius, J Avery, R Polnar, B Caceres, JA Siket, M Hakan, AY AF Helenius, Johanna Avery, Ross Polnar, Bethany Caceres, J. Alfredo Siket, Matthew Hakan, A. Y. TI The Relationship between Acute Stress Hyperglycemia and Infarct Volume in Ischemic Stroke SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Helenius, Johanna] HMS, MGH, Martinos Ctr, Boston, MA USA. [Avery, Ross; Polnar, Bethany; Caceres, J. Alfredo; Siket, Matthew] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hakan, A. Y.] HMS, MGH, Martinos Ctr, Charlestown, MA 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P07032 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204804022 ER PT J AU Howard, G Roubin, G Hopkins, LN Moore, W Gray, W Rosenfield, K Katzen, B Chakhtoura, E Morrish, W Ferguson, R Hye, R Shawl, F Harrigan, M Voeks, J Lal, B Meschia, J Brott, T AF Howard, George Roubin, Gary Hopkins, L. Nelson Moore, Wesley Gray, William Rosenfield, Kenneth Katzen, Barry Chakhtoura, Elie Morrish, William Ferguson, Robert Hye, Robert Shawl, Fayaz Harrigan, Mark Voeks, Jenifer Lal, Brajesh Meschia, James Brott, Thomas TI Did Carotid Stenting and Endarterectomy Outcomes Change over Time in the Carotid Revascularization Endarterectomy Versus Stenting Trial? SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Howard, George; Harrigan, Mark; Voeks, Jenifer] Univ Alabama Birmingham, Birmingham, AL USA. [Roubin, Gary] Lenox Hill Hosp, New York, NY 10021 USA. [Hopkins, L. Nelson] SUNY Buffalo, Dept Neurosurg, Buffalo, NY 14260 USA. [Moore, Wesley] Univ Calif Los Angeles, Los Angeles, CA USA. [Gray, William] Columbia Univ, New York Presbyterian Hosp, Med Ctr, New York, NY USA. [Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Katzen, Barry] Baptist Cardiac & Vasc Inst, Miami, FL USA. [Chakhtoura, Elie] Newark Beth Israel Med Ctr, Newark, NJ USA. [Morrish, William] Univ Calgary, Foothills Med Ctr, Calgary, AB, Canada. [Ferguson, Robert] MetroHlth Med Ctr, Cleveland, OH USA. [Hye, Robert] Kaiser Fdn Hosp, So Calif Permanente Med Grp, San Diego, CA USA. [Shawl, Fayaz] Washington Adventist Hosp, Takoma Pk, MD USA. [Lal, Brajesh] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Meschia, James; Brott, Thomas] Mayo Clin, Jacksonville, FL 32224 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S09005 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800431 ER PT J AU Hwang, D Yagoda, D Currier, P Perrey, H Tehan, T Guanci, M Ananian, L Lipkis-Orlando, R Cobb, JP Rosand, J AF Hwang, David Yagoda, Daniel Currier, Paul Perrey, Hilary Tehan, Tara Guanci, Mary Ananian, Lillian Lipkis-Orlando, Robin Cobb, J. Perren Rosand, Jonathan TI Prevalence of Depression and Anxiety Symptoms among Families of Survivors in a Neurosciences Intensive Care Unit SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Hwang, David; Yagoda, Daniel; Currier, Paul; Perrey, Hilary; Tehan, Tara; Guanci, Mary; Ananian, Lillian; Lipkis-Orlando, Robin; 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P02217 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801087 ER PT J AU Killoran, A Biglan, K Jankovic, J Eberly, S Kayson, E Oakes, D Young, A Shoulson, I AF Killoran, Annie Biglan, Kevin Jankovic, Joseph Eberly, Shirley Kayson, Elise Oakes, David Young, Anne Shoulson, Ira TI Analysis of the Behavioral Features Conferred by the Intermediate Allele for Huntington Disease in the Prospective Huntington at Risk Observational Study (PHAROS) SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Killoran, Annie; Biglan, Kevin; Eberly, Shirley; Kayson, Elise; Oakes, David] Univ Rochester, Rochester, NY USA. [Jankovic, Joseph] Baylor Coll Med, Houston, TX 77030 USA. [Young, Anne] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shoulson, Ira] Georgetown Univ, Washington, DC 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA PL01.003 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802098 ER PT J AU Kim, GM Arsava, EM Helenius, J Hakan, AY AF Kim, Gyeong-Moon Arsava, Ethem Murat Helenius, Johanna Hakan, A. Y. TI White Matter Hyperintensity Predicts Early Ischemic Stroke Recurrence SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Kim, Gyeong-Moon; Helenius, Johanna; Hakan, A. Y.] Harvard Univ, Sch Med, AA Martinos Ctr Biomed Imaging, Dept Radiol & Stroke Serv,Massachusetts Gen Hosp, Charlestown, MA USA. [Arsava, Ethem Murat] Martinos Ctr Biomed Imaging, Ankara, Turkey. 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S19006 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800475 ER PT J AU Lewis, R Wang, J Balkwill, D AF Lewis, Richard Wang, Joanne Balkwill, David TI Perceived Head Orientation and Eye Movements Are Abnormal in Vestibular Migraine during Combined Canal-Otolith Stimulation SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Lewis, Richard] Harvard Univ, Sch Med, Boston, MA USA. [Wang, Joanne] Brown Univ, Sch Med, Providence, RI 02912 USA. [Balkwill, David] Massachussetts Eye & Ear Infirm, 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P02254 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801147 ER PT J AU Ly, I Pine, A Stemmer-Rachamimov, A Hochberg, F Dietrich, J AF Ly, Ina Pine, Alexander Stemmer-Rachamimov, Anat Hochberg, Fred Dietrich, Jorg TI Clinical, Histopathologic, and Magnetic Resonance Imaging (MRI) Findings in Gliomatosis Cerebri SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Ly, Ina] Univ Washington, Seattle, WA 98195 USA. [Pine, Alexander] Cleveland Clin, Lerner Coll Med, Cleveland Hts, OH USA. [Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Charlestown, MA USA. [Hochberg, Fred; Dietrich, Jorg] 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P03139 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801447 ER PT J AU Lyons, J Kamat, A Misra, V Uno, H Singer, E Morgello, S Gabuzda, D AF Lyons, Jennifer Kamat, Anupa Misra, Vikas Uno, Hajime Singer, Elyse Morgello, Susan Gabuzda, Dana TI Monocyte Activation Markers in Cerebrospinal Fluid Are Associated with Impaired Neurocognitive Testing in Advanced HIV Infection SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Lyons, Jennifer; Kamat, Anupa; Misra, Vikas; Uno, Hajime; Gabuzda, Dana] Dana Farber Canc Inst, Boston, MA 02115 USA. [Singer, Elyse] Univ Calif Los Angeles, Los Angeles, CA USA. [Morgello, Susan] Mt Sinai Sch Med, New York, NY 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P01255 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800238 ER PT J AU Marshall, G Lorius, N Gidicsin, C Maye, J Becker, JA Amariglio, R Rentz, D Sperling, R Johnson, K AF Marshall, Gad Lorius, Natacha Gidicsin, Christopher Maye, Jacqueline Becker, J. Alex Amariglio, Rebecca Rentz, Dorene Sperling, Reisa Johnson, Keith TI Instrumental Activities of Daily Living Impairment Is Associated with Temporal and Parietal Hypometabolism in Mild Cognitive Impairment SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Marshall, Gad] Brigham & Womens Hosp, Brookline, MA USA. [Lorius, Natacha; Rentz, Dorene; Sperling, Reisa] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gidicsin, Christopher; Maye, Jacqueline; Becker, J. Alex; Amariglio, Rebecca; Johnson, Keith] 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P04214 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802111 ER PT J AU Martinez-Ramirez, S Ayres, A Gurol, E Rosand, J Greenberg, S Viswanathan, A AF Martinez-Ramirez, Sergi Ayres, Alison Gurol, Edip Rosand, Jonathan Greenberg, Steven Viswanathan, Anand TI Diagnostic Value of Lobar Microbleeds without Hemorrhagic Stroke: A Radiological-Pathological Correlation Study SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Martinez-Ramirez, Sergi; Ayres, Alison; Gurol, Edip; Rosand, Jonathan; Greenberg, Steven; Viswanathan, Anand] 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S23004 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801553 ER PT J AU Mejia, N El-Chemali, Z AF Mejia, Nicte El-Chemali, Zeina TI Psychiatric Comorbidities and Mortality among Hospitalized Parkinson Disease Patients SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Mejia, Nicte; El-Chemali, Zeina] 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P06068 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803425 ER PT J AU Merker, V Esparza, S Smith, M Stemmer-Rachamimov, A Plotkin, S AF Merker, Vanessa Esparza, Sonia Smith, Miriam Stemmer-Rachamimov, Anat Plotkin, Scott TI Clinical Features of the Schwannomatosis Tumor Suppressor Syndrome: A Retrospective Analysis of 87 Patients SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Merker, Vanessa; Esparza, Sonia; Smith, Miriam; Stemmer-Rachamimov, Anat; Plotkin, Scott] 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S45003 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803119 ER PT J AU Miller, T Smith, R Pestronk, A David, W Rothstein, J Simpson, E Andres, P Mahoney, K Allred, P Alexander, K Bishop, K Schoenfeld, D Macklin, E Norris, D Bennett, C Cudkowicz, M AF Miller, Timothy Smith, Richard Pestronk, Alan David, William Rothstein, Jeffrey Simpson, Ericka Andres, Patricia Mahoney, Katy Allred, Peggy Alexander, Katie Bishop, Kathie Schoenfeld, David Macklin, Erin Norris, Daniel Bennett, C. Cudkowicz, Merit TI Results of a Phase 1, Double-Blind, Placebo-Controlled, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of ISIS 333611 Administered Intrathecally to Patients with Familial ALS Due to SOD1 Gene Mutations SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Miller, Timothy; Pestronk, Alan; Allred, Peggy] Washington Univ, St Louis, MO USA. [Smith, Richard] Ctr Neurol Study, La Jolla, CA USA. [David, William; Schoenfeld, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rothstein, Jeffrey] Johns Hopkins Sch Med, Baltimore, MD USA. [Simpson, Ericka] Methodist Neurol Inst, Houston, TX USA. [Andres, Patricia] Massachusetts Gen Hosp, Reading, MA USA. [Mahoney, Katy; Macklin, Erin; Cudkowicz, Merit] Massachusetts Gen Hosp, Charlestown, MA USA. [Alexander, Katie; Bishop, Kathie; Norris, Daniel; Bennett, C.] ISIS Pharmaceut, Carlsbad, CA 92008 USA. RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S25001 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801582 ER PT J AU Nath, A Major, E Aksamit, A Calabrese, L Sejvar, J Kotton, C Barhams, M AF Nath, Avindra Major, Eugene Aksamit, Allen Calabrese, Leonard Sejvar, James Kotton, Camille Barhams, Maria TI Establishment of a Registry To Identify Cases of PML Using Uniform Diagnostic Criteria SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Nath, Avindra; Major, Eugene; Barhams, Maria] NINDS, NIH, Bethesda, MD 20892 USA. [Aksamit, Allen] Mayo Clin, Rochester, MN USA. [Calabrese, Leonard] Cleveland Clin, Cleveland, OH 44106 USA. [Sejvar, James] CDC, Decatur, GA USA. [Kotton, Camille] 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S08002 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800420 ER PT J AU Nayak, L Scott, J Bauchet, L Fraum, T Cooper, A Chao, S Suh, J Abrey, L Peereboom, D Zouaoui, S Fabbro-Peray, P Taillandier, L Rigao, V Vogelbaum, M Mathieu-Daude, H DeAngelis, L Shih, J Iwamoto, F AF Nayak, Lakshmi Scott, Jacob Bauchet, Luc Fraum, Tyler Cooper, Anna Chao, Samuel Suh, John Abrey, Lauren Peereboom, David Zouaoui, Sonia Fabbro-Peray, Pascale Taillandier, Luc Rigao, Valerie Vogelbaum, Michael Mathieu-Daude, Helene DeAngelis, Lisa Shih, Joanna Iwamoto, Fabio TI Recursive Partitioning Analysis Identifies Prognostic Groups for Glioblastoma Patients Aged 70 Years or Older SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Nayak, Lakshmi] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Scott, Jacob] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Radiat Oncol, Tampa, FL 33682 USA. [Bauchet, Luc; Zouaoui, Sonia] Hop St Eloi Gui de Chauliac, Dept Neurosurg, Montpellier, France. [Bauchet, Luc; Zouaoui, Sonia] Hop St Eloi Gui de Chauliac, INSERM, U583, Montpellier, France. [Fraum, Tyler] Duke Univ, Sch Med, Durham, NC USA. [Cooper, Anna] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Vogelbaum, Michael] Cleveland Clin Fdn, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44195 USA. [Abrey, Lauren] F Hoffmann La Roche Ltd, Basel, Switzerland. [Fabbro-Peray, Pascale] Inst Univ Rech Clin, Montpellier, France. [Taillandier, Luc] Hop Neurol, Nancy, France. [Rigao, Valerie] Hop Gui de Chauliac, Dept Pathl, Ctr Hosp Univ, Montpellier, France. [Mathieu-Daude, Helene] Languedoc Roussillon Registre Tumeurs Herault, Grp Neurooncol, Montpellier, France. [DeAngelis, Lisa] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Shih, Joanna] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Rockville, MD 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P07109 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204804095 ER PT J AU Overs, S Fitzpatrick, M Dryden, J Whitham, R Cameron, M AF Overs, Shannon Fitzpatrick, Mary Dryden, John Whitham, Ruth Cameron, Michelle TI The Effects of Dalfampridine on Walking Speed, Endurance, and Community Participation in a Veteran Population: A Retrospective Cohort Study SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Overs, Shannon] Neurol OHSU, Portland, OR USA. [Fitzpatrick, Mary; Whitham, Ruth; Cameron, Michelle] Portland VA Med Ctr, Portland, OR 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P04123 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802357 ER PT J AU Pugh, MJ Amuan, M AF Pugh, Mary Jo Amuan, Megan TI The Nexus of Traumatic Brain Injury and Epilepsy in Veterans from Afghanistan and Iraq SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Pugh, Mary Jo] Verdict S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Amuan, Megan] CHQOER Edith Nourse Rogers Mem VA Hosp, Bedford, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S06001 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800409 ER PT J AU Pugh, MJ Amuan, M AF Pugh, Mary Jo Amuan, Megan TI The Nexus of Traumatic Brain Injury and Epilepsy in Veterans from Afghanistan and Iraq SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Pugh, Mary Jo] Verdict S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Amuan, Megan] CHQOER Edith Nourse Rogers Mem VA Hosp, Bedford, MA 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN52002 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800043 ER PT J AU Reddy, C Mauermann, M Begna, K Ringler, M Jerath, N Amrami, K Spinner, R AF Reddy, Chandan Mauermann, Michelle Begna, Kebede Ringler, Michael Jerath, Nivedita Amrami, Kimberly Spinner, Robert TI Leukemic Infiltration of Peripheral Nerve: Case Series and Review of the Literature SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Reddy, Chandan; Mauermann, Michelle; Begna, Kebede; Ringler, Michael; Amrami, Kimberly; Spinner, Robert] Mayo Clin, Rochester, MN USA. [Jerath, Nivedita] 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P06133 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803390 ER PT J AU Ross, W Duda, J Abbott, R Petrovitch, H Tanner, C Masaki, K Uyehara-Lock, J Launer, L White, L AF Ross, Web Duda, John Abbott, Robert Petrovitch, Helen Tanner, Caroline Masaki, Kamal Uyehara-Lock, Jane Launer, Lenore White, Lon TI Association of Coffee and Caffeine Consumption with Brain Lewy Pathology in the Honolulu-Asia Aging Study SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Ross, Web] VA Pacific Isl Hlth Care Syst, Honolulu, HI USA. [Duda, John] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Abbott, Robert] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Petrovitch, Helen] Pacific Hlth Res & Educ Inst, Kailua, HI USA. [Tanner, Caroline] Parkinsons Inst, Sunnyvale, CA USA. [Masaki, Kamal] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Launer, Lenore] NIA, NIH, Washington, DC USA. [White, Lon] Kuakini Med Ctr, Honolulu, HI USA. [Uyehara-Lock, Jane] U Hawaii John A Burns Sch Med, Honolulu, HI 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S42005 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803107 ER PT J AU Rutkove, S Caress, J Cartwright, M Burns, T Warder, J David, W Goyal, N Maragakis, N Clawson, L Benatar, M Usher, S Sharma, K Gautam, S Narayanaswami, P Raynor, E Watson, ML Shefner, J AF Rutkove, Seward Caress, James Cartwright, Michael Burns, Ted Warder, Judy David, William Goyal, Namita Maragakis, Nicholas Clawson, Lora Benatar, Michael Usher, Sharon Sharma, Khema Gautam, Shiva Narayanaswami, Pushpa Raynor, Elizabeth Watson, Mary Lou Shefner, Jeremy TI Electrical Impedance Myography as a Biomarker To Assess ALS Progression SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Rutkove, Seward; Gautam, Shiva; Narayanaswami, Pushpa; Raynor, Elizabeth] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Caress, James; Cartwright, Michael] Wake Forest Univ, Winston Salem, NC 27109 USA. [Burns, Ted; Warder, Judy] Univ Virginia, Charlottesville, VA USA. [David, William; Goyal, Namita] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Maragakis, Nicholas; Clawson, Lora] Johns Hopkins Univ, Baltimore, MD USA. [Benatar, Michael; Sharma, Khema] Univ Miami, Miami, FL USA. [Usher, Sharon] Emory Univ, Atlanta, GA 30322 USA. [Watson, Mary Lou; Shefner, Jeremy] Upstate Med Ctr, Syracuse, NY 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S25006 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801577 ER PT J AU Salinthone, S Bourdette, D Carr, D AF Salinthone, Sonemany Bourdette, Dennis Carr, Daniel TI The Natural Antioxidant alpha-Tocopherol (Vitamin E) Activates the cAMP Signaling Cascade and Alters Immune Cell Function: Implications for MS Therapy SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Salinthone, Sonemany; Carr, Daniel] Portland VA Med Ctr, Portland, OR USA. [Bourdette, Dennis] Oregon Hlth & Sci Univ, Portland, OR 97201 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P05100 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803082 ER PT J AU Scharf, J Yu, DM Mathews, C Neale, B Stewart, E Fagerness, J Evans, P Gamazon, E Service, S Osiecki, L Illmann, C Cath, D King, R Dion, Y Sandor, P Barr, C Budman, C Lyon, G Grados, M Singer, H Jankovic, J Gilbert, D Hoekstra, P Heiman, G Tischfield, J State, M Robertson, M Kurlan, R Ophoff, R Gibbs, JR Cookson, M Hardy, J Singleton, A Ruiz-Linares, A Rouleau, G Heutink, P Oostra, B McMahon, W Freimer, N Cox, N Pauls, D AF Scharf, Jeremiah Yu, Dongmei Mathews, Carol Neale, Benjamin Stewart, Evelyn Fagerness, Jes Evans, Patrick Gamazon, Eric Service, Susan Osiecki, Lisa Illmann, Cornelia Cath, Danielle King, Robert Dion, Yves Sandor, Paul Barr, Cathy Budman, Cathy Lyon, Gholson Grados, Marco Singer, Harvey Jankovic, Joseph Gilbert, Donald Hoekstra, Pieter Heiman, Gary Tischfield, Jay State, Matthew Robertson, Mary Kurlan, Roger Ophoff, Roel Gibbs, J. Raphael Cookson, Mark Hardy, John Singleton, Andrew Ruiz-Linares, Andres Rouleau, Guy Heutink, Peter Oostra, Ben McMahon, William Freimer, Nelson Cox, Nancy Pauls, David TI Genome-Wide Association Study of Gilles de la Tourette Syndrome SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Yu, Dongmei; Neale, Benjamin] Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA USA. [Stewart, Evelyn] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Fagerness, Jes; Osiecki, Lisa] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mathews, Carol] Psychiat UCSF, San Francisco, CA USA. [Evans, Patrick; Gamazon, Eric; Cox, Nancy] Univ Chicago, Chicago, IL 60637 USA. [Service, Susan; Ophoff, Roel; Freimer, Nelson] Univ Calif Los Angeles, Los Angeles, CA USA. [Illmann, Cornelia] MGH, Boston, MA USA. [Cath, Danielle] Univ Utrecht, Utrecht, Netherlands. [State, Matthew] Yale Univ, Sch Med, New Haven, CT USA. [Dion, Yves; Rouleau, Guy] Univ Montreal, Montreal, PQ, Canada. [Dion, Yves; Sandor, Paul] Univ Toronto, Toronto, ON, Canada. [Budman, Cathy] N Shore LIJ Med Ctr, Manhasset, NY USA. [Lyon, Gholson] Childrens Hosp Philadephia, Philadelphia, PA USA. [Grados, Marco] Johns Hopkins Univ, Baltimore, MD USA. [Jankovic, Joseph] Baylor Coll Med, Houston, TX 77030 USA. [Gilbert, Donald] Cincinnati Childrens Med Ctr, Cincinnati, OH USA. [Hoekstra, Pieter] Univ Groningen, Groningen, Netherlands. [Heiman, Gary; Tischfield, Jay] Rutgers State Univ, Piscataway, NJ USA. [Robertson, Mary] St George Hosp, London, England. [Kurlan, Roger] Atlantic Neurosci Inst, Summit, NJ USA. [Gibbs, J. Raphael; Cookson, Mark; Singleton, Andrew] NIH, Bethesda, MD 20892 USA. [Hardy, John; Ruiz-Linares, Andres] UCL, London, England. [Heutink, Peter] Dept Clin Genet, Amsterdam, Netherlands. [Oostra, Ben] Erasmus Univ, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands. [McMahon, William] Univ Utah, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN101002 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204804240 ER PT J AU Scharf, J Yu, DM Mathews, C Neale, B Stewart, E Fagerness, J Evans, P Gamazon, E Service, S Osiecki, L Illmann, C Cath, D King, R Dion, Y Sandor, P Barr, C Budman, C Lyon, G Grados, M Singer, H Jankovic, J Gilbert, D Hoekstra, P Heiman, G Tischfield, J State, M Robertson, M Kurlan, R Ophoff, R Gibbs, JR Cookson, M Hardy, J Singleton, A Ruiz-Linares, A Rouleau, G Heutink, P Oostra, B McMahon, W Freimer, N Cox, N Pauls, D AF Scharf, Jeremiah Yu, Dongmei Mathews, Carol Neale, Benjamin Stewart, Evelyn Fagerness, Jes Evans, Patrick Gamazon, Eric Service, Susan Osiecki, Lisa Illmann, Cornelia Cath, Danielle King, Robert Dion, Yves Sandor, Paul Barr, Cathy Budman, Cathy Lyon, Gholson Grados, Marco Singer, Harvey Jankovic, Joseph Gilbert, Donald Hoekstra, Pieter Heiman, Gary Tischfield, Jay State, Matthew Robertson, Mary Kurlan, Roger Ophoff, Roel Gibbs, J. Raphael Cookson, Mark Hardy, John Singleton, Andrew Ruiz-Linares, Andres Rouleau, Guy Heutink, Peter Oostra, Ben McMahon, William Freimer, Nelson Cox, Nancy Pauls, David TI Genome-Wide Association Study of Gilles de la Tourette Syndrome SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Yu, Dongmei; Neale, Benjamin; Pauls, David] Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA USA. [Mathews, Carol] Psychiat UCSF, San Francisco, CA USA. [Stewart, Evelyn] Univ British Columbia, Vancouver, BC, Canada. [Fagerness, Jes; Osiecki, Lisa; Illmann, Cornelia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Evans, Patrick; Gamazon, Eric; Cox, Nancy] Univ Chicago, Chicago, IL 60637 USA. [Service, Susan; Ophoff, Roel; Freimer, Nelson] Univ Calif Los Angeles, Los Angeles, CA USA. [Cath, Danielle] Univ Utrecht, Utrecht, Netherlands. [State, Matthew] Yale Univ, Sch Med, New Haven, CT USA. [Dion, Yves; Rouleau, Guy] Univ Montreal, Montreal, PQ, Canada. [Sandor, Paul; Barr, Cathy] Univ Toronto, Toronto, ON, Canada. [Budman, Cathy] N Shore LIJ Med Ctr, Manhasset, NY USA. [Lyon, Gholson] Childrens Hosp Philadephia, Philadelphia, MA USA. [Grados, Marco] Johns Hopkins Univ, Baltimore, MD USA. [Singer, Harvey] Johns Hopkins, Baltimore, MD USA. [Jankovic, Joseph] Baylor Coll Med, Houston, TX 77030 USA. [Gilbert, Donald] Cincinnati Childrens Med Ctr, Cincinnati, OH USA. [Hoekstra, Pieter] Univ Groningen, Groningen, Netherlands. [Heiman, Gary; Tischfield, Jay] Rutgers State Univ, Piscataway, NJ USA. [Robertson, Mary] St George Hosp, London, England. [Kurlan, Roger] Atlantic Neurosci Inst, Summit, NJ USA. [Gibbs, J. Raphael; Cookson, Mark; Singleton, Andrew] NIH, Bethesda, MD 20892 USA. [Hardy, John; Ruiz-Linares, Andres] UCL, London, England. [Heutink, Peter] Dept Clin Genet, Amsterdam, Netherlands. [Oostra, Ben] Erasmus Univ, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands. [McMahon, William] Univ Utah, Salt Lake City, UT USA. RI Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Stewart, Evelyn/K-6961-2014 NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S32006 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802034 ER PT J AU Shapiro, K Bove, R Volpicelli, E Stone, J AF Shapiro, Kevin Bove, Riley Volpicelli, Elgida Stone, John TI Relapsing Course of IgG4-Related Pachymeningitis SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Shapiro, Kevin; Stone, John] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bove, Riley; Volpicelli, Elgida] Brigham & Womens Hosp, Boston, MA 02115 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P01112 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800285 ER PT J AU Shefner, J Andrews, J Bedlack, R Berry, J Goslin, K Jackson, C Kissel, J Lange, D Licht, J Mozaffar, T Pestronk, A Rosenfeld, J Wolff, A Lee, J Masonek, J Jones, D Meng, L Cedarbaum, J AF Shefner, Jeremy Andrews, Jinsy Bedlack, Richard Berry, James Goslin, Kimberly Jackson, Carlayne Kissel, John Lange, Dale Licht, Jonathan Mozaffar, Tahseen Pestronk, Alan Rosenfeld, Jeffrey Wolff, Andrew Lee, Jacqueline Masonek, Jean Jones, Drew Meng, Lisa Cedarbaum, Jesse TI A Study To Evaluate Safety and Tolerability of CK-2017357 (CK-357) in Patients with Amyotrophic Lateral Sclerosis Using a Twice-Daily, Dose-Titration Regimen SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Shefner, Jeremy] SUNY Upstate Med Univ, Syracuse, NY USA. [Andrews, Jinsy] Univ Connecticut, Ctr Hlth, Tappan, NY USA. [Bedlack, Richard] Duke Univ, Durham, NC USA. [Berry, James] Massachusetts Gen Hosp, Charlestown, MA USA. [Goslin, Kimberly] Providence Portland Med Ctr, Portland, OR USA. [Jackson, Carlayne] Univ Texas San Antonio, San Antonio, TX USA. [Kissel, John] Ohio State Univ, Columbus, OH 43210 USA. [Lange, Dale] Hosp Special Surg, New York, NY 10021 USA. [Licht, Jonathan] Univ Calif San Diego, San Diego, CA 92103 USA. [Mozaffar, Tahseen] Univ Calif Irvine, Orange, CA 92668 USA. [Pestronk, Alan] Washington Univ, St Louis, MO USA. [Rosenfeld, Jeffrey] UCSF Fresno, Fresno, CA USA. [Wolff, Andrew; Lee, Jacqueline; Jones, Drew; Cedarbaum, Jesse] Cytokinetics Inc, San Francisco, CA USA. [Masonek, Jean; Meng, Lisa] Cytokinetics, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P04155 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802138 ER PT J AU Sherman, A Leitner, M Sinani, E Katsovskiy, I Cudkowicz, M AF Sherman, Alexander Leitner, Melanie Sinani, Ervin Katsovskiy, Igor Cudkowicz, Merit TI Platform for Clinical Trials Data Integration and Sharing as a Unique Industry, Academic, and Foundation Collaboration Resource in ALS Research SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Sherman, Alexander; Sinani, Ervin; Katsovskiy, Igor; Cudkowicz, Merit] Massachusetts Gen Hosp, Charlestown, MA USA. [Leitner, Melanie] Prize4Life, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P01091 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800152 ER PT J AU Sheth, K Yoo, A Gonzalez, R Kimberly, W Chaudhry, Z Elm, J Jacobson, S Davis, S Donnan, G Albers, G Stern, B AF Sheth, Kevin Yoo, Albert Gonzalez, Roberto Kimberly, William Chaudhry, Zeshan Elm, Jordan Jacobson, Sven Davis, Stephen Donnan, Geoffrey Albers, Gregory Stern, Barney TI Hemisphere Volume Is Associated with Neurological Deterioration and Outcome after Malignant Infarction SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Sheth, Kevin; Stern, Barney] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Yoo, Albert; Gonzalez, Roberto; Kimberly, William; Chaudhry, Zeshan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Elm, Jordan] Med Univ S Carolina, Charleston, SC 29425 USA. [Jacobson, Sven] Remedy Pharmaceut, New York, NY USA. [Davis, Stephen] Univ Melbourne, Parkville, Vic 3052, Australia. [Donnan, Geoffrey] Univ Melbourne, Carlton, Vic, Australia. [Albers, Gregory] Stanford, Stanford, CA 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P07034 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204804024 ER PT J AU Song, S Fonarow, G Pan, WQ Olson, D Hernandez, A Peterson, E Reeves, M Smith, E Schwamm, L Saver, J AF Song, Sarah Fonarow, Gregg Pan, Wenqin Olson, DaiWai Hernandez, Adrian Peterson, Eric Reeves, Mathew Smith, Eric Schwamm, Lee Saver, Jeffrey TI Improved Clinical Outcomes in Medicare Beneficiaries with Acute Ischemic Stroke during Initial Implementation of the Get with the Guidelines-Stroke Program 2003-2008 SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Song, Sarah; Fonarow, Gregg; Saver, Jeffrey] Univ Calif Los Angeles, Los Angeles, CA USA. [Pan, Wenqin; Olson, DaiWai; Hernandez, Adrian; Peterson, Eric] Duke Univ, Sch Med, Durham, NC USA. [Reeves, Mathew] Michigan State Univ, E Lansing, MI 48824 USA. [Smith, Eric] Univ Calgary, Calgary, AB, Canada. [Schwamm, Lee] 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S19003 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800478 ER PT J AU Song, S Fonarow, G Pan, WQ Olson, D Hernandez, A Peterson, E Reeves, M Smith, E Schwamm, L Saver, J AF Song, Sarah Fonarow, Gregg Pan, Wenqin Olson, DaiWai Hernandez, Adrian Peterson, Eric Reeves, Mathew Smith, Eric Schwamm, Lee Saver, Jeffrey TI Improved Clinical Outcomes in Medicare Beneficiaries with Acute Ischemic Stroke during Initial Implementation of the Get with the Guidelines-Stroke Program 2003-2008 SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Song, Sarah; Fonarow, Gregg; Saver, Jeffrey] Univ Calif Los Angeles, Los Angeles, CA USA. [Pan, Wenqin; Olson, DaiWai; Hernandez, Adrian; Peterson, Eric] Duke Univ, Sch Med, Durham, NC USA. [Reeves, Mathew] Michigan State Univ, E Lansing, MI 48824 USA. [Smith, Eric] Univ Calgary, Calgary, AB, Canada. [Schwamm, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN22002 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800010 ER PT J AU Tanaka, Y Ojo, E Spiro, A Cahana-Amitay, D Albert, M AF Tanaka, Yutaka Ojo, Emmanuel Spiro, Avron, III Cahana-Amitay, Dalia Albert, Martin TI Clip Test*: A Brief Test of Motor Skills in Aging and Dementia SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Tanaka, Yutaka] Tanaka Clin, Nara, Japan. [Spiro, Avron, III] Boston Univ, Sch Med, Sch Publ Hlth, Boston, MA 02118 USA. [Cahana-Amitay, Dalia] Boston Univ, Sch Med, Dept Neurol, VA Boston Healthcare Syst, Boston, MA 02118 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P04210 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802115 ER PT J AU Teng, EM Tassniyom, K Lu, P AF Teng, Edmond Tassniyom, Kanida Lu, Po TI Reduced Quality of Life Ratings in Mild Cognitive Impairment: Analyses of Subject and Informant Responses SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Teng, Edmond] Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Tassniyom, Kanida] Khon Kaen Univ, Khon Kaen, Thailand. 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P04208 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802117 ER PT J AU Terry, A Barker, F Leffert, L Bateman, B Souter, I Plotkin, S AF Terry, Anna Barker, Fred Leffert, Lisa Bateman, Brian Souter, Irene Plotkin, Scott TI Outcomes of Hospitalization in Pregnant Women with Brain Tumors: A Population-Based Study SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Terry, Anna; Barker, Fred; Leffert, Lisa; Bateman, Brian; Souter, Irene; Plotkin, Scott] 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P07112 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204804098 ER PT J AU Volz, M Suarez-Contreras, V Mendonca, M Pinheiro, FS Merabet, L Fregni, F AF Volz, Magdalena Suarez-Contreras, Vanessa Mendonca, Mariana Pinheiro, Fernando Santos Merabet, Lotfi Fregni, Felipe TI Modulatory Effects of Somatosensory Tasks on Pain Thresholds and Cortical Excitability SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Volz, Magdalena; Suarez-Contreras, Vanessa; Mendonca, Mariana; Pinheiro, Fernando Santos; Fregni, Felipe] Spaulding Rehabil Hosp, Lab Neuromodulat, Dept Phys Med & Rehabil, Boston, MA USA. [Volz, Magdalena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Merabet, Lotfi] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P01172 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800268 ER PT J AU Wang, NS Gibbons, C Lafo, J Freeman, R AF Wang, Ningshan Gibbons, Christopher Lafo, Jacob Freeman, Roy TI Alpha Synuclein as a Cutaneous Biomarker of Parkinson Disease SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Wang, Ningshan] Beth Isreal Deaconess Med Ctr, Boston, MA USA. [Gibbons, Christopher; Lafo, Jacob; Freeman, Roy] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P05195 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802445 ER PT J AU Yerramilli-Rao, P Giannikopoulos, O Kublis, K Pan, J Eichler, F AF Yerramilli-Rao, Padmaja Giannikopoulos, Ourania Kublis, Kim Pan, Jessica Eichler, Florian TI The Natural History of Late Onset Tay-Sachs Disease SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Yerramilli-Rao, Padmaja] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Giannikopoulos, Ourania; Pan, Jessica] MGH, Charlestown, MA USA. [Kublis, Kim] NTSAD, Boston, MA USA. [Eichler, Florian] Massachusetts Gen Hosp, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P01243 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800287 ER PT J AU Zaidat, O Meagher, S Brant-Zawadzki, M Farkas, J Malek, R Crandall, B Frei, D Hui, F Alexander, M Chong, B Janjua, N Shaff, D Yavagal, D Heck, D Malisch, T Turk, A Hayakawa, M Miskolczi, L Tarr, R Ortiz, R Zauner, A Klucznik, R Zylak, C Yoo, A Mualem, E Bose, A Sit, SP AF Zaidat, Osama Meagher, Sean Brant-Zawadzki, Michael Farkas, Jeffrey Malek, Reza Crandall, Benjamin Frei, Donald Hui, Ferdinand Alexander, Michael Chong, Brian Janjua, Nazli Shaff, Darryn Yavagal, Dileep Heck, Donald Malisch, Tim Turk, Aquilla, III Hayakawa, Minako Miskolczi, Laszlo Tarr, Robert Ortiz, Rafael Zauner, Alois Klucznik, Richard Zylak, Christopher Yoo, Albert Mualem, Elan Bose, Arani Sit, Siu Po CA PICS Investigators TI Image Guided Patient Selection and Its Impact on Outcome: Results of the Penumbra Imaging Collaborative Study (PICS) SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Zaidat, Osama] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Meagher, Sean] OSF St Francis Med Ctr, Peoria, IL USA. [Brant-Zawadzki, Michael] Hoag Hosp, Newport Beach, CA USA. [Farkas, Jeffrey] Maimonides Hosp, Brooklyn, NY 11219 USA. [Malek, Reza] Good Samaritan Hosp, San Jose, CA USA. [Crandall, Benjamin] Abbott NW Hosp, Minneapolis, MN 55407 USA. [Frei, Donald] Swedish Med Ctr, Englewood, CO 80110 USA. [Hui, Ferdinand] Cleveland Clin, Cleveland, OH 44106 USA. [Alexander, Michael] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Chong, Brian] Mayo Clin, Phoenix, AZ USA. [Janjua, Nazli] Long Isl Coll Hosp, Brooklyn, NY 11201 USA. [Shaff, Darryn] Lehigh Valley Hlth Network, Allentown, PA USA. [Yavagal, Dileep] Jackson Mem Hosp, Miami, FL 33136 USA. [Heck, Donald] Forsyth Med Ctr, Winston Salem, NC USA. [Malisch, Tim] Alexian Bros Med Ctr, Elk Grove Village, IL USA. [Turk, Aquilla, III] Med Univ S Carolina, Charleston, SC 29425 USA. [Hayakawa, Minako] Univ Iowa Hlth Care, Iowa City, IA USA. [Miskolczi, Laszlo] Holy Cross Hosp, Ft Lauderdale, FL USA. [Tarr, Robert] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Ortiz, Rafael] Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York, NY USA. [Zauner, Alois] Santa Barbara Cottage Hosp, Santa Barbara, CA USA. [Klucznik, Richard] Methodist Hosp, Houston, TX 77030 USA. [Zylak, Christopher] Providence Sacred Heart Med Ctr, Spokane, WA USA. [Yoo, Albert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mualem, Elan; Bose, Arani; Sit, Siu Po] Penumbra Inc, Alameda, CA USA. [PICS Investigators] PICS, Alameda, CA 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S03004 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800394 ER PT J AU Zaidat, O Meagher, S Brant-Zawadzki, M Farkas, J Malek, R Crandall, B Frei, D Hui, F Alexander, M Chong, B Janjua, N Shaff, D Yavagal, D Heck, D Malisch, T Turk, A Hayakawa, M Miskolczi, L Tarr, R Ortiz, R Zauner, A Klucznik, R Zylak, C Yoo, A Mualem, E Bose, A Sit, SP AF Zaidat, Osama Meagher, Sean Brant-Zawadzki, Michael Farkas, Jeffrey Malek, Reza Crandall, Benjamin Frei, Donald Hui, Ferdinand Alexander, Michael Chong, Brian Janjua, Nazli Shaff, Darryn Yavagal, Dileep Heck, Donald Malisch, Tim Turk, Aquilla, III Hayakawa, Minako Miskolczi, Laszlo Tarr, Robert Ortiz, Rafael Zauner, Alois Klucznik, Richard Zylak, Christopher Yoo, Albert Mualem, Elan Bose, Arani Sit, Siu Po CA PICS Investigators TI Image Guided Patient Selection and Its Impact on Outcome: Results of the Penumbra Imaging Collaborative Study (PICS) SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Zaidat, Osama] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Meagher, Sean] OSF St Francis Med Ctr, Peoria, IL USA. [Brant-Zawadzki, Michael] Hoag Hosp, Newport Beach, CA USA. [Farkas, Jeffrey] Maimonides Hosp, Brooklyn, NY 11219 USA. [Malek, Reza] Good Samaritan Hosp, San Jose, CA USA. [Crandall, Benjamin] Abbott NW Hosp, Minneapolis, MN 55407 USA. [Frei, Donald] Swedish Med Ctr, Englewood, CO 80110 USA. [Hui, Ferdinand] Cleveland Clin, Cleveland, OH 44106 USA. [Alexander, Michael] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Chong, Brian] Mayo Clin, Phoenix, AZ USA. [Janjua, Nazli] Long Isl Coll Hosp, Brooklyn, NY 11201 USA. [Shaff, Darryn] Lehigh Valley Hlth Network, Allentown, PA USA. [Yavagal, Dileep] Jackson Mem Hosp, Miami, FL 33136 USA. [Heck, Donald] Forsyth Med Ctr, Winston Salem, NC USA. [Malisch, Tim] Alexian Bros Med Ctr, Elk Grove Village, IL USA. [Turk, Aquilla, III] Med Univ S Carolina, Charleston, SC USA. [Hayakawa, Minako] Univ Iowa Hlth Care, Iowa City, IA USA. [Miskolczi, Laszlo] Holy Cross Hosp, Ft Lauderdale, FL USA. [Tarr, Robert] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Ortiz, Rafael] St Lukes Roosevelt Hosp, New York, NY USA. [Zauner, Alois] Santa Barbara Cottage Hosp, Santa Barbara, CA USA. [Klucznik, Richard] Methodist Hosp, Houston, TX 77030 USA. [Zylak, Christopher] Providence Sacred Heart Med Ctr, Spokane, WA USA. [Yoo, Albert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mualem, Elan; Bose, Arani; Sit, Siu Po] Penumbra Inc, Alameda, CA USA. [PICS Investigators] PICS Alameda, Alameda, CA 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 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN21002 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800030 ER PT J AU James, IB Wang, Z Hannon, MJ Kwoh, CK AF James, I. B. Wang, Z. Hannon, M. J. Kwoh, C. K. TI SPECIFIC KNEE PAIN PATTERNS ON THE KNEE PAIN MAP ARE ASSOCIATED WITH DIFFERENT LEVELS OF FUNCTIONAL PERFORMANCE - DATA FROM THE OAI SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress on Osteoarthritis CY APR 26-29, 2012 CL Barcelona, SPAIN C1 [James, I. B.; Wang, Z.; Hannon, M. J.; Kwoh, C. K.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kwoh, C. K.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2012 VL 20 SU 1 BP S253 EP S254 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 931MF UT WOS:000303223300527 ER PT J AU Ruhdorfer, AS Dannhauer, T Wirth, W Hudelmaier, M Sattler, M Kwoh, CK Guermazi, A Hunter, DJ Benichou, O Eckstein, F AF Ruhdorfer, A. S. Dannhauer, T. Wirth, W. Hudelmaier, M. Sattler, M. Kwoh, C. K. Guermazi, A. Hunter, D. J. Benichou, O. Eckstein, F. CA OAI Investigators TI THIGH MUSCLE CROSS-SECTIONAL AREAS AND STRENGTH ARE NOT REDUCED IN ADVANCED VERSUS EARLY PAINFUL KNEE OSTEOARTHRITIS - A BETWEEN-KNEE WITHIN-PERSON COMPARISON IN OAI PARTICIPANTS SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress on Osteoarthritis CY APR 26-29, 2012 CL Barcelona, SPAIN C1 [Ruhdorfer, A. S.; Dannhauer, T.; Wirth, W.; Hudelmaier, M.; Sattler, M.; Eckstein, F.] Paracelsus Med Univ, Salzburg, Austria. [Dannhauer, T.; Wirth, W.; Hudelmaier, M.; Eckstein, F.] Chondrometr GmbH, Ainring, Germany. [Kwoh, C. K.] Univ Pittsburgh, Div Rheumatol & Clin Immunol, Pittsburgh, PA USA. [Kwoh, C. K.] VA Pittsburgh Hlthcare Syst, Pittsburgh, PA USA. [Guermazi, A.] Boston Univ, Med Ctr, Dept Radiol, Boston, MA 02118 USA. [Guermazi, A.] BICL, Boston, MA USA. [Hunter, D. J.] Royal N Shore Hosp, Sydney, NSW, Australia. [Hunter, D. J.] Univ Sydney, No Clin Sch, Sydney, NSW 2006, Australia. [Benichou, O.] Eli Lilly & Co, Indianapolis, IN 46285 USA. RI Hunter, David/A-4622-2010 OI Hunter, David/0000-0003-3197-752X NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2012 VL 20 SU 1 BP S215 EP S215 PG 1 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 931MF UT WOS:000303223300454 ER PT J AU Singh, JA Kwoh, C Richardson, D Chen, W Ibrahim, S AF Singh, J. A. Kwoh, C. Richardson, D. Chen, W. Ibrahim, S. TI FEMALE GENDER IS PROTECTIVE FOR OUTCOMES AFTER PRIMARY TOTAL KNEE ARTHROPLASTY: A RISK-ADJUSTED ANALYSIS SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress on Osteoarthritis CY APR 26-29, 2012 CL Barcelona, SPAIN C1 [Singh, J. A.] Univ Alabama, Birmingham, AL USA. [Singh, J. A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Kwoh, C.] Univ Pittsburgh, Pittsburgh, PA USA. [Kwoh, C.] Pittsburgh VA Med Ctr, Pittsburgh, PA USA. [Richardson, D.; Chen, W.; Ibrahim, S.] Univ Penn, Philadelphia, PA 19104 USA. [Richardson, D.; Chen, W.; Ibrahim, S.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2012 VL 20 SU 1 BP S294 EP S294 PG 1 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 931MF UT WOS:000303223300613 ER PT J AU Censor, Y Unkelbach, J AF Censor, Yair Unkelbach, Jan TI From analytic inversion to contemporary IMRT optimization: Radiation therapy planning revisited from a mathematical perspective SO PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS LA English DT Review DE Radiation therapy treatment planning; Algebraic inverse planning; Inverse problem; IMRT ID BEAM ANGLE OPTIMIZATION; ROTATION THERAPY; CONFORMAL RADIOTHERAPY; X-RAYS; ARC; DISTRIBUTIONS; PROJECTIONS; ALGORITHMS; TRANSFORM; DELIVERY AB In this paper we look at the development of radiation therapy treatment planning from a mathematical point of view. Historically, planning for Intensity-Modulated Radiation Therapy (IMRT) has been considered as an inverse problem. We discuss first the two fundamental approaches that have been investigated to solve this inverse problem: Continuous analytic inversion techniques on one hand, and fully-discretized algebraic methods on the other hand. In the second part of the paper, we review another fundamental question which has been subject to debate from the beginning of IMRT until the present day: The rotation therapy approach versus fixed angle IMRT. This builds a bridge from historic work on IMRT planning to contemporary research in the context of Intensity-Modulated Arc Therapy (IMAT). (C) 2011 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved. C1 [Censor, Yair] Univ Haifa, Dept Math, IL-31905 Haifa, Israel. [Unkelbach, Jan] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Unkelbach, Jan] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Censor, Y (reprint author), Univ Haifa, Dept Math, IL-31905 Haifa, Israel. EM yair@math.haifa.ac.il; junkelbach@partners.org FU United States-Israel Binational Science Foundation (BSF) [200912]; National Heart, Lung, And Blood Institute [R01HL070472] FX We thank our colleagues Martin Altschuler, Thomas Bortfeld, Tommy Elfving, James Galvin, Gabor Herman, Uwe Oelfke, William Powlis, Reinhard Schulte, Ying Xiao, Lei Xing and members of their research groups with whom we worked over the years and from whom we learned so much about radiation therapy treatment planning and other inverse problems. We are grateful to the anonymous referees whose insightful comments on earlier versions helped us to improve this paper and to the Editor Fridtjof Nusslin for his unusual encouragement throughout the evaluation and revisions of the paper. The work of Y.C. on this paper was partially supported by a United States-Israel Binational Science Foundation (BSF) Grant number 200912 and by Award Number R01HL070472 from the National Heart, Lung, And Blood Institute. NR 61 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1120-1797 J9 PHYS MEDICA JI Phys. Medica PD APR PY 2012 VL 28 IS 2 BP 109 EP 118 DI 10.1016/j.ejmp.2011.04.002 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 933PF UT WOS:000303373700002 PM 21616694 ER PT J AU Tsai, AC Hung, KJ Weiser, SD AF Tsai, Alexander C. Hung, Kristin J. Weiser, Sheri D. TI Is Food Insecurity Associated with HIV Risk? Cross-Sectional Evidence from Sexually Active Women in Brazil SO PLOS MEDICINE LA English DT Article ID INTIMATE-PARTNER VIOLENCE; CONDOM USE; YOUNG-WOMEN; INTRAHOUSEHOLD ALLOCATION; TRANSACTIONAL SEX; MENTAL-HEALTH; AIDS EPIDEMIC; URBAN KENYA; RURAL INDIA; POPULATION AB Background: Understanding how food insecurity among women gives rise to differential patterning in HIV risks is critical for policy and programming in resource-limited settings. This is particularly the case in Brazil, which has undergone successive changes in the gender and socio-geographic composition of its complex epidemic over the past three decades. We used data from a national survey of Brazilian women to estimate the relationship between food insecurity and HIV risk. Methods and Findings: We used data on 12,684 sexually active women from a national survey conducted in Brazil in 2006-2007. Self-reported outcomes were (a) consistent condom use, defined as using a condom at each occasion of sexual intercourse in the previous 12 mo; (b) recent condom use, less stringently defined as using a condom with the most recent sexual partner; and (c) itchy vaginal discharge in the previous 30 d, possibly indicating presence of a sexually transmitted infection. The primary explanatory variable of interest was food insecurity, measured using the culturally adapted and validated Escala Brasiliera de Seguranc, a Alimentar. In multivariable logistic regression models, severe food insecurity with hunger was associated with a reduced odds of consistent condom use in the past 12 mo (adjusted odds ratio [AOR] = 0.67; 95% CI, 0.48-0.92) and condom use at last sexual intercourse (AOR = 0.75; 95% CI, 0.57-0.98). Self-reported itchy vaginal discharge was associated with all categories of food insecurity (with AORs ranging from 1.46 to 1.94). In absolute terms, the effect sizes were large in magnitude across all outcomes. Underweight and/or lack of control in sexual relations did not appear to mediate the observed associations. Conclusions: Severe food insecurity with hunger was associated with reduced odds of condom use and increased odds of itchy vaginal discharge, which is potentially indicative of sexually transmitted infection, among sexually active women in Brazil. Interventions targeting food insecurity may have beneficial implications for HIV prevention in resource-limited settings. C1 [Tsai, Alexander C.] Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Hung, Kristin J.] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Weiser, Sheri D.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USA. RP Tsai, AC (reprint author), Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. EM atsai@hsph.harvard.edu OI Tsai, Alexander/0000-0001-6397-7917 FU Robert Wood Johnson Foundation; U.S. National Institute of Health [K23 MH079713]; Hellman Family Foundation; Burke Family Foundation FX ACT receives salary support from the Robert Wood Johnson Foundation Health and Society Scholars Program. SDW receives salary support from U.S. National Institute of Health K23 MH079713, the Hellman Family Foundation, and the Burke Family Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 78 TC 26 Z9 26 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD APR PY 2012 VL 9 IS 4 AR e1001203 DI 10.1371/journal.pmed.1001203 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 933VZ UT WOS:000303393800006 PM 22505852 ER PT J AU Tsai, AC Eisa, MA Crosby, SS Sirkin, S Heisler, M Leaning, J Iacopino, V AF Tsai, Alexander C. Eisa, Mohammed A. Crosby, Sondra S. Sirkin, Susannah Heisler, Michele Leaning, Jennifer Iacopino, Vincent TI Medical Evidence of Human Rights Violations against Non-Arabic-Speaking Civilians in Darfur: A Cross-Sectional Study SO PLOS MEDICINE LA English DT Article ID STANDARDIZED PATIENTS; PSYCHOLOGICAL SEQUELAE; CHART ABSTRACTION; SEXUAL VIOLENCE; WAR TRAUMA; TORTURE; MORTALITY; RAPE; CARE; REFUGEES AB Background: Ongoing conflict in the Darfur region of Sudan has resulted in a severe humanitarian crisis. We sought to characterize the nature and geographic scope of allegations of human rights violations perpetrated against civilians in Darfur and to evaluate their consistency with medical examinations documented in patients' medical records. Methods and Findings: This was a retrospective review and analysis of medical records from all 325 patients seen for treatment from September 28, 2004, through December 31, 2006, at the Nyala-based Amel Centre for Treatment and Rehabilitation of Victims of Torture, the only dedicated local provider of free clinical and legal services to civilian victims of torture and other human rights violations in Darfur during this time period. Among 325 medical records identified and examined, 292 (89.8%) patients from 12 different non-Arabic-speaking tribes disclosed in the medical notes that they had been attacked by Government of Sudan (GoS) and/or Janjaweed forces. Attacks were reported in 23 different rural council areas throughout Darfur. Nearly all attacks (321 [98.8%]) were described as having occurred in the absence of active armed conflict between Janjaweed/GoS forces and rebel groups. The most common alleged abuses were beatings (161 [49.5%]), gunshot wounds (140 [43.1%]), destruction or theft of property (121 [37.2%]), involuntary detainment (97 [29.9%]), and being bound (64 [19.7%]). Approximately one-half (36 [49.3%]) of all women disclosed that they had been sexually assaulted, and one-half of sexual assaults were described as having occurred in close proximity to a camp for internally displaced persons. Among the 198 (60.9%) medical records that contained sufficient detail to enable the forensic medical reviewers to render an informed judgment, the signs and symptoms in all of the medical records were assessed to be consistent with, highly consistent with, or virtually diagnostic of the alleged abuses. Conclusions: Allegations of widespread and sustained torture and other human rights violations by GoS and/or Janjaweed forces against non-Arabic-speaking civilians were corroborated by medical forensic review of medical records of patients seen at a local non-governmental provider of free clinical and legal services in Darfur. Limitations of this study were that patients seen in this clinic may not have been a representative sample of persons alleging abuse by Janjaweed/GoS forces, and that most delayed presenting for care. The quality of documentation was similar to that available in other conflict/post-conflict, resource-limited settings. C1 [Tsai, Alexander C.] Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Eisa, Mohammed A.; Crosby, Sondra S.; Sirkin, Susannah; Heisler, Michele; Iacopino, Vincent] Phys Human Rights, Cambridge, MA USA. [Eisa, Mohammed A.] Harvard Univ, Harvard Humanitarian Initiat, Cambridge, MA 02138 USA. [Crosby, Sondra S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Crosby, Sondra S.] Boston Univ, Sch Publ Hlth, Dept Hlth Law Bioeth & Human Rights, Boston, MA USA. [Heisler, Michele] Vet Affairs Ann Arbor Healthcare Syst, Vet Affairs Ctr Clin Management Res, Ann Arbor, MI USA. [Heisler, Michele] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Heisler, Michele] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Leaning, Jennifer] Harvard Univ, Sch Publ Hlth, Francois Xavier Bagnoud Ctr Hlth & Human Rights, Boston, MA 02115 USA. [Iacopino, Vincent] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Iacopino, Vincent] Univ Calif Berkeley, Human Rights Ctr, Berkeley, CA 94720 USA. RP Tsai, AC (reprint author), Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. EM atsai@hsph.harvard.edu RI Heisler, Michele/B-5774-2015; OI Heisler, Michele/0000-0002-6889-2063; Tsai, Alexander/0000-0001-6397-7917 FU Physicians for Human Rights; Open Society Foundations; Community Foundation of Western Massachusetts; Robert Wood Johnson Health & Society Scholars Program; Institute for International Education; Robert F. Kennedy Center for Justice and Human Rights FX This study was funded by Physicians for Human Rights with support from the Open Society Foundations and the Sudan Aid Fund of the Community Foundation of Western Massachusetts. ACT received salary support through the Robert Wood Johnson Health & Society Scholars Program. MAE received salary support through Physicians for Human Rights, the Open Society Foundations, the Sudan Aid Fund of the Community Foundation of Western Massachusetts, the Scholar Rescue Fund of the Institute for International Education, and the Robert F. Kennedy Center for Justice and Human Rights, as well as in-kind support from the Harvard Humanitarian Initiative. No funding bodies had any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 76 TC 2 Z9 2 U1 1 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD APR PY 2012 VL 9 IS 4 AR e1001198 DI 10.1371/journal.pmed.1001198 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 933VZ UT WOS:000303393800001 PM 22509136 ER PT J AU Lopez, MF Sarracino, DA Prakash, A Athanas, M Krastins, B Rezai, T Sutton, JN Peterman, S Gvozdyak, O Chou, S Lo, E Buonanno, F Ning, MM AF Lopez, Mary F. Sarracino, David A. Prakash, Amol Athanas, Michael Krastins, Bryan Rezai, Taha Sutton, Jennifer N. Peterman, Scott Gvozdyak, Oksana Chou, Sherry Lo, Eng Buonanno, Ferdinand Ning, MingMing TI Discrimination of ischemic and hemorrhagic strokes using a multiplexed, mass spectrometry-based assay for serum apolipoproteins coupled to multi-marker ROC algorithm SO PROTEOMICS CLINICAL APPLICATIONS LA English DT Article DE Biomarker; Cerebrovascular; Hemorrhagic; Ischemic; Mass spectrometry ID CARDIOVASCULAR RISK-FACTOR; C-III; A-I; LIPOPROTEIN METABOLISM; HEART-DISEASE; REPRODUCIBILITY; PROTEINS; PLASMA; CIII; MEN AB Purpose Typically, apolipoproteins are individually measured in blood by immunoassay. In this report, we describe the development of a multiplexed selected reaction monitoring (SRM) based assay for a panel of apolipoproteins and its application to a clinical cohort of samples derived from acute stroke patients. Experimental Design An SRM assay for a panel of nine apolipoproteins was developed on a triple quadrupole mass spectrometer. Quantitative data for each apolipoprotein were analyzed to determine expression ratio and receiver operating characteristic (ROC) values for ischemic versus hemorrhagic stroke. Results The optimized SRM assay was used to interrogate a small cohort of well-characterized plasma samples obtained from patients with acute ischemic and hemorrhagic strokes. The ROC analyses demonstrated good classification power for several single apolipoproteins, most notably apoC-III and apoC-I. When a novel multi-marker ROC algorithm was applied, the ischemic versus hemorrhagic groups were best differentiated by a combination of apoC-III and apoA-I with an area under the curve (AUC) value of 0.92. Conclusions and clinical relevance This proof-of-concept study provides interesting and provocative data for distinguishing ischemic versus hemorrhage within first week of symptom onset. However, the observations are based on one cohort of patient samples and further confirmation will be required. C1 [Lopez, Mary F.; Sarracino, David A.; Prakash, Amol; Krastins, Bryan; Rezai, Taha; Sutton, Jennifer N.; Peterman, Scott; Gvozdyak, Oksana] Thermo Fisher Sci, BRIMS, Cambridge, MA 02139 USA. [Athanas, Michael] VAST Sci, Cambridge, MA USA. [Chou, Sherry; Lo, Eng; Buonanno, Ferdinand; Ning, MingMing] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Lopez, MF (reprint author), Thermo Fisher Sci, BRIMS, Cambridge, MA 02139 USA. EM mary.lopez@thermofisher.com RI Chou, Sherry/G-5779-2015 FU NINDS NIH HHS [K23 NS073806, R01 NS067139] NR 42 TC 14 Z9 15 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1862-8346 J9 PROTEOM CLIN APPL JI Proteom. Clin. Appl. PD APR PY 2012 VL 6 IS 3-4 BP 190 EP 200 DI 10.1002/prca.201100041 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 931DJ UT WOS:000303194800006 PM 22532455 ER PT J AU Finley, EP Pugh, MJ Noel, PH Brown, PJ AF Finley, Erin P. Pugh, Mary Jo Noel, Polly H. Brown, Peter J. TI Validating a Measure of Self-Efficacy for Life Tasks in Male OEF/OIF Veterans SO PSYCHOLOGY OF MEN & MASCULINITY LA English DT Article DE OEF/OIF veterans; developmental tasks; depression; anxiety; self-efficacy theory ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH DIAGNOSES; AFGHANISTAN VETERANS; DEVELOPMENTAL TASKS; PERCEIVED CONTROL; IRAQ; ADULTHOOD; DEPRESSION; DEPLOYMENT; ASSOCIATION AB This paper describes the development and preliminary validation of a scale to assess perceived self-efficacy to complete culturally and age-appropriate life tasks (Self-Efficacy for Life Tasks, or SELT) among male veterans of Afghanistan (Operation Enduring Freedom; OEF) and Iraq (Operation Iraqi Freedom; OIF). The SELT scale was developed for this population in a multistage process that included: 1) semi-structured interviews inquiring about expectations of self among OEF/OIF veterans; 2) content analysis to inductively derive a list of priority life tasks; 3) item development; 4) field-testing; and 5) preliminary instrument validation. Forty-one veterans completed the final instrument along with measures of anxiety and depression symptoms, positive and negative social support, and postdeployment life stressors. We tested two scoring methods, one using a simple mean and one a weighted mean. Using either scoring method, SELT had statistically significant negative correlations with anxiety, depression, and being separated from partner, as well as strong positive correlations with postdeployment social support. These findings support the construct validity of the SELT scale in the population of male OEF/OIF veterans. Future research examining the relationship between SELT and long-term outcomes using longitudinal designs will be needed to assess predictive validity. C1 [Finley, Erin P.; Noel, Polly H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA. [Finley, Erin P.; Pugh, Mary Jo; Noel, Polly H.] S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. [Pugh, Mary Jo] S Texas Vet Hlth Care Syst, Dept Epidemiol & Biostat, San Antonio, TX USA. [Brown, Peter J.] Emory Univ, Dept Anthropol, Atlanta, GA 30322 USA. RP Finley, EP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Epidemiol, 7703 Floyd Curl Dr,MSC 7879, San Antonio, TX 78229 USA. EM finleye@uthscsa.edu OI Pugh, Mary Jo/0000-0003-4196-7763; Finley, Erin/0000-0003-4497-7721 NR 54 TC 1 Z9 1 U1 1 U2 6 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1524-9220 J9 PSYCHOL MEN MASCULIN JI Psychol. Men Masculinity PD APR PY 2012 VL 13 IS 2 BP 143 EP 157 DI 10.1037/a0023607 PG 15 WC Psychology, Social SC Psychology GA 932CQ UT WOS:000303268400004 ER PT J AU Dunne, PJ MacIntyre, NR Schmidt, UH Haas, CF Rye, KJB Kauffman, GW Hess, DR AF Dunne, Patrick J. MacIntyre, Neil R. Schmidt, Ulrich H. Haas, Carl F. Rye, Kathy Jones-Boggs Kauffman, Garry W. Hess, Dean R. TI Respiratory Care Year in Review 2011: Long-Term Oxygen Therapy, Pulmonary Rehabilitation, Airway Management, Acute Lung Injury, Education, and Management SO RESPIRATORY CARE LA English DT Review DE acute lung injury; acute respiratory distress syndrome; ARDS; education; endotracheal intubation; long-term oxygen therapy; management; pulmonary rehabilitation ID RANDOMIZED CONTROLLED-TRIAL; END-EXPIRATORY PRESSURE; INTUBATING LARYNGEAL AIRWAY; ASSIST-CONTROL MODE; DISTRESS-SYNDROME; DIFFICULT AIRWAY; TRACHEAL INTUBATION; PROTECTIVE VENTILATION; MECHANICAL VENTILATION; PROSPECTIVE-VALIDATION AB For the busy clinician, educator, or manager, it is becoming an increasing challenge to filter the literature to what is relevant to one's practice and then update one's practice based on the current evidence. The purpose of this paper is to review the recent literature related to long-term oxygen therapy, pulmonary rehabilitation, airway management, acute lung injury and acute respiratory distress syndrome, respiratory care education, and respiratory care management. These topics were chosen and reviewed in a manner that is most likely to have interest to the readers of RESPIRATORY CARE. C1 [Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Schmidt, Ulrich H.; Hess, Dean R.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Kauffman, Garry W.] Wake Forest Baptist Med Ctr, Dept Resp Care, Winston Salem, NC USA. [Dunne, Patrick J.] HealthCare Prod, Fullerton, CA USA. [MacIntyre, Neil R.] Duke Univ, Med Ctr, Dept Pulm & Crit Care Med, Durham, NC USA. [Schmidt, Ulrich H.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Management, Boston, MA 02114 USA. [Haas, Carl F.] Univ Michigan Hosp & Hlth Ctr, Dept Resp Care, Ann Arbor, MI USA. [Rye, Kathy Jones-Boggs] Univ Arkansas Med Sci, Coll Hlth Related Profess, Dept Resp & Surg Technol, Little Rock, AR 72205 USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 125 TC 3 Z9 5 U1 2 U2 5 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD APR PY 2012 VL 57 IS 4 BP 590 EP 606 DI 10.4187/respcare.01776 PG 17 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 927RT UT WOS:000302928500012 PM 22472499 ER PT J AU Henao-Martinez, AF Fernandez, JF Adams, SG Restrepo, C AF Henao-Martinez, Andres F. Fernandez, Juan F. Adams, Sandra G. Restrepo, Carlos TI Lung Bullae With Air-Fluid Levels: What Is the Appropriate Therapeutic Approach? SO RESPIRATORY CARE LA English DT Article DE COPD; air-fluid levels; infection; therapy; inflammation; bullae ID BULLOUS EMPHYSEMA; PERCUTANEOUS DRAINAGE; FILLED BULLA; DISEASE AB Air-fluid levels within emphysematous lung bullae are a relatively uncommon occurrence in patients with preexisting bullous disease, and are not commonly reported. We report 2 cases of new onset air-fluid levels in patients with underlying bullous disease with substantially different clinical presentations but with clinical improvement after medical therapy only. C1 [Henao-Martinez, Andres F.] Univ Colorado, Sch Med, Div Infect Dis, Aurora, CO 80045 USA. [Fernandez, Juan F.; Adams, Sandra G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pulm & Crit Care, San Antonio, TX 78229 USA. [Restrepo, Carlos] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Adams, Sandra G.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Henao-Martinez, AF (reprint author), Univ Colorado, Sch Med, Div Infect Dis, 12700 E 19th Ave, Aurora, CO 80045 USA. EM andres.henaomartinez@ucdenver.edu RI Henao-Martinez, Andres/E-1488-2012 OI Henao-Martinez, Andres/0000-0001-7363-8652 NR 25 TC 1 Z9 1 U1 1 U2 1 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD APR PY 2012 VL 57 IS 4 BP 642 EP 645 DI 10.4187/respcare.01372 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 927RT UT WOS:000302928500018 PM 22005505 ER PT J AU Hasegawa, K Hagiwara, Y Chiba, T Watase, H Walls, RM Brown, DFM Brown, CA AF Hasegawa, Kohei Hagiwara, Yusuke Chiba, Takuyo Watase, Hiroko Walls, Ron M. Brown, David F. M. Brown, Calvin A., III CA Japanese Emergency Med Res TI Emergency airway management in Japan: Interim analysis of a multi-center prospective observational study SO RESUSCITATION LA English DT Article DE Airway management; Intubation; Emergency department; Rapid sequence intubation; Japan; Practice variation ID RAPID-SEQUENCE INTUBATION; ENDOTRACHEAL INTUBATION; MEDICINE-RESIDENCY; CLINICAL-PRACTICE; EDUCATION; COUNCIL AB Objectives: Emergency medicine is increasingly recognized as a medical specialty in Japan. However, comprehensive studies evaluating emergency airway management practice are lacking. We describe emergency department (ED) airway management using a large multi-center registry. Methods: We formed the Japanese Emergency Airway Network, a consortium of 10 academic and community medical centers in Japan, and prospectively collected data on ED intubations from April 2010 to February 2011. All patients undergoing emergency intubation were eligible for inclusion. Data were entered in real time by the intubator using a standardized data form. Variables included patient's age, sex, weight, indication for intubation, methods of intubation, drugs, level of training and specialty of the intubator, number of attempts, success or failure, and adverse events. We present descriptive data as proportions with 95% confidence intervals. Results: We recorded 1486 intubations (compliance rate 99%). Intubation was ultimately successful in 99.7%. The initial method of intubation varied substantially among the hospitals, including rapid sequence intubation (0-79%), sedation without paralysis (4-88%), paralysis without sedation (0-18%), and oral without medication (12-67%), in non-cardiac arrest encounters. Success rates in first and <= 3 attempts ranged from 40 to 83% and from 74 to 100%, respectively. The overall adverse event rate was 11%, without significant difference by the method used. Conclusions: In this multi-center study characterizing ED airway management across Japan, we observed a high overall success rate but a high degree of variation among hospitals in the methods of intubation and success rates. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Hasegawa, Kohei; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hasegawa, Kohei; Walls, Ron M.; Brown, Calvin A., III] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Hagiwara, Yusuke] Kawaguchi Municipal Med Ctr, Dept Emergency Med, Kawaguchi, Saitama 3330833, Japan. [Chiba, Takuyo] Obama Municipal Hosp, Dept Emergency Med, Obama, Fukui 9178567, Japan. [Watase, Hiroko] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Founders 114, Boston, MA 02114 USA. EM khasegawa1@partners.org FU Harvard Affiliated Emergency Medicine Residency; St. Luke's Life Science Institute FX This study was supported by a grant for emergency medicine research from Harvard Affiliated Emergency Medicine Residency, and a grant from St. Luke's Life Science Institute. The study sponsors have no involvement in the study design, in the collection, analysis and interpretation of data, in the writing of the manuscript, and in the decision to submit the manuscript for publication. NR 26 TC 23 Z9 23 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD APR PY 2012 VL 83 IS 4 BP 428 EP 433 DI 10.1016/j.resuscitation.2011.11.027 PG 6 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA 930OO UT WOS:000303149100019 PM 22155701 ER PT J AU Love, JN Howell, JM Hegarty, CB McLaughlin, SA Coates, WC Hopson, LR Hern, GH Rosen, CL Fisher, J Santen, SA AF Love, Jeffrey N. Howell, John M. Hegarty, Cullen B. McLaughlin, Steven A. Coates, Wendy C. Hopson, Laura R. Hern, Gene H. Rosen, Carlo L. Fisher, Jonathan Santen, Sally A. TI Factors That Influence Medical Student Selection of an Emergency Medicine Residency Program: Implications for Training Programs SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID WOMEN AB Objectives: An understanding of student decision-making when selecting an emergency medicine (EM) training program is essential for program directors as they enter interview season. To build upon preexisting knowledge, a survey was created to identify and prioritize the factors influencing candidate decision-making of U.S. medical graduates. Methods: This was a cross-sectional, multi-institutional study that anonymously surveyed U.S. allopathic applicants to EM training programs. It took place in the 3-week period between the 2011 National Residency Matching Program (NRMP) rank list submission deadline and the announcement of match results. Results: Of 1,525 invitations to participate, 870 candidates (57%) completed the survey. Overall, 96% of respondents stated that both geographic location and individual program characteristics were important to decision-making, with approximately equal numbers favoring location when compared to those who favored program characteristics. The most important factors in this regard were preference for a particular geographic location (74.9%, 95% confidence interval [CI] = 72% to 78%) and to be close to spouse, significant other, or family (59.7%, 95% CI = 56% to 63%). Factors pertaining to geographic location tend to be out of the control of the program leadership. The most important program factors include the interview experience (48.9%, 95% CI = 46% to 52%), personal experience with the residents (48.5%, 95% CI = 45% to 52%), and academic reputation (44.9%, 95% CI = 42% to 48%). Unlike location, individual program factors are often either directly or somewhat under the control of the program leadership. Several other factors were ranked as the most important factor a disproportionate number of times, including a rotation in that emergency department (ED), orientation (academic vs. community), and duration of training (3-year vs. 4-year programs). For a subset of applicants, these factors had particular importance in overall decision-making. Conclusions: The vast majority of applicants to EM residency programs employed a balance of geographic location factors with individual program factors in selecting a residency program. Specific program characteristics represent the greatest opportunity to maximize the success of the immediate interview experience/season, while others provide potential for strategic planning over time. A working knowledge of these results empowers program directors to make informed decisions while providing an appreciation for the limitations in attracting applicants. C1 [Love, Jeffrey N.] Georgetown Univ Hosp, Washington Hosp Ctr, MERC CORD Working Grp, Dept Emergency Med, Washington, DC 20007 USA. [Howell, John M.] INOVA Fairfax Hosp, Dept Emergency Med, Fairfax, VA USA. [Hegarty, Cullen B.] Univ Minnesota, Dept Emergency Med, Reg Hosp, Hlth Partners Inst Med Educ Reg Hosp, St Paul, MN 55108 USA. [McLaughlin, Steven A.] Univ New Mexico, Dept Emergency Med, Albuquerque, NM 87131 USA. [Coates, Wendy C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Emergency Med, Harbor UCLA Med Ctr,Los Angeles Biomed Res Inst, Torrance, CA USA. [Hopson, Laura R.] Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA. Alameda Cty Med Ctr Highland, Dept Emergency Med, Oakland, CA USA. [Rosen, Carlo L.; Fisher, Jonathan] Beth Israel Deaconess Med Ctr Harvard Affiliated, Boston, MA USA. [Santen, Sally A.] Emory Sch Med, Dept Emergency Med, Atlanta, GA USA. RP Love, JN (reprint author), Georgetown Univ Hosp, Washington Hosp Ctr, MERC CORD Working Grp, Dept Emergency Med, Washington, DC 20007 USA. EM jeffrey.n.love@medstar.net NR 13 TC 14 Z9 14 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2012 VL 19 IS 4 BP 455 EP 460 DI 10.1111/j.1553-2712.2012.01323.x PG 6 WC Emergency Medicine SC Emergency Medicine GA 926UU UT WOS:000302858200012 PM 22506950 ER PT J AU Koyfman, A AF Koyfman, Alex TI The Doctor Within SO ACADEMIC EMERGENCY MEDICINE LA English DT Editorial Material C1 [Koyfman, Alex] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Koyfman, Alex] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Koyfman, A (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM akoyfman8@gmail.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 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2012 VL 19 IS 4 BP 483 EP 484 DI 10.1111/j.1553-2712.2012.01318.x PG 2 WC Emergency Medicine SC Emergency Medicine GA 926UU UT WOS:000302858200017 ER PT J AU Rapalino, O Kamalian, S Kamalian, S Payabvash, S Souza, LCS Zhang, D Mukta, J Sahani, DV Lev, MH Pomerantz, SR AF Rapalino, O. Kamalian, Shervin Kamalian, Shahmir Payabvash, S. Souza, L. C. S. Zhang, D. Mukta, J. Sahani, D. V. Lev, M. H. Pomerantz, S. R. TI Cranial CT with Adaptive Statistical Iterative Reconstruction: Improved Image Quality with Concomitant Radiation Dose Reduction SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; EXPERIENCE; ALGORITHM AB BACKGROUND AND PURPOSE: To safeguard patient health, there is great interest in CT radiation-dose reduction. The purpose of this study was to evaluate the impact of an iterative-reconstruction algorithm, ASIR, on image-quality measures in reduced-dose head CT scans for adult patients. MATERIALS AND METHODS: Using a 64-section scanner, we analyzed 100 reduced-dose adult head CT scans at 6 predefined levels of ASIR blended with FBP reconstruction. These scans were compared with 50 CT scans previously obtained at a higher routine dose without ASIR reconstruction. SNR and CNR were computed from Hounsfield unit measurements of normal GM and WM of brain parenchyma. A blinded qualitative analysis was performed in 10 lower-dose CT datasets compared with higher-dose ones without ASIA. Phantom data analysis was also performed. RESULTS: Lower-dose scans without ASIA had significantly lower mean GM and WM SNR (P = .003) and similar GM-WM CNR values compared with higher routine-dose scans. However, at ASIR levels of 20%-40%, there was no statistically significant difference in SNR, and at ASIR levels of >= 60%, the SNR values of the reduced-dose scans were significantly higher (P < .011. CNR values were also significantly higher at ASIA levels of >= 40% (P < .011. Blinded qualitative review demonstrated significant improvements in perceived image noise, artifacts, and GM-WM differentiation at ASIA levels >= 60 AD (P < .01). CONCLUSIONS: These results demonstrate that the use of ASIA in adult head CT scans reduces image noise and increases low-contrast resolution, while allowing lower radiation doses without affecting spatial resolution. C1 [Rapalino, O.; Kamalian, Shervin; Kamalian, Shahmir; Payabvash, S.; Souza, L. C. S.; Zhang, D.; Sahani, D. V.; Lev, M. H.; Pomerantz, S. R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mukta, J.] CT Res, GE Healthcare, Boston, MA USA. RP Rapalino, O (reprint author), Massachusetts Gen Hosp, Dept Radiol GRB 273, Boston, MA 02114 USA. EM orapalino@partners.org RI Kamalian, Shervin/D-7667-2013; OI Kamalian, Shervin/0000-0001-8962-4773; Kamalian, Shahmir/0000-0002-9640-8144 FU GE Healthcare; Elsevier; Millennium Pharmaceuticals; CoAxia FX Disclosures: Joshi Mukta-UNRELATED: Employment GE Healthcare. Dushyant Sahani-RELATED: Grant: GE Healthcare;* UNRELATED: Payment for Manuscript Preparation: Bracco Diagnostics; Royalties: Elsevier. Michael Lev-RELATED. GE Healthcare,* Comments: research support (software, hardware), Research Assistant support: Consulting Fee or Honorarium: GE Healthcare, Millennium Pharmaceuticals, CoAxia, Comments: consultant. Stuart Pomerantz-RELATED: Grant: GE Healthcare,* Comments: for research assistant support. *Money paid to institution, NR 21 TC 61 Z9 66 U1 1 U2 5 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 2012 VL 33 IS 4 BP 609 EP 615 DI 10.3174/ajnr.A2826 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 926PI UT WOS:000302842900005 PM 22207302 ER PT J AU Harris, BS Baicu, CF Haghshenas, N Kasiganesan, H Scholz, D Rackley, MS Miquerol, L Gros, D Mukherjee, R O'Brien, TX AF Harris, Brett S. Baicu, Catalin F. Haghshenas, Nicole Kasiganesan, Harinath Scholz, Dimitri Rackley, Mary S. Miquerol, Lucile Gros, Daniel Mukherjee, Rupak O'Brien, Terrence X. TI Remodeling of the peripheral cardiac conduction system in response to pressure overload SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE connexin40; connexin43; connexin45; hyperpolarization-activated cyclic nucleotide-gated channel 4; Purkinje fibers; cardiac hypertrophy; cardiac activation ID BRAIN NATRIURETIC PEPTIDE; FACTOR GENE-EXPRESSION; CURRENT I-F; HEART-FAILURE; COLOCALIZATION ANALYSIS; ATRIAL-FIBRILLATION; PURKINJE-FIBERS; CONNEXIN45; HYPERTROPHY; JUNCTION AB Harris BS, Baicu CF, Haghshenas N, Kasiganesan H, Scholz D, Rackley MS, Miquerol L, Gros D, Mukherjee R, O'Brien TX. Remodeling of the peripheral cardiac conduction system in response to pressure overload. Am J Physiol Heart Circ Physiol 302: H1712-H1725, 2012. First published February 3, 2012; doi: 10.1152/ajpheart.00621.2011.-How chronic pressure overload affects the Purkinje fibers of the ventricular peripheral conduction system (PCS) is not known. Here, we used a connexin (Cx)40 knockout/enhanced green fluorescent protein knockin transgenic mouse model to specifically label the PCS. We hypothesized that the subendocardially located PCS would remodel after chronic pressure overload and therefore analyzed cell size, markers of hypertrophy, and PCS-specific Cx and ion channel expression patterns. Left ventricular hypertrophy with preserved systolic function was induced by 30 days of surgical transaortic constriction. After transaortic constriction, we observed that PCS cardiomyocytes hypertrophied by 23% (P < 0.05) and that microdissected PCS tissue exhibited upregulated markers of hypertrophy. PCS cardiomyocytes showed a 98% increase in the number of Cx40-positive gap junction particles, with an associated twofold increase in gene expression (P < 0.05). We also identified a 50% reduction in Cx43 gap junction particles located at the interface between PCS cardiomyocytes and the working cardiomyocyte. In addition, we measured a fourfold increase of an ion channel, hyperpolarization-activated cyclic nucleotide-gated channel (HCN)4, throughout the PCS (P < 0.05). As a direct consequence of PCS remodeling, we found that pressure-overloaded hearts exhibited marked changes in ventricular activation patterns during normal sinus rhythm. These novel findings characterize PCS cardiomyocyte remodeling after chronic pressure overload. We identified significant hypertrophic growth accompanied by modified expression of Cx40, Cx43, and HCN4 within PCS cardiomyocytes. We found that a functional outcome of these changes is a failure of the PCS to activate the ventricular myocardium normally. Our findings provide a proof of concept that pressure overload induces specific cellular changes, not just within the working myocardium but also within the specialized PCS. C1 [Harris, Brett S.; Haghshenas, Nicole; O'Brien, Terrence X.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. [Baicu, Catalin F.; Kasiganesan, Harinath; Rackley, Mary S.; O'Brien, Terrence X.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Mukherjee, Rupak] Med Univ S Carolina, Dept Cardiothorac Surg, Charleston, SC 29425 USA. [Scholz, Dimitri] UCD Conway, Dublin, Ireland. [Miquerol, Lucile; Gros, Daniel] Univ Aix Marseille 2, Marseille, France. [O'Brien, Terrence X.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Harris, BS (reprint author), Med Univ S Carolina, Dept Regenerat Med & Cell Biol, 173 Ashley Ave, Charleston, SC 29425 USA. EM harrisbs@musc.edu FU National Center for Research Resources [5-P20-RR-016434-010]; Research and Development Service of the Department of Veterans Affairs FX This work was supported by National Center for Research Resources Grant 5-P20-RR-016434-010 (to B. S. Harris) and a Merit Award from the Research and Development Service of the Department of Veterans Affairs (to T. X. O'Brien). NR 42 TC 5 Z9 6 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 2012 VL 302 IS 8 BP H1712 EP H1725 DI 10.1152/ajpheart.00621.2011 PG 14 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 927MK UT WOS:000302911500016 PM 22307665 ER PT J AU Patel, R Albadawi, H Steudel, W Hashmi, FF Kang, JW Yoo, HJ Watkins, MT AF Patel, Rajendra Albadawi, Hassan Steudel, Wolfgang Hashmi, Faraz F. Kang, Jeanwan Yoo, Hyung-Jin Watkins, Michael T. TI Inhalation of carbon monoxide reduces skeletal muscle injury after hind limb ischemia-reperfusion injury in mice SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Carbon monoxide; Reperfusion injury; Heme oxygenase; Skeletal muscle ID HEPATIC ISCHEMIA/REPERFUSION INJURY; MULTIPLE ORGAN INJURY; HEMORRHAGIC-SHOCK; IN-VIVO; PROTECTION; MODEL; ATHEROSCLEROSIS; TRANSPLANTATION; RESUSCITATION; INFLAMMATION AB BACKGROUND: The purpose of this study was to determine if inhaled carbon monoxide (CO) can ameliorate skeletal muscle injury, modulate endogenous heme oxygenase-1 expression, and improve indexes of tissue integrity and inflammation after hind limb ischemia reperfusion. METHODS: C57BL6 mice inhaling CO (250 ppm) or room air were subjected to 1.5 hours of ischemia followed by limb reperfusion for either 3 or 6 hours (total treatment time, 4.5 or 7.5 h). After the initial period of reperfusion, all mice breathed only room air until 24 hours after the onset of ischemia. Mice were killed at either the end of CO treatment or at 24 hours' reperfusion. Skeletal muscle was subjected to histologic and biochemical analysis. RESULTS: CO treatment for 7.5 hours protected skeletal muscle from histologic and structural evidence of skeletal muscle injury. Serum and tissue cytokines were reduced significantly (P < .05) in mice treated with CO for 7.5 hours. Tubulin, heme oxygenase, and adenosine triphosphate levels were higher in CO-treated mice. CONCLUSIONS: Inhaled CO protected muscle from structural injury and energy depletion after ischemia reperfusion. (C) 2012 Elsevier Inc. All rights reserved. C1 [Patel, Rajendra; Albadawi, Hassan; Hashmi, Faraz F.; Kang, Jeanwan; Yoo, Hyung-Jin; Watkins, Michael T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg,Dept Surg, Boston, MA 02114 USA. [Steudel, Wolfgang] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Watkins, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg,Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM mtwatkins@partners.org FU Pacific Vascular Research Foundation; Massachusetts General Hospital; Division of Vascular and Endovascular Surgery; National Institutes of Health [1R01AR055843]; AVA Foundation; Department of Anesthesia and Critical Care at Massachusetts General Hospital FX The authors have received funding from the Pacific Vascular Research Foundation, The Geneen Fund of the Massachusetts General Hospital, the Division of Vascular and Endovascular Surgery, and the National Institutes of Health (grant 1R01AR055843). Dr. Watkins is the Isenberg Fellow in Academic Surgery at Massachusetts General Hospital; Faraz Hashmi received a student research award from the AVA Foundation; and Wolfgang Steudel has been supported by the Department of Anesthesia and Critical Care at Massachusetts General Hospital. NR 36 TC 4 Z9 4 U1 0 U2 4 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD APR PY 2012 VL 203 IS 4 BP 488 EP 495 DI 10.1016/j.amjsurg.2011.05.005 PG 8 WC Surgery SC Surgery GA 927ND UT WOS:000302913700013 PM 22450026 ER PT J AU Subramanian, A Liang, MK AF Subramanian, Anuradha Liang, Mike K. TI A 60-year literature review of stump appendicitis: the need for a critical view SO AMERICAN JOURNAL OF SURGERY LA English DT Review DE Stump appendicitis; Retained appendix; Appendicitis; Perforated appendicitis; Complicated appendicitis; Recurrent appendicitis ID LAPAROSCOPIC APPENDECTOMY; COMPLICATION; PATIENT AB BACKGROUND: Stump appendicitis is an underreported and poorly defined condition. It is the development of obstruction and inflammation of the residual appendix after appendectomy. This is a review of the basic clinical, pathological, and surgical significance of stump appendicitis, and the "critical view" required for prevention. DATA SOURCES: PubMed MEDLINE search was performed using terms "stump appendicitis" and "retained appendix" to obtain reported cases of stump appendicitis. Sixty-one cases were identified. Each case was charted based on 14 variables. Data were analyzed. CONCLUSIONS: Stump appendicitis warrants early detection. Patients can present with abdominal pain, nausea, and vomiting. A prior history of appendectomy can delay the diagnosis. A diagnosis can be made with an abdominal ultrasound or computed tomography scan. If treated early, laparoscopic or open completion appendectomy can be performed. If diagnosis is delayed and perforation is found, extensive resection is often required. A "critical view," as described in this article, is key for prevention. Published by Elsevier Inc. C1 [Subramanian, Anuradha; Liang, Mike K.] Baylor Coll Med, Michael E DeBakey Dept Surg, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Liang, MK (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM ml3@bcm.edu RI Liang, Mike/L-8493-2015 OI Liang, Mike/0000-0001-7063-7291 NR 19 TC 11 Z9 11 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD APR PY 2012 VL 203 IS 4 BP 503 EP 507 DI 10.1016/j.amjsurg.2011.04.009 PG 5 WC Surgery SC Surgery GA 927ND UT WOS:000302913700015 PM 22153086 ER PT J AU Karel, MJ Gatz, M Smyer, MA AF Karel, Michele J. Gatz, Margaret Smyer, Michael A. TI Aging and Mental Health in the Decade Ahead What Psychologists Need to Know SO AMERICAN PSYCHOLOGIST LA English DT Article DE aging; mental health; geropsychology; psychological practice; policy ID ALZHEIMERS ASSOCIATION WORKGROUPS; MILD COGNITIVE IMPAIRMENT; LATE-LIFE DEPRESSION; COMORBIDITY-SURVEY-REPLICATION; RANDOMIZED CONTROLLED-TRIAL; MULTIPLE CHRONIC CONDITIONS; NURSING-HOME RESIDENTS; CATCHMENT-AREA SITES; RISK ALCOHOL-USE; OLDER-ADULTS AB Until relatively recently, most psychologists have had limited professional involvement with older adults. With the baby boomers starting to turn 65 years old in 2011, sheer numbers of older adults will continue to increase. About 1 in 5 older adults has a mental disorder, such as dementia. Their needs for mental and behavioral health services are not now adequately met, and the decade ahead will require an approximate doubling of the current level of psychologists' time with older adults. Public policy in the coming decade will face tensions between cost containment and facilitation of integrated models of care. Most older adults who access mental health services do so in primary care settings, where interdisciplinary, collaborative models of care have been found to be quite effective. To meet the needs of the aging population, psychologists need to increase awareness of competencies for geropsychology practice and knowledge regarding dementia diagnosis, screening, and services. Opportunities for psychological practice are anticipated to grow in primary care, dementia and family caregiving services, decision-making-capacity evaluation, and end-of-life care. Aging is an aspect of diversity that can be integrated into psychology education across levels of training. Policy advocacy for geropsychology clinical services, education, and research remains critical. Psychologists have much to offer an aging society. C1 [Karel, Michele J.] VA Boston Healthcare Syst, Psychol Serv, Brockton, MA USA. [Karel, Michele J.] Harvard Univ, Dept Psychiat, Sch Med, Cambridge, MA 02138 USA. [Gatz, Margaret] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [Smyer, Michael A.] Bucknell Univ, Dept Psychol, Lewisburg, PA 17837 USA. RP Karel, MJ (reprint author), Brockton VA Med Ctr, 3-5-C,940 Belmont St, Brockton, MA 02301 USA. EM michele.karel@va.gov OI Gatz, Margaret/0000-0002-1071-9970 NR 142 TC 37 Z9 37 U1 6 U2 31 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X EI 1935-990X J9 AM PSYCHOL JI Am. Psychol. PD APR PY 2012 VL 67 IS 3 BP 184 EP 198 DI 10.1037/a0025393 PG 15 WC Psychology, Multidisciplinary SC Psychology GA 926MQ UT WOS:000302835600002 PM 21942364 ER PT J AU Levine, M Ruha, AM Goldstein, JN AF Levine, Michael Ruha, Anne-Michelle Goldstein, Joshua N. TI Can Asymptomatic Patients With a Supratherapeutic International Normalized Ratio Be Safely Treated as Outpatients? SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID ORAL VITAMIN-K; WARFARIN-ASSOCIATED COAGULOPATHY; PATIENTS RECEIVING WARFARIN; EXCESSIVE ANTICOAGULATION; EMERGENCY-DEPARTMENT; CONTROLLED TRIAL; PHYTONADIONE; REVERSAL; DISCONTINUATION; MANAGEMENT AB [Ann Emerg Med. 2012;59:318-320.] To determine whether asymptomatic patients with a supratherapeutic international normalized ratio (INR) warrant admission, a MEDLINE and EMBASE search was performed with the terms "warfarin AND anticoagulation," "warfarin AND bleeding," "warfarin and complications," and "warfarin and INR." The references in relevant articles were also searched. A secondary objective was to determine the risk of hemorrhage within 1 week. No randomized trials comparing inpatient versus outpatient management of asymptomatic patients with an increased INR were identified. Several studies examining outcomes after outpatient management, however, were identified. According to this review, it is certainly within the standard of care to manage patients with an asymptomatic, supratherapeutic INR as outpatients. C1 [Levine, Michael; Ruha, Anne-Michelle] Banner Good Samaritan Med Ctr, Dept Med Toxicol, Phoenix, AZ USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Levine, M (reprint author), Banner Good Samaritan Med Ctr, Dept Med Toxicol, Phoenix, AZ USA. EM michael.levine@bannerhealth.com RI Goldstein, Joshua/H-8953-2016 NR 20 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD APR PY 2012 VL 59 IS 4 BP 318 EP 320 DI 10.1016/j.annemergmed.2011.04.023 PG 3 WC Emergency Medicine SC Emergency Medicine GA 927SR UT WOS:000302930900018 PM 21867663 ER PT J AU Burns, JA Friedman, AD Lutch, MJ Zeitels, SM AF Burns, James A. Friedman, Aaron D. Lutch, Matthew J. Zeitels, Steven M. TI Subepithelial Vocal Fold Infusion: A Useful Diagnostic and Therapeutic Technique SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY APR 27-28, 2011 CL Chicago, IL SP Amer Broncho Esophagol Assoc DE microlaryngoscopy; subepithelial infusion; vocal fold ID CHORIOALLANTOIC MEMBRANE; LASER TREATMENT; SURGERY; LARYNX; MODEL AB Objectives: Preservation of the maximum amount of subepithelial superficial lamina propria (SLP) remains an important goal during microlaryngoscopic surgery of phonatory mucosa. Volume expansion of the SLP (Reinke's space) with subepithelial infusion of saline solution has been widely adopted since its introduction in 1991. This technique has evolved so that it is currently used to assist with determining the depth of vocal fold disease, defining residual pliable SLP, enhancing microsurgical precision, and identifying unrecognized disease. The purpose of this investigation was to examine the indications, methods, and benefits of subepithelial infusion of saline solution as an adjunct technique during phonomicrosurgery. Methods: In a prospective case series, we collected data on 280 consecutive microlaryngoscopy procedures performed over a 12-month period. Subepithelial infusion of saline solution was included in 178 procedures. Results: New disease was identified in 20 of the 178 patients (scar in 15, sulcus in 4, and a mucosal bridge in 1). The depth of needle placement varied depending on the specific disease: 118 of the 178 infusions were done just below the epithelial basement membrane, and 60 infusions were performed deeper within the SLP, just superficial to the vocal ligament. The infusion technique provided surgical assistance in multiple ways, including identifying residual SLP (130 patients), defining the SLP-lesion interface (65 patients), lifting scar (60 patients), providing tension for cordotomy (47 patients), expanding the SLP volume to protect against laser damage (45 patients), and providing hydrostatic compression of vascular ectasias or varices for photoangiolysis (7 patients). The microlaryngoscopy procedures during which infusion was not performed (102 of 280 procedures) were primarily for nonglottic cancer (46 patients), stenosis (30 patients), or arytenoid granuloma (13 patients). Conclusions: Subepithelial infusion of the SLP with saline solution is a useful microsurgical adjunct during diagnosis and treatment of phonatory mucosal lesions. C1 [Burns, James A.; Friedman, Aaron D.; Zeitels, Steven M.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Burns, James A.; Friedman, Aaron D.; Zeitels, Steven M.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Lutch, Matthew J.] Kaiser Permanente, So Calif Permanente Med Grp, Dept Head & Neck Surg, San Diego, CA USA. RP Burns, JA (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. NR 24 TC 3 Z9 3 U1 0 U2 1 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 APR PY 2012 VL 121 IS 4 BP 224 EP 230 PN 1 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 927BQ UT WOS:000302882300002 PM 22606925 ER PT J AU Campbell, J Singh, AK Swoboda, JG Gilmore, MS Wilkinson, BJ Walker, S AF Campbell, Jennifer Singh, Atul K. Swoboda, Jonathan G. Gilmore, Michael S. Wilkinson, Brian J. Walker, Suzanne TI An Antibiotic That Inhibits a Late Step in Wall Teichoic Acid Biosynthesis Induces the Cell Wall Stress Stimulon in Staphylococcus aureus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO RECONSTITUTION; GRAM-POSITIVE BACTERIA; HEAT-SHOCK GENES; BACILLUS-SUBTILIS; VANCOMYCIN-INTERMEDIATE; ESCHERICHIA-COLI; SOS RESPONSE; VIRULENCE; RESISTANCE; PATHWAY AB Wall teichoic acids (WTAs) are phosphate-rich, sugar-based polymers attached to the cell walls of most Gram-positive bacteria. In Staphylococcus aureus, these anionic polymers regulate cell division, protect cells from osmotic stress, mediate host colonization, and mask enzymatically susceptible peptidoglycan bonds. Although WTAs are not required for survival in vitro, blocking the pathway at a late stage of synthesis is lethal. We recently discovered a novel antibiotic, targocil, that inhibits a late acting step in the WTA pathway. Its target is TarG, the transmembrane component of the ABC transporter (TarGH) that exports WTAs to the cell surface. We examined here the effects of targocil on S. aureus using transmission electron microscopy and gene expression profiling. We report that targocil treatment leads to multicellular clusters containing swollen cells displaying evidence of osmotic stress, strongly induces the cell wall stress stimulon, and reduces the expression of key virulence genes, including dlt-ABCD and capsule genes. We conclude that WTA inhibitors that act at a late stage of the biosynthetic pathway may be useful as antibiotics, and we present evidence that they could be particularly useful in combination with beta-lactams. C1 [Campbell, Jennifer; Singh, Atul K.; Swoboda, Jonathan G.; Gilmore, Michael S.; Walker, Suzanne] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Gilmore, Michael S.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Singh, Atul K.; Wilkinson, Brian J.] Illinois State Univ, Sch Biol Sci, Normal, IL 61761 USA. [Swoboda, Jonathan G.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Swoboda, Jonathan G.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. RP Walker, S (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. EM suzanne_walker@hms.harvard.edu FU National Institutes of Health [F32AI084316, 1R15AI084006-01, P01AI083214, R01GMO78477] FX This study was supported by the National Institutes of Health (F32AI084316 [J.C.], 1R15AI084006-01 [B.J.W.], and P01AI083214 and R01GMO78477 [S.W.]). NR 72 TC 25 Z9 25 U1 0 U2 17 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 APR PY 2012 VL 56 IS 4 BP 1810 EP 1820 DI 10.1128/AAC.05938-11 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 913SU UT WOS:000301898500018 PM 22290958 ER PT J AU Hu, D Lau, OD Wang, L Wang, GY Schaue, D Zhu, L Huang, M Lin, Y Dennis, M Abemayor, E Elashoff, DA Dubinett, SM McBride, WH Sharma, S Wu, B St John, MA AF Hu, David Lau, Ontario D. Wang, Linda Wang, Guanyu Schaue, Dorthe Zhu, Li Huang, Min Lin, Yuan Dennis, Miranda Abemayor, Elliot Elashoff, David A. Dubinett, Steven M. McBride, William H. Sharma, Sherven Wu, Ben St John, Maie A. TI A Novel Modular Polymer Platform for the Treatment of Head and Neck Squamous Cell Carcinoma in an Animal Model SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID CANCER; RADIOTHERAPY; CISPLATIN; INHIBITION; DELIVERY AB Objective: To evaluate the therapeutic efficacy of a novel modular polymer platform in the treatment of head and neck squamous cell carcinoma (HNSCC). Design: In vivo study. Setting: Academic research laboratory. Subjects and Methods: C3H/HeJ mice and SCID/beige mice were randomized to receive implantation of no polymer, plain polymer, plain polymer with local cisplatin injection, or cisplatin polymer. The 2 groups of mice implanted with cisplatin polymer or no polymer were further randomized to receive 4 Gy of external beam radiation for 4 days or no radiation. Tumor size was measured until the mice were humanely killed. At necropsy, the tumors were excised and weighed. Results: There was a significant reduction in tumor growth using this novel polymer platform. The cisplatin-secreting polymer effectively reduced human head and neck tumor growth in SCID mice by 17-fold and SCC VII/SF tumors in C3H/HeJ mice by more than 16-fold compared with the control, plain polymer, and plain polymer + intratumoral cisplatin injection groups (P = .01 for both). We also observed a statistically significant lower tumor weight in mice treated with cisplatin polymer and concomitant radiation compared with the radiation alone and control groups. Conclusions: We demonstrate the efficacy of a novel polymer platform in delivering cisplatin to a partially resected SCC in a murine model. This polymer may represent a new therapeutic modality for patients with HNSCC. Once this polymer platform is optimized, we will plan for validation in the context of a prospective trial in patients with unresectable advanced or recurrent HNSCC. C1 [Hu, David; Lau, Ontario D.; Dennis, Miranda; Abemayor, Elliot; St John, Maie A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, Dept Surg, Los Angeles, CA 90095 USA. [Wang, Guanyu; Zhu, Li; Lin, Yuan; Dubinett, Steven M.; Sharma, Sherven] Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Wang, Guanyu; Zhu, Li; Lin, Yuan; Dubinett, Steven M.; Sharma, Sherven] Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Dept Med, Los Angeles, CA 90095 USA. [Huang, Min; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Elashoff, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biostat, Los Angeles, CA 90095 USA. [Wu, Ben] Univ Calif Los Angeles, David Geffen Sch Med, Div Adv Prosthodont Biomat & Hosp Dent, Los Angeles, CA 90095 USA. [Wu, Ben] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mat Sci & Engn, Los Angeles, CA 90095 USA. [Wang, Linda; Wu, Ben] Univ Calif Los Angeles, David Geffen Sch Med, Dept Bioengn, Los Angeles, CA 90095 USA. [Schaue, Dorthe; McBride, William H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Los Angeles, CA 90095 USA. [Zhu, Li] Univ Calif Los Angeles, David Geffen Sch Med, Dept Orthoped Surg, Los Angeles, CA 90095 USA. [Huang, Min; Dubinett, Steven M.; Sharma, Sherven] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP St John, MA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, Dept Surg, 37-131 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. RI lin, yuan/E-6062-2011 FU NCATS NIH HHS [UL1 TR000124]; NIDCR NIH HHS [K23 DE021193]; PHS HHS [K23] NR 20 TC 4 Z9 4 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD APR PY 2012 VL 138 IS 4 BP 412 EP 417 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 926YU UT WOS:000302870800013 PM 22508626 ER PT J AU Saunders, JK Rosman, AS Neihaus, D Gouge, TH Melis, M AF Saunders, John K. Rosman, Alan S. Neihaus, Dena Gouge, Thomas H. Melis, Marcovalerio TI Safety of Hepatic Resections in Obese Veterans SO ARCHIVES OF SURGERY LA English DT Article ID BODY-MASS-INDEX; ARTERY-BYPASS-SURGERY; QUALITY IMPROVEMENT PROGRAM; INDEPENDENT RISK-FACTOR; HEPATOCELLULAR-CARCINOMA; DIABETES-MELLITUS; PERIOPERATIVE MORTALITY; COLORECTAL-CANCER; CARDIAC-SURGERY; GRAFT-SURGERY AB Objective: To determine the effects of body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) on outcomes after liver resection performed at Veterans Affairs medical centers. Design, Setting, and Patients: We queried the Veterans Affairs Surgical Quality Improvement Program database for liver resections (2005-2008) and grouped the patients into 5 BMI categories: normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), obese class 1 (BMI 30.0-34.9), obese class 2 (BMI 35.0-39.9), and obese class 3 (BMI >= 40.0). Differences in risk factors and perioperative complications across groups were analyzed in univariate and multivariate analyses. Results: Of 403 patients who underwent hepatectomy, 106 (26%) were normal weight, 161 (40%) were overweight, 94 (23%) were obese class 1, 31 (8%) were obese class 2, and 11 (3%) were obese class 3. Among these groups, higher BMI was associated with increased rates of hypertension (52%, 61%, 77%, 77%, and 73%, respectively; P=.002) and diabetes (18%, 27%, 36%, 39%, and 45%, respectively; P=.04) and lower incidence of smokers (53%, 35%, 30%, 16%, and 9%, respectively; P<.001). The BMI groups were similar in demographic characteristics and metrics correlating with preexisting liver disease. There were no differences across BMI groups in overall and specific morbidity or in length of stay. Compared with the other groups, obese class 3 patients received more blood transfusions (mean [SD], 4.3 [2.7] in obese class 3 patients vs 1.1 [0.2] in normal-weight patients; P=.02) and had a higher 30-day mortality (27% in obese class 3 patients vs 6% in normal-weight patients; P=.05). Multivariate analyses confirmed obese class 3 as an independent predictor of postoperative mortality. Conclusions: Obesity did not increase postoperative complications after liver resection in veterans. After adjusting for other clinical factors, extreme obesity (BMI >= 40.0) was an independent risk factor for increased mortality. C1 [Melis, Marcovalerio] NYU, Sch Med, Dept Surg, New York Harbor Healthcare Syst Vet Affairs Med C, New York, NY 10010 USA. [Rosman, Alan S.] James J Peters Vet Affairs Med Ctr, Div Gastroenterol, Bronx, NY USA. RP Melis, M (reprint author), NYU, Sch Med, Dept Surg, New York Harbor Healthcare Syst Vet Affairs Med C, 423 E 23rd St,Room 4153 N, New York, NY 10010 USA. EM marcovalerio.melis@nyumc.org OI Gouge, Thomas/0000-0001-8381-4146 NR 45 TC 17 Z9 18 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2012 VL 147 IS 4 BP 331 EP 337 DI 10.1001/archsurg.2011.1404 PG 7 WC Surgery SC Surgery GA 927JX UT WOS:000302904600008 PM 22184133 ER PT J AU Smith, M Oudard, S Karsh, L Egerdie, B Van Veldhuizen, P Gomez-Veiga, F Dearnaley, D Ye, Z Dansey, R Goessl, C Glennane, A AF Smith, M. Oudard, S. Karsh, L. Egerdie, B. Van Veldhuizen, P. Gomez-Veiga, F. Dearnaley, D. Ye, Z. Dansey, R. Goessl, C. Glennane, A. TI The effect of denosumab on bone metastasis-free survival in men with castrate-resistant prostate cancer - subgroup analyses of an international, double-blind, randomised, phase 3 trial SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 65th Annual Scientific Meeting on Urological-Society-of-Australia-and-New Zealand CY APR 21-24, 2012 CL Darwin, AUSTRALIA SP Urolog Soc Australia & New Zealand C1 [Smith, M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Oudard, S.] Georges Pompidou Hosp, Paris, France. [Karsh, L.] Urol Ctr Colorado, Dept Clin Res, Denver, CO USA. [Egerdie, B.] Urol Associates Urol Med Res, Med Res, Kitchener, ON, Canada. [Van Veldhuizen, P.] Kansas City VA Med Ctr, Kansas City, KS USA. [Gomez-Veiga, F.] Hosp Univ Juan Canalejo, La Coruna, Spain. [Dearnaley, D.] Royal Marsden Hosp, Inst Canc Res, Sutton, Surrey, England. [Ye, Z.] Amgen Inc, Gobal Biostat Sci, Thousand Oaks, CA 91320 USA. [Dansey, R.; Goessl, C.] Amgen Inc, Hematol Oncol, Thousand Oaks, CA 91320 USA. [Glennane, A.] Amgen Australia Pty Ltd, Sydney, NSW, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD APR PY 2012 VL 109 SU 4 SI SI MA 13 BP 13 EP 13 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 928SL UT WOS:000303003900013 ER PT J AU Anderlini, P Tolar, J Deeg, H Arai, S Horwitz, M Antin, J McCarty, J Adams, R Ewell, M Leifer, E Gersten, I Carter, S Horowitz, M Confer, D Nakamura, R Pulsipher, M DiFronzo, N Eapen, M AF Anderlini, P. Tolar, J. Deeg, H. Arai, S. Horwitz, M. Antin, J. McCarty, J. Adams, R. Ewell, M. Leifer, E. Gersten, I. Carter, S. Horowitz, M. Confer, D. Nakamura, R. Pulsipher, M. DiFronzo, N. Eapen, M. TI Fludarabine-based conditioning for allogeneic marrow transplantation from unrelated donors in severe aplastic anaemia: serious and unexpected adverse events in pre-defined cyclophosphamide dose levels SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 38th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT) CY APR 01-04, 2012 CL Geneva, SWITZERLAND SP European Grp Blood & Marrow Transplantat (EBMT) C1 [Anderlini, P.] UTMDACC, Houston, TX USA. [Tolar, J.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Deeg, H.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Arai, S.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Horwitz, M.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Antin, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McCarty, J.] Virginia Commonwealth Univ Med Coll Virginia, Richmond, VA USA. [Adams, R.] Mayo Clin, Scottsdale, AZ USA. [Ewell, M.; Gersten, I.; Carter, S.] EMMES Corp, Rockville, MD USA. [Leifer, E.; DiFronzo, N.] NHLBI, Bethesda, MD 20892 USA. [Horowitz, M.; Eapen, M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Confer, D.] Natl Marrow Donor Program, Minneapolis, MN USA. [Pulsipher, M.] Univ Utah, Med Ctr, Salt Lake City, UT USA. NR 0 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 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2012 VL 47 SU 1 BP S219 EP S220 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 925GN UT WOS:000302749201275 ER PT J AU Waller, E Harris, W Devine, S Porter, D Ferrara, J McCarty, J Gonzalez, C Spitzer, T Krijanovski, O Howard, A Gurgol, C Logan, B Confer, D Anasetti, C AF Waller, E. Harris, W. Devine, S. Porter, D. Ferrara, J. McCarty, J. Gonzalez, C. Spitzer, T. Krijanovski, O. Howard, A. Gurgol, C. Logan, B. Confer, D. Anasetti, C. TI Grade III-IV acute GvHD and treatment-related mortality are reduced among recipients of larger numbers of donor naive CD8+T-cells and plasmacytoid dendritic cell precursors in allogeneic BM grafts from unrelated donors: results from BMT CTN 0201 SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 38th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT) CY APR 01-04, 2012 CL Geneva, SWITZERLAND SP European Grp Blood & Marrow Transplantat (EBMT) C1 [Waller, E.; Harris, W.] Winship Canc Inst, Atlanta, GA USA. [Devine, S.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Porter, D.] Univ Penn, Philadelphia, PA 19104 USA. [Ferrara, J.] Univ Michigan, Ann Arbor, MI 48109 USA. [McCarty, J.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Gonzalez, C.] Georgetown Univ, Washington, DC USA. [Spitzer, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Krijanovski, O.] Sutter E Bay Med Fdn, Berkeley, CA USA. [Howard, A.; Confer, D.] Natl Marrow Donor Program, Minneapolis, MN USA. [Gurgol, C.] EMMES Corp, Rockville, MD USA. [Logan, B.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Anasetti, C.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2012 VL 47 SU 1 BP S20 EP S20 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 925GN UT WOS:000302749200037 ER PT J AU Karaosmanoglu, AD Blake, MA Lennerz, JK AF Karaosmanoglu, A. D. Blake, M. A. Lennerz, J. K. TI Abundant macroscopic fat in intra-abdominal lymph nodes involved in the course of a patient with chronic lymphocytic leukaemia: presentation of imaging findings with biopsy correlation SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID DISEASE AB The presence of a small amount of macroscopic fat is not unusual in the hilar region of normal lymph nodes. However, abundant replacement of the lymph node with fat is highly unusual and may appear as metastatic lymph node disease in the course of fat-predominant liposarcomas or in the case of coeliac disease complicated by cavitating lymph node syndrome. In this case report, a patient with chronic lymphocytic leukaemia/small lymphocytic lymphoma who demonstrated an increasing abundance of macroscopic fat in the diseased lymph nodes is presented. To the best of our knowledge, the imaging findings of abundant fat in lymph nodes in the course of lymphoma have not been reported before. The presence of macroscopic fat may be seen in the presence of actively involved lymph nodes in the presence of chronic lymphocytic leukaemia. C1 [Karaosmanoglu, A. D.; Blake, M. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Lennerz, J. K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Karaosmanoglu, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St,White 2, Boston, MA 02114 USA. EM alidevrim76@yahoo.com RI Karaosmanoglu, Ali/D-8624-2015 OI Karaosmanoglu, Ali/0000-0003-0027-9593 NR 15 TC 1 Z9 1 U1 0 U2 1 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD APR PY 2012 VL 85 IS 1012 BP E91 EP E93 DI 10.1259/bjr/20677787 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 916XV UT WOS:000302137400006 PM 22457415 ER PT J AU Dellon, EP Sawicki, GS Shores, MD Wolfe, J Hanson, LC AF Dellon, Elisabeth P. Sawicki, Gregory S. Shores, Mitchell D. Wolfe, Joanne Hanson, Laura C. TI Physician Practices for Communicating With Patients With Cystic Fibrosis About the Use of Noninvasive and Invasive Mechanical Ventilation SO CHEST LA English DT Article ID SHARED DECISION-MAKING; LUNG TRANSPLANTATION; RESPIRATORY-FAILURE; LIFE CARE; END; PERSPECTIVES; ADULTS AB Background: Many patients with advanced cystic fibrosis (CF) lung disease receive intensive treatments such as noninvasive and invasive mechanical ventilation for respiratory failure after little or no communication with physicians. Methods: Using surveys and follow-up interviews, physicians at two major CF care centers reported their practices for discussing intensive treatment preferences with patients with CF and about barriers and facilitators to communication. Results: Surveys were completed by 30 (88%) and 26 (76%) of 34 eligible CF physicians who provide care for children (60%), adults (23%), or both (17%). Respondents described variable timing and content of discussions. They identified patient/family factors such as denial of disease severity, optimistic expectations of treatment outcomes, inability of ill patients to participate in discussions, and family disagreements about treatments as primary barriers to discussions. They also acknowledged physician factors, including concern for taking away hope and uncertainty about when to address treatment preferences. Patient/family factors were also the most common facilitators identified, particularly disease severity and inquiry about intensive treatments. They recommended: (1) developing standards for communication, (2) offering training in communication for physicians, (3) creating decision support tools for patients and families, and (4) using the multidisciplinary CF care team to facilitate communication. Conclusions: CF physicians describe numerous patient/family factors barriers to communicating about intensive treatments for respiratory failure. They recommend changing physician and organizational factors to improve practice and promote effective communication. Innovation in clinical training, team roles, and decision support may prompt changes in practice standards. CHEST 2012; 141(4):1010-1017 C1 [Dellon, Elisabeth P.] Univ N Carolina, Sch Med, Dept Pediat, Div Pulmonol, Chapel Hill, NC 27599 USA. [Sawicki, Gregory S.] Childrens Hosp, Div Resp Dis, Dept Med, Boston, MA 02115 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Hanson, Laura C.] Palliat Care Program, Div Geriatr Med, Dept Med, Chapel Hill, NC USA. RP Dellon, EP (reprint author), Univ N Carolina, Sch Med, Dept Pediat, Div Pulmonol, CB 7217,450 MacNider,333 S Columbia St, Chapel Hill, NC 27599 USA. EM epdellon@med.unc.edu FU National Palliative Care Research Center FX This research was supported by a Junior Faculty Career Development Award from the National Palliative Care Research Center. NR 22 TC 7 Z9 7 U1 2 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 APR PY 2012 VL 141 IS 4 BP 1010 EP 1017 DI 10.1378/chest.11-1323 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 923BI UT WOS:000302592700028 PM 21998257 ER PT J AU Schuetz, P Amin, DN Greenwald, JL AF Schuetz, Philipp Amin, Devendra N. Greenwald, Jeffrey L. TI Role of Procalcitonin in Managing Adult Patients With Respiratory Tract Infections SO CHEST LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; VENTILATOR-ASSOCIATED PNEUMONIA; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; COMPETENCE NETWORK CAPNETZ; C-REACTIVE PROTEIN; RANDOMIZED-CONTROLLED-TRIALS; ANTIBIOTIC USE; SERUM PROCALCITONIN; ANTIMICROBIAL THERAPY AB Respiratory infections remain the most common reason why patients seek medical care in ambulatory and hospital settings, and they are the most frequent precursor of sepsis. In light of the limitations of clinical signs and symptoms and traditional microbiologic diagnostics for respiratory infections, blood biomarkers that correlate with the presence and extent of bacterial infections may provide additional useful information to improve diagnostic and prognostic efforts and help with therapeutic decisions in individual patients. A growing body of evidence supports the use of procalcitonin (PCT) to differentiate bacterial from viral respiratory diagnoses, to help risk stratify patients, and to guide antibiotic therapy decisions about initial need for, and optimal duration of, therapy. Although still relatively new on the clinical frontier, a series of randomized controlled trials have evaluated PCT protocols for antibiotic-related decision making and have included patients from different clinical settings and with different severities of respiratory infection. In these trials, initial PCT levels were effective in guiding decisions about the initiation of antibiotic therapy in lower-acuity patients, and subsequent measurements were effective for guiding duration of therapy in higher-acuity patients, without apparent harmful effects. Recent European respiratory infection guidelines now also recognize this concept. As with any other laboratory test, PET should not be used on a stand-alone basis. Rather, it must be integrated into clinical protocols, together with clinical, microbiologic data and with results from clinical risk scores. The aim of this review is to summarize recent evidence about the usefulness of PCT in patients with lower respiratory tract infections and to discuss the potential benefits and limitations of this marker when used for clinical decision making. CHEST 2012; 141(4):1063-1073 C1 [Schuetz, Philipp] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Greenwald, Jeffrey L.] Massachusetts Gen Hosp, Dept Med, Inpatient Clinician Educ Serv, Boston, MA USA. [Amin, Devendra N.] Morton Plant Hosp, Med Surg ICU, Clearwater, FL USA. RP Schuetz, P (reprint author), Harvard Univ, Sch Publ Hlth, 667 Huntington Ave, Boston, MA 02115 USA. EM Schuetzph@gmail.com FU Swiss Foundation for Grants in Biology and Medicine (Schweizerische Stiftung fur medizinisch-biologisc Stipendien) [PASMP3-127684/1] FX The authors have reported to CHEST the following conflicts of interest: Dr Schuetz was supported by a research grant from the Swiss Foundation for Grants in Biology and Medicine (Schweizerische Stiftung fur medizinisch-biologisc Stipendien, PASMP3-127684/1) and received support from BRAHMS Inc and bioMerieux to attend meetings and fulfill speaking engagements. Dr Amin has received support from bioMerieux for speaking engagements. Dr Greenwald has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 78 TC 39 Z9 49 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2012 VL 141 IS 4 BP 1063 EP 1073 DI 10.1378/chest.11-2430 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 923BI UT WOS:000302592700035 PM 22474148 ER PT J AU Caravan, P Zhang, ZD AF Caravan, Peter Zhang, Zhaoda TI Structure-Relaxivity Relationships among Targeted MR Contrast Agents SO EUROPEAN JOURNAL OF INORGANIC CHEMISTRY LA English DT Review DE Gadolinium; Relaxivity; Imaging agents; Proteins; Structure-activity relationships ID AFFINITY FOLATE RECEPTOR; HUMAN SERUM-ALBUMIN; ESTROGEN-RECEPTOR; PROTEIN-BINDING; MAGNETIC-FIELD; IN-VIVO; GADOLINIUM; RELAXATION; MS-325; ANGIOGENESIS AB Paramagnetic gadolinium(III) complexes are widely used to increase contrast in magnetic resonance (MR) images. Contrast enhancement depends on the concentration of the gadolinium complex and on its relaxivity, an inherent property of the complex. Increased relaxivity results in greater image contrast or the ability to detect the contrast agent at a lower concentration. An increase in the relaxivity enables the imaging of abundant molecular targets. Relaxivity depends on the structure of the complex, kinetics of inner-sphere and second-sphere water exchange, and on the rotational dynamics of the molecule. The latter, and in some cases the former, properties of the complex change when it is bound to its target. All of these properties can be rationally tuned to enhance relaxivity. In this Microreview, we summarize our efforts in understanding and optimizing the relaxivity of contrast agents targeted to serum albumin and to fibrin. C1 [Caravan, Peter; Zhang, Zhaoda] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Caravan, Peter; Zhang, Zhaoda] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Caravan, P (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu FU National Institute of Biomedical Imaging and Bioengineering [R01EB009062, R01EB009062-S1]; National Cancer Institute [R01CA161221] FX This work was supported in part by the National Institute of Biomedical Imaging and Bioengineering (awards R01EB009062 and R01EB009062-S1) and by the National Cancer Institute (R01CA161221).. NR 53 TC 20 Z9 21 U1 2 U2 38 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1434-1948 J9 EUR J INORG CHEM JI Eur. J. Inorg. Chem. PD APR PY 2012 IS 12 SI SI BP 1916 EP 1923 DI 10.1002/ejic.201101364 PG 8 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 926WF UT WOS:000302861900004 ER PT J AU Chamberlain, MC Cloughsey, T Reardon, DA Wen, PY AF Chamberlain, Marc C. Cloughsey, Timothy Reardon, David A. Wen, Patrick Y. TI A novel treatment for glioblastoma: integrin inhibition SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE angiogenic inhibition; antiproliferative; cilengitide; glioblastoma; integrins ID PHASE-II TRIAL; NADP(+)-DEPENDENT ISOCITRATE DEHYDROGENASE; NEWLY-DIAGNOSED GLIOBLASTOMA; RECURRENT MALIGNANT GLIOMA; ENDOTHELIAL GROWTH-FACTOR; ADVANCED SOLID TUMORS; ADJUVANT TEMOZOLOMIDE; MONOCLONAL-ANTIBODY; STEM-CELLS; CILENGITIDE EMD-121974 AB Glioblastoma (GBM) is the most common malignant primary brain tumor, which despite combined modality treatment, recurs and is invariably fatal. New therapies for GBM represent an unmet need in neuro-oncology. This review provides an overview of the epidemiology and molecular biology of GBM and focuses, in particular, on integrins, which are heterodimeric transmembrane surface proteins that, when activated, signal through several GBM-relevant pathways, including proliferation, motility, cytoskeleton organization, survival and angiogenesis pathways. Consequently, the potential effects of anti-integrin strategies in anti-GBM therapeutics are threefold: antiangiogenesis; anti-invasion; and anti-tumor. Trials of anti-integrins are most mature in GBM, and this review summarizes the completed and future trials of integrin inhibitors in the treatment of both newly diagnosed and recurrent GBM. C1 [Chamberlain, Marc C.] Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Neurol & Neurol Surg, Div Neurooncol, Seattle, WA 98109 USA. [Cloughsey, Timothy] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Reardon, David A.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Reardon, David A.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [Wen, Patrick Y.] Harvard Univ, Sch Med, Dept Neurol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chamberlain, MC (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Neurol & Neurol Surg, Div Neurooncol, 825 Eastlake Ave E,MS G-4940, Seattle, WA 98109 USA. EM chambemc@uw.edu NR 104 TC 10 Z9 10 U1 0 U2 11 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD APR PY 2012 VL 12 IS 4 BP 421 EP 435 DI 10.1586/ERN.11.188 PG 15 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 928KW UT WOS:000302982600011 PM 22449214 ER PT J AU Salzler, MJ Bluman, EM Noonan, S Chiodo, CP de Asla, RJ AF Salzler, Matthew J. Bluman, Eric M. Noonan, Samantha Chiodo, Christopher P. de Asla, Richard J. TI Injuries Observed in Minimalist Runners SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE Barefoot Running; Jogging; Sneakers, Biomechanics; Sports Medicine ID RUNNING INJURIES; STRESS-FRACTURES; CONTROLLED-TRIAL; BAREFOOT; FOOT; MARATHON; INSOLES; FORCES; SHAPE AB Background: Minimalist runners have been shown to have a different gait pattern with lower impact forces than habitually shod runners. Running in minimalist footwear has been promoted as a means of reducing or eliminating running injuries by returning to a more natural gait. Methods: Ten experienced runners, age 21 to 57 (mean, 43) years, were identified with injuries within 1 year of transition from traditional to minimalist running footwear. Patients were interviewed to determine their running history, injury history, transition to minimalist footwear, and their new injury including its treatment and recovery. Results: Ten patients who ran with traditional footwear ran an average of 25.9 (range, 6 to 45) miles/week for an average of 18.9 (range, 1 to 40) years presented with injuries 2.8 (range 1 to 10) months after switching to minimalist footwear. Their injuries included eight metatarsal stress fractures, a calcaneal stress fracture, and a plantar fascia rupture. All patients had a successful recovery and returned to their previous level of running. Conclusion: Injuries including stress fractures and plantar fascia rupture have been observed in minimalist runners. C1 [Salzler, Matthew J.; Bluman, Eric M.; Noonan, Samantha; Chiodo, Christopher P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [de Asla, Richard J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bluman, EM (reprint author), Brigham Foot & Ankle Ctr, 1153 Ctr St,Ste 56, Boston, MA 02130 USA. EM emb43@cornell.edu NR 25 TC 30 Z9 30 U1 0 U2 64 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD APR PY 2012 VL 33 IS 4 BP 262 EP 266 DI 10.3113/FAI.2012.0262 PG 5 WC Orthopedics SC Orthopedics GA 927DV UT WOS:000302888100003 PM 22735197 ER PT J AU Hahn, ME Wright, ES Segal, AD Orendurff, MS Ledoux, WR Sangeorzan, BJ AF Hahn, Michael E. Wright, Elise S. Segal, Ava D. Orendurff, Michael S. Ledoux, William R. Sangeorzan, Bruce J. TI Comparative Gait Analysis of Ankle Arthrodesis and Arthroplasty: Initial Findings of a Prospective Study SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE Arthritis; Arthrodesis; Arthroplasty; Mobility; Gait Analysis ID TERM-FOLLOW-UP; KINEMATIC CHANGES; TOTAL REPLACEMENT; FUSION; PROSTHESIS; MOVEMENT AB Background: Little is known about functional outcomes of ankle arthroplasty compared with arthrodesis. This study compared pre-surgical and post-surgical gait measures in both patient groups. Methods: Eighteen patients with end-stage ankle arthritis participated in an ongoing longitudinal study (pre-surgery, 12 months post-surgery) involving gait analysis, assessment of pain and physical function. Outcome measures included temporal-distance, kinematic and kinetic data, the Short Form 36 (SF-36) body pain score, and average daily step count. A mixed effects linear model was used to detect effects of surgical group (arthrodesis and arthroplasty, n = 9 each) with walking speed as a covariate (alpha = 0.05). Results: Both groups were similar in demographics and anthropometrics. Followup time was the same for each group. There were no complications in either group. Pain decreased (p < 0.001) and gait function improved (gait velocity, p = 0.02; stride length, p = 0.035) in both groups. Neither group increased average daily step count. Joint range of motion (ROM) differences were observed between groups after surgery (increased hip ROM in arthrodesis, p = 0.001; increased ankle ROM in arthroplasty, p = 0.036). Peak plantar flexor moment increased in arthrodesis patients and decreased in arthroplasty patients (p = 0.042). Conclusion: Initial findings of this ongoing clinical study indicate pain reduction and improved gait function 12 months after surgery for both treatments. Arthroplasty appears to regain more natural ankle joint function, with increased ROM. Longterm follow up should may reveal more clinically meaningful differences. C1 [Hahn, Michael E.; Ledoux, William R.; Sangeorzan, Bruce J.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Ledoux, William R.; Sangeorzan, Bruce J.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. [Hahn, Michael E.; Wright, Elise S.; Segal, Ava D.; Orendurff, Michael S.; Ledoux, William R.; Sangeorzan, Bruce J.] Rehabil Res & Dev Ctr Excellence Limb Loss Preven, VA Puget Sound, Dept Vet Affairs VA, Seattle, WA USA. RP Hahn, ME (reprint author), Ctr Excellence Limb Loss Prevent & Prosthet Engn, VA Puget Sound, 1660 S Columbian Way,MS-151, Seattle, WA 98108 USA. EM mehahn@uw.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU Department of Veterans Affairs [A4513R, A4883C A4843C] FX Funds were received in support of this article from the Department of Veterans Affairs, grants A4513R and A4883C A4843C. NR 28 TC 23 Z9 25 U1 0 U2 13 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD APR PY 2012 VL 33 IS 4 BP 282 EP 289 DI 10.3113/FAI.2012.0282 PG 8 WC Orthopedics SC Orthopedics GA 927DV UT WOS:000302888100006 PM 22735200 ER PT J AU Weber, JR Aubin, PM Ledoux, WR Sangeorzan, BJ AF Weber, Joel R. Aubin, Patrick M. Ledoux, William R. Sangeorzan, Bruce J. TI Second Metatarsal Length is Positively Correlated With Increased Pressure and Medial Deviation of the Second Toe in a Robotic Cadaveric Simulation of Gait SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE Second Metatarsal; Plantar Pressure; Metatarsophalangeal Joint; Second Toe; Gait Simulation AB Background: The term 'crossover second toe' has been used to describe a deformity of the second metatarsophalangeal joint (MTPJ) that includes a progressive migration of the second toe in a dorsal and medial direction. The long onset and complex anatomy of the deformity has led to uncertainty about its etiology and treatment. The purpose of this study was to investigate the relationship between second metatarsal length and second MTPJ plantar pressure and joint angles during gait. We hypothesized that elongation of the second metatarsal would increase the plantar pressure underneath the second MTPJ and be associated with a deviation of the MTPJ angles in a dorsal and medial direction. Methods: Incremental surgical elongation of the second metatarsal was performed on six cadaveric feet. A robotic gait simulator (RGS) simulated physiologic tibial motion, tendon loading, and ground reaction forces (GRF) on the cadaveric feet. We determined the peak pressure and pressure-time integral under the second MTPJ during gait, as well as the transverse and sagittal MTPJ angles. Results: Second metatarsal peak pressure and pressure-time integral were positively correlated with an increase in second metatarsal length. First metatarsal peak pressure and pressure-time integral were significantly negatively associated with second metatarsal length. MTPJ transverse plane angle was positively associated with second metatarsal length but sagittal angle was not. Conclusion: Our results support the hypothesis that second metatarsal length is positively associated with medial deviation of the second toe and increased plantar pressure underneath the second MTPJ. Clinical Relevance: It is biomechanically plausible that this association could lead to the joint instability seen in crossover toe patients. C1 [Ledoux, William R.] RR&D Ctr Excellence Limb Loss Prevent & Prosthet, VA Puget Sound, Seattle, WA 98108 USA. RP Ledoux, WR (reprint author), RR&D Ctr Excellence Limb Loss Prevent & Prosthet, VA Puget Sound, MS 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU Department of Veterans Affairs Rehabilitation Research and Development Service [A4843C]; University of Washington FX Funds were received in support of this article from the Department of Veterans Affairs Rehabilitation Research and Development Service grant A4843C and the University of Washington Medical Student Research Training Program. NR 18 TC 6 Z9 6 U1 2 U2 2 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD APR PY 2012 VL 33 IS 4 BP 312 EP 319 DI 10.3113/FAI.2012.0312 PG 8 WC Orthopedics SC Orthopedics GA 927DV UT WOS:000302888100009 PM 22735203 ER PT J AU Morden, NE Chang, CH Jacobson, JO Berke, EM Bynum, JPW Murray, KM Goodman, DC AF Morden, Nancy E. Chang, Chiang-Hua Jacobson, Joseph O. Berke, Ethan M. Bynum, Julie P. W. Murray, Kimberly M. Goodman, David C. TI End-Of-Life Care For Medicare Beneficiaries With Cancer Is Highly Intensive Overall And Varies Widely SO HEALTH AFFAIRS LA English DT Article ID PALLIATIVE CARE; REGIONAL-VARIATIONS; PATIENT PREFERENCES; CONTROLLED-TRIAL; UNITED-STATES; HOSPICE CARE; LUNG-CANCER; CHEMOTHERAPY; OUTCOMES; SURVIVAL AB Studies have shown that cancer care near the end of life is more aggressive than many patients prefer. Using a cohort of deceased Medicare beneficiaries with poor-prognosis cancer, meaning that they were likely to die within a year, we examined the association between hospital characteristics and eleven end-of-life care measures, such as hospice use and hospitalization. Our study revealed a relatively high intensity of care in the last weeks of life. At the same time, there was more than a twofold variation within hospital groups with common features, such as cancer center designation and for-profit status. We found that these hospital characteristics explained little of the observed variation in intensity of end-of-life cancer care and that none reliably predicted a specific pattern of care. These findings raise questions about what factors may be contributing to this variation. They also suggest that best practices in end-of-life cancer care can be found in many settings and that efforts to improve the quality of end-of-life care should include every hospital category. C1 [Morden, Nancy E.; Berke, Ethan M.; Goodman, David C.] Dartmouth Med Sch, Lebanon, NH USA. [Bynum, Julie P. W.] Dartmouth Inst Hlth Policy & Clin Practice, Ctr Hlth Policy Res, Lebanon, NH USA. [Morden, Nancy E.; Berke, Ethan M.] Dartmouth Hitchcock Norris Cotton Canc Ctr, Canc Control Res Program, Lebanon, NH USA. [Jacobson, Joseph O.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jacobson, Joseph O.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Murray, Kimberly M.] Maine Med Ctr Res Inst, Ctr Outcomes Res & Evaluat, Portland, ME USA. [Goodman, David C.] Dartmouth Inst, Ctr Hlth Policy Res, Dartmouth, NS, Canada. RP Morden, NE (reprint author), Dartmouth Med Sch, Lebanon, NH USA. EM nancy.e.morden@dartmouth.edu FU Robert Wood Johnson Foundation; National Institute on Aging [P01 AG19783, Beeson K23AG028947] FX This research was supported, in part, by the Robert Wood Johnson Foundation and the National Institute on Aging (Grant Nos. P01 AG19783 and Beeson K23AG028947 to Julie Bynum). The authors acknowledge Kristen K. Bronner, managing editor of the Dartmouth Atlas of Health Care, for development of graphic data displays. NR 44 TC 92 Z9 92 U1 3 U2 11 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD APR PY 2012 VL 31 IS 4 BP 786 EP 796 DI 10.1377/hlthaff.2011.0650 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 925QZ UT WOS:000302777400017 PM 22492896 ER PT J AU Rego, EM Kim, HT Ruiz-Arguelles, GJ Uriarte, MD Jacomo, RH Gutierrez-Aguirre, H Melo, RAM Bittencourt, R Pasquini, R Pagnano, K Fagundes, EM Chauffaille, MD Chiattone, C Martinez, L Meillon, LA Gomez-Almaguer, D Kwaan, H Garces-Eisele, J Gallagher, R Niemeyer, CM Lowenberg, B Ribeiro, R LoCoco, F Sanz, MA AF Rego, Eduardo M. Kim, Haesook T. Ruiz-Argueelles, Guillermo J. del Rosario Uriarte, Maria Jacomo, Rafael H. Gutierrez-Aguirre, Homero Melo, Raul A. M. Bittencourt, Rosane Pasquini, Ricardo Pagnano, Katia Fagundes, Evandro M. Chauffaille, Maria de Lourdes Chiattone, Carlos Martinez, Lem Meillon, Luis A. Gomez-Almaguer, David Kwaan, Hau Garces-Eisele, Javier Gallagher, Robert Niemeyer, Charlotte M. Lowenberg, Bob Ribeiro, Raul LoCoco, Francesco Sanz, Miguel A. TI The impact of medical education and networking on the outcome of leukemia treatment in developing countries. The experience of International Consortium on Acute Promyelocytic Leukemia (IC-APL) SO HEMATOLOGY LA English DT Article DE Acute promyelocytic leukemia; Leukemia; Developing countries; All trans retinoic acid ID TRANS-RETINOIC ACID; RISK-ADAPTED TREATMENT; ACUTE MYELOID-LEUKEMIA; ADULT ACUTE-LEUKEMIA; HIGH-FREQUENCY; ANTHRACYCLINE; CONSOLIDATION; FEATURES; LATINOS; PETHEMA AB Objectives: Several clinical trials conducted in Europe and US reported favorable outcomes of patients with APL treated with the combination of all trans retinoic acid (ATRA) and anthracyclines. Nevertheless, the results observed in developing countries with the same regimen was poorer, mainly due to high early mortality mainly due bleeding. The International Consortium on Acute Promyelocytic Leukemia (IC-APL) is an initiative of the International Members Committee of the ASH and the project aims to reduce this gap through the establishment of international network, which was launched in Brazil, Mexico and Uruguay. Methods: The IC-APL treatment protocol is similar to the PETHEMA 2005, but changing idarubicin to daunorubicin. All patients with a suspected diagnosis of APL were immediately started on ATRA, while bone marrow samples were shipped to a national central lab where genetic verification of the diagnosis was performed. The immunofluorescence using an anti-PML antibody allowed a rapid confirmation of the diagnosis and, the importance of supportive measures was reinforced. Results: The interim analysis of 97 patients enrolled in the IC-APL protocol showed that complete remission (CR) rate was 83% and the 2-year overall survival and disease-free survival were 80% and 90%, respectively. Of note, the early mortality rate was reduced to 7.5%. Discussion: The results of IC-APL demonstrate the impact of educational programs and networking on the improvement of the leukemia treatment outcome in developing countries. C1 [Rego, Eduardo M.] Univ Sao Paulo, Fac Med Ribeirao Preto, Med Sch Ribeirao Preto, Hematol Serv, Sao Paulo, Brazil. [Kim, Haesook T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ruiz-Argueelles, Guillermo J.] Clin Ruiz de Puebla, Puebla, Mexico. [del Rosario Uriarte, Maria; Martinez, Lem] Asociac Espanola Primera Socorros Mutuos, Montevideo, Uruguay. [Gutierrez-Aguirre, Homero; Gomez-Almaguer, David] Univ Hosp, Monterrey, Mexico. [Melo, Raul A. M.] HEMOPE, Recife, PE, Brazil. [Bittencourt, Rosane] Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil. [Pasquini, Ricardo] Univ Fed Parana, BR-80060000 Curitiba, Parana, Brazil. [Pagnano, Katia] Univ Estadual Campinas, Campinas, Brazil. [Fagundes, Evandro M.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. [Chauffaille, Maria de Lourdes] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Chiattone, Carlos] Santa Casa Med Sch, Sao Paulo, Brazil. [Meillon, Luis A.] Ctr Med Nacl Siglo XXI, Mexico City, DF, Mexico. [Kwaan, Hau] Northwestern Univ, Chicago, IL 60611 USA. [Gallagher, Robert] Albert Einstein Canc Ctr, Bronx, NY USA. [Niemeyer, Charlotte M.] Univ Med Ctr, Dept Pediat & Adolescent Med, Freiburg, Germany. [Lowenberg, Bob] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Ribeiro, Raul] St Jude Childrens Rsch Hosp, Memphis, TN USA. [LoCoco, Francesco] Univ Roma Tor Vergata, Rome, Italy. [Sanz, Miguel A.] Hosp Univ La Fe, Valencia, Spain. RP Rego, EM (reprint author), Univ Sao Paulo, Fac Med Ribeirao Preto, Med Sch Ribeirao Preto, Hematol Serv, Sao Paulo, Brazil. EM emrego@hcrp.fmrp.usp.br RI Pagnano, Katia/K-6686-2012; Melo, Raul/D-4910-2013; Celulas tronco, Inct/I-1921-2013; Sangue, Inct/I-1919-2013; Rego, Eduardo/A-1058-2012; OI Melo, Raul/0000-0001-7629-7144; Rego, Eduardo/0000-0003-1567-4086; Gutierrez-Aguirre, Cesar Homero/0000-0002-9876-3633 NR 20 TC 3 Z9 3 U1 0 U2 4 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1024-5332 J9 HEMATOLOGY JI Hematology PD APR PY 2012 VL 17 SU 1 BP S36 EP S38 DI 10.1179/102453312X13336169155376 PG 3 WC Hematology SC Hematology GA 927OA UT WOS:000302916200011 PM 22507775 ER PT J AU Babadi, B Tarokh, V AF Babadi, Behtash Tarokh, Vahid TI Distributed Dynamic Spectrum Allocation for Secondary Users in a Vertical Spectrum Sharing Scenario SO IEICE TRANSACTIONS ON COMMUNICATIONS LA English DT Article DE dynamic spectrum allocation; cognitive radios; vertical spectrum sharing ID DIGITAL SUBSCRIBER LINES; INTERFERENCE AVOIDANCE; WIRELESS NETWORKS; SYSTEMS AB In this paper, we study the problem of distributed spectrum allocation under a vertical spectrum sharing scenario in a cognitive radio network. The secondary users share the spectrum licensed to the primary user by observing the activity statistics of the primary users, and regulate their transmission strategy in order to abide by the spectrum sharing etiquette. When the primary user is inactive in a subset of the available frequency bands, from the perspective of the secondary users the problem reduces to a distributed horizontal spectrum sharing. For a specific class of networks, the latter problem is addressed by the recently proposed GADIA algorithm [1]. In this paper, we present analytical and numerical results on the performance of the GADIA algorithm in conjunction with the above-mentioned vertical spectrum sharing scenario. These results reveal near-optimal performance guarantees for the overall vertical spectrum sharing scenario. C1 [Babadi, Behtash; Tarokh, Vahid] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Babadi, Behtash] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Babadi, Behtash] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Babadi, B (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. EM behtash@seas.harvard.edu; vahid@seas.harvard.edu FU ARO MURI [W911NF-07-1-0376] FX This work has been presented in part at the 2012 IEEE Consumer Communications and Networking Conference, Jan. 14-17, Las Vegas, NV, USA [2]. This research is supported in part by ARO MURI grant number W911NF-07-1-0376. The views expressed in this paper are those of the authors alone and not of the sponsor. NR 24 TC 1 Z9 1 U1 0 U2 1 PU IEICE-INST ELECTRONICS INFORMATION COMMUNICATIONS ENG PI TOKYO PA KIKAI-SHINKO-KAIKAN BLDG, 3-5-8, SHIBA-KOEN, MINATO-KU, TOKYO, 105-0011, JAPAN SN 0916-8516 EI 1745-1345 J9 IEICE T COMMUN JI IEICE Trans. Commun. PD APR PY 2012 VL E95B IS 4 BP 1044 EP 1055 DI 10.1587/transcom.E95.B.1044 PG 12 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA 926MC UT WOS:000302834100003 ER PT J AU Singh, SM D'Avila, A Kim, YH Aryana, A Mangrum, M Michaud, GF Dukkipati, SR Callans, DJ Barrett, CD Beras-Jovine, MR Reddy, VY AF Singh, Sheldon M. D'Avila, Andre Kim, Young-Hoon Aryana, Arash Mangrum, Michael Michaud, Gregory F. Dukkipati, Srinivas R. Callans, David J. Barrett, Conor D. Beras-Jovine, Maximo R. Reddy, Vivek Y. TI The Modified Ablation Guided by Ibutilide Use in Chronic Atrial Fibrillation (MAGIC-AF) Study: Clinical Background and Study Design SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE antiarrhythmic drugs; atrial fibrillation; catheter ablation; complex-fractionated electrograms; pulmonary vein isolation ID RADIOFREQUENCY CATHETER ABLATION; PATIENTS RECEIVING AMIODARONE; CONGENITAL HEART-DISEASE; HYPERTROPHIC CARDIOMYOPATHY; FOLLOW-UP; ELECTROGRAMS; EFFICACY; CARDIOVERSION; FLUTTER; ARRHYTHMIAS AB The MAGIC-AF Study. Background: Beyond pulmonary vein isolation (PVI), adjuvant ablation at the sites of complex fractionated atrial electrograms (CFAE) has been shown to improve the long-term success of catheter ablation of persistent atrial fibrillation (AF). However, this approach often requires extensive ablation due to the widespread distribution of CFAE within the left atrium. An optimal strategy would identify areas of CFAE which, when selectively targeted with ablation, result in AF termination with an acceptable long-term freedom from AF. It is possible that the intraprocedural administration of an antiarrhythmic drug may help accomplish this. Objective: The Modified Ablation Guided by Ibutilide Use in Chronic AF (MAGIC-AF) Study is an international multicenter prospective randomized double-blinded clinical trial assessing the utility of the intraprocedural administration of 0.25 mg of intravenous ibutilide before performing CFAE ablation. The primary efficacy endpoint of this study will be the freedom from AF at 1 year after a single procedure off antiarrhythmic agents. Safety endpoints will include procedural and radiofrequency ablation time as well as overall procedural complication rate. Methods: Patients undergoing a first ever catheter ablation procedure for persistent AF will be included. Individuals with hypertrophic cardiomyopathy, complex congenital heart disease including atrial septal defects, and ejection fraction < 35% will be excluded from the study. All patients will first undergo PVI. Those patients who remain in AF will then be randomized in a 1: 1 fashion to receive either 0.25 mg intravenous ibutilide or saline placebo followed by a CFAE based ablation strategy. Two hundred randomized patients will be enrolled in this study-100 in each study arm. Conclusion: The MAGIC-AF study will assess the utility of a combined pharmaco-ablative strategy in patients with persistent AF undergoing a CFAE based ablation strategy. (J Cardiovasc Electrophysiol, Vol. 23, pp. 352-358, April 2012) C1 [Singh, Sheldon M.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Fac Med, Schulich Heart Program,Div Cardiol, Toronto, ON, Canada. [D'Avila, Andre; Dukkipati, Srinivas R.; Barrett, Conor D.; Beras-Jovine, Maximo R.; Reddy, Vivek Y.] Mt Sinai Med Ctr, Mt Sinai Sch Med, Helmsley Cardiac Arrhythmia Serv, New York, NY 10029 USA. [Kim, Young-Hoon] Korea Univ, Med Ctr, Cardiovasc Div, Seoul, South Korea. [Aryana, Arash] Reg Cardiol Associates, Sacramento, CA USA. [Mangrum, Michael] Univ Virginia, Dept Internal Med, Charlottesville, VA USA. [Michaud, Gregory F.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Cardiovasc Div, Boston, MA 02115 USA. [Callans, David J.] Univ Penn, Hosp Univ Penn, Electrophysiol Sect, Cardiovasc Div, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. RP Reddy, VY (reprint author), Helmsley Electrphysiol Ctr, Mt Sinai Sch Med, 1030 1 Gustave L Levy Pl, New York, NY 10029 USA. EM vivek.reddy@mountsinai.org RI d'Avila, Andre/F-8009-2010 OI d'Avila, Andre/0000-0001-8769-1411 FU Boston Scientific FX Dr. Michaud has received grant support from Boston Scientific and honoraria from Medtronic. Drs. Singh and Jovine report no potential conflicts of interest. NR 27 TC 7 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD APR PY 2012 VL 23 IS 4 BP 352 EP 358 DI 10.1111/j.1540-8167.2011.02198.x PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 928QC UT WOS:000302996800003 PM 22034996 ER PT J AU Swearingen, B AF Swearingen, Brooke TI Update on Pituitary Surgery SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ENDOSCOPIC TRANSSPHENOIDAL SURGERY; CUSHINGS-DISEASE; UNITED-STATES; CLINICAL ARTICLE; INTRAOPERATIVE MRI; 10-YEAR EXPERIENCE; ENDONASAL APPROACH; TUMOR RESECTION; SELLAR LESIONS; BRAIN-TUMORS AB Transsphenoidal surgery has an important role in the management of pituitary tumors and remains the primary treatment for most adenomas, with the exception of prolactinomas. This update will review the recent neurosurgical literature; modifications to the traditional microscopic approach, including the potential utility of endoscopy and intraoperative magnetic resonance imaging, are discussed. The value of experienced surgical judgment and expertise remains clear, over and above the possible advantages of current technology. Preliminary data on the relative cost-effectiveness of surgery vs. medical treatment suggest that surgical approaches compare favorably. It will be important to incorporate future technological advances in surgical technique with new medical therapies in a combined multidisciplinary approach for improved treatment algorithms. (J Clin Endocrinol Metab 97: 1073-1081, 2012) C1 [Swearingen, Brooke] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Swearingen, Brooke] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Swearingen, B (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. EM BSwearingen@partners.org NR 72 TC 24 Z9 27 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2012 VL 97 IS 4 BP 1073 EP 1081 DI 10.1210/jc.2011-3237 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 925US UT WOS:000302787800029 PM 22337908 ER PT J AU Bredella, MA Fazeli, PK Freedman, LM Calder, G Lee, H Rosen, CJ Klibanski, A AF Bredella, Miriam A. Fazeli, Pouneh K. Freedman, Lauren M. Calder, Genevieve Lee, Hang Rosen, Clifford J. Klibanski, Anne TI Young Women with Cold-Activated Brown Adipose Tissue Have Higher Bone Mineral Density and Lower Pref-1 than Women without Brown Adipose Tissue: A Study in Women with Anorexia Nervosa, Women Recovered from Anorexia Nervosa, and Normal-Weight Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ENERGY-EXPENDITURE; NONSHIVERING THERMOGENESIS; BODY-COMPOSITION; ADULT HUMANS; PROTEIN; MECHANISMS; FAT; METABOLISM; DIFFERENTIATION; IDENTIFICATION AB Context: Anorexia nervosa (AN) is associated with depletion of body fat, loss of bone mineral density (BMD), and impaired thermogenesis. Brown adipose tissue (BAT) is lower in obese individuals and decreases during aging. Recent studies have suggested a link between BAT and bone metabolism. Objective: Our objective was to investigate the presence and quantity of BAT in patients with AN, recovered AN (AN-R), and normal-weight controls and to study the relationship between BAT and BMD and body composition and investigate hormonal predictors of BAT. Design and Setting: This was a cross-sectional study at a clinical research center. Patients: Patients included 15 women: five with AN (mean age 30 +/- 6.3 yr), five AN-R, and five healthy nonobese controls of comparable age. Main Outcome Measures: Cold-activated BAT was determined by fluorodeoxyglucose-positron emission tomography/computed tomography. BMD of total-body, spine, and hip, fat and lean mass was determined by dual-energy x-ray absorptiometry. Single-slice magnetic resonance imaging at L4 was done for abdominal fat compartments, and preadipocyte factor-1 (Pref-1), T-3, and T-4 were measured. Results: Within the AN group, one of five; in the AN-R group, two of five; and in the healthy nonobese control group, four of five subjects were BAT positive. Subjects were divided into groups based on the presence (n = 7) or absence (n = 8) of BAT. Both groups were of comparable age and body mass index. Women with BAT had higher total-body BMD, higher T3, and lower Pref-1 compared with women without BAT. There was a positive correlation between BAT and BMD that remained significant after controlling for disease status and body mass index. Conclusion: Young women with AN have low cold-activated BAT, which may be due to impaired BAT thermogenesis. Young women with BAT have higher BMD and lower Pref-1 compared with women without BAT, suggesting that BAT may be involved in the regulation of stem cell differentiation into the bone lineage at the expense of adipogenesis. (J Clin Endocrinol Metab 97: E584-E590, 2012) C1 [Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fazeli, Pouneh K.; Freedman, Lauren M.; Calder, Genevieve; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Rosen, Clifford J.] Maine Med Ctr Res Inst, Scarborough, ME 04074 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM mbredella@partners.org FU National Institutes of Health [R24 DK084970, UL1 RR025758] FX This work was supported by National Institutes of Health Grants R24 DK084970 and UL1 RR025758. NR 43 TC 41 Z9 41 U1 0 U2 2 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 APR PY 2012 VL 97 IS 4 BP E584 EP E590 DI 10.1210/jc.2011-2246 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 925US UT WOS:000302787800009 PM 22259053 ER PT J AU Pereira, RI Snell-Bergeon, JK Erickson, C Schauer, IE Bergman, BC Rewers, M Maahs, DM AF Pereira, Rocio I. Snell-Bergeon, Janet K. Erickson, Christopher Schauer, Irene E. Bergman, Bryan C. Rewers, Marian Maahs, David M. TI Adiponectin Dysregulation and Insulin Resistance in Type 1 Diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORONARY-ARTERY CALCIFICATION; ADIPOSE-SPECIFIC PROTEIN; SERUM ADIPONECTIN; SENSITIVITY; ASSOCIATION; OBESITY; CACTI AB Context: Type 1 diabetes (T1D) is associated with insulin resistance despite elevated levels of the insulin-sensitizing protein adiponectin. Whether the expected positive correlation between adiponectin and insulin sensitivity is preserved in a T1D population is unknown. Objective: We measured the correlation between total and high-molecular-weight (HMW) adiponectin and insulin sensitivity in T1D patients and nondiabetic controls and identified determinants of adiponectin levels in patients with T1D. Design and Participants: Fasting total and HMW adiponectin were measured in 86 subjects from the Coronary Artery Calcification in T1D (CACTI) cohort (39 T1D, 47 nondiabetic; age 45 +/- 8 yr; 55% female). The association of adiponectin levels with insulin sensitivity was analyzed. Setting: The study was conducted at an academic research institute. Methods: Fasting total and HMW adiponectin were measured by RIA and ELISA, respectively. Insulin sensitivity was measured by a hyperinsulinemic-euglycemic clamp. Multivariate linear regression was used to identify determinants of adiponectin levels. Results: Adiponectin levels positively correlated with insulin sensitivity in both subject groups (total adiponectin, r = 0.33 P < 0.05 for T1D, r = 0.29 P < 0.05 controls), but insulin sensitivity was lower in T1D subjects at any given level of total or HMW adiponectin. Adiponectin levels were independently associated with age, gender, and trunk fat, but these variables did not account for increased adiponectin in patients with T1D. Conclusion: Adiponectin levels are positively correlated with insulin sensitivity in T1D patients. However, T1D patients have decreased insulin sensitivity compared with controls at every level of adiponectin, suggesting an important adaptive change of adiponectin set point. (J Clin Endocrinol Metab 97: E642-E647, 2012) C1 [Pereira, Rocio I.] Denver Hlth & Hosp Author, Denver, CO 80204 USA. [Pereira, Rocio I.; Erickson, Christopher; Schauer, Irene E.; Bergman, Bryan C.] Univ Colorado, Div Endocrinol Metab & Diabet, Aurora, CO 80045 USA. [Snell-Bergeon, Janet K.; Rewers, Marian; Maahs, David M.] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA. [Schauer, Irene E.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Pereira, RI (reprint author), Univ Colorado, Div Endocrinol, Anschutz Med Campus,MS 8106, Aurora, CO 80045 USA. EM rocio.pereira@ucdenver.edu OI Bergman, Bryan/0000-0002-9561-1052 FU National Institutes of Health [M01 RR000051]; National Institutes of Health, National Heart, Lung, and Blood Institute [R01 HL61753, R01 HL079611]; Diabetes Endocrinology Research Center [P30 DK57516]; National Institutes of Health, National Center for Research Resources [K23 RR022238]; American Diabetes Association [1-10-JF-50, DK075360] FX This study was performed at the Clinical Translational Research Center at the University of Colorado Denver, supported by National Institutes of Health Grant M01 RR000051, and at the Barbara Davis Center for Childhood Diabetes (Aurora, CO). Author contributions included the following: R. I. P. researched data and wrote the manuscript. J.K.S.-B. researched data and contributed to discussion and edited the manuscript. C. E. researched data and reviewed the manuscript. I. S. and B. B. researched data and contributed to discussion and reviewed the manuscript. M. R. contributed to discussion and edited the manuscript. D. M. M. researched data and contributed to discussion and reviewed the manuscript. The contents of this manuscript are solely the responsibility of the authors and do not necessarily reflect the views of the National Institutes of Health or other funders.; This work was supported by the National Institutes of Health, National Heart, Lung, and Blood Institute Grants R01 HL61753 and R01 HL079611, and the Diabetes Endocrinology Research Center Clinical Investigation Core Grant P30 DK57516. Additional support was provided by the National Institutes of Health, National Center for Research Resources Grant K23 RR022238 (to R. I. P.), American Diabetes Association Junior Faculty Award 1-10-JF-50 (to J.K.S.-B.), and Grant DK075360 (to D.M.M.). NR 19 TC 30 Z9 31 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 APR PY 2012 VL 97 IS 4 BP E642 EP E647 DI 10.1210/jc.2011-2542 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 925US UT WOS:000302787800019 PM 22278421 ER PT J AU Raivio, T Avbelj, M McCabe, MJ Romero, CJ Dwyer, AA Tommiska, J Sykiotis, GP Gregory, LC Diaczok, D Tziaferi, V Elting, MW Padidela, R Plummer, L Martin, C Feng, BH Zhang, CK Zhou, QY Chen, HB Mohammadi, M Quinton, R Sidis, Y Radovick, S Dattani, MT Pitteloud, N AF Raivio, Taneli Avbelj, Magdalena McCabe, Mark J. Romero, Christopher J. Dwyer, Andrew A. Tommiska, Johanna Sykiotis, Gerasimos P. Gregory, Louise C. Diaczok, Daniel Tziaferi, Vaitsa Elting, Mariet W. Padidela, Raja Plummer, Lacey Martin, Cecilia Feng, Bihua Zhang, Chengkang Zhou, Qun-Yong Chen, Huaibin Mohammadi, Moosa Quinton, Richard Sidis, Yisrael Radovick, Sally Dattani, Mehul T. Pitteloud, Nelly TI Genetic Overlap in Kallmann Syndrome, Combined Pituitary Hormone Deficiency, and Septo-Optic Dysplasia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; TRANSCRIPTION FACTORS; MUTATIONS; DEFECTS; MOUSE; GLAND AB Context: Kallmann syndrome (KS), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) all result from development defects of the anterior midline in the human forebrain. Objective: The objective of the study was to investigate whether KS, CPHD, and SOD have shared genetic origins. Design and Participants: A total of 103 patients with either CPHD (n = 35) or SOD (n = 68) were investigated for mutations in genes implicated in the etiology of KS(FGFR1, FGF8, PROKR2, PROK2, and KAL1). Consequences of identified FGFR1, FGF8, and PROKR2 mutations were investigated in vitro. Results: Three patients with SOD had heterozygous mutations in FGFR1; these were either shown to alter receptor signaling (p.S450F, p.P483S) or predicted to affect splicing (c.336C > T, p.T112T). One patient had a synonymous change in FGF8 (c.216G > A, p.T72T) that was shown to affect splicing and ligand signaling activity. Four patients with CPHD/SOD were found to harbor heterozygous rare loss-of-function variants in PROKR2 (p.R85G, p.R85H, p.R268C). Conclusions: Mutations in FGFR1/FGF8/PROKR2 contributed to 7.8% of our patients with CPHD/SOD. These data suggest a significant genetic overlap between conditions affecting the development of anterior midline in the human forebrain. (J Clin Endocrinol Metab 97: E694-E699, 2012) C1 [Dwyer, Andrew A.; Sidis, Yisrael; Pitteloud, Nelly] CHU Vaudois, Endocrine Diabet & Metab Serv, CH-1011 Lausanne, Switzerland. [Dwyer, Andrew A.; Sidis, Yisrael; Pitteloud, Nelly] Univ Lausanne, CH-1011 Lausanne, Switzerland. [Raivio, Taneli; Tommiska, Johanna] Univ Helsinki, Childrens Hosp, Helsinki Univ Cent Hosp, Inst Biomed Physiol, FIN-00290 Helsinki, Finland. [Avbelj, Magdalena] Univ Childrens Hosp, Univ Med Ctr Ljubljana, Ljubljana 1000, Slovenia. [McCabe, Mark J.; Gregory, Louise C.; Tziaferi, Vaitsa; Dattani, Mehul T.] UCL, Dev Endocrinol Res Grp, Clin & Mol Genet Unit, Inst Child Hlth, London EC1V 9EL, England. [Romero, Christopher J.; Diaczok, Daniel; Radovick, Sally] Johns Hopkins Univ, Sch Med, Div Pediat Endocrinol, Baltimore, MD 21205 USA. [Sykiotis, Gerasimos P.] Univ Patras, Sch Med, Dept Internal Med, Div Endocrinol, Patras 26500, Greece. [Sykiotis, Gerasimos P.] Univ Patras, Sch Med, Dept Pharmacol, Patras 26500, Greece. [Elting, Mariet W.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet & Human Genet, NL-1081 HL Amsterdam, Netherlands. [Padidela, Raja] Royal Manchester Childrens Hosp, Dept Paediat Endocrinol, Manchester M13 9WL, Lancs, England. [Plummer, Lacey; Martin, Cecilia; Feng, Bihua] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. [Plummer, Lacey; Martin, Cecilia; Feng, Bihua] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Zhang, Chengkang; Zhou, Qun-Yong] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA. [Chen, Huaibin; Mohammadi, Moosa] New York Uniers Sch Med, Dept Pharmacol, New York, NY USA. [Quinton, Richard] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Newcastle Upon Tyne Hosp, Dept Endocrinol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Pitteloud, N (reprint author), CHU Vaudois, Endocrine Diabet & Metab Serv, BH 19-701,Rue Bugon 46, CH-1011 Lausanne, Switzerland. RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014; OI Dwyer, Andrew/0000-0002-7023-6794; Avbelj Stefanija, Magdalena/0000-0002-0836-5114; Tommiska, Johanna/0000-0001-7958-8262; Mohammadi, Moosa/0000-0003-2434-9437; Sykiotis, Gerasimos/0000-0002-9565-4941 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health [R01HD056264, HD15788, U54HD41859, T32 HD007396]; Swiss National Foundation; Academy of Finland; U.K. Endocrine Research Fund; Slovene National Research Agency [P3-0343]; Pew Latin American Fellows Program in the Biomedical Sciences FX This work was supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health Grants R01HD056264, HD15788, and U54HD41859 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research, the Swiss National Foundation, the Academy of Finland, and the U.K. Endocrine Research Fund. Fellowship support was provided by the Slovene National Research Agency Grant P3-0343 (to M.A.), the Pew Latin American Fellows Program in the Biomedical Sciences (to C.M.), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health Grant T32 HD007396 (to B.F.). NR 20 TC 41 Z9 41 U1 0 U2 2 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 APR PY 2012 VL 97 IS 4 BP E694 EP E699 DI 10.1210/jc.2011-2938 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 925US UT WOS:000302787800027 PM 22319038 ER PT J AU Torriani, M Fitch, K Stavrou, E Bredella, MA Lim, R Sass, CA Cypess, AM Grinspoon, S AF Torriani, Martin Fitch, Kathleen Stavrou, Eleni Bredella, Miriam A. Lim, Ruth Sass, Christina A. Cypess, Aaron M. Grinspoon, Steven TI Deiodinase 2 Expression Is Increased in Dorsocervical Fat of Patients with HIV-Associated Lipohypertrophy Syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BROWN ADIPOSE-TISSUE; THYROID-HORMONE; ADULT HUMANS; LIPODYSTROPHY; ADIPOCYTES AB Context: The pathogenesis and function of dorsocervical sc adipose tissue (DSAT) accumulation in HIV-infected patients is not known. Previous investigations using either UCP-1 expression or positron emission tomography have been inconclusive as to whether this depot represents brown adipose tissue (BAT). We investigated DSAT gene expression, including DIO2, a deiodinase that contributes to increased thermogenesis in brown fat, and simultaneously determined [F-18] fluorodeoxyglucose ([F-18]FDG) uptake in lipodystrophic HIV and healthy control subjects. Design: Thirteen HIV-infected and three non-HIV-infected men were recruited. HIV-infected subjects had evidence of significant lipodystrophy, including fat atrophy of the face, arms, and legs, and/or fat accumulation of the neck and abdomen. Subjects were cooled, followed by [ 18F] FDG positron emission tomography/computed tomography, fat biopsy of DSAT, and measurement of resting energy expenditure (REE). HIV-infected subjects were characterized as lipohypertrophic and lipoatrophic and compared. Results: Mean standardized uptake value of [F-18] FDG and UCP-1 expression were not significantly different in DSAT among the groups. However, lipohypertrophic subjects demonstrated increased expression of DIO2 in DSAT compared with lipoatrophic subjects (P = 0.03). Among HIV-infected patients, DIO2 expression was strongly related to REE (r = 0.78, P = 0.002) and was a predictor of REE in multivariate modeling controlling for age, TSH, and lean body mass (r(2) = 0.79, P = 0.008). One control subject demonstrated typical BAT in the supraclavicular area. Conclusions: Adipose tissue accumulating in the dorsocervical area in HIV lipodystrophy does not appear to be classical BAT. However, DIO2 expression is increased in DSAT among patients with HIV lipodystrophy, particularly those with increased visceral adiposity, and is positively associated with energy expenditure. (J Clin Endocrinol Metab 97: E602-E607, 2012) C1 [Torriani, Martin; Bredella, Miriam A.; Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutr Metab, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Fitch, Kathleen; Stavrou, Eleni; Grinspoon, Steven] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Lim, Ruth] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sass, Christina A.; Cypess, Aaron M.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Sass, Christina A.; Cypess, Aaron M.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Div Musculoskeletal Imaging & Intervent, Longfellow 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU National Institutes of Health [1UL1RR025758, 2P30AI060354, K23 DK081604, K24 DK064545]; Harvard Clinical and Translational Science Center, from the National Center for Research Resources [M01-RR-01066, 1 UL1 RR025758-01] FX This work was supported by National Institutes of Health Grants 1UL1RR025758 and 2P30AI060354 to M. T., K23 DK081604 to A. M. C., K24 DK064545 to S. G., and M01-RR-01066 and 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center, from the National Center for Research Resources. NR 13 TC 16 Z9 16 U1 0 U2 2 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 APR PY 2012 VL 97 IS 4 BP E602 EP E607 DI 10.1210/jc.2011-2951 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 925US UT WOS:000302787800011 PM 22259052 ER PT J AU Biederman, J Petty, CR Day, H Goldin, RL Spencer, T Faraone, SV Surman, CBH Wozniak, J AF Biederman, Joseph Petty, Carter R. Day, Helen Goldin, Rachel L. Spencer, Thomas Faraone, Stephen V. Surman, Craig B. H. Wozniak, Janet TI Severity of the Aggression/Anxiety-Depression/Attention Child Behavior Checklist Profile Discriminates Between Different Levels of Deficits in Emotional Regulation in Youth With Attention-Deficit Hyperactivity Disorder SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE affective symptoms; CBCL; bipolar disorder; severity of illness index ID PEDIATRIC BIPOLAR DISORDER; ADHD; COMORBIDITY; ADOLESCENTS; PREDICTS; SCALES AB Objective: We examined whether severity scores (1 SD vs 2 SDs) of a unique profile of the Child Behavior Checklist (CBCL) consisting of the Anxiety/Depression, Aggression, and Attention (AAA) scales would help differentiate levels of deficits in children with attention-deficit hyperactivity disorder (ADHD). Study Design: Subjects were 197 children with ADHD and 224 without ADHD. We defined deficient emotional self-regulation (DESR) as an aggregate cutoff score of > 180 but < 210 (1 SD) on the AAA scales of the CBCL (CBCL-DESR) and Severe Dysregulation as an aggregate cutoff score of >= 210 on the same scales (CBCL-Severe Dysregulation). All subjects were assessed with structured diagnostic interviews and a range of functional measures. Results: Thirty-six percent of children with ADHD had a positive CBCL-DESR profile versus 2% of controls (p < .001) and 19% had a positive CBCL-Severe Dysregulation profile versus 0% of controls (p < .001). The subjects positive for the CBCL-Severe Dysregulation profile differed selectively from those with the CBCL-DESR profile in having higher rates of unipolar and bipolar mood disorders, oppositional defiant and conduct disorders, psychiatric hospitalization at both baseline and follow-up assessments, and a higher rate of the CBCL-Severe Dysregulation in siblings. In contrast, the CBCL-DESR was associated with higher rates of comorbid disruptive behavior, anxiety disorders, and impaired interpersonal functioning compared with other ADHD children. Conclusion: Severity scores of the AAA CBCL profiles can help distinguish 2 groups of emotional regulation problems in children with ADHD. (J Dev Behav Pediatr 33: 236-243, 2012) C1 [Biederman, Joseph; Petty, Carter R.; Day, Helen; Goldin, Rachel L.; Spencer, Thomas; Surman, Craig B. H.; Wozniak, Janet] Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Pediat Psychopharmacol Unit, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. [Biederman, Joseph; Spencer, Thomas; Surman, Craig B. H.; Wozniak, Janet] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Pediat Psychopharmacol Unit, Clin & Res Program Pediat Psychopharmacol & Adult, 55 Fruit St,YAW6A, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU National Institute of Health [R01 HD36317, R01 MH50657]; Shire Pharmaceuticals; Pediatric Psychopharmacology Research Council; Elminda; Janssen; McNeil; Shire; MGH Psychiatry Academy for a tuition; Fundacion Areces (Spain); Medice Pharmaceuticals (Germany); Spanish Child Psychiatry Association; Abbott; Alza; AstraZeneca; Boston University; Bristol Myers Squibb; Celltech; Cephalon; Eli Lilly and Co.; Esai; Forest; Glaxo; Gliatech; Hastings Center; Merck; MMC Pediatric; NARSAD; NIDA; New River; NICHD; NIMH; Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Phase V Communications; Physicians Academy; Prechter Foundation; Quantia Communications; Reed Exhibitions; Stanley Foundation; UCB Pharma Inc.; Veritas; Wyeth; Shire Laboratories, Inc; Glaxo-Smith Kline; Janssen Pharmaceutical; McNeil Pharmaceutical; Novartis Pharmaceuticals; Eli Lilly; Hilda and Preston Davis Foundation; National Institutes of Health; Takeda; Janssen-Ortho; Johnson and Johnson; Sepracor FX This study was supported in part by grants from the National Institute of Health (R01 HD36317 and R01 MH50657; to J.B.) and from Shire Pharmaceuticals (to T. S.) and the Pediatric Psychopharmacology Research Council Fund.; Dr. Joseph Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil, and Shire. In 2011, Dr. Joseph Biederman gave a single unpaid talk for Juste Pharmaceutical Spain, received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course, and received an honorarium for presenting at an international scientific conference on ADHD. He also received an honorarium from Cambridge University Press for a chapter publication. Dr. Biederman received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Eli Lilly, Shire, and AstraZeneca; these royalties are paid to the Department of Psychiatry at MGH. In 2010, Dr. Joseph Biederman received a speaker's fee from a single talk given at Fundacion Dr. Manuel Camelo A.C. in Monterrey Mexico. Dr. Biederman provided single consultations for Shionogi Pharma Inc. and Cipher Pharmaceuticals Inc.; the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. Dr. Biederman received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In 2009, Dr. Joseph Biederman received a speaker's fee from the following sources: Fundacion Areces (Spain), Medice Pharmaceuticals (Germany), and the Spanish Child Psychiatry Association. In previous years, Dr. Joseph Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Boston University, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai, Forest, Glaxo, Gliatech, Hastings Center, Janssen, McNeil, Merck, MMC Pediatric, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Phase V Communications, Physicians Academy, The Prechter Foundation, Quantia Communications, Reed Exhibitions, Shire, The Stanley Foundation, UCB Pharma Inc., Veritas, and Wyeth.; Dr. Thomas Spencer has received research support from, has been a speaker for or on a speaker bureau, or has been an Advisor or on an Advisory Board of the following sources: Shire Laboratories, Inc, Eli Lilly & Company, Glaxo-Smith Kline, Janssen Pharmaceutical, McNeil Pharmaceutical, Novartis Pharmaceuticals, Cephalon, Pfizer, the National Institute of Mental Health, and royalties on adult ADHD scales (research support).; Dr. Surman has received research support from Abbott, Alza, Cephalon, Eli Lilly, the Hilda and Preston Davis Foundation, McNeil, Merck, New River, National Institutes of Health, Organon, Pfizer, Shire, and Takeda; has received support from Janssen-Ortho, McNeil, Novartis, and Shire for speaking and other educational activities; and has been a consultant/advisor for McNeil, Shire, and Takeda. Dr. Surman has also received honoraria from Reed Medical Education (a logistics collaborator for the MGH Psychiatry Academy). Commercial entities supporting the MGH Psychiatry Academy are listed on the Academy's website, www.mghcme.org.; Dr. Janet Wozniak is the author of "Is Your Child Bipolar" published May 2008, Bantam Books. Speaker: Primedia/MGH Psychiatry Academy. Research Support: McNeil, Shire, Janssen, Johnson and Johnson. Her spouse, Dr. John Winkelman: Speakers Bureau: Sanofi-Aventis, Sepracor. Consultant/Advisory Board: Covance, GlaxoSmithKline, Impax Laboratories, Luitpold Pharmaceuticals, Neurogen, Pfizer, UCB, Zeo Inc. Research Support: GlaxoSmithKline, Sepracor.; In the past year, Dr. Faraone received consulting fees and was on Advisory Boards for Shire Development and received research support from Shire and the National Institutes of Health (NIH). In previous years, he received consulting fees or was on Advisory Boards or participated in continuing medical education programs sponsored by Shire, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly. In previous years, he received research support from Eli Lilly, Shire, Pfizer, and the NIH. Dr. Faraone receives royalties from a book published by Guilford Press, "Straight Talk about Your Child's Mental Health." NR 28 TC 38 Z9 39 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD APR PY 2012 VL 33 IS 3 BP 236 EP 243 DI 10.1097/DBP.0b013e3182475267 PG 8 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 926YH UT WOS:000302868500008 PM 22278125 ER PT J AU DuPriest, EA Kupfer, P Lin, B Sekiguchi, K Purnell, JQ Saunders, KE Chatkupt, TT Bagby, SP AF DuPriest, E. A. Kupfer, P. Lin, B. Sekiguchi, K. Purnell, J. Q. Saunders, K. E. Chatkupt, T. T. Bagby, S. P. TI Accelerated growth without prepubertal obesity in nutritionally programmed microswine offspring SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Article DE Appetite; catch-up growth; feed intake; linear growth; maternal protein restriction ID AMINO-ACID-CONCENTRATIONS; LOW-BIRTH-WEIGHT; LOW-PROTEIN DIET; ADULT HYPERTENSION; GESTATIONAL-AGE; FETAL; RESTRICTION; PIGS; RAT; LIFE AB Poor fetal growth and associated prepubertal growth acceleration are linked to increased risk of cardiometabolic dysfunction in later life, but whether obesity is integral to 'catch-up' growth and its ensuing risks are unknown. In microswine offspring exposed to perinatal maternal protein restriction (MPR), we measured body and organ sizes (during MPR); linear growth and weight gain (birth to 5 months of age); feed intake and utilization efficiency (5-14 weeks); and body composition at 6 and 11 weeks of age (by dual-energy X-ray absorptiometry, DEXA). During MPR, low protein offspring (LPO) showed asymmetric growth restriction with reduced body weight (Wt):length (Lth) at birth and elevated heart Wt: liver Wt ratio by 2 weeks of age. In LPO, after slow early postnatal growth (0-5 weeks), subsequent linear growth on ad libitum normal feed was absolutely accelerated (cm/week; P < 0.001) over 6-11 weeks but normal thereafter, whereas absolute weight gain (kg/week) was similar to controls but accelerated relative to lower LPO nadir weights. Concurrently, rates of fat and lean tissue accrual in LPO over 6-11 weeks were similar to normal protein offspring in absolute terms (g/5 weeks) but increased relative to lower mass at 6 weeks, yielding normal lean: Lth but reduced fat: Lth ratios at 11 weeks. LPO had higher relative feed intake (g/kg/meal) in both sexes and higher feed efficiency in females over 5-11 weeks of age. Findings suggest that postnatal linear growth acceleration preserved thinness in juvenile LPO. Given separately reported abnormalities of vascular (Bagby et al., 2011) and adipocyte function in juvenile LPO, (DuPriest et al., 2011) findings demonstrate that perinatal MPR programs catch-up growth and cardiovascular abnormalities independently of obesity. C1 [Bagby, S. P.] Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, Portland, OR 97201 USA. [DuPriest, E. A.; Bagby, S. P.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [DuPriest, E. A.; Kupfer, P.; Lin, B.; Sekiguchi, K.; Bagby, S. P.] Portland VA Med Ctr, Res Serv, Portland, OR USA. [DuPriest, E. A.] Warner Pacific Coll, Dept Nat Sci & Hlth, Portland, OR USA. [Saunders, K. E.; Chatkupt, T. T.] Oregon Hlth & Sci Univ, Dept Comparat Med, Portland, OR 97201 USA. RP Bagby, SP (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, 3303 SW Bond Ave,CH12R, Portland, OR 97201 USA. EM bagbys@ohsu.edu RI Biguzzi, Felipe/E-4724-2015 FU NIH/NICHD [1P01 HD34430, R01 HD042570]; Medical Research Foundation of Oregon; Eagles Foundation of Spokane, WA, USA; American Heart Association [0415530Z]; Oregon Health & Science University FX Work was supported by NIH/NICHD 1P01 HD34430, R01 HD042570, Medical Research Foundation of Oregon and the Eagles Foundation of Spokane, WA, USA. E.A. DuPriest was supported by American Heart Association Pacific Mountain Affiliate Predoctoral Fellowship Award No. 0415530Z and by the Oregon Health & Science University Tartar Trust Fellowship. NR 39 TC 2 Z9 2 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD APR PY 2012 VL 3 IS 2 BP 92 EP 102 DI 10.1017/S2040174412000037 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 929KQ UT WOS:000303061700004 PM 25101919 ER PT J AU de Brito, LCN Teles, FRF Teles, RP Totola, AH Vieira, LQ Sobrinho, APR AF Neves de Brito, Luciana Carla Fonseca Teles, Flavia Rocha Teles, Ricardo Palmier Totola, Antonio Helvecio Vieira, Leda Quercia Ribeiro Sobrinho, Antonio Paulin TI T-Lymphocyte and Cytokine Expression in Human Inflammatory Periapical Lesions SO JOURNAL OF ENDODONTICS LA English DT Article DE Chemokines; cytokines; periapical lesion ID DIFFERENTIAL EXPRESSION; APICAL PERIODONTITIS; CHEMOKINE RECEPTORS; RADICULAR CYSTS; CELLS; TH1; MYCOBACTERIAL; ACTIVATION; GRANULOMAS; RESPONSES AB Introduction: Lymphocytes, among many cells, express different sets of cytokines, chemokines, and receptors, which are considered important mediators of periapical immune response to infection. Methods: The aim of this study was to evaluate the mRNA expression of CD4(+)CD28(+) and CD8(+) T genes and the gene expression of interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-17A, IL-10, CCL2/MCP-1, CCL4, CCL5, CXCR4, CCR5, and receptor activator for nuclear factor kappa B ligand (RANKL) in periapical interstitial fluid from human root canal infections. The samples were collected immediately after root canal cleaning and 7 days later (restrained root canal bacterial load) to characterize those gene expressions. Results: Real-time polymerase chain reaction demonstrated significantly higher levels of CD4(+)CD28(+) and CD8(+) T-cell markers in the former root canal condition and an increase of IL-10 and CXCR4, followed by a decrease of proinflammatory cytokines such as RANKL, interferon-gamma, IL-1 beta, and CCL5. Conclusions: Analyses of T-lymphocyte and cytokine expression in periapical area were able to show that distinct root canal conditions might play regulatory roles in controlling local immune/inflammatory processes. (J Endod 2012;38:481-485) C1 [Neves de Brito, Luciana Carla; Ribeiro Sobrinho, Antonio Paulin] Univ Fed Minas Gerais, Fac Odontol, Dept Odontol Restauradora, BR-31270901 Belo Horizonte, MG, Brazil. [Fonseca Teles, Flavia Rocha; Teles, Ricardo Palmier] Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. [Fonseca Teles, Flavia Rocha; Teles, Ricardo Palmier] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Totola, Antonio Helvecio] Univ Fed Sao Joao Rei, Dept Engn Bioproc, Paraopeba, MG, Brazil. [Vieira, Leda Quercia] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, BR-31270901 Belo Horizonte, MG, Brazil. [Vieira, Leda Quercia] Univ Fed Ouro Preto, Nucleo Pesquisa Ciencias Biol, Ouro Preto, MG, Brazil. RP Sobrinho, APR (reprint author), Univ Fed Minas Gerais, Fac Odontol, Dept Odontol Restauradora, BR-31270901 Belo Horizonte, MG, Brazil. EM sobrinho.bhz@terra.com.br RI Sobrinho, Antonio/H-3245-2012; 3, INCT/H-4497-2013; Redoxoma, Inct/H-9962-2013; Vieira, Leda/G-7487-2014 FU Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) FX Supported by Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq). L.C.N.B. is a CAPES fellow; A.P.R.S. and L.Q.V. are CNPq fellows. NR 31 TC 15 Z9 15 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD APR PY 2012 VL 38 IS 4 BP 481 EP 485 DI 10.1016/j.joen.2011.12.010 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 927QX UT WOS:000302926200012 PM 22414833 ER PT J AU Harrington, AT Hsia, JC Mendez, E Clarridge, JE AF Harrington, Amanda T. Hsia, Jennifer C. Mendez, Eduardo Clarridge, Jill E., III TI A lingual abscess caused by Streptococcus intermedius SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID GLOSSAL ABSCESS; MILLERI GROUP; CONSTELLATUS; ANGINOSUS AB Lingual abscesses are rare. We describe a case in a healthy female with no recent history of trauma. The organism recovered by culture of drainage material collected prior to antibiotic treatment was Streptococcus intermedius, an organism recognized as flora of the oropharynx and associated with abscess formation. The isolate was resistant to clindamycin, which was the antibiotic therapy that the patient received. C1 [Harrington, Amanda T.; Clarridge, Jill E., III] VA Puget Sound Hlth Care Syst, Dept Pathol & Lab Med, Seattle, WA 98108 USA. [Harrington, Amanda T.; Clarridge, Jill E., III] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Hsia, Jennifer C.; Mendez, Eduardo] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Mendez, Eduardo] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA 98108 USA. [Mendez, Eduardo] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. RP Clarridge, JE (reprint author), VA Puget Sound Hlth Care Syst, Dept Pathol & Lab Med, Seattle, WA 98108 USA. EM Jill.clarridge@va.gov FU VA Puget Sound Health Care System, Seattle, Washington FX This material is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, Washington. NR 12 TC 0 Z9 0 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD APR PY 2012 VL 61 IS 4 BP 590 EP 592 DI 10.1099/jmm.0.036913-0 PG 3 WC Microbiology SC Microbiology GA 927CJ UT WOS:000302884300020 PM 22116986 ER PT J AU Foerch, C You, ZR Wang, H Lo, EH Whalen, MJ AF Foerch, Christian You, Zerong Wang, Hui Lo, Eng H. Whalen, Michael J. TI Traumatic Brain Injury during Warfarin Anticoagulation: An Experimental Study in Mice SO JOURNAL OF NEUROTRAUMA LA English DT Article DE animal studies; in vivo studies; models of injury; traumatic brain injury ID RECOMBINANT FACTOR VIIA; INTRACEREBRAL HEMORRHAGE; PREINJURY WARFARIN; INTRACRANIAL HEMORRHAGE; ATRIAL-FIBRILLATION; REDUCES HEMORRHAGE; HEAD-INJURY; MORTALITY; REVERSAL; OUTCOMES AB The number of patients who are on long-term anticoagulation therapy while experiencing traumatic brain injury (TBI) is rising. This experimental study evaluated whether warfarin pre-treatment increases brain hemorrhage and worsens functional outcome after TBI, and whether the rapid reversal of anticoagulation after TBI prevents warfarin-exacerbated brain damage. Normal CD-1 mice (C) and mice pre-treated with warfarin (W) to an International Normalized Ratio of 3.5 +/- 0.9 underwent TBI using a controlled cortical impact model. Mean hemorrhage volume 24 h after TBI was 1.2 +/- 0.4 mu L in C mice and 10.9 +/- 6.9 mu L in W mice (p = 0.029, n = 4 per group). In a second study, anticoagulated mice received either saline (W-S) or prothrombin complex concentrate (W-PCC, 100 U/kg) intravenously 60 min after TBI. Anticoagulation reversal using PCC (W-PCC mice) reduced hemorrhage volumes as compared to W-S animals (7.3 +/- 6.0 versus 19.8 +/- 14.0 mu L, p = 0.045, n = 8 per group). In a third study, we examined motor deficits and lesion volume in C, W-S, and W-PCC mice until 33 days after injury. Functional outcome and lesion volume were no different between groups (n = 10 per group). In conclusion, we characterized an experimental model of TBI occurring during warfarin anticoagulation. Anticoagulation led to higher intracerebral blood volumes, but did not significantly worsen functional outcome. The rapid reversal of anticoagulation may be effective in preventing excess bleeding. C1 [Foerch, Christian] Goethe Univ Frankfurt, Dept Neurol, D-60528 Frankfurt, Germany. [Foerch, Christian; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA. [You, Zerong; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA USA. [You, Zerong; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA USA. [Wang, Hui] Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Bone Marrow Transplantat Sect,Sch Med, Charlestown, MA USA. RP Foerch, C (reprint author), Goethe Univ Frankfurt, Dept Neurol, Schleusenweg 2-16, D-60528 Frankfurt, Germany. EM foerch@em.uni-frankfurt.de FU CSL Behring, Marburg, Germany FX Christian Foerch received a 3-month research grant from CSL Behring, Marburg, Germany, to complete this study. NR 20 TC 4 Z9 4 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD APR PY 2012 VL 29 IS 6 BP 1150 EP 1155 DI 10.1089/neu.2011.2104 PG 6 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 927ZL UT WOS:000302949100015 PM 22142342 ER PT J AU Grudzen, CR Hwang, U Cohen, JA Fischman, M Morrison, S AF Grudzen, Corita R. Hwang, Ula Cohen, Jason A. Fischman, Michael Morrison, Sean TI Characteristics of Emergency Department Patients Who Receive a Palliative Care Consultation SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIAL; LUNG-CANCER; OF-LIFE; INTERVENTION; MANAGEMENT; VALIDITY; PROJECT; SERVICE; IMPACT AB Background: A large gap exists between the practice of emergency medicine and palliative care. Although hospice and palliative medicine has recently been recognized as a subspecialty of emergency medicine, few palliative care teams routinely interact with emergency providers, and primary palliative care skills among emergency providers are lacking. Objective: To identify the proportion and characteristics of patients who receive a palliative care consultation and arrive via the emergency department (ED). Methods: A descriptive study of adult ED patients from an urban, academic tertiary care hospital who received a palliative care consultation in January 2005 or January 2009. Results: In January 2005, 100 of the 161 consults (62%) arrived via the ED versus 63 of 124 consults (51%) in January 2009 (p = 0.06). Mean days from admission to consultation in January 2005 were six days (standard deviation 11), versus nine days (SD 26) in January 2009 (p = 0.35). Three of the 100 consultations (3%) in January 2005 were initiated in the ED, versus 4 of the 64 (6%) in January 2009. Conclusions: At an urban academic medical center with a well-developed palliative care service, the majority of palliative care consultations were for patients who arrive via the ED. Despite this, only a small minority of consultations originated from emergency providers and consultation was on average initiated days into a patient's hospital stay. C1 [Grudzen, Corita R.; Hwang, Ula] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Grudzen, Corita R.; Hwang, Ula; Morrison, Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Hwang, Ula; Morrison, Sean] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Fischman, Michael] St Georges Univ, St Georges, Grenada. RP Grudzen, CR (reprint author), Mt Sinai Sch Med, Dept Emergency Med, 1 Gustave L Levy Pl,Box 1620, New York, NY 10029 USA. EM corita.grudzen@mssm.edu OI Grudzen, Corita/0000-0003-3039-8497 FU American Cancer Society; National Institute on Aging [K23 AG031218, K24 AG022345]; Patricia Levinson Fund FX Dr. Grudzen was supported by a Mentored Research Scholar Grant from the American Cancer Society, Dr. Hwang by a Mentored Patient-Oriented Career Development Award from the National Institute on Aging (K23 AG031218), Dr. Cohen by a grant from the Patricia Levinson Fund, and Dr. Morrison by a Mid-Career Investigator Award in Patient Oriented Research (K24 AG022345) from the National Institute on Aging. NR 30 TC 17 Z9 17 U1 2 U2 7 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 APR PY 2012 VL 15 IS 4 BP 396 EP 399 DI 10.1089/jpm.2011.0376 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 926TM UT WOS:000302854700006 PM 22468771 ER PT J AU Schenker, Y Smith, AK Arnold, RM Fernandez, A AF Schenker, Yael Smith, Alexander K. Arnold, Robert M. Fernandez, Alicia TI "Her Husband Doesn't Speak Much English": Conducting a Family Meeting with an Interpreter SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID CARE-UNIT PATIENTS; LANGUAGE BARRIERS; HEALTH-CARE; MEDICAL INTERPRETATION; RESIDENT PHYSICIANS; PALLIATIVE CARE; COMMUNICATION; SATISFACTION; SERVICES; SPANISH AB A growing percentage of critically ill patients and their families in the United States speak limited English. We present the case of a palliative care consult conducted across language barriers to frame a discussion about the use of interpreters for family meetings, including the evidence for using a professional interpreter, the burden experienced by interpreters involved in end-of-life discussions, potential challenges encountered when conducting a family meeting with an interpreter, and recommended best practices for interpreter use in these settings. C1 [Schenker, Yael; Arnold, Robert M.] Univ Pittsburgh, Div Gen Internal Med, Sect Palliat Care & Med Eth, Pittsburgh, PA 15213 USA. [Smith, Alexander K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Smith, Alexander K.] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94143 USA. [Fernandez, Alicia] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Schenker, Y (reprint author), Univ Pittsburgh, Div Gen Internal Med, Sect Palliat Care & Med Eth, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM schenkery@upmc.edu FU National Palliative Care Research Center; Arnold P. Gold Foundation FX Dr. Schenker was supported by a Junior Faculty Career Development Award from the National Palliative Care Research Center. Dr. Fernandez was supported by an Arnold P. Gold Foundation Professorship. NR 45 TC 2 Z9 2 U1 0 U2 2 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 APR PY 2012 VL 15 IS 4 BP 494 EP 498 DI 10.1089/jpm.2011.0169 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 926TM UT WOS:000302854700025 PM 22107068 ER PT J AU Bystritsky, A Nierenberg, AA Feusner, JD Rabinovich, M AF Bystritsky, A. Nierenberg, A. A. Feusner, J. D. Rabinovich, M. TI Computational non-linear dynamical psychiatry: A new methodological paradigm for diagnosis and course of illness SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Review DE Phenomenology; Mathematical models; Non-linear dynamics; Winner less competition; Psychopathology ID GENERALIZED ANXIETY DISORDER; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; OBSESSIVE-COMPULSIVE SPECTRUM; DSM-IV; MENTAL-DISORDERS; DECISION-MAKING; SYSTEMS BIOLOGY; PANIC DISORDER; NEURAL BASIS; TIME-SERIES AB The goal of this article is to highlight the significant potential benefits of applying computational mathematical models to the field of psychiatry, specifically in relation to diagnostic conceptualization. The purpose of these models is to augment the current diagnostic categories that utilize a "snapshot" approach to describing mental states. We hope to convey to researchers and clinicians that non-linear dynamics can provide an additional useful longitudinal framework to understand mental illness. Psychiatric phenomena are complex processes that evolve in time, similar to many other processes in nature that have been successfully described and understood within deterministic chaos and non-linear dynamic computational models. Dynamical models describe mental processes and phenomena that change over time, more like a movie than a photograph, with multiple variables interacting over time. The use of these models may help us understand why and how current diagnostic categories are insufficient. They may also provide a new, more descriptive and ultimately more predictive approach leading to better understanding of the interrelationship between psychological, neurobiological, and genetic underpinnings of mental illness. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Bystritsky, A.; Feusner, J. D.] Univ Calif Los Angeles, David Geffen Sch Medicine, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Nierenberg, A. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [Rabinovich, M.] Univ Calif San Diego, BioCircuit Inst, San Diego, CA 92103 USA. RP Bystritsky, A (reprint author), Univ Calif Los Angeles, David Geffen Sch Medicine, Semel Inst Neurosci & Human Behav, MC 696824,300 Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM abystritsky@mednet.ucla.edu RI Feusner, Jamie/K-2312-2012 OI Feusner, Jamie/0000-0002-0391-345X FU NIMH [2U01MH058915-05A2, 5K23 MH079212, 1R01 MH085900, 1 K18 OD008085-01]; Saban Family Foundation; Office of Naval Recearch [ONR-N00014-07-1-0741] FX This research is supported in part by a grant from NIMH 2U01MH058915-05A2 and grant from Saban Family Foundation, (Dr. Bystritsky); a grant from the National Institute of Mental Health (5K23 MH079212 and 1R01 MH085900, Dr. Feusner); a grant from the National Institute of Mental Health (1 K18 OD008085-01, Dr. Nierenberg); and a grant from Office of Naval Recearch (ONR-N00014-07-1-0741, Dr. Rabinovich). Special thanks to Ary Goldberger, MD, Professor and Director of the Margret & H. A. Rey Institute for Nonlinear Dynamics in Medicine at the Beth Israel Deaconess MedicalCenter, Harvard Medical School for reviewing the manuscript. NR 54 TC 21 Z9 21 U1 3 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 APR PY 2012 VL 46 IS 4 BP 428 EP 435 DI 10.1016/j.jpsychires.2011.10.013 PG 8 WC Psychiatry SC Psychiatry GA 927FQ UT WOS:000302892900002 PM 22261550 ER PT J AU Brown, A Biederman, J Valera, E Lomedico, A Aleardi, M Makris, N Seidman, LJ AF Brown, Ariel Biederman, Joseph Valera, Eve Lomedico, Alexandra Aleardi, Megan Makris, Nikos Seidman, Larry J. TI Working memory network alterations and associated symptoms in adults with ADHD and Bipolar Disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE fMRI; Bipolar Disorder; ADHD; Working memory; Executive function; Default mode network ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; DEFICIT HYPERACTIVITY DISORDER; COMORBIDITY SURVEY REPLICATION; FUNCTIONAL MRI; NEURONAL ACTIVATION; PREFRONTAL CORTEX; EUTHYMIC PATIENTS; BRAIN ACTIVATION; FAMILIAL SUBTYPE; SEX-DIFFERENCES AB Attention-Deficit/Hyperactivity Disorder (ADHD) and Bipolar Disorder (BPD) co-occur frequently and represent a particularly morbid clinical form of both disorders, however underlying neural circuitry contributing to the comorbidity remain understudied. Our aim was to investigate functional brain circuitry during working memory in a group of participants who meet criteria for both disorders (ADHD + BPD), and to explore the relationship of symptoms of each disorder to brain function. We used fMRI to image brain activity in 18 male adults with both ADHD and BPD, and 18 healthy control participants matched one-to-one on age, sex, and handedness, while they performed a sequential letter N-back task. We investigated differences in activation between these groups, and also correlations of brain activity during the task to symptoms of ADHD and BPD independently. We found significant hypoactivity in the subjects with ADHD + BPD vs. controls across frontal and parietal regions, and further, found that BPD and ADHD symptoms related to activity in anatomically distinct regions that were respectively characterized by activation and suppression during task. We conclude that comorbid ADHD + BPD is associated with alterations across anterior and posterior nodes of the working memory network, and symptoms of each disorder are related to anatomically and functionally distinct brain regions. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Brown, Ariel; Biederman, Joseph; Valera, Eve; Lomedico, Alexandra; Aleardi, Megan; Seidman, Larry J.] Massachusetts Gen Hosp, Clin & Res Program Adult ADHD, Dept Psychiat, Boston, MA 02114 USA. [Brown, Ariel; Biederman, Joseph; Valera, Eve; Lomedico, Alexandra; Aleardi, Megan; Seidman, Larry J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Brown, Ariel] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Ariel; Biederman, Joseph; Valera, Eve; Makris, Nikos; Seidman, Larry J.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Res Program, Boston, MA 02129 USA. [Brown, Ariel; Biederman, Joseph; Valera, Eve; Makris, Nikos; Seidman, Larry J.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Makris, Nikos] Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Boston, MA 02129 USA. [Makris, Nikos] Massachusetts Gen Hosp, Dept Radiol, Ctr Morphometr Anal, Boston, MA 02129 USA. [Makris, Nikos] MGH HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div,Dept Psychiat,Med Sch, Boston, MA 02215 USA. [Brown, Ariel; Biederman, Joseph; Valera, Eve; Lomedico, Alexandra; Aleardi, Megan; Seidman, Larry J.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Dept Psychiat, Boston, MA 02114 USA. RP Brown, A (reprint author), Massachusetts Gen Hosp WRN 637C, Clin & Res Program Pediat Psychopharmacol, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA. EM ariel@nmr.mgh.harvard.edu FU NIMH [MH 62152]; National Association for Research on Schizophrenia and Depression; Boston University School of Medicine, Division of Graduate Medical Sciences; Janssen Pharmaceuticals; Mental Illness and Neuroscience Discovery (MIND) Institute; Kimmerly-Neil Fund for the Study of Cognition and Psychiatric Disorders in Children; Pediatric Psychopharmacology Council; National Center for Research Resources [P41RR14075]; Elminda; Janssen; McNeil; Next Wave Pharmaceuticals; Shire; MGH Psychiatry Academy; Eli Lilly; AstraZeneca; Fundacion Dr.Manuel Camelo A.C. in Monterrey Mexico; Fundacion Areces (Spain); Medice Pharmaceuticals (Germany); Spanish Child Psychiatry Association; Abbott; Alza; Esai; Forest; Glaxo; Gliatech; Merck; NARSAD; NIDA; New River; NICHD; NIMH; Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma, Inc.; Wyeth; [MH 57934]; [MH 071535] FX This research was supported by grants from: NIMH MH 62152 (US), the National Association for Research on Schizophrenia and Depression Distinguished Investigator Award (JB), MH 57934 (SF), MH 071535 (EV); Boston University School of Medicine, Division of Graduate Medical Sciences Graduate Student Research Fellowship (AB); Janssen Pharmaceuticals (JB); the Mental Illness and Neuroscience Discovery (MIND) Institute (US); the Kimmerly-Neil Fund for the Study of Cognition and Psychiatric Disorders in Children; the Pediatric Psychopharmacology Council Fund; and the National Center for Research Resources (P41RR14075). Funding bodies had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.; Dr. Joseph Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil, Next Wave Pharmaceuticals, and Shire. In 2011, Dr. Biederman gave a single unpaid talk for Juste Pharmaceutical Spain, and received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. He also received an honorarium from Cambridge University Press for a chapter publication. Dr. Biederman received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Eli Lilly, Shire and AstraZeneca: these royalties are paid to the Department of Psychiatry at MGH. In 2010, Dr. Biederman received a speaker's fee from a single talk given at Fundacion Dr.Manuel Camelo A.C. in Monterrey Mexico. Dr. Biederman provided single consultations for Shionogi Pharma Inc. and Cipher Pharmaceuticals Inc.; the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. Dr. Biederman received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In 2009, Dr. Joseph Biederman received a speaker's fee from the following sources: Fundacion Areces (Spain), Medice Pharmaceuticals (Germany) and the Spanish Child Psychiatry Association. In previous years, Dr. Joseph Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai, Forest, Glaxo, Gliatech, Janssen, McNeil, Merck, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, Inc. and Wyeth. NR 60 TC 7 Z9 7 U1 2 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 APR PY 2012 VL 46 IS 4 BP 476 EP 483 DI 10.1016/j.jpsychires.2012.01.008 PG 8 WC Psychiatry SC Psychiatry GA 927FQ UT WOS:000302892900009 PM 22272986 ER PT J AU Biederman, J Fried, R Hammerness, P Surman, C Mehler, B Petty, CR Faraone, SV Miller, C Bourgeois, M Meller, B Godfrey, KM Reimer, B AF Biederman, Joseph Fried, Ronna Hammerness, Paul Surman, Craig Mehler, Bruce Petty, Carter R. Faraone, Stephen V. Miller, Carolyn Bourgeois, Michelle Meller, Benjamin Godfrey, Kathryn M. Reimer, Bryan TI The effects of lisdexamfetamine dimesylate on the driving performance of young adults with ADHD: A randomized, double-blind, placebo-controlled study using a validated driving simulator paradigm SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Attention deficit/hyperactivity disorder (ADHD); Driving ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; SALTS EXTENDED-RELEASE; CONTROLLED-TRIAL; PHYSIOLOGICAL AROUSAL; OROS METHYLPHENIDATE; COGNITIVE WORKLOAD; DRIVERS; IMPACT; ADOLESCENTS AB Young adults with Attention Deficit Hyperactivity Disorder (ADHD) have been shown to be at increased risk for impairment in driving behaviors. While stimulant medications have proven efficacy in reducing ADHD symptomatology, there is limited knowledge as to their effects on driving impairment. The main aim of this study was to assess the impact of lisdexamfetamine dimesylate (LDX) on driving performance in young adults with ADHD using a validated driving simulation paradigm. This was a randomized, double-blind, 6-week, placebo-controlled, parallel-design study of LDX vs. a placebo on driving performance in a validated driving simulation paradigm. Subjects were sixty-one outpatients of both sexes, 18-26 years of age, who met DSM-IV criteria for ADHD. Subjects were randomized to receive LDX or placebo after a baseline driving simulation and completed a second driving simulation six weeks after beginning drug or placebo. Examination of reaction time across five surprise events at post-treatment showed a significant positive effect of medication status. LDX treatment was also associated with significantly fewer accidents vs. placebo. LDX treatment was associated with significantly faster reaction times and a lower rate of simulated driving collisions than placebo. These results suggest that LDX may reduce driving risks in young adults with ADHD. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Biederman, Joseph] Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Biederman, Joseph; Fried, Ronna; Hammerness, Paul; Surman, Craig; Petty, Carter R.; Miller, Carolyn; Bourgeois, Michelle; Meller, Benjamin] Massachusetts Gen Hosp, Clin & Res Program Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph; Fried, Ronna; Hammerness, Paul; Surman, Craig] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Mehler, Bruce; Godfrey, Kathryn M.; Reimer, Bryan] MIT, New England Univ Transportat Ctr, Cambridge, MA 02139 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Clin & Res Program Pediat Psychopharmacol, YAW-6A-6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org RI Mehler, Bruce/E-4538-2017; Reimer, Bryan/G-6431-2010; OI Mehler, Bruce/0000-0001-5929-4179; Reimer, Bryan/0000-0003-4850-8738; Faraone, Stephen/0000-0002-9217-3982 FU Shire Pharmaceuticals Inc.; Elminda; Janssen; McNeil; Next Wave Pharmaceuticals; Shire; MGH Psychiatry Academy; Eli Lilly; AstraZeneca; Fundacion Dr.Manuel Camelo A.C. in Monterrey Mexico; Fundacion Areces (Spain); Medice Pharmaceuticals (Germany); Spanish Child Psychiatry Association; Abbott; Alza; Boston University; Bristol Myers Squibb; Celltech; Cephalon; Eli Lilly and Co.; Esai; Forest; Glaxo; Gliatech; Hastings Center; Merck; MMC Pediatric; NARSAD; NIDA; New River; NICHD; NIMH; Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Phase V Communications; Physicians Academy; Prechter Foundation; Quantia Communications; Reed Exhibitions; Stanley Foundation; UCB Pharma Inc.; Veritas; Wyeth; Ortho-McNeil Janssen; Elminda Ltd; GlaxoSmithKline; Johnson Johnson; Takeda; theHilda and Preston Davis Foundation; National Institutes of Health; Janssen-Ortho FX This study was funded by Shire Pharmaceuticals Inc. The study sponsor had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.; Dr. Joseph Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil, Next Wave Pharmaceuticals, and Shire. In 2011, Dr. Joseph Biederman gave a single unpaid talk for Juste Pharmaceutical Spain, and received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. He also received an honorarium from Cambridge University Press for a chapter publication. Dr. Biederman received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Eli Lilly, Shire and AstraZeneca; these royalties are paid to the Department of Psychiatry at MGH. In 2010, Dr. Joseph Biederman received a speaker's fee from a single talk given at Fundacion Dr.Manuel Camelo A.C. in Monterrey Mexico. Dr. Biederman provided single consultations for Shionogi Pharma Inc. and Cipher Pharmaceuticals Inc.: the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. Dr. Biederman received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In 2009, Dr. Joseph Biederman received a speaker's fee from the following sources: Fundacion Areces (Spain), Medice Pharmaceuticals (Germany) and the Spanish Child Psychiatry Association.In previous years, Dr. Joseph Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Boston University, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai, Forest, Glaxo, Gliatech, Hastings Center, Janssen, McNeil, Merck, MMC Pediatric, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Phase V Communications, Physicians Academy, The Prechter Foundation, Quantia Communications, Reed Exhibitions, Shire, The Stanley Foundation, UCB Pharma Inc., Veritas, and Wyeth.; In the past 2 years, Dr. Hammerness has participated in CME activities/professional talks supported by Ortho-McNeil Janssen and Shire and served on the advisory board for Shire. In the past 2 years, Dr. Hammerness has participated, as an investigator/principal investigator, in research studies funded by the following pharmaceutical companies/companies: Cephalon, Eli Lilly, Elminda Ltd, GlaxoSmithKline, Johnson & Johnson, McNeil, Merck, New River, Novartis, Ortho-McNeil Janssen, Pfizer, Shire, Takeda. Dr. Hammerness has also received honoraria from commercial entities supporting the MGH Psychiatry Academy, www.mghcme.org.; Dr. Craig Surman has received research support from Abbott, Alza, Cephalon, Eli Lilly, theHilda and Preston Davis Foundation, McNeil, Merck, New River, National Institutes of Health, Organon, Pfizer, Shire, and Takeda: has received support from Janssen-Ortho, McNeil, Novartis, and Shire for speaking and other educational activities: and has been a consultant/advisor for McNeil, Shire, and Takeda. Dr. Surman has also received honoraria from Reed Medical Education (a logistics collaborator for the MGH Psychiatry Academy). Commercial entities supporting the MGH Psychiatry Academy are listed on the Academy's Web site, www.mghcme.org. NR 38 TC 20 Z9 20 U1 0 U2 12 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 APR PY 2012 VL 46 IS 4 BP 484 EP 491 DI 10.1016/j.jpsychires.2012.01.007 PG 8 WC Psychiatry SC Psychiatry GA 927FQ UT WOS:000302892900010 PM 22277301 ER PT J AU King, DR AF King, David R. TI Continuously recorded oxygen saturation and heart rate during prehospital transport outperform initial measurement in prediction of mortality after trauma EDITORIAL CRITIQUE SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02115 USA. RP King, DR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 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 APR PY 2012 VL 72 IS 4 BP 1011 EP 1012 PG 2 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 925TO UT WOS:000302784600045 PM 22590751 ER PT J AU Miller, MA Liu, WJ Zurakowski, D Smith, RM Harris, MB Vrahas, MS AF Miller, Micah A. Liu, Wanjun Zurakowski, David Smith, Raymond Malcolm Harris, Mitchel B. Vrahas, Mark S. TI Factors predicting failure of patella fixation SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Patella fracture; fracture fixation; tension band ID OPERATIVE TREATMENT; INTERNAL-FIXATION; TENSION BAND; FRACTURES AB BACKGROUND: Surgical fixation of patella fractures is frequently indicated due to disruption of the quadriceps mechanism. Operative technique varies; however, failure rates can be high. The purpose of this study was to compare the effectiveness of various techniques for the fixation of patella fractures and the etiology of fixation failure. METHODS: We retrospectively reviewed 173 patella fractures treated operatively at two Level I trauma centers. Patients with less than 90 days of follow-up, inadequate radiographic studies, and partial or total excision were excluded. Failure was defined as hardware breakage, nonunion, or displacement of fragments from their initial reduced position. Twelve factors were examined independently for predictive value using both univariate and multivariate analyses. A comparison between groups based on reoperation and hardware removal was also performed. RESULTS: One hundred nine patients met the inclusion criteria, and 13 were found to have failed (12%). Both older patient age (p < 0.02) and use of K-wires, with or without tension-band wires (p < 0.04), were found to be significant predictors of failure. Increasing follow-up time was the only significant predictor of reoperation (p < 0.001) and hardware removal (p < 0.001). CONCLUSIONS: As anticipated, increasing age was found to correlate with higher failure rates. Use of K-wires with or without tension-band wires correlated with higher failure rates, compared with the use of screws, both K-wires and screws, or other fixation. Increasing follow-up time predicted both reoperation and hardware removal, with patients having symptomatic hardware and other complications naturally returning to clinic for evaluation and treatment. (J Trauma. 2012; 72:1051-1055. Copyright (C) 2012 by Lippincott Williams & Wilkins) C1 [Miller, Micah A.; Liu, Wanjun; Smith, Raymond Malcolm; Vrahas, Mark S.] Massachusetts Gen Hosp, Dept Orthopaed Trauma, Boston, MA 02114 USA. [Zurakowski, David] Childrens Hosp, Dept Orthoped, Boston, MA 02115 USA. [Harris, Mitchel B.] Brigham & Womens Hosp, Dept Orthopaed Trauma, Boston, MA 02115 USA. RP Vrahas, MS (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,YAW 3C, Boston, MA 02114 USA. EM mvrahas@partners.org NR 13 TC 7 Z9 8 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 APR PY 2012 VL 72 IS 4 BP 1051 EP 1055 DI 10.1097/TA.0b013e3182405296 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 925TO UT WOS:000302784600055 PM 22491626 ER PT J AU Sheridan, RL AF Sheridan, Robert L. TI An inconvenient epidemic SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Letter ID INJURY; ENVIRONMENT; BICYCLISTS; TRAUMA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sheridan, RL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2012 VL 72 IS 4 BP 1117 EP 1118 DI 10.1097/TA.0b013e31824237e7 PG 3 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 925TO UT WOS:000302784600068 PM 22491639 ER PT J AU Gomes, MM Brawner, BM AF Gomes, Melissa M. Brawner, Bridgette M. TI The mistrust endures: Attitudes and beliefs about participation in biobehavioral research among urban adolescent females and their parents SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Gomes, Melissa M.] Virginia Commonwealth Univ, Richmond, VA USA. [Brawner, Bridgette M.] Univ Penn, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2012 VL 21 IS 4 MA P98 BP 38 EP 38 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 926UE UT WOS:000302856600099 ER PT J AU Kharfan-Dabaja, MA Boeckh, M Wilck, MB Langston, AA Chu, AH Wloch, MK Guterwill, DF Smith, LR Rolland, AP Kenney, RT AF Kharfan-Dabaja, Mohamed A. Boeckh, Michael Wilck, Marissa B. Langston, Amelia A. Chu, Alice H. Wloch, Mary K. Guterwill, Don F. Smith, Larry R. Rolland, Alain P. Kenney, Richard T. TI A novel therapeutic cytomegalovirus DNA vaccine in allogeneic haemopoietic stem-cell transplantation: a randomised, double-blind, placebo-controlled, phase 2 trial SO LANCET INFECTIOUS DISEASES LA English DT Article ID BONE-MARROW-TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; VIRAL-LOAD; RECIPIENTS; DISEASE; PREVENTION; GANCICLOVIR; PROPHYLAXIS; ANTIGENEMIA; STRATEGIES AB Background Cytomegalovirus reactivation occurs within 6 months in 60-70% of cytomegalovirus-seropositive patients after allogeneic haemopoietic stem-cell transplantation (HSCT), mainly due to immunosuppression associated with the procedure. Pre-emptive antiviral therapy reduces incidence of cytomegalovirus disease but can be toxic. To reduce the potential for disease and subsequent need for such antiviral drugs, we aimed to assess safety and efficacy of a cytomegalovirus therapeutic DNA vaccine compared with placebo. Methods In this exploratory double-blind, placebo-controlled, parallel group, phase 2 trial, up to 80 donor recipient pairs and 80 unpaired recipients undergoing allogeneic HSCT were planned for enrolment at 16 transplant centres in the USA. Eligible recipients were cytomegalovirus-seropositive, 18-65 years old, without high-risk primary disease, T-cell depletion, previous vaccination for cytomegalovirus, or autoimmune diseases. We randomly allocated participants in both parallel groups in a 1:1 ratio to receive a cytomegalovirus therapeutic DNA vaccine (TransVax; Vical, San Diego, CA, USA) or placebo before conditioning and at 1, 3, and 6 months after transplantation. The vaccine contains plasmids encoding cytomegalovirus glycoprotein B and phosphoprotein 65 formulated with poloxamer CRL1005 and benzalkonium chloride. Randomisation was done by sequential allocation based on Pocock and Simon's method, and stratified by site, donor recipient HLA matching status, and donor's cytomegalovirus serostatus. The primary outcome was the occurrence rate of clinically significant viraemia resulting in initiation of cytomegalovirus-specific antiviral therapy in the per-protocol assessable population. We assessed rates of adverse events in all participants who received at least one dose of vaccine or placebo. This study is registered with ClinicalTrials.gov, number NCT00285259. Findings We randomly allocated 108 participants (94 HSCT recipients and 14 paired donors) between June 29, 2006, and Dec 11, 2009. Enrolment of the paired arm was halted in February 2008 for logistical reasons. Safety was assessed in all participants; the efficacy population was restricted to 74 unpaired recipients. Groups were balanced for demographic and clinical variables. 19 (48%) of 40 vaccine recipients required cytomegalovirus-specific antiviral therapy, compared with 21 (62%) of 34 controls (p=0.145). However, during follow-up vaccine significantly reduced the occurrence and recurrence of cytomegalovirus viraemia and improved the time-to-event for viraemia episodes compared with placebo. The vaccine was well-tolerated; only one participant discontinued after an allergic reaction. Incidence of common adverse events after HSCT (eg, graft-versus-host disease or secondary infections) did not differ between groups. Interpretation We show proof of concept for an immunotherapeutic cytomegalovirus vaccine (TransVax) for clinically significant viraemia in the HSCT setting. The reported safety and efficacy outcomes support further development in a phase 3 trial, notwithstanding a lack of significant reduction in the use of cytomegalovirus-specific antiviral therapy compared with placebo in this phase 2 trial. Funding Vical and US National Institute of Allergy and Infectious Diseases. C1 [Guterwill, Don F.; Kenney, Richard T.] Vical, Dept Clin Dev, San Diego, CA 92121 USA. [Wloch, Mary K.; Smith, Larry R.] Vical, Dept Vaccinol, San Diego, CA 92121 USA. [Rolland, Alain P.] Vical, Prod Dev Dept, San Diego, CA 92121 USA. [Kharfan-Dabaja, Mohamed A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL 33612 USA. [Kharfan-Dabaja, Mohamed A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Oncol Sci, Tampa, FL 33612 USA. [Kharfan-Dabaja, Mohamed A.] Amer Univ Beirut, Med Ctr, Div Hematol Oncol & Bone Marrow Transplantat, Beirut, Lebanon. [Boeckh, Michael] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Wilck, Marissa B.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wilck, Marissa B.] Hosp Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA. [Langston, Amelia A.] Emory Univ, Sch Med, Bone Marrow & Stem Cell Transplant Ctr, Winship Canc Inst, Atlanta, GA USA. RP Kenney, RT (reprint author), Vical, Dept Clin Dev, 10390 Pacific Ctr Court, San Diego, CA 92121 USA. EM richard.kenney@vical.com FU Genzyme; Bristol-Myers Squibb; Boehringer Ingelheim; Chimerix; Genentech/Roche; Vical; Novartis; Astellas; Merck; GlaxoSmithKline; Theraclone; Pfizer; Wyeth; National Institute of Allergy and Infectious Diseases [5R44AI58386-04]; US National Institute of Allergy and Infectious Diseases FX MAK-D has been a member of advisory boards for Vital and has received speaker's fees from Genzyme and Bristol-Myers Squibb. MB has been a consultant or received research funding from Boehringer Ingelheim, Chimerix, Genentech/Roche, Vical, Novartis, Astellas, Merck, GlaxoSmithKline, and Theraclone. MBW has received research funding from Vical and GlaxoSmithKline. AAL has been a member of advisory boards for Merck, Schering-Plough, and Genzyme and received research funding from Vical, Pfizer, Chimerix, and Wyeth. AHC, MKW, DFG, LRS, APR, and RTK are employees of and own stock in Vical.; The study was financed in part by the National Institute of Allergy and Infectious Diseases (grant 5R44AI58386-04) and was otherwise funded by Vical. We thank the recipients of haemopoietic stem-cell transplants and the healthy donors who volunteered for the study; the data and safety monitoring board members D Winston (UCLA Medical Center, CA, USA), G Schiller (UCLA School of Medicine, CA, USA), J Wingard (University of Florida College of Medicine, FL, USA), and C Davis (CSD Biostatistics, CA, USA) for their safety oversight; the former Vical employees D Kaslow (Merck Research Laboratories, PA, USA) and T Evans (Aeras, MD, USA) for their contributions to the design and conduct of the trial; and Schulte (Vical, CA, USA) for his expert data analysis. We thank all of the staff at each institution for their skilful care of participants and careful recording of results, along with the following investigators for their participation in this trial: C Anasetti (H Lee Moffitt Cancer Center, FL, USA), R Betts (University of Rochester Medical Center, NY, USA), P Chandrasekar (Barbara Ann Karmanos Cancer Institute, MI, USA), A Freifeld (Nebraska Medical Center, NE, USA), R Herzig (James Graham Brown Cancer Center, KY, USA), F Marty (Brigham and Women's Hospital, MA, USA), P McCarthy (Roswell Park Cancer Institute, NY, USA),) McGuirk (University of Kansas Cancer Center, KS, USA), R Nakamura (City of Hope Medical Center, CA, USA), G Papanicolaou (Memorial Sloan-Kettering Cancer Center, NY, USA), S Pergam (Fred Hutchinson Cancer Research Center, WA, USA), K Rados (Winship Cancer Institute, GA, USA), S Rowley (Hackensack University Medical Center, NJ, USA), E Vance (Baylor University Medical Center, TX, USA), and A Yeager (Arizona Cancer Center, AZ, USA); and the staff at the Montefiore Medical Center (NY, USA).; Funding Vical and US National Institute of Allergy and Infectious Diseases. NR 34 TC 101 Z9 107 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD APR PY 2012 VL 12 IS 4 BP 290 EP 299 DI 10.1016/S1473-3099(11)70344-9 PG 10 WC Infectious Diseases SC Infectious Diseases GA 922AC UT WOS:000302518200023 PM 22237175 ER PT J AU Richardson, PG Delforge, M Beksac, M Wen, P Jongen, JL Sezer, O Terpos, E Munshi, N Palumbo, A Rajkumar, SV Harousseau, JL Moreau, P Avet-Loiseau, H Lee, JH Cavo, M Merlini, G Voorhees, P Chng, WJ Mazumder, A Usmani, S Einsele, H Comenzo, R Orlowski, R Vesole, D Lahuerta, JJ Niesvizky, R Siegel, D Mateos, MV Dimopoulos, M Lonial, S Jagannath, S Blade, J San Miguel, J Morgan, G Anderson, KC Durie, BGM Sonneveld, P AF Richardson, P. G. Delforge, M. Beksac, M. Wen, P. Jongen, J. L. Sezer, O. Terpos, E. Munshi, N. Palumbo, A. Rajkumar, S. V. Harousseau, J. L. Moreau, P. Avet-Loiseau, H. Lee, J. H. Cavo, M. Merlini, G. Voorhees, P. Chng, W. J. Mazumder, A. Usmani, S. Einsele, H. Comenzo, R. Orlowski, R. Vesole, D. Lahuerta, J. J. Niesvizky, R. Siegel, D. Mateos, M-V Dimopoulos, M. Lonial, S. Jagannath, S. Blade, J. San Miguel, J. Morgan, G. Anderson, K. C. Durie, B. G. M. Sonneveld, P. CA Int Myeloma Working Grp TI Management of treatment-emergent peripheral neuropathy in multiple myeloma SO LEUKEMIA LA English DT Review DE bortezomib; immunomodulatory drug; multiple myeloma; peripheral neuropathy; proteasome inhibitor; thalidomide ID THALIDOMIDE PLUS DEXAMETHASONE; STEM-CELL TRANSPLANTATION; RANDOMIZED CONTROLLED-TRIAL; PEGYLATED LIPOSOMAL DOXORUBICIN; BORTEZOMIB-MELPHALAN-PREDNISONE; PROTEASOME INHIBITOR NPI-0052; COOPERATIVE-ONCOLOGY-GROUP; NEWLY-DIAGNOSED MYELOMA; PHASE-1 CLINICAL-TRIAL; LOW-DOSE DEXAMETHASONE AB Peripheral neuropathy (PN) is one of the most important complications of multiple myeloma (MM) treatment. PN can be caused by MM itself, either by the effects of the monoclonal protein or in the form of radiculopathy from direct compression, and particularly by certain therapies, including bortezomib, thalidomide, vinca alkaloids and cisplatin. Clinical evaluation has shown that up to 20% of MM patients have PN at diagnosis and as many as 75% may experience treatment-emergent PN during therapy. The incidence, symptoms, reversibility, predisposing factors and etiology of treatment-emergent PN vary among MM therapies, with PN incidence also affected by the dose, schedule and combinations of potentially neurotoxic agents. Effective management of treatment-emergent PN is critical to minimize the incidence and severity of this complication, while maintaining therapeutic efficacy. Herein, the state of knowledge regarding treatment-emergent PN in MM patients and current management practices are outlined, and recommendations regarding optimal strategies for PN management during MM treatment are provided. These strategies include early and regular monitoring with neurological evaluation, with dose modification and treatment discontinuation as indicated. Areas requiring further research include the development of MM-specific, patient-focused assessment tools, pharmacogenomic analysis of patient DNA, and trials to assess the efficacy of pharmacological interventions. Leukemia (2012) 26, 595-608; doi:10.1038/leu.2011.346; published online 23 December 2011 C1 [Richardson, P. G.; Wen, P.; Munshi, N.; Anderson, K. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Delforge, M.] Katholieke Univ Leuven Hosp, Louvain, Belgium. [Beksac, M.] Ankara Univ, Ibn i Sina Hosp, TR-06100 Ankara, Turkey. [Jongen, J. L.; Sonneveld, P.] Erasmus MC, Rotterdam, Netherlands. [Jongen, J. L.; Sonneveld, P.] Erasmus Univ, Rotterdam, Netherlands. [Sezer, O.] Univ Med Ctr, Hamburg, Germany. [Terpos, E.; Dimopoulos, M.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Palumbo, A.] Univ Turin, Turin, Italy. [Rajkumar, S. V.] Mayo Clin, Rochester, MN USA. [Harousseau, J. L.; Moreau, P.; Avet-Loiseau, H.] Intergrp Francophone Myelome, Nantes, France. [Lee, J. H.] Gachon Univ, GIL Hosp, Inchon, South Korea. [Cavo, M.] Univ Bologna, Seragnoli Inst Hematol, Sch Med, Bologna, Italy. [Merlini, G.] Univ Pavia, Amyloidosis Res & Treatment Ctr, I-27100 Pavia, Italy. [Voorhees, P.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Chng, W. J.] Natl Univ Hlth Syst, Dept Haematol & Oncol, Singapore, Singapore. [Mazumder, A.] NYU, Sch Med, New York, NY USA. [Usmani, S.] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Einsele, H.] Univ Wurzburg, Wurzburg, Germany. [Comenzo, R.] Tufts Med Ctr, Boston, MA USA. [Orlowski, R.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. [Vesole, D.; Siegel, D.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Lahuerta, J. J.] Hosp Univ 12 Octubre, PETHEMA, Madrid, Spain. [Niesvizky, R.] Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Ctr Excellence Lymphoma & Myeloma, New York, NY 10021 USA. [Mateos, M-V; San Miguel, J.] Hosp Univ Salamanca, CIC, IBMCC, USAL CSIC, Salamanca, Spain. [Lonial, S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Jagannath, S.] Mt Sinai Hosp, New York, NY 10029 USA. [Blade, J.] Univ Barcelona, Inst Hematol & Oncol, Inst Invest Biomed August Pi I Sunyer, Hosp Clin, Barcelona, Spain. [Morgan, G.] Royal Marsden Hosp, London SW3 6JJ, England. [Durie, B. G. M.] Cedars Sinai Comprehens Canc Ctr, Los Angeles, CA USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 1B02, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu RI Usmani, Saad/H-2705-2012; Beksac, Meral/D-6411-2013; richard, chrystelle/K-8595-2015; OI SAN MIGUEL, JESUS/0000-0002-9183-4857; CAVO, MICHELE/0000-0003-4514-3227; Morgan, Glyn/0000-0002-4060-9772; Rajkumar, S. Vincent/0000-0002-5862-1833; Merlini, Giampaolo/0000-0001-7680-3254 FU Rick Corman Multiple Myeloma Research Fund; Millennium Pharmaceuticals, Inc.; Janssen; Novartis; Celgene; Millennium; Roche; Johnson and Johnson; Jansen Cilag FX Administrative assistance was provided in part by Katie Redman and Jane Saunders during the development of this publication, who were supported in part by the Rick Corman Multiple Myeloma Research Fund and by an unrestricted grant from Millennium Pharmaceuticals, Inc., respectively. All authors were fully responsible for the writing, content and final approval of the manuscript.; Paul G Richardson is an advisor for Millennium Pharmaceuticals, Celgene Corporation, Novartis Pharmaceuticals, Johnson & Johnson and Bristol Myers Squibb. Michel Delforge is a consultant for Janssen and Celgene. He has also received speaker's honoraria from these companies. Joost L Jongen has received personal compensation from Pfizer. Orhan Sezer has received honoraria from Amgen, Celgene, Janssen and Novartis. Dr Sezer has also received research funding from Janssen and Novartis. Antonio Palumbo has received honoraria from Celgene, Janssen-Cilag, Merck and Amgen, and is on an advisory committee for Celgene and Janssen-Cilag. Shaji Kumar has received research funding from Celgene, Millennium and Novartis. He is a consultant for Merck. Philippe Moreau has received honoraria from Celgene, Janssen and Millennium. Michele Cavo has received honoraria from Janssen, Celgene and Millennium. Peter Voorhees is on speaker bureaus for Celgene and Millennium. Wee Joo Chng has received honoraria from Janssen, Celgene and Novartis, and has received research funding from Janssen and Roche. Amitabha Mazumder is a consultant for Celgene and Millennium, and has also received honoraria from these companies. Hermann Einsele is on the speaker bureaus for Celgene, Novartis and Janssen-Cilag. Raymond Comenzo is a scientific advisor for Millennium and Onyx, and also a consultant for Neotope and Millennium. He has received research support from Celgene and Millennium. Robert Orlowski has received research funding from Celgene, Millennium and Johnson and Johnson. He is also on advisory boards for Celgene, Millennium, Centocor, Novartis, Cephalon and Onyx, and has received honoraria from these companies. Juan Jose Lahuerta has received honoraria from Celgene and Janssen-Cilag. Ruben Niesvizky is a speaker and consultant for Celgene, Millennium, Onyx and Novartis. He has also received research support from these companies. David Siegel is on speaker bureaus for Celgene and Millennium. Maria-Victoria Mateos has received honoraria from Janssen, Celgene, Millennium and Novartis. Meletios Dimopoulos has received honoraria from Celgene, Ortho-Biotech and Millennium. Sagar Lonial is a consultant for Millennium, Celgene, Novartis, BMS, Merck and Onyx. Joan Blade has received honoraria for lectures from Celgene and Jansen Cilag. He is also on advisory boards for these companies and has received grant support from the same. Jesus San Miguel is on advisory boards for Millennium, Janssen-Cilag and Celgene. Kenneth C Anderson is on advisory boards for Celgene, Millennium, Ony, BMS, Merck and Novartis. He is also the founder of Acetylon. Brian GM Durie is on advisory boards for Millennium, Celgene and Onyx. Pieter Sonneveld is on advisory boards for Janssen, Celgene, Onyx, Novartis and Millennium-Takeda. He has also received research support from Celgene and Janssen. The remaining authors declare no conflict of interest. NR 120 TC 84 Z9 90 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD APR PY 2012 VL 26 IS 4 BP 595 EP 608 DI 10.1038/leu.2011.346 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA 925UX UT WOS:000302788300005 PM 22193964 ER PT J AU Deshpande, A Reddy, MM Schade, GOM Ray, A Chowdary, TK Griffin, JD Sattler, M AF Deshpande, A. Reddy, M. M. Schade, G. O. M. Ray, A. Chowdary, T. K. Griffin, J. D. Sattler, M. TI Kinase domain mutations confer resistance to novel inhibitors targeting JAK2V617F in myeloproliferative neoplasms SO LEUKEMIA LA English DT Article DE myeloid neoplasia; JAK2; drug resistance ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TYROSINE KINASE; JAK2 INHIBITOR; POLYCYTHEMIA-VERA; BCR-ABL; MURINE MODEL; IN-VITRO; CELLS; TRANSFORMATION; MUTAGENESIS AB The transforming JAK2V617F kinase is frequently associated with myeloproliferative neoplasms and thought to be instrumental for the overproduction of myeloid lineage cells. Several small molecule drugs targeting JAK2 are currently in clinical development for treatment in these diseases. We performed a high-throughput in vitro screen to identify point mutations in JAK2V617F that would be predicted to have potential clinical relevance and associated with drug resistance to the JAK2 inhibitor ruxolitinib (INCB018424). Seven libraries of mutagenized JAK2V617F cDNA were screened to specifically identify mutations in the predicted drug-binding region that would confer resistance to ruxolitinib, using a BaF3 cell-based assay. We identified five different non-synonymous point mutations that conferred drug resistance. Cells containing mutations had a 9- to 33-fold higher EC50 for ruxolitinib compared with native JAK2V617F. Our results further indicated that these mutations also conferred cross-resistance to all JAK2 kinase inhibitors tested, including AZD1480, TG101348, lestaurtinib (CEP-701) and CYT-387. Surprisingly, introduction of the 'gatekeeper' mutation (M929I) in JAK2V617F affected only ruxolitinib sensitivity (fourfold increase in EC50). These results suggest that JAK2 inhibitors currently in clinical trials may be prone to resistance as a result of point mutations and caution should be exercised when administering these drugs. Leukemia (2012) 26, 708-715; doi:10.1038/leu.2011.255; published online 16 September 2011 C1 [Deshpande, A.; Reddy, M. M.; Schade, G. O. M.; Ray, A.; Griffin, J. D.; Sattler, M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Deshpande, A.; Reddy, M. M.; Ray, A.; Griffin, J. D.; Sattler, M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Deshpande, A.; Reddy, M. M.; Ray, A.; Griffin, J. D.; Sattler, M.] Harvard Univ, Sch Med, Boston, MA USA. [Chowdary, T. K.] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. RP Sattler, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM martin_sattler@dfci.harvard.edu FU National Institutes of Health [CA134660-04] FX This work was supported in part by National Institutes of Health Grant CA134660-04 (to MS). NR 40 TC 45 Z9 46 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2012 VL 26 IS 4 BP 708 EP 715 DI 10.1038/leu.2011.255 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 925UX UT WOS:000302788300017 PM 21926964 ER PT J AU Gao, X Cassidy, A Schwarzschild, MA Rimm, EB Ascherio, A AF Gao, X. Cassidy, A. Schwarzschild, M. A. Rimm, E. B. Ascherio, A. TI Habitual intake of dietary flavonoids and risk of Parkinson disease SO NEUROLOGY LA English DT Article ID BLOOD-BRAIN-BARRIER; PLASMA URATE; RAT MODEL; POLYPHENOLS; NEURONS; BIOAVAILABILITY; QUESTIONNAIRE; ANTIOXIDANTS; CONSUMPTION; INHIBITION AB Objective: To prospectively examine whether higher intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, and polymers) were associated with a lower risk of developing Parkinson disease (PD). Methods: In the current analysis, we included 49,281 men in the Health Professional Follow-up Study and 80,336 women from the Nurses' Health Study. Five major sources of flavonoid-rich foods (tea, berry fruits, apples, red wine, and orange/orange juice) were also examined. Flavonoid intake was assessed using an updated food composition database and a validated food frequency questionnaire. Results: We identified 805 participants (438 men and 367 women) who developed PD during 20-22 years of follow-up. In men, after adjusting for multiple confounders, participants in the highest quintile of total flavonoids had a 40% lower PD risk than those in the lowest quintile (hazard ratio [HR] = 0.60; 95% confidence interval 0.43, 0.83; p trend = 0.001). No significant relationship was observed in women (p trend = 0.62) or in pooled analyses (p trend = 0.23). In the pooled analyses for the subclasses, intakes of anthocyanins and a rich dietary source, berries, were significantly associated with a lower PD risk (HR comparing 2 extreme intake quintiles were 0.76 for anthocyanins and 0.77 for berries, respectively; p trend < 0.02 for both). Conclusions: Our findings suggest that intake of some flavonoids may reduce PD risk, particularly in men, but a protective effect of other constituents of plant foods cannot be excluded. Neurology (R) 2012;78:1138-1145 C1 [Gao, X.; Rimm, E. B.; Ascherio, A.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Gao, X.; Rimm, E. B.; Ascherio, A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Rimm, E. B.; Ascherio, A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Cassidy, A.] Univ E Anglia, Dept Nutr, Norwich Med Sch, Norwich NR4 7TJ, Norfolk, England. [Schwarzschild, M. A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Gao, X (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 75 Francis St, Boston, MA 02115 USA. EM xiang.gao@channing.harvard.edu FU NIH/NINDS [R01 NS048517, NIH R01 NS061858, NIH K24NS060991]; Unilever and Diabetes UK; US Department of Defense; Michael J. Fox Foundation; Parkinson Disease Foundation; RJG Parkinson's Disease Foundation; American Parkinson Disease Association; American Federation for Aging Research; NIH; National Multiple Sclerosis Society FX Supported by NIH/NINDS grant R01 NS048517, NIH R01 NS061858, and NIH K24NS060991. None of the sponsors participated in the design of this study or in the collection, analysis, or interpretation of the data.; Dr. Gao serves on the Committee on Nutrition, Trauma, and the Brain, Institute of Medicine; has received research support from the NIH/NINDS; and has served as a consultant for Teva Pharmaceutical Industries Ltd. Dr. Cassidy has received research support from Unilever and Diabetes UK. Dr. Schwarzschild has received research support from the NIH/NINDS, the US Department of Defense, the Michael J. Fox Foundation, the Parkinson Disease Foundation, the RJG Parkinson's Disease Foundation, the American Parkinson Disease Association, and the American Federation for Aging Research. Dr Rimm serves on the editorial boards of American Journal of Clinical Nutrition and American Journal of Epidemiology; and receives research support from the NIH. Dr. Ascherio serves on a scientific advisory board for the Michael J. Fox Foundation; serves as Associate Editor for Multiple Sclerosis and Related Disorders and the Journal of Parkinson Disease and on the editorial boards of Neurology (R) and Annals of Neurology; has received speaker honoraria from Merck Serono; and receives research support from the NIH, the US Department of Defense, the Michael J. Fox Foundation, and the National Multiple Sclerosis Society. NR 40 TC 54 Z9 56 U1 3 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 IS 15 BP 1138 EP 1145 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 925WH UT WOS:000302792200009 PM 22491871 ER PT J AU Hooli, BV Mohapatra, G Mattheisen, M Parrado, AR Roehr, JT Shen, Y Gusella, JF Moir, R Saunders, AJ Lange, C Tanzi, RE Bertram, L AF Hooli, B. V. Mohapatra, G. Mattheisen, M. Parrado, A. R. Roehr, J. T. Shen, Y. Gusella, J. F. Moir, R. Saunders, A. J. Lange, C. Tanzi, R. E. Bertram, L. TI Role of common and rare APP DNA sequence variants in Alzheimer disease SO NEUROLOGY LA English DT Article ID CEREBRAL AMYLOID ANGIOPATHY; FAMILY-BASED ASSOCIATION; PRECURSOR PROTEIN GENE; LOCUS DUPLICATION; ONSET; RESOLUTION; PROMOTER; RISK; EXPRESSION; MUTATIONS AB Objectives: More than 30 different rare mutations, including copy number variants (CNVs), in the amyloid precursor protein gene (APP) cause early-onset familial Alzheimer disease (EOFAD), whereas the contribution of common APP variants to disease risk remains controversial. In this study we systematically assessed the role of both rare and common APP DNA variants in Alzheimer disease (AD) families. Methods: Families with EOFAD genetically linked to the APP region were screened for missense mutations and locus duplications of APP. Further, using genome-wide DNA microarray data, we examined the APP locus for CNVs in a total of 797 additional early-and late-onset AD pedigrees. Finally, 423 single nucleotide polymorphisms (SNPs) in the APP locus, including 2 promoter polymorphisms previously associated with AD risk, were tested in up to 4,200 individuals from multiplex AD families. Results: Analyses of 8 21q21-linked families revealed one family carrying a nonsynonymous mutation in exon 17 (Val717Leu) and another family with a partially penetrant 3.5-Mb locus duplication encompassing APP. CNV analysis in the APP locus revealed an additional family carrying a fully penetrant 380-kb duplication, merely spanning APP. Last, contrary to previous reports, association analyses of more than 400 different SNPs in or near APP failed to show significant effects on AD risk. Conclusion: Our study shows that APP mutations and locus duplications are a very rare cause of EOFAD and that the contribution of common APP variants to AD susceptibility is insignificant. Furthermore, duplications of APP may not be fully penetrant, possibly indicating the existence of hitherto unknown protective genetic factors. Neurology (R) 2012;78:1250-1257 C1 [Roehr, J. T.; Bertram, L.] Max Planck Inst Mol Genet, Dept Vertebrate Genom, Neuropsychiat Genet Grp, D-14195 Berlin, Germany. [Hooli, B. V.; Parrado, A. R.; Moir, R.; Tanzi, R. E.] Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA USA. [Mohapatra, G.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Mattheisen, M.; Lange, C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Shen, Y.; Gusella, J. F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Saunders, A. J.] Drexel Univ, Dept Biol, Philadelphia, PA 19104 USA. RP Bertram, L (reprint author), Max Planck Inst Mol Genet, Dept Vertebrate Genom, Neuropsychiat Genet Grp, Ihnestr 73, D-14195 Berlin, Germany. EM bertram@molgen.mpg.de RI Mattheisen, Manuel/B-4949-2012; Bertram, Lars/K-3889-2015 OI Mattheisen, Manuel/0000-0002-8442-493X; Bertram, Lars/0000-0002-0108-124X FU Cure Alzheimer Fund; NIA [5R01-AG23667]; NIMH [5R37-MH60009]; Children's Tumor Foundation; NIH; NINDS; NIGMS; NICHD; Simons Foundation Autism Research Initiative; CHDI Foundation Inc.; Autism Speaks; Huntington's Disease Society of America; Helmsley Foundation; Cure Alzheimer's Fund; NIH/NINDS; NIH/NIMH FX Funded by the Cure Alzheimer Fund (to L.B. and R.E.T.) as part of the "Alzheimer Genome Project (TM)" and by grants from the NIA (5R01-AG23667 to L.B.) and the NIMH (5R37-MH60009 to R.E.T.).; Dr. Hooli, Dr. Mohapatra, Dr. Mattheisen, Dr. Parrado, and J. Roehr report no disclosures. Dr. Shen receives research support from Children's Tumor Foundation. Dr. Gusella serves on a scientific advisory board and as a consultant for Quest Diagnostics, Inc.; serves on editorial advisory boards for DNA and Cell Biology, Neurobiology of Disease, Neurogenetics, Biomed Central Neuroscience, Biomed Central Biology, and Molecular Autism; holds patents re: Methods for altering mRNA splicing and treating familial dysautonomia and other mechanistically related disorders; Methods for detecting mutations associated with familial dysautonomia; Gene for identifying individuals with familial dysautonomia; Vectors for delivering viral and oncogenic inhibitors; Kits for detecting polymorphisms associated with familial dysautonomia; Tumor suppressor merlin and antibodies thereof; Use of genetic markers to diagnose familial dysautonomia; TPR-containing genes; Tumor suppressor gene merlin; Huntingtin DNA, protein and uses thereof; Transport protein gene from the Huntington's disease region; Flexible scheme for admission control of multimedia streams on integrated networks; Use of genetic markers to diagnose familial dysautonomia; DNA encoding a protein-coupled receptor kinase; Test for Huntington's disease; and Isolation and localization of DNA segments; and receives/has received research support from the NIH (NINDS, NIGMS, NICHD), the Simons Foundation Autism Research Initiative, CHDI Foundation Inc., Autism Speaks, and the Huntington's Disease Society of America Coalition for the Cure. Dr. Moir serves as an Assistant Editor for the International Journal of Genetic and Medical Nanotechnology; holds a patent re: A novel method to diagnose and/or treat Alzheimer's disease; and receives research support from the Helmsley Foundation, the NIH, and the Cure Alzheimer's Fund. Dr. Saunders receives research support from the NIH/NINDS and the Cure Alzheimer's Fund. Dr. Lange reports no disclosures. Dr. Tanzi serves as a consultant for and has received funding for travel and speaker honoraria from Pfizer Inc, Eisai Inc., Prana Biotechnology, and Probiodrug AG; serves on the editorial board of Neuron editorial board; and receives research support from the NIH/NIMH and the Cure Alzheimer's Fund. Dr. Bertram serves on editorial advisor boards for Neurogenetics, European Journal of Clinical Investigation, and International Journal of Molecular Epidemiology and Genetics. NR 35 TC 25 Z9 25 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 IS 16 BP 1250 EP 1257 DI 10.1212/WNL.0b013e3182515972 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 927TO UT WOS:000302933200012 PM 22491860 ER PT J AU Lewis, JM Yalla, SV Stanitski, KE Sullivan, MP AF Lewis, Jane M. Yalla, Subbarao V. Stanitski, Kate E. Sullivan, Maryrose P. TI Spectrum of urodynamic abnormalities and renal function changes in adult men with non-neurogenic urinary retention SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE impaired contractility; renal function; urinary retention; urodynamics ID NONOBSTRUCTIVE VOIDING DYSFUNCTION; NATURAL-HISTORY; RISK-FACTORS; FOLLOW-UP; DETRUSOR CONTRACTILITY; TRACT DYSFUNCTION; UNDERACTIVITY; RESECTION; SYMPTOMS AB Introduction The purpose of this study was to identify abnormalities in bladder and renal function in men with urinary retention presumed to be due to BPH. Methods: In this retrospective analysis, urodynamic studies ( UDS) and renal function were evaluated. Bladder contractility and compliance and the severity of bladder outlet obstruction ( BOO) were determined from urodynamics. Renal function ( BUN, creatine, eGFR) was assessed prior to retention, at the time of presentation and after urodynamic evaluation. Results: Of 87 patients with evaluable UDS, 48% did not demonstrate detrusor activity during testing while 52% showed some detrusor contractile activity. Of these, 23% did not have BOO. Diminished bladder compliance was detected in 56%. In the entire cohort, BUN, serum creatinine, and eGFR were significantly changed during retention but were restored after catheterization. In older patients (> 75 years), BUN and creatinine during retention were significantly higher, and eGFR was significantly lower compared to younger patients, but renal function after catheterization was not different between age groups. No significant correlations were found between renal function measurements and bladder compliance or age. Conclusion: The urodynamic spectrum in men with urinary retention ranged from detrusor acontractility to varied degrees of contractility associated with outlet obstruction spanning from equivocal to severe. Moreover, prompt relief of retention restores renal function to baseline levels, regardless of age. This study indicates that prostatic obstruction may not be the only cause of urinary retention in adult men presumed to have BPH and illustrates the value of urodynamic assessment prior to potentially failure-prone surgical interventions. Neurourol. Urodynam. 31: 544-548, 2012. Published 2012. This article is a U. S. Government work and is in the public domain in the USA. C1 [Yalla, Subbarao V.] Harvard Univ, Sch Med, Dept Surg, Div Urol,VA Boston Healthcare Syst, Boston, MA 02132 USA. VA Maine Healthcare Syst, Togus, ME USA. RP Yalla, SV (reprint author), Harvard Univ, Sch Med, Dept Surg, Div Urol,VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. EM subbarao.yalla@va.gov FU Department of Veterans Affairs, Medical Research Service, Washington, D.C. FX Grant sponsor: Department of Veterans Affairs, Medical Research Service, Washington, D.C. NR 15 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD APR PY 2012 VL 31 IS 4 BP 544 EP 548 DI 10.1002/nau.22196 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 928PF UT WOS:000302994500025 PM 22298049 ER PT J AU Lowalekar, SK Cristofaro, V Radisavljevic, ZM Yalla, SV Sullivan, MP AF Lowalekar, Samar K. Cristofaro, Vivian Radisavljevic, Ziv M. Yalla, Subbarao V. Sullivan, Maryrose P. TI Loss of bladder smooth muscle caveolae in the aging bladder SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE aging; bladder smooth muscle; caveolae; caveolin ID URINARY-BLADDER; KNOCKOUT MICE; EXPRESSION; CELLS; DETRUSOR; PROTEINS; RAT; CONTRACTILITY; DISRUPTION; CAVIN AB Aims Caveolae are specialized regions of the cell membrane that modulate signal transduction and alterations in these structures affect bladder smooth muscle (BSM) contraction. Since bladder dysfunctions are common in the elderly, we evaluated the effect of aging on the morphology of caveolae and caveolin protein expression in BSM. C1 [Lowalekar, Samar K.; Cristofaro, Vivian; Radisavljevic, Ziv M.; Yalla, Subbarao V.; Sullivan, Maryrose P.] Harvard Univ, VA Boston Healthcare Syst, Sch Med, Brigham & Womens Hosp,Div Urol,Dept Surg, Boston, MA 02132 USA. RP Sullivan, MP (reprint author), Harvard Univ, VA Boston Healthcare Syst, Sch Med, Brigham & Womens Hosp,Div Urol,Dept Surg, 1400 VFW Pkwy, Boston, MA 02132 USA. EM msullivan@rics.bwh.harvard.edu FU Medical Research Service, Department of Veteran's Affairs, Washington, D.C. FX Grant sponsor: Medical Research Service, Department of Veteran's Affairs, Washington, D.C. NR 32 TC 12 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD APR PY 2012 VL 31 IS 4 BP 586 EP 592 DI 10.1002/nau.21217 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 928PF UT WOS:000302994500033 PM 22374691 ER PT J AU Doheny, L Morey, JA Ringer, SA Lahav, A AF Doheny, Laura Morey, Jo Ann Ringer, Steven Alan Lahav, Amir TI Reduced frequency of apnea and bradycardia episodes caused by exposure to biological maternal sounds SO PEDIATRICS INTERNATIONAL LA English DT Article DE apnea; maternal sounds; neonatal care; preterm ID PRETERM INFANTS; NOISE; NICU; RESPONSES C1 [Doheny, Laura; Morey, Jo Ann; Ringer, Steven Alan; Lahav, Amir] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Newborn Med, Boston, MA 02115 USA. [Lahav, Amir] Harvard Univ, Sch Med, MassGen Hosp Children, Dept Pediat, Boston, MA 02115 USA. RP Lahav, A (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Newborn Med, 75 Francis St, Boston, MA 02115 USA. EM amir@hms.harvard.edu FU Christopher Joseph Concha Foundation; Hailey's Hope Foundation; Capita Foundation; Heather on Earth Foundation; Learning Disabilities Foundation of America; John Alden Trust FX This work was supported in part by the Christopher Joseph Concha Foundation, Hailey's Hope Foundation, Capita Foundation, Heather on Earth Foundation, Learning Disabilities Foundation of America and John Alden Trust. We thank Phil Levine for technical support and Brian Arnold and John Panagiotidis for audio recording of maternal sound. NR 12 TC 0 Z9 0 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1328-8067 J9 PEDIATR INT JI Pediatr. Int. PD APR PY 2012 VL 54 IS 2 BP e1 EP e3 DI 10.1111/j.1442-200X.2012.03575.x PG 3 WC Pediatrics SC Pediatrics GA 927UJ UT WOS:000302935400001 PM 22507169 ER PT J AU O'Brien, JA Daudi, A Finch, P Butt, VS Whitelegge, JP Souda, P Ausubel, FM Bolwell, GP AF O'Brien, Jose A. Daudi, Arsalan Finch, Paul Butt, Vernon S. Whitelegge, Julian P. Souda, Puneet Ausubel, Frederick M. Bolwell, G. Paul TI A Peroxidase-Dependent Apoplastic Oxidative Burst in Cultured Arabidopsis Cells Functions in MAMP-Elicited Defense SO PLANT PHYSIOLOGY LA English DT Article ID POLYGALACTURONASE-INHIBITING PROTEIN; PURPLE ACID-PHOSPHATASE; INNATE IMMUNE-RESPONSE; PHASEOLUS-VULGARIS L.; HYDROGEN-PEROXIDE; PROTEOMIC ANALYSIS; BOTRYTIS-CINEREA; CROSS-LINKING; WALL PROTEINS; PATHOGEN INFECTION AB Perception by plants of so-called microbe-associated molecular patterns (MAMPs) such as bacterial flagellin, referred to as pattern-triggered immunity, triggers a rapid transient accumulation of reactive oxygen species (ROS). We previously identified two cell wall peroxidases, PRX33 and PRX34, involved in apoplastic hydrogen peroxide (H2O2) production in Arabidopsis (Arabidopsis thaliana). Here, we describe the generation of Arabidopsis tissue culture lines in which the expression of PRX33 and PRX34 is knocked down by antisense expression of a heterologous French bean (Phaseolus vulgaris) peroxidase cDNA construct. Using these tissue culture lines and two inhibitors of ROS generation, azide and diphenylene iodonium, we found that perxoxidases generate about half of the H2O2 that accumulated in response to MAMP treatment and that NADPH oxidases and other sources such as mitochondria account for the remainder of the ROS. Knockdown of PRX33/PRX34 resulted in decreased expression of several MAMP-elicited genes, including MYB51, CYP79B2, and CYP81F2. Similarly, proteomic analysis showed that knockdown of PRX33/PRX34 led to the depletion of various MAMP-elicited defense-related proteins, including the two cysteine-rich peptides PDF2.2 and PDF2.3. Knockdown of PRX33/PRX34 also led to changes in the cell wall proteome, including increases in enzymes involved in cell wall remodeling, which may reflect enhanced cell wall expansion as a consequence of reduced H2O2-mediated cell wall cross-linking. Comparative metabolite profiling of a CaCl2 extract of the PRX33/PRX34 knockdown lines showed significant changes in amino acids, aldehydes, and keto acids but not fatty acids and sugars. Overall, these data suggest that PRX33/PRX34-generated ROS production is involved in the orchestration of pattern-triggered immunity in tissue culture cells. C1 [O'Brien, Jose A.; Daudi, Arsalan; Finch, Paul; Butt, Vernon S.; Bolwell, G. Paul] Univ London, Sch Biol Sci, Egham TW20 0EX, Surrey, England. [Whitelegge, Julian P.; Souda, Puneet] Univ Calif Los Angeles, David Geffen Sch Med, Pasarow Mass Spectrometry Lab, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Bolwell, GP (reprint author), Univ London, Sch Biol Sci, Egham TW20 0EX, Surrey, England. EM ausubel@molbio.mgh.harvard.edu; p.bolwell@rhul.ac.uk FU Biotechnology and Biological Sciences Research Council [BB/E021166/1]; Chilean National Scholarship Program for Graduate Studies; National Institutes of Health [R37 GM48707]; National Science Foundation [MCB-0519898] FX This work was supported by the Biotechnology and Biological Sciences Research Council (grant no. BB/E021166/1 to G.P.B.), by the Chilean National Scholarship Program for Graduate Studies (to J.A.O.), by the National Institutes of Health (grant no. R37 GM48707 to F.M.A.), and by the National Science Foundation (grant no. MCB-0519898 to F.M.A.). NR 70 TC 67 Z9 71 U1 1 U2 45 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD APR PY 2012 VL 158 IS 4 BP 2013 EP 2027 DI 10.1104/pp.111.190140 PG 15 WC Plant Sciences SC Plant Sciences GA 928RQ UT WOS:000303001400042 PM 22319074 ER PT J AU Karel, MJ Holley, CK Whitbourne, SK Segal, DL Tazeau, YN Emery, EE Molinari, V Yang, J Zweig, RA AF Karel, Michele J. Holley, Caitlin K. Whitbourne, Susan Krauss Segal, Daniel L. Tazeau, Yvette N. Emery, Erin E. Molinari, Victor Yang, Janet Zweig, Richard A. TI Preliminary Validation of a Tool To Assess Competencies for Professional Geropsychology Practice SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article DE geropsychology; competencies; continuing professional development ID SKILL COMPETENCES; PSYCHOLOGY; MODEL; KNOWLEDGE; FUTURE AB Psychologists will need to develop increased competencies for Geropsychology practice to serve the behavioral and mental health care needs of an aging population. The Council of Professional Geropsychology Training Programs (CoPGTP) developed the Pikes Peak Geropsychology Knowledge and Skill Assessment Tool to help psychologists and geropsychology trainees evaluate professional geropsychology competencies and related training needs. In this study, geropsychologists and geropsychology trainees were asked to complete the competency tool to evaluate its psychometric properties and to assess users' perceptions of its utility. The sample (N = 109) consisted of 75 professionals and 34 graduate students who completed the tool through an online survey. Results provide preliminary support for use of the tool as a self-evaluation instrument for psychologists and graduate students who want to identify areas of continuing professional development in geropsychology. As expected, psychologists rated themselves as having more advanced geropsychology competencies than did graduate students, F(5, 96) = 27.18, p < .01. For psychologists, overall self-rated competency was predicted by extent of formal clinical training and proportion of one's practice devoted to older adults, but not by years in practice or informal training. For graduate trainees, overall self-rated competency was predicted by formal clinical training experiences but not by coursework or clinical hours. Participants provided generally positive feedback about the tool's utility. Results suggest that formal clinical training is a critical contributor to self-perceived geropsychology competence. Innovative models of continuing professional development will be important to help psychologists develop competence for professional geropsychology practice. C1 [Karel, Michele J.] VA Boston Healthcare Syst, Boston, MA USA. [Karel, Michele J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Holley, Caitlin K.] Albany Stratton VA Med Ctr, Albany, NY USA. [Whitbourne, Susan Krauss] Univ Massachusetts, Amherst, MA 01003 USA. [Segal, Daniel L.] Univ Colorado, Colorado Springs, CO 80907 USA. [Tazeau, Yvette N.] Ynt Consulting, San Jose, CA USA. [Emery, Erin E.] Rush Univ, Med Ctr, Chicago, IL USA. [Molinari, Victor] Univ S Florida, Sch Aging Studies, Tampa, FL 33620 USA. [Yang, Janet] Ctr Aging Resources, Pasadena, CA USA. [Zweig, Richard A.] Yeshiva Univ, Older Adult Program, Ferkauf Grad Sch Psychol, New York, NY 10033 USA. RP Karel, MJ (reprint author), Brockton VA Med Ctr 3 5C, 940 Belmont St, Brockton, MA 02301 USA. EM Michele.Karel@va.gov NR 20 TC 11 Z9 11 U1 0 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD APR PY 2012 VL 43 IS 2 BP 110 EP 117 DI 10.1037/a0025788 PG 8 WC Psychology, Multidisciplinary SC Psychology GA 928FO UT WOS:000302968800006 ER PT J AU Li, MW Baridon, B Trainor, A Djan, E Koehne, A Griffey, SM Biggers, JD Toner, M Lloyd, KCK AF Li, Ming-Wen Baridon, Brian Trainor, Amanda Djan, Esi Koehne, Amanda Griffey, Stephen M. Biggers, John D. Toner, Mehmet Lloyd, K. C. Kent TI Mutant mice derived by ICSI of evaporatively dried spermatozoa exhibit expected phenotype SO REPRODUCTION LA English DT Article ID APOLIPOPROTEIN-E; ATHEROSCLEROSIS; MOUSE; DNA; HYPERCHOLESTEROLEMIA; CRYOPRESERVATION; LESIONS; DAMAGE; CELLS AB Apolipoprotein E (Apoe)-deficient knockout mice were used to test the hypothesis that mutant mice preserved as evaporatively dried (ED) spermatozoa, stored at -80 degrees C for 6 months, and then recovered by ICSI will exhibit the same phenotype as before preservation. The birth rate of mice recovered by ICSI of evaporatively dried spermatozoa was lower than that of fresh spermatozoa (17.5 vs 38.0%). Progeny of mice preserved using evaporatively dried spermatozoa were reproductively sound. From these, the second generation of mice produced by natural mating showed lesions typical of APOE deficiency, including severe hypercholesterolemia, hypertriglyceridemia, markedly increased plasma low-density lipoprotein level, and extensive and severe atherosclerotic lesions in the aorta. We conclude that the expected phenotype caused by an induced genetic mutation can be faithfully recapitulated and sustained in subsequent generations of mice preserved and stored as ED spermatozoa and recovered using ICSI. Because it is simpler, faster, and cheaper than conventional (cryopreservation) and nonconventional (freeze-drying) preservation procedures, evaporative drying is a viable, cost-effective, and efficient method for preserving and storing valuable mutant mouse strains. Reproduction (2012) 143 449-453 C1 [Li, Ming-Wen; Baridon, Brian; Trainor, Amanda; Djan, Esi; Lloyd, K. C. Kent] Univ Calif Davis, Sch Vet Med, Mouse Biol Program, Davis, CA 95616 USA. [Koehne, Amanda; Griffey, Stephen M.] Univ Calif Davis, Sch Vet Med, Comparat Pathol Lab, Davis, CA 95616 USA. [Biggers, John D.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02421 USA. [Toner, Mehmet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02115 USA. [Toner, Mehmet] Shriners Hosp Children, Boston, MA 02115 USA. RP Lloyd, KCK (reprint author), Univ Calif Davis, Sch Vet Med, Mouse Biol Program, 2795 2nd St,Suite 400, Davis, CA 95616 USA. EM kclloyd@ucdavis.edu FU NCI NIH HHS [P30 CA093373]; NCRR NIH HHS [R24 RR018934, U42 RR014905]; NIH HHS [U42 OD012210] NR 16 TC 1 Z9 1 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1470-1626 J9 REPRODUCTION JI Reproduction PD APR PY 2012 VL 143 IS 4 BP 449 EP 453 DI 10.1530/REP-12-0005 PG 5 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 928CD UT WOS:000302956600004 PM 22274886 ER PT J AU Smith, RN Colvin, RB AF Smith, R. Neal Colvin, Robert B. TI Chronic alloantibody mediated rejection SO SEMINARS IN IMMUNOLOGY LA English DT Review DE Chronic rejection; Human allografts; Alloantibodies; Complement; Antibody mediated rejections ID RENAL-ALLOGRAFT REJECTION; DONOR-SPECIFIC ANTIBODIES; LEUKOCYTE ANTIGEN ANTIBODIES; ANTI-CD20 MONOCLONAL-ANTIBODY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; KIDNEY-TRANSPLANT PATIENTS; ACUTE HUMORAL REJECTION; CELL-DEFICIENT MICE; B-CELL; HLA ANTIBODIES AB Alloantibodies clearly cause acute antibody mediated rejection, and all available evidence supports their pathogenic etiology in the development of chronic alloantibody mediated rejection (CAMR). But the slow evolution of this disease, the on-going immunosuppression, the variations in titer of alloantibodies, and variation in antigenic targets all complicate identifying which dynamic factors are most important clinically and pathologically. This review highlights the pathological factors related to the diagnosis of CAMR, the time course and natural history of this disease. What is known about CAMR pathogenesis is discussed including alloantibodies, the role of complement, gene activation, and Fc effector cell function. Therapy, which is problematic for this disease, is also discussed, including on-going and potential therapies and their limitations. (C) 2011 Published by Elsevier Ltd. C1 [Smith, R. Neal] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Smith, RN (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM rnsmith@partners.org; colvin@helix.mgh.harvard.edu FU NIAID NIH HHS [U19 AI102405] NR 125 TC 25 Z9 26 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD APR PY 2012 VL 24 IS 2 BP 115 EP 121 DI 10.1016/j.smim.2011.09.002 PG 7 WC Immunology SC Immunology GA 928HA UT WOS:000302972600007 PM 22051115 ER PT J AU Luke, JJ Keohan, ML AF Luke, Jason J. Keohan, Mary Louise TI Advances in the Systemic Treatment of Cutaneous Sarcomas SO SEMINARS IN ONCOLOGY LA English DT Review ID PEGYLATED-LIPOSOMAL DOXORUBICIN; SOFT-TISSUE SARCOMAS; RENAL-TRANSPLANT RECIPIENTS; AIDS MALIGNANCY CONSORTIUM; MATRIX-METALLOPROTEINASE INHIBITOR; PROTEIN-COUPLED RECEPTOR; RANDOMIZED PHASE-II; KAPOSIS-SARCOMA; DERMATOFIBROSARCOMA PROTUBERANS; IMATINIB MESYLATE C1 [Keohan, Mary Louise] Mem Sloan Kettering Canc Ctr, Dept Med, Melanoma Sarcoma Sect, New York, NY 10065 USA. [Luke, Jason J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Keohan, ML (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Melanoma Sarcoma Sect, 300 E 66th St, New York, NY 10065 USA. EM KeohanM@mskcc.org FU NCI NIH HHS [T32 CA009207] NR 129 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2012 VL 39 IS 2 BP 173 EP 183 DI 10.1053/j.seminoncol.2012.01.004 PG 11 WC Oncology SC Oncology GA 926KF UT WOS:000302829200008 PM 22484189 ER PT J AU Eldaief, MC Deckersbach, T Carlson, LE Beucke, JC Dougherty, DD AF Eldaief, Mark C. Deckersbach, Thilo Carlson, Lindsay E. Beucke, Jan C. Dougherty, Darin D. TI Emotional and cognitive stimuli differentially engage the default network during inductive reasoning SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE default network; emotional reasoning; certainty; uncertainty; fMRI ID MEDIAL PREFRONTAL CORTEX; MODE NETWORK; EXECUTIVE FUNCTIONS; FRONTAL-CORTEX; BRAIN-FUNCTION; NEURAL BASES; SELF; FMRI; DEPRESSION; TASK AB The brain's default network (DN) is comprised of several cortical regions demonstrating robust intrinsic connectivity at rest. The authors sought to examine the differential effects of emotional reasoning and reasoning under certainty upon the DN through the employment of an event-related fMRI design in healthy participants. Participants were presented with syllogistic arguments which were organized into a 2 x 2 factorial design in which the first factor was emotional salience and the second factor was certainty/uncertainty. We demonstrate that regions of the DN were activated both during reasoning that is emotionally salient and during reasoning which is more certain, suggesting that these processes are neurally instantiated on a network level. In addition, we present evidence that emotional reasoning preferentially activates the dorsomedial (dMPFC) subsystem of the DN, whereas reasoning in the context of certainty activates areas specific to the DN's medial temporal (MTL) subsystem. We postulate that emotional reasoning mobilizes the dMPFC subsystem of the DN because this type of reasoning relies upon the recruitment of introspective and self-relevant data such as personal bias and temperament. In contrast, activation of the MTL subsystem during certainty argues that this form of reasoning involves the recruitment of mnemonic and semantic associations to derive conclusions. C1 [Eldaief, Mark C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Gen Hosp, Dept Neurol,Div Cognit Neurol,Sch Med, Boston, MA 02215 USA. [Deckersbach, Thilo; Carlson, Lindsay E.; Beucke, Jan C.; Dougherty, Darin D.] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Sch Med, Dept Psychiat,Div Psychiat Neurosci & Neurotherap, Boston, MA 02215 USA. RP Eldaief, MC (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Gen Hosp, Dept Neurol,Div Cognit Neurol,Sch Med, 330 Brookline Ave,KS 230, Boston, MA 02215 USA. EM meldaief@bidmc.harvard.edu FU Athinoula A. Martinos Center for Biomedical Imaging of the Massachusetts General Hospital via 'Center for Functional Neuroimaging Technologies' [P41RR14075]; Mind, Brain and Behavior Interfaculty Initiative at Harvard University FX M.C.E. formulated the hypothesis, assisted with the study design, collected the data, performed the analyses and wrote the article. L. E. C. assisted with data collection and data analyses. J.C.B. assisted with data collection and analyses for the article revisions. T. D. and D. D. D. assisted with hypothesis formulation and study design, and oversaw all aspects of data collection and analysis. All authors reviewed and commented on the article. This work was supported by a pilot grant from the Athinoula A. Martinos Center for Biomedical Imaging of the Massachusetts General Hospital via support from the 'Center for Functional Neuroimaging Technologies' (P41RR14075). In addition, M. C. E. was supported by the Mind, Brain and Behavior Interfaculty Initiative at Harvard University. NR 63 TC 6 Z9 6 U1 3 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD APR PY 2012 VL 7 IS 4 BP 380 EP 392 DI 10.1093/scan/nsr003 PG 13 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 926CF UT WOS:000302808200002 PM 21296864 ER PT J AU Liang, MK Subramanian, A Awad, SS AF Liang, Mike K. Subramanian, Anuradha Awad, Samir S. TI Laparoscopic Transcutaneous Closure of Central Defects in Laparoscopic Incisional Hernia Repair SO SURGICAL LAPAROSCOPY ENDOSCOPY & PERCUTANEOUS TECHNIQUES LA English DT Article DE hernia; incisional hernia; laparoscopic; pseudorecurrence; eventration; diastasis; recurrence; seroma ID PREFASCIAL POLYPROPYLENE MESH; VENTRAL HERNIA; RECURRENCE AB Purpose: The aim of this technical report is to investigate the safety, efficacy, and outcome of transcutaneous closure of central defects (TCCD) for laparoscopic incisional hernia repair (LIHR). Methods: Twenty-two patients with incisional hernias underwent a LIHR-TCCD repair. After clearance of the abdominal wall from adhesions, laparoscopic central closures were performed trans-cutaneously with 0-polypropelene sutures placed every 1 cm of the defect starting at the cranial-most edge of the hernia and ending at the caudal-most edge of the hernia. A standard LIHR was performed with coated polyester mesh placed with at least 6 cm of overlap with mesh on all borders. Transfascial sutures with 0-polypropelene sutures were placed every 4 cm circumferentially, and titanium tacks were used to secure the mesh to the peritoneum every 1cm. Results: The mean age was 52 years and the mean body mass index was 35 kg/m(2). The mean hernia defect was 4.7cm x 7.2 cm with a mean area of 37 cm(2). There were no mortalities and no major peri-operative morbidities. Minor complications included 2 (9%) cases of pneumonia/pneumonitis. There were no clinically significant seromas, no radiographic or clinical eventrations, and no hernia recurrences with a mean follow-up of 21 months. Conclusions: LIHR-TCCD is safe and technically feasible in incisional hernias of width < 10 cm. By closing the central defect, seromas and eventrations can be reduced. C1 [Liang, Mike K.; Subramanian, Anuradha; Awad, Samir S.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. RP Liang, MK (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM ml3@bcm.edu RI Liang, Mike/L-8493-2015 OI Liang, Mike/0000-0001-7063-7291 NR 20 TC 10 Z9 12 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1530-4515 J9 SURG LAPARO ENDO PER JI Surg. Laparosc. Endosc. Pct. Tech. PD APR PY 2012 VL 22 IS 2 BP E66 EP E70 DI 10.1097/SLE.0b013e3182471fd2 PG 5 WC Surgery SC Surgery GA 925OW UT WOS:000302771700005 PM 22487642 ER PT J AU Hinton, DE Rivera, EI Hofmann, SG Barlow, DH Otto, MW AF Hinton, Devon E. Rivera, Edwin I. Hofmann, Stefan G. Barlow, David H. Otto, Michael W. TI Adapting CBT for traumatized refugees and ethnic minority patients: Examples from culturally adapted CBT (CA-CBT) SO TRANSCULTURAL PSYCHIATRY LA English DT Article DE refugees; ethnic minorities; PTSD; CBT; cultural adaptation ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIOR THERAPY; TREATMENT-RESISTANT PTSD; CAMBODIAN REFUGEES; EXPOSURE THERAPY; INTEROCEPTIVE EXPOSURE; PANIC-ATTACKS; EFFICACY; PROSPECTS AB In this article, we illustrate how cognitive behavioral therapy (CBT) can be adapted for the treatment of PTSD among traumatized refugees and ethnic minority populations, providing examples from our treatment, culturally adapted CBT, or CA-CBT. CA-CBT has a unique approach to exposure (typical exposure is poorly tolerated in these groups), emphasizes the treatment of somatic sensations (a particularly salient part of the presentation of PTSD in these groups), and addresses comorbid anxiety disorders and anger. To accomplish these treatment goals, CA-CBT emphasizes emotion exposure and emotion regulation techniques such as meditation and aims to promote emotional and psychological flexibility. We describe 12 key aspects of adapting CA-CBT that make it a culturally sensitive treatment of traumatized refugee and ethnic minority populations. We discuss three models that guide our treatment and that can be used to design culturally sensitive treatments: (a) the panic attack-PTSD model to illustrate the many processes that generate PTSD in these populations, highlighting the role of arousal and somatic symptoms; (b) the arousal triad to demonstrate how somatic symptoms are produced and the importance of targeting comorbid anxiety conditions and psychopathological processes; and (c) the multisystem network (MSN) model of emotional state to reveal how some of our therapeutic techniques (e.g., body-focused techniques: bodily stretching paired with self-statements) bring about psychological flexibility and improvement. C1 [Hinton, Devon E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hinton, Devon E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Barlow, David H.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Hofmann, Stefan G.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 62 TC 30 Z9 31 U1 5 U2 28 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1363-4615 J9 TRANSCULT PSYCHIATRY JI Transcult. Psychiatry PD APR PY 2012 VL 49 IS 2 BP 340 EP 365 DI 10.1177/1363461512441595 PG 26 WC Anthropology; Psychiatry SC Anthropology; Psychiatry GA 926TD UT WOS:000302853700011 PM 22508639 ER PT J AU Podlaha, O Riester, M De, S Michor, F AF Podlaha, Ondrej Riester, Markus De, Subhajyoti Michor, Franziska TI Evolution of the cancer genome SO TRENDS IN GENETICS LA English DT Review ID CHRONIC MYELOGENOUS LEUKEMIA; NAKED MOLE-RAT; BREAST-CANCER; MYELOPROLIFERATIVE NEOPLASMS; DNA METHYLATION; OVARIAN-CANCER; STEM-CELLS; COLORECTAL-CANCER; PANCREATIC-CANCER; GENETIC LANDSCAPE AB Human tumors result from an evolutionary process operating on somatic cells within tissues, whereby natural selection operates on the phenotypic variability generated by the accumulation of genetic, genomic and epigenetic alterations. This somatic evolution leads to adaptations such as increased proliferative, angiogenic, and invasive phenotypes. In this review we outline how cancer genomes are beginning to be investigated from an evolutionary perspective. We describe recent progress in the cataloging of somatic genetic and genomic alterations, and investigate the contributions of germline as well as epigenetic factors to cancer genome evolution. Finally, we outline the challenges facing researchers who investigate the processes driving the evolution of the cancer genome. C1 [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Michor, F (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst, 665 Huntington Ave, Boston, MA 02115 USA. EM michor@jimmy.harvard.edu OI Riester, Markus/0000-0002-4759-8332 FU NCI NIH HHS [U54 CA143798] NR 100 TC 43 Z9 44 U1 2 U2 39 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD APR PY 2012 VL 28 IS 4 BP 155 EP 163 DI 10.1016/j.tig.2012.01.003 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 927PM UT WOS:000302920400002 PM 22342180 ER PT J AU Halyard, MY Wasif, N Harris, EER Arthur, DW Bailey, L Bellon, JR Carey, L Goyal, S Horst, KC Moran, MS MacDonald, SM Haffty, BG AF Halyard, Michele Y. Wasif, Nabil Harris, Eleanor E. R. Arthur, Douglas W. Bailey, Lisa Bellon, Jennifer R. Carey, Lisa Goyal, Sharad Horst, Kathleen C. Moran, Meena S. MacDonald, Shannon M. Haffty, Bruce G. CA Expert Panel Radiation Oncology Br TI ACR Appropriateness Criterias (R) Local-regional Recurrence (LR) and Salvage Surgery Breast Cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Review DE appropriateness criteria; breast cancer; local-regional recurrence; salvage therapy; relapse ID SURGICAL ADJUVANT BREAST; CONSERVING THERAPY; RANDOMIZED-TRIALS; LOCOREGIONAL RECURRENCE; TUMOR RECURRENCE; FOLLOW-UP; NEOADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; 15-YEAR SURVIVAL; LOW-RISK AB Despite the success of both breast conserving surgery and mastectomy, some women will experience a local-regional recurrence (LRR) of their breast cancer. Predictors for LRR after breast-conserving therapy or mastectomy have been identified, including patient, tumor, and treatment-related factors. The role of surgery, radiation, and chemotherapy as treatment has evolved over time and many patients now have the potential for salvage after LRR. This review of LRR of breast cancer and management recommendations, including the use of common clinical scenarios, represents a compilation of evidence-based data and expert opinion of the American College of Radiology Appropriateness Criteria Expert Panel on local-regional recurrence. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Halyard, Michele Y.; Wasif, Nabil] Mayo Clin Scottsdale, Scottsdale, AZ USA. [Halyard, Michele Y.; Wasif, Nabil] Mayo Clin Scottsdale, Phoenix, AZ USA. [Harris, Eleanor E. R.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Arthur, Douglas W.] Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. [Bailey, Lisa] Amer Coll Surg, Alta Bates Summit Med Ctr, Oakland, CA USA. [Horst, Kathleen C.] Stanford Med Ctr, Stanford, CA USA. [Bellon, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [MacDonald, Shannon M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carey, Lisa] Univ N Carolina Hlth Care Syst, Amer Soc Clin Oncol, Chapel Hill, NC USA. [Goyal, Sharad; Haffty, Bruce G.] UMDNJ Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Moran, Meena S.] Yale Univ, Sch Med, New Haven, CT USA. RP Halyard, MY (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM mhalyard@mayo.edu NR 43 TC 8 Z9 8 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 APR PY 2012 VL 35 IS 2 BP 178 EP 182 DI 10.1097/COC.0b013e3182439084 PG 5 WC Oncology SC Oncology GA 914ND UT WOS:000301956300016 PM 22433995 ER PT J AU Kleinberg, L Catalano, P Forastiere, A Keller, S Anne, R Benson, A AF Kleinberg, Lawrence Catalano, Paul Forastiere, Arlene Keller, Steven Anne, Rani Benson, Al TI Long-term Survival (S) and Disease-free Survival (DFS) Outcome of E1201: An Eastern Cooperative Oncology Group (ECOG) Randomized Phase II Trial of Neoadjuvant Preoperative Paclitaxel/Cisplatin/Radiotherapy (RT) or Irinotecan/Cisplatin/RT in Endoscopy with Ultrasound (EUS) Staged Esophageal Adenocarcinoma SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Meeting Abstract C1 [Kleinberg, Lawrence; Forastiere, Arlene] Johns Hopkins Univ, Baltimore, MD USA. [Catalano, Paul] Dana Farber Canc Inst, Boston, MA 02115 USA. [Keller, Steven] Montefiore Med Ctr, Bronx, NY 10467 USA. [Anne, Rani] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Benson, Al] Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 APR PY 2012 VL 35 IS 2 MA 5 BP 186 EP 187 PG 2 WC Oncology SC Oncology GA 914ND UT WOS:000301956300023 ER PT J AU Christiani, DC AF Christiani, David C. TI Invited Commentary: The Action in the Interaction and Exposure Modification SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE environmental health; epidemiology; gene-environment interaction; joint effects AB The study of disease variability in populations is a goal of modern epidemiology. Because most common diseases arise out of a combination of factors and events (exposures, heritability, comorbidities, and chance), developing simple models of characterizing joint events is a daunting task. Dr. Weinberg argues successfully in this issue of the Journal (Am J Epidemiol. 2012;175(7):602-605) that additive null models can capture pure forms of independent causal effects in studies of rare conditions. Moreover, the concept of exposure modification, which characterizes most gene-environment interactions reported to date, is introduced. More cross-talk between biologists and epidemiologists is needed to tackle key issues in chronic disease etiology, and the argument for the use of parsimonious joint models in epidemiology is convincing. C1 [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave,Bldg 1,Room 1401, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2012 VL 175 IS 7 BP 606 EP 608 DI 10.1093/aje/kwr498 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 921NE UT WOS:000302483500003 PM 22306558 ER PT J AU Mekary, RA Hu, FB Willett, WC Chiuve, S Wu, KN Fuchs, C Fung, TT Giovannucci, E AF Mekary, Rania A. Hu, Frank B. Willett, Walter C. Chiuve, Stephanie Wu, Kana Fuchs, Charles Fung, Teresa T. Giovannucci, Edward TI The Joint Association of Eating Frequency and Diet Quality With Colorectal Cancer Risk in the Health Professionals Follow-up Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE colorectal neoplasms; diet; food; nutritional status ID MEAL FREQUENCY; COLON-CANCER; WOMEN; REPRODUCIBILITY; QUESTIONNAIRE; ADHERENCE; ETIOLOGY; VALIDITY; INSULIN; COFFEE AB The results of most case-control studies have suggested a positive association between eating frequency and colorectal cancer risk. Because no prospective cohort studies have done so to date, the authors prospectively examined this association. In 1992, eating frequency was assessed in a cohort of 34,968 US men in the Health Professionals Follow-up Study. Cox proportional hazards regression models were used to estimate relative risks and 95% confidence intervals for various levels of eating frequency. Effect modifications by overall dietary quality (assessed using the Diet Approaches to Stop Hypertension score) and by factors that influence insulin resistance were further assessed. Between 1992 and 2006, a total of 583 cases of colorectal cancer were diagnosed. When comparing the highest eating frequency category (5-8 times/day) with the reference category (3 times/day), the authors found no evidence of an increased risk of colorectal cancer (multivariate relative risk = 0.88, 95% confidence interval: 0.62, 1.26) or colon cancer (multivariate relative risk = 0.78, 95% confidence interval: 0.49, 1.25). There was an implied inverse association with eating frequency among participants who had healthier diets (high Diet Approaches to Stop Hypertension score; P for interaction = 0.01), especially among men in the high-insulin-sensitivity group (body mass index (weight (kg)/height (m)(2)) <25, >= 2 cups of coffee/day, and more physical activity; P for interaction < 0.01, P for trend = 0.01). There was an implied protective association between increased eating frequency of healthy meals and colorectal cancer risk and in men with factors associated with higher insulin sensitivity. C1 [Mekary, Rania A.; Hu, Frank B.; Willett, Walter C.; Chiuve, Stephanie; Wu, Kana; Fung, Teresa T.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hu, Frank B.; Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fung, Teresa T.] Simmons Coll, Dept Nutr, Boston, MA 02115 USA. [Hu, Frank B.; Willett, Walter C.; Chiuve, Stephanie; Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hu, Frank B.; Willett, Walter C.; Chiuve, Stephanie; Giovannucci, Edward] Harvard Univ, Sch Med, Boston, MA USA. [Fuchs, Charles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Mekary, RA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2, Boston, MA 02115 USA. EM rania.mekary@channing.harvard.edu FU National Institutes of Health [CA55075, CA95589] FX This work was supported by National Institutes of Health grants CA55075 and CA95589. NR 30 TC 8 Z9 8 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2012 VL 175 IS 7 BP 664 EP 672 DI 10.1093/aje/kwr363 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 921NE UT WOS:000302483500011 PM 22387430 ER PT J AU Norgaard, M Nielsen, RB Jacobsen, JB Gradus, JL Stenager, E Koch-Henriksen, N Lash, TL Sorensen, HT AF Norgaard, Mette Nielsen, Rikke Beck Jacobsen, Jacob Bonde Gradus, Jaimie L. Stenager, Egon Koch-Henriksen, Nils Lash, Timothy L. Sorensen, Henrik Toft TI RE: "USE OF PENICILLIN AND OTHER ANTIBIOTICS AND RISK OF MULTIPLE SCLEROSIS: A POPULATION-BASED CASE-CONTROL STUDY" REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 [Norgaard, Mette; Nielsen, Rikke Beck; Jacobsen, Jacob Bonde; Lash, Timothy L.; Sorensen, Henrik Toft] Aarhus Univ Hosp, Inst Clin, Dept Clin Epidemiol, DK-8200 Aarhus N, Denmark. [Gradus, Jaimie L.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Gradus, Jaimie L.; Sorensen, Henrik Toft] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Stenager, Egon; Koch-Henriksen, Nils] Univ Copenhagen Hosp, Danish Multiple Sclerosis Registry, DK-2100 Copenhagen N, Denmark. [Stenager, Egon] Univ So Denmark, Inst Reg Hlth Res Serv, DK-5000 Odense, Denmark. [Stenager, Egon] Sonderborg Hosp, Dept Neurol, MS Clin So Jutland Sonderborg Vejle Esbjerg, Sonderborg 6400, Denmark. [Koch-Henriksen, Nils] Arhus Univ Hosp, Dept Neurol, DK-9100 Aalborg, Denmark. RP Norgaard, M (reprint author), Aarhus Univ Hosp, Inst Clin, Dept Clin Epidemiol, DK-8200 Aarhus N, Denmark. EM m.noergaard@rn.dk NR 10 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2012 VL 175 IS 7 BP 728 EP 729 DI 10.1093/aje/kwr443 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 921NE UT WOS:000302483500019 ER PT J AU Fagotti, A Boruta, DM Scambia, G Fanfani, F Paglia, A Escobar, PF AF Fagotti, Anna Boruta, David M., II Scambia, Giovanni Fanfani, Francesco Paglia, Amelia Escobar, Pedro F. TI First 100 early endometrial cancer cases treated with laparoendoscopic single-site surgery: a multicentric retrospective study SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE endometrial cancer; laparoendoscopic single-site surgery; laparoscopy; minimally invasive surgery; single port access ID LAPAROSCOPIC SURGERY; GYNECOLOGIC ONCOLOGY; HYSTERECTOMY; LESS; LYMPHADENECTOMY; LAPAROTOMY; INCISION; OUTCOMES; TRIAL AB OBJECTIVE: We sought to assess feasibility and perioperative outcomes for laparoendoscopic single-site surgery (LESS) in early endometrial cancer. STUDY DESIGN: This was a retrospective multicentric study of 100 early endometrial cancer cases undergoing LESS from July 2009 through July 2011. RESULTS: All patients underwent total hysterectomy and bilateral salpingo-oophorectomy by LESS. Pelvic and paraaortic lymphadenectomy were performed in 48 and 27 patients, respectively. A median of 16 pelvic lymph nodes (range, 1-33) and 7 paraaortic lymph nodes (range, 2-28) were retrieved. Both median operative time (129 minutes; range, 45-321) and estimated blood loss (70 mL; range, 10-500) were greater when staging lymphadenectomy was performed (P values = .001). Four intraoperative and 4 postoperative complications were observed. Conversion to standard laparoscopy and laparotomy was necessary for completion of 1 case each. Patients responded positively regarding cosmetic result and minimal postoperative pain control. CONCLUSION: LESS further minimizes the invasive nature of surgery and is feasible for treatment of early-stage endometrial cancer. C1 [Fagotti, Anna; Scambia, Giovanni; Fanfani, Francesco; Paglia, Amelia] Univ Cattolica Sacro Cuore, Dept Obstet & Gynecol, Div Gynecol Oncol, I-00168 Rome, Italy. [Boruta, David M., II] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. [Escobar, Pedro F.] Cleveland Clin, Womens Hlth Inst, Dept Obstet & Gynecol, Div Gynecol Oncol, Cleveland, OH 44106 USA. RP Fagotti, A (reprint author), Univ Cattolica Sacro Cuore, Dept Obstet & Gynecol, Div Gynecol Oncol, Largo A Gemelli 8, I-00168 Rome, Italy. EM anna.fagotti@rm.unicatt.it RI Fanfani, Francesco/Q-1154-2015 OI Fanfani, Francesco/0000-0003-1991-7284 NR 39 TC 6 Z9 9 U1 0 U2 1 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 APR PY 2012 VL 206 IS 4 AR 353.e1 DI 10.1016/j.ajog.2012.01.031 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 918QS UT WOS:000302266000034 PM 22365037 ER PT J AU Moore, RG Miller, MC Steinhoff, MM Skates, SJ Lu, KH Lambert-Messerlian, G Bast, RC AF Moore, Richard G. Miller, Michael Craig Steinhoff, Margaret M. Skates, Steven J. Lu, Karen H. Lambert-Messerlian, Geralyn Bast, Robert C., Jr. TI Serum HE4 levels are less frequently elevated than CA125 in women with benign gynecologic disorders SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE benign gynecological disease; biomarker; CA125; HE4; healthy women ID EPITHELIAL OVARIAN-CANCER; INDEPENDENT PROGNOSTIC-FACTOR; PELVIC MASS; CA 125; CA-125 CONCENTRATIONS; MONOCLONAL-ANTIBODY; HALF-LIFE; CARCINOMA; DISEASE; CHEMOTHERAPY AB OBJECTIVE: The human epididymis protein 4 (HE4) is a novel biomarker for ovarian cancer. This study measured the HE4 and CA125 levels in women with benign gynecological disorders. STUDY DESIGN: Sera were obtained from women prior to surgery for a pelvic mass and HE4 and CA125 levels were determined. The proportions of patients with elevated biomarker levels were compared. RESULTS: There were 1042 women with benign disease. HE4 levels were less often elevated than CA125 (8% vs 29%, P < .001). A marked difference was observed in patients with endometriosis in which HE4 was elevated in 3% of patients and CA125 in 67% (P < .0001). Serous ovarian tumors were associated with elevated levels of HE4 in 8% of patients and CA125 in 20% (P < .0002); uterine fibroids in 8% vs 26% (P < .0083); dermoids in 1% vs 21% (P < .0004); and inflammatory disease in 10% vs 37% (P < .014). CONCLUSION: HE4 is elevated less frequently than CA125 in benign disease, particularly in premenopausal patients. C1 [Moore, Richard G.; Miller, Michael Craig; Lambert-Messerlian, Geralyn] Brown Univ, Women & Infants Hosp, Ctr Biomarkers & Emerging Technol,Alpert Med Sch, Program Womens Oncol,Dept Obstet & Gynecol, Providence, RI 02905 USA. [Steinhoff, Margaret M.] Brown Univ, Women & Infants Hosp, Alpert Med Sch, Dept Pathol & Lab Med, Providence, RI 02905 USA. [Skates, Steven J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gillette Canc Ctr, Boston, MA USA. [Lu, Karen H.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Bast, Robert C., Jr.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. RP Moore, RG (reprint author), Brown Univ, Women & Infants Hosp, Ctr Biomarkers & Emerging Technol,Alpert Med Sch, Program Womens Oncol,Dept Obstet & Gynecol, 101 Dudley St, Providence, RI 02905 USA. EM rmoore@wihri.org RI Bast, Robert/E-6585-2011; OI Bast, Robert/0000-0003-4621-8462; Messerlian, Geralyn/0000-0002-9440-3411 FU National Cancer Institute [NCI 1 R01 CA136491-01]; Fujirebio Diagnostics Inc; Abbott Diagnostics Inc.; Beckman Coulter Inc; National Cancer Institute's Early Detection Research Network [U01-CA152990]; M. D. Anderson Cancer Center Ovarian SPORE [CA83639]; Fujirebio Diagnostics Inc [CA125]; Scientific Advisory Boards of Vermillion Inc; Illumina Inc. FX R.G.M. is partially supported by National Cancer Institute grant NCI 1 R01 CA136491-01. He also receives research funding from Fujirebio Diagnostics Inc and Abbott Diagnostics Inc. M. C. M. receives consulting fees from Fujirebio Diagnostics Inc. G. L.-M. receives research funding from Fujirebio Diagnostics Inc, Beckman Coulter Inc, and Abbott Diagnostics Inc. S.J.S. is partially supported by grant U01-CA152990 as part of the National Cancer Institute's Early Detection Research Network. R. C. B. is partially supported by M. D. Anderson Cancer Center Ovarian SPORE 1 P50 grant CA83639. He also receives royalties for CA125 from Fujirebio Diagnostics Inc and serves on the Scientific Advisory Boards of Vermillion Inc and Illumina Inc. The remaining authors report no conflict of interest. NR 35 TC 1 Z9 5 U1 1 U2 6 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 APR PY 2012 VL 206 IS 4 AR 351.e1 DI 10.1016/j.ajog.2011.12.029 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 918QS UT WOS:000302266000033 PM 22284961 ER PT J AU Leung, DT Bogetz, J Itoh, M Ganapathi, L Pietroni, MAC Ryan, ET Chisti, MJ AF Leung, Daniel T. Bogetz, Jori Itoh, Megumi Ganapathi, Lakshmi Pietroni, Mark A. C. Ryan, Edward T. Chisti, Mohammod Jobayer TI Factors Associated with Encephalopathy in Patients with Salmonella enterica Serotype Typhi Bacteremia Presenting to a Diarrheal Hospital in Dhaka, Bangladesh SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID HIGH-DOSE DEXAMETHASONE; PROINFLAMMATORY CYTOKINES; CEREBROSPINAL-FLUID; FEVER; CHILDREN; COMPLICATIONS; PERFORATION; INTERFERON; MANAGEMENT; MORBIDITY AB To characterize clinical correlates of typhoid fever-associated encephalopathy, we performed a retrospective chart review of patients with Salmonella enterica serotype Typhi bacteremia who were hospitalized at the International Centre for Diarrhoeal Disease Research, Bangladesh, from February of 2009 to June of 2011. Of 207 patients bacteremic with Salmonella Typhi who were >= 5 years of age, we identified 43 (21%) patients with encephalopathy. Univariate analysis revealed that patients with encephalopathy more often presented at ages of 10-24 years and had severe dehydration, low oxygen saturation, high respiratory rate, low leukocyte count, low platelet count, and Widal flagellar H agglutinin (TH) titer >= 1:640 compared with typhoid patients without encephalopathy. Multivariate analysis using logistic regression showed that age, dehydration, leukocyte count, and Widal TH titer were independently associated with encephalopathy. Our findings suggest that age, severity of disease, and immune responses are associated with encephalopathy during Salmonella Typhi bacteremia, perhaps reflecting the impact of prominent inflammatory responses. C1 [Leung, Daniel T.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bogetz, Jori; Itoh, Megumi] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. [Ganapathi, Lakshmi] Childrens Hosp Boston, Dept Pediat, Boston, MA USA. [Pietroni, Mark A. C.; Chisti, Mohammod Jobayer] Dhaka Hosp, Dhaka, Bangladesh. [Pietroni, Mark A. C.; Chisti, Mohammod Jobayer] Int Ctr Diarrhoeal Dis Res, Ctr Nutr & Food Secur, Intens Care Unit, Dhaka, Bangladesh. [Pietroni, Mark A. C.; Chisti, Mohammod Jobayer] Int Ctr Diarrhoeal Dis Res, Resp Ward, Dhaka, Bangladesh. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Leung, DT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Jackson 504, Boston, MA 02114 USA. EM dleung@partners.org; jbogetz@stanford.edu; mitoh@stanford.edu; Lakshmi.Ganapathi@childrens.harvard.edu; markp@icddrb.org; etryan@partners.org; chisti@icddrb.org OI leung, daniel/0000-0001-8401-0801 FU International Centre for Diarrhoeal Disease Research, Bangladesh; Australian Agency for International Development (AusAID); Government of the People's Republic of Bangladesh; Canadian International Development Agency (CIDA); Swedish International Development Cooperation Agency (Sida); Department for International Development, United Kingdom (DFID); National Institutes of Health; American Recovery and Reinvestment Act Supplement; Harvard Global Health Institute; American Society of Tropical Medicine and Hygiene; National Institute of Allergy and Infectious Diseases [U01-AI077883]; Fogarty International Center [D43-TW005572] FX This research study was funded by International Centre for Diarrhoeal Disease Research, Bangladesh and its donors, which provide unrestricted support to International Centre for Diarrhoeal Disease Research, Bangladesh for its operations and research. Current donors providing unrestricted support include the Australian Agency for International Development (AusAID), the Government of the People's Republic of Bangladesh, the Canadian International Development Agency (CIDA), the Swedish International Development Cooperation Agency (Sida), and the Department for International Development, United Kingdom (DFID). This study was also supported by grants from the National Institutes of Health, including Fogarty International Center Grant D43-TW005572, American Recovery and Reinvestment Act Supplement (to D.T.L.), a Postdoctoral Research Fellowship in Global Infectious Diseases from the Harvard Global Health Institute (D.T.L.), a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society of Tropical Medicine and Hygiene/Burroughs Wellcome Fund (D.T.L.), and National Institute of Allergy and Infectious Diseases Grant U01-AI077883 (to E.T.R.). NR 34 TC 3 Z9 4 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD APR PY 2012 VL 86 IS 4 BP 698 EP 702 DI 10.4269/ajtmh.2012.11-0750 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 922AR UT WOS:000302519700023 PM 22492156 ER PT J AU Gronchi, A Raut, CP AF Gronchi, Alessandro Raut, Chandrajit P. TI The Combination of Surgery and Imatinib in GIST: A Reality for Localized Tumors at High Risk, an Open Issue for Metastatic Ones SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID GASTROINTESTINAL STROMAL TUMORS; ADVANCED/METASTATIC GIST; SURGICAL-MANAGEMENT; KIT MUTATIONS; THERAPY; MESYLATE; RESECTION C1 [Gronchi, Alessandro] Fdn IRCCS Ist Nazl Tumori, Sarcoma Serv, Dept Surg, 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, Sarcoma Serv, Dept Surg, Milan, Italy. EM alessandro.gronchi@istitutotumori.mi.it OI Gronchi, Alessandro/0000-0002-4703-3534 NR 20 TC 15 Z9 16 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2012 VL 19 IS 4 BP 1051 EP 1055 DI 10.1245/s10434-011-2191-4 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 924NG UT WOS:000302698000001 PM 22207052 ER PT J AU Wang, D Zhang, Q Blanke, CD Demetri, GD Heinrich, MC Watson, JC Hoffman, JP Okuno, S Kane, JM von Mehren, M Eisenberg, BL AF Wang, Dian Zhang, Qiang Blanke, Charles D. Demetri, George D. Heinrich, Michael C. Watson, James C. Hoffman, John P. Okuno, Scott Kane, John M. von Mehren, Margaret Eisenberg, Burton L. TI Phase II Trial of Neoadjuvant/adjuvant Imatinib Mesylate for Advanced Primary and Metastatic/recurrent Operable Gastrointestinal Stromal Tumors: Long-term Follow-up Results of Radiation Therapy Oncology Group 0132 SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID DOSE IMATINIB; SOLID TUMORS; GIST; DIAGNOSIS; KIT; PROGRESSION; RESECTION; MANAGEMENT; MUTATIONS; SURVIVAL AB Background. Imatinib inhibits the KIT and PDGFR tyrosine kinases, resulting in its notable antitumor activity in gastrointestinal stromal tumor (GIST). We previously reported the early results of a multi-institutional prospective trial (RTOG 0132) using neoadjuvant/adjuvant imatinib either in primary resectable GIST or as a planned preoperative cytoreduction agent for metastatic/recurrent GIST. Methods.. Patients with primary GIST (>= 5 cm, group A) or resectable metastatic/recurrent GIST (>= 2 cm, group B) received neoadjuvant imatinib (600 mg/day) for approximately 2 months and maintenance postoperative imatinib for 2 years. We have now updated the clinical outcomes including progression-free survival, disease-specific survival, and overall survival at a median follow-up of 5.1 years, and we correlate these end points with duration of imatinib therapy. Results. Sixty-three patients were originally entered (53 analyzable: 31 in group A and 22 in group B). Estimated 5-year progression-free survival and overall survival were 57% in group A, 30% in group B; and 77% in group A, 68% in group B, respectively. Median time to progression has not been reached for group A and was 4.4 years for group B. In group A, in 7 of 11 patients, disease progressed >2 years from registration; 6 of 7 patients with progression had stopped imatinib before progression. In group B, disease progressed in 10 of 13 patients >2 years from registration; 6 of 10 patients with progressing disease had stopped imatinib before progression. There was no significant increase in toxicity compared with our previous short-term analysis. Conclusions. This long-term analysis suggests a high percentage of patients experienced disease progression after discontinuation of 2-year maintenance imatinib therapy after surgery. Consideration should be given to studying longer treatment durations in intermediate- to high-risk GIST patients. C1 [Wang, Dian] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Zhang, Qiang] Ctr Stat, Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Blanke, Charles D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Blanke, Charles D.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Demetri, George D.] Harvard Univ, Sch Med, Boston, MA USA. [Heinrich, Michael C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR USA. [Watson, James C.; Hoffman, John P.; von Mehren, Margaret] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Okuno, Scott] Mayo Clin, Rochester, MN USA. [Kane, John M.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Eisenberg, Burton L.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Wang, D (reprint author), Med Coll Wisconsin, Milwaukee, WI 53226 USA. EM dwang@mcw.edu FU National Cancer Institute (NCI) [RTOG U10 CA21661, CCOP U10 CA37422]; Novartis; Ariad; Lilly; AROG Pharmaceuticals FX Supported in part by grants RTOG U10 CA21661 and CCOP U10 CA37422 from the National Cancer Institute (NCI). The contents of this article are the sole responsibility of the authors and do not necessarily represent the official views of the NCI. The authors received consulting fees, honoraria, and research support as follows: Consulting: Charles D. Blanke (Novartis), George D. Demetri (Novartis), Margaret von Mehren (Novartis), Burt Eisenberg Novartis), Michael Heinrich (Novartis, MolecularMD). Honoraria: Charles D. Blanke (Novartis), George D. Demetri (Novartis), Michael Heinrich (Novartis), Margaret. von Mehren (Novartis), Burt Eisenberg (Novartis). Research support: George D. Demetri (Novartis), Margaret. von Mehren (Novartis). Michael Heinrich (Novartis, Ariad, Lilly, AROG Pharmaceuticals), Scott Okuno (Novartis). Stock ownership: Michael Heinrich (MolecularMD). NR 31 TC 50 Z9 58 U1 2 U2 6 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 APR PY 2012 VL 19 IS 4 BP 1074 EP 1080 DI 10.1245/s10434-011-2190-5 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 924NG UT WOS:000302698000005 PM 22203182 ER PT J AU Gronchi, A Raut, CP AF Gronchi, Alessandro Raut, Chandrajit P. TI The Combination of Surgery and Imatinib in GIST: A Reality for Localized Tumors at High Risk, an Open Issue for Metastatic Ones (vol 19, pg 1051, 2012) SO ANNALS OF SURGICAL ONCOLOGY LA English DT Correction 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 NR 1 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2012 VL 19 IS 4 BP 1370 EP 1370 DI 10.1245/s10434-012-2251-4 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 924NG UT WOS:000302698000048 ER PT J AU Sun, JK Qin, HJ Aiello, LP Melia, M Beck, RW Andreoli, CM Edwards, PA Glassman, AR Pavlica, MR AF Sun, Jennifer K. Qin, Haijing Aiello, Lloyd Paul Melia, Michele Beck, Roy W. Andreoli, Christopher M. Edwards, Paul A. Glassman, Adam R. Pavlica, Michael R. CA Diabetic Retinopathy Clinical Res TI Evaluation of Visual Acuity Measurements After Autorefraction vs Manual Refraction in Eyes With and Without Diabetic Macular Edema SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article AB Objective: To compare visual acuity (VA) scores after autorefraction vs manual refraction in eyes of patients with diabetes mellitus and a wide range of VAs. Methods: The letter score from the Electronic Visual Acuity (EVA) test from the electronic Early Treatment Diabetic Retinopathy Study was measured after autorefraction (AR-EVA score) and after manual refraction (MR-EVA score), which is the research protocol of the Diabetic Retinopathy Clinical Research Network. Testing order was randomized, study participants and VA examiners were masked to refraction source, and a second EVA test using an identical supplemental manual refraction (MR-EVAsuppl score) was performed to determine test-retest variability. Results: In 878 eyes of 456 study participants, the median MR-EVA score was 74 (Snellen equivalent, approximately 20/32). The spherical equivalent was often similar for manual refraction and autorefraction (median difference, 0.00; 5th-95th percentile range, -1.75 to 1.13 diopters). However, on average, the MR-EVA scores were slightly better than the AR-EVA scores, across the entire VA range. Furthermore, the variability between the AR-EVA scores and the MR-EVA scores was substantially greater than the test-retest variability of the MR-EVA scores (P<.001). The variability of differences was highly dependent on the autorefractor model. Conclusions: Across a wide range of VAs at multiple sites using a variety of autorefractors, VA measurements tend to be worse with autorefraction than manual refraction. Differences between individual autorefractor models were identified. However, even among autorefractor models that compare most favorably with manual refraction, VA variability between autorefraction and manual refraction is higher than the test-retest variability of manual refraction. The results suggest that, with current instruments, autorefraction is not an acceptable substitute for manual refraction for most clinical trials with primary outcomes dependent on best-corrected VA. C1 [Qin, Haijing; Melia, Michele; Beck, Roy W.; Glassman, Adam R.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Sun, Jennifer K.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA. [Sun, Jennifer K.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Res Sect, Boston, MA USA. [Andreoli, Christopher M.] Harvard Univ, Sch Med, Dept Ophthalmol, Harvard Vanguard Med Associates, Boston, MA USA. [Edwards, Paul A.] Henry Ford Hlth Syst, Dept Ophthalmol, Detroit, MI USA. [Edwards, Paul A.] Henry Ford Hlth Syst, Eye Care Serv, Detroit, MI USA. [Pavlica, Michael R.] Family Eye Grp, Lancaster, PA USA. RP Qin, HJ (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Ste 350, Tampa, FL 33647 USA. EM drcrstat3@jaeb.org FU National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health, Department of Health and Human Services) [EY14231, EY14229, EY018817] FX This study was supported by a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health, Department of Health and Human Services grants EY14231, EY14229, and EY018817). NR 13 TC 6 Z9 6 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 APR PY 2012 VL 130 IS 4 BP 470 EP 479 DI 10.1001/archophthalmol.2011.377 PG 10 WC Ophthalmology SC Ophthalmology GA 922OK UT WOS:000302557100008 PM 22159173 ER PT J AU Jakobiec, FA Zakka, FR Kirzhner, M Kim, N AF Jakobiec, Frederick A. Zakka, Fouad R. Kirzhner, Maria Kim, Nancy TI Epstein-Barr Virus-Positive T-Cell Lymphoma Involving the Lacrimal Gland of an Adult SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter C1 [Jakobiec, Frederick A.] Harvard Univ, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Div Oculoplast Surg, Sch Med, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Sch Med, 243 Charles St,Room 321, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 10 TC 2 Z9 2 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 APR PY 2012 VL 130 IS 4 BP 523 EP 525 PG 4 WC Ophthalmology SC Ophthalmology GA 922OK UT WOS:000302557100020 PM 22491926 ER PT J AU Suri, P Rainville, J Hunter, DJ Li, L Katz, JN AF Suri, Pradeep Rainville, James Hunter, David J. Li, Ling Katz, Jeffrey N. TI Recurrence of Radicular Pain or Back Pain After Nonsurgical Treatment of Symptomatic Lumbar Disk Herniation SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Intervertebral disk displacement; Outcome assessment (health care); Rehabilitation ID OUTCOMES; INDICATORS; DISKECTOMY; SCIATICA; EPISODE AB Suni P, Rainville J, Hunter DJ, Li L, Katz JN. Recurrence of radicular pain or back pain after nonsurgical treatment of symptomatic lumbar disk herniation. Arch Phys Med Rehabil 2012;93:690-5. Objectives: To determine recurrence rates of lower-extremity radicular pain after nonsurgical treatment of acute symptomatic lumbar disk herniation (LDH), and to identify predictors of recurrence. Design: Prospective inception cohort. Setting: Outpatient spine clinic. Participants: Patients (N=79) reporting resolution of radicular pain after magnetic resonance imaging confirmation of LDH. Interventions: Individualized nonsurgical treatment tailored to the patient. All patients received education, but other treatments varied depending on the individual. Main Outcome Measures: Resolution of radicular pain was defined as a pain-free period of >= 1 month. Patients who reported resolution of radicular pain within 1 year after seeking care for acute LDH were asked whether pain had recurred at 1 year after seeking care and were also reassessed 1 year after the time of resolution of radicular pain and 2 years after seeking care. Patients reported on recurrence and the date of recurrence, if any. We evaluated the I-year incidence of recurrence, using Kaplan-Meier survival plots. We examined predictors of recurrence using bivariate and multivariate Cox proportional hazards models. We examined the secondary outcome of back pain recurrence using identical methods. Results: Twenty-five percent (95% confidence interval [CI], 15-35) of individuals with resolution of radicular pain for at least 1 month reported subsequent recurrence of pain within 1 year after resolution. The only factor independently associated with radicular pain recurrence was the number of months prior to resolution of pain (hazard ratio per month=1.24; 95% CI, 1.13-1.37; P<.001). The 1-year incidence of back pain recurrence was 43% (95% CI, 30-56), and older age decreased the hazard of recurrence. Conclusions: Recurrence of radicular pain is relatively common after nonsurgical treatment of LDH and is predicted by longer time to initial resolution of pain. C1 [Suri, Pradeep] VA Boston Healthcare Syst, Div PM&R, Boston, MA USA. [Suri, Pradeep] Spaulding Rehabil Hosp, Boston, MA USA. [Suri, Pradeep; Rainville, James; Hunter, David J.; Li, Ling] New England Baptist Hosp, Boston, MA USA. [Suri, Pradeep; Rainville, James] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Hunter, David J.] Univ Sydney, No Clin Sch, Sydney, NSW 2006, Australia. RP Suri, P (reprint author), VA Boston Healthcare Syst, Div PM&R, 150 S Huntington Ave, Boston, MA USA. EM pradeep.suri@va.gov RI Hunter, David/A-4622-2010 OI Hunter, David/0000-0003-3197-752X FU National Institutes of Health [K12 HD001097-12]; Rehabilitation Medicine Scientist Training Program; Australian Research Council; National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases [P60 AR 47782] FX Supported by the Rehabilitation Medicine Scientist Training Program; the National Institutes of Health (grant no. K12 HD001097-12); an Australian Research Council Future Fellowship; and the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant no. P60 AR 47782). NR 25 TC 8 Z9 8 U1 7 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD APR PY 2012 VL 93 IS 4 BP 690 EP 695 DI 10.1016/j.apmr.2011.11.028 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 922AX UT WOS:000302520300020 PM 22464091 ER PT J AU Maemura, T Kinoshita, M Shin, M Miyazaki, H Tsujimoto, H Ono, S Hase, K Saitoh, D AF Maemura, Tomoyuki Kinoshita, Manabu Shin, Michael Miyazaki, Hiromi Tsujimoto, Hironori Ono, Satoshi Hase, Kazuo Saitoh, Daizoh TI Assessment of a Tissue-Engineered Gastric Wall Patch in a Rat Model SO ARTIFICIAL ORGANS LA English DT Article DE Gastric wall patch; Tissue-engineered stomach; Gastrectomy ID STOMACH AB Stenosis or deformity of the remaining stomach can occur after gastrectomy and result in stomach malfunction. The objective of this study is to demonstrate the feasibility of transplanting a tissue-engineered gastric wall patch in a rat model to alleviate the complications after resection of a large area of the gastric wall. Tissue-engineered gastric wall patches were created from gastric epithelial organoid units and biodegradable polymer scaffolds. In the first treatment group, gastric wall defects were created in recipient rats and covered with fresh tissue-engineered gastric wall patches (simultaneous transplantation). In the second treatment group, the tissue-engineered gastric wall patches were frozen for 12 weeks, and then transplanted in recipient rats (metachronous transplantation). Tissue-engineered gastric wall patches were successfully used as a substitute of the resected native gastric wall in both simultaneous and metachronous transplantation groups. The defrosted wall patches showed almost the same cell viability as the fresh ones. Twenty-four weeks after transplantation, the defect in the gastric wall was well-covered with tissue-engineered gastric wall patch, and the repaired stomach showed no deformity macroscopically in both groups. Histology showed continuous mucosa and smooth muscle layers at the tissue-engineered stomach wall margin. The feasibility of transplanting a tissue-engineered patch to repair a defect in the native gastric wall has been successfully shown in a rat model, thereby taking one step closer toward the transplantation of an entire tissue-engineered stomach in the future. C1 [Maemura, Tomoyuki; Miyazaki, Hiromi; Ono, Satoshi; Saitoh, Daizoh] Natl Def Med Coll, Res Inst, Div Basic Traumatol, Tokorozawa, Saitama 3598513, Japan. [Maemura, Tomoyuki; Tsujimoto, Hironori; Hase, Kazuo] Natl Def Med Coll, Dept Surg, Tokorozawa, Saitama 3598513, Japan. [Kinoshita, Manabu] Natl Def Med Coll, Dept Immunol & Microbiol, Tokorozawa, Saitama 3598513, Japan. [Shin, Michael] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Shin, Michael] Harvard Univ, Sch Med, Boston, MA USA. RP Maemura, T (reprint author), Natl Def Med Coll, Res Inst, Div Basic Traumatol, Namiki 3-2, Tokorozawa, Saitama 3598513, Japan. EM maemura@ndmc.ac.jp NR 9 TC 6 Z9 6 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD APR PY 2012 VL 36 IS 4 BP 409 EP 417 DI 10.1111/j.1525-1594.2011.01360.x PG 9 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 923EF UT WOS:000302601400013 PM 22040317 ER PT J AU Haggerty, TJ Dunn, IS Rose, LB Newton, EE Kurnick, JT AF Haggerty, Timothy J. Dunn, Ian S. Rose, Lenora B. Newton, Estelle E. Kurnick, James T. TI A Screening Assay to Identify Agents That Enhance T-Cell Recognition of Human Melanomas SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; DIFFERENTIATION ANTIGEN-EXPRESSION; CALCIUM-ANTAGONIST FLUNARIZINE; PHASE-II TRIAL; MELANOCYTE DIFFERENTIATION; METASTATIC MELANOMA; IN-VIVO; ANTITUMOR-ACTIVITY; HSP90 INHIBITORS; HETEROGENEOUS EXPRESSION AB Although a series of melanoma differentiation antigens for immunotherapeutic targeting has been described, heterogeneous expression of antigens such as Melan-A/MART-1 and gp100 results from a loss of antigenic expression in many late stage tumors. Antigen loss can represent a means for tumor escape from immune recognition, and a barrier to immunotherapy. However, since antigen-negative tumor phenotypes frequently result from reversible gene regulatory events, antigen enhancement represents a potential therapeutic opportunity. Accordingly, we have developed a cell-based assay to screen for compounds with the ability to enhance T-cell recognition of melanoma cells. This assay is dependent on augmentation of MelanA/MART-1 antigen presentation by a melanoma cell line (MU89). T-cell recognition is detected as interleukin-2 production by a Jurkat T cell transduced to express a T-cell receptor specific for an HLA-A2 restricted epitope of the Melan-A/MART-1 protein. This cellular assay was used to perform a pilot screen by using 480 compounds of known biological activity. From the initial proof-of-principle primary screen, eight compounds were identified as positive hits. A panel of secondary screens, including orthogonal assays, was used to validate the primary hits and eliminate false positives, and also to measure the comparative efficacy of the identified compounds. This cell-based assay, thus, yields consistent results applicable to the screening of larger libraries of compounds that can potentially reveal novel molecules which allow better recognition of treated tumors by T cells. C1 [Haggerty, Timothy J.] CytoCure LLC, Cummings Ctr 100, Beverly, MA 01915 USA. [Haggerty, Timothy J.; Kurnick, James T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Haggerty, TJ (reprint author), CytoCure LLC, Cummings Ctr 100, Suite 430C, Beverly, MA 01915 USA. EM thaggerty@cytocure.com FU NIH [R43-CA86153, R43-CA96271, R43-CA94700, R43-CA128309]; International Cancer Research Scholarship FX The authors would like to thank the members of the ICCB Longwood Screening Facility at Harvard Medical School; especially Caroline Shamu, Stewart Rudnicki, and Andrew Daab, for their assistance with our screen and in maintaining and providing the small molecule libraries used in this study. They would also like to thank James L. Riley (University of Pennsylvania, Philadelphia, PA) for assistance in lentiviral transduction of TCRs. This work was supported in part by grants from the NIH: R43-CA86153, R43-CA96271, R43-CA94700, R43-CA128309, and from the International Cancer Research Scholarship. NR 80 TC 4 Z9 4 U1 1 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-658X J9 ASSAY DRUG DEV TECHN JI ASSAY DRUG DEV. TECHNOL. PD APR PY 2012 VL 10 IS 2 BP 187 EP 201 DI 10.1089/adt.2011.0379 PG 15 WC Biochemical Research Methods; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 925WG UT WOS:000302792100007 PM 22085019 ER PT J AU Holmes, LB Westgate, MN AF Holmes, Lewis B. Westgate, Marie-Noel TI Using ICD-9 codes to establish prevalence of malformations in newborn infants SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE ICD-9 codes; malformations; exclusion criteria ID CONGENITAL-MALFORMATIONS; PRENATAL-DIAGNOSIS; PREDICTIVE-VALUE; DOWN-SYNDROME; DEFECTS; EPIDEMIOLOGY; TRENDS AB BACKGROUND The International Classification of Disease (ICD-9) codes are used to identify, after discharge, diagnoses from a review of the medical record and provide the basis for reimbursement. These codes have been used to establish the prevalence of malformations and to assess potential teratogens. We have analyzed the accuracy of codes 740 to 759.9 to identify newborn infants with malformations. METHODSThe diagnoses and ICD-9 codes in the medical records of 1000 consecutive live-born and stillborn infants were compared to the information provided in the medical records of those infants. RESULTSOne hundred twenty-seven of the 1000 infants had ICD-9 codes between 740 and 759.9. 67 (52.8%) of the codes identified minor features, such as birth marks and minor anomalies. Twenty-three (18.1%) of the codes designated a malformation and were correct. Two types of errors were identified in another 33 infants (26%) whose codes designated a malformation: either the pediatricians' notes described a less severe finding or the fact that there was no such abnormality. In addition, four malformed infants were missed in pregnancies that were either terminated electively or stillborn, as they did not have medical records. CONCLUSIONThe ICD-9 codes 740 to 759.9 identified accurately some infants (18%) with malformations, but identified incorrectly many others. The accuracy of the coding for identifying malformations would be improved if (1) the findings of the examining pediatricians were considered; (2) normal features of prematurity, such as patent foramen ovale and patent ductus arteriosus, were not considered malformations; (3) minor physical features were not assigned ICD-9 codes within the 740 to 759.9 sequence. Birth Defects Research (Part A) 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Holmes, Lewis B.] MassGen Hosp Children, Genet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Newborn Med, Act Malformat Surveillance Program, Boston, MA 02115 USA. RP Holmes, LB (reprint author), MassGen Hosp Children, Genet Unit, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM holmes.lewis@mgh.harvard.edu FU Center for Birth Defects Research and Prevention in the Massachusetts Department of Public Health, Boston, Massachusetts FX Supported by a subcontract from the Center for Birth Defects Research and Prevention in the Massachusetts Department of Public Health, Boston, Massachusetts NR 29 TC 11 Z9 11 U1 0 U2 3 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 APR PY 2012 VL 94 IS 4 BP 208 EP 214 DI 10.1002/bdra.23001 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 923GC UT WOS:000302606600002 PM 22451461 ER PT J AU Bhalla, K Hwang, BJ Dewi, RE Twaddel, W Goloubeva, OG Wong, KK Saxena, NK Biswal, S Girnun, GD AF Bhalla, Kavita Hwang, Bor Jang Dewi, Ruby E. Twaddel, William Goloubeva, Olga G. Wong, Kwok-Kin Saxena, Neeraj K. Biswal, Shyam Girnun, Geoffrey D. TI Metformin Prevents Liver Tumorigenesis by Inhibiting Pathways Driving Hepatic Lipogenesis SO CANCER PREVENTION RESEARCH LA English DT Article ID ACTIVATED PROTEIN-KINASE; FATTY-ACID SYNTHASE; ATP-CITRATE LYASE; BREAST-CANCER CELLS; HIGH-ENERGY DIET; HEPATOCELLULAR-CARCINOMA; UNITED-STATES; IN-VIVO; DIABETIC-PATIENTS; GROWTH AB A number of factors have been identified that increase the risk of hepatocellular carcinoma (HCC). Recently it has become appreciated that type II diabetes increases the risk of developing HCC. This represents a patient population that can be identified and targeted for cancer prevention. The biguanide metformin is a first-line therapy for the treatment of type II diabetes in which it exerts its effects primarily on the liver. A role of metformin in HCC is suggested by studies linking metformin intake for control of diabetes with a reduced risk of HCC. Although a number of preclinical studies show the anticancer properties of metformin in a number of tissues, no studies have directly examined the effect of metformin on preventing carcinogenesis in the liver, one of its main sites of action. We show in these studies that metformin protected mice against chemically induced liver tumors. Interestingly, metformin did not increase AMPK activation, often shown to be a metformin target. Rather metformin decreased the expression of several lipogenic enzymes and lipogenesis. In addition, restoring lipogenic gene expression by ectopic expression of the lipogenic transcription factor SREBP1c rescues metformin-mediated growth inhibition. This mechanism of action suggests that metformin may also be useful for patients with other disorders associated with HCC in which increased lipid synthesis is observed. As a whole these studies show that metformin prevents HCC and that metformin should be evaluated as a preventive agent for HCC in readily identifiable at-risk patients. Cancer Prev Res; 5(4); 544-52. (C) 2012 AACR. C1 [Bhalla, Kavita; Hwang, Bor Jang; Dewi, Ruby E.; Goloubeva, Olga G.; Saxena, Neeraj K.; Girnun, Geoffrey D.] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Twaddel, William] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Biswal, Shyam] Johns Hopkins Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. [Wong, Kwok-Kin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Girnun, GD (reprint author), Univ Maryland, Dept Biochem & Mol Biol, Greenebaum Canc Ctr, 655 W Baltimore St,BRB Room 10-039, Baltimore, MD 21201 USA. EM ggirnun@som.umaryland.edu OI wong, kwok kin/0000-0001-6323-235X FU University of Maryland Greenebaum Cancer Center CRF; NIDDK [DK064685] FX This work was supported by the University of Maryland Greenebaum Cancer Center CRF and in part by the NIDDK, grant# DK064685 to G.D. Girnun. NR 50 TC 65 Z9 67 U1 2 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD APR PY 2012 VL 5 IS 4 BP 544 EP 552 DI 10.1158/1940-6207.CAPR-11-0228 PG 9 WC Oncology SC Oncology GA 922TY UT WOS:000302572400009 PM 22467080 ER PT J AU Yurgelun, MB Goel, A Hornick, JL Sen, A Turgeon, DK Ruffin, MT Marcon, NE Baron, JA Bresalier, RS Syngal, S Brenner, DE Boland, CR Stoffel, EM AF Yurgelun, Matthew B. Goel, Ajay Hornick, Jason L. Sen, Ananda Turgeon, Danielle Kim Ruffin, Mack T. Marcon, Norman E. Baron, John A. Bresalier, Robert S. Syngal, Sapna Brenner, Dean E. Boland, C. Richard Stoffel, Elena M. TI Microsatellite Instability and DNA Mismatch Repair Protein Deficiency in Lynch Syndrome Colorectal Polyps SO CANCER PREVENTION RESEARCH LA English DT Article ID NONPOLYPOSIS COLON-CANCER; REDUCING MORBIDITY; TESTING STRATEGIES; GERMLINE MUTATION; YOUNG-PATIENTS; ADENOMAS; INDIVIDUALS; HOMOLOG; HNPCC; RECOMMENDATIONS AB Colorectal cancers associated with Lynch syndrome are characterized by deficient DNA mismatch repair (MMR) function. Our aim was to evaluate the prevalence of microsatellite instability (MSI) and loss of MMR protein expression in Lynch syndrome-associated polyps. Sixty-two colorectal polyps-37 adenomatous polyps, 23 hyperplastic polyps, and 2 sessile serrated polyps (SSP)-from 34 subjects with germline MMR gene mutations were tested for MSI using a single pentaplex PCR for five mononucleotide repeat microsatellite markers, and also for expression of MLH1, MSH2, MSH6, and PMS2 proteins by immunohistochemistry. High-level MSI (MSI-H) was seen in 15 of 37 (41%) adenomatous polyps, one of 23 (4%) hyperplastic polyps, and one of two (50%) SSPs. Loss of MMR protein expression was seen in 18 of 36 (50%) adenomatous polyps, zero of 21 hyperplastic polyps, and zero of two SSPs. Adenomatous polyps 8 mm or larger in size were significantly more likely to show MSI-H [OR, 9.98; 95% confidence interval (CI), 1.52-65.65; P = 0.02] and deficient MMR protein expression (OR, 3.17; 95% CI, 1.20-8.37; P = 0.02) compared with those less than 8 mm in size. All (six of six) adenomatous polyps 10 mm or larger in size showed both MSI-H and loss of MMR protein expression by immunohistochemistry. Our finding that the prevalence of MMR deficiency increases with the size of adenomatous polyps suggests that loss of MMR function is a late event in Lynch syndrome-associated colorectal neoplasia. Although testing large adenomatous polyps may be of value in the diagnostic evaluation of patients with suspected Lynch syndrome, the absence of an MMR-deficient phenotype in an adenoma cannot be considered as a strong evidence against Lynch syndrome, as it is with colorectal carcinomas. Cancer Prev Res; 5(4); 574-82. (C) 2012 AACR. C1 [Stoffel, Elena M.] Univ Michigan Hlth Syst, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Yurgelun, Matthew B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Hornick, Jason L.; Syngal, Sapna] Brigham & Womens Hosp, Boston, MA 02115 USA. [Syngal, Sapna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goel, Ajay; Boland, C. Richard] Baylor Univ, Med Ctr, Baylor Res Inst, Dallas, TX USA. [Goel, Ajay; Boland, C. Richard] Charles A Sammons Canc Ctr, Dallas, TX USA. [Turgeon, Danielle Kim; Ruffin, Mack T.; Marcon, Norman E.; Baron, John A.; Bresalier, Robert S.; Syngal, Sapna; Brenner, Dean E.] Early Detect Res Network GLNE EDRN, Great Lakes New England Clin Epidemiol & Validat, Ann Arbor, MI USA. [Brenner, Dean E.] VA Med Ctr, Ann Arbor, MI USA. [Marcon, Norman E.] Wellesley Site St Michaels Hosp, Toronto, ON, Canada. [Baron, John A.] Univ N Carolina, Chapel Hill, NC USA. [Bresalier, Robert S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Stoffel, EM (reprint author), Univ Michigan Hlth Syst, Div Gastroenterol, 1500 E Med Ctr Dr,Taubman Ctr 3912, Ann Arbor, MI 48109 USA. EM estoffel@med.umich.edu OI Ruffin, Mack/0000-0001-8336-478X FU NCI [CA 86400, CA72851-16]; NIH-NCI [K07 CA 120448-05]; American Society for Gastrointestinal Endoscopy ASGE [K24 113433] FX The study was supported by NCI grant CA 86400 Early Detection Research Network (D.E. Brenner), NIH-NCI K07 CA 120448-05 (E.M. Stoffel), American Society for Gastrointestinal Endoscopy ASGE 2006 Research Outcomes and Effectiveness Award (E.M. Stoffel), K24 113433 (S. Syngal), and NCI grant CA72851-16 (C.R. Boland and A. Goel) NR 41 TC 36 Z9 37 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD APR PY 2012 VL 5 IS 4 BP 574 EP 582 DI 10.1158/1940-6207.CAPR-11-0519 PG 9 WC Oncology SC Oncology GA 922TY UT WOS:000302572400012 PM 22262812 ER PT J AU Stevens, KN Fredericksen, Z Vachon, CM Wang, XS Margolin, S Lindblom, A Nevanlinna, H Greco, D Aittomaki, K Blomqvist, C Chang-Claude, J Vrieling, A Flesch-Janys, D Sinn, HP Wang-Gohrke, S Nickels, S Brauch, H Ko, YD Fischer, HP Schmutzler, RK Meindl, A Bartram, CR Schott, S Engel, C Godwin, AK Weaver, J Pathak, HB Sharma, P Brenner, H Muller, H Arndt, V Stegmaier, C Miron, P Yannoukakos, D Stavropoulou, A Fountzilas, G Gogas, HJ Swann, R Dwek, M Perkins, A Milne, RL Benitez, J Zamora, MP Perez, JIA Bojesen, SE Nielsen, SF Nordestgaard, BG Flyger, H Guenel, P Truong, T Menegaux, F Cordina-Duverger, E Burwinkel, B Marme, F Schneeweiss, A Sohn, C Sawyer, E Tomlinson, I Kerin, MJ Peto, J Johnson, N Fletcher, O Silva, ID Fasching, PA Beckmann, MW Hartmann, A Ekici, AB Lophatananon, A Muir, K Puttawibul, P Wiangnon, S Schmidt, MK Broeks, A Braaf, LM Rosenberg, EH Hopper, JL Apicella, C Park, DJ Southey, MC Swerdlow, AJ Ashworth, A Orr, N Schoemaker, MJ Anton-Culver, H Ziogas, A Bernstein, L Dur, CC Shen, CY Yu, JC Hsu, HM Hsiung, CN Hamann, U Dunnebier, T Rudiger, T Ulmer, HU Pharoah, PP Dunning, AM Humphreys, MK Wang, Q Cox, A Cross, SS Reed, MW Hall, P Czene, K Ambrosone, CB Ademuyiwa, F Hwang, H Eccles, DM Garcia-Closas, M Figueroa, JD Sherman, ME Lissowska, J Devilee, P Seynaeve, C Tollenaar, RAEM Hooning, MJ Andrulis, IL Knight, JA Glendon, G Mulligan, AM Winqvist, R Pylkas, K Jukkola-Vuorinen, A Grip, M John, EM Miron, A Alnaes, GG Kristensen, V Borresen-Dale, AL Giles, GG Baglietto, L McLean, CA Severi, G Kosel, ML Pankratz, VS Slager, S Olson, JE Radice, P Peterlongo, P Manoukian, S Barile, M Lambrechts, D Hatse, S Dieudonne, AS Christiaens, MR Chenevix-Trench, G Beesley, J Chen, XQ Mannermaa, A Kosma, VM Hartikainen, JM Soini, Y Easton, DF Couch, FJ AF Stevens, Kristen N. Fredericksen, Zachary Vachon, Celine M. Wang, Xianshu Margolin, Sara Lindblom, Annika Nevanlinna, Heli Greco, Dario Aittomaki, Kristiina Blomqvist, Carl Chang-Claude, Jenny Vrieling, Alina Flesch-Janys, Dieter Sinn, Hans-Peter Wang-Gohrke, Shan Nickels, Stefan Brauch, Hiltrud Ko, Yon-Dschun Fischer, Hans-Peter Schmutzler, Rita K. Meindl, Alfons Bartram, Claus R. Schott, Sarah Engel, Christoph Godwin, Andrew K. Weaver, JoEllen Pathak, Harsh B. Sharma, Priyanka Brenner, Hermann Mueller, Heiko Arndt, Volker Stegmaier, Christa Miron, Penelope Yannoukakos, Drakoulis Stavropoulou, Alexandra Fountzilas, George Gogas, Helen J. Swann, Ruth Dwek, Miriam Perkins, Annie Milne, Roger L. Benitez, Javier Pilar Zamora, Maria Arias Perez, Jose Ignacio Bojesen, Stig E. Nielsen, Sune F. Nordestgaard, Borge G. Flyger, Henrik Guenel, Pascal Therese Truong Menegaux, Florence Cordina-Duverger, Emilie Burwinkel, Barbara Marme, Frederick Schneeweiss, Andreas Sohn, Christof Sawyer, Elinor Tomlinson, Ian Kerin, Michael J. Peto, Julian Johnson, Nichola Fletcher, Olivia dos Santos Silva, Isabel Fasching, Peter A. Beckmann, Matthias W. Hartmann, Arndt Ekici, Arif B. Lophatananon, Artitaya Muir, Kenneth Puttawibul, Puttisak Wiangnon, Surapon Schmidt, Marjanka K. Broeks, Annegien Braaf, Linde M. Rosenberg, Efraim H. Hopper, John L. Apicella, Carmel Park, Daniel J. Southey, Melissa C. Swerdlow, Anthony J. Ashworth, Alan Orr, Nicholas Schoemaker, Minouk J. Anton-Culver, Hoda Ziogas, Argyrios Bernstein, Leslie Dur, Christina Clarke Shen, Chen-Yang Yu, Jyh-Cherng Hsu, Huan-Ming Hsiung, Chia-Ni Hamann, Ute Duennebier, Thomas Ruediger, Thomas Ulmer, Hans Ulrich Pharoah, Paul P. Dunning, Alison M. Humphreys, Manjeet K. Wang, Qin Cox, Angela Cross, Simon S. Reed, Malcom W. Hall, Per Czene, Kamila Ambrosone, Christine B. Ademuyiwa, Foluso Hwang, Helena Eccles, Diana M. Garcia-Closas, Montserrat Figueroa, Jonine D. Sherman, Mark E. Lissowska, Jolanta Devilee, Peter Seynaeve, Caroline Tollenaar, Rob A. E. M. Hooning, Maartje J. Andrulis, Irene L. Knight, Julia A. Glendon, Gord Mulligan, Anna Marie Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Grip, Mervi John, Esther M. Miron, Alexander Alnaes, Grethe Grenaker Kristensen, Vessela Borresen-Dale, Anne-Lise Giles, Graham G. Baglietto, Laura McLean, Catriona A. Severi, Gianluca Kosel, Matthew L. Pankratz, V. S. Slager, Susan Olson, Janet E. Radice, Paolo Peterlongo, Paolo Manoukian, Siranoush Barile, Monica Lambrechts, Diether Hatse, Sigrid Dieudonne, Anne-Sophie Christiaens, Marie-Rose Chenevix-Trench, Georgia Beesley, Jonathan Chen, Xiaoqing Mannermaa, Arto Kosma, Veli-Matti Hartikainen, Jaana M. Soini, Ylermi Easton, Douglas F. Couch, Fergus J. CA GENICA Network kConFab Investigators AOCS Grp TI 19p13.1 Is a Triple-Negative-Specific Breast Cancer Susceptibility Locus SO CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; COMMON VARIANTS; RISK-FACTORS; CONFER SUSCEPTIBILITY; 14Q24.1 RAD51L1; TUMOR SUBTYPES; BRCA1; POPULATION; CONSORTIUM; COMPLEX AB The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05-1.15; P = 3.49 x 10(-5)] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13-1.31; P = 2.22 x 10(-7)). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89-1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18-1.33; P = 3.31 x 10-(13)]. Thus, 19p13.1 is the first triple-negativespecific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. 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[Hatse, Sigrid; Dieudonne, Anne-Sophie; Christiaens, Marie-Rose] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium. [Chenevix-Trench, Georgia; Beesley, Jonathan; Chen, Xiaoqing; AOCS Grp] Queensland Inst Med Res, Herston, Qld 4006, Australia. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.; Soini, Ylermi] Univ Eastern Finland, Dept Pathol, Inst Clin Med, Kuopio, Finland. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.; Soini, Ylermi] Kuopio Univ Hosp, Bioctr Kuopio, SF-70210 Kuopio, Finland. RP Couch, FJ (reprint author), Mayo Clin, Dept Lab Med & Pathol, Stabile 2-42,200 1st St SW, Rochester, MN 55905 USA. EM couch.fergus@mayo.edu RI Shen, CY/F-6271-2010; Knight, Julia/A-6843-2012; Garcia-Closas, Montserrat /F-3871-2015; Hartikainen, Jaana/E-6256-2015; Vrieling, Alina/A-2725-2016; Bowtell, David/H-1007-2016; Brenner, Hermann/B-4627-2017; Verdrengh, Evelien/H-4571-2012; truong, therese/A-2837-2013; Kerin, Michael/D-6748-2013; Ekici, Arif/C-3971-2013; Andrulis, Irene/E-7267-2013; Radice, Paolo/O-3119-2013; manoukian, siranoush/E-7132-2017 OI ADEMUYIWA, FOLUSO/0000-0002-6766-2258; Giles, Graham/0000-0003-4946-9099; Arndt, Volker/0000-0001-9320-8684; Schoemaker, Minouk/0000-0001-8403-2234; Greco, Dario/0000-0001-9195-9003; Czene, Kamila/0000-0002-3233-5695; Rosenberg, Efraim/0000-0002-3859-6941; Cross, Simon/0000-0003-2044-1754; Lissowska, Jolanta/0000-0003-2695-5799; Dunning, Alison Margaret/0000-0001-6651-7166; Nevanlinna, Heli/0000-0002-0916-2976; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Yannoukakos, Drakoulis/0000-0001-7509-3510; Park, Daniel/0000-0002-6354-0931; Garcia-Closas, Montserrat /0000-0003-1033-2650; Bowtell, David/0000-0001-9089-7525; Brenner, Hermann/0000-0002-6129-1572; manoukian, siranoush/0000-0002-6034-7562 FU NIH [CA122340, RFA-CA-06-503, R01 CA77398, CA58860, CA92044]; SPORE [CA116201]; Komen Foundation for the Cure; Breast Cancer Research Foundation (BCRF); Cancer Research UK [C1287/A10118, C1287/A12014]; European Community [223175, HEALTH-F2-2009-223175]; European Union COST [BM0606]; Institute for Cancer Studies; ABCS; Dutch Cancer Society [NKI 2009-4363, NKI 2007-3839]; Dutch National Genomics Initiative; ACP: Breast Cancer Research Trust, UK; National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre; Guy's & St. Thomas' NHS Foundation; Oxford Biomedical Research Centre; ABCFS; NC-BCFR; OFBCR; National Cancer Institute; Cancer Care Ontario [U01 CA69467]; Northern California Cancer Center [U01 CA69417]; University of Melbourne [U01 CA69638]; ABCFS: National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); Victorian Breast Cancer Research Consortium; Asociacion Espanola Contra el Cancer; Fondo de Investigacion Sanitario [PI081583, PI081120]; The California Teachers Study; California Breast Cancer Act of 1993; Lon V Smith Foundation [LVS39420]; California Breast Cancer Research Fund [97-10500]; UCIBCS; ESTHER; Baden Wurttemberg Ministry of Science; German Cancer Aid (Deutsche Krebshilfe) FX This work was supported by the NIH grant CA122340, a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), the Komen Foundation for the Cure and the Breast Cancer Research Foundation (BCRF); the BCAC is funded by Cancer Research UK (C1287/A10118 and C1287/A12014), by the European Community's Seventh Framework Programme under grant agreement no. 223175 (HEALTH-F2-2009-223175; COGS), and by the European Union COST programme (BM0606). D.F. Easton is a Principal Research Fellow of Cancer Research UK; SBCS: Breast Cancer Campaign (2004 Nov 49 to A. Cox) and Yorkshire Cancer Research Core Funding (Institute for Cancer Studies); ABCS: Dutch Cancer Society grant (NKI 2009-4363 and NKI 2007-3839 to M.K. Schmidt) and the Dutch National Genomics Initiative; ACP: Breast Cancer Research Trust, UK. E. Sawyer is funded by National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London. I. Tomlinson is funded by the Oxford Biomedical Research Centre; ABCFS, NC-BCFR and OFBCR: National Cancer Institute, NIH under RFA-CA-06-503, and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Northern California Cancer Center (U01 CA69417), University of Melbourne (U01 CA69638); ABCFS: National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia), and the Victorian Breast Cancer Research Consortium. J.L. Hopper is a National Health and Medical Research Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research Consortium Group Leader. M.C. Southey is an NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader; CNIO-BCS: Genome Spain Foundation, the Red Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espanola Contra el Cancer and the Fondo de Investigacion Sanitario (PI081583 and PI081120); The California Teachers Study: California Breast Cancer Act of 1993, NIH (R01 CA77398), the Lon V Smith Foundation [LVS39420]), and the California Breast Cancer Research Fund (contract 97-10500); UCIBCS: NIH (CA58860 and CA92044) and the Lon V Smith Foundation (LVS39420); ESTHER: Baden Wurttemberg Ministry of Science, Research and Arts, and the VERDI study supported by a grant from the German Cancer Aid (Deutsche Krebshilfe); GENICA: Federal Ministry of Education and Research (BMBF) Germany (01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114), the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, and the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany: KBCP: Finnish Cancer Society, the Academy of Finland (grant number 127220), the special Government Funding (EVO) of Kuopio University Hospital (grant number 5654113 and 5501) and by the strategic funding of the University of Eastern Finland; OBCS: Finnish Cancer Foundation, the Academy of Finland, the University of Oulu, the Oulu University Hospital and Biocenter Oulu; RPCI: P30 grant to RPCI (CA016056-32); The Breakthrough Generations Study: Breakthrough Breast Cancer and the Institute of Cancer Research (ICR).; ICR acknowledges NHS funding to the NIHR Biomedical Research Centre; PBCS: Intramural Research Funds of the National Cancer Institute, Bethesda, MD; HEBCS: Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation; MARIE: Deutsche Krebshilfe e.V., grant number 70-2892-BR I, the Hamburg Cancer Society, the German Cancer Research Center (DKFZ), and the Federal Ministry of Education and Research (BMBF) Germany grant 01KH0402; GESBC: Deutsche Krebshilfe e. V. (70492) and the state of Baden-Wurttemberg through the Medical Faculty of the University of Ulm (P.685); BSUCH: Dietmar Hopp Foundation, the German Cancer Research Center, DKFZ, and the Helmholtz association; GC-HBOC: Deutsche Krebshilfe (107054), the Center of Molecular Medicine, Cologne, the German Cancer Research Center, DKFZ, and the Helmholtz society; BBCS: Cancer Research UK, Breakthrough Breast Cancer and the National Cancer Research Network (NCRN); kConFab: National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, the Cancer Foundation of Western Australia, and Cancer Australia #628333; LMBC: 'Stichting tegen Kanker' (232-2008 and 196-2010); MCCS: Australian National Health and Medical Research Council (grants #209057, 251533, 396414, and 504711), Cancer Council Victoria, and VicHealth; ORIGO: Dutch Cancer Society; SEARCH: Cancer Research UK (C8197/A10123, C8197/A10123, and C490/A10124). A.M. Dunning was supported by Cancer Research UK grant (C8197/A10865) and by the Joseph Mitchell Fund; FCCC: NIH (U01 CA69631, 5U01 CA113916 to A.K. Godwin), the Eileen Stein Jacoby Fund, The University of Kansas Cancer Center, and the Kansas Bioscience Authority Eminent Scholar Program. A.K. Godwin is the Chancellors Distinguished Chair in Biomedical Sciences endowed Professor. NR 24 TC 42 Z9 43 U1 1 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2012 VL 72 IS 7 BP 1795 EP 1803 DI 10.1158/0008-5472.CAN-11-3364 PG 9 WC Oncology SC Oncology GA 922MO UT WOS:000302551800022 PM 22331459 ER PT J AU Pham, H Robinson-Cohen, C Biggs, ML Ix, JH Mukamal, KJ Fried, LF Kestenbaum, B Siscovick, DS de Boer, IH AF Pham, Hien Robinson-Cohen, Cassianne Biggs, Mary L. Ix, Joachim H. Mukamal, Kenneth J. Fried, Linda F. Kestenbaum, Bryan Siscovick, David S. de Boer, Ian H. TI Chronic Kidney Disease, Insulin Resistance, and Incident Diabetes in Older Adults SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; IMPAIRED GLUCOSE-TOLERANCE; GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR-DISEASE; RISK-FACTORS; ASYMMETRIC DIMETHYLARGININE; CYSTATIN-C; VITAMIN-D; SECRETION; HEALTH AB Background and objectives Insulin resistance is a complication of advanced CKD. Insulin resistance is less well characterized in earlier stages of CKD. The response of the pancreatic beta cell, effects on glucose tolerance, and risk of diabetes are not clear. Design, setting, participants, & measurements The Cardiovascular Health Study included 4680 adults without baseline diabetes. The Chronic Kidney Disease Epidemiology Collaboration creatinine equation was used to obtain the estimated GFR (eGFR). Insulin resistance was evaluated as fasting insulin concentration. The insulin sensitivity index, beta cell function, and glucose tolerance were assessed by oral glucose tolerance testing. Incident diabetes was defined as fasting glucose >= 126 mg/dl, nonfasting glucose >= 200 mg/dl, or use of glucose-lowering medications. Results Mean age was 72.5 years (range, 65-98 years). Mean eGFR was 72.2 (SD 17.1) ml/min per 1.73 m(2). After adjustment, each 10 ml/min per 1.73 m(2) lower eGFR was associated with a 2.2% higher fasting insulin concentration (95% confidence interval [CI], 1.4%, 2.9%; P<0.001) and a 1.1% lower insulin sensitivity index (95% Cl, 0.03%, 2.2%; P=0.04). Surprisingly, eGFR was associated with an augmented beta cell function index (P<0.001), lower 2-hour glucose concentration (P=0.002), and decreased risk of glucose intolerance (P=0.006). Over a median 12 years' follow-up, 437 participants (9.3%) developed diabetes. eGFR was not associated with the risk of incident diabetes. Conclusions Among older adults, lower eGFR was associated with insulin resistance. However, with lower eGFR, beta cell function was appropriately augmented and risks of impaired glucose tolerance and incident diabetes were not increased. Clin J Am Soc Nephrol 7: 588-594, 2012. doi: 10.2215/CJN.11861111 C1 [Pham, Hien; Kestenbaum, Bryan; de Boer, Ian H.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Pham, Hien; Kestenbaum, Bryan; de Boer, Ian H.] Univ Washington, Kidney Res Inst, Dept Med, Seattle, WA 98195 USA. [Robinson-Cohen, Cassianne; Kestenbaum, Bryan; Siscovick, David S.; de Boer, Ian H.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Biggs, Mary L.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Mukamal, Kenneth J.] Harvard Univ, Sch Med, Boston, MA USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Fried, Linda F.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Fried, Linda F.] Univ Pittsburgh, Sch Med, Renal Electrolytr Div, Pittsburgh, PA USA. [Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med & Epidemiol, Seattle, WA 98195 USA. RP Pham, H (reprint author), Univ Washington, Div Nephrol, 1959 NE Pacific St, Seattle, WA 98195 USA. EM hiena@uw.edu OI Robinson-Cohen, Cassianne/0000-0003-4783-7046 FU National Heart, Lung, and Blood Institute [HL080295, N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133]; National Institute on Aging [AG-023629, AG-15928, AG-20098, AG-027058]; National Institute of Diabetes and Digestive and Kidney Diseases [DK-087726] FX This research was supported by the National Heart, Lung, and Blood Institute (Grant HL080295 and Contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, and N01-HC-45133), with additional contributions from the National Institute of Neurological Disorders and Stroke. Additional support was provided by the National Institute on Aging (Grants AG-023629, AG-15928, AG-20098, and AG-027058) and the National Institute of Diabetes and Digestive and Kidney Diseases (Grant DK-087726). NR 44 TC 18 Z9 19 U1 1 U2 2 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 APR PY 2012 VL 7 IS 4 BP 588 EP 594 DI 10.2215/CJN.11861111 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 918WK UT WOS:000302281900011 PM 22383749 ER PT J AU Carter, CE Gansevoort, RT Scheven, L Lambers Heerspink, HJ Shlipak, MG de Jong, PE Ix, JH AF Carter, Caitlin E. Gansevoort, Ronald T. Scheven, Lieneke Lambers Heerspink, Hiddo J. Shlipak, Michael G. de Jong, Paul E. Ix, Joachim H. TI Influence of Urine Creatinine on the Relationship between the Albumin-to-Creatinine Ratio and Cardiovascular Events SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; ABNORMAL DIURNAL RHYTHM; MUSCLE MASS; BLOOD-PRESSURE; ALBUMIN/CREATININE RATIO; NONDIABETIC INDIVIDUALS; EXCRETION; RISK; MICROALBUMINURIA; DISEASE AB Background and objectives In the albumin-to-creatinine ratio (spot-ACR), urine creatinine corrects for tonicity but also reflects muscle mass. Low muscle mass is associated with cardiovascular disease (CVD). We hypothesized that the spot-ACR would be higher in women, lower-weight persons, and older individuals, independent of timed urine albumin excretion (24hr-UAE), and accordingly, that spot-ACR would be more strongly associated with CVD events than 24hr-UAE in these subgroups. Design, setting, participants, & methods 2627 PREVEND (Prevention of Renal and Vascular End-stage Disease) participants with 24hr-UAE <30 mg/d were followed for CVD events for 11 years. Cox regression evaluated associations of spot-ACR and 24hr-UAE with CVD events by sex, weight, and age. Results Female sex (26%), lower weight (2% per 5 kg), and older age (4% per 5 years) were associated with higher spot-ACR independent of 24hr-UAE (P<0.001). Spot urine albumin concentration (hazard ratio [HR], 1.26 per In-SD higher) and 1/spot urine creatinine concentration (HR, 1.16 per In-SD higher) were associated with CVD events. Spot-ACR was more strongly associated with CVD events than either component of the ratio (HR, 1.41 per In-SD higher). Associations of spot-ACR >= 10 mg/g versus less (FIR, 2.33) and 24hr-UAE >= 10 mg/d versus less (HR, 2.09) with CVD events were similar, and there were no significant differences across subgroups (P for interactions >0.06). Conclusions In community-living individuals with 24hr-UAE <30 mg/d, spot-ACR is higher in women, older persons, and lower-weight persons, independent of 24hr-UAE. Low spot urine creatinine is associated with CVD risk, but high urine albumin is a stronger determinant of the association of spot-ACR with CVD than is low urine creatinine. Clin J Am Soc Nephrol 7: 595-603, 2012. doi: 10.2215/CJN.09300911 C1 [Carter, Caitlin E.; Ix, Joachim H.] Univ Calif San Diego, Div Nephrol & Hypertens, Dept Med, San Diego, CA 92161 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Prevent Med, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Gansevoort, Ronald T.; Scheven, Lieneke; Lambers Heerspink, Hiddo J.; de Jong, Paul E.] Univ Groningen, Univ Med Ctr Groningen, Div Nephrol, Dept Internal Med, Groningen, Netherlands. [Shlipak, Michael G.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Ctr, San Diego, CA USA. RP Ix, JH (reprint author), Univ Calif San Diego, Div Nephrol & Hypertens, Dept Med, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu RI Lambers Heerspink, Hiddo/K-3358-2014 OI Lambers Heerspink, Hiddo/0000-0002-3126-3730 FU National Heart, Lung, and Blood Institute [T32 HL007261, R01HL096851]; Dutch Kidney Foundation; Veterans Affairs San Diego Healthcare System FX This study was supported by grants T32 HL007261 (C.E.C.) and R01HL096851 (J.H.I.) from the National Heart, Lung, and Blood Institute. The PREVEND Study was made possible by grants from the Dutch Kidney Foundation. Dade Behring (Marburg, Germany) generously supplied equipment (Behring Nephelometer II) and reagents for nephelometric measurement of urinary albumin concentration. This material is the result of work supported with resources of the Veterans Affairs San Diego Healthcare System. NR 36 TC 12 Z9 12 U1 1 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD APR PY 2012 VL 7 IS 4 BP 595 EP 603 DI 10.2215/CJN.09300911 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 918WK UT WOS:000302281900012 PM 22383750 ER PT J AU Burnett-Bowie, SAM Leder, BZ Henao, MP Baldwin, CM Hayden, DL Finkelstein, JS AF Burnett-Bowie, Sherri-Ann M. Leder, Benjamin Z. Henao, Maria P. Baldwin, Chantel M. Hayden, Douglas L. Finkelstein, Joel S. TI Randomized Trial Assessing the Effects of Ergocalciferol Administration on Circulating FGF23 SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID VITAMIN-D SUPPLEMENTATION; FIBROBLAST GROWTH FACTOR-23; X-LINKED HYPOPHOSPHATEMIA; HEALTHY-MEN; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; CALCIUM SUPPLEMENTATION; REPLACEMENT THERAPY; 25-HYDROXYVITAMIN D; MAJOR METABOLITES; DIETARY PHOSPHATE AB Background and objectives Fibroblast growth factor 23 is a phosphate- and vitamin D-regulating hormone. The objective of this study was to determine the effect of ergocalciferol administration on fibroblast growth factor 23 levels in healthy vitamin D deficient subjects. Design, setting, participants, & measurements In this 12-week trial conducted in a clinical research center, 18- to 45-year-old subjects (n=90) with 25-hydroxyvitamin D levels <= 20 ng/ml (by chemiluminescent immunoassay) were randomized to weekly ergocalciferol treatment of 50,000 international units or placebo, while consuming a self-selected diet. Changes in fibroblast growth factor 23, 25-hydroxyvitamin D (by liquid chromatography/tandem mass spectroscopy), 1,25-dihydroxyvitamin D, parathyroid hormone, and serum phosphate were measured. Results Mean 25-hydroxyvitamin D (P<0.0001), 1,25-dihydroxyvitamin D (P=0.01), and fibroblast growth factor 23 (P=0.003) increased in the treatment versus placebo group. In the treatment group, 25-hydroxyvitamin D increased from 18 +/- 7 to 40 +/- 12 ng/ml at week 4 (P<0.0001) and remained stable at 43 +/- 12 ng/ml at week 12 (P<0.0001); 1,25-dihydroxyvitamin D increased from 42 +/- 17 to 52 +/- 18 pg/ml at week 4 (P<0.001) and then remained stable, and fibroblast growth factor 23 increased from 43 +/- 17 to 60 +/- 33 pg/ml at week 8 (P=0.001) and 74 +/- 42 pg/ml at week 12 (P<0.0001). Urinary phosphate excretion increased within the treatment group, but parathyroid hormone and serum phosphate were unchanged. Conclusions Ergocalciferol administration increases circulating fibroblast growth factor 23. When measuring fibroblast growth factor 23, concurrent 25-hydroxyvitamin D measurements should be obtained, because vitamin D deficiency may lower circulating fibroblast growth factor 23 levels. Clin J Am Soc Nephrol 7: 624-631, 2012. doi: 10.2215/CJN.10030911 C1 [Burnett-Bowie, Sherri-Ann M.; Leder, Benjamin Z.; Henao, Maria P.; Baldwin, Chantel M.; Hayden, Douglas L.; Finkelstein, Joel S.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Burnett-Bowie, SAM (reprint author), 50 Blossom St,Thier 1051, Boston, MA 02114 USA. EM sburnett-bowie@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X FU National Institutes of Health [K23-DK-073356]; Harvard Clinical and Translational Science Center from the National Center for Research Resources [M01-RR-01066]; Massachusetts General Hospital; Boston Area Diabetes and Endocrinology Research Center; Harvard Medical School Office for Diversity and Community Partnership FX We are indebted to our funding sources: National Institutes of Health Grant K23-DK-073356 (to S.M.B.), Harvard Clinical and Translational Science Center from the National Center for Research Resources Grant M01-RR-01066, Massachusetts General Hospital Physician-Scientist Development Award (to S.M.B.), Boston Area Diabetes and Endocrinology Research Center Grant (to S.M.B.), and the Harvard Medical School Office for Diversity and Community Partnership Award (to S.M.B.). NR 49 TC 21 Z9 21 U1 0 U2 0 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 APR PY 2012 VL 7 IS 4 BP 624 EP 631 DI 10.2215/CJN.10030911 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 918WK UT WOS:000302281900016 PM 22300739 ER PT J AU Kraut, JA Madias, NE AF Kraut, Jeffrey A. Madias, Nicolaos E. TI Differential Diagnosis of Nongap Metabolic Acidosis: Value of a Systematic Approach SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID RENAL TUBULAR-ACIDOSIS; URINE OSMOLAL GAP; SERUM ELECTROLYTE PATTERNS; ANION GAP; BASE DISTURBANCES; AMMONIUM-CHLORIDE; EXCRETION; FAILURE; DISEASE; PCO2 AB Nongap metabolic acidosis is a common form of both acute and chronic metabolic acidosis. Because derangements in renal acid-base regulation are a common cause of nongap metabolic acidosis, studies to evaluate renal acidification often serve as the mainstay of differential diagnosis. However, in many cases, information obtained from the history and physical examination, evaluation of the electrolyte pattern (to determine if a nongap acidosis alone or a combined nongap and high anion gap metabolic acidosis is present), and examination of the serum potassium concentration (to characterize the disorder as hyperkalemic or hypokalemic in nature) is sufficient to make a presumptive diagnosis without more sophisticated studies. If this information proves insufficient, indirect estimates or direct measurement of urinary NH4+ concentration, measurement of urine pH, and assessment of urinary HCO3- excretion can help in establishing the diagnosis. This review summarizes current information concerning the pathophysiology of this electrolyte pattern and the value and limitations of all of the diagnostic studies available. It also provides a systematic and cost-effective approach to the differential diagnosis of nongap metabolic acidosis. Clin J Am Soc Nephrol 7: 671-679, 2012. doi: 10.2215/CJN.09450911 C1 [Kraut, Jeffrey A.] Vet Adm Greater Angeles Healthcare Syst VHAGLA, Med Res Serv, Los Angeles, CA USA. [Madias, Nicolaos E.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Madias, Nicolaos E.] St Elizabeths Med Ctr, Div Nephrol, Dept Med, Boston, MA USA. [Kraut, Jeffrey A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kraut, Jeffrey A.] Univ Calif Los Angeles, Membrane Biol Lab, Los Angeles, CA 90095 USA. [Kraut, Jeffrey A.] Vet Adm Greater Los Angeles Healthcare Syst VHAGL, Div Nephrol, Los Angeles, CA USA. RP Kraut, JA (reprint author), VHAGLA Healthcare Syst, Div Nephrol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkraut@ucla.edu FU Veterans Administration FX This work is supported in part by funds from the Veterans Administration. NR 54 TC 6 Z9 6 U1 2 U2 8 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 APR PY 2012 VL 7 IS 4 BP 671 EP 679 DI 10.2215/CJN.09450911 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 918WK UT WOS:000302281900022 PM 22403272 ER PT J AU Kim, HT Gray, R AF Kim, Haesook Teresa Gray, Robert TI Three-component cure rate model for nonproportional hazards alternative in the design of randomized clinical trials SO CLINICAL TRIALS LA English DT Article ID SAMPLE-SIZE; CONDITIONAL POWER; SURVIVAL AB Background Cure rate models have been extensively studied and widely used in time-to-event data in cancer clinical trials. Purpose Although cure rate models based on the generalized exponential distribution have been developed, they have not been used in the design of randomized cancer clinical trials, which instead have relied exclusively on two-component exponential cure rate model with a proportional hazards (PH) alternative. In some studies, the efficacy of the experimental treatment is expected to emerge some time after randomization. Since this does not conform to a PH alternative, such studies require a more flexible model to describe the alternative hypothesis. Methods In this article, we report the study design of a phase III clinical trial of acute myeloid leukemia using a three-component exponential cure rate model to reflect the alternative hypothesis. A newly developed power calculation program that does not require PH assumption was used. Results Using a custom-made three-component cure rate model as an alternative hypothesis, the proposed sample size was 409, compared with a sample size of 209 under the assumption of exponential distribution and 228 under the PH alternative. A simulation study was performed to present the degree of power loss when the alternative hypothesis is not appropriately specified. Limitations The power calculation program used in this study is for a single analysis and does not account for group sequential tests in phase III trials. However, the loss in power is small, and this was handled by inflating the sample size by 5%. Conclusion Misspecification of the alternative hypothesis can result in a seriously underpowered study. We report examples of clinical trials that required a custom-made alternative hypothesis to reflect a later indication of experimental treatment efficacy. The proposed three-component cure rate model could be very useful for specifying non-PH alternative. Clinical Trials 2011; 9: 155-163.http://ctj.sagepub.com C1 [Kim, Haesook Teresa; Gray, Robert] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Kim, Haesook Teresa; Gray, Robert] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. RP Kim, HT (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM kim.haesook@jimmy.harvard.edu FU NIH from the National Cancer Institute [CA142106-06A2]; National Institute of Allergy and Infectious Diseases [AI029530] FX This research was supported in part by two NIH grants: CA142106-06A2 from the National Cancer Institute and AI029530 from the National Institute of Allergy and Infectious Diseases (HTK). NR 18 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD APR PY 2012 VL 9 IS 2 BP 155 EP 163 DI 10.1177/1740774512436614 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 923RN UT WOS:000302636500002 PM 22353928 ER PT J AU Beauharnais, CC Larkin, ME Zai, AH Boykin, EC Luttrell, J Wexler, DJ AF Beauharnais, Catherine C. Larkin, Mary E. Zai, Adrian H. Boykin, Emily C. Luttrell, Jennifer Wexler, Deborah J. TI Efficacy and cost-effectiveness of an automated screening algorithm in an inpatient clinical trial SO CLINICAL TRIALS LA English DT Article ID HOSPITAL INFORMATION-SYSTEMS; IMPROVING PATIENT RECRUITMENT; PRIMARY-CARE; ROUTINE DATA; PARTICIPATION AB Introduction Screening and recruitment for clinical trials can be costly and time-consuming. Inpatient trials present additional challenges because enrollment is time sensitive based on length of stay. We hypothesized that using an automated prescreening algorithm to identify eligible subjects would increase screening efficiency and enrollment and be cost-effective compared to manual review of a daily admission list. Methods Using a before-and-after design, we compared time spent screening, number of patients screened, enrollment rate, and cost-effectiveness of each screening method in an inpatient diabetes trial conducted at Massachusetts General Hospital. Manual chart review (CR) involved reviewing a daily list of admitted patients to identify eligible subjects. The automated prescreening (APS) method used an algorithm to generate a daily list of patients with glucose levels >= 180 mg/dL, an insulin order, and/or admission diagnosis of diabetes mellitus. The census generated was then manually screened to confirm eligibility and eliminate patients who met our exclusion criteria. We determined rates of screening and enrollment and cost-effectiveness of each method based on study sample size. Results Total screening time (prescreening and screening) decreased from 4 to 2 h, allowing subjects to be approached earlier in the course of the hospital stay. The average number of patients prescreened per day increased from 13 +/- 4 to 30 +/- 16 (P < 0.0001). Rate of enrollment increased from 0.17 to 0.32 patients per screening day. Developing the computer algorithm added a fixed cost of US$3000 to the study. Based on our screening and enrollment rates, the algorithm was cost-neutral after enrolling 12 patients. Larger sample sizes further favored screening with an algorithm. By contrast, higher recruitment rates favored individual CR. Limitations Because of the before-and-after design of this study, it is possible that unmeasured factors contributed to increased enrollment. Conclusion Using a computer algorithm to identify eligible patients for a clinical trial in the inpatient setting increased the number of patients screened and enrolled, decreased the time required to enroll them, and was less expensive. Upfront investment in developing a computerized algorithm to improve screening may be cost-effective even for relatively small trials, especially when the recruitment rate is expected to be low. Clinical Trials 2012; 9: 198-203. http://ctj.sagepub.com C1 [Wexler, Deborah J.] Massachusetts Gen Hosp, MGH Diabet Unit, Ctr Diabet, Boston, MA 02114 USA. [Larkin, Mary E.; Zai, Adrian H.; Wexler, Deborah J.] Harvard Univ, Sch Med, Boston, MA USA. [Zai, Adrian H.; Luttrell, Jennifer] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. RP Wexler, DJ (reprint author), Massachusetts Gen Hosp, MGH Diabet Unit, Ctr Diabet, Bulfinch 408,55 Fruit St, Boston, MA 02114 USA. EM dwexler@partners.org OI Zai, Adrian/0000-0002-2972-6839 FU National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK 080 228] FX This research study was funded by a Career Development Award from the National Institute of Diabetes and Digestive and Kidney Diseases to DJW (K23 DK 080 228). NR 24 TC 9 Z9 9 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD APR PY 2012 VL 9 IS 2 BP 198 EP 203 DI 10.1177/1740774511434844 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 923RN UT WOS:000302636500006 PM 22308560 ER PT J AU Pianykh, OS AF Pianykh, Oleg S. TI Perfusion linearity and its applications in perfusion algorithm analysis SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article DE Perfusion; Deconvolution; TSVD; Regularization; Computed tomography ID CEREBRAL-BLOOD-FLOW; INDEPENDENT COMPONENT ANALYSIS; SINGULAR-VALUE DECOMPOSITION; RESIDUE FUNCTION; DECONVOLUTION; MRI; CT; REGULARIZATION; RESOLUTION; TIME AB Perfusion analysis computes blood flow parameters (blood volume, blood flow, and mean transit time) from the observed flow of a contrast agent passing through the patient's vascular system. Perfusion deconvolution has been widely accepted as the principal numerical tool for perfusion analysis, and is used routinely in clinical applications. The extensive use of perfusion in clinical decision-making makes numerical stability and robustness of perfusion computations vital for accurate diagnostics and patient safety. The main goal of this paper is to propose a novel approach for validating numerical properties of perfusion algorithms. The approach is based on the Perfusion Linearity Property (PLP), which is fundamental to virtually all perfusion data processing. PLP allows one to study perfusion values as weighted averages of the original imaging data. This, in turn, uncovers hidden problems with the existing perfusion techniques, and may be used to suggest more reliable computational approaches and methodology. (C) 2011 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, BIDMC, Boston, MA 02215 USA. RP Pianykh, OS (reprint author), Harvard Univ, Sch Med, BIDMC, 330 Brookline Ave, Boston, MA 02215 USA. EM opianykh@bidmc.harvard.edu RI Pianykh, Oleg/N-2456-2015 OI Pianykh, Oleg/0000-0002-9107-5432 NR 23 TC 1 Z9 1 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-6111 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD APR PY 2012 VL 36 IS 3 BP 204 EP 214 DI 10.1016/j.compmedimag.2011.08.001 PG 11 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 920UK UT WOS:000302433300003 PM 21871781 ER PT J AU Shurin, MR Naiditch, H Gutkin, DW Umansky, V Shurin, GV AF Shurin, M. R. Naiditch, H. Gutkin, D. W. Umansky, V. Shurin, G. V. TI ChemoImmunoModulation: Immune Regulation by the Antineoplastic Chemotherapeutic Agents SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE Chemotherapy; chemomodulation; chemoimmunomodulation; immunostimulation; immunosuppression; paclitaxel ID SUPPRESSOR T-CELLS; LOW-DOSE CYCLOPHOSPHAMIDE; ANTIGEN-PROCESSING MACHINERY; ACUTE LYMPHOBLASTIC-LEUKEMIA; ADVANCED BREAST-CANCER; VIRUS-INDUCED LYMPHOMA; HUMAN DENDRITIC CELLS; ADOPTIVE IMMUNOTHERAPY; MEDIATED-IMMUNITY; ANTICANCER DRUGS AB Since 1948, when Farber et al. introduced aminopterin, the first chemotherapeutic agent, more than 100 such agents have come into use. Initially, antitumor chemotherapies were thought to produce only antiproliferative or cytotoxic effects on dividing tumor cells as it was often associated with the damage to healthy tissues and the development of resistant tumor clones. However, that view has been changing as a consequence of recent demonstrations that several antineoplastic drugs, even at low doses, have antiangiogenic and sometimes immunomodulating effects. In addition, new studies indicate that lowering the dose of conventional cytotoxic agents and combining chemotherapy with other modalities may not only decrease the toxicity of conventional chemotherapy, but also up-regulate the efficacy of different anticancer therapies. Giving chemotherapy in this manner has several potential advantages, including impediment of the onset of mutation-dependent mechanisms of acquired drug resistance and increase in the efficacy and durability of combinatorial therapeutic modalities. Certain "immunogenic" forms of cancer chemotherapy may cause indirect activation of immune cells due to the accessibility of tumor antigens and certain "danger" signals. Furthermore, new findings indicate that several chemotherapeutic agents can directly activate immune cells when used in ultra low noncytotoxic concentrations, the new phenomenon that was termed chemoimmunomodulation. The goal of this review is to analyze the immune modulating properties of antineoplastic chemotherapeutic agents and present new evidence of the immunostimulating potentials of several agents used in low and ultra low nontoxic doses. Therapeutic potentials of combined chemo-immunotherapeutic regimens have been extensively reviewed in a variety of recent publications and will not be discussed. C1 [Shurin, M. R.; Naiditch, H.; Gutkin, D. W.; Shurin, G. V.] Univ Pittsburgh, Dept Pathol, Med Ctr, Pittsburgh, PA USA. [Shurin, M. R.] Univ Pittsburgh, Dept Immunol, Med Ctr, Pittsburgh, PA USA. [Gutkin, D. W.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Umansky, V.] German Canc Res Ctr, Skin Canc Unit, D-6900 Heidelberg, Germany. [Umansky, V.] Univ Hosp Mannheim, Heidelberg, Germany. RP Shurin, MR (reprint author), UPMC, Dept Pathol, 3550 Terrace St,Scaife Hall S735, Pittsburgh, PA 15261 USA. EM shurinmr@upmc.edu FU NIH NCI [RO1 CA154369]; Dr. Mildred Scheel Foundation [108992]; Helmholtz Association within the Helmholtz Alliance on Immunotherapy of Cancer FX This work was supported by the NIH NCI RO1 CA154369 grant (M. R. S.), Dr. Mildred Scheel Foundation for Cancer Research Grant 108992 (V. U.), and the Initiative and Networking Fund of the Helmholtz Association within the Helmholtz Alliance on Immunotherapy of Cancer (V. U.). NR 135 TC 15 Z9 15 U1 0 U2 9 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD APR PY 2012 VL 19 IS 12 BP 1792 EP 1803 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 925VD UT WOS:000302789000007 PM 22414087 ER PT J AU Wilson, LS Pregenzer, M Basu, R Bertenthal, D Torres, J Asgari, M Chren, MM AF Wilson, Leslie S. Pregenzer, Mark Basu, Rituparna Bertenthal, Daniel Torres, Jeanette Asgari, Maryam Chren, Mary-Margaret TI Fee Comparisons of Treatments for Nonmelanoma Skin Cancer in a Private Practice Academic Setting SO DERMATOLOGIC SURGERY LA English DT Article ID BASAL-CELL CARCINOMA; MOHS MICROGRAPHIC SURGERY; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; SURGICAL EXCISION; FOLLOW-UP; FACE; COST; MANAGEMENT; CARE AB OBJECTIVE To compare fees for biopsy, treatment procedure, repair, and 2-month follow-up for nonmelanoma skin cancer (NMSC) treatments: electrodesiccation and curettage (ED&C), excision, and Mohs micrographic surgery (MMS). METHODS A cost comparison of 936 primary NMSCs diagnosed in 1999/2000 at a University affiliated dermatology practice. Clinical data was from medical record review. 2007 Medicare Fee Schedule costs determined fees for surgical care. Pearson chi-square tests, t-tests and analysis of variance compared fee differences. Linear regression determined independent effects of tumor and treatment characteristics on fees. RESULTS Mean fees/lesion were $463 for ED&C, $1,222 for excision, and $2,085 for MMS (p < .001). For all treatments, primary procedure costs were highest (38%, 45%, and 41%). Total repair fees were higher with MMS ($735) vs excisions ($197). Fees were higher for head and neck tumors (p < .001), H-zone tumors (p < .001), and tumors smaller than 10 mm in diameter (p = .04). Regression models predicted that the treatment fees would be $2,109 for MMS and $1,252 for excision (p < .001). Tumor size greater than 10 mm in diameter (added $128), tumors on the head and neck (added $966), and MMS (added $857 vs excision) were independently related to higher fees (p < .001). CONCLUSION Even after adjusting for risk factors, MMS has higher fees than excision for primary NMSC. Repairs accounted for the majority of this difference. These fee comparisons provide a basis for comparative effectiveness studies of treatments for this common cancer. C1 [Wilson, Leslie S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Wilson, Leslie S.] Univ Calif San Francisco, Dept Pharm, San Francisco, CA USA. [Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Pregenzer, Mark] Univ Calif Los Angeles, Dept Pharmaceut Serv, Ronald Reagan Med Ctr, Los Angeles, CA USA. [Basu, Rituparna] San Francisco VA Med Ctr, Dept Pharm, San Francisco, CA USA. [Basu, Rituparna] San Francisco VA Med Ctr, Dept Dermatol, San Francisco, CA USA. [Bertenthal, Daniel; Chren, Mary-Margaret] Vet Adm Med Ctr, Dept Dermatol, San Francisco, CA 94121 USA. [Torres, Jeanette] San Francisco VA Med Ctr, No Calif Inst Res & Educ, Oakland, CA USA. [Asgari, Maryam] Kaiser Permanente No Calif, Dept Dermatol, Oakland, CA USA. RP Wilson, LS (reprint author), 3333 Calif St,Box 0613,Suite 420, San Francisco, CA 94013 USA. EM wilsonl@pharmacy.ucsf.edu RI Asgari, Maryam/O-4947-2016 FU NIAMS NIH HHS [K24 AR052667, R01 AR054983] NR 36 TC 12 Z9 12 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD APR PY 2012 VL 38 IS 4 BP 570 EP 584 DI 10.1111/j.1524-4725.2011.02231.x PG 15 WC Dermatology; Surgery SC Dermatology; Surgery GA 917DH UT WOS:000302152200005 PM 22145798 ER PT J AU Durazzo, TC Meyerhoff, DJ Nixon, SJ AF Durazzo, Timothy C. Meyerhoff, Dieter J. Nixon, Sara Jo TI A comprehensive assessment of neurocognition in middle-aged chronic cigarette smokers SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Cigarette smoking; Cognition; Neurocognition; Assessment; Middle-age ID ANTISOCIAL PERSONALITY-DISORDER; ALCOHOL-DEPENDENT INDIVIDUALS; COGNITIVE DECLINE; FEMALE ALCOHOLICS; SMOKING HISTORY; BRAIN; INTELLIGENCE; EFFICIENCY; NICOTINE; ADULTS AB Background: The majority of studies investigating the neurocognitive consequences of chronic smoking have been conducted with adults 60 years and older. Therefore, the scope of neurocognitive dysfunction associated with chronic cigarette smoking in middle age (i.e., 30-60 age range) has not been fully delineated. Methods: Twenty-seven (44 +/- 9 years of age; 4 females) non-smoking and 30 smoking (49 +/- 8 years of age; 4 females) participants completed a comprehensive neurocognitive battery and measures of fine motor dexterity and postural stability. All participants were free of biomedical or psychiatric conditions that may have influenced neurocognitive and motor function. Results: Smokers performed significantly worse than non-smokers on the following domains: auditory-verbal and visuospatial learning, visuospatial memory, cognitive efficiency, executive skills, general intelligence, processing speed, fine motor dexterity and postural stability. The differences between smokers and non-smokers evidenced moderate to strong effect sizes and were not mediated by age, education, vocational level, estimated verbal intelligence or alcohol consumption. In smokers, a greater number of lifetime years of smoking was related to poorer performance on measures of cognitive efficiency, processing speed and visuospatial skills. Conclusions: Results from this middle-aged cohort replicated previous research and provides novel findings indicating that chronic smoking was associated with inferior performance on measures of general intelligence, visuospatial learning and memory and fine motor dexterity. Research that relates measures of neurobiological function/integrity to neurocognition is needed to better understand the mechanisms contributing to the poorer performance across multiple domains demonstrated by smokers. Published by Elsevier Ireland Ltd. C1 [Durazzo, Timothy C.; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis CIND, San Francisco, CA 94121 USA. [Durazzo, Timothy C.; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Nixon, Sara Jo] Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA. [Nixon, Sara Jo] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu RI Nixon, Sara/L-1369-2014 OI Nixon, Sara/0000-0003-1179-2851 FU National Institute on Drug Abuse [DA24136, DA13677]; National Institute on Alcohol Abuse and Alcoholism [AA10788] FX This material is the result of work supported by the National Institute on Drug Abuse DA24136 to TCD and DA13677 to SJN, the National Institute on Alcohol Abuse and Alcoholism AA10788 to DJM, with resources and the use of facilities at the San Francisco Veterans Administration Medical Center, San Francisco CA. The sponsors had no role in study design, data collection, analysis and interpretation, manuscript preparation and in the decision to submit the manuscript for publication. NR 63 TC 32 Z9 32 U1 1 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 1 PY 2012 VL 122 IS 1-2 BP 105 EP 111 DI 10.1016/j.drugalcdep.2011.09.019 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 925CW UT WOS:000302739300015 PM 21992872 ER PT J AU Calkins, H Kuck, KH Cappato, R Brugada, J Camm, AJ Chen, SA Crijns, HJG Damiano, RJ Davies, DW DiMarco, J Edgerton, J Ellenbogen, K Ezekowitz, MD Haines, DE Haissaguerre, M Hindricks, G Iesaka, Y Jackman, W Jalife, J Jais, P Kalman, J Keane, D Kim, YH Kirchhof, P Klein, G Kottkamp, H Kumagai, K Lindsay, BD Mansour, M Marchlinski, FE McCarthy, PM Mont, JL Morady, F Nademanee, K Nakagawa, H Natale, A Nattel, S Packer, DL Pappone, C Prystowsky, E Raviele, A Reddy, V Ruskin, JN Shemin, RJ Tsao, HM Wilber, D Ad, N Cummings, J Gillinov, AM Heidbuchel, H January, C Lip, G Markowitz, S Nair, M Ovsyshcher, IE Pak, HN Tsuchiya, T Shah, D Siong, TW Vardas, PE AF Calkins, Hugh Kuck, Karl Heinz Cappato, Riccardo Brugada, Josep Camm, A. John Chen, Shih-Ann Crijns, Harry J. G. Damiano, Ralph J., Jr. Davies, D. Wyn DiMarco, John Edgerton, James Ellenbogen, Kenneth Ezekowitz, Michael D. Haines, David E. Haissaguerre, Michel Hindricks, Gerhard Iesaka, Yoshito Jackman, Warren Jalife, Jose Jais, Pierre Kalman, Jonathan Keane, David Kim, Young-Hoon Kirchhof, Paulus Klein, George Kottkamp, Hans Kumagai, Koichiro Lindsay, Bruce D. Mansour, Moussa Marchlinski, Francis E. McCarthy, Patrick M. Mont, J. Lluis Morady, Fred Nademanee, Koonlawee Nakagawa, Hiroshi Natale, Andrea Nattel, Stanley Packer, Douglas L. Pappone, Carlo Prystowsky, Eric Raviele, Antonio Reddy, Vivek Ruskin, Jeremy N. Shemin, Richard J. Tsao, Hsuan-Ming Wilber, David Ad, Niv Cummings, Jennifer Gillinov, A. Mark Heidbuchel, Hein January, Craig Lip, Gregory Markowitz, Steven Nair, Mohan Ovsyshcher, I. Eli Pak, Hui-Nam Tsuchiya, Takeshi Shah, Dipen Siong, Teo Wee Vardas, Panos E. TI 2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Patient Selection, Procedural Techniques, Patient Management and Follow-up, Definitions, Endpoints, and Research Trial Design SO EUROPACE LA English DT Article DE Atrial fibrillation; Catheter ablation; Surgical ablation C1 [Calkins, Hugh] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Kuck, Karl Heinz] Allgemeines Krankenhaus St Georg, Hamburg, Germany. [Cappato, Riccardo] IRCCS Policlin San Donato, Arrhythmia & EP Ctr, Milan, Italy. [Chen, Shih-Ann] Taichung Vet Gen Hosp, Taichung, Taiwan. [Prystowsky, Eric] Care Grp LLC, Indiana, PA USA. [Natale, Andrea] St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, Austin, TX USA. [Haines, David E.] William Beaumont Hosp, Troy, MI USA. [Marchlinski, Francis E.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Davies, D. Wyn] Imperial Coll Healthcare NHS Trust, St Marys Hosp, London, England. [Lindsay, Bruce D.] Cleveland Clin Fdn, Cleveland, OH USA. [Damiano, Ralph J., Jr.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Packer, Douglas L.] Mayo Fdn, Rochester, MN USA. [Brugada, Josep; Mont, J. Lluis] Univ Barcelona, Hosp Clin, E-08007 Barcelona, Spain. [Camm, A. John] St Georges Univ London, London, England. [Crijns, Harry J. G.] Univ Hosp Maastricht, Maastricht, Netherlands. [DiMarco, John] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Edgerton, James] Heart Hosp Baylor Plano, Plano, TX USA. [Edgerton, James] Cardiopulm Res Sci & Technol Inst, Dallas, TX USA. [Ellenbogen, Kenneth] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Ezekowitz, Michael D.] Jefferson Med Coll, Philadelphia, PA USA. [Haissaguerre, Michel; Jais, Pierre] Univ Bordeaux, Hop Cardiol, Bordeaux, France. [Hindricks, Gerhard] Univ Leipzig, Leipzig, Germany. [Iesaka, Yoshito] Tsuchiura Kyodo Gen Hosp, Tsuchiura, Ibaraki, Japan. [Jackman, Warren; Nakagawa, Hiroshi] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. [Jalife, Jose] Univ Michigan, Ann Arbor, MI 48109 USA. [Kalman, Jonathan] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Keane, David] St Vincents Univ Hosp, Dublin 4, Ireland. [Kim, Young-Hoon] Korea Univ, Med Ctr, Seoul, South Korea. [Kirchhof, Paulus] Univ Birmingham, Ctr Cardiovasc Sci, Birmingham, W Midlands, England. [Kirchhof, Paulus] Univ Munster, Dept Cardiol, Munster, Germany. [Klein, George] Univ Hosp, London, ON, Canada. [Kottkamp, Hans] Clin Hirslanden Zurich, Zurich, Switzerland. [Kumagai, Koichiro] Fukuoka Sanno Hosp, Fukuoka, Japan. [Mansour, Moussa; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McCarthy, Patrick M.] NW Mem Hosp, Chicago, IL USA. [Morady, Fred] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Nademanee, Koonlawee] Pacific Rim EP Res Inst, Los Angeles, CA USA. [Nattel, Stanley] Montreal Heart Inst, Quebec City, PQ, Canada. [Pappone, Carlo] Maria Cecilia Hosp, Cotignola, Italy. [Raviele, Antonio] Umberto I Hosp, Venice, Italy. [Reddy, Vivek] Mt Sinai Sch Med, New York, NY USA. [Shemin, Richard J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Tsao, Hsuan-Ming] Natl Yang Ming Univ Hosp, Taipei, Taiwan. [Wilber, David] Loyola Univ, Med Ctr, New Orleans, LA 70118 USA. RP Calkins, H (reprint author), Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RI Pak, Hui-Nam/C-4266-2015; Pappone, Carlo/J-9853-2016; Jalife, Jose/L-4833-2015; OI Pak, Hui-Nam/0000-0002-3256-3620; Pappone, Carlo/0000-0002-0901-6135; Jalife, Jose/0000-0003-0080-3500; Marchlinski, Francis/0000-0001-7962-9423; BRUGADA, JOSEP/0000-0002-5662-8302; Kirchhof, Paulus/0000-0002-1881-0197 NR 0 TC 593 Z9 627 U1 3 U2 37 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD APR PY 2012 VL 14 IS 4 BP 528 EP 606 DI 10.1093/europace/eus027 PG 79 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919DO UT WOS:000302301800015 PM 22389422 ER PT J AU Dallongeville, J Bhatt, DL Steg, PG Ravaud, P Wilson, PW Eagle, KA Goto, S Mas, JL Montalescot, G AF Dallongeville, Jean Bhatt, Deepak L. Steg, Ph Gabriel Ravaud, Philippe Wilson, Peter W. Eagle, Kim A. Goto, Shinya Mas, Jean-Louis Montalescot, Gilles CA REACH Registry Investigators TI Relation between body mass index, waist circumference, and cardiovascular outcomes in 19,579 diabetic patients with established vascular disease: the REACH Registry SO EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY LA English DT Article DE Body mass index; cardiovascular outcomes; diabetes; vascular disease; waist circumference; obesity; metabolic syndrome ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; ABDOMINAL OBESITY; ARTERY-DISEASE; EVENT RATES; FOLLOW-UP; HIGH-RISK; MORTALITY; IMPACT; FAILURE AB Aims: Obesity is frequent in type 2 diabetic patients with myocardial infarction (MI) or established cardiovascular disease. Earlier studies suggest that elevated body mass index (BMI) is associated with a favorable prognosis for persons with established vascular disease. We sought to analyse the associations between raised BMI and waist circumference with the 2-year event rate in type 2 diabetic patients with established vascular disease. Methods and results: Patients from the Reduction of Atherothrombosis for Continued Health (REACH) Registry, an international, prospective cohort of patients at high risk of atherothrombosis, were selected if they were diabetic and had established atherosclerotic arterial disease (n = 19,579). The main outcomes after 2-year follow-up were: all-cause death, cardiovascular death, MI, stroke, cardiovascular death/MI/stroke, and cardiovascular death/MI/stroke/rehospitalization. The rates of all-cause death, cardiovascular death, and cardiovascular death/MI/stroke decreased across increasing BMI quintile categories, whereas the same rates were stable across waist categories. The hazard ratios, adjusted for confounders, decreased significantly with increasing BMI for all-cause death (p < 0.0001), cardiovascular death (p = 0.0009), cardiovascular death/MI/stroke (p = 0.0004), and all events (p = 0.002), but not for greater waist circumference. Conclusion: There is an apparent obesity paradox (better outcome with increasing obesity) when obesity is measured by BMI but not when measured by waist circumference in diabetic subjects. C1 [Dallongeville, Jean] Inst Pasteur, INSERM, U744, F-59019 Lille, France. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Steg, Ph Gabriel] INSERM, U698, Paris, France. [Steg, Ph Gabriel] Univ Paris 07, Paris, France. [Steg, Ph Gabriel] Hop Bichat Claude Bernard, AP HP, F-75877 Paris 18, France. [Ravaud, Philippe] INSERM, U738, Ctr Epidemiol Clin, Paris, France. [Wilson, Peter W.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. [Eagle, Kim A.] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Goto, Shinya] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan. [Mas, Jean-Louis] Paris Descartes Univ, INSERM, Hop St Anne, U894,Dept Neurol, Paris, France. [Montalescot, Gilles] Univ Paris 06, INSERM, Hop La Pitie Salpetriere, AP HP,Serv Cardiol,U856, Paris, France. RP Dallongeville, J (reprint author), Inst Pasteur, INSERM, U744, Rue Pr Calmette, F-59019 Lille, France. EM jean.dallongeville@pasteur-lille.fr OI Ravaud, Philippe/0000-0001-8264-9206 FU Sanofi Aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan); Astra Zeneca; Pfizer; Eisai; Ethicon; Heartscape; Medicines Company; Blue Cross Blue Shield of Michigan; NIH; Mardigian Foundation; GORE; Hewlett Foundation; Daiichi-Sankyo; GlaxoSmithKline; Bristol-Myers Scribb; Otsuka; Bayer; Schering-Plough; Takeda; Astellas; Novartis; Kowa; Ono; Servier; Boehringer Ingelheim; Sanofi Aventis Group; Eli Lilly; Guerbet Medical; Medtronic; Boston Scientific; Centocor; Fondation de France; INSERM; Federation Francaise de Cardiologie; Societe Francaise de Cardiologie; Merck Sharpe Dohme; Cordis; Stago FX The REACH Registry is sponsored by Sanofi Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan).; Dr Dallongeville received institutional research grants from Astra Zeneca, Pfizer, Sanofi Aventis and participated in boards from Astra Zeneca, MSD, Sanofi Aventis.; Dr Bhatt received institutional research grants from Astra Zeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi Aventis, The Medicines Company.; Dr Eagle has received grant/research support from Bristol Myers Squibb, Blue Cross Blue Shield of Michigan, NIH, Sanofi Aventis, the Mardigian Foundation Varbedian Fund, GORE, and the Hewlett Foundation; and is a consultant for NIH NHLBI, Sanofi Aventis and the Robert Wood Johnson Foundation.; Dr Goto has received honoraria and consulting fees from Eisai, Sanofi Aventis, Daiichi-Sankyo, GlaxoSmithKline, Bristol-Myers Scribb, Otsuka, Bayer, Schering-Plough, Takeda, Astellas, AstraZeneca, Novartis and Kowa; research grants from Pfizer, Ono, Eisai, Otsuka, Daiichi-Sankyo, Sanofi Aventis, Takeda and Astellas within the past 3 years.; Dr Mas has received consulting fees from Sanofi Aventis, Servier, and Bristol-Myers Squibb; and lecture fees from Sanofi Aventis, Bristol-Myers Squibb, and Boehringer Ingelheim.; Dr Montalescot discloses the following relationships: Research Grants from Bristol Myers Squibb, Sanofi Aventis Group, Eli Lilly, Guerbet Medical, Medtronic, Boston Scientific, Cordis, Stago, Centocor, Fondation de France, INSERM, Federation Francaise de Cardiologie, Societe Francaise de Cardiologie; Consulting fees from Sanofi Aventis Group, Eli Lilly, Bristol-Myers Squibb, The Medicines Company, and Schering-Plough. He has also received lecture fees from Sanofi Aventis, Eli Lilly, Bristol-Myers Squibb, Merck Sharpe & Dohme, Cordis, GlaxoSmithKline, and Schering-Plough. NR 30 TC 12 Z9 13 U1 7 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 2047-4873 J9 EUR J PREV CARDIOL JI Eur. J. Prev. Cardiol. PD APR PY 2012 VL 19 IS 2 BP 241 EP 249 DI 10.1177/1741826710394305 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 921AD UT WOS:000302449500015 PM 21450609 ER PT J AU Roth, CL Elfers, CT Figlewicz, DP Melhorn, SJ Morton, GJ Hoofnagle, A Yeh, MM Nelson, JE Kowdley, KV AF Roth, Christian L. Elfers, Clinton T. Figlewicz, Dianne P. Melhorn, Susan J. Morton, Gregory J. Hoofnagle, Andrew Yeh, Matthew M. Nelson, James E. Kowdley, Kris V. TI Vitamin D deficiency in obese rats exacerbates nonalcoholic fatty liver disease and increases hepatic resistin and toll-like receptor activation SO HEPATOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE; 25-HYDROXYVITAMIN D-3; HYPOVITAMINOSIS-D; OXIDATIVE STRESS; HUMAN MONOCYTES; CHILDREN; ADOLESCENTS; EXPRESSION; MICE AB Childhood obesity is associated with type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD). Recent studies have found associations between vitamin D deficiency (VDD), insulin resistance (IR), and NAFLD among overweight children. To further explore mechanisms mediating these effects, we fed young (age 25 days) Sprague-Dawley rats with a low-fat diet (LFD) alone or with vitamin D depletion (LFD+VDD). A second group of rats was exposed to a Westernized diet (WD: high-fat/high-fructose corn syrup) that is more typically consumed by overweight children, and was either replete (WD) or deficient in vitamin D (WD+VDD). Liver histology was assessed using the nonalcoholic steatohepatitis (NASH) Clinical Research Network (CRN) scoring system and expression of genes involved in inflammatory pathways were measured in liver and visceral adipose tissue after 10 weeks. In VDD groups, 25-OH-vitamin D levels were reduced to 29% (95% confidence interval [CI]: 23%-36%) compared to controls. WD+VDD animals exhibited significantly greater hepatic steatosis compared to LFD groups. Lobular inflammation as well as NAFLD Activity Score (NAS) were higher in WD+VDD versus the WD group (NAS: WD+VDD 3.2 +/- 0.47 versus WD 1.50 +/- 0.48, P < 0.05). Hepatic messenger RNA (mRNA) levels of Toll-like receptors (TLR)2, TLR4, and TLR9, as well as resistin, interleukins (IL)-1 beta, IL-4, and IL-6 and oxidative stress marker heme oxygenase (HO)-1, were higher in WD+VDD versus WD animals (P < 0.05). Logistic regression analyses showed significant associations between NAS score and liver mRNA levels of TLRs 2, 4, and 9, endotoxin receptor CD14, as well as peroxisome proliferator activated receptor (PPAR)?, and HO-1. Conclusion: VDD exacerbates NAFLD through TLR-activation, possibly by way of endotoxin exposure in a WD rat model. In addition it causes IR, higher hepatic resistin gene expression, and up-regulation of hepatic inflammatory and oxidative stress genes. (HEPATOLOGY 2012) C1 [Roth, Christian L.] Seattle Childrens Hosp, Res Inst, Div Endocrinol, Seattle, WA 98101 USA. [Figlewicz, Dianne P.; Melhorn, Susan J.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Morton, Gregory J.; Hoofnagle, Andrew; Yeh, Matthew M.; Kowdley, Kris V.] Univ Washington, Dept Med, Seattle, WA USA. [Nelson, James E.; Kowdley, Kris V.] Benaroya Res Inst, Seattle, WA USA. [Kowdley, Kris V.] Virginia Mason Med Ctr, Inst Digest Dis, Seattle, WA 98101 USA. RP Roth, CL (reprint author), Seattle Childrens Hosp, Res Inst, Div Endocrinol, 1900 9th Ave, Seattle, WA 98101 USA. EM christian.roth@seattlechildrens.org FU Center of Integrative Brain Research, Seattle Children's Research Institute FX Supported by pilot funding from the Center of Integrative Brain Research, Seattle Children's Research Institute, granted (to C.L.R.). NR 47 TC 82 Z9 87 U1 4 U2 30 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2012 VL 55 IS 4 BP 1103 EP 1111 DI 10.1002/hep.24737 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 916AW UT WOS:000302069900013 PM 21994008 ER PT J AU Epstein, SK Huckins, DS Liu, SW Pallin, DJ Sullivan, AF Lipton, RI Camargo, CA AF Epstein, Stephen K. Huckins, David S. Liu, Shan W. Pallin, Daniel J. Sullivan, Ashley F. Lipton, Robert I. Camargo, Carlos A., Jr. TI Emergency department crowding and risk of preventable medical errors SO INTERNAL AND EMERGENCY MEDICINE LA English DT Article DE Emergency services; Crowding; Medical errors ID ACUTE MYOCARDIAL-INFARCTION; COMMUNITY-ACQUIRED PNEUMONIA; PRACTICE GUIDELINES; MISSED DIAGNOSES; PATIENT-SAFETY; ACUTE ASTHMA; TASK-FORCE; CARE; ASSOCIATION; PAIN AB The objective of the study is to determine the association between emergency department (ED) crowding and preventable medical errors (PME). This was a retrospective cohort study of 533 ED patients enrolled in the National ED Safety Study (NEDSS) in four Massachusetts EDs. Individual patients' average exposure to ED crowding during their ED visit was compared with the occurrence of a PME (yes/no) for the three diagnostic categories in NEDSS: acute myocardial infarction, asthma exacerbation, and dislocation requiring procedural sedation. To accommodate site-to-site differences in available administrative data, ED crowding was measured using one of three previously validated crowding metrics (ED Work Index, ED Workscore, and ED Occupancy). At each site, the continuous measure was placed into site-specific quartiles, and these quartiles then were combined across sites. We found that 46 (8.6%; 95% confidence interval, 6.4-11.3%) of the 533 patients experienced a PME. For those seen during higher levels of ED crowding (quartile 4 vs. quartile 1), the occurrence of PMEs was more than twofold higher, both on unadjusted analysis and adjusting for two potential confounders (diagnosis, site). The association appeared non-linear, with most PMEs occurring at the highest crowding level. We identified a direct association between high levels of ED crowding and risk of preventable medical errors. Further study is needed to determine the generalizability of these results. Should such research confirm our findings, we would suggest that mitigating ED crowding may reduce the occurrence of preventable medical errors. C1 [Epstein, Stephen K.; Lipton, Robert I.] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Huckins, David S.] Newton Wellesley Hosp, Dept Emergency Med, Newton, MA USA. [Liu, Shan W.; Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Epstein, SK (reprint author), Beth Israel Deaconess Med Ctr, Dept Emergency Med, W-CC-2,1 Deaconess Rd, Boston, MA 02215 USA. EM sepstein@bidmc.harvard.edu RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 FU Riggs Family/Emergency Medicine Foundation (Dallas, TX); Agency for Healthcare Research and Quality (Rockville, MD) [5 R01 HS013099] FX We gratefully acknowledge the contribution of Dr. David Blumenthal to the NEDSS study that made this work possible, and of Dr. Sharolyn Medina, Director of Clinical Informatics, Picis, Inc. for her assistance with data extraction. We gratefully acknowledge the support of the Riggs Family/Emergency Medicine Foundation Health Policy Grant (Dallas, TX). The National ED Safety Study was supported by grant 5 R01 HS013099 from the Agency for Healthcare Research and Quality (Rockville, MD). NR 38 TC 26 Z9 27 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1828-0447 J9 INTERN EMERG MED JI Intern. Emerg. Med. PD APR PY 2012 VL 7 IS 2 BP 173 EP 180 DI 10.1007/s11739-011-0702-8 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 921MY UT WOS:000302482900011 PM 22009553 ER PT J AU Baugh, CW Reisner, AT AF Baugh, Christopher William Reisner, Andrew Tomas TI QTc pseudoprolongation and hypokalemia-induced T-U fusion: the authors reply SO INTERNAL AND EMERGENCY MEDICINE LA English DT Letter C1 [Baugh, Christopher William] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Reisner, Andrew Tomas] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Baugh, CW (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM cbaugh@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1828-0447 J9 INTERN EMERG MED JI Intern. Emerg. Med. PD APR PY 2012 VL 7 IS 2 BP 195 EP 195 DI 10.1007/s11739-011-0747-8 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 921MY UT WOS:000302482900016 PM 22161293 ER PT J AU Lamunu, D Chapman, KN Nsubuga, P Muzanyi, G Mulumba, Y Mugerwa, MA Goldberg, S Bozeman, L Engle, M Saukkonen, J Mastranunzio, S Mayanja-Kizza, H Johnson, JL AF Lamunu, D. Chapman, K. N. Nsubuga, P. Muzanyi, G. Mulumba, Y. Mugerwa, M. A. Goldberg, S. Bozeman, L. Engle, M. Saukkonen, J. Mastranunzio, S. Mayanja-Kizza, H. Johnson, J. L. TI Reasons for non-participation in an international multicenter trial of a new drug for tuberculosis treatment SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE tuberculosis; non-participation; clinical trial; moxifloxacin; anti-tuberculosis agents ID RANDOMIZED CONTROLLED-TRIALS; CLINICAL-TRIALS; PARTICIPATION; RECRUITMENT; GUIDELINES; ATTITUDES; SELF AB SETTING: Clinical trials can provide a high standard of patient care and contribute to scientific knowledge; however, only a fraction of the patients screened participate and receive treatment as part of a trial. OBJECTIVE: To explore reasons why patients were not enrolled in an international tuberculosis (TB) treatment trial and to compare experiences among study sites. DESIGN: An analysis of reasons why patients were not enrolled was conducted among patients screened for a TB clinical trial at 26 sites in North and South America, Africa, and Europe. RESULTS: Staff at study sites screened 1119 potential candidates for the trial: 61% (n = 686) were not enrolled due to 1) failure to meet eligibility criteria (n = 405, 59%), 2) site's decision (n = 168, 24%), or 3) candidate's choice (n = 113, 16%). Study staff recorded a total of 144 reasons for why they believed patients chose not to participate, including concerns over research (28%), conflicts with work or school (21%), and lifestyle and family issues (20%). Socio-demographic and geographic factors also influenced participation. CONCLUSION: Increased evaluation of screening outcomes and of specific interventions, such as improved education and communication about trial procedures, may increase the efficiency of screening and enrollment in clinical trials. C1 [Lamunu, D.; Nsubuga, P.; Muzanyi, G.; Mulumba, Y.; Mugerwa, M. A.; Mastranunzio, S.; Mayanja-Kizza, H.; Johnson, J. L.] Uganda CWRU Res Collaborat, Kampala, Uganda. [Chapman, K. N.; Goldberg, S.; Bozeman, L.] Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. [Engle, M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Engle, M.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Saukkonen, J.] Boston Univ, Sch Med, Ctr Pulm, Dept Med, Boston, MA 02118 USA. [Mayanja-Kizza, H.] Makerere Univ, Fac Med, Coll Hlth Sci, Dept Med, Kampala, Uganda. [Johnson, J. L.] Case Western Reserve Univ, Sch Med, Dept Med, Div Infect Dis, Cleveland, OH 44106 USA. [Johnson, J. L.] Univ Hosp Case Med Ctr, Cleveland, OH USA. RP Lamunu, D (reprint author), Uganda CWRU Res Collaborat, POB 663, Kampala, Uganda. EM DLamunu@mucwru.or.ug OI Mayanja-Kizza, Harriet/0000-0002-9297-6208 FU Tuberculosis Trials Consortium; United States Centers for Disease Control and Prevention; Centers for Disease Control and Prevention; Global Alliance for Tuberculosis Drug Development FX The authors thank the volunteers and site staff who participated in this study, P-J Feng and N Scott for their outstanding statistical and epidemiological support and assistance, W McKenzie for editorial review, and A Vernon for technical and editorial review. This study was supported by the Tuberculosis Trials Consortium and the United States Centers for Disease Control and Prevention.; Tuberculosis Clinical Trials Consortium Study 28 was supported by the Centers for Disease Control and Prevention and the Global Alliance for Tuberculosis Drug Development. MFX and MFX placebo tablets were donated by Bayer Pharmaceuticals. NR 17 TC 3 Z9 3 U1 1 U2 5 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD APR PY 2012 VL 16 IS 4 BP 480 EP 485 DI 10.5588/ijtld.11.0434 PG 6 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 919OA UT WOS:000302336300011 PM 22640513 ER PT J AU Yonker, LM Permaul, P Baker, MC Hesterberg, P Iyengar, R Peled, JU Walter, J Castells, MC AF Yonker, Lael M. Permaul, Perdita Baker, Matthew C. Hesterberg, Paul Iyengar, Rajashri Peled, Jonathan U. Walter, Jolan Castells, Mariana C. CA CVID Working Grp TI Common Variable Immunodeficiency: Massachusetts General Hospital Cohort Outcomes and Analysis SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Yonker, Lael M.; Permaul, Perdita; Iyengar, Rajashri; Walter, Jolan] Massachusetts Gen Hosp Children, Boston, MA USA. [Baker, Matthew C.; Hesterberg, Paul; Peled, Jonathan U.; Castells, Mariana C.; CVID Working Grp] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 374 EP 374 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200085 ER PT J AU Jacobson, JO Mulvey, TM AF Jacobson, Joseph O. Mulvey, Therese Marie TI Time to Focus on Inpatient Safety: Revision of the American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID INFUSION CHEMOTHERAPY; OUTPATIENT TREATMENT; CANCER; QUALITY; REGIMEN; TRANSPLANTATION; MANAGEMENT; CARE C1 [Jacobson, Joseph O.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mulvey, Therese Marie] Southcoast Hosp Grp, Fall River, MA USA. RP Jacobson, JO (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 24 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2012 VL 30 IS 10 BP 1021 EP 1022 DI 10.1200/JCO.2011.40.9409 PG 2 WC Oncology SC Oncology GA 923PN UT WOS:000302631300004 PM 22312104 ER PT J AU Kastrinos, F Syngal, S AF Kastrinos, Fay Syngal, Sapna TI Screening Patients With Colorectal Cancer for Lynch Syndrome: What Are We Waiting For? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID MISMATCH-REPAIR GENES; BETHESDA GUIDELINES; GERMLINE MUTATIONS; PREDICTIVE MODELS; IDENTIFICATION; STRATEGIES; CRITERIA C1 [Kastrinos, Fay] Columbia Univ, Med Ctr, New York, NY 10027 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kastrinos, F (reprint author), Columbia Univ, Med Ctr, New York, NY 10027 USA. FU NCI NIH HHS [K07 CA151769, K24 CA113433] NR 20 TC 15 Z9 15 U1 0 U2 0 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 APR 1 PY 2012 VL 30 IS 10 BP 1024 EP 1027 DI 10.1200/JCO.2011.40.7171 PG 5 WC Oncology SC Oncology GA 923PN UT WOS:000302631300006 PM 22355054 ER PT J AU Lipshultz, SE Miller, TL Scully, RE Lipsitz, SR Rifai, N Silverman, LB Colan, SD Neuberg, DS Dahlberg, SE Henkel, JM Asselin, BL Athale, UH Clavell, LA Laverdiere, C Michon, B Schorin, MA Sallan, SE AF Lipshultz, Steven E. Miller, Tracie L. Scully, Rebecca E. Lipsitz, Stuart R. Rifai, Nader Silverman, Lewis B. Colan, Steven D. Neuberg, Donna S. Dahlberg, Suzanne E. Henkel, Jacqueline M. Asselin, Barbara L. Athale, Uma H. Clavell, Luis A. Laverdiere, Caroline Michon, Bruno Schorin, Marshall A. Sallan, Stephen E. TI Changes in Cardiac Biomarkers During Doxorubicin Treatment of Pediatric Patients With High-Risk Acute Lymphoblastic Leukemia: Associations With Long-Term Echocardiographic Outcomes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Scientific Sessions of the American-Heart-Association on Resuscitation Science Symposium CY NOV 13-17, 2010 CL Chicago, IL SP Amer Heart Assoc ID BRAIN NATRIURETIC PEPTIDE; C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; HIGH-DOSE CHEMOTHERAPY; DEPENDENT FOLLOW-UP; PROGNOSTIC VALUE; CARDIOVASCULAR EVENTS; MYOCARDIAL INJURY; CHILDHOOD-CANCER; TROPONIN-I AB Purpose Doxorubicin causes cardiac injury and cardiomyopathy in children with acute lymphoblastic leukemia (ALL). Measuring biomarkers during therapy might help individualize treatment by immediately identifying cardiac injury and cardiomyopathy. Patients and Methods Children with high-risk ALL were randomly assigned to receive doxorubicin alone (n = 100; 75 analyzed) or doxorubicin with dexrazoxane (n = 105; 81 analyzed). Echocardiograms and serial serum measurements of cardiac troponin T (cTnT; cardiac injury biomarker), N-terminal pro-brain natriuretic peptide (NT-proBNP; cardiomyopathy biomarker), and high-sensitivity C-reactive protein (hsCRP; inflammatory biomarker) were obtained before, during, and after treatment. Results cTnT levels were increased in 12% of children in the doxorubicin group and in 13% of the doxorubicin-dexrazoxane group before treatment but in 47% and 13%, respectively, after treatment (P = .005). NT-proBNP levels were increased in 89% of children in the doxorubicin group and in 92% of children in the doxorubicin-dexrazoxane group before treatment but in only 48% and 20%, respectively, after treatment (P = .07). The percentage of children with increased hsCRP levels did not differ between groups at any time. In the first 90 days of treatment, detectable increases in cTnT were associated with abnormally reduced left ventricular (LV) mass and LV end-diastolic posterior wall thickness 4 years later (P < .01); increases in NT-proBNP were related to an abnormal LV thickness-to-dimension ratio, suggesting LV remodeling, 4 years later (P = .01). Increases in hsCRP were not associated with any echocardiographic variables. Conclusion cTnT and NT-proBNP may hold promise as biomarkers of cardiotoxicity in children with high-risk ALL. Definitive validation studies are required to fully establish their range of clinical utility. C1 [Lipshultz, Steven E.] Univ Miami, Miller Sch Med, Dept Pediat D820, Miami, FL 33101 USA. [Lipshultz, Steven E.; Miller, Tracie L.] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33101 USA. [Lipsitz, Stuart R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Silverman, Lewis B.; Neuberg, Donna S.; Dahlberg, Suzanne E.; Sallan, Stephen E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Silverman, Lewis B.; Colan, Steven D.; Sallan, Stephen E.] Childrens Hosp, Boston, MA 02115 USA. [Asselin, Barbara L.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Athale, Uma H.] McMaster Univ, Hamilton, ON, Canada. [Laverdiere, Caroline] Hop St Justine, Montreal, PQ H3T 1C5, Canada. [Michon, Bruno] CHU Laval, Laval, PQ, Canada. [Schorin, Marshall A.] Inova Fairfax Hosp Children, Fairfax, VA 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 OI Scully, Rebecca/0000-0002-6887-9600 FU NCI NIH HHS [CA068484, CA127642, P01 CA068484, R01 CA127642]; NHLBI NIH HHS [HL087708, F31 HL094100, HL004537, HL007188, HL053392, HL072705, HL078522, HL079233, HL087000, HL094100, HL095127, K30 HL004537, R01 HL053392, R01 HL072705, R01 HL078522, R01 HL087000, R01 HL095127, R13 HL087708, T32 HL007188]; NIAID NIH HHS [AI50274, U01 AI050274]; NICHD NIH HHS [HD052102, HD052104, HD80002, U01 HD052102, U01 HD052104] NR 42 TC 78 Z9 82 U1 0 U2 3 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 APR 1 PY 2012 VL 30 IS 10 BP 1042 EP 1049 DI 10.1200/JCO.2010.30.3404 PG 8 WC Oncology SC Oncology GA 923PN UT WOS:000302631300010 PM 22370326 ER PT J AU Landrum, MB Keating, NL Lamont, EB Bozeman, SR Krasnow, SH Shulman, L Brown, JR Earle, CC Rabin, M McNeil, BJ AF Landrum, Mary Beth Keating, Nancy L. Lamont, Elizabeth B. Bozeman, Samuel R. Krasnow, Steven H. Shulman, Lawrence Brown, Jennifer R. Earle, Craig C. Rabin, Michael McNeil, Barbara J. TI Survival of Older Patients With Cancer in the Veterans Health Administration Versus Fee-for-Service Medicare SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; QUALITY-OF-CARE; COLORECTAL-CANCER; MYOCARDIAL-INFARCTION; PROPENSITY SCORE; ADVERSE EVENTS; AFFAIRS; CHEMOTHERAPY; SYSTEM; COMORBIDITY AB Purpose The Veterans Health Administration (VHA) provides high-quality preventive chronic care and cancer care, but few studies have documented improved patient outcomes that result from this high-quality care. We compared the survival rates of older patients with cancer in the VHA and fee-for-service (FFS) Medicare and examined whether differences in the stage at diagnosis, receipt of guideline-recommended therapies, and unmeasured characteristics explain survival differences. Patients and Methods We used propensity-score methods to compare all-cause and cancer-specific survival rates for men older than age 65 years who were diagnosed or received their first course of treatment for colorectal, lung, lymphoma, or multiple myeloma in VHA hospitals from 2001 to 2004 to similar FFS-Medicare enrollees diagnosed in Surveillance, Epidemiology, and End Results (SEER) areas in the same time frame. We examined the role of unmeasured factors by using sensitivity analyses. Results VHA patients versus similar FFS SEER-Medicare patients had higher survival rates of colon cancer (adjusted hazard ratio [HR], 0.87; 95% CI, 0.82 to 0.93) and non-small-cell lung cancer (NSCLC; HR, 0.91; 95% CI, 0.88 to 0.95) and similar survival rates of rectal cancer (HR, 1.05; 95% CI, 0.95 to 1.16), small-cell lung cancer (HR, 0.99; 95% CI, 0.93 to 1.05), diffuse large-B-cell lymphoma (HR, 1.02; 95% CI, 0.89 to 1.18), and multiple myeloma (HR, 0.92; 95% CI, 0.83 to 1.03). The diagnosis of VHA patients at earlier stages explained much of the survival advantages for colon cancer and NSCLC. Sensitivity analyses suggested that additional adjustment for the severity of comorbid disease or performance status could have substantial effects on estimated differences. Conclusion The survival rate for older men with cancer in the VHA was better than or equivalent to the survival rate for similar FFS-Medicare beneficiaries. The VHA provision of high-quality care, particularly preventive care, can result in improved patient outcomes. C1 [Landrum, Mary Beth] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.; McNeil, Barbara J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Shulman, Lawrence; Brown, Jennifer R.; Rabin, Michael] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bozeman, Samuel R.] ABT Associates Inc, Cambridge, MA 02138 USA. [Krasnow, Steven H.] DC Vet Affairs Med Ctr, Washington, DC USA. [Earle, Craig C.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. RP Landrum, MB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM landrum@hcp.med.harvard.edu FU Department of Veterans Affairs through the Office of Policy and Planning; Department of Veterans Affairs; Celgene, Genzyme FX Supported by the Department of Veterans Affairs through the Office of Policy and Planning.; Steven H. Krasnow, Department of Veterans Affairs; Jennifer R. Brown, Celgene, Genzyme NR 38 TC 30 Z9 30 U1 1 U2 2 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 APR 1 PY 2012 VL 30 IS 10 BP 1072 EP 1079 DI 10.1200/JCO.2011.35.6758 PG 8 WC Oncology SC Oncology GA 923PN UT WOS:000302631300014 PM 22393093 ER PT J AU Jagannathan, JP Ramaiya, NH Shinagare, AB Hornick, JL George, S AF Jagannathan, Jyothi P. Ramaiya, Nikhil H. Shinagare, Atul B. Hornick, Jason L. George, Suzanne TI Intracranial Metastasis From Pediatric GI Stromal Tumor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID IMATINIB MESYLATE; SUCCINATE-DEHYDROGENASE; MUTATIONS; SURVIVAL; KIT C1 [Jagannathan, Jyothi P.; Ramaiya, Nikhil H.; Shinagare, Atul B.; George, Suzanne] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jagannathan, Jyothi P.; Ramaiya, Nikhil H.; Shinagare, Atul B.; Hornick, Jason L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Jagannathan, JP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 20 TC 7 Z9 7 U1 0 U2 0 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 APR 1 PY 2012 VL 30 IS 10 BP E122 EP E125 DI 10.1200/JCO.2011.38.1798 PG 4 WC Oncology SC Oncology GA 923PN UT WOS:000302631300003 PM 22370323 ER PT J AU Kachadourian, LK Taft, CT O'Farrell, TJ Doron-LaMarca, S Murphy, CM AF Kachadourian, Lorig K. Taft, Casey T. O'Farrell, Timothy J. Doron-LaMarca, Susan Murphy, Christopher M. TI Correlates of Intimate Partner Psychological Aggression Perpetration in a Clinical Sample of Alcoholic Men SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE psychological aggression perpetration; alcoholic men; relationship adjustment ID PHYSICAL AGGRESSION; EARLY MARRIAGE; VERBAL AGGRESSION; MARITAL VIOLENCE; SCALES; ADJUSTMENT; COUPLES; WIVES; RISK AB This study longitudinally examined correlates of intimate partner psychological aggression in a sample of 178 men seeking treatment for alcoholism and their partners, building on a previous investigation examining correlates of intimate partner physical aggression (Taft et al., 2010). The men were largely Caucasian; average age was 41.0 years. Participants completed a battery of questionnaires that assessed distal and proximal predictors of psychological aggression perpetration. Distal factors, assessed at baseline, included initial alcohol problem severity, beliefs about alcohol, and antisocial personality characteristics. Proximal factors, assessed at baseline and at follow-ups 6 and 12 months later, included alcohol and drug use, relationship adjustment, and anger. Psychological aggression was assessed at all three time points. Findings showed that both groups of variables were associated with psychological aggression perpetration. Beliefs that drinking causes relationship problems and variables related to alcohol consumption exhibited the strongest associations with psychological aggression. The findings are consistent with theoretical models that emphasize both distal and proximal effects of drinking on intimate partner aggression. Implications for clinical interventions and directions for future research are discussed. C1 [Kachadourian, Lorig K.; Taft, Casey T.; Doron-LaMarca, Susan] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Kachadourian, Lorig K.; Taft, Casey T.; Doron-LaMarca, Susan] Boston Univ, Sch Med, Boston, MA 02215 USA. [O'Farrell, Timothy J.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Murphy, Christopher M.] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. [O'Farrell, Timothy J.] VA Boston Healthcare Syst, Families & Addict Program, Boston, MA USA. RP Kachadourian, LK (reprint author), VA Boston Healthcare Syst 116B 2, 150 S Huntington Ave, Boston, MA 02130 USA. EM lorig.kachadourian@va.gov FU NIAAA NIH HHS [R01 AA010796-04, R01 AA010796]; NIMH NIH HHS [T32 MH019836, T32MH019836] NR 38 TC 6 Z9 7 U1 2 U2 11 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD APR PY 2012 VL 26 IS 2 BP 206 EP 214 DI 10.1037/a0027436 PG 9 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 921RU UT WOS:000302495800005 PM 22409160 ER PT J AU Cohen, S Schulz, MS Weiss, E Waldinger, RJ AF Cohen, Shiri Schulz, Marc S. Weiss, Emily Waldinger, Robert J. TI Eye of the Beholder: The Individual and Dyadic Contributions of Empathic Accuracy and Perceived Empathic Effort to Relationship Satisfaction SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE couples; empathy; relationship satisfaction; empathic accuracy; perceived empathic effort ID MARITAL ADJUSTMENT; GENDER-DIFFERENCES; MARRIAGE; ATTRIBUTIONS; COUPLES; PERSPECTIVE; SIMILARITY; MOTIVATION; PARTNER; HEALTH AB This study examined links between two distinct facets of empathy empathic accuracy and perceived empathic effort and one's own and one's partner's relationship satisfaction. Using a video recall procedure, participants (n = 156 couples in committed relationships) reported on their own emotions and their perceptions of partners' emotions and partners' empathic intentions during moments of high affect in laboratory-based discussions of upsetting events. Partners' data were correlated as a measure of how accurately they were able to read what the other was feeling and to what degree they felt the other was trying to be empathic at those moments. The perception of empathic effort by one's partner was more strongly linked with both men's and women's relationship satisfaction than empathic accuracy. Men's relationship satisfaction was related to the ability to read their partners' positive emotions accurately, whereas women's relationship satisfaction was related to their partners' ability to read women's negative emotions accurately. Women's ability to read their husbands' negative emotions was positively linked to both men's and women's relationship satisfaction. Findings suggest that the perception of a partner's empathic effort as distinct from empathic accuracy is uniquely informative in understanding how partners may derive relationship satisfaction from empathic processes. When working with couples in treatment, heightening partners' perceptions of each other's empathic effort, and helping partners learn to demonstrate effort, may represent particularly powerful opportunities for improving satisfaction in relationships. C1 [Cohen, Shiri] Massachusetts Gen Hosp, Lab Adult Dev, Dept Psychiat, Boston, MA 02114 USA. [Cohen, Shiri; Waldinger, Robert J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Schulz, Marc S.; Weiss, Emily] Bryn Mawr Coll, Dept Psychol, Bryn Mawr, PA 19010 USA. RP Cohen, S (reprint author), Massachusetts Gen Hosp, Lab Adult Dev, Dept Psychiat, 151 Merrimac St,2nd Floor, Boston, MA 02114 USA. EM scohen17@partners.org RI Brower, Susan/C-7090-2009 FU NIMH NIH HHS [K08 MH 01555, T32 MH 016259-29] NR 32 TC 22 Z9 23 U1 3 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD APR PY 2012 VL 26 IS 2 BP 236 EP 245 DI 10.1037/a0027488 PG 10 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 921RU UT WOS:000302495800008 PM 22369462 ER PT J AU Taft, CT Kachadourian, LK Suvak, MK Pinto, LA Miller, MM Knight, JA Marx, BP AF Taft, Casey T. Kachadourian, Lorig K. Suvak, Michael K. Pinto, Lavinia A. Miller, Mark M. Knight, Jeffrey A. Marx, Brian P. TI Examining Impelling and Disinhibiting Factors for Intimate Partner Violence in Veterans SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE trauma; veterans; violence; aggression; head injury ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; AGGRESSION; PERPETRATION; PERSONALITY; VALIDITY; SCALE AB We examined correlates of intimate partner violence (IPV) in a military Veteran sample (N = 129) using Finkel's (2007) framework for understanding the interactions between impelling and disinhibiting risk factors. Correlates investigated included head contact events (HCEs), posttraumatic stress disorder (PTSD) symptoms, and antisocial features. Results indicated that antisocial features were significantly associated with IPV at the bivariate level. PTSD symptoms also were associated with IPV, but this association was marginally significant. Tests of moderation provided support for the expectation that HCEs would potentiate associations between antisocial features and IPV. HCEs also moderated the association between PTSD symptoms and IPV. However, contrary to expectations, the opposite pattern emerged such that PTSD symptoms were associated with a higher rate of IPV for those without a history of HCEs. Study findings have potentially important implications for furthering our understanding of the complex etiology of IPV in this population. C1 [Taft, Casey T.; Kachadourian, Lorig K.; Miller, Mark M.; Knight, Jeffrey A.; Marx, Brian P.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Taft, Casey T.; Kachadourian, Lorig K.; Miller, Mark M.; Knight, Jeffrey A.; Marx, Brian P.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Suvak, Michael K.] Suffolk Univ, Dept Psychol, Boston, MA USA. [Pinto, Lavinia A.] Kent State Univ, Dept Psychol, Kent, OH USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave 116B-4, Boston, MA 02130 USA. EM Casey.Taft@va.gov FU NIMH NIH HHS [R01 MH079806, K08 MH7311701A2] NR 23 TC 8 Z9 8 U1 0 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD APR PY 2012 VL 26 IS 2 BP 285 EP 289 DI 10.1037/a0027424 PG 5 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 921RU UT WOS:000302495800014 PM 22369461 ER PT J AU Lindenhovius, A Karanicolas, PJ Bhandari, M Ring, D AF Lindenhovius, Anneluuk Karanicolas, Paul Jack Bhandari, Mohit Ring, David CA COAST Collaborative TI Radiographic Arthrosis After Elbow Trauma: Interobserver Reliability SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Arthritis; arthrosis; elbow; interobserver; reliability; trauma ID KNEE OSTEOARTHRITIS; RADIAL HEAD; AGREEMENT; FRACTURE; EXCISION AB Purpose This study measured observer variation in radiographic rating of elbow arthrosis. Methods Thirty-seven independent orthopedic surgeons graded the extent of elbow arthrosis in 20 consecutive sets of plain radiographs, according to the Broberg and Morrey rating system (grade 0, normal joint; grade 1, slight joint-space narrowing with minimum osteophyte formation; grade 2, moderate joint-space narrowing with moderate osteophyte formation; and grade 3, severe degenerative change with gross destruction of the joint). The kappa multirater measure (kappa) was used to estimate reliability between observers, with 0 indicating no agreement above chance, and 1 indicating perfect agreement. Results There was fair agreement in arthrosis ratings between surgeons. Surgeons with more than 10 years of experience had greater agreement than did surgeons with less experience, and surgeons who treated more than 10 elbow fractures per year had better agreement than did those treating fewer fractures. In post hoc analyses, 2 simplified binary rating systems (eg, "none or mild" vs "moderate or severe" arthrosis) resulted in moderate agreement among observers. Conclusions The 4 grades of the Broberg and Money classification system have only fair interobserver reliability that is influenced by subspecialty and experience. Binary rating systems might be more reliable. (J Hand Surg 2012;37A:755-759. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, NL-1105 AZ Amsterdam, Netherlands. Univ Western Ontario, Dept Surg, London, ON N6A 3K7, Canada. McMaster Univ, Hamilton, ON, Canada. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, 55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org RI Kampen, A./H-8056-2014; Page, Richard/K-6327-2015; OI Page, Richard/0000-0002-2225-7144; Frihagen, Frede/0000-0002-4811-669X NR 16 TC 5 Z9 6 U1 2 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD APR PY 2012 VL 37A IS 4 BP 755 EP 759 DI 10.1016/j.jhsa.2011.12.043 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 925JA UT WOS:000302756300019 PM 22397846 ER PT J AU Ring, D AF Ring, David TI Probability and Pathophysiology SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Letter C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD APR PY 2012 VL 37A IS 4 BP 860 EP 860 DI 10.1016/j.jhsa.2012.02.036 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 925JA UT WOS:000302756300040 PM 22464237 ER PT J AU Donde, A Wong, H Frelinger, J Power, K Balmes, JR Arjomandi, M AF Donde, Aneesh Wong, Hofer Frelinger, Jessica Power, Karron Balmes, John R. Arjomandi, Mehrdad TI Effects of Exercise on Systemic Inflammatory, Coagulatory, and Cardiac Autonomic Parameters in an Inhalational Exposure Study SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID HEART-RATE-VARIABILITY; DIESEL-EXHAUST INHALATION; VASCULAR DYSFUNCTION; ULTRAFINE PARTICLES; PHYSICAL-EXERCISE; OZONE; YOUNG; MEN; FIBRINOLYSIS; VENTILATION AB Background: Intermittent moderate-intensity exercise is used in human inhalational exposure studies to increase the effective dose of air pollutants. Objective: To investigate the inflammatory, coagulatory, and autonomic effects of intermittent moderate-intensity exercise. Methods: We measured hemodynamic, electrocardiographic, inflammatory, and coagulatory parameters in peripheral blood of 25 healthy subjects across an exercise protocol that included running on a treadmill or pedaling a cycle ergometer for 30 minutes every hour over 4 hours in a climate-controlled chamber with a target ventilation of 20 L/min/m(2) body surface area. Results: Intermittent moderate-intensity exercise induced a systemic proinflammatory response characterized by increases in leukocyte counts, C-reactive protein, monocyte chemoattractant protein-I, and interleukin-6, but did not change coagulation tendency or heart rate variability. Conclusion: Interpretation of pollutant-induced inflammatory responses in inhalational exposure studies should account for signals and noises caused by exercise, especially when the effect size is small. C1 [Arjomandi, Mehrdad] Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco Vet Affairs Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Donde, Aneesh; Wong, Hofer; Frelinger, Jessica; Power, Karron; Balmes, John R.; Arjomandi, Mehrdad] Univ Calif San Francisco, Human Exposure Lab, Div Occupat & Environm Med, San Francisco, CA 94121 USA. [Balmes, John R.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Frelinger, Jessica; Arjomandi, Mehrdad] Vet Affairs Med Ctr, Pulm Res Grp, San Francisco, CA 94121 USA. RP Arjomandi, M (reprint author), Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco Vet Affairs Med Ctr, Dept Med, Bldg 203,Room 3A-128,Mailstop 111-D,4150 Clement, San Francisco, CA 94121 USA. EM mehrdad.arjomandi@ucsf.edu FU California Air Resources Board; NIH/NHLBI [K23 HL083099]; Northern California Institute for Research and Education; University of California San Francisco Cardiovascular Research Institute FX This study was funded by California Air Resources Board, NIH/NHLBI K23 HL083099, the Northern California Institute for Research and Education, and the University of California San Francisco Cardiovascular Research Institute Faculty Development Funds. NR 35 TC 5 Z9 5 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD APR PY 2012 VL 54 IS 4 BP 466 EP 470 DI 10.1097/JOM.0b013e318246f1d4 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 923AB UT WOS:000302589300013 PM 22418276 ER PT J AU Hawn, MT Graham, LA Richman, JR Itani, KMF Plomondon, ME Altom, LK Henderson, WG Bryson, CL Maddox, TM AF Hawn, Mary T. Graham, Laura A. Richman, Joshua R. Itani, Kamal M. F. Plomondon, Margaret E. Altom, Laura K. Henderson, William G. Bryson, Christopher L. Maddox, Thomas M. TI The Incidence and Timing of Noncardiac Surgery after Cardiac Stent Implantation SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 123rd Annual Meeting of the Southern-Surgical-Association CY DEC, 2011 CL Hot Springs, VA SP So Surg Assoc ID DRUG-ELUTING STENTS; PERCUTANEOUS CORONARY INTERVENTION; PERIOPERATIVE CARDIOVASCULAR EVALUATION; ANTIPLATELET THERAPY; VASCULAR-SURGERY; LATE THROMBOSIS; BARE-METAL; DISCONTINUATION; PREVENTION; GUIDELINES AB BACKGROUND: In November 2007, national guidelines were released recommending delay of elective noncardiac surgery after cardiac revascularization with drug eluting stents (DES) for 12 months compared with 6 weeks after implantation of bare metal stents (BMS). STUDY DESIGN: To determine the incidence of noncardiac surgery within 24 months after stent placement, national VA data on cardiac stent implantation were merged with data from the VA National Surgery Office and Medicare. Using chi-square tests and log-rank analyses, we measured the incidence of noncardiac surgery after BMS and DES in relation to guideline release and surgical characteristics. RESULTS: From 2000 to 2010, 126,773 stent procedures were followed by 25,977 (20.5%) noncardiac operations within 24 months. Overall, 11.8% of the BMS surgery cohort had early surgery (less than 6 weeks) compared with 46.7% of the DES surgery cohort, which had early surgery (less than 12 months). The incidence of surgery differed significantly by stent type (BMS 24.1% vs DES 17.5%, p < 0.001) and in relation to guideline release (pre-24.6% vs postguideline 13.1%, p < 0.001). Higher complexity operations (work relative value units) were more likely to occur in the early period for both BMS (p < 0.0001) and DES (p < 0.003). After guideline release, the incidence of surgery within 12 months decreased from 16.7% to 10.0% (p < 0.0001). CONCLUSIONS: We found evidence that guidelines recommending delaying surgery appear to be effective in decreasing the incidence of early surgery; however, early surgery is still a frequent occurrence. Additional research is needed to better define the risk of cardiac and bleeding complications in patients undergoing subsequent noncardiac surgery, as well as the optimal time for surgery and method of antiplatelet management. (J Am Coll Surg 2012;214:658-667. (C) 2012 by the American College of Surgeons) C1 [Hawn, Mary T.] Univ Alabama, Dept Surg, Sect Gastrointestinal Surg, Birmingham, AL 35294 USA. [Hawn, Mary T.; Graham, Laura A.; Richman, Joshua R.; Altom, Laura K.] Univ Alabama, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Altom, Laura K.] Univ Alabama, Hlth Serv Comparat Effectiveness Res Training Pro, Birmingham, AL 35294 USA. [Itani, Kamal M. F.] Boston Univ, VA Boston Healthcare Syst, Boston, MA 02215 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. [Plomondon, Margaret E.; Maddox, Thomas M.] Univ Colorado, VA Eastern Colorado Hlth Care Syst, Denver, CO 80202 USA. [Henderson, William G.] Univ Colorado, Hlth Outcomes Program, Aurora, CO 80202 USA. [Bryson, Christopher L.] Dept Vet Affairs Med Ctr, Seattle, WA USA. [Bryson, Christopher L.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. RP Hawn, MT (reprint author), Univ Alabama, Dept Surg, Sect Gastrointestinal Surg, 1922 7th Ave S,KB 428, Birmingham, AL 35294 USA. EM mary.hawn@ccc.uab.edu NR 28 TC 19 Z9 19 U1 0 U2 1 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 APR PY 2012 VL 214 IS 4 BP 658 EP 666 DI 10.1016/j.jamcollsurg.2011.12.011 PG 9 WC Surgery SC Surgery GA 921NW UT WOS:000302485300055 PM 22341201 ER PT J AU Fick, DM Semla, TP AF Fick, Donna M. Semla, Todd P. TI 2012 American Geriatrics Society Beers Criteria: New Year, New Criteria, New Perspective SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material DE Beers list; Beers criteria; medications; older adults; drugs ID OLDER HOSPITALIZED-PATIENTS C1 [Fick, Donna M.] Penn State Univ, Sch Nursing, University Pk, PA 16802 USA. [Fick, Donna M.] Penn State Univ, Coll Med, Dept Psychiat, University Pk, PA 16802 USA. [Semla, Todd P.] US Dept Vet Affairs, Natl Pharm Benefits Management Serv, Hines, IL USA. RP Fick, DM (reprint author), Care of Campanellu CM, Amer Geriatr Soc, 40 Fulton St,18th Floor, New York, NY 10038 USA. FU NINR NIH HHS [R01 NR011042] NR 4 TC 36 Z9 36 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 IS 4 BP 614 EP 615 DI 10.1111/j.1532-5415.2012.03922.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 923MR UT WOS:000302623900003 PM 22376003 ER PT J AU Fick, D Semla, T Beizer, J Dombrowski, R Brandt, N DuBeau, CE Flanagan, N Hanlon, J Hollmann, P Linnebur, S Nau, D Rehm, B Sandhu, S Steinman, M AF Fick, Donna Semla, Todd Beizer, Judith Dombrowski, Robert Brandt, Nicole DuBeau, Catherine E. Flanagan, Nina Hanlon, Joseph Hollmann, Peter Linnebur, Sunny Nau, David Rehm, Bob Sandhu, Satinderpal Steinman, Michael CA Amer Geriatrics Soc 2012 Beers TI American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Beers list; medications; Beers Criteria; drugs; older adults ID ADVERSE DRUG-REACTIONS; EXPLICIT CRITERIA; CLINICAL-TRIALS; OUTPATIENTS; POPULATION; EVENTS; SCALE; AGE C1 [Amer Geriatrics Soc 2012 Beers] Amer Geriatr Soc, New York, NY USA. [Fick, Donna] Penn State Univ, Sch Nursing, University Pk, PA 16802 USA. [Fick, Donna] Penn State Univ, Coll Med, Dept Psychiat, University Pk, PA 16802 USA. [Semla, Todd] Natl Pharm Benefits Management Serv, US Dept Vet Affairs, Chicago, IL USA. [Semla, Todd] Northwestern Univ, Chicago, IL 60611 USA. [Beizer, Judith] St Johns Univ, New York, NY USA. [Brandt, Nicole] Univ Maryland, Baltimore, MD 21201 USA. [Dombrowski, Robert] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. [DuBeau, Catherine E.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Flanagan, Nina] Binghamton Univ, Dunmore, PA USA. [Hanlon, Joseph] Univ Pittsburgh, Sch Med, Dept Med Geriatr Med, Pittsburgh, PA USA. [Hanlon, Joseph] Vet Adm Hlth Syst, Geriatr Educ & Res & Clin Ctr, Pittsburgh, PA USA. [Hollmann, Peter] Blue Cross Blue Shield Rhode Isl, Cranston, RI USA. [Linnebur, Sunny] Univ Colorado, Sch Pharm & Pharmaceut Sci, Aurora, CO USA. [Nau, David] Pharm Qual Alliance Inc, Baltimore, MD USA. [Rehm, Bob] Natl Comm Qual Assurance, Washington, DC USA. [Sandhu, Satinderpal] MetroHlth Med Ctr, Cleveland, OH USA. [Sandhu, Satinderpal] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Steinman, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Steinman, Michael] San Francisco VA Med Ctr, San Francisco, CA USA. RP Fick, D (reprint author), Care of Campanelli CM, Amer Geriatr Soc, 40 Fulton St,18th Floor, New York, NY 10038 USA. FU John A. Hartford Foundation; Talyst; Econometrics; Health Resources and Services Administration; State of Maryland Office of Health Care Quality; National Institute of Health (NIH) for National Institute of Nursing Research [R01 NR011042, R01NR012242]; National Institute on Aging [R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056]; National Institute of Nursing Research [R01 NR010135]; Agency for Healthcare Research and Quality [R01 HS017695, R01HS018721] FX Sue Radcliff, Independent Researcher, Denver, Colorado, provided research services. Susan E. Aiello, DVM, ELS, provided editorial services. Christine Campanelli and Elvy Ickowicz, MPH, provided additional research and administrative support. The development of this paper was supported in part by an unrestricted grant from the John A. Hartford Foundation.; Drs. Dombrowski, Flanagan, Hanlon, Hollmann, Rehm, Sandhu, and Steinman indicated no conflicts of interest. Dr. Beizer is an author and editor for LexiComp, Inc. She is on the Pharmacy and Therapeutics Committee for Part D at Medco Health Solutions. Dr. Brandt is on the Pharmacy and Therapeutics Committees at Omnicare and receives grants from Talyst (research grant), Econometrics (research grant), Health Resources and Services Administration (educational grant), and the State of Maryland Office of Health Care Quality (educational grant). Dr. Dubeau serves as a consultant for Pfizer, Inc. (urinary incontinence) and the New England Research Institute (nocturia). Dr. Fick is partially supported by the National Institute of Health (NIH) for National Institute of Nursing Research grants R01 NR011042 and R01NR012242. Dr. Hanlon is supported in part by National Institute on Aging grants and contracts (R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056), a National Institute of Nursing Research grant (R01 NR010135), and Agency for Healthcare Research and Quality grants (R01 HS017695, R01HS018721). Dr. Linnebur receives an honorarium for serving as a member of the Pharmacy and Therapeutics NR 35 TC 436 Z9 463 U1 4 U2 48 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 APR PY 2012 VL 60 IS 4 BP 616 EP 631 DI 10.1111/j.1532-5415.2012.03923.x PG 16 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 923MR UT WOS:000302623900004 ER PT J AU Thorpe, CT Thorpe, JM Kind, AJH Bartels, CM Everett, CM Smith, MA AF Thorpe, Carolyn T. Thorpe, Joshua M. Kind, Amy J. H. Bartels, Christie M. Everett, Christine M. Smith, Maureen A. TI Receipt of Monitoring of Diabetes Mellitus in Older Adults with Comorbid Dementia SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE diabetes mellitus; dementia; guideline adherence; care quality; Medicare ID MEDICARE CLAIMS DATA; ALZHEIMERS-DISEASE; UNITED-STATES; CARE; RISK; VALIDATION; IMPACT; PREVALENCE; ACCURACY; INDEX AB OBJECTIVES: To examine the extent to which receipt of recommended monitoring of diabetes mellitus (DM) differed for participants with and without comorbid dementia, as well as the effect of other comorbidities on monitoring of DM in individuals with comorbid dementia. DESIGN: Retrospective cohort study. SETTING: Secondary analysis of 2005/2006 claims and enrollment data for a 5% national random sample of Medicare beneficiaries. PARTICIPANTS: Two hundred eighty-eight thousand eight hundred five Medicare fee-for-service beneficiaries with a diagnosis of DM before 2006, 44,717 (16%) of whom had evidence of comorbid dementia in claims. MEASUREMENTS: Established algorithms were used to determine whether patients received at least one glycosylated hemoglobin (HbA1c) test, one low-density lipoprotein cholesterol (LDL-C) test, and one annual eye examination in 2006 and to construct variables representing comorbidities common in DM, sociodemographic characteristics, and patterns of healthcare utilization. RESULTS: In unadjusted and fully adjusted models, the presence of dementia reduced the likelihood of receiving HbA1c tests, LDL-C tests, and eye examinations, with effects being smallest for HbA1c tests. The effects of other comorbidities on DM monitoring in participants with dementia varied according to the nature of the comorbidity and the specific test. CONCLUSION: Dementia reduces the likelihood that individuals with DM will receive recommended annual monitoring for DM. More research is needed to understand reasons for lower monitoring in this subgroup and how this affects functioning, adverse events, and quality of life. J Am Geriatr Soc 60:644-651, 2012. C1 [Thorpe, Carolyn T.; Thorpe, Joshua M.] Univ Pittsburgh, Dept Pharm & Therapeut, Sch Pharm, Pittsburgh, PA 15261 USA. [Thorpe, Carolyn T.; Thorpe, Joshua M.] Vet Affairs Pittsburgh Healthcare Syst, Hlth Serv Res & Dev, Pittsburgh, PA USA. [Kind, Amy J. H.] Univ Wisconsin, Div Geriatr, Sch Med & Publ Hlth, Madison, WI USA. [Bartels, Christie M.] Univ Wisconsin, Rheumatol Sect, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Everett, Christine M.; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Everett, Christine M.; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. [Kind, Amy J. H.] William S Middleton Hosp, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, Madison, WI USA. RP Thorpe, CT (reprint author), Univ Pittsburgh, Dept Pharm & Therapeut, Sch Pharm, 919 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. EM ctthorpe@pitt.edu RI Thorpe, Joshua/C-1188-2013 FU Health Innovation Program; University of Wisconsin Institute for Clinical and Translational Research; National Center for Research Resources, National Institutes of Health [1UL1RR025011]; University of Wisconsin School of Medicine and Public Health FX Support was provided by the Health Innovation Program and the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research, Grant 1UL1RR025011 from the Clinical and Translational Science Award program of the National Center for Research Resources, National Institutes of Health. Additional funding for this project was provided by the University of Wisconsin School of Medicine and Public Health from the Wisconsin Partnership Program. NR 36 TC 13 Z9 13 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 IS 4 BP 644 EP 651 DI 10.1111/j.1532-5415.2012.03907.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 923MR UT WOS:000302623900007 PM 22428535 ER PT J AU Espinoza, SE Jung, I Hazuda, H AF Espinoza, Sara E. Jung, Inkyung Hazuda, Helen TI Frailty Transitions in the San Antonio Longitudinal Study of Aging SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE frailty; older adults; transitions ID OLDER MEXICAN-AMERICANS; CARDIOVASCULAR HEALTH; WOMENS HEALTH; ADULTS; EXERCISE; OBESITY; INFLAMMATION; MORTALITY; PEOPLE AB OBJECTIVES: To examine frailty transitions in Mexican American (MA) and European American (EA) older adults. DESIGN: Longitudinal, observational cohort study. SETTING: Socioeconomically diverse neighborhoods in San Antonio, Texas. PARTICIPANTS: Three hundred twelve MA and 285 EA community-dwelling older adults (>65) with frailty information at baseline (1992-1996) and transition information at follow-up (2000/01) in the San Antonio Longitudinal Study of Aging. MEASUREMENTS: Five frailty characteristics (weight loss, exhaustion, weakness, slowness, and low physical activity), frailty score (0-5), and overall frailty state (nonfrail = 0 characteristics, prefrail = 1 or 2, frail = >= 3) were assessed at baseline. Transitions (progressed, regressed, or no change) were assessed for frailty score and state. Odds ratios (ORs) of progression and regression in individual characteristics were estimated using generalized estimating equations adjusted for age, sex, ethnic group, socioeconomic status, comorbidity, diabetes, and follow-up interval. RESULTS: Diabetes mellitus with macrovascular complications (OR = 1.84, 95% confidence interval (CI) = 1.02-3.33), fewer years of education (OR = 0.96, 95% CI = 0.93-1.0) and follow-up interval (OR = 1.3, 95% CI = 1.17-1.46) were significant predictors of progression in any frailty characteristic. Mortality increased with greater frailty state, and prefrail individuals were more likely than frail individuals to regress. CONCLUSION: Diabetes mellitus with macrovascular complications and fewer years of education are important predictors of progression in any frailty characteristic. Because of greater risk of death than for the nonfrail state and greater likelihood of regression than for the frail state, the prefrail state may be an optimal target for intervention. J Am Geriatr Soc 60:652-660, 2012. C1 [Espinoza, Sara E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr Gerontol & Palliat Med, San Antonio, TX 78229 USA. [Espinoza, Sara E.] Univ Texas Hlth Sci Ctr San Antonio, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Hazuda, Helen] Univ Texas Hlth Sci Ctr San Antonio, Vet Res Disseminat & Implementat Ctr, S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. [Espinoza, Sara E.; Hazuda, Helen] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA. [Espinoza, Sara E.; Hazuda, Helen] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Jung, Inkyung] Yonsei Univ, Coll Med, Dept Biostat, Seoul, South Korea. RP Espinoza, SE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr Gerontol & Palliat Med, 7703 Floyd Curl Dr,Mail Code 7875, San Antonio, TX 78229 USA. EM espinozas2@uthscsa.edu FU National Institute on Aging [R01-AG10444, R01-AG16518]; National Center for Research Resources (NCRR) [M01-RR01345]; Harold Amos Medical Faculty Development Program; Robert Wood Johnson Foundation; NCRR [KL2 RR025766] FX This research was supported by National Institute on Aging Grants R01-AG10444 and R01-AG16518 and National Center for Research Resources (NCRR) Grant M01-RR01345. This work was also supported by The Harold Amos Medical Faculty Development Program with the Robert Wood Johnson Foundation and Clinical Translational Science Award KL2 RR025766 from NCRR. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCRR of the National Institutes of Health. 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 U. S. government. This material is the result of work supported with resources and the use of facilities at the Audie Murphy Veterans Affairs Medical Center, San Antonio, Texas. The authors gratefully acknowledge Adrienne Boulton for her assistance in writing the computer programs used to construct the criteria for classifying frailty in the SALSA study. NR 32 TC 36 Z9 37 U1 2 U2 9 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 APR PY 2012 VL 60 IS 4 BP 652 EP 660 DI 10.1111/j.1532-5415.2011.03882.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 923MR UT WOS:000302623900008 PM 22316162 ER PT J AU Huh, JT Weaver, CM Martin, JL Caskey, NH O'Riley, A Kramer, BJ AF Huh, Joung T. Weaver, Christopher M. Martin, Jennifer L. Caskey, Nicholas H. O'Riley, Alisa Kramer, Betty Josea TI Effects of a Late-Life Suicide Risk-Assessment Training on Multidisciplinary Healthcare Providers SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE late-life suicide; suicide prevention training; multidisciplinary education ID COMPLETED SUICIDE; OLDER PATIENTS; AGE; IDEATION; ADULTS AB Older adults are among the highest at risk for completing suicide, and they are more likely to seek mental health services from providers outside of traditional mental health care, but providers across the spectrum of care have limited training in suicide risk assessment and management and particularly lack training in suicide prevention for older adults. An educational program was developed to increase awareness and improve suicide risk assessment and management training for a range of healthcare providers who may see older adults in their care settings. One hundred thirty-two participants from two Veterans Affairs Medical Centers participated in a 6.5-hour-long workshop in the assessment and management of suicide risk in older adults. Participants were asked to complete pre- and postworkshop case notes and report on subjective changes in knowledge, attitudes, and confidence in assessment and managing suicide risk in older adults. Participants included social workers, nurses, physicians, psychologists, and occupational therapists from a variety of care settings, including outpatient and inpatient medical, outpatient and inpatient mental health, specialty clinics, home, and community. After the workshop, participants demonstrated improvement in the overall quality of case notes (P = .001), greater ability to recognize important conceptual suicide risk categories (P = .003), and reported heightened awareness of the importance of late-life suicide. The results suggest that educational training may have beneficial effect on the ability of multidisciplinary care providers to identify and manage suicide risk in elderly adults. J Am Geriatr Soc 60:775-780, 2012. C1 [Huh, Joung T.] Palo Alto Univ, Geriatr Res Educ & Clin Ctr, Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. [Weaver, Christopher M.] Palo Alto Univ, Dept Psychol, Palo Alto, CA 94304 USA. [Martin, Jennifer L.; Caskey, Nicholas H.; Kramer, Betty Josea] Vet Affairs Greater Los Angeles Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Martin, Jennifer L.; Kramer, Betty Josea] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr Med, Los Angeles, CA 90095 USA. [Caskey, Nicholas H.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. [O'Riley, Alisa] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. RP Huh, JT (reprint author), Palo Alto Univ, Geriatr Res Educ & Clin Ctr, Vet Affairs Palo Alto Hlth Care Syst, 3801 Miranda Ave,182B, Palo Alto, CA 94304 USA. EM terri.huh@va.gov FU VA Palo Alto Health Care System; VA Greater Los Angeles Health Care System; National Institutes of Health, National Institute on Aging [K23 AG028452] FX This material is the result of work supported with resources and facilities at the VA Palo Alto Health Care System, the VA Greater Los Angeles Health Care System, and by National Institutes of Health, National Institute on Aging Grant K23 AG028452 (Martin). NR 16 TC 6 Z9 6 U1 0 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 IS 4 BP 775 EP 780 DI 10.1111/j.1532-5415.2011.03843.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 923MR UT WOS:000302623900025 PM 22288717 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI If the Choices Are All the Same, Why Not Prefer the Less-Expensive Option? 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 3 TC 2 Z9 2 U1 0 U2 0 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 APR PY 2012 VL 10 IS 4 BP 425 EP 426 PG 2 WC Oncology SC Oncology GA 920YO UT WOS:000302445400001 PM 22491041 ER PT J AU Benson, A Arnoletti, JP Bekaii-Saab, T Chan, E Chen, YJ Choti, MA Cooper, HS Dilawari, RA Engstrom, PF Enzinger, PC Fakih, MG Fleshman, JW Fuchs, CS Grem, JL Leong, LA Lin, E May, KS Mulcahy, MF Murphy, K Rohren, E Ryan, DP Saltz, L Sharma, S Shibata, D Skibber, JM Small, W Sofocleous, CT Venook, AP Willett, C Freedman-Cass, DA AF Benson, Al B. Arnoletti, J. Pablo Bekaii-Saab, Tanios Chan, Emily Chen, Yi-Jen Choti, Michael A. Cooper, Harry S. Dilawari, Raza A. Engstrom, Paul F. Enzinger, Peter C. Fakih, Marwan G. Fleshman, James W., Jr. Fuchs, Charles S. Grem, Jean L. Leong, Lucille A. Lin, Edward May, Kilian Salerno Mulcahy, Mary F. Murphy, Kate Rohren, Eric Ryan, David P. Saltz, Leonard Sharma, Sunil Shibata, David Skibber, John M. Small, William, Jr. Sofocleous, Constantinos T. Venook, Alan P. Willett, Christopher Freedman-Cass, Deborah A. TI Anal Carcinoma, Version 2.2012 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID HUMAN-PAPILLOMAVIRUS; INTRAEPITHELIAL NEOPLASIA; QUADRIVALENT VACCINE; CANCER; INFECTION; PREVALENCE; LESIONS; TRIAL; WOMEN; RISK AB The workup and management of squamous cell anal carcinoma, which represents the most common histologic form of the disease, are addressed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Anal Carcinoma. These NCCN Guidelines Insights provide a summary of major discussion points of the 2012 NCCN Anal Carcinoma Panel meeting. In summary, the panel made 4 significant changes to the 2012 NCCN Guidelines for Anal Carcinoma: 1) local radiation therapy was added as an option for the treatment of patients with metastatic disease; 2) multifield technique is now preferred over anteroposterior-posteroanterior (AP-PA) technique for radiation delivery and the AP-PA technique is no longer recommended as the standard of care; 3) PET/CT should now be considered for radiation therapy planning; and 4) a section on risk reduction was added to the discussion section. In addition, the panel discussed the use of PET/CT for the workup of anal canal cancer and decided to maintain the recommendation that it can be considered in this setting. They also discussed the use of PET/CT for the workup of anal margin cancer and for the assessment of treatment response. They reaffirmed their recommendation that PET/CT is not appropriate in these settings. (JNCCN 2012;10:449-454) C1 [Benson, Al B.; Mulcahy, Mary F.; Small, William, Jr.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Arnoletti, J. Pablo] Univ Alabama, Comprehens Canc Ctr, Birmingham, W Midlands, England. [Bekaii-Saab, Tanios] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Bekaii-Saab, Tanios] Solove Res Inst, Columbus, OH USA. [Chan, Emily] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Chen, Yi-Jen; Leong, Lucille A.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Choti, Michael A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Cooper, Harry S.; Engstrom, Paul F.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Dilawari, Raza A.] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Enzinger, Peter C.; Fuchs, Charles S.] Dana Farber Brigham & Womens Canc Ctr, Birmingham, AL USA. [Fakih, Marwan G.] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA. [Fleshman, James W., Jr.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Grem, Jean L.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE 68198 USA. [Lin, Edward] Fred Hutchinson Canc Res Ctr Seattle Canc Care Al, Seattle, WA USA. [May, Kilian Salerno] Roswell Pk Canc Inst, Buffalo, NY USA. [Ryan, David P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Saltz, Leonard; Sofocleous, Constantinos T.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Sharma, Sunil] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. RP Benson, A (reprint author), Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. RI Bekaii-Saab, Tanios/E-2733-2011; OI Saltz, Leonard/0000-0001-8353-4670 NR 29 TC 36 Z9 37 U1 0 U2 2 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 APR PY 2012 VL 10 IS 4 BP 449 EP 454 PG 6 WC Oncology SC Oncology GA 920YO UT WOS:000302445400005 PM 22491045 ER PT J AU Ettinger, DS Armstrong, DK Barbour, S Berger, MJ Bierman, PJ Bradbury, B Ellis, G Kirkegaard, S Kloth, DD Kris, MG Lim, D Michaud, LB Nabati, L Noonan, K Rugo, HS Siler, D Sorscher, SM Stelts, S Stucky-Marshall, L Todaro, B Urba, SG AF Ettinger, David S. Armstrong, Debra K. Barbour, Sally Berger, Michael J. Bierman, Philip J. Bradbury, Bob Ellis, Georgianna Kirkegaard, Steve Kloth, Dwight D. Kris, Mark G. Lim, Dean Michaud, Laura Boehnke Nabati, Lida Noonan, Kim Rugo, Hope S. Siler, Darby Sorscher, Steven M. Stelts, Sundae Stucky-Marshall, Lisa Todaro, Barbara Urba, Susan G. TI Antiemesis Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; antiemesis; nausea and vomiting; chemotherapy-induced; 5-HT3-receptor antagonists; NK-1 receptor antagonists ID CHEMOTHERAPY-INDUCED NAUSEA; MODERATELY-EMETOGENIC CHEMOTHERAPY; HIGH-DOSE CISPLATIN; METOCLOPRAMIDE PLUS DEXAMETHASONE; RANDOMIZED CONTROLLED-TRIAL; MULTIPLE-DAY CHEMOTHERAPY; 5-HYDROXYTRYPTAMINE-3 RECEPTOR ANTAGONIST; ACUPUNCTURE-POINT STIMULATION; RECEIVING CANCER-CHEMOTHERAPY; PLACEBO-CONTROLLED TRIAL C1 [Ettinger, David S.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Armstrong, Debra K.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Barbour, Sally] Duke Canc Inst, Durham, England. [Berger, Michael J.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Bierman, Philip J.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Ellis, Georgianna] Fred Hutchinson Canc Res Ctr Seattle Canc Care Al, Seattle, WA USA. [Kirkegaard, Steve] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Kloth, Dwight D.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Kris, Mark G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lim, Dean] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Michaud, Laura Boehnke] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Nabati, Lida; Noonan, Kim] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Rugo, Hope S.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Siler, Darby] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Sorscher, Steven M.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Sorscher, Steven M.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Stelts, Sundae] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Stucky-Marshall, Lisa] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Todaro, Barbara] Roswell Pk Canc Inst, Buffalo, NY USA. [Urba, Susan G.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Ettinger, DS (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. NR 152 TC 34 Z9 34 U1 2 U2 9 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 APR PY 2012 VL 10 IS 4 BP 456 EP 485 PG 30 WC Oncology SC Oncology GA 920YO UT WOS:000302445400006 PM 22491046 ER PT J AU Motzer, RJ Agarwal, N Beard, C Bhayani, S Bolger, GB Buyyounouski, MK Carducci, MA Chang, SS Choueiri, TK Gupta, S Hancock, SL Hudes, GR Jonasch, E Kuzel, TM Lau, C Levine, EG Lin, DW Margolin, KA Michaelson, MD Olencki, T Pili, R Ratliff, TW Redman, BG Robertson, CN Ryan, CJ Sheinfeld, J Wang, J Wilder, RB AF Motzer, Robert J. Agarwal, Neeraj Beard, Clair Bhayani, Sam Bolger, Graeme B. Buyyounouski, Mark K. Carducci, Michael A. Chang, Sam S. Choueiri, Toni K. Gupta, Shilpa Hancock, Steven L. Hudes, Gary R. Jonasch, Eric Kuzel, Timothy M. Lau, Clayton Levine, Ellis G. Lin, Daniel W. Margolin, Kim A. Michaelson, M. Dror Olencki, Thomas Pili, Roberto Ratliff, Thomas W. Redman, Bruce G. Robertson, Cary N. Ryan, Charles J. Sheinfeld, Joel Wang, Jue Wilder, Richard B. TI Testicular Cancer Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; testicular cancer; germ cell tumors; alpha-fetoprotein; lactate dehydrogenase; human chorionic gonadotropin; cisplatin; seminoma; nonseminoma ID GERM-CELL TUMORS; LYMPH-NODE DISSECTION; STAGE-I SEMINOMA; POSITRON-EMISSION-TOMOGRAPHY; MEDICAL-RESEARCH-COUNCIL; HIGH-DOSE CHEMOTHERAPY; INDIANA-UNIVERSITY EXPERIENCE; TERM-FOLLOW-UP; GEMCITABINE SALVAGE CHEMOTHERAPY; CISPLATIN-BASED CHEMOTHERAPY C1 [Motzer, Robert J.; Sheinfeld, Joel] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Beard, Clair; Choueiri, Toni K.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Bhayani, Sam] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Bhayani, Sam] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Bolger, Graeme B.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, W Midlands, England. [Buyyounouski, Mark K.; Hudes, Gary R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Carducci, Michael A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Chang, Sam S.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Hancock, Steven L.] Stanford Canc Inst, Stanford, CA USA. [Jonasch, Eric] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kuzel, Timothy M.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Lau, Clayton] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Levine, Ellis G.; Pili, Roberto] Roswell Pk Canc Inst, Buffalo, NY USA. [Lin, Daniel W.] Univ Washington Seattle Canc Care Alliance, Seattle, WA USA. [Margolin, Kim A.] Fred Hutchinson Canc Res Ctr Seattle Canc Care Al, Seattle, WA USA. [Michaelson, M. Dror] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Olencki, Thomas] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Olencki, Thomas] Solove Res Inst, Columbus, OH USA. [Ratliff, Thomas W.] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Redman, Bruce G.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Robertson, Cary N.] Duke Canc Inst, Durham, NC USA. [Ryan, Charles J.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Wang, Jue] Nebraska Med Ctr, UNMC Eppeley Canc Ctr, Omaha, NE USA. RP Motzer, RJ (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 149 TC 28 Z9 30 U1 0 U2 8 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 APR PY 2012 VL 10 IS 4 BP 502 EP 535 PG 34 WC Oncology SC Oncology GA 920YO UT WOS:000302445400009 PM 22491049 ER PT J AU Fung, C Fossa, SD Beard, CJ Travis, LB AF Fung, Chunkit Fossa, Sophie D. Beard, Clair J. Travis, Lois B. TI Second Malignant Neoplasms in Testicular Cancer Survivors SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID GERM-CELL TUMORS; LONG-TERM SURVIVORS; RANDOMIZED-TRIAL; PROSPECTIVE MULTICENTER; CARDIOVASCULAR-DISEASE; COMPUTED-TOMOGRAPHY; RESEARCH STRATEGIES; RADIATION-EXPOSURE; FOLLOW-UP; STAGE IIA AB Second malignant neoplasms (SMNs) are a potentially life-threatening late effect of testicular cancer (TC) and its therapy. Although the increased risk for developing solid tumors among TC survivors is largely attributed to radiotherapy, chemotherapy may also be associated with excess risks. However, the baseline risks of developing site-specific SMNs in TC survivors have not yet been quantified, nor have interactions between treatments and other risk factors been elucidated. Studies to date report overall relative risks ranging from 1.4- to 2.8-fold for SMN in TC survivors, with significantly elevated risks apparent for more than 35 years. Analytic investigations show relationships between increasing radiation dose and/or field size and solid tumor risk. Small excess risks of leukemia follow treatment with either chemotherapy or radiotherapy. Recently, concern has been expressed about the increased risk of SMN from radiation exposure during imaging surveillance for recurrence. A small number of studies have examined this issue, generating inconclusive results. Given the current changes in TC treatment that result in lower radiation doses, in the future solid tumors will likely have a considerably lower impact on the lives of TC survivors, although diligent follow-up will be required to accurately quantify long-term risks and to ascertain risks associated with chemotherapy. (JNCCN 2012;10:545-556) C1 [Travis, Lois B.] Univ Rochester, Med Ctr, Rubin Ctr Canc Survivorship, Rochester, NY 14642 USA. [Travis, Lois B.] Univ Rochester, Med Ctr, Dept Radiat Oncol, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. [Fung, Chunkit] Univ Rochester, Med Ctr, Dept Med Oncol, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. [Fossa, Sophie D.] Norwegian Radium Hosp, Oslo, Norway. [Beard, Clair J.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. RP Travis, LB (reprint author), Univ Rochester, Med Ctr, Rubin Ctr Canc Survivorship, 265 Crittenden Blvd,Box CU420318, Rochester, NY 14642 USA. EM lois_travis@urmc.rochester.edu NR 73 TC 13 Z9 13 U1 0 U2 2 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 APR PY 2012 VL 10 IS 4 BP 545 EP 556 PG 12 WC Oncology SC Oncology GA 920YO UT WOS:000302445400011 PM 22491051 ER PT J AU O'Connor, OJ Buckley, JM Arellano, RS AF O'Connor, Owen J. Buckley, Julliette M. Arellano, Ronald S. TI Doctor, Would You Drain This Collection? SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material ID EXPERIENCE C1 [O'Connor, Owen J.; Arellano, Ronald S.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Buckley, Julliette M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP O'Connor, OJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM owen.oconnor7@gmail.com NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD APR PY 2012 VL 23 IS 4 BP 519 EP 519 DI 10.1016/j.jvir.2012.01.054 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 920IA UT WOS:000302396300015 PM 22464716 ER PT J AU Kanai, R Zaupa, C Sgubin, D Antoszczyk, SJ Martuza, RL Wakimoto, H Rabkin, SD AF Kanai, Ryuichi Zaupa, Cecile Sgubin, Donatella Antoszczyk, Slawomir J. Martuza, Robert L. Wakimoto, Hiroaki Rabkin, Samuel D. TI Effect of gamma 34.5 Deletions on Oncolytic Herpes Simplex Virus Activity in Brain Tumors SO JOURNAL OF VIROLOGY LA English DT Article ID CANCER STEM-CELLS; MUTANT EXPRESSING ICP34.5; PROTEIN PHOSPHATASE 1; MALIGNANT GLIOMA; IN-VITRO; GAMMA(1)34.5 PROTEIN; GLIOBLASTOMA CELLS; NUCLEAR ANTIGEN; NULL MUTANTS; AUTOPHAGY AB The ICP34.5 protein of herpes simplex virus (HSV) is involved in many aspects of viral pathogenesis; promoting neurovirulence, inhibiting interferon-induced shutoff of protein synthesis, interacting with PCNA and TBK1, inhibiting dendritic cell (DC) maturation, and binding to Beclin 1 to interfere with autophagy. Because of its key role in neuropathogenicity, the gamma 34.5 gene is deleted in all oncolytic HSVs (oHSVs) currently in clinical trial for treating malignant gliomas. Unfortunately, deletion of gamma 34.5 attenuates virus replication in cancer cells, especially human glioblastoma stem cells (GSCs). To develop new oHSVs for use in the brain and that replicate in GSCs, we explored the effect of deleting the gamma 34.5 Beclin 1 binding domain (BBD). To ensure cancer selectivity and safety, we inactivated the ICP6 gene (UL39, large subunit of ribonucleotide reductase), constructing ICP6 mutants with different gamma 34.5 genotypes: Delta 68HR-6, intact gamma 34.5; Delta 68H-6, gamma 34.5 BBD deleted; and 1716-6, gamma 34.5 deleted. Multimutated Delta 68H-6 exhibited minimal neuropathogenicity in HSV-1-susceptible mice, as opposed to Delta 68H and Delta 68HR-6. It replicated well in human glioma cell lines and GSCs, effectively killing cells in vitro and prolonging survival of mice bearing orthotopic brain tumors. In contrast, 1716 and 1716-6 barely replicated in GSCs. Infection of glioma cells with Delta 68H-6 and 1716-6 induced autophagy and increased phosphorylation of eIF2 alpha, while inhibition of autophagy, by Beclin 1 short hairpin RNA (shRNA) knockdown or pharmacological inhibition, had no effect on virus replication or phosphorylated eIF2 alpha (p-eIF2 alpha) levels. Thus, Delta 68H-6 represents a new oHSV vector that is safe and effective against a variety of brain tumor models. C1 [Rabkin, Samuel D.] Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rabkin, SD (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Boston, MA 02114 USA. EM rabkin@helix.mgh.harvard.edu RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU Public Health Service from NINDS [NS-032677]; Department of Defense [W81XWH-07-1-0359] FX This work was supported in part by Public Health Service grant NS-032677 from NINDS to R.L.M. and Department of Defense grant W81XWH-07-1-0359 to S.D.R. NR 71 TC 19 Z9 23 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2012 VL 86 IS 8 BP 4420 EP 4431 DI 10.1128/JVI.00017-12 PG 12 WC Virology SC Virology GA 917NU UT WOS:000302185400036 PM 22345479 ER PT J AU Singh, G Robinson, CM Dehghan, S Schmidt, T Seto, D Jones, MS Dyer, DW Chodosh, J AF Singh, Gurdeep Robinson, Christopher M. Dehghan, Shoaleh Schmidt, Timothy Seto, Donald Jones, Morris S. Dyer, David W. Chodosh, James TI Overreliance on the Hexon Gene, Leading to Misclassification of Human Adenoviruses SO JOURNAL OF VIROLOGY LA English DT Article ID ACUTE RESPIRATORY-DISEASE; COMPLETE GENOME SEQUENCE; EPIDEMIC KERATOCONJUNCTIVITIS; BIOINFORMATICS ANALYSIS; COMPUTATIONAL ANALYSIS; MOLECULAR EVOLUTION; RECOMBINATION; ANNOTATION; SEROTYPE; ARTEMIS AB The genome of human adenovirus (HAdV) D30 was sequenced in depth. Sequence assembly and analysis revealed two distinct viral sequences with identical hexon genes, which were the same as the one previously reported for HAdV-D30. However, one of the two viruses was found to be a recombinant of HAdV-D29. Exclusive reliance on serum neutralization can lead to mischaracterization of adenoviruses and miss coinfections. Whole-genome sequencing remains the gold standard for proper classification of HAdVs. C1 [Singh, Gurdeep; Robinson, Christopher M.; Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Howe Lab, Boston, MA 02115 USA. [Dehghan, Shoaleh; Seto, Donald; Jones, Morris S.] George Mason Univ, Sch Syst Biol, Manassas, VA USA. [Schmidt, Timothy; Dyer, David W.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA. RP Chodosh, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Howe Lab, Boston, MA 02115 USA. EM james_chodosh@meei.harvard.edu FU NIH [EY013124, P30EY014104]; Research to Prevent Blindness, Inc., New York, NY; Massachusetts Lions Eye Research Fund FX This study was supported by NIH grants EY013124 and P30EY014104, a Senior Scientific Investigator Award (to J.C.) from Research to Prevent Blindness, Inc., New York, NY, and the Massachusetts Lions Eye Research Fund. NR 30 TC 14 Z9 16 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2012 VL 86 IS 8 BP 4693 EP 4695 DI 10.1128/JVI.06969-11 PG 3 WC Virology SC Virology GA 917NU UT WOS:000302185400063 PM 22301156 ER PT J AU Ambrose, Z Lee, K Ndjomou, J Xu, HZ Oztop, I Matous, J Takemura, T Unutmaz, D Engelman, A Hughes, SH KewalRamani, VN AF Ambrose, Zandrea Lee, KyeongEun Ndjomou, Jean Xu, Hongzhan Oztop, Ilker Matous, James Takemura, Taichiro Unutmaz, Derya Engelman, Alan Hughes, Stephen H. KewalRamani, Vineet N. TI Human Immunodeficiency Virus Type 1 Capsid Mutation N74D Alters Cyclophilin A Dependence and Impairs Macrophage Infection SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 INFECTION; DENDRITIC CELLS; NUCLEAR IMPORT; RESTRICTION; COMPLEX; PROTEIN; REPLICATION; RESISTANCE; PARTICLES; SAMHD1 AB The antiviral factor CPSF6-358 interferes with the nuclear entry of human immunodeficiency virus type 1 (HIV-1). HIV-1 acquires resistance to CPSF6-358 through the N74D mutation of the capsid (CA), which alters its nuclear entry pathway. Here we show that compared to wild-type (WT) HIV-1, N74D HIV-1 is more sensitive to cyclosporine, has increased sensitivity to nevirapine, and is impaired in macrophage infection prior to reverse transcription. These phenotypes suggest a difference in the N74D reverse transcription complex that manifests early after infection and prior to interaction with the nuclear pore. Overall, our data indicate that N74D HIV-1 replication in transformed cells requires cyclophilin A but is dependent on other interactions in macrophages. C1 [Ambrose, Zandrea; Ndjomou, Jean; Xu, Hongzhan; Matous, James] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15260 USA. [Lee, KyeongEun; Takemura, Taichiro; Hughes, Stephen H.; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Oztop, Ilker; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Unutmaz, Derya] NYU, Sch Med, Dept Pathol & Microbiol, New York, NY USA. RP Ambrose, Z (reprint author), Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15260 USA. EM zaa4@pitt.edu; vineet@mail.nih.gov FU Pittsburgh Center for HIV Protein Interactions; National Cancer Institute's intramural Center for Cancer Research; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [1 UL1 RR024153]; NIH Roadmap for Medical Research; NIH [GM082251, AI078839, AI052014] FX This work was supported by a contribution from the Pittsburgh Center for HIV Protein Interactions and was supported by the National Cancer Institute's intramural Center for Cancer Research, which supports the HIV Drug Resistance Program (S. H. H. and V.N.K.), grant number 1 UL1 RR024153 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research (Z.A.), and NIH grants GM082251 (Z.A.), AI078839 (D.U.), and AI052014 (A.E.). NR 30 TC 39 Z9 39 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2012 VL 86 IS 8 BP 4708 EP 4714 DI 10.1128/JVI.05887-11 PG 7 WC Virology SC Virology GA 917NU UT WOS:000302185400066 PM 22301145 ER PT J AU Liedke, PER Goss, PE AF Liedke, Pedro E. R. Goss, Paul E. TI Aromatase inhibitors and musculoskeletal adverse events SO LANCET ONCOLOGY LA English DT Editorial Material ID BREAST-CANCER; POSTMENOPAUSAL WOMEN; TRIAL C1 [Liedke, Pedro E. R.; Goss, Paul E.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Liedke, Pedro E. R.; Goss, Paul E.] Harvard Univ, Massachusetts Gen Hosp, Avon Int Breast Canc Program, Sch Med, Boston, MA USA. RP Liedke, PER (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. EM pgoss@partners.org NR 9 TC 2 Z9 2 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2012 VL 13 IS 4 BP 333 EP 334 DI 10.1016/S1470-2045(11)70345-X PG 2 WC Oncology SC Oncology GA 918YG UT WOS:000302287000033 PM 22265696 ER PT J AU Kauvar, A Lloyd, J Cheung, W Zabinska, E Owczarek, W Majewski, S Farinelli, W Anderson, RR Sakamoto, F AF Kauvar, Arielle Lloyd, Jenifer Cheung, Wang Zabinska, Ewa Owczarek, Witold Majewski, Sebastian Farinelli, William Anderson, R. Rox Sakamoto, Fernanda TI SELECTIVE PHOTOTHERMOLYSIS OF THE SEBACEOUS FOLLICLE WITH GOLD-COATED NANOSHELLS FOR TREATMENT OF ACNE SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 32nd Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY APR 18-22, 2012 CL Kissimmee, FL SP Amer Soc Laser Med & Surg (ASLMS) C1 New York Laser & Skin Care, New York, NY USA. Lloyd Dermatol & Laser Ctr, Youngstown, OH USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Czas Kobiety, Krakow, Poland. Mil Inst Med, Warsaw, Poland. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2012 VL 44 IS 4 MA LB3 BP 351 EP 351 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 923JL UT WOS:000302615500014 ER PT J AU Advani, RH Hong, FX Horning, SJ Kahl, BS Manola, J Swinnen, LJ Habermann, TM Ganjoo, K AF Advani, Ranjana H. Hong, Fangxin Horning, Sandra J. Kahl, Brad S. Manola, Judith Swinnen, Lode J. Habermann, Thomas M. Ganjoo, Kristen TI Cardiac toxicity associated with bevacizumab (Avastin) in combination with CHOP chemotherapy for peripheral T cell lymphoma in ECOG 2404 trial SO LEUKEMIA & LYMPHOMA LA English DT Letter DE PTCL; avastin; cardiac ID ENDOTHELIAL GROWTH-FACTOR; PROGNOSTIC-SIGNIFICANCE; CANCER-PATIENTS; RITUXIMAB C1 [Advani, Ranjana H.; Ganjoo, Kristen] Stanford Univ, Stanford, CA 94305 USA. [Hong, Fangxin; Manola, Judith] Dana Farber Canc Inst, Boston, MA 02115 USA. [Horning, Sandra J.] Genentech Inc, San Francisco, CA 94080 USA. [Kahl, Brad S.] Univ Wisconsin, Madison, WI USA. [Swinnen, Lode J.] Johns Hopkins Univ, Baltimore, MD USA. [Habermann, Thomas M.] Mayo Clin, Rochester, MN USA. RP Advani, RH (reprint author), Stanford Univ, 875 Blake Wilbur Dr,CC 2338, Stanford, CA 94305 USA. EM radvani@stanford.edu FU NCI NIH HHS [U10 CA023318, CA66636, U10 CA016116, CA23318, CA21076, U10 CA066636, U10 CA013650, U10 CA021076, CA13650, U10 CA021115, CA16116, CA21115] NR 15 TC 14 Z9 14 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD APR PY 2012 VL 53 IS 4 BP 718 EP 720 DI 10.3109/10428194.2011.623256 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 915ZV UT WOS:000302067100030 PM 21916830 ER PT J AU De La Garza, BH Muir, ER Shih, YYI Duong, TQ AF De La Garza, Bryan H. Muir, Eric R. Shih, Yen-Yu I. Duong, Timothy Q. TI 3D magnetic resonance microscopy of the ex vivo retina SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE ultra high-resolution MRI; high field; MRI contrast agents; T1 and T2 contrast; manganese; MEMRI; photoreceptors ID OPTICAL COHERENCE TOMOGRAPHY; BLOOD-FLOW; FUNCTIONAL MRI; RAT RETINA; MOUSE; RESOLUTION; DEGENERATION; QUANTIFICATION; LAYERS; BRAIN AB 3D-MR microscopy at 11.7T and 20 x 20 x 57 mu m resolution was performed on formalin-fixed rat eyes with: (I) no contrast agent and (II) Gadodiamide (Omniscan (R)) added to the fixative. Group I data showed generally poor contrast among layers. Group II data showed markedly better lamina-specific contrast with the nerve fiber + ganglion cell layer and inner nuclear layer being hypointense, and the inner plexiform, outer plexiform, outer nuclear layer, and the segments being hyperintense. The signal-to-noise ratio in group II was higher than group I, consistent with Gadodiamide acting as a T1-contrast agent. All major retinal layers were assigned and their thicknesses quantified with corroboration by histology. MR microscopy allows nondestructive examination of valuable specimens and could have applications in disease and in vivo. Magn Reson Med, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [De La Garza, Bryan H.; Muir, Eric R.; Shih, Yen-Yu I.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, Div Res, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; Muir, Eric/H-8830-2013; OI Shih, Yen-Yu Ian/0000-0001-6529-911X FU NIH/NEI [R01 EY014211, EY018855, R01EY09702]; Department of Veterans Affairs FX Grant sponsor: NIH/NEI; Grant numbers: R01 EY014211, EY018855, and R01EY09702; Grant sponsor: MERIT Award from the Department of Veterans Affairs. NR 24 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD APR PY 2012 VL 67 IS 4 BP 1154 EP 1158 DI 10.1002/mrm.23082 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 909AF UT WOS:000301533500031 PM 22009721 ER PT J AU Pennarola, BW Rodday, AM Mayer, DK Ratichek, SJ Davies, SM Syrjala, KL Patel, S Bingen, K Kupst, MJ Schwartz, L Guinan, EC Hibbard, JH Parsons, SK AF Pennarola, Brian W. Rodday, Angie Mae Mayer, Deborah K. Ratichek, Sara J. Davies, Stella M. Syrjala, Karen L. Patel, Sunita Bingen, Kristin Kupst, Mary Jo Schwartz, Lisa Guinan, Eva C. Hibbard, Judith H. Parsons, Susan K. CA HSCT-CHESS Study TI Factors Associated With Parental Activation in Pediatric Hematopoietic Stem Cell Transplant SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE cancer; oncology; hematopoietic stem cell transplant (HSCT); children; patient activation; Patient Activation Measure ID QUALITY-OF-LIFE; PATIENT ACTIVATION; SELF-EFFICACY; CHRONIC ILLNESS; CHRONIC DISEASE; MEASURE PAM; HEALTH; CHILDREN; CARE; MANAGEMENT AB Patient activation, the extension of self-efficacy into self-management, is an essential component of effective chronic care. In pediatric populations, caregiver activation is also needed for proper disease management. This study investigates the relationships between parental activation and other characteristics of parent-child dyads (N = 198) presenting for pediatric hematopoietic stem cell transplant. Parental activation concerning their child's health was assessed using the Parent Patient Activation Measure (Parent-PAM), a modified version of the well-validated Patient Activation Measure (PAM). Using hierarchical linear regression and following the Belsky process model for determining parenting behaviors, a multivariate model was created for parental activation on behalf of their child that showed that the parent's age, rating of their own general health, self-activation, and duration of the child's illness were significantly related to Parent-PAM score. Our findings characterize a potentially distinct form of activation in a parent-child cohort preparing for a demanding clinical course. C1 [Parsons, Susan K.] Tufts Med Ctr, ICRHPS, Hlth Inst, Boston, MA 02111 USA. [Mayer, Deborah K.] Univ N Carolina, Chapel Hill, NC USA. [Davies, Stella M.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Syrjala, Karen L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Patel, Sunita] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Bingen, Kristin; Kupst, Mary Jo] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Schwartz, Lisa] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Guinan, Eva C.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Guinan, Eva C.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Hibbard, Judith H.] Univ Oregon, Eugene, OR 97403 USA. RP Parsons, SK (reprint author), Tufts Med Ctr, ICRHPS, Hlth Inst, 800 Washington St,345, Boston, MA 02111 USA. EM sparsons@tuftsmedicalcenter.org FU National Cancer Institute [R01 CA 119196] FX Funding for this study was provided from the National Cancer Institute (R01 CA 119196, SKP). NR 44 TC 11 Z9 11 U1 3 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD APR PY 2012 VL 69 IS 2 BP 194 EP 214 DI 10.1177/1077558711431460 PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 920WA UT WOS:000302438100004 PM 22203645 ER PT J AU Miller, DD Emley, A Yang, S Richards, JE Lee, JE Deng, A Hoang, MP Mahalingam, M AF Miller, Daniel D. Emley, Andrew Yang, Shi Richards, Joanna E. Lee, Jung Eun Deng, April Hoang, Mai P. Mahalingam, Meera TI Mixed versus pure variants of desmoplastic melanoma: a genetic and immunohistochemical appraisal SO MODERN PATHOLOGY LA English DT Article DE BRAF; CD117; desmoplasia; DNA sequencing; KIT; melanoma; RET ID CUTANEOUS MALIGNANT-MELANOMA; CLINICOPATHOLOGICAL ANALYSIS; NEUROTROPIC MELANOMA; PROGNOSTIC-FACTORS; NESTIN EXPRESSION; MUTATIONS; KIT; CANCER; TUMORS; BRAF AB Desmoplastic melanoma is subclassified into pure and mixed variants with a higher rate of lymph node metastasis in the latter. Given that reasons for these biological differences are not currently known, we investigated these subtypes with techniques that included genetic and immunohistochemical analyses of 43 cases of desmoplastic melanoma (24 pure, 19 mixed). Direct DNA sequencing was performed on BRAFV600E, RET gene (coding region on exon 11) and KIT (exons 11, 13 and 17). Immunohistochemical stains were performed with antibodies to markers of significance with respect to biological potential of nevomelanocytic proliferations and/or desmoplastic melanoma (Ki-67, CD117, nestin, clusterin, SOX10 and CD271/p75NTR). Polymorphism at the RET coding region (RETp) was noted in 33% of pure (8/24 cases) versus 24% of mixed (4/17 cases); BRAFV600E was absent in all cases of pure (0/24 cases) versus 6% of mixed (1/17 cases); no mutations were found in any of the cases on analyses of exons 11, 13 and 17 of the c-KIT gene (P=NS for all). For immunohistochemical analyses of pure versus mixed: mean percentage of Ki-67 nuclear positivity was 5% (s.d. = 5.6) versus 28% (s.d. = 12.6, P<0.001); CD117 stained 26% (6/23 cases) versus 78% (14/18 cases, P<0.01); nestin stained 83% (n=19/23 cases) versus 89% (16/18 cases, P=NS); clusterin stained 4% (1/23 cases) versus 6% (1/18 cases, P= NS); SOX10 87% (20/23 cases) versus 94% (17/18 cases, P= NS) and CD271 stained 61% (14/23 cases) versus 67% (12/18 cases, P= NS). Increased CD117 staining in the mixed variant suggests that alterations in the KIT protein may be involved in tumor progression. In addition, the proliferative index of the mixed variant was higher than that of the pure variant. Modern Pathology (2012) 25, 505-515; doi:10.1038/modpathol.2011.196; published online 9 December 2011 C1 [Miller, Daniel D.; Emley, Andrew; Richards, Joanna E.; Lee, Jung Eun; Mahalingam, Meera] Boston Univ, Sch Med, Dept Dermatol, Dermatopathol Sect, Boston, MA 02118 USA. [Yang, Shi] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [Deng, April] UMASS Med Sch, Dept Pathol, Worcester, MA USA. [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mahalingam, M (reprint author), Boston Univ, Sch Med, Dept Dermatol, Dermatopathol Sect, 609 Albany St,J-301, Boston, MA 02118 USA. EM mmahalin@bu.edu OI Yang, Shi/0000-0001-8316-6484; Mahalingam, Meera/0000-0002-2800-9985 NR 45 TC 26 Z9 29 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD APR PY 2012 VL 25 IS 4 BP 505 EP 515 DI 10.1038/modpathol.2011.196 PG 11 WC Pathology SC Pathology GA 922AZ UT WOS:000302520500002 PM 22157936 ER PT J AU McMillin, DW Jacobs, HM Delmore, JE Buon, L Hunter, ZR Monrose, V Yu, J Smith, PG Richardson, PG Anderson, KC Treon, SP Kung, AL Mitsiades, CS AF McMillin, Douglas W. Jacobs, Hannah M. Delmore, Jake E. Buon, Leutz Hunter, Zachary R. Monrose, Val Yu, Jie Smith, Peter G. Richardson, Paul G. Anderson, Kenneth C. Treon, Steven P. Kung, Andrew L. Mitsiades, Constantine S. TI Molecular and Cellular Effects of NEDD8-Activating Enzyme Inhibition in Myeloma SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID MULTIPLE-MYELOMA; CLINICAL-IMPLICATIONS; BORTEZOMIB; SIGNATURE; CANCER; CELLS AB The NEDD8-activating enzyme is upstream of the 20S proteasome in the ubiquitin/proteasome pathway and catalyzes the first step in the neddylation pathway. NEDD8 modification of cullins is required for ubiquitination of cullin-ring ligases that regulate degradation of a distinct subset of proteins. The more targeted impact of NEDD8-activating enzyme on protein degradation prompted us to study MLN4924, an investigational NEDD8-activating enzyme inhibitor, in preclinical multiple myeloma models. In vitro treatment with MLN4924 led to dose-dependent decrease of viability (EC50 = 25-150 nmol/L) in a panel of human multiple myeloma cell lines. MLN4924 was similarly active against a bortezomib-resistant ANBL-6 subline and its bortezomib-sensitive parental cells. MLN4924 had submicromolar activity (EC50 values < 500 nmol/L) against primary CD138(+) multiple myeloma patient cells and exhibited at least additive effect when combined with dexamethasone, doxorubicin, and bortezomib against MM.1S cells. The bortezomib-induced compensatory upregulation of transcripts for ubiquitin/proteasome was not observed with MLN4924 treatment, suggesting distinct functional roles of NEDD8-activating enzyme versus 20S proteasome. MLN4924 was well tolerated at doses up to 60 mg/kg 2x daily and significantly reduced tumor burden in both a subcutaneous and an orthotopic mouse model of multiple myeloma. These studies provide the framework for the clinical investigation of MLN4924 in multiple myeloma. Mol Cancer Ther; 11(4); 942-51. (C) 2012 AACR. C1 [McMillin, Douglas W.; Jacobs, Hannah M.; Delmore, Jake E.; Buon, Leutz; Richardson, Paul G.; Anderson, Kenneth C.; Mitsiades, Constantine S.] Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02215 USA. [Hunter, Zachary R.; Treon, Steven P.] Harvard Univ, Sch Med, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02215 USA. [Monrose, Val; Kung, Andrew L.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [McMillin, Douglas W.; Jacobs, Hannah M.; Delmore, Jake E.; Buon, Leutz; Richardson, Paul G.; Anderson, Kenneth C.; Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Yu, Jie; Smith, Peter G.] Millennium Pharmaceut Inc, Cambridge, MA USA. RP Mitsiades, CS (reprint author), Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst,Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Constantine_Mitsiades@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013; OI Hunter, Zachary/0000-0002-1689-1691; Kung, Andrew/0000-0002-9091-488X FU Millennium; Celgene; Amgen Pharmaceuticals; AVEO Pharma; EMD Serono; Sunesis; Gloucester Pharmaceuticals; Johnson Johnson; Chambers Medical Foundation; Steven Cobb Foundation; R.J. Corman Fund for Myeloma Research; Stepanian Fund for Myeloma Research; Honickman Fund; NIH [RO1-50947, PO-1-78378]; Dana-Farber Cancer Institute FX D.W. McMillin is a founder and equity holder in Axios Biosciences. H. M. Jacobs, J.E. Delmore, L. Buon, Z.R. Hunter, V. Monrose, and A. L. Kung have nothing to disclose. J. Yu and P. G. Smith are employees of Millennium Pharmaceuticals (The Takeda Oncology Company); P. G. Richardson has participated in advisory boards of Millennium, Celgene, Novartis, Johnson & Johnson, and Bristol-Myers Squibb. K. C. Anderson has received research grants and honoraria from Millennium and Celgene, has been a consultant for Millennium, Celgene, Novartis, Bristol-Myers Squibb, Merck, and Onyx, and is a founder of Acetylon Pharmaceuticals. S. P. Treon has received honoraria from and is consultant/member of advisory board for Millennium. C. S. Mitsiades has received in the past consultant honoraria from Millennium Pharmaceuticals, Novartis Pharmaceuticals, Bristol-Myers Squibb, Merck & Co., Kosan Pharmaceuticals, Pharmion, Johnson & Johnson, and Amnis Therapeutics, licensing royalties from PharmaMar, and research funding from Amgen Pharmaceuticals, AVEO Pharma, EMD Serono, Sunesis, Gloucester Pharmaceuticals, and Johnson & Johnson.; This work was supported in part by the Chambers Medical Foundation (C. S. Mitsiades and P. G. Richardson), the Steven Cobb Foundation (D. W. McMillin and C. S. Mitsiades), the R.J. Corman Fund for Myeloma Research (P. G. Richardson and C. S. Mitsiades), the Stepanian Fund for Myeloma Research (P. G. Richardson and C. S. Mitsiades), the Honickman Fund (P. G. Richardson and C. S. Mitsiades), NIH grants RO1-50947 (C. S. Mitsiades and K. C. Anderson), and PO-1-78378 (K. C. Anderson). C. S. Mitsiades is supported by the Dunkin Donuts Rising Stars Program at the Dana-Farber Cancer Institute. NR 19 TC 28 Z9 28 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD APR PY 2012 VL 11 IS 4 BP 942 EP 951 DI 10.1158/1535-7163.MCT-11-0563 PG 10 WC Oncology SC Oncology GA 926CP UT WOS:000302809200014 PM 22246439 ER PT J AU Morse, D Tannous, BA AF Morse, Danielle Tannous, Bakhos A. TI A Water-Soluble Coelenterazine for Sensitive In Vivo Imaging of Coelenterate Luciferases SO MOLECULAR THERAPY LA English DT Letter ID REPORTER-GENE-EXPRESSION; RENILLA-LUCIFERASE; T-CELLS; MOUSE; MICE C1 [Morse, Danielle; Tannous, Bakhos A.] Harvard Univ, Sch Med, Dept Neurol, Expt Therapeut & Mol Imaging Lab,Neurosci Ctr, Boston, MA 02115 USA. [Morse, Danielle; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02115 USA. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Neurosci Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu FU NCI NIH HHS [4R00CA126839, R00 CA126839]; NINDS NIH HHS [1R01NS064983, P30 NS045776, P30 NS045776-07, P30NS045776, R01 NS064983] NR 15 TC 9 Z9 9 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD APR PY 2012 VL 20 IS 4 BP 692 EP 693 DI 10.1038/mt.2012.38 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 919XE UT WOS:000302364700002 PM 22472977 ER PT J AU Morley, JF Xie, SX Hurtig, HI Stern, MB Colcher, A Horn, S Dahodwala, N Duda, JE Weintraub, D Chen-Plotkin, AS Van Deerlin, V Falcone, D Siderowf, A AF Morley, James F. Xie, Sharon X. Hurtig, Howard I. Stern, Matthew B. Colcher, Amy Horn, Stacy Dahodwala, Nabila Duda, John E. Weintraub, Daniel Chen-Plotkin, Alice S. Van Deerlin, Vivianna Falcone, Dana Siderowf, Andrew TI Genetic influences on cognitive decline in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE genetics; Parkinson's disease; cognitive symptoms; apolipoprotein E; microtubule-associated protein tau ID DEMENTIA RATING-SCALE; APOLIPOPROTEIN-E; ALPHA-SYNUCLEIN; RISK; APOE; ALLELE; TAU; ONSET; SUSCEPTIBILITY; ASSOCIATION AB The role of genetic factors in cognitive decline associated with Parkinson's disease (PD) is unclear. We examined whether variations in apolipoprotein E (APOE), microtubule-associated protein tau (MAPT), or catechol-O-methytransferase (COMT) genotypes are associated with cognitive decline in PD. We performed a prospective cohort study of 212 patients with a clinical diagnosis of PD. The primary outcome was change in Mattis Dementia Rating Scale version 2 score. Linear mixed-effects models and survival analysis were used to test for associations between genotypes and change in cognitive function over time. The e4 allele of APOE was associated with more rapid decline (loss of 2.9; 95% confidence interval [CI]: 1.74.1) of more points per year; P < 0.001) in total score and an increased risk of a =10 point drop during the follow-up period (hazard ratio, 2.8; 95% CI: 1.45.4; P = 0.003). MAPT haplotype and COMT genotype were associated with measures of memory and attention, respectively, over the entire follow-up period, but not with the overall rate of cognitive decline. These results confirm and extend previously described genetic associations with cognitive decline in PD and imply that individual genes may exert effects on specific cognitive domains or at different disease stages. Carrying at least one APOE e4 allele is associated with more rapid cognitive decline in PD, supporting the idea of a component of shared etiology between PD dementia and Alzheimer's disease. Clinically, these results suggest that genotyping can provide information about the risk of future cognitive decline for PD patients. (C) 2012 Movement Disorder Society C1 [Morley, James F.; Hurtig, Howard I.; Stern, Matthew B.; Colcher, Amy; Horn, Stacy; Dahodwala, Nabila; Duda, John E.; Chen-Plotkin, Alice S.; Siderowf, Andrew] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19107 USA. [Xie, Sharon X.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19107 USA. [Weintraub, Daniel] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19107 USA. [Van Deerlin, Vivianna; Falcone, Dana] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19107 USA. [Xie, Sharon X.; Hurtig, Howard I.; Stern, Matthew B.; Colcher, Amy; Horn, Stacy; Duda, John E.; Weintraub, Daniel; Chen-Plotkin, Alice S.; Van Deerlin, Vivianna; Falcone, Dana; Siderowf, Andrew] Univ Penn, Sch Med, Morris K Udall Ctr Excellence Parkinsons Dis Res, Philadelphia, PA 19107 USA. [Morley, James F.; Duda, John E.; Weintraub, Daniel] Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. RP Siderowf, A (reprint author), Univ Penn, Sch Med, Dept Neurol, 330 S 9th St,2nd Floor, Philadelphia, PA 19107 USA. EM andrew.siderowf@uphs.upenn.edu FU Morris K. Udall Parkinson's Disease Research Center of Excellence; National Institute for Neurological Disorders and Stroke [NS-053488]; Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement [SAP4100027296] FX This work was supported by a Morris K. Udall Parkinson's Disease Research Center of Excellence grant from the National Institute for Neurological Disorders and Stroke (NS-053488) and by SAP4100027296, a health research grant awarded by the Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement under Act 2001-77. NR 43 TC 41 Z9 42 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2012 VL 27 IS 4 BP 512 EP 518 DI 10.1002/mds.24946 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 921HP UT WOS:000302469000050 PM 22344634 ER PT J AU Walker, RH Schulz, VP Tikhonova, IR Mahajan, MC Mane, S Muniz, MA Gallagher, PG AF Walker, Ruth H. Schulz, Vincent P. Tikhonova, Irina R. Mahajan, Milind C. Mane, Shrikant Muniz, Maritza Arroyo Gallagher, Patrick G. TI Genetic diagnosis of neuroacanthocytosis disorders using exome sequencing SO MOVEMENT DISORDERS LA English DT Article DE exome sequencing; neuroacanthocytosis; chorea; chorea-acanthocytosis ID CHOREA-ACANTHOCYTOSIS; PERSONALIZED MEDICINE; MUTATION; DISCOVERY; FRAMEWORK; ALIGNMENT; ACCURATE; DISEASE; PATIENT; PROTEIN AB Neuroacanthocytoses are neurodegenerative disorders marked by phenotypic and genetic heterogeneity. There are several associated genetic loci, and many defects, including gene deletions and insertions, and missense, nonsense, and splicing mutations, have been found spread over hundreds of kilobases of genomic DNA. In some cases, specific diagnosis is unclear, particularly in the early stages of disease or when there is an atypical presentation. Determination of the precise genetic defect allows assignment of the diagnosis and permits carrier detection and genetic counseling. The objective of this report was to utilize exome sequencing for genetic diagnosis in the neuroacanthocytosis syndromes. Genomic DNA from 2 patients with clinical features of chorea-acanthocytosis was subjected to targeted exon capture. Captured DNA was subjected to ultrahigh throughput next-generation sequencing. Sequencing data were assembled, filtered against known human variant genetic databases, and results were analyzed. Both patients were compound heterozygotes for mutations in the VPS13A gene, the gene associated with chorea-acanthocytosis. Patient 1 had a 4-bp deletion that removes the 5' donor splice site of exon 58 and a nucleotide substitution that disrupts the 5' donor splice site of exon 70. Patient 2 had a dinucleotide deletion in exon 16 and a dinucleotide insertion in exon 33. No mutations were identified in the XK, PANK2, or JPH3 gene loci. Exome sequencing is a valuable diagnostic tool in the neuroacanthocytosis syndromes. These studies may provide a better understanding of the function of the associated proteins and provide insight into the pathogenesis of these disorders. (c) 2011 Movement Disorder Society C1 [Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY 10468 USA. [Walker, Ruth H.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Schulz, Vincent P.; Gallagher, Patrick G.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Tikhonova, Irina R.; Mahajan, Milind C.; Mane, Shrikant; Gallagher, Patrick G.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Tikhonova, Irina R.; Mahajan, Milind C.; Mane, Shrikant] Yale Univ, Yale Ctr Genome Anal, Orange, CT USA. [Muniz, Maritza Arroyo] Univ Puerto Rico, Dept Med, Neurol Sect, San Juan, PR 00936 USA. RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Dept Neurol, 130 W Kingsbridge Rd,127, Bronx, NY 10468 USA. EM ruth.walker@mssm.edu OI Schulz, Vincent/0000-0001-6333-4284 NR 32 TC 9 Z9 9 U1 0 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 APR PY 2012 VL 27 IS 4 BP 539 EP 543 DI 10.1002/mds.24020 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 921HP UT WOS:000302469000054 PM 22038564 ER PT J AU Jin, YM Ratnam, K Chuang, PY Fan, Y Zhong, YF Dai, Y Mazloom, AR Chen, EY D'Agati, V Xiong, HB Ross, MJ Chen, N Ma'ayan, A He, JC AF Jin, Yuanmeng Ratnam, Krishna Chuang, Peter Y. Fan, Ying Zhong, Yifei Dai, Yan Mazloom, Amin R. Chen, Edward Y. D'Agati, Vivette Xiong, Huabao Ross, Michael J. Chen, Nan Ma'ayan, Avi He, John Cijiang TI A systems approach identifies HIPK2 as a key regulator of kidney fibrosis SO NATURE MEDICINE LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; HIV-ASSOCIATED NEPHROPATHY; RENAL INTERSTITIAL FIBROSIS; DNA-DAMAGE RESPONSE; TGF-BETA; URETERAL OBSTRUCTION; N-ACETYLCYSTEINE; APOPTOSIS; MICE; TRANSCRIPTION AB Kidney fibrosis is a common process that leads to the progression of various types of kidney disease. We used an integrated computational and experimental systems biology approach to identify protein kinases that regulate gene expression changes in the kidneys of human immunodeficiency virus (HIV) transgenic mice (Tg26 mice), which have both tubulointerstitial fibrosis and glomerulosclerosis. We identified homeo-domain interacting protein kinase 2 (HIPK2) as a key regulator of kidney fibrosis. HIPK2 was upregulated in the kidneys of Tg26 mice and in those of patients with various kidney diseases. HIV infection increased the protein concentrations of HIPK2 by promoting oxidative stress, which inhibited the seven in absentia homolog 1 (SIAH1)-mediated proteasomal degradation of HIPK2. HIPK2 induced apoptosis and the expression of epithelial-to-mesenchymal transition markers in kidney epithelial cells by activating the p53, transforming growth factor beta (TGF-beta)-SMAD family member 3 (Smad3) and Wnt-Notch pathways. Knockout of HIPK2 improved renal function and attenuated proteinuria and kidney fibrosis in Tg26 mice, as well as in other murine models of kidney fibrosis. We therefore conclude that HIPK2 is a potential target for anti-fibrosis therapy. C1 [Jin, Yuanmeng; Ratnam, Krishna; Chuang, Peter Y.; Fan, Ying; Zhong, Yifei; Dai, Yan; Ross, Michael J.; He, John Cijiang] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. [Jin, Yuanmeng; Chen, Nan] Jiao Tong Univ Sch Med, Ruijin Hosp, Dept Nephrol, Shanghai, Peoples R China. [Mazloom, Amin R.; Chen, Edward Y.; Ma'ayan, Avi; He, John Cijiang] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY USA. [Mazloom, Amin R.; Chen, Edward Y.; Ma'ayan, Avi] SBCNY, New York, NY USA. [D'Agati, Vivette] Columbia Univ, Dept Pathol, New York, NY USA. [Xiong, Huabao] Mt Sinai Sch Med, Immunobiol Ctr, New York, NY USA. [He, John Cijiang] James J Peters Vet Adm Med Ctr, New York, NY USA. RP He, JC (reprint author), Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. EM avi.maayan@mssm.edu; cijiang.he@mssm.edu FU US National Institutes of Health (NIH) [1R01DK078897]; Veterans Affairs Merit Award; NIH [1R01DK088541, P01-DK-56492, 1RC4DK090860, RC2OD006536, 5P50GM071558, 5K08DK082760]; Chinese 973 fund [2012CB517601] FX The authors acknowledge and thank G.L. Gusella (Mount Sinai School of Medicine, New York) for providing the lentiviral construct, E. Huang (University of California San Francisco) for providing the HIPK2 KO mice, P. Mundel (Massachusetts General Hospital, Boston) for synaptopodin antibody and conditionally immortalized murine podocyte cell line, L. Holzman (University of Pennsylvania, Philadelphia) for nephrin antibody and R.H. Goodman (Oregon Health and Science University, Portland) for WT-HIPK2 and KD-HIPK2 constructs. We also thank R. Iyengar and P. Klotman for critical suggestions on experimental design and for other valuable contributions. J.C.H. is supported by US National Institutes of Health (NIH) grant 1R01DK078897 and a Veterans Affairs Merit Award; J.C.H. and A.M. are supported by NIH 1R01DK088541, NIH P01-DK-56492 and NIH 1RC4DK090860; A.M. is supported by NIH RC2OD006536 and 5P50GM071558; P.Y.C. is supported by NIH 5K08DK082760. N.C. is supported by Chinese 973 fund 2012CB517601. NR 56 TC 52 Z9 53 U1 4 U2 25 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 APR PY 2012 VL 18 IS 4 BP 580 EP 588 DI 10.1038/nm.2685 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 923KI UT WOS:000302617800035 PM 22406746 ER PT J AU Humayun, MS Dorn, JD da Cruz, L Dagnelie, G Sahel, JA Stanga, PE Cideciyan, AV Duncan, JL Eliott, D Filley, E Ho, AC Santos, A Safran, AB Arditi, A Del Priore, LV Greenberg, RJ AF Humayun, Mark S. Dorn, Jessy D. da Cruz, Lyndon Dagnelie, Gislin Sahel, Jose-Alain Stanga, Paulo E. Cideciyan, Artur V. Duncan, Jacque L. Eliott, Dean Filley, Eugene Ho, Allen C. Santos, Arturo Safran, Avinoam B. Arditi, Aries Del Priore, Lucian V. Greenberg, Robert J. CA Argus II Study Grp TI Interim Results from the International Trial of Second Sight's Visual Prosthesis SO OPHTHALMOLOGY LA English DT Article ID PARS-PLANA VITRECTOMY; ELECTRICAL-STIMULATION; RETINAL PROSTHESIS; PERCEPTUAL THRESHOLDS; VISION; BLIND; IMPLANTATION; PERFORMANCE; RETINITIS; SURGERY AB Purpose: This study evaluated the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) in blind subjects with severe outer retinal degeneration. Design: Single-arm, prospective, multicenter clinical trial. Participants: Thirty subjects were enrolled in the United States and Europe between June 6, 2007, and August 11, 2009. All subjects were followed up for a minimum of 6 months and up to 2.7 years. Methods: The electronic stimulator and antenna of the implant were sutured onto the sclera using an encircling silicone band. Next, a pars plana vitrectomy was performed, and the electrode array and cable were introduced into the eye via a pars plana sclerotomy. The microelectrode array then was tacked to the epiretinal surface. Main Outcome Measures: The primary safety end points for the trial were the number, severity, and relation of adverse events. Principal performance end points were assessments of visual function as well as performance on orientation and mobility tasks. Results: Subjects performed statistically better with the system on versus off in the following tasks: object localization (96% of subjects), motion discrimination (57%), and discrimination of oriented gratings (23%). The best recorded visual acuity to date is 20/1260. Subjects' mean performance on orientation and mobility tasks was significantly better when the system was on versus off. Seventy percent of the patients did not have any serious adverse events (SAEs). The most common SAE reported was either conjunctival erosion or dehiscence over the extraocular implant and was treated successfully in all subjects except in one, who required explantation of the device without further complications. Conclusions: The long-term safety results of Second Sight's retinal prosthesis system are acceptable, and most subjects with profound visual loss perform better on visual tasks with system than without it. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:779-788 (C) 2012 by the American Academy of Ophthalmology. C1 [Humayun, Mark S.; Argus II Study Grp] Univ So Calif, Doheny Eye Inst, Los Angeles, CA USA. [Dorn, Jessy D.; Greenberg, Robert J.] Second Sight Med Prod Inc, Sylmar, CA USA. [da Cruz, Lyndon] Moorfields Eye Hosp, NIHR Biomed Res Ctr Ophthalmol, London, England. [Dagnelie, Gislin; Del Priore, Lucian V.] Johns Hopkins Univ, Lions Vis Res & Rehab Ctr, Baltimore, MD USA. [Sahel, Jose-Alain] Hosp Natl Ophtalmol Quinze Vingts, Paris, France. [Stanga, Paulo E.] Univ Manchester, Manchester Royal Eye Hosp, Manchester Biomed Res Ctr, Manchester, Lancs, England. [Cideciyan, Artur V.] Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA. [Duncan, Jacque L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Eliott, Dean] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Filley, Eugene] Retina Fdn SW, Dallas, TX USA. [Ho, Allen C.] Thomas Jefferson Univ, Wills Eye Hosp, Philadelphia, PA 19107 USA. [Santos, Arturo] Escuela Med, SC, Ctr Retina Med & Quirurg, Guadalajara, Jalisco, Mexico. [Safran, Avinoam B.] Hop Cantonal Univ Geneva, Geneva, Switzerland. [Arditi, Aries] Lighthouse Int, New York, NY USA. [Del Priore, Lucian V.] Columbia Univ, New York, NY USA. RP Humayun, MS (reprint author), DVRC 117,1355 San Pablo St, Los Angeles, CA 90033 USA. EM humayun@usc.edu RI Sahel, Jose-Alain/F-3172-2017 FU Second Sight Medical Products, Inc.; National Institutes of Health, Bethesda, Maryland [5R01EY012893-10]; Second Sight Medical Products, Inc., Sylmar, California FX Mark S. Humayun - Equity owner - Second Sight Medical Products, Inc.; Employee - an institution that receives funds from Second Sight Medical Products, Inc.; Aries Arditi - Consultant - Second Sight Medical Products, Inc.; Employee - an institution that receives funds from Second Sight Medical Products, Inc.; Artur V. Cideciyan - Employee - an institution that receives funds from Second Sight Medical Products, Inc.; Lyndon da Cruz - Employee - an institution that receives funds from Second Sight Medical Products, Inc.; Gislin Dagnelie - Employee - an institution that receives funds from Second Sight Medical Products, Inc.; Dean Eliott - Employee - an institution that receives funds from Second Sight Medical Products, Inc.; Eugene Filley - Employee - an institution that receives funds from Second Sight Medical Products, Inc.; Avinoam B. Safran - Employee - an institution that receives funds from Second Sight Medical Products, Inc.; Jose-Alain Sahel - Employee - an institution that receives funds from Second Sight Medical Products, Inc.; Supported by the National Institutes of Health, Bethesda, Maryland (grant no.: 5R01EY012893-10 [RJG]). Sponsored by Second Sight Medical Products, Inc., Sylmar, California. The sponsor participated in the design of the study, conducting the study, data collection, data management, data analysis, interpretation of the data, preparation, and review of the manuscript. NR 27 TC 214 Z9 219 U1 8 U2 76 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 APR PY 2012 VL 119 IS 4 BP 779 EP 788 DI 10.1016/j.ophtha.2011.09.028 PG 10 WC Ophthalmology SC Ophthalmology GA 919UQ UT WOS:000302355400017 PM 22244176 ER PT J AU Cidav, Z Marcus, SC Mandell, DS AF Cidav, Zuleyha Marcus, Steven C. Mandell, David S. TI Implications of Childhood Autism for Parental Employment and Earnings SO PEDIATRICS LA English DT Article DE autism; developmental disabilities; family impact; economic burden ID HEALTH-CARE UTILIZATION; SPECTRUM DISORDERS; UNITED-STATES; CHILDREN; EXPENDITURES; FAMILIES; COSTS; DISABILITIES; MEDICAID AB OBJECTIVE: To examine changes in parental labor force participation, hours of work, and annual earnings associated with childhood autism spectrum disorders (ASD). METHODS: We used the 2002-2008 Medical Expenditure Panel Survey to examine parental labor market outcomes of children with ASD relative to children with another health limitation and children without health limitations. A logit model was used to estimate parental labor force participation. A tobit model was used to estimate parental hours of work and earnings. RESULTS: On average, mothers of children with ASD earn 35% ($7189) less than the mothers of children with another health limitation and 56% ($14 755) less than the mothers of children with no health limitation. They are 6% less likely to be employed and work 7 hours less per week, on average, than mothers of children with no health limitation. There were no statistically significant differences in fathers' labor market outcomes across 3 groups. On average, children with ASD are 9% less likely to have both parents working. Family earnings of children with ASD are 21% ($10 416) less than those of children with another health limitation and 28% ($17 763) less than those of children with no health limitation. Family weekly hours of work are an average of 5 hours less than those of children with no health limitation. CONCLUSIONS: Families of children with ASD face significant economic burden. Given the substantial health care expenses associated with ASD, the economic impact of having lower income in addition to these expenses is substantial. It is essential to design universal health care and workplace policies that recognize the full impact of autism. Pediatrics 2012;129:617-623 C1 [Cidav, Zuleyha] Univ Penn, Childrens Hosp Philadelphia, Ctr Autism Res, Ctr Mental Hlth Policy & Serv Res,Perelman Sch Me, Philadelphia, PA 19104 USA. [Cidav, Zuleyha; Mandell, David S.] Univ Penn, Perelman Sch Med, Ctr Mental Hlth Policy & Serv Res, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Cidav, Z (reprint author), Univ Penn, Childrens Hosp Philadelphia, Ctr Autism Res, Ctr Mental Hlth Policy & Serv Res,Perelman Sch Me, 3535 Market St,3rd Floor, Philadelphia, PA 19104 USA. EM zcidav@upenn.edu RI Mandell, David/H-2730-2012 OI Mandell, David/0000-0001-8240-820X FU National Institute of Mental Health [R01 MH 077000] FX This study is funded by a grant from the National Institute of Mental Health (R01 MH 077000). NR 24 TC 49 Z9 50 U1 5 U2 21 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 APR PY 2012 VL 129 IS 4 BP 617 EP 623 DI 10.1542/peds.2011-2700 PG 7 WC Pediatrics SC Pediatrics GA 922IX UT WOS:000302541700038 PM 22430453 ER PT J AU Durall, A Zurakowski, D Wolfe, J AF Durall, Amy Zurakowski, David Wolfe, Joanne TI Barriers to Conducting Advance Care Discussions for Children With Life-Threatening Conditions SO PEDIATRICS LA English DT Article DE advance care planning; barriers; end-of-life ID PEDIATRIC PALLIATIVE CARE; LEFT-HEART SYNDROME; INTENSIVE-CARE; COMMUNICATION-SKILLS; NURSES PERCEPTIONS; HEALTH-CARE; END; PERSPECTIVES; QUALITY; UNIT AB BACKGROUND AND OBJECTIVE: Advance care discussions (ACD) occur infrequently or are initiated late in the course of illness. Although data exist regarding barriers to ACD among the care of adult patients, few pediatric data exist. The goal of this study was to identify barriers to conducting ACD for children with life-threatening conditions. METHODS: Physicians and nurses from practice settings where advance care planning typically takes place were surveyed to collect data regarding their attitudes and behaviors regarding ACD. RESULTS: A total of 266 providers responded to the survey: 107 physicians and 159 nurses (54% response rate). The top 3 barriers were: unrealistic parent expectations, differences between clinician and patient/parent understanding of prognosis, and lack of parent readiness to have the discussion. Nurses identified lack of importance to clinicians (P = .006) and ethical considerations (P < .001) as impediments more often than physicians. Conversely, physicians believed that not knowing the right thing to say (P = .006) was more often a barrier. There are also perceived differences among specialties. Cardiac ICU providers were more likely to report unrealistic clinician expectations (P < .001) and differences between clinician and patient/parent understanding of prognosis (P = .014) as common barriers to conducting ACD. Finally, 71% of all clinicians believed that ACD happen too late in the patient's clinical course. CONCLUSIONS: Clinicians perceive parent prognostic understanding and attitudes as the most common barriers to conducting ACD. Educational interventions aimed at improving clinician knowledge, attitudes, and skills in addressing these barriers may help health care providers overcome perceived barriers. Pediatrics 2012;129:e975-e982 C1 [Durall, Amy; Zurakowski, David] Childrens Hosp Boston, Div Crit Care, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Wolfe, Joanne] Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Div Pediat Palliat Care, Boston, MA 02115 USA. RP Durall, A (reprint author), Childrens Hosp Boston, Div Crit Care, Dept Anesthesiol Perioperat & Pain Med, 300 Longwood Ave,Bader 634, Boston, MA 02115 USA. EM amy.durall@childrens.harvard.edu NR 43 TC 40 Z9 41 U1 4 U2 15 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 APR PY 2012 VL 129 IS 4 BP E975 EP E982 DI 10.1542/peds.2011-2695 PG 8 WC Pediatrics SC Pediatrics GA 922IX UT WOS:000302541700016 PM 22392177 ER PT J AU Smith, DM Damschroder, LJ Kim, SYH Ubel, PA AF Smith, Dylan M. Damschroder, Laura J. Kim, Scott Y. H. Ubel, Peter A. TI What's It Worth? Public Willingness to Pay to Avoid Mental Illnesses Compared With General Medical Illnesses SO PSYCHIATRIC SERVICES LA English DT Article ID HEALTH-SERVICES; CARE; PREFERENCES; DEPRESSION; STIGMA; EXPENDITURE; RESOURCES; KNOWLEDGE; INTERNET; SCALE AB Objective: Allocation of resources for the treatment of mental illness is low relative to the burden imposed by these illnesses. The reason for this discrepancy has not been established. Few studies have directly and systematically compared public evaluations of the importance of treating mental illnesses and general medical illnesses. This study assessed public willingness to pay for treatments of mental health conditions and of general medical conditions to determine whether willingness to pay less for mental health treatments is due to the perception that mental health conditions are less burdensome. Methods: U.S. adults (N=710) in a nationally representative sample were provided with descriptions of two mental and three general medical illnesses. Respondents rated their willingness to pay to avoid each illness and then their perception of the burdensomeness of each illness. Results: Participants rated the two mental illnesses as relatively more burdensome than the general medical illnesses, but the amount they were willing to pay to avoid the mental illnesses was lower. Specifically, participants were willing to pay 40% less to avoid the mental illnesses compared with the general medical conditions, for a comparable benefit in terms of quality of life. Conclusions: Even though respondents recognized that severe mental illnesses can dramatically lower quality of life, they were less willing to pay to avoid such illnesses than they were to pay to cure less burdensome general medical illnesses. (Psychiatric Services 63:319-324, 2012; doi: 10.1176/appi.ps.201000036) C1 [Smith, Dylan M.] SUNY Stony Brook, Dept Prevent Med, Hlth Sci Ctr, Stony Brook, NY 11794 USA. [Damschroder, Laura J.] Hlth Serv Res & Dev Serv, US Dept Vet Affairs, Med Ctr, Ann Arbor, MI USA. [Kim, Scott Y. H.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Kim, Scott Y. H.] Univ Michigan, Sch Med, Ctr Bioeth & Social Sci Med, Ann Arbor, MI USA. [Ubel, Peter A.] Duke Univ, Fuqua Sch Business, Durham, NC 27706 USA. [Ubel, Peter A.] Duke Univ, Sanford Sch Publ Policy, Durham, NC 27706 USA. RP Smith, DM (reprint author), SUNY Stony Brook, Dept Prevent Med, Hlth Sci Ctr, Level 3 080, Stony Brook, NY 11794 USA. EM dylan.m.smith@stonybrook.edu OI Damschroder, Laura/0000-0002-3657-8459 FU National Institute of Child Health and Development [R01HD040789] FX This research was supported by grant R01HD040789 from the National Institute of Child Health and Development. The authors are grateful for the assistance of the team at Knowledge Networks, especially Mike Dennis, Ph.D., Bill McCready, Ph.D., Vicki Pineau, M.S., and Poom Nukulkij, M.A. NR 32 TC 6 Z9 6 U1 6 U2 40 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2012 VL 63 IS 4 BP 319 EP 324 DI 10.1176/appi.ps.201000036 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 925KN UT WOS:000302760200006 PM 22388473 ER PT J AU Duffy, SA Kilbourne, AM Austin, KL Dalack, GW Woltmann, EM Waxmonsky, J Noonan, D AF Duffy, Sonia A. Kilbourne, Amy M. Austin, Karen L. Dalack, Gregory W. Woltmann, Emily M. Waxmonsky, Jeanette Noonan, Devon TI Risk of Smoking and Receipt of Cessation Services Among Veterans With Mental Disorders SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; CIGARETTE-SMOKING; HEALTH-CARE; AFRICAN-AMERICANS; SCHIZOPHRENIA; PREVALENCE; MOTIVATION; SMOKERS; IMPACT AB Objective: The purpose of this study was to determine rates of smoking and receipt of provider recommendations to quit smoking among patients with mental disorders treated in U.S. Department of Veterans Affairs (VA) treatment settings. Methods: The authors conducted a secondary analysis of the yearly, cross-sectional 2007 Veterans Health Administration Outpatient Survey of Healthcare Experiences of Patients (N=224,193). Logistic regression was used to determine the independent association of mental health diagnosis and the dependent variables of smoking and receipt of provider recommendations to quit smoking. Results: Patients with mental disorders had greater odds of smoking, compared with those without mental disorders (p<.05). Those with various mental disorders reported similar rates of receiving services (more than 60% to 80% reported receiving selected services), compared with those without these disorders, except that those with schizophrenia had more than 30% lower odds of receiving advice to quit smoking from their physicians (p<.05). Moreover, those who had co-occurring posttraumatic stress disorder or substance use disorders had significantly greater odds of reporting that they received advice to quit, recommendations for medications, and physician discussions of quitting methods, compared with those without these disorders (p<.05). Older patients, male patients, members of ethnic minority groups, those who were unmarried, those who were disabled or unemployed, and those living in rural areas had lower odds of receiving selected services (p<.05). Conclusions: The majority of patients with mental disorders served by the VA reported receiving cessation services, yet their smoking rates remained high, and selected groups were at risk for receiving fewer cessation services, suggesting the continued need to disseminate cessation services. (Psychiatric Services 63:325-332, 2012; doi: 10.1176/appi.ps.201100097) C1 [Duffy, Sonia A.; Kilbourne, Amy M.; Austin, Karen L.; Woltmann, Emily M.] US Dept Vet Affairs, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor Ctr Clin Management Res, Ann Arbor, MI 48105 USA. [Duffy, Sonia A.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [Kilbourne, Amy M.; Dalack, Gregory W.; Noonan, Devon] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Waxmonsky, Jeanette] Univ Colorado, Depress Ctr, Sch Med, Aurora, CO USA. [Waxmonsky, Jeanette] Univ Colorado, Dept Psychiat, Sch Med, Aurora, CO USA. RP Duffy, SA (reprint author), US Dept Vet Affairs, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor Ctr Clin Management Res, 2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM bump@umich.edu RI Waxmonsky, Jeanette/L-4739-2013 FU U.S. Department of Veterans Affairs (VA); Health Services Research and Development Service [HR 07-115]; National Institute of Mental Health [MH 74509] FX This work was supported by the U.S. Department of Veterans Affairs (VA), Health Services Research and Development Service (HR 07-115) and grant MH 74509 from the National Institute of Mental Health. The authors thank the VA Office of Quality and Performance for providing access to the Survey of Healthcare Experiences of Patients (SHEP) data. The views expressed in this article are those of the authors and do not necessarily represent the views of the VA. NR 60 TC 18 Z9 18 U1 3 U2 7 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 APR PY 2012 VL 63 IS 4 BP 325 EP 332 DI 10.1176/appi.ps.201100097 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 925KN UT WOS:000302760200007 PM 22337005 ER PT J AU Nath, SB Marcus, SC AF Nath, Sara Bressi Marcus, Steven C. TI Impact of Psychotic Disorders on Discharge Dispositions of Adults 65 or Older After a General Medical Inpatient Stay SO PSYCHIATRIC SERVICES LA English DT Article ID MENTAL-HEALTH-SERVICES; EXCESS MORTALITY; SCHIZOPHRENIA; ILLNESS; CARE; COMORBIDITY; ASSOCIATION; COSTS AB Objective: This study examined the extent to which a psychotic disorder, as well as demographic and clinical characteristics, predicted the discharge disposition of adults aged 65 or older after a hospital stay for a general medical illness. Methods: Data from a nationally representative sample of hospital discharges among persons 65 years of age or older (N=2,334,130) were drawn from the 2007 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project. A series of multivariate logistic regression models were constructed to examine the impact of psychotic disorders and demographic and clinical characteristics on four discharge dispositions-routine discharge, home care, nursing facility, or in-hospital mortality-among patients with or without a psychotic disorder. Results: Patients with a psychotic disorder (N=23,751) were significantly more likely than those without a psychotic disorder (N=2,310,379) to be discharged to home care (OR=1.60) or to a nursing facility (OR=4.49) or to die in the hospital (OR=1.95). Patients with a psychotic disorder were more likely than patients without a psychotic disorder to be discharged to a nursing facility if they were also male (OR=4.96), between 65 and 74 years old (OR=6.05), or admitted from another inpatient facility (OR=6.14) or if their illness was of mild or moderate severity (OR=4.87). Conclusions: The significantly increased likelihood for referral to skilled home care and nursing facilities after hospital discharge among psychotic patients highlights the need for viable and dynamic community-based care options for maintaining the health and well-being of older adults with a psychotic disorder after an acute care event. (Psychiatric Services 63: 333-337, 2012; doi: 10.1176/appi.ps.201100332) C1 [Nath, Sara Bressi] Bryn Mawr Coll, Grad Sch Social Work & Social Res, Bryn Mawr, PA 19010 USA. [Marcus, Steven C.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Nath, SB (reprint author), Bryn Mawr Coll, Grad Sch Social Work & Social Res, 300 Airdale Rd, Bryn Mawr, PA 19010 USA. EM snath@brynmawr.edu FU Ortho-McNeil Janssen FX Dr. Marcus has received grant support from Ortho-McNeil Janssen and has served as a consultant to AstraZeneca. Dr. Bressi Nath reports no competing interests. NR 26 TC 3 Z9 3 U1 4 U2 10 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 APR PY 2012 VL 63 IS 4 BP 333 EP 337 DI 10.1176/appi.ps.201100332 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 925KN UT WOS:000302760200008 PM 22337008 ER PT J AU Godleski, L Darkins, A Peters, J AF Godleski, Linda Darkins, Adam Peters, John TI Outcomes of 98,609 US Department of Veterans Affairs Patients Enrolled in Telemental Health Services, 2006-2010 SO PSYCHIATRIC SERVICES LA English DT Article ID TELEPSYCHIATRY; MANAGEMENT; IMPLEMENTATION; TELEHEALTH; TELEVISION AB Objective: The study assessed clinical outcomes of 98,609 mental health patients before and after enrollment in telemental health services of the U.S. Department of Veterans Affairs between 2006 and 2010. Methods: The study compared number of inpatient psychiatric admissions and days of psychiatric hospitalization among patients who participated in remote clinical videoconferencing during an average period of six months before and after their enrollment in the telemental health services. Results: Between. 2006 and 2010, psychiatric admissions of telemental health patients decreased by an average of 24.2% (annual range 16.3%-38.7%), and the patients' days of hospitalization decreased by an average of 26.6% (annual range 16.5%-43.5%). The number of admissions and the days of hospitalization decreased for both men and women and in 83.3% of the age groups. Conclusions: This four-year study, the first large-scale assessment of telemental health services, found that after initiation of such services, patients' hospitalization utilization decreased by an average of approximately 25%. (Psychiatric Services 63:383-385, 2012; doi: 10.1176/appi.ps.201100206) C1 [Godleski, Linda] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Godleski, Linda] US Dept Vet Affairs, Natl Telemental Hlth Ctr, West Haven, CT 06516 USA. [Darkins, Adam; Peters, John] US Dept Vet Affairs, Off Telehlth Serv, Washington, DC USA. RP Godleski, L (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. EM linda.godles-ki2@va.gov NR 15 TC 39 Z9 39 U1 1 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 APR PY 2012 VL 63 IS 4 BP 383 EP 385 DI 10.1176/appi.ps.201100206 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 925KN UT WOS:000302760200017 PM 22476305 ER PT J AU Capezza, NM Najavits, LM AF Capezza, Nicole M. Najavits, Lisa M. TI Rates of Trauma-Informed Counseling at Substance Abuse Treatment Facilities: Reports From Over 10,000 Programs SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; WOMEN; SERVICES; OUTCOMES; DRUG AB Objective: Trauma-informed treatment increasingly is recognized as an important component of service delivery. This study examined differences in treatment-related characteristics of facilities that offer moderate or high levels of trauma-informed counseling versus those that offer no or low levels of such counseling. Methods: Responses from 13,223 substance abuse treatment facilities surveyed in 2009 by the National Survey of Substance Abuse Treatment Services (NSSATS) were used. Results: A majority (66.6%) of facilities reported using trauma counseling sometimes or always or often. Facilities that provided moderate or high levels of trauma counseling were more likely to provide additional treatment services, such as disease testing and specialized group therapy, as well as child care, employment counseling, and other ancillary services. Conclusions: A majority of facilities reported provision of trauma counseling. Additional training and resources may be needed for programs that reported low rates of trauma counseling. (Psychiatric Services 63:390-394, 2012; doi: 10.1176/appi.ps.201000560) C1 [Capezza, Nicole M.] Univ Massachusetts, Sch Med, Newton Ctr, MA 02459 USA. [Najavits, Lisa M.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Najavits, Lisa M.] Boston Healthcare Syst, Dept Vet Affairs, Boston, MA USA. RP Capezza, NM (reprint author), Univ Massachusetts, Sch Med, 28 Westbourne Rd, Newton Ctr, MA 02459 USA. EM capezza.nicole@gmail.com NR 14 TC 6 Z9 6 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 APR PY 2012 VL 63 IS 4 BP 390 EP 394 DI 10.1176/appi.ps.201000560 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 925KN UT WOS:000302760200019 PM 22476307 ER PT J AU Garg, D Nagar, A Philips, S Takahashi, N Prasad, SR Shanbhogue, AK Sahani, DV AF Garg, Deepak Nagar, Arpit Philips, Shaile Takahashi, Naoki Prasad, Srinivasa R. Shanbhogue, Alampady K. Sahani, Dushyant V. TI Immunological diseases of the pancreatico-hepatobiliary system: update on etiopathogenesis and cross-sectional imaging findings SO ABDOMINAL IMAGING LA English DT Article DE Autoimmune hepatitis; Primary biliary cirrhosis; Primary sclerosing cholangitis; IgG-4-related disease; Computed tomography; Magnetic resonance imaging ID PRIMARY BILIARY-CIRRHOSIS; PRIMARY SCLEROSING CHOLANGITIS; AUTOIMMUNE PANCREATITIS; LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA; MRI FINDINGS; HEPATITIS; CT; FEATURES; MANAGEMENT AB Immunological diseases of the hepatobiliary system and the pancreas include a broad spectrum of disorders that manifest characteristic histopathology/serology and variable clinical features and imaging findings. Recent studies have thrown fresh light on the complex role of genetics and autoimmunity in the pathogenesis and natural history of these diverse disorders that include autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, IgG4-related cholangitis, overlap/outlier syndromes, and autoimmune pancreatitis. C1 [Prasad, Srinivasa R.] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Garg, Deepak; Philips, Shaile; Shanbhogue, Alampady K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Nagar, Arpit] Ohio State Univ, Dept Radiol, Med Ctr, Columbus, OH 43210 USA. [Takahashi, Naoki] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Prasad, SR (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiol, 1400 Pressler St, Houston, TX 77030 USA. EM sprasad2@mdander-son.org NR 55 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD APR PY 2012 VL 37 IS 2 BP 261 EP 274 DI 10.1007/s00261-011-9759-0 PG 14 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 918MO UT WOS:000302254100012 PM 21597892 ER PT J AU Burgess, DJ Joseph, A van Ryn, M Carnes, M AF Burgess, Diana Jill Joseph, Anne van Ryn, Michelle Carnes, Molly TI Does Stereotype Threat Affect Women in Academic Medicine? SO ACADEMIC MEDICINE LA English DT Article ID TEST-PERFORMANCE; MATH PERFORMANCE; GENDER DISCRIMINATION; AFRICAN-AMERICANS; LEADERSHIP; IDENTITY; SEX; MEN; FACULTY; NEGOTIATIONS AB Multiple complex factors contribute to the slow pace of women's advancement into leadership positions in academic medicine. In this article, the authors propose that stereotype threat-under which individuals who are members of a group characterized by negative stereotypes in a particular domain perform below their actual abilities in that domain when group membership is emphasized-may play an important role in the underrepresentation of women in leadership positions in academic medicine. Research to objectively assess the impact of stereotype threat for women in academic medicine is feasible and necessary to confirm this hypothesis. Still, a number of conditions present in the academic medicine community today have been shown to trigger stereotype threat in other settings, and stereotype threat fits with existing research on gender in academic medicine. In the meantime, academic health centers should implement relatively simple measures supported by experimental evidence from other settings to reduce the risk of stereotype threat, including (1) introducing the concept of stereotype threat to the academic medicine community, (2) engaging all stakeholders, male and female, to promote identity safety by enacting and making faculty aware of policies to monitor potential instances of discrimination, and training faculty to provide performance feedback that is free of gender bias, (3) counteracting the effects of sex segregation at academic health centers by increasing exposure to successful female leaders, (4) reducing gender stereotype priming by avoiding stereotypically male criteria for promotion, grants, and awards, and (5) building leadership efficacy among female physicians and scientists. C1 [Burgess, Diana Jill] Univ Minnesota, Minneapolis VA Med Ctr, CCDOR, Dept Vet Affairs Med Ctr,Sch Med, Minneapolis, MN 55417 USA. [Burgess, Diana Jill] Univ Minnesota, Dept Med, Sch Med, Minneapolis, MN 55417 USA. [Joseph, Anne] Univ Minnesota, Appl Clin Res Program, Sch Med, Minneapolis, MN 55417 USA. [van Ryn, Michelle] Univ Minnesota, Dept Family Med & Community Hlth, Sch Med, Minneapolis, MN 55417 USA. [Carnes, Molly] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI USA. [Carnes, Molly] Univ Wisconsin, Dept Med, Madison, WI USA. [Carnes, Molly] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. [Carnes, Molly] Meriter Hosp, Madison, WI USA. [Carnes, Molly] Univ Wisconsin, Sch Med & Publ Hth, Madison, WI USA. [Carnes, Molly] Univ Wisconsin, Dept Ind & Syst Engn, Coll Engn, Madison, WI USA. [Carnes, Molly] Univ Wisconsin, Women Sci & Engn Leadership Inst, Coll Engn, Madison, WI USA. [Carnes, Molly] William S Middleton Mem Vet Adm Med Ctr, Women Vet Hlth Program, Madison, WI USA. RP Burgess, DJ (reprint author), Univ Minnesota, Minneapolis VA Med Ctr, CCDOR, Dept Vet Affairs Med Ctr,Sch Med, 1 Vet Dr,152-2E, Minneapolis, MN 55417 USA. EM Diana.Burgess@va.gov RI Burgess, Diana/A-1946-2016 FU National Institutes of Health [R01 GM088477, DP4 GM096822] FX Dr. Carnes is funded in part by grants from the National Institutes of Health (R01 GM088477 and DP4 GM096822). NR 66 TC 33 Z9 34 U1 1 U2 43 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD APR PY 2012 VL 87 IS 4 BP 506 EP 512 DI 10.1097/ACM.0b013e318248f718 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 917AB UT WOS:000302143200025 PM 22361794 ER PT J AU Blumenthal, DM Bernard, K Bohnen, J Bohmer, R AF Blumenthal, Daniel M. Bernard, Ken Bohnen, Jordan Bohmer, Richard TI Addressing the Leadership Gap in Medicine: Residents' Need for Systematic Leadership Development Training SO ACADEMIC MEDICINE LA English DT Article ID INTENSIVE-CARE-UNIT; HEALTH-CARE; PHYSICIAN LEADERSHIP; PATIENT OUTCOMES; TEAM LEADERSHIP; MANAGEMENT; MORTALITY; ASSOCIATION; HOSPITALS; PROGRAM AB All clinicians take on leadership responsibilities when delivering care. Evidence suggests that effective clinical leadership yields superior clinical outcomes. However, few residency programs systematically teach all residents how to lead, and many clinicians are inadequately prepared to meet their day-to-day clinical leadership responsibilities. The purpose of this article is twofold: first, to make the case for the need to refocus residency education around the development of outstanding "frontline" clinical leaders and, second, to provide an evidence-based framework for designing formal leadership development programs for residents. The authors first present a definition of clinical leadership and highlight evidence that effective frontline clinical leadership improves both clinical outcomes and satisfaction for patients and providers. The authors then discuss the health care "leadership gap" and describe barriers to implementing leadership development training in health care. Next, they present evidence that leaders are not just "born" but, rather, can be "made," and offer a set of best practices to facilitate the design of leadership development programs. Finally, the authors suggest approaches to mitigating barriers to implementing leadership development programs and highlight the major reasons why health care delivery organizations, residency programs, and national accreditation bodies must make comprehensive leadership education an explicit goal of residency training. C1 [Bohmer, Richard] Harvard Univ, Sch Business, Dept Technol & Operat Management, Boston, MA 02163 USA. [Blumenthal, Daniel M.; Bohnen, Jordan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bernard, Ken] Harvard Affiliated Emergency Med Residency Progra, Boston, MA USA. RP Bohmer, R (reprint author), Harvard Univ, Sch Business, Dept Technol & Operat Management, Morgan Hall,Soldiers Field Rd, Boston, MA 02163 USA. EM rbohmer@hbs.edu NR 74 TC 36 Z9 37 U1 3 U2 27 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD APR PY 2012 VL 87 IS 4 BP 513 EP 522 DI 10.1097/ACM.0b013e31824a0c47 PG 10 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 917AB UT WOS:000302143200026 PM 22361800 ER PT J AU Niederhauser, A Lukas, CV Parker, V Ayello, EA Zulkowski, K Berlowitz, D AF Niederhauser, Andrea Lukas, Carol VanDeusen Parker, Victoria Ayello, Elizabeth A. Zulkowski, Karen Berlowitz, Dan TI Comprehensive Programs for Preventing Pressure Ulcers: A Review of the Literature SO ADVANCES IN SKIN & WOUND CARE LA English DT Review DE preventing pressure ulcers; multidisciplinary interventions to prevent pressure ulcers; reducing incidence of pressure ulcers ID NURSING-HOME; ACUTE-CARE; QUALITY; IMPLEMENTATION; OUTCOMES; PROJECT; REDUCE; RISK; UNIT AB OBJECTIVE: The objective of this study was to examine the evidence supporting the combined use of interventions to prevent pressure ulcers (PrUs) in acute care and long-term-care facilities. DESIGN: A systematic review of the literature describing multifaceted PrU prevention programs was performed. Articles were included if they described an intervention implemented in acute care settings or long-term-care facilities, incorporated more than 1 intervention component, involved a multidisciplinary team, and included information about outcomes related to the intervention. MAIN RESULTS: Twenty-four studies were identified. Recurring components used in the development and implementation of PrU prevention programs included preparations prior to the start of a program, PrU prevention best practices, staff education, clinical monitoring and feedback, skin care champions, and cues to action. Ten studies reported PrU prevalence rates; 9 of them reported decreased prevalence rates at the end of their programs. Of the 6 studies reporting PrU incidence rates, 5 reported a decrease in incidence rates. Four studies measured care processes: 1 study reported an overall improvement; 2 studies reported improvement on some, but not all, measures; and 1 study reported no change. CONCLUSIONS: There is a growing literature describing multi-pronged, multidisciplinary interventions to prevent PrUs in acute care settings and long-term-care facilities. Outcomes reported in these studies suggest that such programs can be successful in reducing PrU prevalence or incidence rates. However, to strengthen the level of evidence, sites should be encouraged to rigorously evaluate their programs and to publish their results. C1 [Niederhauser, Andrea; Lukas, Carol VanDeusen; Parker, Victoria; Berlowitz, Dan] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Lukas, Carol VanDeusen] Boston Healthcare Syst, Ctr Org Leadership & Management Res, Vet Hlth Adm, Boston, MA USA. [Ayello, Elizabeth A.] Excelsior Coll Nursing, Albany, NY USA. [Ayello, Elizabeth A.] John A Hartford Inst Geriatr Nursing, New York, NY USA. [Ayello, Elizabeth A.] Ayello Harris & Associates, New York, NY USA. [Zulkowski, Karen] Montana State Univ, Bozeman, MT 59717 USA. [Berlowitz, Dan] Bedford Vet Affairs Hosp, Ctr Hlth Qual Outcomes & Econ Res, Boston, MA USA. RP Niederhauser, A (reprint author), Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NR 40 TC 39 Z9 43 U1 1 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-7941 J9 ADV SKIN WOUND CARE JI Adv. Skin Wound Care PD APR PY 2012 VL 25 IS 4 BP 167 EP 188 PG 22 WC Dermatology; Nursing; Surgery SC Dermatology; Nursing; Surgery GA 916TL UT WOS:000302126000004 PM 22441049 ER PT J AU Majumder, S Caccamo, A Medina, DX Benavides, AD Javors, MA Kraig, E Strong, R Richardson, A Oddo, S AF Majumder, Smita Caccamo, Antonella Medina, David X. Benavides, Adriana D. Javors, Martin A. Kraig, Ellen Strong, Randy Richardson, Arlan Oddo, Salvatore TI Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL-1 ss and enhancing NMDA signaling SO AGING CELL LA English DT Article DE learning and memory; mTOR; NMDA; aging; IL-1 ss; cytokines ID LONG-TERM-MEMORY; PROTEIN-SYNTHESIS; AMYLOID-BETA; SPAN; MTOR; TOR; PATHWAY; LTP; CONSOLIDATION; INTERLEUKIN-1 AB Understanding the factors that contribute to age-related cognitive decline is imperative, particularly as age is the major risk factor for several neurodegenerative disorders. Levels of several cytokines increase in the brain during aging, including IL-1 beta, whose levels positively correlate with cognitive deficits. Previous reports show that reducing the activity of the mammalian target of rapamycin (mTOR) extends lifespan in yeast, nematodes, Drosophila, and mice. It remains to be established, however, whether extending lifespan with rapamycin is accompanied by an improvement in cognitive function. In this study, we show that 18-month-old mice treated with rapamycin starting at 2 months of age perform significantly better on a task measuring spatial learning and memory compared to age-matched mice on the control diet. In contrast, rapamycin does not improve cognition when given to 15-month-old mice with pre-existing, age-dependent learning and memory deficits. We further show that the rapamycin-mediated improvement in learning and memory is associated with a decrease in IL-1 beta levels and an increase in NMDA signaling. This is the first evidence to show that a small molecule known to increase lifespan also ameliorates age-dependent learning and memory deficits. C1 [Majumder, Smita; Caccamo, Antonella; Medina, David X.; Oddo, Salvatore] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Majumder, Smita; Caccamo, Antonella; Medina, David X.; Strong, Randy; Richardson, Arlan; Oddo, Salvatore] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Benavides, Adriana D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Kraig, Ellen; Richardson, Arlan] S Texas Vet Hlth Care Syst, Dept Cellular & Struct Biol, San Antonio, TX USA. [Strong, Randy] S Texas Vet Hlth Care Syst, Dept Pharmacol, San Antonio, TX USA. [Javors, Martin A.] S Texas Vet Hlth Care Syst, Dept Psychiat, San Antonio, TX USA. [Strong, Randy; Richardson, Arlan] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. [Strong, Randy; Richardson, Arlan] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. RP Oddo, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM oddo@uthscsa.edu FU NIA [K99/R00AG29729-4, R01AG037637, RC2AG036613]; Glenn Foundation FX This work was supported by NIA grant awards: K99/R00AG29729-4 and R01AG037637 (Oddo, Principal Investigator); RC2AG036613 (Richardson, Principal Investigator, Strong and Oddo, Project Co-leaders), and by an award from the Glenn Foundation to S.O. NR 45 TC 74 Z9 79 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD APR PY 2012 VL 11 IS 2 BP 326 EP 335 DI 10.1111/j.1474-9726.2011.00791.x PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 908WF UT WOS:000301523000018 PM 22212527 ER PT J AU Sun, CC Vaja, V Babitt, JL Lin, HY AF Sun, Chia Chi Vaja, Valentina Babitt, Jodie L. Lin, Herbert Y. TI Targeting the hepcidin-ferroportin axis to develop new treatment strategies for anemia of chronic disease and anemia of inflammation SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Review ID CHRONIC KIDNEY-DISEASE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; IRON-DEFICIENCY ANEMIA; REGULATORY HORMONE HEPCIDIN; PLACEBO-CONTROLLED TRIAL; QUALITY-OF-LIFE; HEMODIALYSIS-PATIENTS; IN-VIVO; INTRAVENOUS IRON; HEREDITARY HEMOCHROMATOSIS AB Anemia of chronic disease (ACD) or anemia of inflammation is prevalent in patients with chronic infection, autoimmune disease, cancer, and chronic kidney disease. ACD is associated with poor prognosis and lower quality of life. Management of ACD using intravenous iron and erythropoiesis stimulating agents are ineffective for some patients and are not without adverse effects, driving the need for new alternative therapies. Recent advances in our understanding of the molecular mechanisms of iron regulation reveal that increased hepcidin, the iron regulatory hormone, is a key factor in the development of ACD. In this review, we will summarize the role of hepcidin in iron homeostasis, its contribution to the pathophysiology of ACD, and novel strategies that modulate hepcidin and its target ferroportin for the treatment of ACD. Am. J. Hematol. 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Sun, Chia Chi; Vaja, Valentina; Babitt, Jodie L.; Lin, Herbert Y.] Harvard Univ, Massachusetts Gen Hosp, Program Membrane Biol,Div Nephrol, Ctr Syst Biol,Richard B Simches Res Ctr,Med Sch, Boston, MA 02114 USA. [Vaja, Valentina] Univ Milan, Fdn Ist Ricovero & Cura Carattere Sci Ca Granda, Milan, Italy. RP Lin, HY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Program Membrane Biol,Div Nephrol, Ctr Syst Biol,Richard B Simches Res Ctr,Med Sch, 185 Cambridge St,CPZN-8216, Boston, MA 02114 USA. EM Lin.Herbert@mgh.harvard.edu FU NIH [K08 DK075846, RO1 DK087727, RO1 DK069533, RO1 DK071837]; Massachusetts General Hospital FX Contract grant sponsor: NIH; Contract grant numbers: K08 DK075846, RO1 DK087727 (to JLB), RO1 DK069533 and RO1 DK071837 (to H.Y.L.).; Contract grant sponsor: Claflin Distinguished Scholar Award from the Massachusetts General Hospital (to J.L.B.). NR 161 TC 82 Z9 88 U1 1 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 2012 VL 87 IS 4 BP 392 EP 400 DI 10.1002/ajh.23110 PG 9 WC Hematology SC Hematology GA 907PH UT WOS:000301429300009 PM 22290531 ER PT J AU Saini, N Jacobson, JO Jha, S Saini, V Weinger, R AF Saini, Neeraj Jacobson, Joseph O. Jha, Smita Saini, Vivek Weinger, Ronald TI The perils of not digging deep enough-Uncovering a rare cause of acquired anemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID PROTEIN-SYNTHESIS; TOXICITY; THROMBOCYTOPENIA; MYELODYSPLASIA; MUTATIONS; DISEASE C1 [Saini, Neeraj; Jha, Smita] NSMC, Salem, MA USA. [Jacobson, Joseph O.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Saini, N (reprint author), NSMC, 81 Highland Ave, Salem, MA USA. EM lymphomalogy@gmail.com OI saini, Neeraj/0000-0001-7435-0933 NR 20 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 2012 VL 87 IS 4 BP 413 EP 416 DI 10.1002/ajh.22235 PG 4 WC Hematology SC Hematology GA 907PH UT WOS:000301429300012 PM 22120958 ER PT J AU Kim, YA Makar, RS AF Kim, Yeowon A. Makar, Robert S. TI Detection of fetomaternal hemorrhage SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID FETAL-MATERNAL HEMORRHAGE; RED-BLOOD-CELLS; FLOW-CYTOMETRIC METHOD; ANTI-D IMMUNOGLOBULIN; RH IMMUNE GLOBULIN; HEREDITARY PERSISTENCE; WEAK-D; F-CELLS; HEMOGLOBIN; QUANTIFICATION AB The prevention of Rhesus D alloimmunization through Rh immune globulin (RhIg) administration is the major indication for the accurate detection and quantification of fetomaternal hemorrhage (FMH). In the setting of D incompatibility, D-positive fetal cells can sensitize the D-negative mother, resulting in maternal anti-D alloantibody production. These anti-D alloantibodies may lead to undesirable sequelae such as hemolytic disease of the newborn (HDN). Since the widespread adoption of FMH screening and RhIg immunoprophylaxis, the overall risk of Rh alloimmunization and infant mortality from HDN has substantially decreased. The rosette screen, the initial test of choice, is highly sensitive in qualitatively detecting 10 mL of fetal whole blood in the maternal circulation. As the screen is reliant on the presence of the D antigen to distinguish fetal from maternal cells, it cannot be used to detect FMH in D-positive mothers or in D-negative mothers carrying a D-negative fetus. The Kleihauer-Betke acid-elution test, the most widely used confirmatory test for quantifying FMH, relies on the principle that fetal RBCs contain mostly fetal hemoglobin (HbF), which is resistant to acid-elution whereas adult hemoglobin is acid-sensitive. Although the Kleihauer-Betke test is inexpensive and requires no special equipment, it lacks standardization and precision, and may not be accurate in conditions with elevated F-cells. Anti-HbF flow cytometry is a promising alternative, although its use is limited by equipment and staffing costs. Hematology analyzers with flow cytometry capabilities may be adapted for fetal cell detection, thus giving clinical laboratories a potentially attractive automated alternative for quantifying FMH. Am. J. Hematol., 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Kim, Yeowon A.; Makar, Robert S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kim, YA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Warren 2, Boston, MA 02114 USA. EM ykim13@partners.org NR 55 TC 14 Z9 14 U1 1 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 2012 VL 87 IS 4 BP 417 EP 423 DI 10.1002/ajh.22255 PG 7 WC Hematology SC Hematology GA 907PH UT WOS:000301429300013 PM 22231030 ER PT J AU Vijayan, A Palevsky, PM AF Vijayan, Anitha Palevsky, Paul M. TI Dosing of Renal Replacement Therapy in Acute Kidney Injury SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Review DE Acute kidney injury; renal replacement therapy; hemodialysis; hemofiltration; hemodiafiltration; continuous renal replacement therapy ID CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; CONTINUOUS VENOVENOUS HEMOFILTRATION; ULTRAFILTRATION FLOW-RATES; TOTAL-BODY WATER; INTERMITTENT HEMODIALYSIS; SOLUTE CLEARANCES; RANDOMIZED-TRIAL; ACUTE DIALYSIS; UREA REMOVAL AB The impact of the intensity of renal replacement therapy on outcomes in patients with acute kidney injury has been studied intensively during the past decade. In this review, we consider the concept of dose of renal replacement therapy in acute kidney injury and summarize the recent clinical trials addressing this topic. Although several single-center trials suggest that more intensive therapy is associated with improved outcomes, 2 large multicenter randomized trials do not find a benefit with higher doses of therapy. Based on these studies, we provide recommendations for the delivered intensity of renal replacement therapy in acute kidney injury. Am J Kidney Dis. 59(4): 569-576. 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 [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. [Vijayan, Anitha] Washington Univ, Sch Med, Div Renal, St Louis, MO 63110 USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Rm 7E123 111F-U,Univ Dr, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 FU Cytopherx Inc; B. Braun; Spectral Diagnostics Inc. FX Financial Disclosure: Dr Vijayan is a consultant for Astute Medical and receives research support from Cytopherx Inc and B. Braun. Dr Palevsky is a consultant for Sanofi-Aventis and Cytopherx Inc and receives research support from Spectral Diagnostics Inc. NR 51 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2012 VL 59 IS 4 BP 569 EP 576 DI 10.1053/j.ajkd.2011.11.035 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 916QE UT WOS:000302117500328 PM 22244680 ER PT J AU Delos Santos, R Obhrai, J Norman, D Watnick, S AF Delos Santos, Rowena Obhrai, Jagdeep Norman, Douglas Watnick, Suzanne TI CARDIOVASCULAR RISK IN THE KIDNEY TRANSPLANT POPULATION SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY MAY 09-13, 2012 CL Washington, DC SP Natl Kidney Fdn C1 [Delos Santos, Rowena; Obhrai, Jagdeep; Norman, Douglas] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Watnick, Suzanne] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2012 VL 59 IS 4 MA 69 BP A32 EP A32 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 916QE UT WOS:000302117500071 ER PT J AU Malhotra, R Hamadeh, Z Acharya, A Ansari, N AF Malhotra, Rakesh Hamadeh, Zaher Acharya, Anjali Ansari, Naheed TI OCCULT RENAL INVOLVEMENT IN POLYARTERITIS NODOSA: THE ROLE OF RENAL ANGIOGRAPHY SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY MAY 09-13, 2012 CL Washington, DC SP Natl Kidney Fdn C1 [Malhotra, Rakesh] Mt Sinai Sch Med, James J Peters VA Med Ctr, Bronx, NY USA. [Hamadeh, Zaher; Acharya, Anjali; Ansari, Naheed] Albert Einstein Coll Med, Jacobi Med Ctr, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2012 VL 59 IS 4 MA 157 BP A54 EP A54 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 916QE UT WOS:000302117500159 ER PT J AU Yu, M Young, B Rodriguez, R Himmelfarb, J Kestenbaum, B AF Yu, Margaret Young, Bessie Rodriguez, Rudy Himmelfarb, Jonathan Kestenbaum, Bryan TI A RARE CASE OF CONCURRENT HEREDITARY HYPOPHOSPHATEMIA AND GLOMERULONEPHRITIS SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY MAY 09-13, 2012 CL Washington, DC SP Natl Kidney Fdn C1 [Yu, Margaret; Young, Bessie; Rodriguez, Rudy; Himmelfarb, Jonathan; Kestenbaum, Bryan] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Kidney Res Inst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2012 VL 59 IS 4 MA 307 BP A91 EP A91 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 916QE UT WOS:000302117500309 ER PT J AU Iezzoni, LI Ogg, M AF Iezzoni, Lisa I. Ogg, Michael TI PATIENT'S PERSPECTIVE Hard Lessons from a Long Hospital Stay SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material DE certified nursing assistants; multiple sclerosis; patient transfer; pressure ulcer; supportive care AB This narrative is related in the alternating voices of the two authors. One author, a 55-year-old man, quadriplegic from primary progressive multiple sclerosis, describes the 10 weeks he spent in four facilities for treatment of a stage IV ischial pressure ulcer. The other author, his friend and health care proxy, describes the advocacy and personal assistance she gave him in the face of often inadequate care that at times threatened his safety, comfort, and emotional well-being. The authors describe their differing perspectives on this care, which involved a transfer onto his open wound, frequently missed meals, and poor bowel management and personal hygiene. They believe that inadequate staffing and insufficient training and supervision of nursing assistants, among other factors, underlay these problems. C1 [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Boston, MA USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. EM liezzoni@partners.org NR 1 TC 0 Z9 0 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD APR PY 2012 VL 112 IS 4 BP 39 EP 42 DI 10.1097/01.NAJ.0000413457.53110.3a PG 4 WC Nursing SC Nursing GA 918PA UT WOS:000302261400017 PM 22456565 ER PT J AU Theodossiadis, PG Achtsidis, V Theodoropoulou, S Tentolouris, N Komninos, C Fountas, KN AF Theodossiadis, Panagiotis G. Achtsidis, Vasilis Theodoropoulou, Sofia Tentolouris, Nicholas Komninos, Christos Fountas, Kostas N. TI The Effect of Alpha Antagonists on Pupil Dynamics: Implications for the Diagnosis of Intraoperative Floppy Iris Syndrome SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CATARACT-SURGERY; TAMSULOSIN; ASSOCIATION; DIAMETER; PUPILLOMETRY; DOXAZOSIN; ALFUZOSIN AB PURPOSE: To assess pupil dynamics quantitatively in relation to the use of alpha(1)-adrenoceptor antagonists, which contribute to the features of intraoperative floppy iris syndrome, using a new, hand-held, digital pupillometer. DESIGN: Prospective case-control study. METHODS: We studied 15 and 25 patients administered tamsulosin and alfuzosin, respectively, as well as 25 control patients. Resting pupil diameter and subsequent contraction, latency, constriction velocity, and dilation velocity were recorded using an electronic pupillometer. All pupil measurements were performed before and after pharmacologic dilation. RESULTS: In predilation pupillary measurements, we detected a significant decrease in maximum pupillary diameter by 0.50 +/- 0.19 mm (P = .011) and in the mean percentage of diameter reduction after stimulation (5.23 +/- 2.42%, P = .035) in the tamsulosin group. Alfuzosin also induced a significant decrease in maximum pupillary diameter (0.49 +/- 0.17 mm, P = .005). Constriction velocity was significantly reduced by 0.70 +/- 0.20 m/s (P = .001) in the tamsulosin group and by 0.54 +/- 0.18 m/s (P = .004) in the alfuzosin group. In terms of postdilation measurements, maximum and minimum pupil diameters were reduced significantly only in the tamsulosin group (by 1.09 +/- 0.31 mm [P = .0011 and by 0.89 +/- 0.36 mm [P = .0161, respectively). CONCLUSIONS: We describe a reliable, accurate, and rapid method to acquire quantitative pupil measurements and identify the tendency for intraoperative floppy iris syndrome before cataract surgery after the use of alfuzosin and tamsulosin. This investigation also analyzed the similarities and differences induced by the 2 drugs in predilation and postdilation pupil dynamics, demonstrating that tamsulosin is more potent than alfuzosin in inducing intraoperative floppy iris syndrome. (Am J Ophthalmol 2012;153:620-626. (C) 2012 by Elsevier Inc. All rights reserved.) C1 [Theodossiadis, Panagiotis G.] Univ Athens, Attikon Univ Hosp, Dept Ophthalmol 2, Athens 12462, Greece. [Achtsidis, Vasilis] St Panteleimon Gen Hosp Nikaia, Dept Ophthalmol, Piraeus, Greece. [Komninos, Christos] St Panteleimon Gen Hosp Nikaia, Dept Urol, Piraeus, Greece. [Theodoropoulou, Sofia] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Tentolouris, Nicholas] Univ Athens, Laiko Gen Hosp, Sch Med, Dept Propaedeut Med 1, Athens, Greece. [Fountas, Kostas N.] Univ Thessaly, Univ Hosp Larissa, Dept Neurosurg, Sch Med, Larisa, Greece. RP Theodossiadis, PG (reprint author), Univ Athens, Attikon Univ Hosp, Dept Ophthalmol 2, 1 Rimini Str, Athens 12462, Greece. EM patheo@med.uoa.gr NR 41 TC 8 Z9 10 U1 0 U2 5 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 APR PY 2012 VL 153 IS 4 BP 620 EP 626 DI 10.1016/j.ajo.2011.09.030 PG 7 WC Ophthalmology SC Ophthalmology GA 920FC UT WOS:000302387100006 PM 22265152 ER PT J AU Ackerman, KE Slusarz, K Guereca, G Pierce, L Slattery, M Mendes, N Herzog, DB Misra, M AF Ackerman, Kathryn E. Slusarz, Katherine Guereca, Gabriela Pierce, Lisa Slattery, Meghan Mendes, Nara Herzog, David B. Misra, Madhusmita TI Higher ghrelin and lower leptin secretion are associated with lower LH secretion in young amenorrheic athletes compared with eumenorrheic athletes and controls SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE amenorrhea; adolescents; luteinizing hormone; energy ID LUTEINIZING-HORMONE PULSATILITY; GONADOTROPIN-RELEASING-HORMONE; POLYCYSTIC-OVARY-SYNDROME; ANOREXIA-NERVOSA; ADOLESCENT GIRLS; HEALTHY ADOLESCENTS; ACYLATED GHRELIN; PLASMA LEPTIN; PUBERTY; WOMEN AB Ackerman KE, Slusarz K, Guereca G, Pierce L, Slattery M, Mendes N, Herzog DB, Misra M. Higher ghrelin and lower leptin secretion are associated with lower LH secretion in young amenorrheic athletes compared with eumenorrheic athletes and controls. Am J Physiol Endocrinol Metab 302: E800-E806, 2012. First published January 17, 2012; doi: 10.1152/ajpendo.00598.2011.-Amenorrhea is common in young athletes and is associated with low fat mass. However, hormonal factors that link decreased fat mass with altered gonadotropin pulsatility and amenorrhea are unclear. Low levels of leptin (an adipokine) and increased ghrelin (an orexigenic hormone that increases as fat mass decreases) impact gonadotropin pulsatility. Studies have not examined luteinizing hormone (LH) secretory dynamics in relation to leptin or ghrelin secretory dynamics in adolescent and young adult athletes. We hypothesized that 1) young amenorrheic athletes (AA) would have lower LH and leptin and higher ghrelin secretion than eumenorrheic athletes (EA) and nonathletes and 2) higher ghrelin and lower leptin would be associated with lower LH secretion. This was a cross-sectional study. We examined ghrelin and leptin secretory patterns (over 8 h, from 11 PM to 7 AM) in relation to LH secretory patterns in AA, EA, and nonathletes aged 14-21 yr. Ghrelin and leptin were assessed every 20 min and LH every 10 min. Groups did not differ for age, bone age, or BMI. However, fat mass was lower in AA than in EA and nonathletes. AA had lower LH and higher ghrelin pulsatile secretion and AUC than nonathletes and lower leptin pulsatile secretion and AUC than EA and nonathletes. Percent body fat was associated positively with LH and leptin secretion and inversely with ghrelin. In a regression model, ghrelin and leptin secretory parameters were associated independently with LH secretory parameters. We conclude that higher ghrelin and lower leptin secretion in AA related to lower fat mass may contribute to altered LH pulsatility and amenorrhea. C1 [Ackerman, Kathryn E.; Slusarz, Katherine; Guereca, Gabriela; Pierce, Lisa; Slattery, Meghan; Mendes, Nara; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Ackerman, Kathryn E.; Slusarz, Katherine; Guereca, Gabriela; Pierce, Lisa; Slattery, Meghan; Mendes, Nara; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA. [Ackerman, Kathryn E.] Childrens Hosp Boston, Div Sports Med, Boston, MA USA. [Herzog, David B.] Massachusetts Gen Hosp, Harris Ctr, Boston, MA 02114 USA. [Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org RI Mendes Estella, Nara/E-4682-2013; Mendes Estella, Nara/A-1469-2015 FU National Institutes of Health [1-UL-1-RR-025758-01, 1-R01-HD-060827-01A1, NCT00946192] FX This study was supported by National Institutes of Health Grants 1-UL-1-RR-025758-01 and 1-R01-HD-060827-01A1 (Clinical Trial Registration No. NCT00946192). NR 35 TC 16 Z9 16 U1 1 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR PY 2012 VL 302 IS 7 BP E800 EP E806 DI 10.1152/ajpendo.00598.2011 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 919QA UT WOS:000302342100006 PM 22252944 ER PT J AU Nishino, M Jagannathan, JP Krajewski, KM O'Regan, K Hatabu, H Shapiro, G Ramaiya, NH AF Nishino, Mizuki Jagannathan, Jyothi P. Krajewski, Katherine M. O'Regan, Kevin Hatabu, Hiroto Shapiro, Geoffrey Ramaiya, Nikhil H. TI Personalized Tumor Response Assessment in the Era of Molecular Medicine: Cancer-Specific and Therapy-Specific Response Criteria to Complement Pitfalls of RECIST SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE CT; personalized medicine; RECIST; response assessment ID RENAL-CELL CARCINOMA; GASTROINTESTINAL STROMAL TUMORS; GROWTH-FACTOR RECEPTOR; LUNG-CANCER; IMATINIB MESYLATE; METASTATIC MELANOMA; TARGETED THERAPY; SOLID TUMORS; TYROSINE KINASE; PHASE-II AB OBJECTIVE. The purpose of this article is to review cancer-and therapy-specific tumor response assessment criteria used in clinical trials and in practice, with illustrative case examples, and to discuss future directions toward "personalized" tumor response assessment. CONCLUSION. Although Response Evaluation Criteria in Solid Tumors will remain as the primary generalized criteria for response assessment, newer cancer-and therapy-specific criteria will play an important role in providing state-of-the-art response assessment of tumor following molecular targeted therapy and will contribute to personalized cancer care in the era of molecular medicine. C1 [Nishino, Mizuki; Jagannathan, Jyothi P.; Krajewski, Katherine M.; O'Regan, Kevin; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Nishino, Mizuki; Jagannathan, Jyothi P.; Krajewski, Katherine M.; O'Regan, Kevin; Hatabu, Hiroto; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Shapiro, Geoffrey] Dana Farber Canc Inst, Early Drug Dev Ctr, Dept Med Oncol, Boston, MA 02215 USA. RP Nishino, M (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM Mizuki_Nishino@dfci.harvard.edu FU Agfa HealthCare/RSNA; National Institutes of Health [1K23CA157631-01A1, 5 R21 CA11627-02] FX The investigators were supported by 2009-2011 Agfa HealthCare/RSNA Research Scholar Grant (to M. Nishino) and the National Institutes of Health grant 1K23CA157631-01A1 (grant 5 R21 CA11627-02 to H. Hatabu). NR 57 TC 59 Z9 60 U1 0 U2 5 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 APR PY 2012 VL 198 IS 4 BP 737 EP 745 DI 10.2214/AJR.11.7483 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 916UP UT WOS:000302129000016 PM 22451534 ER PT J AU Goldberg-Stein, SA Liu, B Hahn, PF Lee, SI AF Goldberg-Stein, Shlomit A. Liu, Bob Hahn, Peter F. Lee, Susanna I. TI Radiation Dose Management: Part 2, Estimating Fetal Radiation Risk From CT During Pregnancy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE ALARA; CT; dose; dose estimation; fetus; pregnancy; radiation ID PATIENT AB OBJECTIVE. The purpose of this article is to review fetal radiation doses and associated risks resulting from CT performed during pregnancy. The scanning parameters that influence dose and the techniques for estimating and reducing dose are explained. CONCLUSION. Fetal radiation doses for CT examinations in which the fetus is not directly imaged-for example, head or chest CT-are minimal and need not figure in the risk-benefit analysis to perform the examination. In contrast, radiation dose should be considered with abdominopelvic CT because the fetus is likely to be exposed directly to the scanning beam. Safe implementation of CT in this setting requires an understanding of the factors influencing radiation dose. With this knowledge, when a risk-benefit analysis in a given clinical situation favors imaging using CT, the radiologist need not withhold or delay the examination and can achieve diagnostic-quality images while reducing radiation exposure. C1 [Goldberg-Stein, Shlomit A.; Lee, Susanna I.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Webster Ctr Radiat Res & Educ,Med Sch, Boston, MA 02114 USA. [Liu, Bob] Massachusetts Gen Hosp, Dept Radiol Phys, Boston, MA 02114 USA. RP Goldberg-Stein, SA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Webster Ctr Radiat Res & Educ,Med Sch, 55 Fruit St,FND 216, Boston, MA 02114 USA. EM sgoldberg-stein@partners.org NR 12 TC 6 Z9 6 U1 0 U2 8 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 APR PY 2012 VL 198 IS 4 BP W352 EP W356 DI 10.2214/AJR.11.7458 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 916UP UT WOS:000302129000004 PM 22451572 ER PT J AU Bieliauskas, S Tubbs, RR Bacon, CM Eshoa, C Foucar, K Gibson, SE Kroft, SH Sohani, AR Swerdlow, SH Cook, JR AF Bieliauskas, Shannon Tubbs, Raymond R. Bacon, Chris M. Eshoa, Camellia Foucar, Kathryn Gibson, Sarah E. Kroft, Steven H. Sohani, Aliyah R. Swerdlow, Steven H. Cook, James R. TI Gamma Heavy-chain Disease: Defining the Spectrum of Associated Lymphoproliferative Disorders Through Analysis of 13 Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE gamma heavy-chain disease; lymphoplasmacytic lymphoma; plasmacytic differentiation; small B-cell lymphoma ID B-CELL LYMPHOMAS; SMALL-INTESTINAL DISEASE; MARGINAL ZONE LYMPHOMAS; PLASMACYTIC DIFFERENTIATION; LYMPHOPLASMACYTIC LYMPHOMA; CHRONIC ARTHRITIS; PATHOGENIC LINK; GENE; IMMUNOGLOBULIN; REARRANGEMENTS AB Gamma heavy-chain disease (gHCD) is defined as a lymphoplasmacytic neoplasm that produces an abnormally truncated immunoglobulin gamma heavy-chain protein that lacks associated light chains. There is scant information in the literature regarding the morphologic findings in this rare disorder, but cases have often been reported to resemble lymphoplasmacytic lymphoma (LPL). To clarify the spectrum of lymphoproliferative disorders that may be associated with gHCD, this study reports the clinical, morphologic, and phenotypic findings in 13 cases of gHCD involving lymph nodes (n = 7), spleen (n = 2), bone marrow (n = 8), or other extranodal tissue biopsies (n = 3). Clinically, patients showed a female predominance (85%) with frequent occurrence of autoimmune disease (69%). Histologically, 8 cases (61%) contained a morphologically similar neoplasm of small lymphocytes, plasmacytoid lymphocytes, and plasma cells that was difficult to classify with certainty, whereas the remaining 5 cases (39%) showed the typical features of one of several other well-defined entities in the 2008 WHO classification. This report demonstrates that gHCD is associated with a variety of underlying lymphoproliferative disorders but most often shows features that overlap with cases previously reported as "vaguely nodular, polymorphous" LPL. These findings also provide practical guidance for the routine evaluation of small B-cell neoplasms with plasmacytic differentiation that could represent a heavy-chain disease and give suggestions for an improved approach to the WHO classification of gHCD. C1 [Cook, James R.] Cleveland Clin, Pathol & Lab Med Inst, Dept Mol Pathol, Cleveland, OH 44195 USA. [Bacon, Chris M.] Newcastle Univ, No Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Bacon, Chris M.] Newcastle Upon Tyne Hosp NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England. [Kroft, Steven H.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Foucar, Kathryn] Univ New Mexico, Albuquerque, NM 87131 USA. [Gibson, Sarah E.; Swerdlow, Steven H.] Univ Pittsburgh, Pittsburgh, PA USA. [Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sohani, Aliyah R.] Harvard Univ, Sch Med, Boston, MA USA. RP Cook, JR (reprint author), Cleveland Clin, Pathol & Lab Med Inst, Dept Mol Pathol, 9500 Euclid Ave,Mail Stop L11, Cleveland, OH 44195 USA. EM cookj2@ccf.org FU NCATS NIH HHS [UL1 TR000005]; NCRR NIH HHS [UL1 RR024153] NR 34 TC 12 Z9 12 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2012 VL 36 IS 4 BP 534 EP 543 DI 10.1097/PAS.0b013e318240590a PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 916ZQ UT WOS:000302142100006 PM 22301495 ER PT J AU Alessandrini, A Bromberg, JS AF Alessandrini, Alessandro Bromberg, Jonathan S. TI LITERATURE Watch Implications for transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material C1 [Alessandrini, Alessandro] Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. [Alessandrini, Alessandro] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Bromberg, Jonathan S.] Univ Maryland, Div Transplantat, Baltimore, MD 21201 USA. RP Alessandrini, A (reprint author), Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2012 VL 12 IS 4 BP 801 EP 801 DI 10.1111/j.1600-6143.2012.04058.x PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 915WP UT WOS:000302058600002 PM 22458381 ER PT J AU Kutner, NG Johansen, KL Zhang, R Huang, Y Amaral, S AF Kutner, N. G. Johansen, K. L. Zhang, R. Huang, Y. Amaral, S. TI Perspectives on the New Kidney Disease Education Benefit: Early Awareness, Race and Kidney Transplant Access in a USRDS Study SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Access to transplantation; African Americans; kidney transplantation; patient education; United States Renal Data System; waiting list ID STAGE RENAL-DISEASE; PATIENT EDUCATION; DIALYSIS; HEMODIALYSIS AB Education services for Stage-IV chronic kidney disease patients were added in 2010 as a Part B covered benefit under the Medicare Improvements for Patients and Providers Act. Desired outcomes include early pursuit of kidney transplantation by more patients and reduction of racial disparities in access to transplantation. During 20052007, a United States Renal Data System (USRDS) special study surveyed 1123 patients in a national cohort who had recently started dialysis, identified themselves as black or white, and were reported by their physician as potentially eligible transplant candidates. Patients were asked if kidney transplantation had been discussed with them before they initiated renal replacement therapy, and survey responses were linked with subsequent wait listing and transplant events in USRDS registry files. KaplanMeier analyses showed a significant association between early transplant awareness and subsequent wait listing. Adjusted Cox models showed a significant race/early transplant awareness interaction, however, with the impact of early awareness on wait listing much stronger for whites. Ongoing support and education about kidney transplantation for patients after dialysis start could help to build on early education and foster greater quality improvement in patient outcomes. C1 [Kutner, N. G.; Johansen, K. L.; Zhang, R.; Huang, Y.] Emory Univ, Rehabil Qual Life Special Studies Ctr, US Renal Data Syst, Atlanta, GA 30322 USA. [Johansen, K. L.] Univ Calif San Francisco, San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94143 USA. [Johansen, K. L.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Amaral, S.] Childrens Hosp Philadelphia, Div Nephrol, Philadelphia, PA 19104 USA. RP Kutner, NG (reprint author), Emory Univ, Rehabil Qual Life Special Studies Ctr, US Renal Data Syst, Atlanta, GA 30322 USA. EM nkutner@emory.edu FU National Institutes of Health [HHSN267200715004C, N01-DK-7-5004] FX This study was supported by National Institutes of Health contract HHSN267200715004C, ADB No. N01-DK-7-5004 (Dr. Kutner). The interpretation and reporting of the data presented here are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government. We are grateful for patients' participation in the study and for contributions of the CDS Steering Committee: Glenn M. Chertow, George A. Kaysen, Kirsten L. Johansen and Jordi Goldstein, USRDS Nutrition Special Studies Center; Lawrence Hunsicker, USRDS Economics Special Studies Center; Donna Brogan and Nancy G. Kutner, USRDS Rehabilitation/Quality of Life Special Studies Center; Allan J. Collins, Shu-Cheng Chen and Sarah Pederson, USRDS Coordinating Center; Doug Marsh and Vickie Peters, ESRD Network Coordinating Center; Sondra Frenz, DataBanque Research Services; Lawrence Y. Agodoa and Paul W. Eggers, NIDDK; Pam Frederick and Condict Martak, CMS. NR 22 TC 12 Z9 12 U1 3 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2012 VL 12 IS 4 BP 1017 EP 1023 DI 10.1111/j.1600-6143.2011.03898.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 915WP UT WOS:000302058600028 PM 22226386 ER PT J AU Bedoya, CA Wiebe, JS Castro, FG Rodriguez, VM AF Bedoya, C. Andres Wiebe, John S. Castro, Felipe G. Rodriguez, Vivian M. TI ADAPTATION OF EVIDENCE-BASED INTERVENTIONS FOR LATINO MEDICAL POPULATIONS: STRATEGIES, LESSONS LEARNED AND FUTURE DIRECTIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Bedoya, C. Andres] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bedoya, C. Andres] Harvard Univ, Sch Med, Boston, MA USA. [Wiebe, John S.; Castro, Felipe G.] Univ Texas El Paso, El Paso, TX 79968 USA. [Rodriguez, Vivian M.] Virginia Commonwealth Univ, Richmond, VA USA. EM abedoya@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2012 VL 43 SU 1 BP S63 EP S63 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400243 ER PT J AU Benedict, C Llabre, M Penedo, FJ Traeger, L Soloway, M Kava, BR Schneiderman, N Antoni, MH AF Benedict, Catherine Llabre, Maria Penedo, Frank J. Traeger, Lara Soloway, Mark Kava, Bruce R. Schneiderman, Neil Antoni, Michael H. TI SEXUAL DYSFUNCTION AND QUALITY OF LIFE AFTER TREATMENT FOR LOCALIZED PROSTATE CANCER: THE ROLE OF SEXUAL DESIRE AND BOTHER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Benedict, Catherine; Llabre, Maria; Penedo, Frank J.; Schneiderman, Neil; Antoni, Michael H.] Univ Miami, Coral Gables, FL 33124 USA. [Penedo, Frank J.; Antoni, Michael H.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Traeger, Lara] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM cbenedict@psy.miami.edu NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2012 VL 43 SU 1 BP S280 EP S280 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092401178 ER PT J AU Bennett, GG Warner, E Glasgow, R Askew, S Emmons, KM Rosner, B Colditz, GA AF Bennett, Gary G. Warner, Erica Glasgow, Russell Askew, Sandy Emmons, Karen M. Rosner, Bernard Colditz, Graham A. TI WEIGHT LOSS AMONG SOCIOECONOMICALLY DISADVANTAGED PRIMARY CARE PATIENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Bennett, Gary G.; Askew, Sandy] Duke Univ, Durham, NC 27608 USA. [Warner, Erica; Emmons, Karen M.; Rosner, Bernard] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Glasgow, Russell] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci,Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. EM gary.bennett@duke.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S272 EP S272 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092401145 ER PT J AU Cooley, ME Wang, Q Shi, L Roper, K Finn, K Marcoux, JP Zaner, K Hayman, LL AF Cooley, Mary E. Wang, Qian Shi, Ling Roper, Kristin Finn, Kathleen Marcoux, J. Paul Zaner, Ken Hayman, Laura L. TI THE RELATIONSHIPS AMONG STRESS, MULTIPLE RISK BEHAVIORS AND HEALTH-RELATED QUALITY OF LIFE IN LUNG CANCER PATIENT-FAMILY MEMBER DYADS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Cooley, Mary E.; Wang, Qian; Roper, Kristin; Marcoux, J. Paul] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cooley, Mary E.; Shi, Ling; Roper, Kristin; Hayman, Laura L.] Boston Univ, Boston, MA 02215 USA. [Finn, Kathleen; Zaner, Ken] Boston Med Ctr, Boston, MA USA. EM mary_cooley@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 3 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 APR PY 2012 VL 43 SU 1 BP S82 EP S82 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400318 ER PT J AU Cuevas, A O'Brien, K Press, N Poat, J Saha, S AF Cuevas, Adolfo O'Brien, Kerth Press, Nancy Poat, Jennifer Saha, Somnath TI RACE CONCORDANT PATIENT-PROVIDER RELATIONSHIPS IN DIABETES AND HYPERTENSION CARE: VIEWS OF PATIENTS FROM THREE CULTURAL GROUPS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Cuevas, Adolfo; O'Brien, Kerth] Portland State Univ, Portland, OR 97207 USA. [Press, Nancy; Poat, Jennifer; Saha, Somnath] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. EM acuevas@pdx.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S230 EP S230 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400896 ER PT J AU Elsesser, SA O'Cleirigh, C Taylor, SW Bradford, JB AF Elsesser, Steven A. O'Cleirigh, Conall Taylor, S. Wade Bradford, Judith B. TI DESCRIPTIVE CHARACTERISTICS OF SEXUAL MINORITIES WHO ENGAGE IN TOBACCO USE: IMPLICATIONS FOR IMPROVING SMOKING CESSATION PROGRAMS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Elsesser, Steven A.; O'Cleirigh, Conall; Taylor, S. Wade; Bradford, Judith B.] Fenway Inst, Boston, MA 02215 USA. [O'Cleirigh, Conall] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM selsesser@fenwayhealth.org NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S129 EP S129 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400501 ER PT J AU Gilleland, J Reed-Knight, B Brand, S Griffin, A Wasilewski-Masker, K Meacham, L Mertens, A AF Gilleland, Jordan Reed-Knight, Bonney Brand, Sarah Griffin, Anya Wasilewski-Masker, Karen Meacham, Lillian Mertens, Ann TI ASSESSMENT OF FAMILY PSYCHOSOCIAL ADJUSTMENT IN SURVIVORS OF PEDIATRIC CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Gilleland, Jordan; Wasilewski-Masker, Karen; Meacham, Lillian; Mertens, Ann] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30342 USA. [Gilleland, Jordan; Griffin, Anya; Wasilewski-Masker, Karen; Meacham, Lillian; Mertens, Ann] Childrens Healthcare Atlanta, Aflac Canc Ctr, Atlanta, GA USA. [Reed-Knight, Bonney] Univ Georgia, Athens, GA 30602 USA. [Brand, Sarah] Dana Farber Canc Inst, Boston, MA 02115 USA. EM jordan.gilleland@choa.org NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2012 VL 43 SU 1 BP S173 EP S173 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400670 ER PT J AU Greaney, ML Puleo, E Sprunck-Harrild, K Bennett, GG Viswanath, K Coeling, M Emmons, KM AF Greaney, Mary L. Puleo, Elaine Sprunck-Harrild, Kim Bennett, Gary G. Viswanath, K. Coeling, Molly Emmons, Karen M. TI AUTOMATED VOICE REMINDERS OR SMS TEXT REMINDERS: WHAT IS ASSOCIATED WITH PREFERRED MODALITY? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Greaney, Mary L.; Sprunck-Harrild, Kim; Viswanath, K.; Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Puleo, Elaine] Univ Massachusetts, Amherst, MA 01003 USA. [Bennett, Gary G.] Duke Univ, Durham, NC USA. [Coeling, Molly] Univ Chicago, Chicago, IL 60637 USA. EM mary_greaney@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 2 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 APR PY 2012 VL 43 SU 1 BP S106 EP S106 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400411 ER PT J AU Greer, J Pirl, W Jackson, V Gallagher, E Temel, J AF Greer, Joseph Pirl, William Jackson, Vicki Gallagher, Emily Temel, Jennifer TI PERCEPTIONS OF HEALTH STATUS AND SURVIVAL IN PATIENTS WITH METASTATIC LUNG CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Greer, Joseph; Pirl, William; Jackson, Vicki; Gallagher, Emily; Temel, Jennifer] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jgreer2@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S83 EP S83 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400319 ER PT J AU Heckman, C Darlow, S Cohen-Filipic, J Kloss, J Munshi, T Manne, S AF Heckman, Carolyn Darlow, Susan Cohen-Filipic, Jessye Kloss, Jacqueline Munshi, Teja Manne, Sharon TI PSYCHIATRIC SYMPTOMS OF YOUNG ADULT FEMALE INDOOR TANNERS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Heckman, Carolyn; Darlow, Susan; Munshi, Teja] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Cohen-Filipic, Jessye] Portland VA Med Ctr, Portland, OR USA. [Kloss, Jacqueline] Drexel Univ, Philadelphia, PA 19104 USA. [Manne, Sharon] Canc Inst New Jersey, New Brunswick, NJ USA. EM carolyn.heckman@fccc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S160 EP S160 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400621 ER PT J AU Hoerster, KD Jakupcak, M AF Hoerster, Katherine D. Jakupcak, Matthew TI ASSOCIATION BETWEEN MENTAL HEALTH AND PHYSICAL ACTIVITY ENGAGEMENT AMONG IRAQ/AFGHANISTAN WAR VETERANS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hoerster, Katherine D.; Jakupcak, Matthew] VA Puget Sound Healthcare Syst, Seattle Div, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Hoerster, Katherine D.; Jakupcak, Matthew] Univ Washington, Seattle, WA 98195 USA. EM k_hoerster@hotmail.com NR 0 TC 0 Z9 0 U1 1 U2 3 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 APR PY 2012 VL 43 SU 1 BP S42 EP S42 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400160 ER PT J AU Kupperman, E Gonzalez, JS Psaros, C Feldman, J Safren, S AF Kupperman, Elyse Gonzalez, Jeffrey S. Psaros, Christina Feldman, Jonathan Safren, Steven TI SOCIAL SUPPORT, DEPRESSION AND TREATMENT ADHERENCE AMONG TYPE 2 DIABETES PATIENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kupperman, Elyse; Gonzalez, Jeffrey S.; Feldman, Jonathan] Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY USA. [Gonzalez, Jeffrey S.] Albert Einstein Coll Med, Diabet Res Ctr, Bronx, NY 10467 USA. [Psaros, Christina; Safren, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Psaros, Christina; Safren, Steven] Harvard Univ, Sch Med, Boston, MA USA. EM Ekupperman@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 4 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 APR PY 2012 VL 43 SU 1 BP S156 EP S156 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400604 ER PT J AU Labbe, AK O'Cleirigh, C Traeger, L Safren, SA AF Labbe, Allison K. O'Cleirigh, Conall Traeger, Lara Safren, Steven A. TI MODERATING EFFECTS OF ILLICIT SUBSTANCE USE ON MAINTENANCE OF DEPRESSION TREATMENT EFFECTS AMONG HIV-POSITIVE PATIENTS RECEIVING CBT FOR ADHERENCE AND DEPRESSION (CBT-AD) SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Labbe, Allison K.; O'Cleirigh, Conall; Traeger, Lara; Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM aklabbe@partners.org NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S263 EP S263 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092401109 ER PT J AU Lombardero, A Campbell, DG Harris, KJ Chaney, EF Lanto, AB Rubenstein, LV AF Lombardero, Anayansi Campbell, Duncan G. Harris, Kari J. Chaney, Edmund F. Lanto, Andrew B. Rubenstein, Lisa V. TI PREVALENCE AND CORRELATES OF SMOKING STATUS AMONG PATIENTS WITH DEPRESSION IN VA PRIMARY CARE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Harris, Kari J.] Univ Montana, Sch Publ Hlth Sci, Missoula, MT 59812 USA. [Chaney, Edmund F.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Chaney, Edmund F.] Vet Affairs Puget Sound, Hlth Serv Res & Dev, Seattle, WA USA. [Lanto, Andrew B.] Vet Affairs Greater Angeles, Hlth Serv Res & Dev, Los Angeles, CA USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. EM anayansi.lombardero@umontana.ed NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2012 VL 43 SU 1 BP S46 EP S46 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400179 ER PT J AU Lovejoy, TI Dobscha, SK Morasco, BJ AF Lovejoy, Travis I. Dobscha, Steven K. Morasco, Benjamin J. TI CHRONIC PAIN TREATMENT AND MEDICAL UTILIZATION AMONG PATIENTS WITH HEPATITIS C SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Lovejoy, Travis I.; Dobscha, Steven K.; Morasco, Benjamin J.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97239 USA. EM travis.lovejoy@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S248 EP S248 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092401049 ER PT J AU Martin, E Williams, NG Winett, R AF Martin, Emily Williams, Neville Galloway Winett, Richard TI MANUAL DEVELOPMENT FOR A MINDFULNESS BASED INTERVENTION TO INCREASE CARDIORESPIRATORY FITNESS IN SEDENTARY ADULTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Martin, Emily; Williams, Neville Galloway; Winett, Richard] Virginia Tech, Blacksburg, VA USA. [Martin, Emily] VA Boston Healthcare Syst, Boston Consortium Clin Psychol, Jamaica Plain, MA USA. EM emilymar@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 4 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 APR PY 2012 VL 43 SU 1 BP S252 EP S252 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092401068 ER PT J AU Martin, L Wolf, E Mori, D AF Martin, Luci Wolf, Erika Mori, DeAnna TI COGNITIVE AND PSYCHOSOCIAL PREDICTORS OF MORTALITY IN VETERANS WITH END STAGE RENAL DISEASE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Martin, Luci] Univ La Verne, La Verne, CA 91750 USA. [Martin, Luci; Mori, DeAnna] VA Boston Healthcare Syst, Med Psychol, Boston, MA USA. [Wolf, Erika] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Wolf, Erika; Mori, DeAnna] BU Sch Med, Boston, MA USA. EM luci7martin@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S215 EP S215 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400839 ER PT J AU Mimiaga, MJ Closson, EF Pantalone, DW Taylor, SW Garber, M Safren, SA Mitty, JA AF Mimiaga, Matthew J. Closson, Elizabeth F. Pantalone, David W. Taylor, S. Wade Garber, Michael Safren, Steven A. Mitty, Jennifer A. TI AN OPEN PHASE PILOT OF BEHAVIORAL ACTIVATION TO SUSTAIN AND ENHANCE THE EFFECT OF CONTINGENCY MANAGEMENT FOR REDUCING STIMULANT USE AMONG HIV-INFECTED PATIENTS IN CARE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02214 USA. [Mimiaga, Matthew J.; Closson, Elizabeth F.; Pantalone, David W.; Taylor, S. Wade; Garber, Michael; Safren, Steven A.; Mitty, Jennifer A.] Fenway Inst, Boston, MA USA. [Pantalone, David W.] Suffolk Univ, Boston, MA 02114 USA. [Mitty, Jennifer A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02214 USA. EM mmimiaga@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2012 VL 43 SU 1 BP S262 EP S262 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092401106 ER PT J AU Park, ER Dusek, J AF Park, Elyse R. Dusek, Jeffery TI A NEW TREATMENT PARADIGM FOR COPING WITH CHRONIC STRESS: THE RELAXATION RESPONSE RESILIENCY PROGRAM SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Park, Elyse R.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Dusek, Jeffery] Abbott NW Hosp, Inst Hlth & Living, Minneapolis, MN 55407 USA. EM epark@partners.org NR 0 TC 0 Z9 0 U1 1 U2 5 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 APR PY 2012 VL 43 SU 1 BP S2 EP S2 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400006 ER PT J AU Quintiliani, LM Stoddard, AM Lederman, R Harden, EA Sorensen, G AF Quintiliani, Lisa M. Stoddard, Anne M. Lederman, Ruth Harden, Elizabeth A. Sorensen, Glorian TI DISSEMINATION OF A TOBACCO CESSATION PROGRAM FOR UNIONIZED WORKERS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Quintiliani, Lisa M.] Boston Univ, Boston, MA 02118 USA. [Stoddard, Anne M.] New England Res Inst, Watertown, MA 02172 USA. [Lederman, Ruth; Harden, Elizabeth A.; Sorensen, Glorian] Dana Farber Canc Inst, Boston, MA 02115 USA. EM lmquinti@bu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S257 EP S257 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092401088 ER PT J AU Sharff, M Mays, D DeMarco, T Peshkin, B Garber, J Schneider, K Patenaude, A Tercyak, KP AF Sharff, McKane Mays, Darren DeMarco, Tiffani Peshkin, Beth Garber, Judy Schneider, Katherine Patenaude, Andrea Tercyak, Kenneth P. TI CHILDREN'S QUALITY OF LIFE SURROUNDING MATERNAL SCREENING FOR HEREDITARY BREAST AND OVARIAN CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Sharff, McKane; Mays, Darren; DeMarco, Tiffani; Peshkin, Beth; Tercyak, Kenneth P.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Garber, Judy; Schneider, Katherine; Patenaude, Andrea] Dana Farber Canc Inst, Boston, MA 02115 USA. EM tercyakk@georgetown.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S176 EP S176 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400683 ER PT J AU Smitherman, AH Clements, KL Thorn, B Ward, LC Kilgo, GR AF Smitherman, Anna H. Clements, Kristi L. Thorn, Beverly Ward, L. Charles Kilgo, Gary R. TI VALIDATION OF A NEW THREE FACTOR MODEL OF CATASTROPHIZING IN A CLINICAL SAMPLE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Smitherman, Anna H.; Thorn, Beverly] Univ Alabama, Tuscaloosa, AL 35487 USA. [Clements, Kristi L.] Birmingham VA Med Ctr, Birmingham, AL USA. [Ward, L. Charles] Tuscaloosa VA Med Ctr, Tuscaloosa, AL USA. [Kilgo, Gary R.] Kilgo Headache Clin, Tuscaloosa, AL USA. EM ahsmitherman@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S38 EP S38 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400145 ER PT J AU Smitherman, AH Clements, KL Thorn, B Ward, LC AF Smitherman, Anna H. Clements, Kristi L. Thorn, Beverly Ward, L. Charles TI MEASURING CATASTROPHIZING: A NEW LOOK AT COMPONENTS OF THE CONSTRUCT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Smitherman, Anna H.; Thorn, Beverly] Univ Alabama, Tuscaloosa, AL 35487 USA. [Clements, Kristi L.] Birmingham VA Med Ctr, Birmingham, AL USA. [Ward, L. Charles] Tuscaloosa VA Med Ctr, Tuscaloosa, AL USA. EM ahsmitherman@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2012 VL 43 SU 1 BP S38 EP S38 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400146 ER PT J AU Tamers, SL Okechukwu, C Allen, J Yang, M Sorensen, G AF Tamers, Sara L. Okechukwu, Cassandra Allen, Jennifer Yang, May Sorensen, Glorian TI EXPLORING THE ROLE OF FAMILY, FRIEND, AND NEIGHBOR SOCIALTIES AND SUPPORT ON DIETARY AND PHYSICAL ACTIVITY BEHAVIORS AMONG LOW-INCOME RESIDENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Tamers, Sara L.; Okechukwu, Cassandra; Allen, Jennifer; Sorensen, Glorian] Harvard, Boston, MA 02115 USA. [Tamers, Sara L.; Allen, Jennifer; Sorensen, Glorian] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yang, May] New England Res Inst, Boston, MA USA. EM sara_tamers@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2012 VL 43 SU 1 BP S192 EP S192 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400746 ER PT J AU Tercyak, KP Mays, D DeMarco, T Peshkin, B Garber, J Schneider, K Patenaude, A AF Tercyak, Kenneth P. Mays, Darren DeMarco, Tiffani Peshkin, Beth Garber, Judy Schneider, Katherine Patenaude, Andrea TI PRELIMINARY OUTCOMES OF A RANDOMIZED CONTROLLED TRIAL TO INFORM MATERNAL DECISIONS ABOUT COMMUNICATING CANCER GENETIC TEST RESULTS TO CHILDREN SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Tercyak, Kenneth P.; Mays, Darren; DeMarco, Tiffani; Peshkin, Beth] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Garber, Judy; Schneider, Katherine; Patenaude, Andrea] Dana Farber Canc Inst, Boston, MA 02115 USA. EM tercyakk@georgetown.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S149 EP S149 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400577 ER PT J AU Tucker-Seeley, R Chi, D AF Tucker-Seeley, Reginald Chi, Donald TI GENDER DIFFERENCES IN THE ASSOCIATION BETWEEN FINANCIAL HARDSHIP AND ORAL HEALTH SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Tucker-Seeley, Reginald] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Chi, Donald] Univ Washington, Dept Oral Hlth Sci, Seattle, WA 98195 USA. EM retucker@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2012 VL 43 SU 1 BP S34 EP S34 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400131 ER PT J AU Wang, ML Peterson, KE Richmond, TK Spadano-Gasbarro, J Greaney, ML Mezgebu, S McCormick, M Austin, SB AF Wang, Monica L. Peterson, Karen E. Richmond, Tracy K. Spadano-Gasbarro, Jennifer Greaney, Mary L. Mezgebu, Solomon McCormick, Marie Austin, S. Bryn TI FAMILY MEAL AND PHYSICAL ACTIVITY PRACTICES ASSOCIATED WITH DISORDERED WEIGHT CONTROL BEHAVIORS IN A MULTIETHNIC SAMPLE OF MIDDLE SCHOOL YOUTH SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Wang, Monica L.; Peterson, Karen E.; Spadano-Gasbarro, Jennifer; Greaney, Mary L.; McCormick, Marie; Austin, S. Bryn] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Peterson, Karen E.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Richmond, Tracy K.; Austin, S. Bryn] Childrens Hosp, Boston, MA 02115 USA. [Richmond, Tracy K.] Harvard Univ, Sch Med, Boston, MA USA. [Greaney, Mary L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mezgebu, Solomon] Massachusetts Dept Publ Hlth, Boston, MA USA. EM Mlwang@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S86 EP S86 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400332 ER PT J AU Swanson, SJ Meyers, BF Gunnarsson, CL Moore, M Howington, JA Maddaus, MA McKenna, RJ Miller, DL AF Swanson, Scott J. Meyers, Bryan F. Gunnarsson, Candace L. Moore, Matthew Howington, John A. Maddaus, Michael A. McKenna, Robert J. Miller, Daniel L. TI Video-Assisted Thoracoscopic Lobectomy Is Less Costly and Morbid Than Open Lobectomy: A Retrospective Multiinstitutional Database Analysis SO ANNALS OF THORACIC SURGERY LA English DT Article ID THORACIC-SURGERY LOBECTOMY; CELL LUNG-CANCER; SAFETY; THORACOTOMY AB Background. The Premier Perspective Database (Premier Inc, Charlotte, NC) was used to compare hospital costs and perioperative outcomes for video-assisted thoracoscopic surgery (VATS) and open lobectomy procedures in the United States. Methods. Eligible patients underwent a lobectomy for cancer by a thoracic surgeon, by VATS or open thoracotomy and were captured in the database between third quarter of 2007 and through 2008. Multivariable logistic regression analyses were performed for binary outcomes. Ordinary least-squares regressions were used to estimate continuous outcomes. All models were adjusted for patient and hospital characteristics. Results. A total of 3,961 patients underwent a lobectomy by a thoracic surgeon by open (n = 2,907) or VATS (n = 1,054) approach. Hospital costs were higher for open versus VATS; $21,016 versus $20,316 (p = 0.027). Adjustment for surgeon experience with VATS over the 6 months prior to each operation showed a significant association between surgeon experience and cost. Average costs ranged from $22,050 for low volume surgeons to $18,133 for high volume surgeons. For open lobectomies, cost differences by surgeon experience were not significant and both levels were estimated at $21,000. Length of stay was 7.83 versus 6.15 days, for open versus VATS (p = 0.000). Surgery duration was shorter for open procedures at 3.75 versus 4.09 for VATS (p = 0.000). The risk of adverse events was significantly lower in the VATS group, odds ratio of 1.22 (p = 0.019). Conclusions. Lobectomy performed by the VATS approach as compared with an open technique results in shorter length of stay, fewer adverse events, and less cost to the hospital. Economic impact is magnified as the surgeon's experience increases. (Ann Thorac Surg 2012;93:1027-32) (C) 2012 by The Society of Thoracic Surgeons C1 [Swanson, Scott J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Thorac Surg, Boston, MA 02115 USA. Washington Univ, Div Cardiothorac Surg, St Louis, MO USA. Ethicon Endosurg Inc, Cincinnati, OH USA. S2 Stat Solut Inc, Cincinnati, OH USA. Northwestern Univ, Evanston Hosp, Dept Surg, Evanston, IL 60201 USA. Univ Minnesota, Div Thorac Surg, Duluth, MN 55812 USA. Cedars Sinai Med Ctr, Div Thorac Surg, Los Angeles, CA 90048 USA. Emory Univ Clin, Div Cardiothorac Surg, Atlanta, GA USA. RP Swanson, SJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM sjswanson@partners.org FU Ethicon Endo-Surgery, Inc, Cincinnati, Ohio FX This study was funded by Ethicon Endo-Surgery, Inc, Cincinnati, Ohio. NR 10 TC 71 Z9 79 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 APR PY 2012 VL 93 IS 4 BP 1027 EP 1032 DI 10.1016/j.athoracsur.2011.06.007 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 916RF UT WOS:000302120200013 PM 22130269 ER PT J AU Mishra, DK Thrall, MJ Baird, BN Ott, HC Blackmon, SH Kurie, JM Kim, MP AF Mishra, Dhruva K. Thrall, Michael J. Baird, Brandi N. Ott, Harald C. Blackmon, Shanda H. Kurie, Jonathan M. Kim, Min P. TI Human Lung Cancer Cells Grown on Acellular Rat Lung Matrix Create Perfusable Tumor Nodules SO ANNALS OF THORACIC SURGERY LA English DT Article ID EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; EPITHELIAL-CELLS; IN-VITRO; DIFFERENTIATION; SCAFFOLDS; CULTURE; VIVO AB Background. Extracellular matrix allows lung cancer to form its shape and grow. Recent studies on organ reengineering for orthotopic transplantation have provided a new avenue for isolating purified native matrix to use for growing cells. Whether human lung cancer cells grown in a decellularized rat lung matrix would create perfusable human lung cancer nodules was tested. Methods. Rat lungs were harvested and native cells were removed using sodium dodecyl sulfate and Triton X-100 in a decellularization chamber to create a decellularized rat lung matrix. Human A549, H460, or H1299 lung cancer cells were placed into the decellularized rat lung matrix and grown in a customized bioreactor with perfusion of oxygenated media for 7 to 14 days. Results. Decellularized rat lung matrix showed preservation of matrix architecture devoid of all rat cells. All three human lung cancer cell lines grown in the bioreactor developed tumor nodules with intact vasculature. Moreover, the lung cancer cells developed a pattern of growth similar to the original human lung cancer. Conclusions. Overall, this study shows that human lung cancer cells form perfusable tumor nodules in a customized bioreactor on a decellularized rat lung matrix created by a customized decellularization chamber. The lung cancer cells grown in the matrix had features similar to the original human lung cancer. This ex vivo model can be used potentially to gain a deeper understanding of the biologic processes involved in human lung cancer. (Ann Thorac Surg 2012;93:1075-82) (C) 2012 by The Society of Thoracic Surgeons C1 [Kim, Min P.] Methodist Hosp, Weill Cornell Med Coll, Dept Surg, Houston, TX 77030 USA. Methodist Hosp, Res Inst, Dept Surg, Houston, TX 77030 USA. Methodist Hosp, Dept Pathol & Genom Med, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dept Surg, Harvard Stem Cell Inst,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kim, MP (reprint author), Methodist Hosp, Weill Cornell Med Coll, Dept Surg, 6550 Fannin St,Ste 1661, Houston, TX 77030 USA. EM mpkim@tmhs.org RI Mishra, Dhruva/H-3880-2012 FU NCI NIH HHS [P50 CA070907] NR 21 TC 34 Z9 34 U1 0 U2 6 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 APR PY 2012 VL 93 IS 4 BP 1075 EP 1082 DI 10.1016/j.athoracsur.2012.01.011 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 916RF UT WOS:000302120200020 PM 22385822 ER PT J AU Bandla, S Pennathur, A Luketich, JD Beer, DG Lin, L Bass, AJ Godfrey, TE Little, VR AF Bandla, Santhoshi Pennathur, Arjun Luketich, James D. Beer, David G. Lin, Lin Bass, Adam J. Godfrey, Tony E. Little, Virginia R. TI Comparative Genomics of Esophageal Adenocarcinoma and Squamous Cell Carcinoma SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the Southern-Thoracic-Surgical-Association/Basic Science Forum CY NOV 09-12, 2011 CL San Antonio, TX SP So Thorac Surg Assoc ID BREAST-CANCER; EXPRESSION; SURVIVAL; DISEASE; GENES; PROFILE; CARDIA; LUNG AB Background. Esophageal cancer consists of two major histologic types: esophageal squamous cell carcinoma (ESCC), predominant globally, and esophageal adenocarcinoma (EAC), which has a higher incidence in westernized countries. Five-year overall survival is 15%. Clinical trials frequently combine histologic types although they are different diseases with distinct origins. In the evolving era of personalized medicine and targeted therapies, we hypothesized that ESCC and EAC have genomic differences important for developing new therapeutic strategies for esophageal cancer. Methods. We explored DNA copy number abnormalities in 70 ESCCs with publicly available array data and 189 EACs from our group. All data was from single nucleotide polymorphism arrays. Analysis was performed using a segmentation algorithm. Log ratio thresholds for copy number gain and loss were set at +/- 0.2 (approximately 2.3 and 1.7 copies, respectively). Results. The ESCC and EAC genomes showed some copy number abnormalities with similar frequencies (eg, CDKN2A, EGFR, KRAS, MYC, CDK6, MET) but also many copy number abnormalities with different frequencies between histologic types, most of which were amplification events. Some of these regions harbor genes for which targeted therapies are currently available (VEGFA, ERBB2) or for which agents are in clinical trials (PIK3CA, FGER1). Other regions contain putative oncogenes that may be targeted in the future. Conclusions. Using single nucleotide polymorphism arrays we compared genomic abnormalities in a large cohort of EACs and ESCCs. We report here the similar and different frequencies of copy number abnormalities in ESCC and EAC. These results may allow development of histology-specific therapeutic agents for esophageal cancer. (Ann Thorac Surg 2012;93:1101-6) (C) 2012 by The Society of Thoracic Surgeons C1 [Little, Virginia R.] Univ Rochester, Sch Med & Dent, Dept Surg, Rochester, NY 14642 USA. Univ Pittsburgh, Heart Lung & Esophageal Surg Inst, Dept Cardiothorac Surg, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Little, VR (reprint author), Univ Rochester, Sch Med & Dent, Dept Surg, Box SURG,601 Elmwood Ave, Rochester, NY 14642 USA. EM virginia_litle@urmc.rochester.edu RI Godfrey, Tony/A-5572-2013 OI Godfrey, Tony/0000-0002-3283-6983 FU NCI NIH HHS [K08 CA134931, R01 CA130853] NR 33 TC 40 Z9 43 U1 0 U2 7 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 APR PY 2012 VL 93 IS 4 BP 1101 EP 1106 DI 10.1016/j.athoracsur.2012.01.064 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 916RF UT WOS:000302120200024 PM 22450065 ER PT J AU Ye, MX Zhao, YL Zhang, J AF Ye, Ming-Xiang Zhao, Yi-Lin Zhang, Jian TI Lung Cysts as Radiological Manifestations of Benign and Malignant Diseases: Pitfalls in the Diagnosis SO ARCHIVOS DE BRONCONEUMOLOGIA LA Spanish DT Letter C1 [Ye, Ming-Xiang; Zhang, Jian] Fourth Mil Med Univ, Dept Pulm Med, Xijing Hosp, Xian 710032, Peoples R China. [Zhao, Yi-Lin] Fourth Mil Med Univ, Dept Pulm Med, Tangdu Hosp, Xian 710032, Peoples R China. [Zhang, Jian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. RP Zhang, J (reprint author), Fourth Mil Med Univ, Dept Pulm Med, Xijing Hosp, Xian 710032, Peoples R China. EM zhangjian197011@gmail.com NR 5 TC 1 Z9 1 U1 0 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 APR PY 2012 VL 48 IS 4 BP 138 EP 138 DI 10.1016/j.arbres.2011.11.009 PG 1 WC Respiratory System SC Respiratory System GA 918NV UT WOS:000302257700008 PM 22325073 ER PT J AU Li, J Hsu, HC Yang, P Wu, Q Li, H Edgington, LE Bogyo, M Kimberly, RP Mountz, JD AF Li, Jun Hsu, Hui-Chen Yang, PingAr Wu, Qi Li, Hao Edgington, Laura E. Bogyo, Matthew Kimberly, Robert P. Mountz, John D. TI Treatment of Arthritis by Macrophage Depletion and Immunomodulation Testing an Apoptosis-Mediated Therapy in a Humanized Death Receptor Mouse Model SO ARTHRITIS AND RHEUMATISM LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; COLONY-STIMULATING FACTOR; RHEUMATOID-ARTHRITIS; SYNOVIAL FIBROBLASTS; INFLAMMATORY ARTHRITIS; MONOCLONAL-ANTIBODY; ANTI-DR5 ANTIBODY; NECROSIS-FACTOR; T-LYMPHOCYTES; C57BL/6 MICE AB Objective. To determine the therapeutic efficacy and immunomodulatory effect of an anti-human death receptor 5 (DR5) antibody, TRA-8, in eliminating macrophage subsets in a mouse model of type II collagen-induced arthritis (CIA). Methods. A human/mouse-chimeric DR5-transgenic mouse, under the regulation of a mouse 3-kb promoter and a loxP-flanked STOP cassette, was generated and crossed with an ubiquitous Cre (Ubc.Cre) mouse and a lysozyme M-Cre (LysM.Cre)-transgenic mouse to achieve inducible or macrophage-specific expression. Chicken type II collagen was used to induce CIA in mice, which were then treated with an anti-human DR5 antibody, TRA-8. Clinical scores, histopathologic severity, macrophage apoptosis and depletion, and T cell subset development were evaluated. Results. In human/mouse DR5-transgenic Ubc.Cre mice with CIA, transgenic DR5 was most highly expressed on CD11b+ macrophages, with lower expression on CD4+ T cells. In human/mouse DR5-transgenic LysM.Cre mice, transgenic DR5 was restrictively expressed on macrophages. Both in vivo near-infrared imaging of caspase activity and TUNEL staining demonstrated that TRA-8 rapidly induced apoptosis of macrophages in inflamed synovium. Depletion of pathogenic macrophages by TRA-8 led to significantly reduced clinical scores for arthritis; decreased macrophage infiltration, synovial hyperplasia, osteoclast formation, joint destruction, cathepsin activity, and inflammatory cytokine expression in joints; reduced numbers of Th17 cells; and an increased number of Treg cells in draining lymph nodes. Conclusion. The anti-human DR5 antibody TRA-8 was efficacious in reducing the severity of arthritis via targeted depletion of macrophages and immunomodulation. Our data provide preclinical evidence that TRA-8 is a potential novel biologic agent for rheumatoid arthritis therapy. C1 [Mountz, John D.] Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Hsu, Hui-Chen; Yang, PingAr; Wu, Qi; Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. [Edgington, Laura E.; Bogyo, Matthew] Stanford Univ, Stanford, CA 94305 USA. RP Mountz, JD (reprint author), Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Suite 307,Shel Bldg,1825 Univ Blvd, Birmingham, AL 35294 USA. EM jdmountz@uab.edu RI Li, Hao/N-7406-2015; OI Li, Hao/0000-0002-2171-8826; Kimberly, Robert/0000-0002-5330-3086; Edgington-Mitchell, Laura/0000-0002-6810-6149 FU Lupus Research Institute; Daiichi Sankyo; Arthritis Foundation; American College of Rheumatology Research and Education Foundation; Alliance for Lupus Research; Department of Veterans Affairs [1I01BX000600-01]; NIH [R01-AI-083705-01A2, 1-R01-EB-005011-06, 1-AI-071110-01A1, ARRA-R01-AI-71110-02S1, P30-AR-048311, P30-AR-046031] FX Supported by grants from the Lupus Research Institute (to Dr. Hsu) and Daiichi Sankyo (to Dr. Mountz). Additional support was provided by the Arthritis Foundation (Postdoc Fellowship Award to Dr. J. Li), the American College of Rheumatology Research and Education Foundation (Within Our Reach grant), the Alliance for Lupus Research (Target Identification in Lupus grant), the Department of Veterans Affairs (Merit Review grant 1I01BX000600-01), and the NIH (grants R01-AI-083705-01A2 to Dr. Hsu, 1-R01-EB-005011-06 to Dr. Bogyo, 1-AI-071110-01A1 and ARRA-R01-AI-71110-02S1 to Dr. Mountz, P30-AR-048311 to the Rheumatic Diseases Core Centers including Analytical Genomics and Transgenics Core, Comprehensive Flow Cytometry Core, and Analytic Imaging and Immunoreagent Core, and P30-AR-046031 to the Center for Metabolic Bone Disease-Histomorphometry and Molecular Analysis Core). NR 48 TC 19 Z9 19 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD APR PY 2012 VL 64 IS 4 BP 1098 EP 1109 DI 10.1002/art.33423 PG 12 WC Rheumatology SC Rheumatology GA 921KC UT WOS:000302475500019 PM 22006294 ER PT J AU Wilson, KJ Mill, CP Gallo, RM Cameron, EM VanBrocklin, H Settleman, J Riese, DJ AF Wilson, Kristy J. Mill, Christopher P. Gallo, Richard M. Cameron, Elizabeth M. VanBrocklin, Henry Settleman, Jeffrey Riese, David J., II TI The Q43L mutant of neuregulin 2 beta is a pan-ErbB receptor antagonist SO BIOCHEMICAL JOURNAL LA English DT Article DE antagonist; epidermal growth factor receptor; ErbB3; ErbB4; neuregulin ID EPIDERMAL-GROWTH-FACTOR; TYROSINE-KINASE INHIBITORS; BREAST-CANCER; INTRACELLULAR DOMAIN; CELLULAR-RESPONSE; COLONY FORMATION; PHOSPHORYLATION; AMPHIREGULIN; FAMILY; CELLS AB The ErbB4 receptor tyrosine kinase possesses both tumour suppressor and oncogenic activities. Thus pharmacological agents are needed to help elucidate ErbB4 functions. However, limitations of existing ErbB4 agonists and antagonists have led us to seek novel ErbB4 antagonists. The Q43L mutant of the ErbB4 agonist NRG2 beta (neuregulin 2) stimulates ErbB4 tyrosine phosphorylation, yet fails to stimulate ErbB4 coupling to cell proliferation. Thus in the present paper we hypothesize that NRG2 beta/Q43L may be an ErbB4 antagonist. NRG2 beta/Q43L competitively antagonizes agonist stimulation of ErbB4 coupling to cell proliferation. NRG2 beta/Q43L stimulates less ErbB4 tyrosine phosphorylation than does NRG2 beta. In addition, NRG2 beta stimulation of cell proliferation requires PI3K (phosphoinositide 3-kinase) activity and NRG2 beta stimulates greater Akt phosphorylation than does NRG2 beta/Q43L. Moreover, EGER [EGF (epidermal growth factor) receptor] kinase activity (but not that of ErbB4) is critical for coupling ErbB4 to proliferation. Experiments utilizing ErbB4 splicing isoforms and mutants suggest that NRG2 beta and NRG2 beta/Q43L may differentially stimulate ErbB4 coupling to the transcriptional coregulator YAP (Yes-associated protein). Finally, NRG2 beta/Q43L competitively antagonizes agonist stimulation of EGFR and ErbB2/ErbB3, indicating that NRG2 beta/Q43L is a pan-ErbB antagonist. Thus we postulate that NRG2 beta/Q43L and other antagonistic ligands stimulate ErbB tyrosine phosphorylation on a set of residues distinct from that stimulated by agonists, thus suggesting a novel mechanism of ErbB receptor regulation. Moreover, NRG2 beta/Q43L and related ligand-based antagonists establish a paradigm for the discovery of anti-ErbB therapeutics. C1 [Wilson, Kristy J.; Mill, Christopher P.; Gallo, Richard M.; Cameron, Elizabeth M.; Riese, David J., II] Purdue Univ, Coll Pharm, W Lafayette, IN 47907 USA. [Wilson, Kristy J.; Mill, Christopher P.; Gallo, Richard M.; Cameron, Elizabeth M.; Riese, David J., II] Purdue Univ, Ctr Canc Res, W Lafayette, IN 47907 USA. [Wilson, Kristy J.] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. [Mill, Christopher P.; Riese, David J., II] Auburn Univ, Harrison Sch Pharm, Auburn, AL 36849 USA. [VanBrocklin, Henry] Univ Calif San Francisco, Dept Radiol, Ctr Mol & Funct Imaging, San Francisco, CA 94598 USA. [Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA 02129 USA. [Settleman, Jeffrey] Genentech Inc, Discovery Oncol, San Francisco, CA 94080 USA. RP Riese, DJ (reprint author), Purdue Univ, Coll Pharm, W Lafayette, IN 47907 USA. EM driese@auburn.edu FU National Cancer Institute [F33CA085049, R01CA094253, R01CA115830, R21CA080770, R01CA114209]; U.S. Army [DAMD17-00-1-0416]; American Cancer Society [IRG-58-006]; Indiana Elks Foundation; Purdue University Center for Cancer Research; National Institutes of Health [T32GM008737, K12GM000680] FX This work was supported by the National Cancer Institute [grant numbers F33CA085049 (to R.P.H.), R01CA094253 (to H.V.B.), R01CA115830 (to J.S.), R21CA080770 and R01CA114209 (to D.J.R.]; the U.S. Army Breast Cancer Research Program [grant number DAMD17-00-1-0416]; the American Cancer Society [grant number IRG-58-006]; the Indiana Elks Foundation; and the Purdue University Center for Cancer Research. K.J.W. was supported, in part, by a National Institutes of Health predoctoral training grant [grant number T32GM008737] to the Purdue University Biochemistry and Molecular Biology graduate program and the FIRST post-doctoral fellowship [grant number K12GM000680]. NR 47 TC 1 Z9 1 U1 0 U2 9 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD APR 1 PY 2012 VL 443 BP 133 EP 144 DI 10.1042/BJ20110921 PN 1 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 923AN UT WOS:000302590500015 PM 22216880 ER PT J AU Liu, N Yu, ZY Xiang, SL Zhao, S Tjarnlund-Wolf, A Xing, CH Zhang, J Wang, XY AF Liu, Ning Yu, Zhanyang Xiang, Shuanglin Zhao, Song Tjarnlund-Wolf, Anna Xing, Changhong Zhang, Jian Wang, Xiaoying TI Transcriptional regulation mechanisms of hypoxia-induced neuroglobin gene expression SO BIOCHEMICAL JOURNAL LA English DT Article DE gene regulation; hypoxia; mouse; neuroglobin; promoter; transcription factor ID NF-KAPPA-B; INDUCIBLE FACTOR-I; FACTOR C-REL; DNA-BINDING; HIPPOCAMPAL-NEURONS; BRAIN-INJURY; SP1; ACTIVATION; CELLS; EGR-1 AB Ngb (neuroglobin) has been identified as a novel endogenous neuroprotectant. However, little is known about the regulatory mechanisms of Ngb expression, especially under conditions of hypoxia. In the present study, we located the core proximal promoter of the mouse Ngb gene to a 554 bp segment, which harbours putative conserved NF-kappa B (nuclear factor kappa B)- and Egr (early growth-response factor 1) -binding sites. Overexpression and knockdown of transcription factors p65, p50, Egr1 or Sp1 (specificity protein 1) increased and decreased Ngb expression respectively. Experimental assessments with transfections of mutational Ngb gene promoter constructs, as well as EMSA (electrophoretic mobility-shift assay) and ChIP (chromatin immunoprecipitation) assays, demonstrated that NF-kappa B family members (p65, p50 and cite!), Egr1 and Sp1 bound in vitro and in vivo to the proximal promoter region of the Ngb gene. Moreover, a kappa B3 site was found as a pivotal cis-element responsible for hypoxia-induced Ngb promoter activity. NF-kappa B (p65) and Sp1 were also responsible for hypoxia-induced up-regulation of Ngb expression. Although there are no conserved HREs (hypoxia-response elements) in the promoter of the mouse Ngb gene, the results of the present study suggest that HIF-1 alpha (hypoxia-inducible factor-1 alpha) is also involved in hypoxia-induced Ngb up-regulation. In conclusion, we have identified that NF-kappa B, Egr1 and Sp1 played important roles in the regulation of basal Ngb expression via specific interactions with the mouse Ngb promoter. NF-kappa B, Sp1 and HIF-1 alpha contributed to the up-regulation of mouse Ngb gene expression under hypoxic conditions. C1 [Liu, Ning; Xiang, Shuanglin; Zhang, Jian] Hunan Normal Univ, Coll Life Sci, Educ Minist China, Key Lab Prot Chem & Dev Biol, Changsha 410081, Hunan, Peoples R China. [Liu, Ning; Yu, Zhanyang; Zhao, Song; Tjarnlund-Wolf, Anna; Xing, Changhong; Wang, Xiaoying] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA 02129 USA. [Liu, Ning; Yu, Zhanyang; Zhao, Song; Tjarnlund-Wolf, Anna; Xing, Changhong; Wang, Xiaoying] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Zhao, Song] Jilin Univ, Hosp 1, Spine Div, Dept Orthoped, Changchun 130023, Jilin, Peoples R China. [Tjarnlund-Wolf, Anna] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Sect Clin Neurosci & Rehabil, Gothenburg, Sweden. RP Zhang, J (reprint author), Hunan Normal Univ, Coll Life Sci, Educ Minist China, Key Lab Prot Chem & Dev Biol, Changsha 410081, Hunan, Peoples R China. EM zhangjian@hunnu.edu.cn; wangxi@helix.mgh.harvard.edu FU National Institutes of Health [R01NS049476]; American Heart Association [12POST9720007] FX This work was supported, in part, by the National Institutes of Health [grant number R01NS049476 (to X.W.)], and the American Heart Association (Postdoctoral Fellowship, grant number 12POST9720007 (to Z.Y.)]. NR 46 TC 19 Z9 23 U1 0 U2 6 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD APR 1 PY 2012 VL 443 BP 153 EP 164 DI 10.1042/BJ20111856 PN 1 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 923AN UT WOS:000302590500017 PM 22239089 ER PT J AU Kronman, AC Paasche-Orlow, M Orlander, JD AF Kronman, Andrea C. Paasche-Orlow, Michael Orlander, Jay D. TI Factors associated with disclosure of medical errors by housestaff SO BMJ QUALITY & SAFETY LA English DT Article ID MORTALITY CONFERENCES; ADVERSE EVENTS; RESIDENTS; MISTAKES; SAFETY; MORBIDITY; CULTURE; EXPERIENCES; PHYSICIANS; BEHAVIOR AB Purpose: Attributes of the organisational culture of residency training programmes may impact patient safety. Training environments are complex, composed of clinical teams, residency programmes, and clinical units. We examined the relationship between residents' perceptions of their training environment and disclosure of or apology for their worst error. Method: Anonymous, self-administered surveys were distributed to Medicine and Surgery residents at Boston Medical Center in 2005. Surveys asked residents to describe their worst medical error, and to answer selected questions from validated surveys measuring elements of working environments that promote learning from error. Subscales measured the microenvironments of the clinical team, residency programme, and clinical unit. Univariate and bivariate statistical analyses examined relationships between trainee characteristics, their perceived learning environment(s), and their responses to the error. Results: Out of 109 surveys distributed to residents, 99 surveys were returned (91% overall response rate), two incomplete surveys were excluded, leaving 97: 61% internal medicine, 39% surgery, 59% male residents. While 31% reported apologising for the situation associated with the error, only 17% reported disclosing the error to patients and/or family. More male residents disclosed the error than female residents (p=0.04). Surgery residents scored higher on the subscales of safety culture pertaining to the residency programme (p=0.02) and managerial commitment to safety (p=0.05). Our Medical Culture Summary score was positively associated with disclosure (p=0.04) and apology (p=0.05). Conclusion: Factors in the learning environments of residents are associated with responses to medical errors. Organisational safety culture can be measured, and used to evaluate environmental attributes of clinical training that are associated with disclosure of, and apology for, medical error. C1 [Kronman, Andrea C.] Boston Univ, Med Ctr, Sect Gen Internal Med, Evans Dept Med,Sch Med, Boston, MA 02118 USA. [Kronman, Andrea C.] Boston Univ, Sch Med, Womens Hlth Interdisciplinary Res Ctr, Boston, MA 02118 USA. [Orlander, Jay D.] VA Boston Healthcare Syst, Med Serv, Boston, MA USA. RP Kronman, AC (reprint author), Boston Univ, Med Ctr, Sect Gen Internal Med, Evans Dept Med,Sch Med, 801 Massachusetts Ave,Suite 470, Boston, MA 02118 USA. EM andrea.kronman@bmc.org OI Orlander, Jay/0000-0003-0204-8449; Paasche-Orlow, Michael/0000-0002-9276-7190 FU American Cancer Society [PT APM 97 185 04]; Boston University Medical Center FX This work was supported by an American Cancer Society Physician Training Award in Preventive Medicine (PT APM 97 185 04, Jane Liebshutz, Principal Investigator) and a Boston University Medical Center Risk Management Grant (Andrea Kronman, Principal Investigator). NR 37 TC 10 Z9 11 U1 6 U2 14 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD APR PY 2012 VL 21 IS 4 BP 271 EP 278 DI 10.1136/bmjqs-2011-000084 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 916SI UT WOS:000302123100002 PM 21949438 ER PT J AU Shahian, DM Meyer, GS Mort, E Atamian, S Liu, X Karson, AS Ramunno, LD Zheng, H AF Shahian, David M. Meyer, Gregg S. Mort, Elizabeth Atamian, Susan Liu, Xiu Karson, Andrew S. Ramunno, Lawrence D. Zheng, Hui TI Association of National Hospital Quality Measure adherence with long-term mortality and readmissions SO BMJ QUALITY & SAFETY LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; CARE PERFORMANCE-MEASURES; CLINICAL-OUTCOMES; HEALTH-CARE; SOCIOECONOMIC-STATUS; OF-CARE; MEDICARE BENEFICIARIES; ANTIMICROBIAL THERAPY AB Background: In existing studies, the association between adherence with recommended hospital care processes and subsequent outcomes has been inconsistent. This has substantial implications because process measure scores are used for accountability, quality improvement and reimbursement. Our investigation addresses methodological concerns with previous studies to better clarify the process-outcomes association for three common conditions. Methods: The study included all patients discharged from Massachusetts General Hospital between 1 July 2004 and 31 December 2007 with a principle diagnosis of acute myocardial infarction (AMI), heart failure (HF) or pneumonia (PN) who were eligible for at least one National Hospital Quality Measure. The number of patients analysed varied by measure (374 to 3020) depending on Centers for Medicare and Medicaid Services eligibility criteria. Hospital data were linked with state administrative data to determine mortality and readmissions. For patients with multiple admissions, the time-weighted impact of measure failures on mortality was estimated using exponential decay functions. All patients had follow-up for at least 1 year or until death or readmission. Cox models were used to estimate HRs adjusted for transfer status, age, gender, race, census block-group socioeconomic status, number of Elixhauser comorbidities, and do not resuscitate orders. Results: Adjusted survival and freedom from readmission for AMI and PN showed superior results for 100% and 50-99% adherence compared with 0-49% adherence. For HF, the results were inconsistent and sometimes paradoxical, although several individual measures (eg, ACE inhibitor/angiotensin receptor blockade) were associated with improved outcomes. Conclusion: Adherence with recommended AMI and PN care processes is associated with improved long-term outcomes, whereas the results for HF measures are inconsistent. The evidence base for all process measures must be critically evaluated, including the strength of association between these care processes and outcomes in real-world populations. Some currently recommended processes may not be suitable as accountability measures. C1 [Shahian, David M.; Meyer, Gregg S.; Mort, Elizabeth; Atamian, Susan; Liu, Xiu; Karson, Andrew S.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Shahian, David M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Shahian, David M.; Meyer, Gregg S.; Mort, Elizabeth; Karson, Andrew S.] Harvard Univ, Sch Med, Boston, MA USA. [Meyer, Gregg S.; Mort, Elizabeth; Karson, Andrew S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Ctr Qual & Safety, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org NR 66 TC 17 Z9 18 U1 0 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD APR PY 2012 VL 21 IS 4 BP 325 EP 336 DI 10.1136/bmjqs-2011-000615 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 916SI UT WOS:000302123100009 PM 22389022 ER EF